Covalent inhibition of the SARS-CoV-2 NiRAN domain via an active-site cysteine.

The kinase-like NiRAN domain of nsp12 in SARS-CoV-2 catalyzes the formation of the 5' RNA cap structure. This activity is required for viral replication, offering a new target for the development of antivirals. Here, we develop a high-throughput assay to screen for small molecule inhibitors targeting the SARS-CoV-2 NiRAN domain.

Molecular identification of whole squids and calamari at fairs and markets in regions of Latin America.

The commercial importance of cephalopods has increased considerably, being an important fishing resource. However, during the preparation for commercialization of those species, they suffer the process known as "finning" which includes removing and separating the head, arm, skin or even having the body structure cut into rings, which ends up making it difficult or often prevents the identification of the species, which can lead to replacements. In this sense, the present study aimed to use the large ribosomal region, rrnL (16S rDNA) to genetically identify cephalopod species sold in markets and fairs in Latin America.

Bicyclic Inhibitors of Branched-Chain α-Keto Acid Dehydrogenase Kinase (BDK) with In Vivo Activity.

Elevated levels of the branched chain α-amino acids valine, leucine, and isoleucine are associated with heart disease and metabolic disorders. The kinase BDK, also known as branched-chain ketoacid dehydrogenase kinase (BCKDK), is a negative regulator of branched-chain α-amino acid metabolism through deactivation of BCKDC, the branched-chain α-ketoacid dehydrogenase complex. Inhibitors of BDK increase the activity of BCKDC and could be useful therapeutic leads for cardiometabolic diseases.

A Chronic Hepatitis B Identification and Surveillance Program Improves Care in an Integrated Health Plan.

Introduction: Optimal management of patients with chronic hepatitis B (CHB) requires surveillance for hepatocellular carcinoma (HCC) and identification of antiviral therapy candidates, but few dedicated CHB surveillance models have been described. Kaiser Permanente Northern California developed a systematic CHB surveillance and management program in 2012. We report the results of the program's performance over the initial 8-year period.

Comparing the Risk of Poor Outcomes Among Hepatitis C-Infected, Cured, and Never-Infected Controls.

Background And Aims: Studies show decreased rates of poor outcomes after hepatitis C virus (HCV) cure. However, there are no data comparing risk of poor outcomes to that of HCV never infected; results that could have implications for those who may not need ongoing specialty follow-up after cure.

Methods: Retrospective cohort study conducted among Kaiser Permanente Northern California adults ages 18 and up between 2002 and 2019.

Asymmetric Catalytic Hydroboration of Enol Carbamates Enables an Enantioselective Matteson Homologation.

Rh-catalyzed asymmetric hydroboration of enol carbamates yields α-boryl carbamates in good enantioselectivity. The enol carbamate starting materials can be prepared with moderate selectivity using a modified Juila olefination and used as an mixture, taking advantage of the faster reactivity of the major isomer in the directed hydroboration. Optically active α-boryl carbamates participate in a Matteson-type homologation with Grignard reagents in which the O-carbamate is substituted with high conservation of optical activity to provide enantioenriched secondary boronic esters.

Identification of potent and reversible piperidine carboxamides that are species-selective orally active proteasome inhibitors to treat malaria.

Malaria remains a global health concern as drug resistance threatens treatment programs. We identified a piperidine carboxamide (SW042) with anti-malarial activity by phenotypic screening. Selection of SW042-resistant Plasmodium falciparum (Pf) parasites revealed point mutations in the Pf_proteasome β5 active-site (Pfβ5).

Identification of pre-flexion fish larvae from the western South Atlantic using DNA barcoding and morphological characters.

Knowledge on species composition is the first step necessary for the proper conservation and management of biological resources and ecologically relevant species. High species diversity and a lack of diagnostic characters for some groups can impose difficulties for taxonomic identification through traditional methodologies, and ichthyoplankton (fish larvae and eggs) are a good example of such a scenario. With more than 35.

Genomic evidence reveals three W-autosome fusions in Heliconius butterflies.

Sex chromosomes are evolutionarily labile in many animals and sometimes fuse with autosomes, creating so-called neo-sex chromosomes. Fusions between sex chromosomes and autosomes have been proposed to reduce sexual conflict and to promote adaptation and reproductive isolation among species. Recently, advances in genomics have fuelled the discovery of such fusions across the tree of life.

All-in-One, Wireless, Multi-Sensor Integrated Athlete Health Monitor for Real-Time Continuous Detection of Dehydration and Physiological Stress.

Athletes are at high risk of dehydration, fatigue, and cardiac disorders due to extreme performance in often harsh environments. Despite advancements in sports training protocols, there is an urgent need for a non-invasive system capable of comprehensive health monitoring. Although a few existing wearables measure athlete's performance, they are limited by a single function, rigidity, bulkiness, and required straps and adhesives.

Thiophenyl Derivatives of Nicotinamide Are Metabolized by the NAD Salvage Pathway into Unnatural NAD Derivatives That Inhibit IMPDH and Are Toxic to Peripheral Nerve Cancers.

N-Pyridinylthiophene carboxamide (compound 21) displays activity against peripheral nerve sheath cancer cells and mouse xenografts by an unknown mechanism. Through medicinal chemistry, we identified a more active derivative, compound , and found that only analogues with structures similar to nicotinamide retained activity. Genetic screens using compound found that both NAMPT and NMNAT1, enzymes in the NAD salvage pathway, are necessary for activity.

Predictors of Reoperation and Survival Experience (Minimum 1 Year) for Primary Versus Conversion Total Hip Arthroplasty in Young Patients.

Background: Total hip arthroplasty (THA), including primary and conversion procedures, is commonly used for many types of joint disease in patients aged below 65 years, though few studies have evaluated THA outcomes in young patients (≤ 40 years old). This study examined a large cohort of patients who underwent THA at a young (≤ 40 years old) age to identify predictors of reoperation and compare survivorship between primary and conversion THAs.

Methods: A retrospective study was conducted on 497 patients who underwent 612 primary and conversion THAs at 40 years old or younger between 1990 and 2020.

Chemoselective and Stereoselective Allylation of Bis(alkenyl)boronates.

Bis(alkenyl)boronates react with optically active Ir(π-allyl) species in a process that involves allylation of the more substituted olefin and 1,2-metalate shift of the less substituted olefin. The method constructs valuable enantioenriched tertiary allylic boronic esters with high chemoselectivity, enantioselectivity and diastereoselectivity. Allylic functionalization reactions transform the 1,3-stereodiad to 1,5- and 1,6-stereochemical relationships.

Predictors of reoperation and survival experience for primary total knee arthroplasty in young patients with degenerative and inflammatory arthritis.

Introduction: While total knee arthroplasty (TKA) is typically implemented in patients > 65 years old, young patients may need to undergo TKA for pain relief and functional improvement. Current data are limited by older cohorts and short-term survival rates. This study aimed to examine a large sample size of patients with degenerative and inflammatory conditions who underwent primary TKA at a young (≤ 40) age to identify predictors of reoperation, as well 15-year survivorship.

Convergent and environmentally associated chromatic polymorphism in Bryconops Kner, 1858 (Ostariophysi: Characiformes: Iguanodectidae).

Bryconops Kner, 1858, includes two well defined subgenera based on morphological evidence, with each containing at least one species (B. (Bryconops) caudomaculatus and B. (Creatochanes) melanurus) with a very wide distribution, within which regional populations present color variations.

effector AvrB is a glycosyltransferase that rhamnosylates plant guardee protein RIN4.

The plant pathogen encodes a type III secretion system avirulence effector protein, AvrB, that induces a form of programmed cell death called the hypersensitive response in plants as a defense mechanism against systemic infection. Despite the well-documented catalytic activities observed in other Fido (c, c, and AvrB) proteins, the enzymatic activity and target substrates of AvrB have remained elusive. Here, we show that AvrB is an unprecedented glycosyltransferase that transfers rhamnose from UDP-rhamnose to a threonine residue of the guardee protein RIN4.

Imaging of Light-Enhanced Extracellular Vesicle-Mediated Delivery of Oxaliplatin to Colorectal Cancer Cells via Laser Ablation, Inductively Coupled Plasma Mass Spectrometry.

Extracellular vesicles (EVs) are lipid bilayer structures released by all cells that mediate cell-to-cell communication via the transfer of bioactive cargo. Because of the natural origin of EVs, their efficient uptake by recipient cells, capacity to stabilize and transport biomolecules and their potential for cell/tissue targeting and preferential uptake by cancer cells, they have enormous potential for bioengineering into improved and targeted drug delivery systems. In this work, we investigated the use of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) as a tool to measure the loading of platinum-based chemotherapeutic agents.

Molecular analyses of carangid fish diets reveal inter-predation, dietary overlap, and the importance of early life stages in trophic ecology.

Carangid fishes are commercially important in fisheries and aquaculture. They are distributed worldwide in both tropical and subtropical marine ecosystems. Their role in food webs is often unclear since their diet cannot be easily identified by traditional gut content analysis.

Enzymatic Resolution and Decarboxylative Functionalization of α-Sulfinyl Esters.

α-Sulfinyl esters can be readily prepared through thiol substitution of α-bromo esters followed by oxidation to the sulfoxide. Enzymatic resolution with lipoprotein lipase provides both the unreacted esters and corresponding α-sulfinyl carboxylic acids in high yields and enantiomeric ratios. Subsequent decarboxylative halogenation, dihalogenation, trihalogenation and cross-coupling gives rise to functionalized sulfoxides.

Inducible mismatch repair streamlines forward genetic approaches to target identification of cytotoxic small molecules.

Orphan cytotoxins are small molecules for which the mechanism of action (MoA) is either unknown or ambiguous. Unveiling the mechanism of these compounds may lead to useful tools for biological investigation and new therapeutic leads. In selected cases, the DNA mismatch repair-deficient colorectal cancer cell line, HCT116, has been used as a tool in forward genetic screens to identify compound-resistant mutations, which have ultimately led to target identification.

Detection, survival, and persistence of Staphylococcus capitis NRCS-A in neonatal units in England.

Background: The multidrug-resistant Staphylococcus capitis clone, NRCS-A, is increasingly associated with late-onset sepsis in low birthweight newborns in neonatal intensive care units (NICUs) in England and globally. Understanding where this bacterium survives and persists within the NICU environment is key to developing and implementing effective control measures.

Aim: To investigate the potential for S.

Merging two eDNA metabarcoding approaches and citizen-science-based sampling to facilitate fish community monitoring along vast Sub-Saharan coastlines.

The coastline of Sub-Saharan Africa hosts highly diverse fish communities of great conservation value, which are also key resources for local livelihoods. However, many costal ecosystems are threatened by overexploitation and their conservation state is frequently unknown due to their vast spatial extent and limited monitoring budgets. Here, we evaluated the potential of citizen science-based eDNA surveys to alleviate such chronic data deficiencies and assessed fish communities in Mozambique using two 12S metabarcoding primer sets.