Viral interference between severe acute respiratory syndrome coronavirus 2 and influenza A viruses -
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+Some respiratory viruses can cause a viral interference through the activation of the interferon (IFN) pathway that reduces the replication of another virus. Epidemiological studies of coinfections between SARS-CoV-2 and other respiratory viruses have been hampered by non-pharmaceutical measures applied to mitigate the spread of SARS-CoV-2 during the COVID-19 pandemic. With the ease of these interventions, SARS-CoV-2 and influenza A viruses can now co-circulate. It is thus of prime importance to characterize their interactions. In this work, we investigated viral interference effects between an Omicron variant and a contemporary influenza A/H3N2 strain, in comparison with an ancestral SARS-CoV-2 strain and the 2009 pandemic influenza A/H1N1 virus. We infected nasal human airway epitheliums with SARS-CoV-2 and influenza, either simultaneously or 24 h apart. Viral load was measured by RT-qPCR and IFN-/{beta}/{lambda}1/{lambda}2 proteins were quantified by immunoassay. Expression of four interferon-stimulated genes (ISGs; OAS1/IFITM3/ISG15/MxA) was also measured by RT-droplet digital PCR. Additionally, susceptibility of each virus to IFN-/{beta}/{lambda}2 recombinant proteins was determined. Our results showed that influenza A, and especially A/H3N2, interfered with both SARS-CoV-2 viruses, but that SARS-CoV-2 only interfered with A/H1N1. Consistently with these results, influenza, and particularly the A/H3N2 strain, caused a higher production of IFN proteins and expression of ISGs than SARS-CoV-2. The IFN production induced by SARS-CoV-2 was marginal and its presence during coinfections with influenza was associated with a reduced IFN response. All viruses were susceptible to exogenous IFNs, with the ancestral SARS-CoV-2 and Omicron being less susceptible to type I and type III IFNs, respectively. Thus, influenza A causes a viral interference towards SARS-CoV-2 most likely through an IFN response. The opposite is not necessarily true, and a concurrent infection with both viruses leads to a lower IFN response. Taken together, these results help us to understand how SARS-CoV-2 interacts with another major respiratory pathogen.
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Development of a cell-based DIFF-rGFP assay system for generalized discovery of viral protease Inhibitors -
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+Viral protease is an attractive target for antiviral therapeutics, but current viral protease inhibitor screening methods still need to be improved. Here, we systematically investigated the sites that may accommodate exogenous short peptides within Enhanced Green Fluorescent Protein (EGFP)and constructed a series of recombinant green fluorescent proteins (rGFPs). Meanwhile, a cell-based, simple and reliable assay system named DIFF-rGFP was developed relying on the co-expression of rGFP and the protease for protease inhibitor screening with the example of 3CLpro, in which the fluorescence intensity increases with the action of the inhibitor. The DIFF-rGFP assay avoided the requirement of a higher biosafety lab and can be performed in a high-throughput manner. For proof of concept, we demonstrated this method to discover novel inhibitors against SARS-CoV-2. We believe the proposed method, in combination with available drug libraries, may accelerate the identification of novel antivirals.
+
OpenSAFELY: a platform for analysing electronic health records designed for reproducible research -
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+Electronic health records (EHRs) and other administrative health data are increasingly used in research to generate evidence on the effectiveness, safety, and utilisation of medical products and services, and to inform public health guidance and policy. Reproducibility is a fundamental step for research credibility and promotes trust in evidence generated from EHRs. At present, ensuring research using EHRs is reproducible can be challenging for researchers. Research software platforms can provide technical solutions to enhance the reproducibility of research conducted using EHRs. In response to the COVID-19 pandemic, we developed the secure, transparent, analytic open-source software platform OpenSAFELY designed with reproducible research in mind. OpenSAFELY mitigates common barriers to reproducible research by: standardising key workflows around data preparation; removing barriers to code-sharing in secure analysis environments; enforcing public sharing of programming code and codelists; ensuring the same computational environment is used everywhere; integrating new and existing tools that encourage and enable the use of reproducible working practices; and providing an audit trail for all code that is run against the real data to increase transparency. This paper describes OpenSAFELY’s reproducibility-by-design approach in detail.
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Recapitulating memory B cell responses in a Lymphoid Organ-Chip to evaluate mRNA vaccine boosting strategies -
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+Predicting the immunogenicity of candidate vaccines in humans remains a challenge. To address this issue, we developed a Lymphoid Organ-Chip (LO chip) model based on a microfluidic chip seeded with human PBMC at high density within a 3D collagen matrix. Perfusion of the SARS-CoV-2 Spike protein mimicked a vaccine boost by inducing a massive amplification of Spike-specific memory B cells, plasmablast differentiation, and Spike-specific antibody secretion. Features of lymphoid tissue, including the formation of activated CD4+ T cell/B cell clusters and the emigration of matured plasmablasts, were recapitulated in the LO chip. Importantly, myeloid cells were competent at capturing and expressing mRNA vectored by lipid nanoparticles, enabling the assessment of responses to mRNA vaccines. Comparison of on-chip responses to Wuhan monovalent and Wuhan/Omicron bivalent mRNA vaccine boosts showed equivalent induction of Omicron neutralizing antibodies, pointing at immune imprinting as reported in vivo. The LO chip thus represents a versatile platform suited to the preclinical evaluation of vaccine boosting strategies.
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Stratification of viral shedding patterns in saliva of COVID-19 patients -
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+Living with COVID-19 requires continued vigilance against the spread and emergence of variants of concern (VOCs). Rapid and accurate saliva diagnostic testing, alongside basic public health responses, is a viable option contributing to effective transmission control. Nevertheless, our knowledge regarding the dynamics of SARS-CoV-2 infection in saliva is not as advanced as our understanding of the respiratory tract. Here we analyzed longitudinal viral load data of SARS-CoV-2 in saliva samples from 144 patients with mild COVID-19 (a combination of our collected data and published data). Using a mathematical model, we successfully stratified infection dynamics into three distinct groups with clear patterns of viral shedding: viral shedding durations in the three groups were 11.5 days (95% CI: 10.6 to 12.4), 17.4 days (16.6 to 18.2), and 30.0 days (28.1 to 31.8), respectively. Surprisingly, this stratified grouping remained unexplained despite our analysis of 47 types of clinical data, including basic demographic information, clinical symptoms, results of blood tests, and vital signs. Additionally, we quantified the expression levels of 92 micro-RNAs in a subset of saliva samples, but these also failed to explain the observed stratification, although the mir-1846 level may have been weakly correlated with peak viral load. Our study provides insights into SARS-CoV-2 infection dynamics in saliva, highlighting the challenges in predicting the duration of viral shedding without indicators that directly reflect an individual's immune response, such as antibody induction. Given the significant individual heterogeneity in the kinetics of saliva viral shedding, identifying biomarker(s) for viral shedding patterns will be crucial for improving public health interventions in the era of living with COVID-19.
+
Adaptive Regularized Tri-Factor Non-Negative Matrix Factorization for Cell Type Deconvolution -
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+Motivation: Accurate deconvolution of cell types from bulk gene ex- pression is crucial for understanding cellular compositions and uncovering cell-type specific differential expression and physiological states of diseased tissues. Existing deconvolution methods have limitations, such as requiring complete cellular gene expression signatures or neglecting partial biological information. Moreover, these methods often overlook varying cell-type mRNA amounts, leading to biased proportion estimates. Additionally, they do not effectively utilize valuable reference information from external studies, such as means and ranges of population cell-type proportions. Results: To address these challenges, we introduce an Adaptive Regular- ized Tri-factor non-negative matrix factorization approach for deconvolution (ARTdeConv). We rigorously establish the numerical convergence of our algorithm. Through benchmark simulations, we demonstrate the superior per- formance of ARTdeConv compared to state-of-the-art reference-free methods. In a real-world application, our method accurately estimates cell proportions, as evidenced by the nearly perfect Pearson’s correlation between ARTdeConv estimates and flow cytometry measurements in a dataset from a trivalent influenza vaccine study. Moreover, our analysis of ARTdeConv estimates in COVID-19 patients reveals patterns consistent with important immunological phenomena observed in other studies. Availability and implementation: The proposed method, ARTdeConv, is implemented as an R package and can be accessed on GitHub for researchers and practitioners at https://github.com/gr8lawrence/ARTDeConv. Keywords: Cell-type deconvolution, Convergence analysis, Multiplicative update algorithm, Non-negative matrix factorization, RNA sequencing, Single cell data
+
The pandemic’s comparative impact on constitutional checks and balances within the EU -
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+COVID-19 has changed public and private live significantly. Some changes remain permanently. Although COVID-19 is no longer an immediate global health crisis, which has brought healthcare systems in particular close to collapse, the impact on social and economic systems is still being felt. Despite government subsidies, many companies have not survived the effects of the crisis. In addition, many people’s working lives and education have changed. Digital tools, such as online meetings and the option to work from home, are now part of everyday life, unlike before the pandemic. During the pandemic, short-term and fast-acting measures were necessary, which had to be issued by the various powers in special procedures. In most countries, the executive branch took on a central role in order to ensure the ability to act. At the same time, the legislative powers were restricted in their mode of operation. Plenary sessions of the parliaments could only be held to a very limited extent. The measures taken must be reviewed in terms of their effectiveness, but also in terms of their impact on constitutional checks and balances, in order to be able to take more effective, proportionate and constitutional measures for future pandemics. This research paper thus analyses and discusses the consequences of pandemic crisis measures on constitutional democracy in a number of European countries—in particular Germany, France, the UK, Italy, Sweden—, by examining the effects of Covid-19 measures on constitutional checks and balances, and the relations between the executives and legislatures. With a glimpse over the Atlantic some actions will be compared to those on US federal as well as state level.
+
Simultaneous Identification of Changepoints and Model Parameters in Switching Dynamical Systems -
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+Many complex natural systems undergo shifts in dynamics at particular points in time. Examples include phase transitions in gene expression during the cell cycle, introduced species affecting predator-prey interactions, and disease outbreaks responding to intervention measures. Such changepoints partition timeseries into different dynamical regimes characterized by distinct parameter sets, and inference on both the changepoints and regime-specific dynamical parameters is of primary interest. Conventional approaches to analyzing switching dynamical systems first estimate changepoints, and then estimate dynamical parameters assuming the changepoints are fixed and known. Such two-stage approaches are ad-hoc, can introduce biases in the analysis, and do not fully account for uncertainty. Here, we introduce a rigorous, simulation-based inference framework that simultaneously estimates changepoints and model parameters from noisy data while admitting full uncertainty. We use simulation studies of oscillatory predator-prey dynamics and stochastic gene expression to demonstrate that our method yields accurate estimates of changepoints and model parameters together with appropriate uncertainty bounds. We then apply our approach to a real-world case study of COVID-19 intervention effects, and show that our inferred changepoints aligned closely with the actual dates of intervention implementation. Taken together, these results suggest that our framework will have broad utility in diverse scientific domains.
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The Effect of COVID-19 on Home Advantage in High- and Low-Stake Situations: Evidence from the European National Football Competitions -
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+The Covid-19 pandemic has significantly altered the way sporting events are observed. With the absence or limited presence of spectators in stadiums, the traditional advantage enjoyed by home teams has diminished considerably. This underscores the notion that the support of home fans can often be considered a key factor of the home advantage (HA) phenomenon, wherein teams perform better in front of their own supporters. However, the impact of reduced attendance on games with higher stakes, as opposed to low-stakes friendly matches, remains uncertain. In this study, we investigate the recently concluded European football championship (EURO 20), wherein several teams had the advantage of playing at home in high-stakes games with only one-third of the stadium capacity filled. Firstly, we demonstrate that the Covid-19 restrictions, leading to reduced fan attendance, resulted in a nearly 50% decrease in HA compared to the HA exhibited by the same teams during the qualification stage preceding EURO 20, even after accounting for team strength. Secondly, we show that while low-stakes friendly matches generally exhibit a smaller overall HA compared to high-stakes games, the absence of fans led to a similar reduction in HA during the low-stakes matches. Utilizing the recently developed Home Advantage Mediated (HAM) model (Bilalić et al., 2021, Scientific Reports, 21558), we were able to attribute the reduction in both high- and low-stakes games to poorer team performance, with no significant contribution from referee bias.
+
Young people’s condom use during the COVID-19 pandemic: Cross-cultural differences and what predict them -
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+According to the Behavioural Immune System (BIS) theory, humans are motivated to avoid exposure to harmful pathogens. However, most sources of infection are impossible to avoid completely, leading to the development of tools to reduce pathogen threat. Condoms are one example of an effective tool that can be used to avoid exposure to sexually transmitted infections (STIs). Within this framework, it would be expected that condom use would increase after the spread of a novel coronavirus (i.e., COVID-19), but the evidence to date is inconsistent. The present study aimed to clarify these inconsistencies by examining changes in condom use cross-culturally. First, Study 1 aimed to uncover whether condom use after the initial outbreak period was consistent with the BIS theory among an Australian sample (N1 = 129). Contrary to the BIS, but inline with other findings in Australia, there was a general decline of condom use. Second, Study 2 aimed to examine whether cross-cultural condom use was consistent with the BIS. Sexually active participants (N2 = 3843) across 17 countries were asked about their condom use. Results revealed a significant decline in Canada, Portugal, Vietnam, Uganda, and Taiwan. Vaccination percentage and lockdown stringency were associated with this decline cross-culturally. In sum, there was no evidence supporting the BIS theory, and these findings continue to add concerns about the spread of STIs among young people during the pandemic.
+
Multiple crises in mind, biodiversity out of sight? Insights from a behavioral study in Germany -
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+Biodiversity loss is one of the key challenges of our time. This paper explores how negative information due to other societal challenges influences attention toward biodiversity loss. With the help of an information provision experiment, we remind experimental participants recruited from the general population of Germany of Covid-19 and the war in Ukraine. We find less priority given to biodiversity loss after being reminded of these societal crises. However, this effect is both low in magnitude and not statistically significant at any conventional level. In contrast, personal importance of biodiversity to individuals is a much stronger behavioral predictor.
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A novel microporous biomaterial vaccine platform for long-lasting antibody mediated immunity against viral infection. -
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+Current antigen delivery platforms, such as alum and nanoparticles, are not readily tunable, thus may not generate optimal adaptive immune responses. We created an antigen delivery platform by loading lyophilized Microporous Annealed Particle (MAP) with aqueous solution containing target antigens. Upon administration of antigen loaded MAP (VaxMAP), the biomaterial reconstitution forms an instant antigen-loaded porous scaffold area with a sustained release profile to maximize humoral immunity. VaxMAP induced CD4+ T follicular helper (Tfh) cells and germinal center (GC) B cell responses in the lymph nodes similar to Alum. VaxMAP loaded with SARS-CoV-2 spike protein improved the magnitude and duration of anti-receptor binding domain antibodies compared to Alum and mRNA-vaccinated mice. A single injection of Influenza specific HA1-loaded-VaxMAP enhanced neutralizing antibodies and elicited greater protection against influenza virus challenge than HA1-loaded-Alum. Thus, VaxMAP is a platform that can be used to promote adaptive immune cell responses to generate more robust neutralizing antibodies, and better protection upon pathogen challenge.
+
An isothermal calorimetry assay for determining steady state kinetic and enzyme inhibition parameters for SARS-CoV-2 3CL-protease -
+
+This manuscript describes the application of Isothermal Titration Calorimetry (ITC) to characterize the kinetics of 3CLpro from the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) and its inhibition by Ensitrelvir, a known non-covalent inhibitor. 3CLpro is the main protease that plays a crucial role of producing the whole array of proteins necessary for the viral infection that caused the spread of COVID-19, responsible for millions of deaths worldwide as well as global economic and healthcare crises in recent years. The proposed calorimetric method proved to have several advantages over the two types of enzymatic assays so far applied to this system, namely Forster Resonance Energy Transfer (FRET) and Liquid Chromatography-Mass Spectrometry (LC-MS). The developed ITC-based assay provided a rapid response to 3CLpro activity, which was used to directly derive the kinetic enzymatic constants KM and kcat reliably and reproducibly, as well as their temperature dependence, from which the activation energy of the reaction was obtained for the first time. The assay further revealed the existence of two modes of inhibition of 3CLpro by Ensitrelvir, namely a competitive mode as previously inferred by crystallography as well as an unprecedented uncompetitive mode, further yielding the respective inhibition constants with high precision. The calorimetric method described in this paper is thus proposed to be generally and widely used in the discovery and development of drugs targeting 3CLpro.
+
Spike N354 glycosylation augments SARS-CoV-2 fitness for human adaptation through multiple mechanisms -
+
+Selective pressures have given rise to a number of SARS-CoV-2 variants during the prolonged course of the COVID-19 pandemic. Recently evolved variants differ from ancestors in additional glycosylation within the spike protein receptor-binding domain (RBD). Details of how the acquisition of glycosylation impacts viral fitness and human adaptation are not clearly understood. Here, we dissected the role of N354-linked glycosylation, acquired by BA.2.86 sub-lineages, as a RBD conformational control element in attenuating viral infectivity. The reduced infectivity could be recovered in the presence of heparin sulfate, which targets the N354 pocket to ease restrictions of conformational transition resulting in a RBD-up state, thereby conferring an adjustable infectivity. Furthermore, N354 glycosylation improved spike cleavage and cell-cell fusion, and in particular escaped one subset of ADCC antibodies. Together with reduced immunogenicity in hybrid immunity background, these indicate a single spike amino acid glycosylation event provides selective advantage in humans through multiple mechanisms.
+
A general platform for targeting MHC-II antigens via a single loop -
+
+Class-II major histocompatibility complexes (MHC-IIs) are central to the communications between CD4+ T cells and antigen presenting cells (APCs), but intrinsic structural features associated with MHC-II make it difficult to develop a general targeting system with high affinity and antigen specificity. Here, we introduce a protein platform, Targeted Recognition of Antigen-MHC Complex Reporter for MHC-II (TRACeR-II), to enable the rapid development of peptide-specific MHC-II binders. TRACeR-II has a small helical bundle scaffold and uses an unconventional mechanism to recognize antigens via a single loop. This unique antigen-recognition mechanism renders this platform highly versatile and amenable to direct structural modeling of the interactions with the antigen. We demonstrate that TRACeR-II binders can be rapidly evolved across multiple alleles, while computational protein design can produce specific binding sequences for a SARS-CoV-2 peptide of unknown complex structure. TRACeR-II sheds light on a simple and straightforward approach to address the MHC peptide targeting challenge, without relying on combinatorial selection on complementarity determining region (CDR) loops. It presents a promising basis for further exploration in immune response modulation as well as a broad range of theragnostic applications.
+
A Study to Learn About a Combined COVID-19 and Influenza Shot in Healthy Adults - Conditions: Influenza, Human, SARS-CoV-2 Infection, COVID-19 Interventions: Biological: BNT162b2 (Omi XBB.1.5)/RIV; Biological: BNT162b2 (Omi XBB.1.5); Biological: RIV; Other: Normal saline placebo Sponsors: Pfizer Not yet recruiting
+
The Effects of Nutritional Intervention on Health Parameters in Participants With Type 2 Diabetes Mellitus - Conditions: Diabetes Mellitus Type 2; Diabetes Mellitus Type 2 in Obese; Diabetes; Diabetes Mellitus Non-insulin-dependent; Hypertension; Type 2 Diabetes Mellitus Interventions: Behavioral: Nutritional Intervention Sponsors: Sao Jose do Rio Preto Medical School; Fundação de Amparo à Pesquisa do Estado de São Paulo Completed
+
The Impact of the Covid-19 Pandemic on Orthopedic Trauma Management - Conditions: Trauma; COVID-19 Pandemic Interventions: Other: epidemyolojical Sponsors: Bakirkoy Dr. Sadi Konuk Research and Training Hospital Completed
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Open-label, Multi-centre, Non-Inferiority Study of Safety and Immunogenicity of BIMERVAX for the Prevention of COVID-19 in Adolescents From 12 Years to Less Than 18 Years of Age. - Conditions: SARS CoV 2 Infection Interventions: Biological: BIMERVAX Sponsors: Hipra Scientific, S.L.U; Veristat, Inc.; VHIR; Asphalion Recruiting
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A Study of Amantadine for Cognitive Dysfunction in Patients With Long-Covid - Conditions: Long COVID; Post-Acute COVID-19 Syndrome Interventions: Drug: Amantadine; Other: Physical, Occupational, Speech Therapy; Other: Provider Counseling; Other: Medications for symptoms management Sponsors: University of Texas Southwestern Medical Center Not yet recruiting
+
Study on the Effect of Incentive Spirometer-based Respiratory Training on the Long COVID-19 - Conditions: COVID-19 Pandemic; Diabetes; Hypertension; Cardiac Disease; Long COVID Interventions: Behavioral: Incentive Spirometer respiratory training Sponsors: National Taipei University of Nursing and Health Sciences; Tri-Service General Hospital Not yet recruiting
+
Balance Acceptance and Commitment Therapy for Long COVID - Conditions: Post-COVID-19 Syndrome; Long COVID Interventions: Behavioral: Balance Acceptance and Commitment Therapy Sponsors: King’s College London Not yet recruiting
+
Predict + Protect Study: Exploring the Effectiveness of a Predictive Health Education Intervention on the Adoption of Protective Behaviors Related to ILI - Conditions: Influenza; Influenza A; Influenza B; COVID-19; Respiratory Syncytial Virus (RSV) Interventions: Behavioral: ILI Predictive Alerts, Reactive Content, and Proactive Content; Behavioral: ILI Predictive Alerts, Reactive Content; Behavioral: Proactive Content; Behavioral: No Intervention Sponsors: Evidation Health; Biomedical Advanced Research and Development Authority Not yet recruiting
+
Thrombohemorrhagic Complications of COVID-19 - Conditions: COVID-19 (Coronavirus Disease 2019) Interventions: Diagnostic Test: Prevention algorithm Sponsors: Volgograd State Medical University Active, not recruiting
+
Long COVID-19 [11C]CPPC Study - Conditions: COVID Long-Haul Interventions: Drug: [11C]CPPC Injection; Drug: [11C]CPPC Injection Sponsors: Johns Hopkins University; Radiological Society of North America Recruiting
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Combined Use of Immunoglobulin and Pulse Steroid Therapies in Severe Covid-19 Patients - Conditions: Pulse Steroid and Immunoglobulins Drugs in Covid 19 Patients Interventions: Drug: pulse steroid and nanogam Sponsors: Konya City Hospital Completed
+
Beneficial Effects of Natural Products on Management of Xerostomia - Conditions: Xerostomia; Diabetes Mellitus; Hypertension; Post COVID-19 Condition Interventions: Other: (Manuka honey-green tea- ginger) Sponsors: British University In Egypt Completed
Structural Basis for coronaviral main proteases Inhibition by a 3CL Protease Inhibitor- GC376 - The main protease (M^(pro)) of coronaviruses participates in viral replication, serving as a hot target for drug design. GC376 is able to effectively inhibit the activity of M^(pro), which is due to nucleophilic addition of GC376 by binding covalently with Cys145 in M^(pro) active site. Here, we used fluorescence resonance energy transfer (FRET) to analyze the IC(50) values of GC376 against M^(pro)s from six different coronaviruses (SARS-CoV-2, HCoV-229E, HCoV-HUK1, MERS-CoV, SARS-CoV,…
+
PCSK9 inhibition with orally administered NNC0385-0434 in hypercholesterolaemia: a randomised, double-blind, placebo-controlled and active-controlled phase 2 trial - BACKGROUND: Currently available injectable drugs that target proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce serum LDL cholesterol and improve cardiovascular outcomes. This phase 2 study assessed NNC0385-0434, an oral PCSK9 inhibitor, in individuals receiving oral lipid-lowering therapy.
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In vitro broad-spectrum antiviral activity of MIT-001, a mitochondria-targeted reactive oxygen species scavenger, against severe acute respiratory syndrome coronavirus 2 and multiple zoonotic viruses - The COVID-19 pandemic caused by SARS-CoV-2 becomes a serious threat to global health and requires the development of effective antiviral therapies. Current therapies that target viral proteins have limited efficacy with side effects. In this study, we investigated the antiviral activity of MIT-001, a small molecule reactive oxygen species (ROS) scavenger targeting mitochondria, against SARS-CoV-2 and other zoonotic viruses in vitro. The antiviral activity of MIT-001 was quantified by RT-qPCR and…
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Exploration of the P1 residue in 3CL protease inhibitors leading to the discovery of a 2-tetrahydrofuran P1 replacement - The virally encoded 3C-like protease (3CL^(pro)) is a well-validated drug target for the inhibition of coronaviruses including Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Most inhibitors of 3CL^(pro) are peptidomimetic, with a γ-lactam in place of Gln at the P1 position of the pseudopeptide chain. An effort was pursued to identify a viable alternative to the γ-lactam P1 mimetic which would improve physicochemical properties while retaining affinity for the target. Discovery of…
+
In-situ synthesized and induced vertical growth of cobalt vanadium layered double hydroxide on few-layered V2CTx MXene for high energy density supercapacitors - Two-dimensional (2D) MXene nanomaterials display great potential for green energy storage. However, as a result of self-stacking of MXene nanosheets and the presence of conventional binders, MXene-based nanomaterials are significantly hindered in their rate capability and cycling stability. We successfully constructed a self-supported stereo-structured composite (TMA-V(2)CT(x)/CoV-LDH/NF) by in-situ growing 2D cobalt vanadium layered double hydroxide (CoV-LDH) vertically on 2D few-layered…
+
Possible pharmacological targets and mechanisms of sivelestat in protecting acute lung injury - Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a life-threatening syndrome induced by various diseases, including COVID-19. In the progression of ALI/ARDS, activated neutrophils play a central role by releasing various inflammatory mediators, including elastase. Sivelestat is a selective and competitive inhibitor of neutrophil elastase. Although its protective effects on attenuating ALI/ARDS have been confirmed in several models of lung injury, clinical trials have presented…
+
Natural products from Streptomyces spp. as potential inhibitors of the major factors (holoRdRp and nsp13) for SARS-CoV-2 replication: an in silico approach - The COVID-19 pandemic caused unprecedented damage to humanity, and while vaccines have been developed, they are not fully effective against the SARS-CoV-2 virus. Limited targeted drugs, such as Remdesivir and Paxlovid, are available against the virus. Hence, there is an urgent need to explore and develop new drugs to combat COVID-19. This study focuses on exploring microbial natural products from soil-isolated bacteria Streptomyces sp. strain 196 and RI.24 as a potential source of new targeted…
+
NSP6 inhibits the production of ACE2-containing exosomes to promote SARS-CoV-2 infectivity - The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global pandemic, which severely endangers public health. Our and others’ works have shown that the angiotensin-converting enzyme 2 (ACE2)-containing exosomes (ACE2-exos) have superior antiviral efficacies, especially in response to emerging variants. However, the mechanisms of how the virus counteracts the host and regulates ACE2-exos remain unclear. Here, we identified that SARS-CoV-2 nonstructural…
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Activity and inhibition of the SARS-CoV-2 Omicron nsp13 R392C variant using RNA duplex unwinding assays - SARS-CoV-2 nsp13 helicase is an essential enzyme for viral replication and a promising target for antiviral drug development. This study compares the double-stranded RNA (dsRNA) unwinding activity of nsp13 and the Omicron nsp13^(R392C) variant, which is predominant in currently circulating lineages. Using in vitro gel- and fluorescence-based assays, we found that both nsp13 and nsp13^(R392C) have dsRNA unwinding activity with equivalent kinetics. Furthermore, the R392C mutation had no effect on…
+
Phospho-eIF4E stimulation regulates coronavirus entry by selective expression of cell membrane-residential factors - The eukaryotic translation initiation factor eIF4E can regulate cellular translation via phosphorylation on serine 209. In a recent study, by two rounds of TMT relative quantitative proteomics, we found that phosphorylated eIF4E (p-eIF4E) favors the translation of selected mRNAs, and the encoded proteins are mainly involved in ECM-receptor, focal adhesion, and PI3K-Akt signaling. The current paper is focused on the relationship between p-eIF4E and the downstream host cell proteins, and their…
+
Comparative immunogenicity and neutralizing antibody responses post heterologous vaccination with CoronaVac (Sinovac) and Vaxzevria (AstraZeneca) in HIV-infected patients with varying CD4+ T lymphocyte counts - The immune response to heterologous coronavirus disease (COVID-19) vaccination in people living with HIV (PLWH) is still unclear. Herein, our prospective cohort study aimed to compare the immune response of heterologous vaccination with CoronaVac (Sinovac) and Vaxzevria (AstraZeneca) between PLWH having CD4 counts ≤ 200 cells/µL (low CD4+) and > 200 cells/µL (high CD4+). Anti-receptor-binding domain (RBD) immunoglobulin G (IgG) levels and the percentage inhibition of neutralizing antibodies…
+
Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial - Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual…
+
Effects of antineoplastic and immunomodulating agents on postvaccination SARS-CoV-2 breakthrough infections, antibody response, and serological cytokine profile - CONCLUSIONS: Antineoplastic and immunomodulating medications associate with an elevated risk of postimmunization SARS-CoV-2 infection in a drug-specific manner. This comprehensive, unbiased analysis of all WHO ATC classified antineoplastic and immunomodulating medications identifies medications associated with greatest risk. These findings are crucial in guiding and refining vaccination strategies for patients prescribed these treatments, ensuring optimized protection for this susceptible…
+
G3BP1-dependent condensation of translationally inactive viral RNAs antagonizes infection - G3BP1 is an RNA binding protein that condenses untranslating messenger RNAs into stress granules (SGs). G3BP1 is inactivated by multiple viruses and is thought to antagonize viral replication by SG-enhanced antiviral signaling. Here, we show that neither G3BP1 nor SGs generally alter the activation of innate immune pathways. Instead, we show that the RNAs encoded by West Nile virus, Zika virus, and severe acute respiratory syndrome coronavirus 2 are prone to G3BP1-dependent RNA condensation,…
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Triple in silico targeting of IMPDH enzyme and RNA-dependent RNA polymerase of both SARS-CoV-2 and Rhizopus oryzae - Aim: Mucormycosis has been associated with SARS-CoV-2 infections during the last year. The aim of this study was to triple-hit viral and fungal RNA-dependent RNA polymerases (RdRps) and human inosine monophosphate dehydrogenase (IMPDH). Materials & methods: Molecular docking and molecular dynamics simulation were used to test nucleotide inhibitors (NIs) against the RdRps of SARS-CoV-2 and Rhizopus oryzae RdRp. These same inhibitors targeted IMPDH. Results: Four NIs revealed a comparable binding…
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The Friendship Challenge - How envy destroyed the perfect connection between two teen-age girls. - link
+
The Art World Before and After Thelma Golden, by Calvin Tomkins - When Golden was a young curator in the nineties, her shows, centering Black artists, were unprecedented. Today, those artists are the stars of the art market. - link
+
A Teen’s Fatal Plunge Into the London Underworld - After Zac Brettler mysteriously plummeted into the Thames, his grieving parents were shocked to learn that he’d been posing as an oligarch’s son. Would the police help them solve the puzzle of his death? - link
+
Photos from a Late-Stage Abortion Clinic - At a clinic in Maryland, desperate patients arrive from all over the country to terminate their pregnancies. - link
+
How Nikola Jokić Became the World’s Best Basketball Player - He doesn’t run very fast or jump very high, and seems to prefer the company of horses. But he has mastered the game’s new geometry like nobody else. - link
+Today, Explained is expanding into a multi-platform news brand, starting with a daily newsletter offering clarity on the day’s most significant story.
+
+
+Hey, welcome to Vox’s new daily newsletter!
+
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+We’re calling it Today, Explained, and it’ll be run by me, Caroline Houck.
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+I’m Vox’s senior editor of news, a role I’ve come to after five years at Vox, covering some of the biggest stories of those years. That included the Trump impeachments, the 2020 election, and one of the biggest Supreme Court terms in recent memory,before I took over our international section just in time for the US withdrawal from Afghanistan and Vladimir Putin’s invasion of Ukraine.
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+Now I’m here overseeing this newsletter, and I am psyched.
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+When something happens in the world — whether it’s an explosion abroad, one at home, or even a metaphorical explosion in, say, the world of American academia — my first instinct is always to ask my Vox colleagues about it. I want to lurk in their Slack channels and pop over to their desks to listen in on how they’re breaking down the big stories. That’s how I navigated Covid and how I processed what was going on with the American judicial system after the Supreme Court overturned Roe v. Wade. And it’s how I had something to say about one half of 2023’s summer movie sensation (because yes, I admit it: I still haven’t watched Oppenheimer).
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+My favorite way to understand the world is through the eyes of our newsroom.
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+And now, each day in your inbox, we’re going to bring that view to you.
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+What does that mean?
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+It means that every day, Monday through Friday, we’ll start Today, Explained with a classic Vox explainer about something interesting and important happening in the world.
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+It’ll work like this: A reporter, producer, or editor will walk us through that one big story, explaining it with nuance and clarity. It’ll be about as long as this email — maybe a little shorter or a little longer, depending on the topic. And it will always be conversational and approachable, even as we weave in the deep research, reporting, and analysis you’ll always find at Vox.
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+So today, if we weren’t introducing this newsletter to you, we might have covered the Grammys or dug into economic news after Friday’s impressive jobs report. We want to explain the news. So I’ll look around the newsroom each day and see which Voxxer might be best positioned to do so, then bring them to your inboxes.
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+Whether we’re covering something that’s in the news or not, though, I want all of you to know you’re always going to walk away from Today, Explained with the day explained. We’ll curate the most important news of the day and the most interesting conversations happening around the internet here in the second half of the newsletter. These are the stories that we at Vox are paying attention to — and that we’ll deliver to you.
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+We’ll also share the latest episode from Today, Explained (the podcast). The team there — led by hosts Sean Rameswaram and Noel King — shares our mission of explaining the world in a way that’s accessible, informative, and often fun. I might be biased, but you should listen. And we’ll include one link to a great piece of Vox journalism every day, be it an article, video, or podcast.
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+If you want breadth or depth — or both! — we’ve got you covered. Sign up here, and we’ll see you tomorrow!
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Abortion rights groups don’t want to “restore Roe” — but they won’t fight Biden on it -
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+President Joe Biden speaks during a campaign rally to restore Roe at Hylton Performing Arts Center in Manassas, Virginia, on January 23, 2024. | Saul Loeb/AFP via Getty Images
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+Many reproductive health organizations want to codify stronger standards. They’re not going to pick that fight this year.
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+When Joe Biden and Kamala Harris held their first joint campaign event of 2024 last month in northern Virginia, they left no doubt that codifying abortion rights would be central to the president’s reelection bid. With the rally timed to honor what would have been the 51st anniversary of Roe v. Wade, Biden stood under a large “Restore Roe” sign and beside supporters holding smaller posters to “Defend Choice.”
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+“We need the protections of Roe v. Wade in every state. And we can do it. You can do it,” Biden stressed at the event. “Give me a Democratic House of Representatives and give me a bigger — a bigger Democratic Senate, and we will pass a new law restoring the protections of Roe v. Wade, and I will sign it immediately.”
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+ Saul Loeb/AFP via Getty Images
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+First lady Jill Biden, President Joe Biden, Vice President Kamala Harris, and her husband Doug Emhoff wave following a campaign rally to restore Roe at Hylton Performing Arts Center in Manassas, Virginia, on January 23, 2024.
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+In subsequent campaign blasts, the Biden-Harris team reiterated the Roe message. “A vote for Joe Biden and Kamala Harris is a vote to restore Roe,” said Julie Chávez Rodriguez, Biden’s campaign manager. “It’s simple,” the president tweeted to his nearly 34 million followers, under a graphic calling to “Restore the Protections of Roe v. Wade Once and For All.”
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+After the 2022 and 2023 election cycles, it may not be surprising that Biden is running on an abortion rights platform. What’s new, though, is that prominent abortion rights groups are biting their tongues about Roe and “pro-choice” messaging they disdain and have been trying to steer politicians away from.
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+In the weeks and months following the June 2022 Dobbs v. Jackson decision, it was more common to hearinfluential leaders within the abortion rights movement talk about the necessity of going beyond Roe v. Wade, not going back to it. The old legal standard, they argued,was never good enough, and left too many people without access to the reproductive healthcare they needed.
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+When a bipartisan group of lawmakers introduced a bill in summer 2022 to codify the legal protections that existed under Roe just before the Dobbs decision was issued, a coalition of reproductive rights groups came out quickly against it. Activists instead had their eyes set on the Women’s Health Protection Act, a more sweeping federal bill that would not only restore the pre-Dobbs status quo but also ban most state-level restrictions as well as religious exemptions for health care providers. (WHPA passed the House in 2021 but failed twice in the Senate.)
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+The groups’ opposition to anything incremental meant a more moderate, compromise effort to protect abortion rights in Congress was never seriously attempted after Roe.
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+The hope to go beyond Roe hasn’t disappeared. Bolstered by decisive ballot measures to protect abortion rights over the last 18 months, election wins for Democrats who campaigned heavily on reproductive freedom, and surveys that suggest voters have grown even more supportive of abortion rights since Roe’s repeal, many activists have pressed Democrats to avoid using “Roe” language at all, and even steer clear of popular “pro-choice” messaging they believe helped normalize restricting abortion over the years.
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+Yet with the 2024 election now closer and stakes on abortion access even higher, reproductive rights groups have decided to swallow their concerns and enthusiastically endorse the president’s reelection strategy. Vox reached out to a dozen abortion rights groups, and while many offered statements about the need to do more to protect abortion access, no organization went so far as to say they disagreed with the president on his call to restore Roe, or explicitly object to his language.
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+Most groups handled the tension by saying they supported codifying “real protections” that restore the “original promise” of Roe — even if the restoration of Roe could mean restoring the legal rights available before Dobbs.
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+“Planned Parenthood Action Fund’s long-term vision includes short-term strategies, and it’s very simple,” Alexis McGill Johnson, the president and CEO of Planned Parenthood Action Fund, told Vox. “This November, voters will have to decide between an administration that continues to work with us in the fight for freedom or an administration that caused our current public health crisis and will go further with a national abortion ban. We have a very clear choice between holding the line or descending further into what will be irreparable chaos and confusion.”
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+Planned Parenthood endorsed Biden’s reelection bid last June and recently published a glowing review of the administration’s record on abortion access. “You can be certain that we are fighting for more than Roe v. Wade,” McGill Johnson told me.
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+“We absolutely need to restore the protections of Roe v. Wade, and so much more,” said Katie O’Connor, the National Women’s Law Center’s director of federal abortion policy. “We are proud to have endorsed President Biden, and pleased he has committed to signing a bill that would lock the federal right to abortion into law,” Mini Timmaraju, president and CEO of Reproductive Freedom for All,added.
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+“Restore Roe” is Biden’s politics, not his policy
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+Biden’s campaign and surrogates are quick to point out that the president has already taken steps to protect abortion rights that go beyond the standards of Roe v. Wade. He’s on record supporting the Women’s Health Protection Act, and his administration has expanded access to abortion pills via telemedicine and at pharmacies.
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+So abortion rights groups and their congressional allies looking to pass stronger protections have decided to tolerate the president’s Roemessaging, trusting his team will do more if reelected, despite what he’s saying publicly now to voters.
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+“I support President Biden’s campaign message to restore Roe and his administration’s actions to defend abortion access,” Democratic Sen. Elizabeth Warren told me, drawing a distinction between his campaign rhetoric and his executive policies.
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+Whether voters know that “restoring Roe” is not the president’s end goal for abortion policy, though, is less clear. He’s never specifically articulated that fact, and his surrogates are wary to do so on the record, either. They suggest, rather, that a person should be able to infer the president’s policy goals based on a close reading of his administration’s record.
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+The Biden campaign, for its part, wants to keep the conversation stationed on friendly political ground — where codifying or restoring Roe simply means legalizing or protecting abortion rights. This is safer territory, since most Americans believe abortion should be legal in all or most cases and that overturning Roe v. Wade was a mistake. However, when one starts drilling down into the details about specific limits or restrictions, public opinion becomes murkier and more complex.
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+Where things get tricky is that Biden has not just praised Roe as a shorthand for legal abortion rights. He also continues to praise the specifics of the Supreme Court decision itself.
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+“It was a decision on a complex matter that drew a careful balance between a woman’s right to choose earlier in her pregnancy and the state’s ability to regulate later in her pregnancy,” the president said when the Dobbs ruling came down. “A decision with broad national consensus that most Americans of faiths and backgrounds found acceptable.”
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+Even at this recent Virginia campaign event in January the president went so far as to say, “I believe Roe v. Wade got it right, and so do a majority of Americans.”
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+This tendency to try and have it both ways on Roe has been frustrating for anti-abortion groups, as they point out the administration will praise the Supreme Court decision that endorsed limits and regulations but won’t say today which, if any, limits they’d now support.
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+For example, last fall, when Harris was asked if there should be any limits on the right to an abortion, said at least five times that “we need to restore the protections of Roe v. Wade” but dodged clarifying what she meant by that in practice.
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+Some Democratic political strategists say this waffling is simply necessary to get through November, to avoid Republicans spreading the lie that third-trimester abortions will become more common if Biden is reelected. Recently the Republican National Committee claimed in a press release that Biden supports “abortion-on-demand up until the moment of birth and after.”
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+The GOP also tried to attack Democrats in Virginia for supporting abortion “up until birth” in the recent 2023 election cycle, but voters didn’t seem to buy it. While Americans do tend to be more uncomfortable with third-trimester abortions, they also seem to understand they are extremely rare, and are typically associated with fetal anomalies, threats to a mother’s life, and barriers to care that delay access to the procedure.
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+Abortion rights groups still plan to push for more than Roe
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+As of now, the two major bills to codify abortion rights on the federal level are the Women’s Health Protection Act and the Reproductive Freedom for All Act, which would legalize abortion before fetal viability and permit so-called conscience protections for health care providers who oppose abortion.
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+When I asked a dozen abortion rights groups if they’d support codifying reproductive rights in legislation if the proposed federal bill did not go as far as the Women’s Health Protection Act, most organizations demurred or declined to answer directly. Only Catholics for Choice offered a clear affirmative statement that they’d be willing to consider any bill that allows a pregnant person to choose abortion. “This is not a time to make good legislation the enemy of the perfect,” president Jamie Manson told me.
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+A spokesperson for Democratic Sen. Tim Kaine, one of the lead sponsors of the Reproductive Freedom for All Act, told Vox that he remains focused on passing his bill to codify “the essential holdings of Roe and related cases to protect reproductive freedom and access to contraception.” In a press interview following Biden’s Virginia campaign event, Kaine stressed his bill is the only bipartisan one pending in Congress now to restore Roe as a statutory protection.
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+Despite his campaign mantra to restore Roe, the Biden campaign declined to comment on whether the president would sign the Reproductive Freedom for All Act if it passed Congress.
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+Democratic Sen. Tina Smith suggested lawmakers would be open to different pieces of legislation to protect abortion rights. “Our goal is to restore women’s reproductive freedoms,” she told me. “If that’s the Women’s Health Protection Act or something else remains to be seen, but that’s where I stand.”
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America is exporting more arms than ever. Here’s why. -
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+A soldier of the 128th Separate Mountain Assault Brigade of the Zakarpattia Land Forces of the Armed Forces of Ukraine is seen during special training exercises to maintain professional skills involving T-72 tanks in the Zaporizhzhia sector of southeastern Ukraine. | Dmytro Smolienko/Ukrinform/Future Publishing via Getty Images
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+Record arms exports are a sign of America’s commitment to Europe — and its foreign policy failures during the war in Ukraine.
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+US foreign military sales recently reached a record high, largely driven by Russia’s war in Ukraine.
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+The 2023 fiscal year, ending October 1, saw $80.9 billion in US government arms transfers, foreign defense services, and security cooperation — a figure up more than 55 percent from $51.9 billion in 2022. Direct commercial sales by US arms manufacturers to other countries also rose from $153.6 billion to $157.5 billion over the previous fiscal year. (The US government approves both types of sales but is only directly involved in negotiations for the former, making that a stronger indicator of US foreign policy priorities.)
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+ Nicole Narea/Vox
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+US officials have indicated that they intend to starve the Russian arms export industry, encouraging their allies in Europe and globally to buy American weapons instead.
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+“We see that because Russia’s defense industry is denied the resources that come from exports, that helps to contribute to Russian strategic failure on the battlefield,” Mira Resnick, who runs the State Department’s Office of Regional Security and Arms Transfers, told Politico.
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+The military transfers also serve the purpose of signaling the Biden administration’s commitment to its European partners. Some European allies are buying US weapons in preparation for a feared broader war in Europe against Russia; the European Union approved $50 billion in funding for Ukraine Thursday.
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+But the increase in US arms sales is not necessarily a testament to the success of Biden’s foreign policy, said Elias Yousif, a research analyst with the Stimson Center’s Conventional Defense Program.
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+“This really reflects just a degree of insecurity in Europe and anxieties about the war in Ukraine,” he said. “I’m not sure that the acceleration of arms transfers is really a cure.”
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+Every one of these foreign military transfers goes through a detailed agency review process that involves evaluating whether it serves a partner country’s legitimate self-defense, and most major sales have to be approved by Congress with rare exceptions for emergencies.
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+These deals are often completed over multiple years. The $80.9 billion figure encompasses deals that were actually implemented over the last fiscal year, but the US has also announced some major deals with European allies that may not yet count towards that total: Ukraine’s neighbor Poland, for example, struck a series of deals amounting to more than $45 billion, per congressional disclosures.
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+There’s a question whether those deals will actually be implemented going forward. Poland’s annual military budget is just $16 billion, and it also made a big purchase from South Korea last year, so “they’ll either need to jack up their military budget dramatically, or spread out payment over many years, or scale back their ambitions,” said WilliamHartung, a senior research fellow at the Quincy Institute for Responsible Statecraft.
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+While Poland made the largest commitment in the last fiscal year, the US also made sales agreements with other European countries, including ones valued at about $11.4 billion with Germany and $6.3 billion with the Czech Republic, as well as smaller deals with Norway and Bulgaria.
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+These massive deals will help reduce European reliance on Russian arms. But they should also be raising concern about how well the US is reassuring its allies and what it’s doing to decrease the demand for these weapons in the first place, Yousif said. In that sense, the increased military transfers reflect Europe’s uncertainty about the US’s commitments to its allies in an unstable world, as well as the US’s explicit attempts to placate them.
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+How the war in Gaza is impacting weapons sales
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+Israel’s war in Gaza wasn’t a factor in the 2023 increase in sales, since the war started after the fiscal year ended. Much of what’s being transferred to Israel now is part of sales that Congress was notified of in previous years, but the fulfillment of those orders has been accelerated since Hamas’s October 7 attack on Israel, Yousif said. In other words, those sales were already tallied up in previous years’ totals. But there are some new sales: Biden twice circumvented Congress to make emergency weapons sales to Israel in December, totaling over $250 million.
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+Much like the Ukraine war, Israel’s war in Gaza could become a major driver of arms transfers going forward as regional tensions escalate and US allies work to ensure their militaries are well supplied for any potential conflict. Arms deals could also be a part of any normalization deal between Israel and Saudi Arabia — an agreement the US had made great efforts to broker before the outbreak of the war.
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+“Next year could be the ‘year of the Middle East’ as regional tensions sparked by the Gaza war and the Biden administration’s desire to cozy up to Saudi Arabia to persuade it to join the Abraham Accords could spur large new sales,” Hartung said.
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+Regardless of what happens with other partners in the Middle East, arms transfers to Israel appear likely to continue. That’s despite the fact that continued sales to Israel “violate the spirit and letter of US law as well as stated Biden administration policy, and they make a mockery of the administration’s claims to support a ‘rules-based international order,’” Hartung said.
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+Some foreign affairs experts have argued that existing US laws meant to safeguard human rights, including the “Leahy Law,” should have long restricted the flow of such assistance to Israel due to the high death toll in its conflict. Unlike with respect to Ukraine, whose use of controversial weapons like cluster munitions and landmines has led to restrictions on US aid, that law has not been adequately enforced against Israel, they say.
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+But the Biden administration has maintained that it is abiding by the law and is on track to make 2024 another strong year for weapons sales.
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From The Hindu: Sports
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To be adventurous or safe — the Mercedes conundrum after Hamilton’s shock exit - Replacing arguably one of the greatest drivers in the sport’s history is not going to be an easy task for the German marquee; who it selects could indicate how the team looks to build its post-Hamilton future
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Dash, and Rush show out -
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Magnus and Stellantis impress -
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Ranji Trophy | Tamil Nadu cruises to seven-wicket win over Goa - This is Tamil Nadu’s third consecutive win and it retains the top spot in Group-C with 21 points and superior run quotient over Karnataka
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Ind vs Eng 2nd Test | India dismiss England for 292, register series-levelling 106-run win - England’s no holds barred approach did not pay off as India picked up nine wickets over the course of two sessions to bounce back in the five-match series
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From The Hindu: National News
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Kerala Budget 2024-25: State to adopt Chinese model of development at Vizhinjam - Special development zones will be created in partnership with the private sector by attracting investment from institutions and individuals, including non-resident Keralites.
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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. Curated and written by Nalme Nachiyar.
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Suspended Panjagutta SHO nabbed in Guntakal, Andhra Pradesh by Hyderabad police -
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Bihar Congress MLAs in Hyderabad to avoid the lure of NDA Govt - The MLAs are likely to be in Hyderabad till February 11; the floor test for the new government is on February 12
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Stones pelted at Chennai-Tirunelveli Vande Bharat Express damage glass windows in six coaches - The incident took place when the train was running between Gangaikondan and Naraikinaru stations around 10 p.m. on February 4; the police are surveilling CCTV footage to identify the culprits
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From BBC: Europe
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Does Germany’s economy need more than a cup of coffee? - Germany’s growth is being held back by the twin shocks of expensive energy and higher interest rates.
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Dozens dead in strike on Russia-held Ukraine city - Russia blames Ukraine for the attack on a bakery, which the Kremlin said left 28 people dead.
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Parisians vote for rise in parking fees for SUVs - The vote was called by mayor Anne Hidalgo, who says SUVs are dangerous and bad for the environment.
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UN top court can rule on Ukraine case against Russia - Ukraine brought the case in 2022, accusing Russia of falsely using genocide law to justify its invasion.
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Thunberg cleared after unlawful protest arrest - Greta Thunberg was arrested at a protest in October, with the judge ruling the law was unclear.
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From Ars Technica
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Humans are living longer than ever no matter where they come from - Disease outbreaks and human conflicts help dictate regional differences in longevity. - link
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Hermit crabs find new homes in plastic waste: Shell shortage or clever choice? - The crustaceans are making the most of what they find on the seafloor. - link
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The 2024 Rolex 24 at Daytona put on very close racing for a record crowd - The around-the-clock race marked the start of the North American racing calendar. - link
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Google will no longer back up the Internet: Cached webpages are dead - Google Search will no longer make site backups while crawling the web. - link
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Our oldest microbial ancestors were way ahead of their time - Specialized internal structures were present over 1.5 billion years ago. - link
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From Jokes Subreddit
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My wife minored in psychology. She’s always using all her amateur psychology when we argue. -
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+Husband; When I fired the pool boy, she said, “Well, you know, you’re only firing him because he’s so young and good looking, and you feel threatened and insecure, because it reminds you of your own mortality, and you’re projecting all these insecurities onto someone else in a very passive/aggressive way, because these feelings are just too traumatic for you to deal with.”
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+His wife screams, “You fucking Idiot,” my hair and makeup are a mess, the house has not been cleaned , the dishes aren’t done, I’m still in my pyjamas, I can’t be bothered to cook and it’s my time of the month! Why the fuck did you bring him home? The husband replies “Because he is thinking of getting married”…
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+I went downstairs for breakfast hoping my wife would be pleasant and say, ‘Happy Birthday,’ and possibly have a small present for me. As it turned out, she barely said good morning, let alone ‘Happy Birthday.’ I thought …. well, that’s marriage for you, but the kids …. they will remember. My kids came bouncing down stairs to breakfast and didn’t say a word. So when I left for work I felt pretty low and somewhat dejected. As I walked into my office, my hot boss, Pam, said, ‘Good morning, and by the way Happy Birthday!’ It felt a little better that at least someone had remembered. I worked until one o’clock, when Pam knocked on my door and said, ‘It’s such a beautiful day outside, and it is your birthday, what do you say we go out to lunch, just you and me.’ I said, ‘Thanks, Pam, that’s the greatest thing I’ve heard all day. Let’s go!’ We went to lunch. But we didn’t go where we normally would go. She chose instead a quiet bistro with a private table. We had two red wines each and I enjoyed the meal tremendously. On the way back to the office, Pam said, ‘It’s such a beautiful day … we don’t need to go straight back to work, do we?’ I responded, ‘I guess not. What do you have in mind?’ She said, ‘Let’s drop by my place, it’s just around the corner. After arriving at her house, Pam turned to me and said, ’If you don’t mind, I’m going to step into the bedroom for just a moment. I’ll be right back.’ ‘Ok.’ I nervously replied. She went into the bedroom and, after a couple of minutes, she came out carrying a huge birthday cake, followed by my wife, my kids, and dozens of my friends and co-workers, all singing ‘Happy Birthday.’ And I just sat there …. on the sofa …. butt naked.
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Saul Loeb/AFP via Getty Images
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Nicole Narea/Vox
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