Environmental selection and advective transport shape the distribution of two cyst-forming Acantharia clades in the Canadian Arctic.

Anthropogenic induced climate perturbations are seen in changes in oceanic circulation patterns, and Arctic water masses defined by salinity are vulnerable to change. Biogeography of marine microbial eukaryotes is expected to be impacted by changes in local environmental conditions and advective processes, but tracking the extent of plankton distribution requires understanding routes for both active and passive tracers. To identify such tracers, we focused on samples collected in the western (Canada Basin) and eastern (Nares Strait); extremes of the Canadian High Arctic that are connected by an east flowing current north of Canada.

Zanubrutinib, Obinutuzumab, and Venetoclax for First-Line Treatment of Mantle Cell Lymphoma with a TP53 Mutation.

TP53-mutant mantle cell lymphoma (MCL) is associated with poor survival outcomes with standard chemoimmunotherapy. Dual BTK and BCL2-inhibition with or without anti-CD20 monoclonal antibody therapy has shown promising activity in TP53-mutant MCL. We conducted a multi-center phase 2 study of zanubrutinib, obinutuzumab, and venetoclax (BOVen) in untreated MCL patients with TP53 mutation.

Neuronal lipid droplets play a conserved and sex-biased role in maintaining whole-body energy homeostasis.

Lipids are essential for neuron development and physiology. Yet, the central hubs that coordinate lipid supply and demand in neurons remain unclear. Here, we combine invertebrate and vertebrate models to establish the presence and functional significance of neuronal lipid droplets (LD) .

Lacticaseibacillus rhamnosus HA-114 and Bacillus subtilis R0179 Prolong Lifespan and Mitigate Amyloid-β Toxicity in C. elegans via Distinct Mechanisms.

Background: Recent advances linking gut dysbiosis with neurocognitive disorders such as Alzheimer's disease (AD) suggest that the microbiota-gut-brain axis could be targeted for AD prevention, management, or treatment.

Objective: We sought to identify probiotics that can delay Aβ-induced paralysis.

Methods: Using C.

Diverse winter communities and biogeochemical cycling potential in the under-ice microbial plankton of a subarctic river-to-sea continuum.

Unlabelled: Winter conditions greatly alter the limnological properties of lotic ecosystems and the availability of nutrients, carbon, and energy resources for microbial processes. However, the composition and metabolic capabilities of winter microbial communities are still largely uncharacterized. Here, we sampled the winter under-ice microbiome of the Great Whale River (Nunavik, Canada) and its discharge plume into Hudson Bay.

Outcomes at 7 Years of Age of Former Very Preterm Neonates with Repeated Surfactant Treatment for Prolonged Respiratory Distress in the Neonatal Period.

This study aimed at evaluating the 7-year outcomes of 118 very preterm newborns (VPNs, gestational age = 26 ± 1.4 w) involved in a randomized controlled trial. They presented neonatal respiratory distress (RDS), requiring ventilation for 14 ± 2 days post-natal age (PNA).

Modulating the selectivity of inhibitors for prolyl oligopeptidase inhibitors and fibroblast activation protein-α for different indications.

We have previously described several different chemical series of bicyclic prolyl oligopeptidase (POP) inhibitors as probes for neurodegenerative diseases that demonstrated nanomolar activity in vitro and submicromolar activity in cellulo. The more recent implication of POP in cancer, together with homologous fibroblast activation protein α (FAP), implicated in tumor growth, led us to consider developing POP/FAP dual inhibitors as a promising strategy for the development of cancer therapeutics. At this stage, we thought to evaluate the requirements for selectivity of inhibitors for POP over FAP and to evaluate molecular platforms that would enable the development of selective POP and dual POP/FAP inhibitors.

Genetic and pharmacological PARP inhibition reduces axonal degeneration in C. elegans models of ALS.

Axonal degeneration is observed in early stages of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). This degeneration generally precedes apoptosis and therefore may be a promising therapeutic target. An increasing number of genes have been identified to actively regulate axonal degeneration and regeneration; however, only a few potential therapeutic targets have been identified in the context of neurodegenerative diseases.

Docking Ligands into Flexible and Solvated Macromolecules. 8. Forming New Bonds─Challenges and Opportunities.

Over the years, structure-based design programs and specifically docking small molecules to proteins have become prominent in drug discovery. However, many of these computational tools have been developed to primarily dock enzyme inhibitors (and ligands to other protein classes) relying heavily on hydrogen bonds and electrostatic and hydrophobic interactions. In reality, many drug targets either feature metal ions, can be targeted covalently, or are simply not even proteins (e.

Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CL covalent inhibitors.

Severe diseases such as the ongoing COVID-19 pandemic, as well as the previous SARS and MERS outbreaks, are the result of coronavirus infections and have demonstrated the urgent need for antiviral drugs to combat these deadly viruses. Due to its essential role in viral replication and function, 3CL (main coronaviruses cysteine-protease) has been identified as a promising target for the development of antiviral drugs. Previously reported SARS-CoV 3CL non-covalent inhibitors were used as a starting point for the development of covalent inhibitors of SARS-CoV-2 3CL.

A single copy transgenic mutant FUS strain reproduces age-dependent ALS phenotypes in .

Mutations in the human DNA/RNA binding protein FUS are associated with amyotrophic lateral sclerosis and frontotemporal lobar degeneration, including some aggressive and juvenile onset forms. Cytoplasmic inclusions of human FUS proteins are observed in various neurodegenerative disorders, such as Huntington's disease or spinocerebellar ataxia, suggesting that FUS proteinopathy may be a key player in neurodegeneration. To better understand the pathogenic mechanisms of FUS, we created single copy transgenic strains expressing full-length, untagged human FUS in the worm's GABAergic neurons.

Niche adaptation promoted the evolutionary diversification of tiny ocean predators.

Unicellular eukaryotic predators play a crucial role in the functioning of the ocean ecosystem by recycling nutrients and energy that are channeled to upper trophic levels. Traditionally, these evolutionarily diverse organisms have been combined into a single functional group (heterotrophic flagellates), overlooking their organismal differences. Here, we investigated four evolutionarily related species belonging to one cosmopolitan group of uncultured marine picoeukaryotic predators: marine stramenopiles (MAST)-4 (species A, B, C, and E).

Comparative genomics reveals new functional insights in uncultured MAST species.

Heterotrophic lineages of stramenopiles exhibit enormous diversity in morphology, lifestyle, and habitat. Among them, the marine stramenopiles (MASTs) represent numerous independent lineages that are only known from environmental sequences retrieved from marine samples. The core energy metabolism characterizing these unicellular eukaryotes is poorly understood.

Gene expression during bacterivorous growth of a widespread marine heterotrophic flagellate.

Phagocytosis is a fundamental process in marine ecosystems by which prey organisms are consumed and their biomass incorporated in food webs or remineralized. However, studies searching for the genes underlying this key ecological process in free-living phagocytizing protists are still scarce, in part due to the lack of appropriate ecological models. Our reanalysis of recent molecular datasets revealed that the cultured heterotrophic flagellate Cafeteria burkhardae is widespread in the global oceans, which prompted us to design a transcriptomics study with this species, grown with the cultured flavobacterium Dokdonia sp.

Inhibition of vascular calcification by inositol phosphates derivatized with ethylene glycol oligomers.

Myo-inositol hexakisphosphate (IP6) is a natural product known to inhibit vascular calcification (VC), but with limited potency and low plasma exposure following bolus administration. Here we report the design of a series of inositol phosphate analogs as crystallization inhibitors, among which 4,6-di-O-(methoxy-diethyleneglycol)-myo-inositol-1,2,3,5-tetrakis(phosphate), (OEG)-IP4, displays increased in vitro activity, as well as more favorable pharmacokinetic and safety profiles than IP6 after subcutaneous injection. (OEG)-IP4 potently stabilizes calciprotein particle (CPP) growth, consistently demonstrates low micromolar activity in different in vitro models of VC (i.

Comparative genomic analysis of the 'pseudofungus' .

Eukaryotic microbes have three primary mechanisms for obtaining nutrients and energy: phagotrophy, photosynthesis and osmotrophy. Traits associated with the latter two functions arose independently multiple times in the eukaryotes. The Fungi successfully coupled osmotrophy with filamentous growth, and similar traits are also manifested in the Pseudofungi (oomycetes and hyphochytriomycetes).

Comparative authentication of Hypericum perforatum herbal products using DNA metabarcoding, TLC and HPLC-MS.

Many herbal products have a long history of use, but there are increasing concerns over product efficacy, safety and quality in the wake of recent cases exposing discrepancies between labeling and constituents. When it comes to St. John's wort (Hypericum perforatum L.

Characterization of Calcium Phosphate Nanoparticles Based on a PEGylated Chelator for Gene Delivery.

Calcium phosphate (CaP) nanoparticles are promising gene delivery carriers due to their bioresorbability, ease of preparation, high gene loading efficacy, and endosomal escape properties. However, the rapid aggregation of the particles needs to be addressed in order to have potential in vivo. In addition, there is a need to better understand the relationship between CaP nanoparticle properties and their interactions with cells.

Neurodevelopmental long-term outcome in children with hydrocephalus requiring neonatal surgical treatment.

Purpose: To assess long-term neurodevelopmental outcome in children with hydrocephalus requiring neurosurgical treatment during the neonatal period.

Methods: This prospective longitudinal population-based study included 43 children with neonatal shunted hydrocephalus. The 43 children were prospectively reviewed in the presence of their parents at the outpatient clinic.

Chloroplast phylogenomic analysis of chlorophyte green algae identifies a novel lineage sister to the Sphaeropleales (Chlorophyceae).

Background: The class Chlorophyceae (Chlorophyta) includes morphologically and ecologically diverse green algae. Most of the documented species belong to the clade formed by the Chlamydomonadales (also called Volvocales) and Sphaeropleales. Although studies based on the nuclear 18S rRNA gene or a few combined genes have shed light on the diversity and phylogenetic structure of the Chlamydomonadales, the positions of many of the monophyletic groups identified remain uncertain.

The spinal control of locomotion and step-to-step variability in left-right symmetry from slow to moderate speeds.

When speed changes during locomotion, both temporal and spatial parameters of the pattern must adjust. Moreover, at slow speeds the step-to-step pattern becomes increasingly variable. The objectives of the present study were to assess if the spinal locomotor network adjusts both temporal and spatial parameters from slow to moderate stepping speeds and to determine if it contributes to step-to-step variability in left-right symmetry observed at slow speeds.

Merging Partially Labelled Trees: Hardness and a Declarative Programming Solution.

Intraspecific studies often make use of haplotype networks instead of gene genealogies to represent the evolution of a set of genes. Cassens et al. proposed one such network reconstruction method, based on the global maximum parsimony principle, which was later recast by the first author of the present work as the problem of finding a minimum common supergraph of a set of t partially labelled trees.