Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating -
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+The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here we elucidate functional features of each VOC linked to variations in replication rate. Patient-derived primary nasal cultures grown at air-liquid-interface (ALI) were used to model upper-respiratory infection and human lung epithelial cell lines used to model lower-respiratory infection. All VOCs replicated to higher titers than the ancestral virus, suggesting a selection for replication efficiency. In primary nasal cultures, Omicron replicated to the highest titers at early time points, followed by Delta, paralleling comparative studies of population sampling. All SARS-CoV-2 viruses entered the cell primarily via a transmembrane serine protease 2 (TMPRSS2)-dependent pathway, and Omicron was more likely to use an endosomal route of entry. All VOCs activated and overcame dsRNA-induced cellular responses including interferon (IFN) signaling, oligoadenylate ribonuclease L degradation and protein kinase R activation. Among the VOCs, Omicron infection induced expression of the most IFN and IFN stimulated genes. Infections in nasal cultures resulted in cellular damage, including a compromise of cell-barrier integrity and loss of nasal cilia and ciliary beating function, especially during Delta infection. Overall, Omicron was optimized for replication in the upper-respiratory system and least-favorable in the lower-respiratory cell line; and Delta was the most cytopathic for both upper and lower respiratory cells. Our findings highlight the functional differences among VOCs at the cellular level and imply distinct mechanisms of pathogenesis in infected individuals.
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Integrated histopathology, spatial and single cell transcriptomics resolve cellular drivers of early and late alveolar damage in COVID-19 -
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+The most common cause of death due to COVID-19 remains respiratory failure. Yet, our understanding of the precise cellular and molecular changes underlying lung alveolar damage is limited. Here, we integrate single cell transcriptomic data of COVID-19 donor lungs with spatial transcriptomic data stratifying histopathological stages of diffuse alveolar damage (DAD). We identify changes in cellular composition across progressive DAD, including waves of molecularly distinct macrophages and depleted epithelial and endothelial populations throughout different types of tissue damage. Predicted markers of pathological states identify immunoregulatory signatures, including IFN-alpha and metallothionein signatures in early DAD, and fibrosis-related collagens in organised DAD. Furthermore, we predict a fibrinolytic shutdown via endothelial upregulation of SERPINE1/PAI-1. Cell-cell interaction analysis revealed macrophage-derived SPP1/osteopontin signalling as a key regulator during early DAD. These results provide the first comprehensive, spatially resolved atlas of DAD stages, highlighting the cellular mechanisms underlying pro-inflammatory and pro-fibrotic pathways across alveolar damage progression.
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Deep profiling of antigen-specific B cells from different pathogens identifies novel compartments in the IgG memory B cell and antibody-secreting cell lineages -
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+A better understanding of the bifurcation of human B cell differentiation into memory B cells (MBC) and antibody-secreting cells (ASC) and identification of MBC and ASC precursors is crucial to optimize vaccination strategies or block undesired antibody responses. To unravel the dynamics of antigen-induced B cell responses, we compared circulating B cells reactive to SARS-CoV-2 (Spike, RBD and Nucleocapsid) in COVID-19 convalescent individuals to B cells specific to Influenza-HA, RSV-F and TT, induced much longer ago. High-dimensional spectral flow cytometry indicated that the decision point between ASC- and MBC-formation lies in the CD43+CD71+IgG+ Activated B cell compartment, showing properties indicative of recent germinal center activity and recent antigen encounter. Within this Activated B cells compartment, CD86+ B cells exhibited close phenotypical similarity with ASC, while CD86- B cells were closely related to IgG+ MBCs. Additionally, different activation stages of the IgG+ MBC compartment could be further elucidated. The expression of CD73 and CD24, regulators of survival and cellular metabolic quiescence, discerned activated MBCs from resting MBCs. Activated MBCs (CD73- CD24lo) exhibited phenotypical similarities with CD86- IgG+ Activated B cells and were restricted to SARS-CoV-2 specificities, contrasting with the resting MBC compartment (CD73-/CD24hi) that exclusively encompassed antigen-specific B cells established long ago. Overall, these findings identify novel stages for IgG+ MBC and ASC formation and bring us closer in defining the decision point for MBC or ASC differentiation.
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Predicting the Trend of SARS-CoV-2 Mutation Frequencies Using Historical Data -
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+As the SARS-CoV-2 virus rapidly evolves, predicting the trajectory of viral variations has become a critical yet complex task. A deep understanding of future mutation patterns, in particular the mutations that will prevail in the near future, is vital in steering diagnostics, therapeutics, and vaccine strategies in the coming months. In this study, we developed a model to forecast future SARS-CoV-2 mutation surges in real-time, using historical mutation frequency data from the USA. To improve upon the accuracy of traditional time-series models, we transformed the prediction problem into a supervised learning framework using a sliding window approach. This involved breaking the time series of mutation frequencies into very short segments. Considering the time-dependent nature of the data, we focused on modeling the first-order derivative of the mutation frequency. We predicted the final derivative in each segment based on the preceding derivatives, employing various machine learning methods including random forest, XGBoost, support vector machine, and neural network models, in this supervised learning setting. Empowered by the novel transformation strategy and the high capacity of machine learning models, we witnessed low prediction error that is confined within 0.1% and 1% when making predictions for future 30 and 80 days respectively. In addition, the method also led to a notable increase in prediction accuracy compared to traditional time-series models, as evidenced by lower MAE, and MSE for predictions made within different time horizons. To further assess the method's effectiveness and robustness in predicting mutation patterns for unforeseen mutations, we categorized all mutations into three major patterns. The model demonstrated its robustness by accurately predicting unseen mutation patterns when training on data from two pattern categories while testing on the third pattern category, showcasing its potential in forecasting a variety of mutation trajectories. To enhance accessibility and utility, we built our methodology into an R-shiny app (https://swdatpredicts.shinyapps.io/rshiny_predict/), a tool with potential applicability in studying other infectious diseases, thus extending its relevance beyond the current pandemic.
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Inverse folding of protein complexes with a structure-informed language model enables unsupervised antibody evolution -
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+Large language models trained on sequence information alone are capable of learning high level principles of protein design. However, beyond sequence, the three-dimensional structures of proteins determine their specific function, activity, and evolvability. Here we show that a general protein language model augmented with protein structure backbone coordinates and trained on the inverse folding problem can guide evolution for diverse proteins without needing to explicitly model individual functional tasks. We demonstrate inverse folding to be an effective unsupervised, structure-based sequence optimization strategy that also generalizes to multimeric complexes by implicitly learning features of binding and amino acid epistasis. Using this approach, we screened ~30 variants of two therapeutic clinical antibodies used to treat SARS-CoV-2 infection and achieved up to 26-fold improvement in neutralization and 37-fold improvement in affinity against antibody-escaped viral variants-of-concern BQ.1.1 and XBB.1.5, respectively. In addition to substantial overall improvements in protein function, we find inverse folding performs with leading experimental success rates among other reported machine learning-guided directed evolution methods, without requiring any task-specific training data.
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Cell type-specific adaptation of the SARS-CoV-2 spike -
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+SARS-CoV-2 can infect various human tissues and cell types, principally via interaction with its cognate receptor ACE2. However, how the virus evolves in different cellular environments is poorly understood. Here, we used experimental evolution to study the adaptation of the SARS-CoV-2 spike to four human cell lines expressing different levels of key entry factors. After 20 passages, cell type-specific phenotypic changes were observed. Selected spike mutations were identified and functionally characterized in terms of entry efficiency, ACE2 affinity, spike processing, TMPRSS2 usage, entry pathway and syncytia formation. We found that the effects of these mutations varied across cell types. Interestingly, two spike mutations (L48S and A372T) that emerged in cells expressing low ACE2 levels increased receptor affinity, syncytia induction, and entry efficiency under low-ACE2 conditions. Our results demonstrate specific adaptation of the SARS-CoV-2 spike to different cell types and have implications for understanding SARS-CoV-2 tissue tropism and evolution.
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Temperature impacts SARS-CoV-2 spike fusogenicity and evolution -
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+SARS-CoV-2 infects both the upper and lower respiratory tracts, which are characterized by different temperatures (33 degrees C and 37 degrees C, respectively). In addition, fever is a common COVID-19 symptom. SARS-CoV-2 has been shown to replicate more efficiently at low temperatures but the effect of temperature on different viral proteins remains poorly understood. Here, we investigate how temperature affects the SARS-CoV-2 spike function and evolution. We first observed that rising temperature from 33 degrees C to 37 degrees C or 39 degrees C increased spike-mediated cell-cell fusion. We then experimentally evolved a recombinant vesicular stomatitis virus expressing the SARS-CoV-2 spike at these different temperatures. We found that spike-mediated cell-cell fusion was maintained during evolution at 39 degrees C, but was lost in a high proportion of viruses evolved at 33 degrees C or 37 degrees C. Consistently, sequencing of the spikes evolved at 33 degrees C or 37 degrees C revealed the accumulation of mutations around the furin cleavage site, a region that determines cell-cell fusion, whereas this did not occur in spikes evolved at 39 degrees C. Finally, using site-directed mutagenesis, we found that disruption of the furin cleavage site had a temperature-dependent effect on spike-induced cell-cell fusion and viral fitness. Our results suggest that variations in body temperature may affect the activity and diversification of the SARS-CoV-2 spike.
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Is Covid-19 âvaccine uptakeâ in postsecondary education a âproblemâ? A critical policy inquiry -
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+Since the launch of the Covid-19 global vaccination campaign, postsecondary institutions have strongly promoted vaccination, often through mandates, and the academic literature has identified âvaccine uptakeâ among postsecondary students as a problem deserving monitoring, research, and intervention. However, with the admission that vaccines do not stop viral spread, that older-age and co-morbidities are major determinants of poor outcomes, and that many vaccine side effects disproportionately affect the young, it cannot be assumed that a risk-benefit analysis favours vaccinating postsecondary students. Drawing from critical policy studies, I appraise the literature on Covid-19 vaccine uptake in postsecondary education. I find that this literature reflects the âscientific consensusâ, hardly acknowledging contradictory medical evidence, ignoring coercive elements underlying âvaccine acceptanceâ, and neglecting ethical tensions built into the very design of vaccination policies. I discuss potential explanations for my findings, and their implications for academiaâs role in society in the COVID-19 era and beyond.
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COVID-19 vaccines and autoimmune disorders: A scoping review protocol -
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+Background Two years into the global vaccination program, important questions about the association between COVID-19 vaccines and autoimmune diseases have arisen. A growing number of reports have documented associations between COVID-19 vaccination and autoimmunity, suggesting, for example, a causal link between vaccination and new-onset and/or relapsing autoimmune disorders such as type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, Graves disease, and Hashimotoâs thyroiditis. These autoimmune phenomena have occurred with various COVID-19 vaccines and research is required to elucidate the underlying mechanisms and causal directions, for example, whether persons with no history of autoimmune disorders may experience them upon vaccination or persons with autoimmune disorders may experience exacerbation or new adverse events post-vaccination. Methods and analysis Specific objectives of this scoping review will address the following questions: Can COVID-19 vaccination trigger and/or exacerbate autoimmune disorders? Are persons with autoimmune disorders at higher risk of experiencing additional autoimmune disorders? What are the mechanisms connecting autoimmune disorders with COVID-19 vaccination? Can COVID-19 vaccination interact with immunosuppressive therapy in persons with autoimmune disorders? Does the risk of autoimmune disorders following COVID-19 vaccination differ by vaccine type, age, gender, or other still unidentified characteristics (e.g., SES)? What is the consensus of care concerning COVID-19 vaccination in persons with autoimmune disorders and what evidence informs it? Our review will follow Arksey and OâMalleyâs (2005) framework, enhanced by Levac et al.âs team-based approach (2010), and adhering to the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist. To capture the broadest range of perspectives on the phenomenon of interest, data will be synthesized through numerical summaries describing general characteristics of included studies and thematic analysis. Subgroup analysis of primary outcomes will be performed to compare findings according to 1) the previous existence of autoimmune disorder, 2) the presence of relevant co-morbidities, 3) vaccine type; and other relevant factors that we may encounter as the research proceeds. Significance COVID-19 has triggered the largest vaccination campaign in history, targeting literally the global human community. Drug safety is a crucial aspect of any medical intervention, critical to a proper assessment of the balance of risks and benefits. Our investigation should yield information useful to improve medical and public health practice in multiple ways, including assisting in clinical decision-making, policy development, and ethical medical practice.
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Advances and pitfalls in measuring transportation equity -
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+Transportation systems play a pivotal role in facilitating access to out-of-home activities, enabling participation in various aspects of social life. But because of budgetary and physical limitations, they cannot provide equal access everywhere; inevitably, some locations will be better served than others. This realization gives rise to two fundamental concerns in transportation equity research and practice: 1) accessibility inequality and 2) accessibility poverty. Accessibility inequalities may rise to the level of injustice when some socioeconomic groups systematically have lower access to opportunities than others. Accessibility poverty occurs when people are unable to meet their daily needs and live a dignified, fulfilling life because of a lack of access to essential services and opportunities. In this paper, we review two of the most widely used approaches for evaluating transport justice concerns related to accessibility inequality and accessibility poverty: Gini coefficients/Lorenz curves and needs-gap/transit desert approaches, respectively. We discuss how their theoretical underpinnings are inconsistent with egalitarian and sufficientarian concerns in transport justice and show how the underlying assumptions of these methods and their applications found in the transportation equity literature embody many previously unacknowledged limitations that severely limit their utility. We substantiate these concerns by analysing the equity impacts of Covid-19-related service cuts undertaken in Washington, D.C. during 2020. The paper also discusses how alternative methods for measuring transportation equity both better comport with the known impacts of such changes and are consistent with underlying moral concerns.
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Policy makers believe money motivates more than it does -
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+To motivate contributions to public goods, should policy makers employ financial incentives like taxes, fines, subsidies, and rewards? While these are widely considered as the classic policy approach, a substantial academic literature suggests the impact of financial incentives is not always positive; they can sometimes fail or even backfire. To test whether policy makers are overly bullish about financial incentives, we asked county heads, mayors, and municipal government representatives of medium-to-large towns in Germany to predict the effects of a financial incentive on COVID-19 vaccination, and tested the exact same incentive in a field experiment involving all 41,548 inhabitants (clustered in 10,032 addresses) of the German town of Ravensburg. Whereas policy makers overwhelmingly predict that the financial incentive will increase vaccinationâby 15.3 percentage points on averageâthe same financial incentive yielded a precisely estimated null effect on vaccination. We discuss when financial incentives are most likely to fail, and conclude that it is critical to educate policy makers on the potential pitfalls of employing financial incentives to promote contributions to public goods.
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Coping with Covid 19 lockdown: Optimism and Intolerance of Uncertainty in India -
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+Background: Kerala state in India has been hailed as an exceptional model in containing the Covid 19 pandemic within a low resource setting Insights from such a setting are valuable for mental health research during an epidemic situation, especially for resource poor countries. Aims:The study examined the relationship between optimism intolerance of uncertainty (IU), and socio- demographic factors among participants from Kerala, India. Methods: An observational design was used and data was collected using online survey. Snowball sampling method was employed. Sample consisted of 121 adults belonging to Kerala. Standardised tools and customised questionnaire were used for data collection. Descriptive and inferential statistics were employed. Results: A strong relationship existed between inhibitory anxiety and optimism. Socio-demographic factors did not determine either intolerance of uncertainty or optimism. The unprecedented uncertainty brought about by the pandemic needs further exploration. Conclusions: The present pandemic has presented an unprecedented situation regarding well being of individuals. Further studies on anxiety and related issues, and protective factors during situations of uncertainty are needed for policy and practice related to community level disaster preparedness.
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+Immune evasion is a pivotal force shaping the evolution of viruses. Nonetheless, the extent to which virus evolution varies among populations with diverse immune backgrounds remains an unsolved mystery. Prior to the widespread SARS-CoV-2 infections in December 2022 and January 2023, the Chinese population possessed a markedly distinct (less potent) immune background due to its low infection rate, compared to countries experiencing multiple infection waves, presenting an unprecedented opportunity to investigate how the virus has evolved under different immune contexts. We compared the mutation spectrum and functional potential of BA.5.2.48, BF.7.14, and BA.5.2.49-variants prevalent in China-with their counterparts in other countries. We found that mutations in the RBD region in these lineages were more widely dispersed and evenly distributed across different epitopes. These mutations led to a higher ACE2 binding affinity and reduced potential for immune evasion compared to their counterparts in other countries. These findings suggest a milder immune pressure and less evident immune imprinting within the Chinese population. Despite the emergence of numerous immune-evading variants in China, none of them exhibited a transmission advantage. Instead, they were replaced by the imported XBB variant with stronger immune evasion since April 2023. Our findings demonstrated that the continuously changing immune background led to varying evolutionary pressures on SARS-CoV-2. Thus, in addition to the viral genome surveillance, immune background surveillance is also imperative for predicting forthcoming mutations and understanding how these variants spread in the population.
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PandoGen: Generating complete instances of future SARS-CoV-2 sequences using Deep Learning -
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+Deep generative models have achieved breakthrough performance in generating computer code, instances of human language and images. We explore the use of these models to create as yet undiscovered instances of viral sequences in a pandemic situation. Towards this goal, we formulate a novel framework for training models to align the sequence generation problem to the characteristics of a pandemic. We applied our method to modeling the SARS-CoV2 Spike protein, the primary driver of the COVID-19 pandemic, and compared our method to models trained via prevalent practices applied to biological sequence modeling. Our method substantially outperforms a state-of-the-art generative model finetuned on SARS-CoV2 data, producing samples containing sequences which are four times as likely to be real, undiscovered sequences, and ten times as infectious. Our method can forecast novel lineages of the virus up to approximately 3 months in advance. Given a limited sequence budget, our method generates sequences belonging to the Delta variant and multiple dominant Omicron subvariants up to a month in advance.
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Robust detection of SARS-CoV-2 exposure in population using T-cell repertoire profiling -
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+The COVID-19 pandemic offers a powerful opportunity to develop methods for monitoring the spread of infectious diseases based on their signatures in population immunity. Adaptive immune receptor repertoire sequencing (AIRR-seq) has become the method of choice for identifying T cell receptor (TCR) biomarkers encoding pathogen specificity and immunological memory. AIRR-seq can detect imprints of past and ongoing infections and facilitate the study of individual responses to SARS-CoV-2, as shown in many recent studies. Here, we have applied a machine learning approach to two large AIRR-seq datasets with more than 1,200 high-quality repertoires from healthy and COVID-19-convalescent donors to infer TCR repertoire features that were induced by SARS-CoV-2 exposure. The new batch effect correction method allowed us to use data from different batches together, as well as combine the analysis for data obtained using different protocols. Proper standardization of AIRR-seq batches, access to human leukocyte antigen (HLA) typing, and the use of both - and {beta}-chain sequences of TCRs resulted in a high-quality biomarker database and a robust and highly accurate classifier for COVID-19 exposure. This classifier is applicable to individual TCR repertoires obtained using different protocols, paving the way to AIRR-seq-based immune status assessment in large cohorts of donors.
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Evaluate the Efficacy and Safety of âFormosa 1-Breath Free (NRICM101)â in Subjects With the Symptoms of COVID-19 or Influenza-like Disease - Conditions: Influenza Viral Infections; COVID-19 Interventions: Drug: Formosa 1-Breath Free (NRICM101); Drug: Placebo control drug Sponsors: China Medical University Hospital; Tian-I Pharmaceutical,. Co. Ltd.; China Medical University, China; Qualitix Clinical Research Co., Ltd. Not yet recruiting
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A Phase 3 Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of Booster Vaccination With Recombinant COVID-19 (XBB) Trimer Protein Vaccine (Sf9 Cell) (WSK-V102D). - Conditions: COVID-19 Interventions: Biological: Recombinant COVID-19 (XBB) Trimer Protein Vaccine (Sf9 Cell) (WSK-V102D); Biological: Recombinant COVID-19 Variant Vaccine (Sf9 Cell) (WSK-V102); Biological: Placebo Sponsors: WestVac Biopharma Co., Ltd.; WestVac Biopharma (Guangzhou) Co., Ltd. Not yet recruiting
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Restoring Energy With Sub-symptom Threshold Optimized Rehabilitation Exercise for Long COVID - Conditions: Long Covid19; Exercise Intolerance, Riboflavin-Responsive Interventions: Behavioral: Restoring Energy with Sub-symptom Threshold Aerobic Rehabilitation Exercise; Behavioral: Light Stretching/Breathing Exercises Sponsors: Columbia University; New York University Recruiting
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A Pilot Study of Liraglutide (A Weight Loss Drug) in High Risk Obese Participants With Cognitive and Memory Issues - Conditions: Multiple Sclerosis; Long COVID; Long Covid19; Obese; Obesity; Obesity, Morbid; Acute Leukemia in Remission Interventions: Drug: Liraglutide Pen Injector [Saxenda]; Other: Medication Diary Sponsors: University of Chicago Not yet recruiting
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EXERCISE TRAINING USING AN APP ON PHYSICAL CARDIOVASCULAR FUNCTION INDIVIDUALS WITH POST-COVID-19 SYNDROME - Conditions: Post-Acute COVID-19 Syndrome Interventions: Behavioral: Exercise; Behavioral: Control Sponsors: University of Nove de Julho Not yet recruiting
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A Phase 1 Trial of Recombinant COVID-19 Trivalent Protein Vaccine ïŒCHO CellïŒLYB002V14 in Booster Vaccination - Conditions: SARS-CoV-2; COVID-19 Vaccine Interventions: Biological: 30ÎŒg dose of LYB002V14; Biological: 60ÎŒg dose of LYB002V14; Biological: placebo Sponsors: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd. Not yet recruiting
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COVID-19 Vaccine Effectiveness Against Recurrent Infection Among Lung Cancer Patients and Biomarker Research - Conditions: COVID-19 Recurrent; Lung Cancer; Vaccination; Antibody; Chemotherapy; Immune Checkpoint Inhibitor Interventions: Biological: Any Chinese government-recommended COVID-19 booster vaccine Sponsors: Peking Union Medical College Hospital Recruiting
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IMMUNERECOV CONTRIBUTES TO IMPROVEMENT OF RESPIRATORY AND IMMUNOLOGICAL RESPONSE IN POST-COVID-19 PATIENTS. - Conditions: Long Covid19; Dietary Supplements; Respiratory Tract Infections; Inflammation Interventions: Dietary Supplement: Nutritional blend (ImmuneRecov). Sponsors: Federal University of SĂŁo Paulo Recruiting
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Physical Activity Coaching in Patients With Post-COVID-19 - Conditions: Post-COVID-19 Syndrome Interventions: Behavioral: Self-monitoring; Behavioral: Goal setting and review; Behavioral: Education; Behavioral: Feedback; Behavioral: Contact; Behavioral: Exercise; Behavioral: Report; Behavioral: Social support; Behavioral: Group activities; Behavioral: World Health Organization recommendations for being physically active Sponsors: University of Alcala; Colegio Profesional de Fisioterapeutas de la Comunidad de Madrid Not yet recruiting
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Study on Post-Acute COVID-19 Syndrome in Improvement of COVID-19 Rehabilitated Patients by Respiratory Training - Conditions: COVID-19, Post-Acute COVID-19 Syndrome, Dyspnea, Incentive Spirometer Interventions: Device: breathing training Sponsors: Tri-Service General Hospital Active, not recruiting
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Ensitrelvir for Viral Persistence and Inflammation in People Experiencing Long COVID - Conditions: Long COVID; Post Acute Sequelae of COVID-19; Post-Acute COVID-19 Interventions: Drug: Ensitrelvir; Other: Placebo Sponsors: Timothy Henrich; Shionogi Inc. Not yet recruiting
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Low-intensity Aerobic Training Associated With Global Muscle Strengthening in Post-COVID-19 - Conditions: COVID-19 Interventions: Procedure: muscle strengthening Sponsors: Centro UniversitĂĄrio Augusto Motta Completed
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From PubMed
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Synthetic graphene-copper nanocomposites interact with the hACE-2 enzyme and inhibit its biochemical activity - This study demonstrates the copper nanocomposite-induced enzymatic inhibition of human angiotensin I-converting enzyme-2 (hACE-2) by complex stabilization through the formation of the enzyme nanocomposite. The immediate application of this work is related to ACE-2 as a mechanism of SARS-CoV-2 entry into cells. Moreover, ACE-2 enzyme regulation is a potential therapeutic strategy in hypertension and cardiovascular disease, diabetes, lung injury, and fibrotic disorders. Thus, inhibition of ACE-2âŠ
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A two-stage design enhanced biodegradation of high concentrations of a C16-alkyl quaternary ammonium compound in oxygen-based membrane biofilm reactors - Quaternary ammonia compounds (QAC), such as hexadecyltrimethyl-ammonium (CTAB), are widely used as disinfectants and in personal-care products. Their use as disinfectants grew during the SARS-CoV-2 (COVID-19) pandemic, leading to increased loads to wastewater treatment systems and the environment. Though low concentrations of CTAB are biodegradable, high concentrations are toxic to bacteria. Sufficient O(2) delivery is a key to achieve high CTAB removal, and the O(2)-based Membrane BiofilmâŠ
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CNP blocks mitochondrial depolarization and inhibits SARS-CoV-2 replication in vitro and in vivo - The COVID-19 pandemic has claimed over 6.5 million lives worldwide and continues to have lasting impacts on the worldâs healthcare and economic systems. Several approved and emergency authorized therapeutics that inhibit early stages of the virus replication cycle have been developed however, effective late-stage therapeutical targets have yet to be identified. To that end, our lab identified that 2â,3â cyclic-nucleotide 3â-phosphodiesterase (CNP) inhibits SARS-CoV-2 virion assembly. We showâŠ
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Molecular insights to the anti-COVID-19 potential of α-, ÎČ- and Îł-cyclodextrins - SARS-CoV-2 viral infection is regulated by the host cell receptors ACE2 and TMPRSS2, and therefore the effect of various natural and synthetic compounds on these receptors has recently been the subject of investigations. Cyclodextrins, naturally occurring polysaccharides derived from starch, are soluble in water and have a hydrophobic cavity at their center enabling them to accommodate small molecules and utilize them as carriers in the food, supplements, and pharmaceutical industries to improveâŠ
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Combined in vitro/in silico approaches, molecular dynamics simulations and safety assessment of the multifunctional properties of thymol and carvacrol: A comparative insight - Bioactive compounds derived from medicinal plants have acquired immense attentiveness in drug discovery and development. The present study investigated in vitro and predicted in silico the antibacterial, antifungal, and antiviral properties of thymol and carvacrol, and assessed their safety. The performed microbiological assays against Pseudomonas aeruginosa, Escherichia coli, Salmonella enterica Typhimurium revealed that the minimal inhibitory concentration values ranged from (0.078 to 0.312âŠ
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Molecular dynamics, molecular docking, DFT, and ADMET investigations of the Co(II), Cu(II), and Zn(II) chelating on the antioxidant activity and SARS-CoV-2 main protease inhibition of quercetin - The natural flavonol quercetin (Q) is found in many vegetables, fruits, and beverages, and it is known as a strong antioxidant. Its metal ion chelation may increase its antioxidant activity. The present study aims to explore the Co(II), Cu(II), and Zn(II) chelating on the antioxidant effectiveness and severe acute respiratory syndrome coronavirus 2 (SARSâCoVâ2) main protease (M^(pro)) inhibitory of quercetin using Density-functional theory (DFT), molecular docking, and molecular dynamicsâŠ
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Integrated metabolomics and transcriptomics analyses reveal metabolic responses to TGEV infection in porcine intestinal epithelial cells - Transmissible gastroenteritis virus (TGEV) is a coronavirus that infects piglets with severe diarrhoea, vomiting, dehydration, and even death, causing huge economic losses to the pig industry. The underlying pathogenesis of TGEV infection and the effects of TGEV infection on host metabolites remain poorly understood. To investigate the critical metabolites and regulatory factors during TGEV infection in intestinal porcine epithelial cells (IPEC-J2), we performed metabolomic and transcriptomicâŠ
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Inhibition potential of natural flavonoids against selected omicron (B.1.19) mutations in the spike receptor binding domain of SARS-CoV-2: a molecular modeling approach - The omicron (B.1.19) variant of contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is considered a variant of concern (VOC) due to its increased transmissibility and highly infectious nature. The spike receptor-binding domain (RBD) is a hotspot of mutations and is regarded as a prominent target for screening drug candidates owing to its crucial role in viral entry and immune evasion. To date, no effective therapy or antivirals have been reported; therefore, there is anâŠ
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Inhibition of the lysine demethylase LSD1 modulates the balance between inflammatory and antiviral responses against coronaviruses - Innate immune responses to coronavirus infections are highly cell specific. Tissue-resident macrophages, which are infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients but are inconsistently infected in vitro, exert critical but conflicting effects by secreting both antiviral type I interferons (IFNs) and tissue-damaging inflammatory cytokines. Steroids, the only class of host-targeting drugs approved for the treatment of coronavirus disease 2019 (COVID-19),âŠ
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Toxin release by conditional remodelling of ParDE1 from Mycobacterium tuberculosis leads to gyrase inhibition - Mycobacterium tuberculosis, the causative agent of tuberculosis, is a growing threat to global health, with recent efforts towards its eradication being reversed in the wake of the COVID-19 pandemic. Increasing resistance to gyrase-targeting second-line fluoroquinolone antibiotics indicates the necessity to develop both novel therapeutics and our understanding of M. tuberculosis growth during infection. ParDE toxin-antitoxin systems also target gyrase and are regulated in response to bothâŠ
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Unraveling viral drug targets: a deep learning-based approach for the identification of potential binding sites - The coronavirus disease 2019 (COVID-19) pandemic has spurred a wide range of approaches to control and combat the disease. However, selecting an effective antiviral drug target remains a time-consuming challenge. Computational methods offer a promising solution by efficiently reducing the number of candidates. In this study, we propose a structure- and deep learning-based approach that identifies vulnerable regions in viral proteins corresponding to drug binding sites. Our approach takes intoâŠ
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Inhibition of SARS-CoV-2 NSP-15 by Uridine-5â-Monophosphate Analogues Using QSAR Modelling, Molecular Dynamics Simulations, and Free Energy Landscape - SARS-CoV-2 is accountable for severe social and economic disruption around the world causing COVID-19. Non-structural protein-15 (NSP15) possesses a domain that is vital to the viral life cycle and is known as uridylate-specific endoribonuclease (EndoU). This domain binds to the uridine 5â-monophosphate (U5P) so that the protein may carry out its native activity. It is considered a vital drug target to inhibit the growth of the virus. Thus, in this current study, ML-based QSAR and virtualâŠ
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Human super antibody to viral RNA-dependent RNA polymerase produced by a modified Sortase self-cleave-bacteria surface display system - CONCLUSION: The functionalized super antibody to RNA virus RdRp was successfully produced by using combined Sortase self-cleave and bacterial surface display systems with modification. The display system is suitable for downstream processing in a large-scale production of the super antibody. It is applicable also for production of other recombinant proteins in soluble free-folding form.
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Contemporary Public Health Finance: Varied Definitions, Patterns, and Implications - The financing of public health systems and services relies on a complex and fragmented web of partners and funding priorities. Both underfunding and âdys-fundingâ contribute to preventable mortality, increases in disease frequency and severity, and hindered social and economic growth. These issues were both illuminated and magnified by the COVID-19 pandemic and associated responses. Further complicating issues is the difficulty in constructing adequate estimates of current public healthâŠ
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Investigation of the mutated antimicrobial peptides to inhibit ACE2, TMPRSS2 and GRP78 receptors of SARS-CoV-2 and angiotensin II type 1 receptor (AT1R) as well as controlling COVID-19 disease - SARS-CoV-2 is a global problem nowadays. Based on studies, some human receptors are involved in binding to SARS-CoV-2. Thus, the inhibition of these receptors can be effective in the treatment of Covid-19. Because of the proven benefits of antimicrobial peptides (AMPs) and the side effects of chemical drugs, they can be known as an alternative to recent medicines. RCSB PDB to obtain PDB id, StraPep and PhytAMP to acquire Bio-AMPs information and 3-D structure, and AlgPred, Toxinpred,âŠ
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From Patent Search
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How Netanyahuâs Right-Wing Critics See Israelâs Future - Danny Danon, the former Israeli Ambassador to the United Nations, believes thereâs no path forward for a Palestinian state. - link
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An Unpermitted Shooting Range Upends Life in a Quiet Town - Residents of Pawlet, Vermont, were accustomed to calm and neighborly interactions. Then a new resident moved in. - link
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There Are No Safe Places in Gaza - As Israelâs military campaign has expanded into southern Gaza, displaced families have been forced to move again and again. - link
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The Disturbing Impact of the Cyberattack at the British Library - The library has been incapacitated since October, and the effects have spread beyond researchers and book lovers. - link
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When a Border Closure Hits Americans - The shutting of a crossing in Arizona has reduced access to a popular Mexican beach town, leading to outrage from unfamiliar sources. - link
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From Vox
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Mourning winter in a warming world -
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+Yelena Bryksenkova for Vox
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+Could a whole season â and a way of life â be melting before our very eyes?
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+A snowy winter in New York City brings with it a kind of magic. The air goes crisp, then bitter, and fragile snowflakes sift down in the early dark, silvering the trees and blanketing the sledding hills in the parks. After the first big snow, children and adults alike rush out to make snowmen, creations that delight passersby for the next two frigid months, until the snow finally thaws. When I took my older son, then a toddler, out for his first-ever sledding session, he squealed with awe at the crystalline world before him, shouting, âIt looks like Frozen!â
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+Today heâs 5, and I doubt he remembers what sledding feels like. Itâs been more than 650 days since Central Park, where snow is measured daily, got more than an inch of snowfall at one time; last winter, the park got just 2.3 inches in total, less than one-tenth the normal amount. In early December, Brooklyn saw a few anemic flurries, and my son told me excitedly that his friends had tried to build a snowman during recess. But there was nowhere near enough material to work with. They settled for âa pile of snowflakes.â
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+This sense of winter melting away before our eyes is not unique to New York: While blazing-hot summers and stormy autumns come with their own dangers, scientists say winter is actually the fastest-warming season. Snowfall is decreasing across the Northeast, the flakes slowly replaced by raindrops. The Great Lakes have experienced a 22 percent drop in maximum ice cover since 1973, and are frozen for a shorter percentage of the year. In December 2022, Utqiagvik, the northernmost city in Alaska, posted its warmest winter temperature ever at 40 degrees Fahrenheit, a full 36 degrees above the frigid average for that time of year.
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+The effects are felt around the world, from the Southern Cone to the Arctic Circle. For some, the loss of cold is already an emergency, as winter warming exacts a devastating environmental and human toll. But for many, itâs a slow drip, something they notice in the small details of daily life.
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+These incremental changes alter the way we celebrate holidays, the way we get dressed to go outside, and even, on a deep level, the way we feel. The philosopher Glenn Albrecht has coined the term âsolastalgia,â or âthe homesickness we feel while still at home,â to describe the disorientation some of us experience as the planet we once knew changes drastically around us.
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+âThereâs this sort of existential offness,â said Heather Hansman, a Colorado-based ski journalist and author of the book Powder Days: Ski Bums, Ski Towns, and the Future of Chasing Snow. âMy body knows that this isnât right.â
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+Winter is woven into the fabric of human life
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+Like worsening summer heat waves, winter warming is caused by companies and governments burning fossil fuels. The resulting emissions intensify the greenhouse effect, in which the earthâs atmosphere traps heat from the sun, making temperatures on the ground warmer. The greenhouse effect is strongest at the poles, and itâs also most pronounced during winter, said Kenneth Blumenfeld, a senior climatologist with the Minnesota State Climatology Office.
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+As a result, the frigid winters many people remember are slowly giving way to something warmer â and weirder. In Minnesota, âItâs not that it never gets cold, because it sure does,â Blumenfeld said. But âit doesnât get cold as dependably, as frequently, or as severely as it used to.â
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+âI have some winter jackets that have been two years in the closet without any use,â Juan Antonio Rivera, a researcher at the Argentine Institute for Snow Research, Glaciology, and Environmental Sciences, said in an email. âFrosts in the winter mornings now are a rare thing to see.â (A winter heat wave earlier this year pushed the temperature to 86 degrees in Buenos Aires, where winter highs are usually in the 60s.)
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+Warmer temperatures around the world are bringing more rain and less snow. As I write this, for example, the Christmas trees for sale down the block are being soaked in a very un-Christmassy downpour. But even as overall snowfall declines, extreme snowstorms are increasing in some places, and thereâs some evidence that climate change is leading to more intense cold snaps in places like Texas and California, where the infrastructure simply isnât built for snow and ice.
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+Winter can be a bleak and unforgiving season, but itâs also one for which different cultures around the world have developed unique coping mechanisms â and even one many people have come to love. In northern Minnesota, where the season can stretch for six long, dark months, âitâs sort of built into how we live,â Blumenfeld said. Residents have made winter pastimes like ice-fishing, skating, and snowshoeing into thriving industries, with specialized gear and dedicated vacation destinations. âFrom the outside, it looks like itâs a celebration of winter, but itâs really just what people do.â
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+When social psychologist Kari Leibowitz conducted research in Tromso and Svalbard, Norway, hundreds of miles north of the Arctic circle, she found residents had what she calls a âpositive wintertime mindsetâ: Rather than approaching the winter with dread, they tended to talk about what they were looking forward to, from sitting in front of a fire to skiing to watching the beautiful four-hour sunsets of the polar night. âThe winter is a really special time in Tromso,â said Leibowitz, author of the forthcoming bookHow to Winter: Harnessing Your Mindset to Embrace All Seasons of Life.
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+But as winters warm, many of the activities humans have developed to survive and thrive during the colder months are slowly vanishing. Skiing, for example, is becoming more difficult in Norway and around the world as rain replaces snow. Leibowitz said that she fears that climate change will leave Norway with the darkness of polar winter but none of its joys. âWe wonât have snow to reflect the light. We wonât have ice to make beautiful patterns. And we wonât have all of the recreational activities that come with snow and ice.â One study estimates that, in a worst-case scenario, the majority of US ski resorts will be unable before the centuryâs end.
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+The decline of sports like skiing has real economic and social effects, experts say. When the weather isnât cold, âpeople donât book vacations, they donât buy gear, they donât think about winter,â Hansman said. In towns that rely on skiing and other outdoor tourism, the entire economy can suffer.
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+In mountain towns in the US, the loss of a source of connection, meaning â and jobs â can also have psychological effects. âA lot of cold places in the Mountain West have remarkably high suicide rates and poor mental health outcomes,â Hansman said. âIf you donât have that sense of purpose, if you donât have that sense of community, if youâre not seeing your friends out and about, that can have a negative impact.â
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+The change to winter can also affect peopleâs sense of who they are. âIn Svalbard in the winter, you can snowmobile across the fjord to go camping, you can go ice climbing,â Leibowitz said. âIn Tromso, you can ski to work.â
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+âThese activities are a part of the fabric and culture of these countries,â she said. Losing them is âreally going to change peopleâs relationship with the places where they live.â
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+Experts sometimes use the terms climate grief and climate anxiety to capture the emotional impact of the current environmental crisis. In a 2005 paper, Albrecht described developing the term solastalgia to capture the pain expressed by residents of Australiaâs Hunter Region as they saw their local landscape scarred by open-pit coal mining. He combined the word nostalgia, which originally referred to an actual illness caused by displacement from oneâs home, with the concepts of solace and desolation.
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+Nostalgia for winter could help save it, some experts say
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+While the warming of winter still manifests in some parts of the world as a sneaking sense of something amiss, it has already reached crisis proportions across much of the Arctic and subarctic. In Alaska, for example, the disappearance of sea ice, habitat destruction, and disease caused by warming waters have made it difficult or impossible for indigenous hunters to catch marine mammals, a practice that has been their livelihood for thousands of years. âA relatively small temperature change in sea ice, and also in sea temperatures in the Arctic and subarctic, results in complete ecosystem collapse,â said Joan Naviyuk Kane, an Inupiaq poet and essayist who grew up in Alaska. For many of her friends and community members, âa subsistence lifestyle is no longer within reach.â
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+People who live and work in cold climates are finding ways to adapt to their new reality. In Alaska, some indigenous communities are learning reindeer herding from Sami practitioners, Kane said. When hunters can no longer rely on the sea, âsome of these land-based practices actually may help us continue to survive into the future,â she said.
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+For Kane, sorrow isnât a meaningful frame for thinking about the loss of peopleâs way of life. âIndigenous people can perform grief and perform our trauma endlessly if thatâs what non-Indigenous people want,â she said. But âby doing so weâre taking away time and energy and resources to engage our anger and to meaningfully enact policy change in the Arctic.â
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+Some experts believe that nostalgia for a vanishing winter can be harnessed to fight climate change, reaching people who havenât yet been personally affected by the crisis in more immediate ways. âFor a lot of people, recreation or a family vacation or the places where theyâre open to the environmentâ can provide a much more relatable, concrete example of the unfolding disaster than statistics about global temperature change, Hansman said. The group Protect Our Winters, for example, founded by pro snowboarder Jeremy Jones, brings together winter sports enthusiasts to reach out to voters and lobby lawmakers on climate issues. It is already making headway influencing legislation on renewable energy infrastructure and more.
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+Meanwhile, the long, chilly winters of yesteryear â and the way people responded to them â may still have something to teach us. Positive wintertime mindset is about adapting to your circumstances, both realistically and optimistically, Leibowitz said. That same can-do spirit can help us âthink about whatâs possibleâ when it comes to fighting climate change, she said.
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+âOur mindset can help empower us to see opportunities in difficult things,â and it can help us feel âinspired to work towards protecting winter,â Leibowitz said. âChanging our relationship with the darkness might inspire us to say, what else can I envision?â
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How a Yemeni rebel group is creating chaos in the global economy -
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+A screen grab captured from a video shows Yemenâs Houthi fightersâ takeover of the cargo ship Galaxy Leader in the Red Sea on November 20, 2023. | Houthi Movement via Getty Images
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+The Houthi attacks in the Red Sea, explained.
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+Container ship captains who make the run between Europe and Asia are about to become reacquainted with the Cape of Good Hope, making a long swing around Africa in a route that has been largely obsolete since the opening of the Suez Canal more than 150 years ago.
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+Since mid-November, Houthi rebels in the Middle Eastern country of Yemen have been attacking shipping in the Red Sea, firing drones and missiles and, in some cases, boarding and seizing vessels. The Houthis, who are backed by Iran, say the attacks are in solidarity with their Palestinian allies in Hamas. In response, most of the worldâs largest container-shipping companies â including Denmarkâs Maersk, Germanyâs Hapag-Lloyd, and Chinaâs Cosco â have stopped shipments through the Red Sea. The oil company BP is doing so as well. An estimated 7 million barrels of oil normally travel through the sea per day.
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+Itâs an unexpected consequence of the two-month-old Israel-Hamas war, which is rapidly escalating into a wider conflict with both regional and global ripple effects.
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+âThe impact is no longer on one country,â Noam Raydan, a Middle East shipping analyst at the Washington Institute for Near East Policy, told Vox. âNow, it is global.â
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+These reroutes will add thousands of miles and days of travel time to their journey, costing companies millions of dollars in extra fuel and other costs. While there are still ships braving the Red Sea, the tracking site VesselFinder shows that many have their transponders set to broadcast that they are carrying armed guards on board.
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+US, French, and British ships in the region have been shooting down dozens of Houthi drones, but Western governments have come under pressure to do more to protect global shipping. On Tuesday, the US announced the formation of a 10-country naval task force to protect shipping in the region. Biden administration officials are also reportedly considering operations for direct military strikes against the Houthis.
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+But there appears to be no easy way out of the crisis, which shows how a confluence of geography, economics, technology, and geopolitics can allow a relatively small rebel group to cause a surprising amount of havoc on the global economy.
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+Who are the Houthis?
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+They call themselves Ansar Allah, but the Houthis are more frequently referred to by the name of their founder, Hussein al-Houthi. Members of a minority Shia Muslim sect in northern Yemen, they emerged as a rebel group fighting the government of Yemeni dictator Ali Abdullah Saleh in the 1990s. Saleh was ultimately overthrown amid Arab Springâlinked protests in 2012, and the Houthis took advantage of the ensuing power vacuum to seize the capital, Sanaa, in 2014. They still hold the capital today but are generally not recognized by the international community as Yemenâs legitimate government.
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+Since 2014, Yemen has endured a brutal civil war that pitsthe Houthis â who receive substantial funding and weaponry from Iran â against Yemenâs internationally recognized government and an international coalition led by Saudi Arabia (and supported by the United States). As of last year, the United Nations estimated that the nearly decade-old war has killed more than 377,000 people â most due to malnutrition, unsafe water, and poor medical services, all exacerbated by conflict â though the violence has died down since a UN-brokered ceasefire in 2022. Today, the Houthis control about one-third of Yemenâs territory and 70 percent of its population.
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+To the extent that the outside world has paid attention to the war, the focus has mainly been on the humanitarian crisis and Americaâs controversial backing of the Saudis. But as the recent events in the Red Sea demonstrate, the Houthisâ war in Yemen isnât staying in Yemen.
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+Globalizing the conflict
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+The Houthis have never exactly been subtle about their geopolitical views. The groupâs official slogan is âGod is great, death to the US, death to Israel, curse the Jews, and victory for Islam.â But until now, outsiders have mostly thought of them as a concern only in their native Yemen.
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+Fatima Abo Alasrar, a Yemeni political analyst at the Middle East Institute in Washington, DC, told Vox that policymakers outside Yemen have underestimated the Houthisâ international goals because âtheyâve never tried to act as boldlyâ as they are now, but Houthi propaganda has always played up what they see as the Saudisâ too-friendly relations with Israel. Theyâve told their fighters, whose ranks include a substantial number of child soldiers, that they are fighting a war against the US and Israel for control of Yemen. Now, Alasrar says, âtheyâre putting their money where their mouth is.â
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+Following the October 7 Hamas attacks and the Israeli military operation in Gaza that followed, Iran-backed armed groups throughout the region â which some refer to collectively as the Axis of Resistance and which also include Lebanonâs Hezbollah and various militias in Iraq and Syria â have all stepped up their attacks on Israel and on US military targets. (The government of Iran itself, by contrast, has made clear it doesnât plan to intervene directly with its own forces.)
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+Of all these groups, the Houthisâ actions in the conflict have in some ways been the most audacious, if only because of their physical distance from the fighting. Since October, the Houthis have been regularly firing missiles and drones at Israel, which sits more than 1,000 miles from Yemen. The Houthis have previously attacked targets in Saudi Arabia and the United Arab Emirates with missiles, but the launches against Israel â which have all been intercepted so far, either by Israeli missile defenses or US naval ships in the Red Sea â are by far their longest-range strikes.
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+On November 19, helicopter-borne Houthi rebels boarded and seized the Galaxy Leader, a cargo ship partially owned by an Israeli businessman. The ship is still being held off the coast of Yemen, its crew held hostage and allowed only âmodest contactâ with the outside world. Since then, there have been attacks of various degrees against at least 12 different commercial vessels, most of them with little or no direct connection to Israel.
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+Some of these attacks have demonstrated startling technical capabilities, including what may be the first-ever combat use of an antiship ballistic missile by any military. These missiles, which travel at much higher altitudes and greater speeds than cruise missiles, could dramatically extend the range at which militaries can strike enemy ships and render many existing defenses obsolete. The models used by the Houthis appear to be somewhat less sophisticated than those tested by countries like China and rely on drones for spotting.
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+A critical chokepoint
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+About 12 percent of global trade and 10 percent of the maritime oil trade passes through the Red Sea, a body of water defined by two chokepoints: to the north, Egyptâs Suez Canal, and to the south the Bab al-Mandab, or âGate of Tears,â a strait between Yemen and Djibouti on the east coast of Africa that is about 20 miles wide at its narrowest point and where making of the attacks are taking place.
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+âThis is a chokepoint on the most densely used trade route on the planet,â said Sal Mercogliano, a former merchant mariner and shipping historian. âAny disruption is going to impact the entire supply chain.â
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+The route has been cut off before, most recently in 2021 when the container ship Ever Given ran aground in the Suez Canal, blocking traffic for a week. The current disruption, though, has the potential to last much longer, with much more serious consequences.
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+Some countries may feel the impact directly, such as the cash-strapped government of Egypt, which earns more than $9 billion a year from Suez Canal transit fees. But given the complex web of global trade woven by maritime shipping, other nations will experience knock-on effects.
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+Rachel Ziemba, an energy and economics analyst at the Center for a New American Security, pointed out that the disruption comes at a time when many European economies have been forced to increase their reliance on shipborne oil and natural gas, much of it from the Middle East, in an effort to wean themselves off Russian pipelines. Russia, meanwhile, has increased its own oil exports to India, China, and other markets in Asia â and much of that oil travels by ship through the Red Sea as well. âIf anything, when it comes to shipping, thereâs been more reliance on shipping rather than less,â said Ziemba.
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+The crisis couldnât come at a worse time for the global shipping industry, which is in a slump as global industrial output flatlines and post-pandemic consumer demand normalizes. The issue for shippers is not just the risk to their vessels, cargo, and crews, but also the cost of insuring against that risk. The war risk premiums charged by insurance companies for shipping in the Red Sea have already jumped from around 0.07 percent of a shipâs value in early December to around 0.5 percent now. Considering that oil tankers can be valued in the hundreds of millions of dollars, these premiums could make Red Sea shipping prohibitively expensive if they rise further.
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+The Bab al-Mandab is also not the only global shipping chokepoint under stress. The Panama Canal is currently operating at reduced capacity due to low water levels caused by a historic drought, which limits the number of ships that can pass through. Analysts are also concerned that the turmoil in the Middle East could affect the Strait of Hormuz, the gateway to the Arabian Sea between Iran and the UAE. Given its importance as a route for oil shipments, that could have a much more significant impact on energy prices.
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+âIt really only highlights the importance of having different supply chains, of having the ability to redirect,â Ziemba said. But the costs of developing these alternatives are starting to add up.
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+Firing back
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+Global shippers have been leading the calls for global governments to do something about the Houthis. In a striking recent editorial, Lloydâs List, the leading journal of the shipping industry, drew explicit comparisons to the use of the British Navy to protect shipping during the 19th century, writing, âLet gunboat diplomacy be confined to the past. But there are legitimate uses of gunboats in the 21st century; the continued flow of world trade is one of them.â
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+On Monday, Defense Secretary Lloyd Austin announced the formation of Operation Prosperity Guardian, a multinational naval mission meant to protect shipping in the area. But itâs still unclear how large this task force will be or how it will operate. âI donât think youâll see World War IIâstyle convoys escorting ships,â said Mercogliano. The scale of shipping involved makes such escorts implausible. âYouâre more likely to see naval vessels basically putting themselves between Yemen and the main shipping channel and acting like gatekeepers.â
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+The coalition, which includes a number of European countries as well as Bahrain and the Seychelles â a small island nation of just 100,000 people â also has some notable absences. Missing is China, which has a military base in nearby Djibouti and is heavily reliant on importing Middle Eastern oil and exporting consumer goods to Europe via ship. Beijing has been playing a more active role in the regionâs politics lately, including brokering a historic diplomatic deal between Saudi Arabia and Iran earlier this year, while Hong Kong-flagged container ships have been among those attacked. Yet while the US and Chinese navies have collaborated in the region before, including in efforts to combat Somali piracy a decade ago, geopolitical tensions between the two nations are much higher now. Far from Beijing joining the multinational task force, the Pentagon has accused Chinese naval vessels of ignoring a distress call from an Israeli-owned tanker that came under attack in late November.
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+Another missing country: Saudi Arabia, which is all the more surprising given that the country has been fighting the Houthis for years. But Saudi leaders, who recently have been taking steps to disentangle themselves from the bloody and costly Yemen conflict and have hosted several rounds of peace talks with the Houthis, have reportedly urged the US to show restraint in responding to the shipping attacks.
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+Alasrar suggests Saudi leaders are likely still resentful over what they see as a lackluster response by Washington to Houthi and Iranian attacks on Saudi and Emirati oil facilities in recent years. âAt this point, the Saudis are probably more interested in being a spectator because the Houthis are addressing Israel and the United States more directly,â she said. The Saudis are ânot interested in escalating because it hasnât gotten them anywhere.â
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+In addition to the new task force, the US has moved the Dwight D. Eisenhower carrier strike group to waters near Yemen to support a possible further US response to the attacks. Politico recently reported that Biden administration officials have been weighing options to strike back against Houthi targets in Yemen itself.
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+There is some precedent. In 2016, under President Obama, the US launched Tomahawk missiles at three Houthi radar sites in response to a previous round of Houthi attacks on US Navy ships in the region. The US has also launched hundreds of drone strikes on suspected terrorist targets in Yemen over the past two decades. But it would represent something of a reversal for the Biden administration, which announced a halt to US support for the Saudi-led coalition in Yemen as one of its first foreign policy actions back in 2021 and has been scaling back the US drone war as well.
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+The Houthis, for their part, say they are undeterred by the new task force, with a spokesperson telling the Washington Post, âOur war is a moral war, and therefore, no matter how many alliances America mobilizes, our military operations will not stop.â
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+However the situation resolves, it could have lasting repercussions far beyond the Red Sea. The global economy remains as reliant on shipping as ever â it accounts for around 80 percent of global trade. And between the disruption of grain shipping through the Black Sea as a result of Russiaâs naval blockade of Ukraine and the Houthisâ operations in the Red Sea, recent years have given ample demonstration of how armed conflict can disrupt that trade.
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+More disruptions may loom. Last year, in response to a visit to Taiwan by then-House Speaker Nancy Pelosi, Chinaâs navy conducted live-fire drills around the island, effectively blockading international shipping lanes for several days. There are growing fears that China could enact a longer blockade, either in the lead-up to a full-scale war on Taiwan or instead of one.
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+Mercogliano says recent events have upended assumptions about the balance of naval power. âWe saw what the Ukrainians could do to the Russian Black Sea fleet without an advanced navy,â he said, referring to Moscowâs decision to mostly withdraw the fleet from its traditional base in Crimea after a slew of attacks by Ukrainian aerial and maritime drones. âNow weâre seeing what the Houthis can do without any navy at all. Now, imagine what a Taiwan scenario would look like.â
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+The Houthis will likely struggle to respond to a true US-led response, but their audacity â and their strategy â could also be offering a preview of greater disruptions to come.
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Big Wool wants you to believe itâs nice to animals and the environment. Itâs not. -
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+Lambs several days after birth at a sheep farm in Poland. | Andrew Skowron / We Animals Media
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+Woolâs cozy image masks a polluting, violent reality.
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+But thereâs one big domain of livestock production that is often seen as exempt from the hard trade-offs of farming animals for human consumption: animals raised for clothing, like the more than 1.2 billion sheep farmed for wool, or the tens of millions of cows whose skin is processed into leather. Both species, as ruminants, emit massive volumes of methane (the potent greenhouse gas that is responsible for about a quarter of global warming) and take up vast land areas that could otherwise host native, carbon-sequestering ecosystems.
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+According to one analysis of wool production in Australia, by far the worldâs top exporter, the wool required to make one knit sweater is responsible for 27 times more greenhouse gases than a comparable Australian cotton sweater, and requires 247 times more land. Sheep farming threatens native species around the world, from koalas in Australia to sage grouse in the US. Domesticated sheep in the American West have, as my colleague Paige Vega has reported, been implicated in mass die-offs of their wild cousins, Rocky Mountain bighorn sheep, through the spread of the lethal pathogen Mycoplasma ovipneumoniae.
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+Ruminant farmingâs hunger for land has made it a prime engine for colonial expansion around the world; we see this in Brazil, for example, where cattle ranching is driving illegal seizures of Indigenous land. Sheep brought by colonists to Australia âimmediately trampled and destroyed all of the native yams and edible vegetables that Aboriginal people had. The land that Aboriginal people never ceded was taken for pastoral practices,â said Emma Hakansson, the Australia-based founding director of Collective Fashion Justice, which advocates for what she calls a âtotal ethicsâ fashion system: one thatâs fair to people, animals, and the planet. âAnimal-derived materials in particular are a focus for us because itâs in those supply chains that all three of those groups are consistently harmed.â
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+Yet animal-based textiles benefit froma natural, planet-friendly image. Itâs still common to see media and the industry itself misleadingly report that animal-based fabrics are just a byproduct of meat production that would otherwise be thrown in the trash and that itâs better for the environment to use them â a claim that obfuscates the economy of animal production.
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+âWool and leather are not byproducts of meat production, theyâre co-products: producers support their livestock operations by selling meat as well as wool and hides, all of which keeps them afloat,â Matthew Hayek, an assistant professor of environmental studies at New York University, told me in an email.
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+Wool in particular evokes biblical scenes of sheep farming that are especially conspicuous during the Christmas season. Itâs âa mass-market commodity that operates stealthily under many layers of mythology, from legends of the golden fleece to bucolic images of sheep peacefully grazing in open pasture,â as a 2021 report by the Center for the Biological Diversity and Collective Fashion Justice put it. âBut wool is not a fiber simply provided by nature â it is a scaled product of modern industrial, chemical, ecological and genetic intervention thatâs a significant contributor to the climate crisis, land degradation, water use, pollution and biodiversity loss.â
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+Although wool shearing is widely misperceived as merely a benign âhaircutâ for sheep, the modern sheep industry, like all industries that mass produce animals, is egregiously violent. Sheep are subjected to painful mutilations like tail docking and mulesing, a procedure in which skin from their hindquarters is cut off to prevent flystrike, a parasitic infection the animals are prone to because of how theyâve been bred.
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+Some brands and certificationprograms have banned mulesing in their supply chains, but that practice just skims the surface of the industryâs cruelty. Many appalling undercover videos of wool production haveemerged over the years, showing sheep beaten and wounded by clippers as workers restrain them and shear off their hair as quickly as possible. Eventually, theyâre sent to slaughter.
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+ Zuzana Mit / We Animals Media
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+A sheep is sheared at a dairy farm in Slovakia.
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+The lesser of two evils?
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+Wary of climate regulation, wool producers are embracing the same greenwashing diversions as the meat industry â they are, after all, the same industry. Misleading âregenerative woolâ claims â a phrase that âlacks any standard definitions or accountability,â as a 2023 report by the Center for Biodiversity and Collective Fashion Justice put it â have proliferated at progressive-coded fashion brands like Allbirds, Everlane, and Reformation.
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+Many (though by no means all) of the alternatives to wool on the market are made of fossil fuel-based synthetic materials like polyester, acrylic, and nylon. These materials have their own terrible externalities, contributing to carbon emissions and microplastic pollution, the effects of which weâre only beginning to comprehend. Fabrics like wool contribute to this problem, too, when theyâre coated in dyes that release microplastics, and wool generates significant chemical pollution through scouring â the highlypolluting, detergent-intensive process used to remove the grease from sheepâs hair.
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+While thereâs an increasing variety of novel, low-resource, plant-based alternatives (Hakansson points to Tencel, a silky smooth fabric made of wood pulp, hemp, and recycled materials), the fashion industry largely lacks the incentive to invest in these at scale. Until better options become more widely accessible, consumers who decide to buy new clothes for the winter are often choosing between animal fibers or synthetic ones.
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+âBoth cause harm. Deforestation, wild habitat loss, emissions, overgrazing, and erosion for wool, and fossil fuel extraction and microplastic pollution for polyester,â Hayek pointed out. âThe most climate-compatible system of making materials such as clothing fibers involves moving away from both fossil fuels and over-abundant animal production.â
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+But we live in a world of trade-offs, and the planetary impacts of wool and synthetics have to be considered in comparison to one another, not in a vacuum. On that score, wool consistently ranks worse than synthetics.
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+âWe know from data across the wool industry, the leather industry, the fur industry, that synthetic alternatives almost always have a significantly lower climate impact,â Hakansson said (though her organization still rightly campaigns to end the fashion industryâs dependence on fossil-based synthetics).
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+To name just one example, a 2021 study using data from the Swiss sustainability assessment nonprofit Ecoinvent found that wool had far higher greenhouse gas emissions than alternatives for the same amount of fabric, including nearly nine times more than polyester. This, combined with the dreadful animal welfare consequences of wool farming, makes the choice between a wool coat and a long-lasting synthetic one very clear. The same is true of leather, which has truly atrocious environmental impacts versus its synthetic alternatives (and there are now far better leather alternatives, made from plants like cactus, apple, and pineapple).
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+But the problem goes deeper than wool versus synthetics because these industries have made good bedfellows. Widespread cheap synthetics have enabled fast fashion, making it possible for brands to produce stupefying volumes of disposable fabrics. These are now very commonly combined with wool to create hybrid garments. According to the Center for Biodiversity and Collective Fashion Justiceâs recent analysis of 13 top clothing brands, more than half of wool items were blended with synthetics, giving them in-demand properties like machine washability â meaning, in other words, that synthetics are being used to enhance the appeal of wool.
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+Itâs unfortunate, in this context, to see fashion critics who ought to know better fetishize unadulterated animal fibers instead of thinking clearly about their outsize role in a many-layered harmful system. âThe climate, biodiversity and ethical impacts of the wool and cashmere industries are so poorly understoodâ in fashion circles, Hakansson said in an email. One prominent fashion influencer, for example, when asked which fabrics were the most ethical, recently said that ânaturalâ fibers (including animal ones like wool) were best because theyâre biodegradable.
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+This is sometimes true, though not always â it depends on how the fabric is processed, for example, as wool made with certain dyes or coated with plastic is rendered not biodegradable. But a contextless statement about biodegradability is more misleading than useful in helping people understand the full picture of how their clothing affects the environment. So itâs not surprising that the public is just as confused about the impacts of animal-based garments; a 2017 global consumer survey, for example, found that 87 percent of respondents believed wool is âsafe for the environment,â and more than half said it was âsustainably produced.â
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+Our naturalistic fantasies
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+Several times this year, after suffering through lectures by various influencers extolling animal fibers, I thought back to a widely discussed piece by data scientist Hannah Ritchie on the naturalistic fallacies that pervade popular understanding of whatâs good for the planet. âWeâre skeptical of synthetic stuff that comes out of a factory,â she wrote, while we find virtue in things that seem natural or primordial. For example, consumers are consistently more likely to say that eating locally grown food instead of food shipped across the world is better for the planet than eating less meat, even though decidedly the opposite is true.
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+Iâd take Ritchieâs point a step further. Perceptions of the natural donât emerge from nowhere; theyâre invented and marketed. And animal agribusiness is especially good at selling a folksy image that masks the industryâs violence and environmental destruction.
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+In the minds of many consumers, the wool industry has naturalized itself with the idea that weâre doing sheep a favor by shearing off their hair, a myth so persistent that itâs become lodged in the minds of even some people who think about animal ethics for a living. âSheep that are not regularly shorn, as theyâve now evolved to be, suffer from having their heavy coat dragging them down,â philosopher Martha Nussbaum, who recently wrote a book on what we owe nonhuman animals, told the Boston Review in defense of wool earlier this year.
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+Nussbaumâs account has it entirely backward. Sheep were bred by humans to overproduce hair, they didnât evolve that way â and unlike wild animals, domesticated sheep donât simply reproduce without human management. Theyâre products, brought into the world by agribusiness according to demand for their hair, milk, and meat, and with exactly as much regard for their welfare as will maximize profit. We could choose to simply stop breeding them and restore native ecosystems in their place.
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+ Jo-Anne McArthur / We Animals Media
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+A worker with an electric prod loads sheep, purchased at an auction sales yard, onto a transport truck in Australia. Theyâll be taken to slaughter, to a new farm, or shipped overseas.
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+Other animal wools, like goat and alpaca, are smaller industries than sheep, âbut on the basis of each spool of wool being produced, they all cause pretty comparable greenhouse gas emissions,â Hayek said. Theyâre also no lesscruel.
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+While defenders of animal-based materials often claim that theyâre higher quality from a consumer perspective than synthetics and therefore less likely to end up in a landfill, this is not the whole picture. The manufacturing process and treatment of workers, not just the material itself, affect the quality of a garment. If you know where to look, there are plenty of durable, warm, stylish, animal-free fabrics on offer (like the Canadian outerwear brand Noize, which, in my anecdotal experience, is universally beloved by people who avoid animal fibers.) Innovative plant-based fabrics like vegetable cashmere, made from soybeans, are also on the rise.
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+We still, in the end, have to wear clothes. So what should we wear? In a reasonable world, ordinary people wouldnât have to exhaust themselves sifting through contradictory sustainability claims because fast fashion and animal agriculture would bewell-regulated. But in this world, we have to use our judgment. And we have to be extremely skeptical of letting nostalgic appeals to nature commandeer our ethical reasoning.
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+With 100 billion new garments manufactured globally every year and overwhelming volumes of discarded clothing, both Hayek and Hakansson stressed that the best option is to buy a lot less clothing overall, and buy used when possible. âHow much raw material production do we really need?â Hakansson said. âIf people are desperate to have a product like wool, you should be buying it secondhand.â There are also coats made from post-consumer recycled synthetics, which she opts for to keep warm.
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+âTheyâre not necessarily perfect,â she said, âbut we need to be at least making the best decision we can. And animal-derived materials across the board fail to meet what should be considered best practice.â
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Legendary Striker, Crown Angel, Pacific and Raffinato work well -
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Rieko, Exceed and Philosophy shine -
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Enabler, Magileto and Constable catch the eye -
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Sakshi Malik quits wrestling after Brij Bhushan loyalist Sanjay Singh becomes WFI chief - âWe fought from our heart but if a man like Brij Bhushan, his business partner and a close aide is elected as the president of WFI, I quit wrestling,â said a teary-eyed Olympic medal winner Sakshi Malik
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Birj Bhushan loyalist Sanjay Singh becomes new Wrestling Federation of India president - Devender Singh Kadian, who runs a chain of food joints on National Highways and is considered to be close to protesting wrestlers, claimed the senior vice presidentâs post
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From The Hindu: National News
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Three-day build tech expo in Dharwad from tomorrow -
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âNeruâ movie review: Jeethu Joseph-Mohanlal courtroom drama almost delivers a cathartic high - Mohanlal is back to form with an understated performance while Jeethu Joseph has found his mojo in this mostly riveting legal drama
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BMP-II infantry combat vehicles finish floatation trials at Malkapur lake -
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Advisory on water safety put out for rain-hit southern districts - Residents have been asked to only use boiled and cooled water or chlorinated water for drinking and cooking
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Here are the big stories from Karnataka today - Welcome to the Karnataka Today newsletter, your guide from The Hindu on the major news stories to follow today.
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From BBC: Europe
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European Super League: Uefa and Fifa rules banning breakaway league unlawful, says court - Uefa and Fifa rules banning clubs joining breakaway competitions like the European Super League are unlawful, the European Court of Justice rules.
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How pro-Russian âyachtâ propaganda influenced US debate over Ukraine aid - A false rumour spread by a dubious AI-powered website caught the attention of leading politicians.
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Ukraine war: Male citizens living abroad to be asked to join army - The defence minister says Kyiv is considering sanctions for those who do not comply.
Tide turns for Channel smugglers but the migrant crossings go on - UK funds have helped French police drive down the number of small boat crossings - but not stop them.
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From Ars Technica
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Great British Bake Offâs festive Christmas desserts arenât so naughty after all - Study: Several ingredients actually reduce rather than increase risk of death or disease. - link
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For the first time, ULAâs Vulcan rocket is fully stacked at Cape Canaveral - A lunar lander from Intuitive Machines is still waiting for a SpaceX launch slot. - link
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7.1 million miles, 3 minor injuries: Waymoâs safety data looks good - Waymo says its cars cause injuries six times less often than human drivers. - link
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Lian Li has discovered a new frontier for LCD screens: $47 PC case fans - 120 and 140 mm fans can add to the blinding glow of your gaming PCâs RGB setup. - link
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Wireless TVs use built-in cameras, NFC readers to sell you stuff you see on TV - TV makers are getting more aggressive about using their hardware for ads. - link
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From Jokes Subreddit
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