Virological characteristics of the SARS-CoV-2 JN.1 variant -
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+The SARS-CoV-2 BA.2.86 lineage, first identified in August 2023, is phylogenetically distinct from the currently circulating SARS-CoV-2 Omicron XBB lineages, including EG.5.1 and HK.3. Comparing to XBB and BA.2, BA.2.86 carries more than 30 mutations in the spike (S) protein, indicating a high potential for immune evasion. BA.2.86 has evolved and its descendant, JN.1 (BA.2.86.1.1), emerged in late 2023. JN.1 harbors S:L455S and three mutations in non-S proteins. S:L455S is a hallmark mutation of JN.1: we have recently shown that HK.3 and other "FLip" variants carry S:L455F, which contributes to increased transmissibility and immune escape ability compared to the parental EG.5.1 variant. Here, we investigated the virological properties of JN.1.
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Distance to Vaccine Sites is Associated with Lower COVID-19 Vaccine Uptake -
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+COVID-19 remains a leading cause of mortality in the U.S., despite widespread availability of vaccines. Conventional wisdom ties failure to vaccinate primarily to vaccine-skeptic beliefs (e.g., conspiracy theories, partisanship). Yet in this research, we find that vaccination is also hindered by travel distance to vaccine sites (a form of friction, or structural barriers). In study 1, Californians living farther from vaccine sites had lower vaccination rates, and this effect held regardless of partisanship. In study 2, Chicago zip codes saw an uptick in vaccination following vaccine site opening. These results proved robust in multiverse analyses accounting for a wide range of covariates, outcomes, and distance indicators. COVID-19 vaccination is hampered not just by vaccine hesitancy, but also structural barriers like distance. Efforts to boost vaccination could benefit from minimizing friction.
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SARS-CoV-2 infection is associated with intestinal permeability, systemic inflammation, and microbial dysbiosis in hospitalized COVID-19 patients -
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+Coronavirus disease 2019 (COVID-19) and associated severity has been linked to uncontrolled inflammation and may be associated with changes in the microbiome of mucosal sites including the gastrointestinal tract and oral cavity. These sites play an important role in host-microbe homeostasis and disruption of epithelial barrier integrity during COVID-19 may potentially lead to exacerbated inflammation and immune dysfunction. Outcomes in COVID-19 are highly disparate, ranging from asymptomatic to fatal, and the impact of microbial dysbiosis on disease severity is unclear. Here, we obtained plasma, rectal swabs, oropharyngeal swabs, and nasal swabs from 86 patients hospitalized with COVID-19 and 12 healthy volunteers. We performed 16S rRNA sequencing to characterize the microbial communities in the mucosal swabs and measured circulating cytokines, markers of gut barrier integrity, and fatty acids in the plasma samples. We compared these plasma concentrations and microbiomes between healthy volunteers and the COVID-19 patients who had survived or unfortunately died by the end of study enrollment, and between severe disease and healthy controls, as well as performed a correlation analysis between plasma variables and bacterial abundances. The rectal swabs of COVID-19 patients had reduced abundances of several commensal bacteria including Faecalibacterium prausnitsii, and an increased abundance of the opportunistic pathogens Eggerthella lenta and Hungatella hathewayi. Furthermore, the oral pathogen Scardovia wiggsiae was more abundant in the oropharyngeal swabs of COVID-19 patients who died. The abundance of both H. hathewayi and S. wiggsiae correlated with circulating inflammatory markers including IL-6, highlighting the possible role of the microbiome in COVID-19 severity, and providing potential therapeutic targets for managing COVID-19.
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Effects of remote work on population distribution across cities: US evidence from a QSE model -
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+This study investigates the impact of remote work adoption on the size and competitiveness of cities in the United States. As a contribution to the ongoing debate sparked by the Covid-19 pandemic, the research initially establishes city-specific upper-bound measures of potential remote work adoption, utilizing the share of employment in remotely-performable occupations for each city. Subsequently, it employs a Quantitative Spatial Economic model, incorporating shipping and commuting costs, to assess the counterfactual effects that these potential levels of remote work adoption would have on population distribution across US cities. Model predictions indicate that upon full remote-work adoption, only select highly productive cities would grow in size and productivity, tothe detriment of the majority of locations. Nevertheless, the emerging spatial equilibrium yields generalized welfare gains characterized by reduced markups in larger cities, extending even to shrinking cities through the pro-competitive effect of trade. The findings suggest a policy-relevant dual role of remote work, concurrently enhancing welfare while reinforcing agglomeration and inequality across cities.
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Prediction of mental well-being from individual characteristics and circumstances during the COVID-19 pandemic -
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+The âMental Health Impact of COVID-19 Pandemic on NIMH Patients and Volunteersâ study was a longitudinal study launched in spring 2020 by researchers at NIMH, to investigate the effect of the emerging COVID-19 pandemic on mental health. For each participant, the study collected personal characteristics, such as demographics, psychological traits, and clinical history, together with personal circumstances at regular intervals during their enrollment in the study. In this paper, we examine the degree to which a variety of mental health outcomes over time for an individual can be predicted from personal characteristics and their changing circumstances, using regression models trained on other study participants. We find that it is possible to predict the variation of a participantâs mental health outcomes from time point to time point, for most of the outcomes we consider. This capability is dominated by information about the primary outcome measures that were collected at the time of study enrollment but can be improved by considering personal characteristics and circumstances.
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+The COVID-19 pandemic has highlighted the importance of biosafety in the biomedical sciences. While it is often assumed that biosafety is purely technical matter that has little to do with philosophy or the humanities, biosafety raises important ethical issues that have not been adequately examined in the scientific or bioethics literature. This article reviews some pivotal events in the history of biosafety and biosecurity and explores three different biosafety topics that generate significant ethical concerns, i.e., risk assessment, risk management, and risk distribution. The article also discusses the role of democratic governance in the oversight of biosafety and offers some suggestions for incorporating bioethics into biosafety practice, education, and policy.
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COVID-19 Lockdowns and Childrenâs Access to Justice: An Interrupted Time Series Analysis of Moroccan Family court filings -
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+The COVID-19 is a social disaster that has affected the operation of judicial systems globally. Access to justice is a vital right that ensures all other rights can be upheld. This study investigates how national lockdown affected the operation of family courts and childrenâs access to justice in Morocco. National lockdowns were enforced between March 21th and June 10th 2020 in response to the spread of coronavirus. The general closure of civil society was not extended to the judicial system and family courts were expected to continue operating and provide access to protection and justice. How well the court system mentioned to function under the constraints of stay-at-home orders is an open question. To investigate the impact of the national COVID-19 lockdown on family court systems and access to justice for children in Morocco this study used publicly available court filings (N= 77,335) pertaining to child abuse and neglect from 1st January 2020 to 30th December 2020 spanning the pre-lockdown, lockdown, and post-lockdown periods. Interrupted time series analysis was conducted to assess the impact of the COVID-19 lockdown on court filing outcomes across different case types including penal, civil, complaints, and reports at the national, regional, and court level, controlling for time trends and regional fixed effects. National lockdowns were associated with decrease in cases filed and an increase in the percentages of cases with delays. Average case length differed by case type. Post-lockdown, case numbers recovered however there was large weekly variation likely due to rolling regional lockdowns. Evidence suggests that national lockdowns had a significant adverse impact on the judicial systems ability to provide access to justice for children.
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From Viral Infections to Alzheimerâs Disease: Unveiling the Mechanistic Links Through Systems Bioinformatics -
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+Emerging evidence suggests that certain microorganisms, including viral infections, may contribute to the onset and/or progression of Alzheimer's Disease (AD), a neurodegenerative condition characterized by memory impairment and cognitive decline. However, the precise extent of their involvement and the underlying mechanisms through which specific viruses increase AD susceptibility risk remain elusive. We used an integrative systems bioinformatics approach to identity viral-mediated pathogenic mechanisms by which specific viral species, namely Herpes Simplex Virus 1 (HSV-1), Human Cytomegalovirus (HCMV), Epstein-Barr Virus (EBV), Kaposi Sarcoma-associated Herpesvirus (KSHV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Influenza A virus (IAV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), could facilitate the pathogenesis of AD via virus-host protein-protein interactions (PPIs). We also sought to uncover potential synergistic pathogenic effects resulting from the reactivation of specific herpesviruses (HSV-1, HCMV and EBV) during acute SARS-CoV-2 infection, potentially increasing AD susceptibility. Our findings show that Herpesviridae Family members (HSV-1, EBV, KSHV, HCMV) impact AD-related processes like amyloid-beta formation, neuronal death, and autophagy. Hepatitis viruses (HBV, HCV) influence processes crucial for cellular homeostasis and dysfunction. Importantly, hepatitis viruses affect microglia activation via virus-host PPIs. Reactivation of HCMV during SARS-CoV-2 infection could potentially foster a lethal interplay of neurodegeneration, via synergistic pathogenic effects on AD-related processes like response to unfolded protein, regulation of autophagy, response to oxidative stress and amyloid-beta formation. Collectively, these findings underscore the complex link between viral infections and AD development. Perturbations in AD-related processes by viruses can arise from both shared and distinct mechanisms among viral species in different categories, potentially influencing variations in AD susceptibility.
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In Silico Therapeutic Intervention on Cytokine Storm in COVID-19 -
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+The recent global COVID-19 outbreak, attributed by the World Health Organization to the rapid spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), underscores the need for an extensive exploration of virological intricacies, fundamental pathophysiology, and immune responses. This investigation is vital to unearth potential therapeutic avenues and preventive strategies. Our study delves into the intricate interaction between SARS-CoV-2 and the immune system, coupled with exploring therapeutic interventions to counteract dysfunctional immune responses like the 'cytokine storm' (CS), a driver of disease progression. Understanding these immunological dimensions informs the design of precise multiepitope-targeted peptide vaccines using advanced immunoinformatics and equips us with tools to confront the cytokine storm. Employing a control theory-based approach, we scrutinize the perturbed behavior of key proteins associated with cytokine storm during COVID-19 infection. Our findings support ACE2 activation as a potential drug target for CS control and confirm AT1R inhibition as an alternative strategy. Leveraging deep learning, we identify potential drugs to individually target ACE2 and AT1R, with Lomefloxacin and Fostamatinib emerging as standout options due to their close interaction with ACE2. Their stability within the protein-drug complex suggests superior efficacy among many drugs from our deep-learning analysis. Moreover, there is a significant scope for optimization in fine-tuning protein-drug interactions. Strong binding alone may not be the sole determining factor for potential drugs; precise adjustments are essential. The application of advanced computational power offers novel solutions, circumventing time-consuming lab work. In scenarios necessitating both ACE2 and AT1R targeting, optimal drug combinations can be derived from our analysis of drug-drug interactions, as detailed in the manuscript.
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COVID-19-related conspiracy beliefs and their relationship with perceived stress and pre-existing conspiracy beliefs in a Prolific Academic sample: A replication and extension of Georgiou et al. (2020) -
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+The authors reanalyzed the data and conducted a close replication of a study by Georgiou et al. (2020), who found amongst 660 (reported in abstract) or 640 (reported in participant section) participants that 1) COVID-19 related conspiracy theory beliefs were strongly related to broader conspiracy theory beliefs, that 2) COVID-19 related conspiracy beliefs were higher in those with lower levels of education, and that 3) COVID-19 related conspiracy beliefs were positively (although weakly) correlated with more negative attitudes towards different individual items measuring the governmentâs response. Finally, Georgiou et al. (2020) found that 4) COVID-19 beliefs were unrelated to self-reported stress. Reanalyzing their data and adjusting the analytical framework, the authors only found that an average of attitudes towards the appropriateness of the government response towards the pandemic was negatively related to conspiracy beliefs in general (not just COVID-19). In the present replication and extension study, random forest analyses show that attitude towards government responses (like the original study), stress (unlike the original study), and attachment avoidance towards the partner (unlike the original study) are the most important predictors of conspiracy beliefs. However, the explained variance of the whole random forest model (3.5-7.5%) was low and model fit of the presently and widely used conspiracy belief inventories was poor. Measurement error is a likely explanation for the differences between the original and replication study and independent development-validation studies therefore need to be conducted to better measure conspiracy beliefs.
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Algorithm for selecting potential SARS-CoV-2 dominant variants based on POS-NT frequency -
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+COVID-19, currently prevalent worldwide, is caused by a novel coronavirus, SARS-CoV-2. Similar to other RNA viruses, SARS-CoV-2 continues to evolve through random mutations, creating numerous variants, such as Alpha, Beta, and Delta. It is, therefore, necessary to predict the mutations constituting the dominant variant before they are generated. This can be achieved by continuously monitoring the mutation trends and patterns. Hence, in the current study, we sought to design a dominant variant candidate (DVC) selection algorithm. To this end, we obtained COVID-19 sequence data from GISAID and extracted position-nucleotide (POS-NT) frequency ratio data by country and date through data preprocessing. We then defined the dominant dates for each variant in the USA and developed a frequency ratio prediction model for each POS-NT. Based on this model, we applied DVC criteria to develop the selection algorithm, verified for Delta and Omicron. Using Condition 3 as the DVC criterion, 69 and 102 DVC POS-NTs were identified for Delta and Omicron an average of 47 and 82 days before the dominant dates, respectively. Moreover, 13 and 44 Delta- and Omicron-defining POS-NTs were recognized 18 and 25 days before the dominant dates, respectively. We identified all DVC POS-NTs before the dominant dates, including soaring and gently increasing POS-NTs. Considering that we successfully defined all POS-NT mutations for Delta and Omicron, the DVC algorithm may represent a valuable tool for providing early predictions regarding future variants, helping improve global health.
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Harmonizing Government Responses to the COVID-19 Pandemic -
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+Public health and safety measures (PHSM) made in response to the COVID-19 pandemic have been singular, rapid, and profuse compared to the content, speed, and volume of normal policy-making. Not only can they have a profound effect on the spread of the virus, but they may also have multitudinous secondary effects, in both the social and natural worlds. Unfortunately, despite the best efforts by numerous research groups, existing data on COVID-19 PHSM only partially captures their full geographical scale and policy scope for any significant duration of time. This paper introduces our effort to harmonize data from the eight largest such efforts for policies made before September 21, 2021 into the taxonomy developed by the CoronaNet Research Project in order to respond to the need for comprehensive, high quality COVID-19 data. In doing so, we present a comprehensive comparative analysis of existing data from different COVID-19 PHSM datasets, introduce our novel methodology for harmonizing COVID-19 PHSM data, and provide a clear-eyed assessment of the pros and cons of our efforts.
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SARS-CoV-2 NSP5 Antagonizes MHC II Expression by Subverting Histone Deacetylase 2 -
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+SARS-CoV-2 interferes with antigen presentation by downregulating MHC II on antigen presenting cells, but the mechanism mediating this process is unelucidated. Herein, analysis of protein and gene expression in human antigen presenting cells reveals that MHC II is downregulated by the SARS-CoV-2 main protease, NSP5. This suppression of MHC II expression occurs via decreased expression of the MHC II regulatory protein CIITA. This downregulation of CIITA is independent of NSP5âs proteolytic activity, but rather, NSP5 delivers HDAC2 to IRF3 at an IRF binding site within the CIITA promoter. Here, HDAC2 deacetylates and inactivates the CIITA promoter. This loss of CIITA expression prevents further expression of MHC II, with this suppression alleviated by ectopic expression of CIITA or knockdown of HDAC2. These results identify a mechanism by which SARS-CoV-2 limits MHC II expression, thereby delaying or weakening the subsequent adaptive immune response. Importance: SARS-CoV-2 alters the expression of many immunoregulatory proteins to limit and delay the host antiviral response, thereby producing a more severe and longer-lasting infection. Preventing and limiting the activation of helper T cells by reducing MHC II expression on antigen presenting cells is one of these strategies, but while this mechanism was identified early in the pandemic, the mechanism allowing SARS-CoV-2 to limit MHC II expression has remained unclear. Herein, we demonstrate that this occurs via a tripartite interaction between viral NSP5 and host HDAC2 and IRF3, where a complex of NSP5 and HDAC2 is recruited to IRF3 bound to the promoter of CIITA - the master regulator of MHC II expression - with the delivery of HDAC2 then mediating the deacetylation of the CIITA promoter and the suppression of MHC II expression.
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+In the realm of antibody therapeutics development, increasing the binding affinity of an antibody to its target antigen is a crucial task. This paper presents GearBind, a pretrainable deep neural network designed to be effective for in silico affinity maturation. Leveraging multi-level geometric message passing alongside contrastive pretraining on protein structural data, GearBind capably models the complex interplay of atom-level interactions within protein complexes, surpassing previous state-of-the-art approaches on SKEMPI v2 in terms of Pearson correlation, mean absolute error (MAE) and root mean square error (RMSE). In silico experiments elucidate that pretraining helps GearBind become sensitive to mutation-induced binding affinity changes and reflective of amino acid substitution tendency. Using an ensemble model based on pretrained GearBind, we successfully optimize the affinity of CR3022 to the spike (S) protein of the SARS-CoV-2 Omicron strain. Our strategy yields a high success rate with up to 17-fold affinity increase. GearBind proves to be an effective tool in narrowing the search space for in vitro antibody affinity maturation, underscoring the utility of geometric deep learning and adept pre-training in macromolecule interaction modeling.
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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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Intravenous Immunoglobulin Replacement Therapy for Persistent COVID-19 in Patients With B-cell Impairment - Conditions: COVID-19 Interventions: Drug: Immunoglobulins Sponsors: Jaehoon Ko Not yet recruiting
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Effect of Inhaled Hydroxy Gas on Long COVID Symptoms - Conditions: Post-Acute COVID-19 Syndrome Interventions: Device: Hydroxy gas Sponsors: Oxford Brookes University Recruiting
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PROmotion of COVID-19 BOOSTer VA(X)Ccination in the Emergency Department - PROBOOSTVAXED - Conditions: COVID-19 Interventions: Behavioral: Vaccine Messaging; Behavioral: Vaccine Acceptance Question Sponsors: University of California, San Francisco; National Institute of Allergy and Infectious Diseases (NIAID); Pfizer; Duke University; Baylor College of Medicine; Thomas Jefferson University Not yet recruiting
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Community Care Intervention to Decrease COVID-19 Vaccination Inequities - Conditions: COVID-19 Vaccination Interventions: Behavioral: Community Health Worker Intervention to Enhance Vaccination Behavior (CHW-VB) Sponsors: RAND; Clinical Directors Network; National Institute on Minority Health and Health Disparities (NIMHD) Recruiting
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Evaluating a Comprehensive Multimodal Outpatient Rehabilitation Program for PASC Program to Improve Functioning of Persons Suffering From Post-COVID Syndrome: A Randomized Controlled Trial - Conditions: Post-Acute COVID-19; Post-Acute COVID-19 Syndrome; Post-Acute COVID-19 Infection; Long COVID; Long Covid19; Dyspnea; Orthostasis; Cognitive Impairment Interventions: Other: Comprehensive Rehabilitation; Other: Augmented Usual Care Sponsors: University of Pennsylvania; Medical College of Wisconsin; National Institutes of Health (NIH) Not yet recruiting
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Stem Cell Study for Long COVID-19 Neurological Symptoms - Conditions: Post-Acute COVID-19 Syndrome Interventions: Biological: Stem Cell Sponsors: Charles Cox; CBR Systems, Inc. Not yet recruiting
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Pursuing Reduction in Fatigue After COVID-19 Via Exercise and Rehabilitation (PREFACER): A Randomized Feasibility Trial - Conditions: Long-COVID; Long Covid19; Post-COVID-19 Syndrome; Post-COVID Syndrome; Fatigue Interventions: Other: COVIDEx Sponsors: Lawson Health Research Institute; Western University Not yet recruiting
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Multilevel Intervention of COVID-19 Vaccine Uptake Among Latinos - Conditions: Vaccine Hesitancy Interventions: Behavioral: Multilevel Intervention Sponsors: San Diego State University Not yet recruiting
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Effect of Metformin in Reducing Fatigue in Long COVID in Adolescents - Conditions: Long COVID Interventions: Drug: Metformin; Other: Placebo Sponsors: Trust for Vaccines and Immunization, Pakistan Not yet recruiting
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A Randomized Trial Evaluating a mRNA VLP Vaccineâs Immunogenicity and Safety for COVID-19 - Conditions: COVID-19; SARS-CoV-2 Infection Interventions: Biological: AZD9838; Biological: Licensed mRNA vaccine Sponsors: AstraZeneca Not yet recruiting
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From PubMed
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Danshensu inhibits SARS-CoV-2 by targeting its main protease as a specific covalent inhibitor and discovery of bifunctional compounds eliciting antiviral and anti-inflammatory activity - The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to human. Since there are still no effective treatment options against the new emerging variants of SARS-CoV-2, it is necessary to devote a continuous endeavor for more targeted drugs and the preparation for the next pandemic. Salvia miltiorrhiza and its active ingredients possess wide antiviral activities, including against SARS-CoV-2. Danshensu, as one ofâŠ
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Exciting Advances in Sustainable Spectrophotometric Micro-Quantitation of an Innovative Painkiller âTramadol and Celecoxibâ Mixture in the Presence of Toxic Impurity, Promoting Greenness and Whiteness Studies - CONCLUSION: The methodologies developed were thoroughly validated in compliance with ICH guidelines. Student t and F-tests revealed no statistically substantial variation among the current methods and the reported method.
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The possible role of nuclear factor erythroid-2-related factor 2 activators in the management of Covid-19 - COVID-19 is caused by a novel SARS-CoV-2 leading to pulmonary and extra-pulmonary manifestations due to oxidative stress (OS) development and hyperinflammation. COVID-19 is primarily asymptomatic though it may cause acute lung injury (ALI), acute respiratory distress syndrome (ARDS), systemic inflammation, and thrombotic events in severe cases. SARS-CoV-2-induced OS triggers the activation of different signaling pathways, which counterbalances this complication. One of these pathways is nuclearâŠ
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Generation and Characterization of Monoclonal Antibodies against Swine Acute Diarrhea Syndrome Coronavirus Spike Protein - Swine acute diarrhea syndrome coronavirus (SADS-CoV), a member of the family Coronaviridae and the genus Alphacoronavirus, primarily affects piglets under 7 days old, causing symptoms such as diarrhea, vomiting, and dehydration. It has the potential to infect human primary and passaged cells in vitro, indicating a potential risk of zoonotic transmission. In this study, we successfully generated and purified six monoclonal antibodies (mAbs) specifically targeting the spike protein of SADS-CoV,âŠ
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Dual Effects of 3-epi-betulin from Daphniphyllum glaucescens in Suppressing SARS-CoV-2-Induced Inflammation and Inhibiting Virus Entry - The continuous emergence of SARS-CoV-2 variants has led to a protracted global COVID-19 pandemic with significant impacts on public health and global economy. While there are currently available SARS-CoV-2 vaccines and therapeutics, most of the FDA-approved antiviral agents directly target viral proteins. However, inflammation is the initial immune pathogenesis induced by SARS-CoV-2 infection, there is still a need to find additional agents that can control the virus in the early stages ofâŠ
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Discovery of Anti-Coronavirus Cinnamoyl Triterpenoids Isolated from Hippophae rhamnoides during a Screening of Halophytes from the North Sea and Channel Coasts in Northern France - The limited availability of antiviral therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spurred the search for novel antiviral drugs. Here, we investigated the potential antiviral properties of plants adapted to high-salt environments collected in the north of France. Twenty-five crude methanolic extracts obtained from twenty-two plant species were evaluated for their cytotoxicity and antiviral effectiveness against coronaviruses HCoV-229E and SARS-CoV-2. Then, aâŠ
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The Effect of SARS-CoV-2 Spike Protein RBD-Epitope on Immunometabolic State and Functional Performance of Cultured Primary Cardiomyocytes Subjected to Hypoxia and Reoxygenation - Cardio complications such as arrhythmias and myocardial damage are common in COVID-19 patients. SARS-CoV-2 interacts with the cardiovascular system primarily via the ACE2 receptor. Cardiomyocyte damage in SARS-CoV-2 infection may stem from inflammation, hypoxia-reoxygenation injury, and direct toxicity; however, the precise mechanisms are unclear. In this study, we simulated hypoxia-reoxygenation conditions commonly seen in SARS-CoV-2-infected patients and studied the impact of the SARS-CoV-2âŠ
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Thrombotic anti-PF4 immune disorders: HIT, VITT, and beyond - Antibodies against the chemokine platelet factor 4 (PF4) occur often, but only those that activate platelets induce severe prothrombotic disorders with associated thrombocytopenia. Heparin-induced thrombocytopenia (HIT) is the prototypic anti-PF4 disorder, mediated by strong activation of platelets through their FcÎłIIa (immunoglobulin G [IgG]) receptors (FcÎłRIIa). Concomitant pancellular activation (monocytes, neutrophils, endothelium) triggers thromboinflammation with a high risk for venous andâŠ
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Comparison of kits for SARS-CoV-2 extraction in liquid and passive samples - Effective extraction and detection of viral nucleic acids from sewage are fundamental components of a successful SARS-CoV-2 sewage surveillance program. As there is no standard method employed in sewage surveillance, understanding the performance of different extraction kits in the recovery of SARS-CoV-2 and the impact that PCR inhibitors have on quantification is essential to minimise data discrepancies caused by sample extraction. Three commercial nucleic acid extraction kits: RNeasy PowerSoilâŠ
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New anti-SARS-CoV-2 aminoadamantane compounds as antiviral candidates for the treatment of COVID-19 - Here, the antiviral activity of aminoadamantane derivatives were evaluated against SARS-CoV-2. The compounds exhibited low cytotoxicity to Vero, HEK293 and CALU-3 cells up to a concentration of 1,000 ”M. The inhibitory concentration (IC(50)) of aminoadamantane was 39.71 ”M in Vero CCL-81 cells and the derivatives showed significantly lower IC(50) values, especially for compounds 3F4 (0.32 ”M), 3F5 (0.44 ”M) and 3E10 (1.28 ”M). Additionally, derivatives 3F5 and 3E10 statistically reduced theâŠ
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Pan-antiviral effects of a PIKfyve inhibitor on respiratory virus infection in human nasal epithelium and mice - Endocytosis, or internalization through endosomes, is a major cell entry mechanism used by respiratory viruses. Phosphoinositide 5-kinase (PIKfyve) is a critical enzyme for the synthesis of phosphatidylinositol (3, 5)biphosphate (PtdIns (3, 5)P2) and has been implicated in virus trafficking via the endocytic pathway. In fact, antiviral effects of PIKfyve inhibitors against SARS-CoV-2 and Ebola have been reported, but there is little evidence regarding other respiratory viruses. In this study, weâŠ
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Analysis of bioactive compounds of Olea europaea as potential inhibitors of SARS-CoV-2 main protease: a pharmacokinetics, molecular docking and molecular dynamics simulation studies - COVID-19 is a highly infectious disease caused by a new type of extremely contagious coronavirus called SARS-CoV-2. The virusâs main protease enzyme, SARS-CoV-2 Mpro, is essential for its replication and transcription processes. Targeting this enzyme presents a promising avenue for antiviral drug development. Researchers have explored the intricate three-dimensional configurations of the enzyme, analyzing its interactions with various inhibitors. These findings provide a foundation for designingâŠ
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Design, synthesis and biological evaluation of biaryl amide derivatives against SARS-CoV-2 with dual-target mechanism - The COVID-19 pandemic highlights the urgent need to develop effective small-molecule antivirals. Thirty-three novel biaryl amide derivatives were synthesized and evaluated for anti-coronaviral activity. Some significant SARs were uncovered and the intensive structure modifications led to the most active compounds 8b and 8h. The broad-spectrum anti-coronaviral effects of 8h were validated at RNA and protein levels. 8h inhibits coronavirus replication at multiple stages, from virus entry to virusâŠ
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Inhibition of SARS-CoV-2 infection and replication by Petasites hybridus CO2-extract (Ze 339) - CONCLUSION: Thereby, Ze 339 attenuated epithelial infection by SARS-CoV-2 and modeled the IFN response. In conclusion, this study highlights Ze 339 as a potential treatment option for COVID-19 that limits infection-associated cell intrinsic immune responses.
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Integrin α5ÎČ1 contributes to cell fusion and inflammation mediated by SARS-CoV-2 spike via RGD-independent interaction - The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infects host cells by engaging its spike (S) protein with human ACE2 receptor. Recent studies suggest the involvement of integrins in SARS-CoV-2 infection through interaction with the S protein, but the underlying mechanism is not well understood. This study investigated the role of integrin α(5)ÎČ(1), which recognizes the Arg-Gly-Asp (RGD) motif in its physiological ligands, in S-mediated virus entry and cell-cell fusion. OurâŠ
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From Patent Search
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What October 7th Did and Didnât Change About Israeli Politics - A pollster examines support for a two-state solution, Benjamin Netanyahuâs falling approval ratings, and why the next Prime Minister may not change course on relations with Palestinians. - link
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What Would Sandra Day OâConnor Have Thought About Affirmative Action for Men? - For decades, college-admissions offices have quietly imposed higher standards on female applicants. - link
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The Capital Has a Bad Case of Year-End Panic - Worries about a second Trump term and the end of aid to Ukraine are entirely justified. - link
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How Hamas Used Sexual Violence on October 7th - Physicians for Human Rights Israel issued a report collecting evidence of sexual and gender-based violence. One of its authors lays out their findings. - link
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The Israel-Hamas Prisoner Swap, from the West Bank - Outside a prison where detained Palestinians were released, celebration and chaos. - link
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From Vox
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Resilience is invaluable in tough times. Hereâs how to build it. -
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+Getty Images/fStop
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+Adapting to change is never easy, but you can shift how you respond to stress.
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+When Luana Marques was growing up in Brazil, life was not easy. Her parents had her when they were very young, and they didnât know how to take care of themselves, much less their children. Drugs and alcohol were also a problem. âBetween the many instances of domestic violence, I often felt scared, wondering when something bad would happen next,â she says. She lived in poverty with a single mother and experienced a lot of trauma and adversity. Eventually, she moved in with her grandmother, who taught her how to approach her fears without avoiding them, and to tolerate discomfort. âMy grandmother would call that being the water, not the rock,â she says. âWhen change happens, some of us become stuck, like the rock. The opposite is being the water. You flow around the change.â
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+Years later, when Marques, now an associate professor of psychology at Harvard Medical School, was studying cognitive behavioral therapy, she realized that her grandmother had been giving her lessons in resilience.
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+The American Psychological Association defines resilience as âsuccessfully adapting to difficult or challenging life experiences, especially through mental, emotional, and behavioral flexibility,â but Marques puts it more simply: âThe way I think about it is the ability to build mental strength in such a way that your brain has whatâs known as âcognitive flexibility,ââ she says. âIt means that when life throws you curveballs or adversity, you are able to make decisions that are aligned with your values.â
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+As stressors like war in Ukraine and the Middle East pile on top of the pandemic, inflation, layoffs, and growing rates of anxiety and depression, cognitive flexibility can be an important skill to hone and keep in our emotional toolboxes.
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+But the good news is, resilience isnât a fixed asset. Though studies show that some people are naturally more resilient than others, just as some people are naturally more optimistic, there are ways to strengthen those muscles. Heidemarie Laurent, a professor of caring and compassion at Penn State University (yes, this is really a thing), focuses on resilience in her work at the schoolâs College of Health and Human Development. âThere is no one prescription,â she says. âFor each person, itâs finding what you can really integrate into your life and stick with.â
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+Pause so you can respond better
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+The first step to becoming more resilient is to understand how your brain works. When youâre stressed, your amygdala, the part of your brain that handles fear, is activated, and you have a fight-or-flight response. âWhen you say to someone, âIâm so anxious, I canât think straight,â thatâs actually your biology,â Marques says. âYou canât think straight because your prefrontal cortex is offline.â Instead of immediately reacting, Marques recommends that you recognize your emotional response to stress and take a pause. âThatâs our superpower that we donât use enough,â she says. âThe ability to say, âOkay, Iâm really angry, but I donât have to act on that anger yet.â Creating that pause builds resilience.â
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+Build community and improve self-talk
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+Taking a beat allows you to reframe the way youâre looking at a situation. When experiencing stress, one of the first things we typically do is appraise it to determine how taxing it may be. Social support is one of the biggest assets that plays into that appraisal, says Jennifer Wegmann, a professor of health and wellness studies at Binghamton University whose research focuses on stress mindsets. Just knowing that you have a text chain of friends you can vent to or family that can drop off groceries while youâre sick makes you feel as though youâre better able to handle the situation. âSocial connectedness is honestly a game changer when it comes to stress,â she says. âIt is one of the most powerful strategies and tools that we have.â
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+Itâs also something that you can grow. Communities shifted in myriad ways during the pandemic years, and making friends as an adult has never been easy. If youâre feeling unmoored or unsupported, look for ways you can expand your social circle by joining clubs, asking a coworker to get coffee, starting playground meet-ups, or volunteering. âPivoting outward to the needs of others in your networks can reinforce the realization that youâre a part of an interdependent network of humans,â says Laurent. âHelping others can be a really powerful strategy for improving our well-being.
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+Another big piece of reframing your view of stress is changing the way you talk to yourself. Too often, when weâre scared, we get trapped in cycles of negative thoughts, bullying ourselves in a way we never would a friend. To widen your perspective, Marques recommends asking yourself, âHow would I talk to a friend in this scenario?â Would you tell them thereâs no way they can finish a test on time or that a work project just isnât good enough? Make a conscious effort to give yourself the support you would give a friend.
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+Approach your fears head-on
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+Sometimes, itâs hard for us to even think about the things that stress us out, much less face them head-on. Or we look so far into the future that we canât deal with the decisions of the present moment. But, âresilient people walk toward their anxiety and stress,â Marques says. To ease that fear, she recommends finding ways to make your stressor less scary. If youâre afraid to ask for a raise, stopping to sit and write down five reasons you deserve it can help reinforce your own worthiness. If you have a stack of bills piling up, taking the first step of opening the envelopes and not putting pressure on yourself to take a second and third step could ease the process in the long run. Itâs about âremoving that extra layer of struggle with reality that gets in the way of meeting a situation as skillfully as possible,â Laurent says. âIf Iâm stuck getting frustrated with âthis shouldnât be so,â itâs actually just creating more suffering within me. If I start with, âHere is the situation, and how can I meet that whether I like it or not?â I leave space for myself to act.â
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+Mindfulness can also help. Itâs a term people love to chat about on social media, but Laurent defines it as âfully living moment to moment with awareness of what is actually happening, and not our internal stories about what is happening.â Building mindfulness might involve activities like meditation or spiritual practices, but it can also mean going for a walk in nature or taking in artwork, music, or other things you find beautiful. It can also involve spending time with other people where youâre having a more thoughtful conversation that leads to deep awareness about whatâs going on with you and the other person.
+
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+Align with your values
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+A huge part of resilience is making sure that you make decisions that match your values. If you say family is very important to you but you donât make it home for dinner every night, thereâs a dissonance there. âIf you live a life where values are aligned with actions, you have less stress, less anxiety, and more life satisfaction,â Marques says.
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+And though you may think you already know what your values are, Wegmann recommends sitting down and thinking about what matters to you. âThat takes time,â she says. âYou have to be present and really be reflective to get to the nitty-gritty of, âWhat are my top values? What is most important to me?ââ If your decisions are not lining up with those values, itâs time to make some changes and possibly set some boundaries. Are there things you can do to adjust your work/life balance? Do you need to start saying no to more things to protect the time you need to exercise, or spend time with valued friends? âOur willingness and our ability to put these bumper guards around us is one of the ways in which we can highlight our resilient nature because it changes how we navigate through the stress process,â Wegmann says.
+
+
+Gratitude can be a piece of it, too. Keeping a gratitude journal or making a practice of finding five things youâre grateful for every day can not only help reveal things you value, but also lead to more positive feelings, she says. âItâs really connected to happiness,â
+
+
+Focus on healthy habits
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+Even the most stress-resistant humans are going to have trouble bouncing back from adversity if theyâre not taking care of themselves. The very basic healthy habits weâre all told to work toward â enough sleep, a healthy diet, regular exercise â are the foundations that hold up our ability to deal with stress. âIf youâre not sleeping enough, if youâre not moving your body and youâre not eating enough, you just donât have enough energy in your body to even get your brain to function,â Marques says. âAnd so whenever somebody comes to me and says, âI need help with anxiety,â I say, âHowâs your eating? Howâs your sleeping? Howâs your exercise?â Because if I donât get your foundation right, then you donât even know if youâre hungry or youâre anxious.â
+
+
+Know that resilience is a process
+
+
+The process is not linear, and thatâs okay. âA personâs journey to becoming more resilient is more of a spiral or a labyrinth,â Laurent says. âAt times, it might feel like youâre going backward from where you started. But all those twists and turns are taking you along this path. And seeing that is part of having a broader perspective.â Itâs important to look back and give yourself credit for the stressors you have moved through and all the adversity you have overcome. You can remind yourself that if youâve gotten this far, you know you can take on the next thing that comes your way.
+
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+Marques, who wrote Bold Move: A 3-Step Plan to Transform Anxiety Into Power, has seen people who have focused on resilient practices change the trajectory of their lives. In working with a nonprofit focused on men transitioning out of prison, she met a young man who told her that after a challenging look from another man, he asked a friend to bring him a gun so he could shoot him. But in the time it took for the gun to arrive, he paused, thought about his options and what he wanted, and walked away. After a presentation, a woman came up to her and said Marques had convinced her not to quit her job and deal with problems at work instead, and she got a promotion. But most of all, Marques knows that her grandmotherâs lessons in resilience are the reason she was able to leave Brazil and make it to Harvard. âIf her advice didnât work, I wouldnât be sitting here right now,â she says.
+
+
Can Democrats overcome their deep divisions over Gaza? -
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+US Reps. Ayanna Pressley (D-MA), Alexandria Ocasio-Cortez (D-NY), and Rashida Tlaib (D-MI) listen during a news conference calling for a ceasefire in Gaza outside the US Capitol building on November 13, 2023, in Washington, DC. | Anna Moneymaker/Getty Images
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+The party is fractured over President Joe Bidenâs unequivocal support for Israel as it continues its military campaign in Gaza ahead of 2024.
+
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+Democratic divisions over the war in Gaza have spilled out into the open in recent weeks, raising questions about the potential electoral consequences ahead of 2024.
+
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+On Tuesday, the House passed a resolution proposed by Republicans that equates anti-Zionism with antisemitism. Republicans said they intended to curb a very real outpouring of antisemitism amid the war. But the actual outcome of the resolution â which advances a misleading premise that criticism of a diverse pro-Israel political movement is equivalent to hatred of Jews â merely put Democratic discord on display.
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+Some 95 Democrats voted for the resolution to show their support for Israel following the October 7 attack by Hamas, a Palestinian militant group designated a terrorist organization by many countries. Another 92 Democrats, including several Jewish Democrats, voted âpresent,â neither supporting nor opposing the resolution. The remaining 13 Democrats, mostly progressives who have called for a ceasefire as the death toll in Gaza surpasses 17,000, voted against the resolution.
+
+
+The divisions go beyond the resolution, however. Rep. Pramila Jayapal (D-WA) has also recently faced backlash from her colleagues for what they perceive as her not being forceful enough in condemning widespread sexual violence that Israel claims Hamas committed on October 7. The criticism came after Jayapal said in an interview with CNN last weekend that while using rape as a tool of war is âhorrific,â âwe have to be balanced about bringing in the outrages against Palestinians.â Several Democrats have since started drafting a resolution condemning the alleged sexual violence, which Hamas has denied despite witness testimony, crime scene photos, and videos posted by Hamas fighters themselves.
+
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+And progressives have sought to place conditions on any military aid sent to Israel, which President Joe Biden and Vice President Kamala Harris have rejected as the administration maintains its unequivocal support for the war. More than a dozen Democratic senators have called for an amendment to a pending $111 billion foreign-aid package â around $10 billion of which would go to Israel â requiring that Israel âabide by US and international law, prioritize the protection of civilians, assure the provision of desperately needed humanitarian assistance to civilians in Gaza, and align with a long-term vision for peace, security, and two-state diplomatic solution,â as Sen. Ed Markey (D-MA) described it in a statement. Moderate Democrats have not joined those calls, and the AP reported that some believe the amendment is unnecessary given that US law already requires that recipients of US military aid respect human rights.
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+Democrats have prided themselves for years on staying unified around core issues in contrast to Republican disarray, but are now facing bitter disagreement about the USâs relationship with Israel.
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+âThereâs a huge cleave in their coalition right now,â said Jason Cabel Roe, a GOP strategist based in Michigan. The state has a large Muslim-American community frustrated with Bidenâs handling of the war, and some political strategists believe that could cost him the critical swing state where a recent poll showed him trailing former President Donald Trump. âHow forceful Biden has been in his support of Israel creates a real problem and forces every Democrat to now pick a side within their coalition,â said Roe.
+
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+Will Democratsâ disagreements actually matter in 2024?
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+
+The division within the Democratic caucus reflects a national debate Republicans believe they can use to their advantage in next yearâs elections.
+
+âPeople are angry about this,â Cahaly said.
+
+
+But Simon Rosenberg, a Democratic strategist who correctly predicted Democratsâ strong performance in the midterms, said that Republicans shouldnât be licking their chops yet. Polls have repeatedly shown that most Democrats approve of Bidenâs approach to the war. There is a sizable share of Democrats who donât approve â 39 percent in a December AP-NORC Center survey, which is consistent with other recent polls by Quinnipiac, Marist, and YouGov. But the question is whether their disagreement with the president will matter when it comes time to vote.
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+âItâs highly unlikely that for other than a small number of people this will be a determinative voting issue for them 11 months from now,â Rosenberg said. âBased on history, where foreign policy issues often are not determinative for many voters, itâs unlikely that this is going to become something that creates a major fissure in the Democratic Party.â
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+So far, it doesnât seem like the war has meaningfully hurt Biden in head-to-head matchups with Trump. There have been six such polls released in the last week in which Biden was ahead or tied with Trump, and in several, he had improved his standing since November. And in a Harvard Institute of Politics poll released earlier this week, Biden was beating Trump among 18- to 29-year-olds by 24 percentage points â the same margin he won by in 2020, according to exit polls.
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+âThere is an important debate happening inside the Democratic Party right now,â Rosenberg said. âIs it going to be corrosive and divisive? Of course, it could be. There isnât a lot of evidence that it is right now.â
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+Democrats still need to be careful about how they manage the war, both in terms of communicating with the American people and in terms of ensuring that the war is âconducted in a way thatâs consistent with our values and policies,â Rosenberg said. So far, he added, Biden has been effective in responding to his more progressive criticsâ calls for a ceasefire while ultimately preserving his pro-Israel stance. The ceasefire, brokered by Qatar and Egypt, was welcomed by Biden, but was only temporary, lifting on December 1 after negotiations between Israel and Hamas deteriorated with each side blaming the other.
+
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+Still, Republicans perceive opportunities to pick up voters who might be alienated by Bidenâs support for Israel.
+
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+That might include Jews who feel Democrats havenât been full-throated enough in their support for the war, Roe said. While any gains with that group might have limited impact in terms of winning elections given that Jewish voters are concentrated in large, mostly Democratic cities, it could be a boon for fundraising, he added.
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+âWhen it comes to defending Jews in America today, Republicans are out there forcefully and aggressively, and obviously, thereâs political opportunity there,â Roe said. âHow are these voters still lined up with Democrats?â
+
+
+Cahaly said that the war may help Republicans reframe the narrative around extremism in their camp, allowing them to point the finger at Democrats for espousing what they perceive as antisemitism. Itâs worth noting, however, that some Republicans who have recently taken up the argument that Democrats belong to an extreme, antisemitic party, including Rep. Elise Stefanik (R-NY) and Rep. Marjorie Taylor Greene (R-GA), are notorious peddlers of antisemitic conspiracy theories themselves.
+
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+Cahaly also sees an opportunity for Republicans to win over disaffected Democrats and independents and energize members of their base who see the pro-Palestinian views of young people as the product of left-wing ideas run amok at institutions like universities. âThere is a price for having the next generation taught a bunch of nonsense,â he said.
+
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+Otherwise, all Republicans really need to do is âsit back and watch [Democrats] burn their house down,â Cahaly said. In his view, thatâs especially the case given the swath of potential independent and third-party candidates angling to enter the race for president, and primary challenges that pro-Israel groups like AIPAC have threatened against Democrats who donât support the war.
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+âThere are going to be a lot of alternatives for people to vote for and make known their displeasure with Biden without having to vote for Trump,â Cahaly said.
+
+
+But while votes like the one on Tuesday create an opportunity for Republicans to keep Democratic divisions in the news and on the minds of voters, Rosenberg argues the Democratic coalition has shown no signs of fraying in actual elections over the last year. The party has notched critical victories in the Virginia legislature, a Wisconsin Supreme Court race, and in preserving abortion rights in Ohio.
+
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+â[Republicans] are the ones that are getting their ass kicked all over the country,â Rosenberg said.
+
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+
+
The many layers of May December -
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+
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+Natalie Portman and Charles Melton in May December. | Courtesy of Netflix
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+
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+May December isnât camp. So what is it?
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+In the opening moments of Todd Haynesâs May December, scandalous tabloid subject-turned-homemaker Gracie (Julianne Moore) opens a refrigerator, dramatically accompanied by a sudden piano sting and an ominous camera zoom.
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+The twist? They might not have enough hot dogs for their upcoming cookout.
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+If that strikes you as funny, youâre not alone. This is a film that reportedly had audiences laughing out loud during its debut, a story the New York Times called âthe most fun filmâ at Cannes 2023. And yet, itâs also a film based on the horrifying real-life story of a sexual predator and her child victim.
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+Viewers have been debating since its December 1 platform release. Is it camp? Is it supposed to be funny? Is Natalie Portman a bad actor or is she just very good at playing a bad one?
+
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+These are all interesting questions to consider, but they arguably obscure the biggest question of all: What does it mean that audiences are laughing at a story as dark as this one â and does that say more about the film or its viewers? Is May December critiquing the exploitative nature of media, or is it an example of the very thing it seeks to deconstruct?
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+[Note: This review contains spoilers.]
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+May December adapts a real-life tabloid scandal
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+May December fictionalizes the story of Mary Kay Letourneau and Vili Fualaau. The pair met when she was a teacher and he was in second grade. After years of plying Fualaau with gifts and special attention, Letourneau became pregnant by Fualaau when he was just 13. Convicted of rape, she was released after just three months but immediately violated parole to become pregnant with Fualaauâs second child. In 2005, after serving a seven-year sentence during which she continued her relationship with Fualaau, Letourneau married him. The couple separated in 2019, shortly before Letourneauâs death from cancer.
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+This crime would be properly viewed today as that of a child predator who successfully spent years grooming her target. In the â90s, however, the media framed it as a star-crossed love story, allowing Letourneau to direct the narrative, so much so that even Fualaauâs own family defended her, insisting the pair were in love and that Fualaau was âextremely matureâ for his age.
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+The film picks up where our cultural memory leaves off. The fictional Gracie and her victim, Joe Yoo (Charles Melton), have been together 24 years. Still living in Savannah, Georgia, where the scandal occurred, theyâre preparing for the graduation day of their younger daughter and son. Into this dynamic saunters a fictional celebrity, Elizabeth (Natalie Portman). But Elizabeth, whoâs trying to get to know Gracie in order to play her for an upcoming film adaptation, isnât an objective observer.
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+Haynesâs directorial choices make it extremely clear that this relationship was far from rosy, indicting not just Letourneau but the onlookers, too â the tabloid media who hyped the story as a romance, the Hollywood machine that made it the stuff of Lifetime movie lore, and the real-life audiences who ate it up. To do that, he utilizes a tonal approach that suggests his three main characters are in three different movies within the movie, each one clashing with the other.
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+May December utilizes clashing perspectives to keep us discomfited
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+Gracie is inside a movie about star-crossed soulmates who find each other against all odds â a movie where she is the hero and the whole world is rooting for her. The hot dog scene is our first tell that Gracieâs world is a delusion. Itâs the kind of overly dramatic stinger we might find in a â90s made-for-TV movie, applied to something vapid. In Gracieâs narcissistic point of view, however, little things become magnified. Today, her tightly controlled world could be disrupted by missing hot dogs; tomorrow, it could be something much worse.
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+Her lawyer reveals to Elizabeth at one point that Gracieâs friends are all Norma Desmonding her â humoring her attempts to set herself up as a baker by ordering cakes they donât eat, just to give her something to do. Gracie clings to this vision of herself; the smallest disturbance leaves her sobbing, desperate for comfort from Joe. She relies on him for everything, and he shoulders everything from emotional support to parenting duties.
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+Yet Joe, much like Fualaau toward the end of his relationship with Letourneau, undergoes an awakening during the film. Over a series of heartbreaking moments beautifully acted by Melton, we see him slowly come to know what the rest of us already do: He was a victim, not a willing participant, in the âlove storyâ planned out for him by Letourneau. In one devastating scene, he watches his son smoke a joint with a look of palpable yearning, reminding viewers that he never got the chance to do something so mundane as a teen because he was robbed of a normal adolescence.
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+ François Duhamel/Courtesy of Netflix
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+Charles Melton and Natalie Portman in May December.
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+Of our three different narratives, only Joeâs is an accurate reflection of reality. That reality is full of troubling conflict; Joeâs devastation at his lost childhood mixes with pride in and love for his kids. He moves through the film with quiet care for his children, for Gracie, for the butterflies heâs been nursing, helping protect them until they, like his own children, can leave their cocoons and fly away.
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+As he begins to understand his situation, Joe seeks help and understanding from Elizabeth; later, he unsuccessfully pleads for help from Gracie herself. But any hope that Elizabeth can be a moral arbiter here quickly dies. Instead, within the tableau of perspectives on Gracieâs crime, she represents the tabloid view, one that sees the âMay-December romanceâ as not only shocking but titillating â ultimately erotic rather than dangerous. She reminds us throughout that in reality, Vili Fualaau was a victim, not just of Letourneau, but of a media machine and a society that was quick to sexualize him.
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+Once we understand this, Portmanâs performance becomes anything but phoned-in. She becomes the key to unlocking the whole movie.
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+Portmanâs performance is crucial to understanding Haynesâs project
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+If this were a typical cautionary tale, Portmanâs character would be the vehicle for the audienceâs moral outrage â the character weâre allowed to relate to and empathize with who serves as our tour guide through the distorted landscape of Gracie and Joeâs relationship.
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+But Elizabeth winds up aiding and abetting the distortion. Portman plays her like an ingenue, a starlet whoâs still in her starlet mode, even though in the world of the film, sheâs an industry veteran of 36 â the same age Gracie was when her relationship with Joe came to light.
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+Over the course of the film, she falls for the fantasy of becoming Gracie. She smiles flirtatiously at teen boys. She gets lost in a wildly inappropriate description of filming sex to a group of high schoolers. Later, she pantomimes sex at the literal scene of the crime â in the pet shop stockroom where Gracie and Joe were ultimately caught.
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+In one charged scene, she allows Gracie to do her makeup and reacts to their intimacy with a homoerotic mix of repulsion and elation. Ultimately, she has sex with Joe â then, finally, fully transforms into the older seductress by performing one of Gracieâs love letters as a monologue.
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+ Courtesy of Netflix
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+Julianne Moore and Natalie Portman serving homoerotic vibes (but donât call it camp!).
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+The more she is drawn into this version of the story, the more callous Elizabeth becomes. After viewing footage of 13-year-olds auditioning for the role of Joe in the movie sheâs in, she complains to the director that they arenât âsexy enough.â When Joe angrily insists to her that his life isnât a story, she says calmly, âThereâs no need to get so worked up about itâ â exactly the kind of thing Gracie herself might say. She becomes fully swept up in a story thatâs all about her and her repressed sexual desires coming to the fore.
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+The difficulty audiences have had in parsing what Portman is doing reveals just how smart her performance is: Sheâs so believable that not everyone believes sheâs acting. (Portman first championed the script to Haynes, so itâs likely that she was thinking about the layered dynamics at play here long before anyone else.)
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+Our frustrated expectations of Portmanâs role are also tied to confusion over the film itself. With two divas each getting carried away with the idea of themselves as the hero of a fantastical (but in fact disintegrating) love story, itâs easy to see how claims have arisen that May December is a work of camp. It doesnât help that Haynes has a penchant for lush, indulgent dramas (Velvet Goldmine, Carol) that sometimes nudge the campy line between melodrama and farce.
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+So, to really understand May December, we have to understand the ways in which it could be camp â but ultimately isnât.
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+May December isnât camp, but thinking about it through the lens of camp is useful
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+Camp is what happens when societal expectations collide with a character or a persona who canât perform those expectations convincingly. Instead, their attempt at performance unwittingly reveals and magnifies the artifice of those expectations. Camp is closely related to queer identity and performance, which expose the artifice of heteronormativity. Gender and sexual deviance of all kinds are likewise camp-adjacent because they often reveal how absurd the mechanics of repression can be.
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+In Gracieâs case, she is a true sexual deviant whoâs deeply invested in adhering to societal rules. They help validate her version of the narrative. But because sheâs a true deviant, ultimately unable to perform normative social behavior, she breaks the illusion of normalcy in ways that border on hysterical.
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+A perfect example of this is the moment Gracie gushes to Elizabeth about a card Joe gave her years earlier, featuring a banal love note. Then she casually adds that the card was a classroom assignment, reminding Elizabeth and the audience that Joe was a seventh grader. Itâs a hilarious, deeply disturbing moment. These two emotions converging is the essence of camp.
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+For something to truly be camp, however, its presentation has to align with the destabilizing worldview. If the subject, the camera, or the direction is too knowing, the effect can become satirical, and in some cases cringe. (This is also, incidentally, why the Met Gala âcampâ theme was a disaster; you canât plan camp.) But Haynes never allows the artificial, fantasist narratives of Gracie and Elizabeth to overshadow the anguish Melton conveys. As Elizabeth becomes more entranced by Gracieâs story, her performance as Gracie becomes more campy and less effective. Meanwhile, Gracieâs performance of the role of perfect housewife fails to convince anyone but herself.
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+When Joe finally confronts Gracie about the truth of their lives together, the scene is anything but camp. Itâs a deeply troubling reminder that society gave its stamp of approval to a relationship that left him with lifelong trauma. Adding to the discomfort of this moment is that screenwriter Samy Burch uses dialogue from a jaw-dropping real-life 2018 interview with Australian journalist Matt Doran. In the segment, the adult Letourneau and Fualaau have a tense exchange in which she tells him repeatedly, in front of a shocked Doran, that he was âthe bossâ in their relationship.
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+So many contemporary movies and shows based on real events traffic in imitation, with uncanny impressions seen as the highest achievement. What May December does to incorporate this moment is 1000x more interesting. pic.twitter.com/hNQIlQtzZQ
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+Outside of the film, itâs easy to be aghast by this clip. Inside of the film, this moment shatters the idea of âyounger boy pursuing an older womanâ as a legitimate narrative. âYou seduced me,â Gracie tells Joe with complete confidence. Itâs terrifying how effortless Moore makes playing a fictional Letourneau seem.
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+But the film isnât really that interested in condemning Gracie â what would be the point? Instead, its sharpest castigation rests with Elizabeth. In a single role, she is able to embody the amoral self-interest of the tabloids, Hollywood, the public who consumed the story as entertainment, and everyone around Fualaau who left him to his fate.
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+We might ask whether Haynes himself is part of that web of exploitation â after all, isnât May December a coy treatment of a scandal?
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+Yes and no. One function of the filmâs funnier moments is to allow the audience its share of nervous laughter, an exhalation amid our escalating discomfort. If May December were less self-aware, it might belong in the category of camp or failed melodrama; if it were less earnest, it might earn the title of tongue-in-cheek satire. But ultimately, the movieâs discordant aesthetic isnât coy. Itâs about revealing the nightmarish circus that Joe has survived with quiet resilience.
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+And itâs about us: The circus attendees, arriving with popcorn â prepared to laugh, when perhaps we should be in mourning.
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From The Hindu: Sports
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Judy Blue Eyes and Reminiscence catch the eye -
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Ashwini Ponnappa-Tanisha Crasto win Guwahati Masters Super 100 title - The second-seeded Indian combination, which finished runners-up at the Syed Modi International Super 300 tournament last week in Lucknow, beat the world no. 81 combination in a 40-minute final.
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India beats USA 3-2 to finish ninth at Junior Womenâs hockey World Cup - The tense penalty shootout witnessed Mumtaz Khan and Rutaja Dadaso Pisal successfully converting their chances for India, while the latter also scored in sudden death to secure the win for India
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Pakistan cricket team in Australia without a doctor - Sohail Saleem, who was named as the official team doctor for the series in Australia and New Zealand, is yet to join the team
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Pitch was tricky but not as challenging as we made it appear: Deepti Sharma - The hosts, who lost the opening T20I by 38 runs, were shot out for a mere 80 in 16.2 overs on Saturday night
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From The Hindu: National News
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New land allotment policy brings cheer to industries -
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Consumer protection association wants clampdown against âunauthorisedâ fees for LPG delivery persons -
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Durham University: A U.K. collegiate system with a difference - Durham is the only collegiate university in the U.K. apart from Oxford and Cambridge, but its colleges are communities providing personal development and growth, while departments provide teaching
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Ballia man booked for morphing U.P. CM Adityanathâs picture -
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SIT on the money trail in bitcoin scam: were âdivertedâ bitcoins cashed out in local banks? - Investigation has reportedly given SIT officials leads that bitcoins, âdivertedâ from hacker Srikrishna Ramesh alias Sriki, may have been encashed in local Indian banks, through a web of transactions.
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From BBC: Europe
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Polandâs popcorn moment as pro-EU leader Tusk returns to power - Judges, journalists and womenâs groups watch as Polandâs Donald Tusk inches closer to power.
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Aleksandar Vucic: The man who remade Serbia - Aleksandar Vucic has dominated Serbian politics but rivals see elections as a first step in removing him.
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Laura Kuenssberg: Ukraine in âmortal dangerâ without aid, Olena Zelenska warns - Ukraineâs first lady tells Sunday with Laura Kuenssberg that continued Western support is life or death.
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AI: EU agrees landmark deal on regulation of artificial intelligence - The proposed rules cover the use of AI in systems like ChatGPT and by law enforcement.
A locally grown solution for period poverty - A Kenyan tinkerer and Stanford engineer team up to make maxi pads from agave fibers. - link
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The quest to turn basalt dust into a viable climate solution - Sprinkling rock dust on farmland to soak up atmospheric carbon will be tested at large scale. - link
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Hubble back in service after gyro scareâNASA still studying reboost options - NASA is still evaluating Hubble servicing studies from SpaceX and other companies. - link
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EU agrees to landmark rules on artificial intelligence - Legislation lays out restrictive regime for emerging technology. - link
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Revisiting the Ford Mustang Mach-Eâhowâs the pony EV doing 3 years later? - This midsize crossover EV has a lot more competition than when it debuted in 2021. - link
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From Jokes Subreddit
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A little girl wakes up and is hungry. Her mom normally makes her breakfast, but she is in the shower -
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+The girl tells her dad she is really hungry. Dad makes her toast with butter, and squirts some honey on top
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+The girl hasnât had that before, and she really likes it. She says âDaddy, what did you put on top of the bread?â
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+The dad says, âItâs a name your mom always calls me!â
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+Mom comes out of the shower and sees her daughter eating and really happy. She asks the girl, âWhat did your dad make you for breakfast?â
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+The girl said, âDaddy made me toast with asshole!â
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+/cdn.vox-cdn.com/uploads/chorus_asset/file/25141336/MAYDEC_11_04.2022_FD_0078_R.JPG)
François Duhamel/Courtesy of Netflix
+/cdn.vox-cdn.com/uploads/chorus_asset/file/25141341/May_December_n_01_13_08_05_R.JPG)
Courtesy of Netflix
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