Engineering and structures of Crimean-Congo hemorrhagic fever virus glycoprotein complexes.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tickborne virus that can cause severe disease in humans with case fatality rates of 10%-40%. Although structures of CCHFV glycoproteins GP38 and Gc have provided insights into viral entry and defined epitopes of neutralizing and protective antibodies, the structure of glycoprotein Gn and its interactions with GP38 and Gc have remained elusive. Here, we use structure-guided protein engineering to produce a stabilized GP38-Gn-Gc heterotrimeric glycoprotein complex (GP38-Gn-Gc).

Chromosome scale genome assembly and annotation of coconut cultivar Chowghat Green Dwarf.

The high-quality genome of coconut (Cocos nucifera L.) is a crucial resource for enhancing agronomic traits and studying genome evolution within the Arecaceae family. We sequenced the Chowghat Green Dwarf cultivar, which is resistant to the root (wilt) disease, utilizing Illumina, PacBio, ONT, and Hi-C technologies to produce a chromosome-level genome of ~ 2.

Composition of carbohydrate, protein and lipid derived from microalgae using thermally pretreated solid waste.

Microalgae are widely recognized for their capacity to generate value-added products in a variety of sectors, including the pharmaceutical and food industries, bioenergy industries and wastewater industries. The quality of a microalga is significantly influenced by its proliferation. Along with growth, the biochemical profile may also vary based on the nutrient that is supplemented.

Limited Short-Term Evolution of SARS-CoV-2 RNA-Dependent RNA Polymerase under Remdesivir Exposure in Upper Respiratory Compartments.

Background: The extent of the SARS-CoV-2 short-term evolution under Remdesivir (RDV) exposure and whether it varies across different upper respiratory compartments are not fully understood.

Methods: Patients hospitalized for COVID-19, with or without RDV therapy, were enrolled and completed up to three visits, in which they provided specimens from four respiratory compartments. Near full-length genome SARS-CoV-2 sequences were obtained from viral RNA, standard lineage and variant assignments were performed, and viral mutations in the RNA-dependent RNA polymerase (RdRp) region-the RDV target gene-were detected and compared between participants with and without RDV, across the four compartments, within participants across visits, and versus a larger sequence dataset.

Network analysis and molecular modeling studies of pinocembrin a bioactive phytochemical of against Parkinson's disease.

Parkinson's disease, a neurodegenerative disorder, is quickly progressing and accounts for 15% of dementia cases. Parkinson's disease is the second most frequent form of neuronal degeneration after Alzheimer's, with an average age of 55 years for individuals exhibiting neuropsychiatric and physiological symptoms. Due to the effectiveness, low toxicity, and low side effects, bioactive compounds from plants have received increased attention recently as therapeutic drugs.

MECHANISMS OF TECOVIRIMAT ANTIVIRAL ACTIVITY AND POXVIRUS RESISTANCE.

Mpox is a zoonotic disease endemic in central and west Africa. However, since 2022, human-adapted mpox virus (MPXV) strains are causing large outbreaks spreading outside these regions, leading the World Health Organization to declare public health emergency twice. Tecovirimat, the most widely used drug to treat these infections, blocks viral egress through a poorly understood mechanism.

Unraveling aortic hemodynamics using fluid structure interaction: biomechanical insights into bicuspid aortic valve dynamics with multiple aortic lesions.

Aortic lesions, exemplified by bicuspid aortic valves (BAVs), can complicate congenital heart defects, particularly in Turner syndrome patients. The combination of BAV, dilated ascending aorta, and an elongated aortic arch presents complex hemodynamics, requiring detailed analysis for tailored treatment strategies. While current clinical decision-making relies on imaging modalities offering limited biomechanical insights, integrating high-performance computing and fluid-structure interaction algorithms with patient data enables comprehensive evaluation of diseased anatomy and planned intervention.

Selective Use of Positive-Pressure Ventilation for Preoxygenation During Air Medical Rapid Sequence Intubation.

Background: Preoxygenation is critical to safe performance of rapid sequence intubation (RSI). The use of positive-pressure ventilation (PPV) has been advocated during preoxygenation but may increase the risk of aspiration.

Objective: To explore the risk-benefit analysis of using PPV during air medical RSI.

Macular neovascularization.

Neovascularization of the macula, a common complication of many chorioretinal diseases such as neovascular age-related macular degeneration, polypoidal choroidal vasculopathy, and pathologic myopia results from increased synthesis of vascular endothelial growth factor (VEGF) by the retinal pigment epithelium and/or Müller cells because of localized ischemia and inflammation. The Consensus on Neovascular AMD Nomenclature (CONAN) study group acknowledged that these vessels may originate from either the choriocapillaris or the retinal microvasculature, prompting them to propose the term 'macular neovascularization' (MNV) to include intraretinal, subretinal, and sub-pigment epithelial neovascularization localized to the macula. MNV frequently appears as a grey-green macular lesion with overlying intraretinal thickening and/or subretinal exudation, causing metamorphopsia, reduced central vision, relative central scotoma, decreased reading speed, and problems with color recognition.

Simulation-driven design of stabilized SARS-CoV-2 spike S2 immunogens.

The full-length prefusion-stabilized SARS-CoV-2 spike (S) is the principal antigen of COVID-19 vaccines. Vaccine efficacy has been impacted by emerging variants of concern that accumulate most of the sequence modifications in the immunodominant S1 subunit. S2, in contrast, is the most evolutionarily conserved region of the spike and can elicit broadly neutralizing and protective antibodies.

A viral vaccine design harnessing prior BCG immunization confers protection against Ebola virus.

Previous studies have demonstrated the efficacy and feasibility of an anti-viral vaccine strategy that takes advantage of pre-existing CD4 helper T (Th) cells induced by bacille Calmette-Guérin (BCG) vaccination. This strategy uses immunization with recombinant fusion proteins comprised of a cell surface expressed viral antigen, such as a viral envelope glycoprotein, engineered to contain well-defined BCG Th cell epitopes, thus rapidly recruiting Th cells induced by prior BCG vaccination to provide intrastructural help to virus-specific B cells. In the current study, we show that Th cells induced by BCG were localized predominantly outside of germinal centers and promoted antibody class switching to isotypes characterized by strong Fc receptor interactions and effector functions.

Crimean-Congo hemorrhagic fever survivors elicit protective non-neutralizing antibodies that target 11 overlapping regions on glycoprotein GP38.

Crimean-Congo hemorrhagic fever virus can cause lethal disease in humans yet there are no approved medical countermeasures. Viral glycoprotein GP38, exclusive to Nairoviridae, is a target of protective antibodies and is a key antigen in preclinical vaccine candidates. Here, we isolate 188 GP38-specific antibodies from human survivors of infection.

A deep learning based cognitive model to probe the relation between psychophysics and electrophysiology of flicker stimulus.

The flicker stimulus is a visual stimulus of intermittent illumination. A flicker stimulus can appear flickering or steady to a human subject, depending on the physical parameters associated with the stimulus. When the flickering light appears steady, flicker fusion is said to have occurred.

Distinct pathway for evolution of enhanced receptor binding and cell entry in SARS-like bat coronaviruses.

Understanding the zoonotic risks posed by bat coronaviruses (CoVs) is critical for pandemic preparedness. Herein, we generated recombinant vesicular stomatitis viruses (rVSVs) bearing spikes from divergent bat CoVs to investigate their cell entry mechanisms. Unexpectedly, the successful recovery of rVSVs bearing the spike from SHC014, a SARS-like bat CoV, was associated with the acquisition of a novel substitution in the S2 fusion peptide-proximal region (FPPR).

Wastewater threshold as an indicator of COVID-19 cases in correctional facilities for public health response: A modeling study.

Although prison facilities are not fully isolated from the communities in which they are located, most of the population is confined and requires high levels of health vigilance and protection. This study aimed to examine the dynamic relationship between facility-level wastewater viral concentrations and the probability of at least one positive COVID-19 case within the facility. The study period was from January 11, 2021 to May 8, 2023.

Fine-tuning spatial-temporal dynamics and surface receptor expression support plasma cell-intrinsic longevity.

Durable serological memory following vaccination is critically dependent on the production and survival of long-lived plasma cells (LLPCs). Yet, the factors that control LLPC specification and survival remain poorly resolved. Using intravital two-photon imaging, we find that in contrast to most plasma cells (PCs) in the bone marrow (BM), LLPCs are uniquely sessile and organized into clusters that are dependent on APRIL, an important survival factor.

Fructosamine and HbA1c: A Correlational Study in a Southeast Asian Population.

Objectives: Fructosamine correlates well with glycated haemoglobin (HbA1c) in Caucasians. This study investigates this correlation and whether fructosamine can reliably estimate glycated haemoglobin in Southeast Asians.

Methods: We recruited 193 participants based on 4 HbA1c bands (<6.

A viral vaccine design harnessing prior BCG immunization confers protection against Ebola virus.

Previous studies have demonstrated the efficacy and feasibility of an anti-viral vaccine strategy that takes advantage of pre-existing CD4 helper T (Th) cells induced by bacille Calmette-Guérin (BCG) vaccination. This strategy uses immunization with recombinant fusion proteins comprised of a cell surface expressed viral antigen, such as a viral envelope glycoprotein, engineered to contain well-defined BCG Th cell epitopes, thus rapidly recruiting Th cells induced by prior BCG vaccination to provide intrastructural help to virus-specific B cells. In the current study, we show that Th cells induced by BCG were localized predominantly outside of germinal centers and promoted antibody class switching to isotypes characterized by strong Fc receptor interactions and effector functions.

RNASEH2B loss and PARP inhibition in advanced prostate cancer.

BACKGROUNDClinical trials have suggested antitumor activity from PARP inhibition beyond homologous recombination deficiency (HRD). RNASEH2B loss is unrelated to HRD and preclinically sensitizes to PARP inhibition. The current study reports on RNASEH2B protein loss in advanced prostate cancer and its association with RB1 protein loss, clinical outcome, and clonal dynamics during treatment with PARP inhibition in a prospective clinical trial.

Chest Decompressions - The Driver of CPR Efficacy: Exploring the Relationship Between Compression Rate, Depth, Recoil Velocity, and End-Tidal CO2.

Objective: Cardiopulmonary arrest survival is dependent on optimization of perfusion high quality cardiopulmonary resuscitation (CPR), defined by a complex dynamic between rate, depth, and recoil velocity. Here we explore the interaction between these metrics and create a model that explores the impact of these variables on compression efficacy.

Methods: This study was performed in a large urban/suburban fire-based emergency medical services (EMS) system over a nine-month period from 2019 to 2020.