The SARS-CoV-2 antibody-dependent enhancement façade.

Antibody-dependent enhancement (ADE) is an immunological paradox whereby sensitization following a primary viral infection results in the subsequent enhancement of a similar secondary infection. This idiosyncratic immune response has been established in dengue virus infections, driven by four antigenically related serotypes co-circulating in endemic regions. Several coronaviruses exhibit antibody-mediated mechanisms of viral entry, which has led to speculation of an ADE capacity for SARS-CoV-2, though in vivo and epidemiological evidence do not currently support this phenomenon.

SHC-3: a previously unidentified C. elegans Shc family member functions in the insulin-like signaling pathway to enhance survival during L1 arrest.

Shc (Src homologous and collagen) proteins function in many different signaling pathways where they mediate phosphorylation-dependent protein-protein interactions. These proteins are characterized by the presence of two phosphotyrosine-binding domains, an N-terminal PTB and a C-terminal SH2. We describe a previously unrecognized Caenorhabditis elegans Shc gene, shc-3 and characterize its role in stress response.

Lessons from assembling a microbial natural product and pre-fractionated extract library in an academic laboratory.

Unlabelled: Microbial natural products are specialized metabolites that are sources of many bioactive compounds including antibiotics, antifungals, antiparasitics, anticancer agents, and probes of biology. The assembly of libraries of producers of natural products has traditionally been the province of the pharmaceutical industry. This sector has gathered significant historical collections of bacteria and fungi to identify new drug leads with outstanding outcomes-upwards of 60% of drug scaffolds originate from such libraries.

Simple model systems reveal conserved mechanisms of Alzheimer's disease and related tauopathies.

The lack of effective therapies that slow the progression of Alzheimer's disease (AD) and related tauopathies highlights the need for a more comprehensive understanding of the fundamental cellular mechanisms underlying these diseases. Model organisms, including yeast, worms, and flies, provide simple systems with which to investigate the mechanisms of disease. The evolutionary conservation of cellular pathways regulating proteostasis and stress response in these organisms facilitates the study of genetic factors that contribute to, or protect against, neurodegeneration.

Hemoglobin variant in disguise.

Background: Hemoglobinopathies include thalassemia syndromes, where production of one or more globin subunits of hemoglobin (Hb) is reduced, and structural Hb variants. Over 1000 disorders of Hb synthesis and/or structure have been identified and characterized, with phenotypes ranging from having severe clinical manifestations to clinically silent. Various analytical methods are used to phenotypically detect Hb variants.

Combining multi-marker metabarcoding and digital holography to describe eukaryotic plankton across the Newfoundland Shelf.

The planktonic diversity throughout the oceans is vital to ecosystem functioning and linked to environmental change. Plankton monitoring tools have advanced considerably with high-throughput in-situ digital cameras and genomic sequencing, opening new challenges for high-frequency observations of community composition, structure, and species discovery. Here, we combine multi-marker metabarcoding based on nuclear 18S (V4) and plastidial 16S (V4-V5) rRNA gene amplicons with a digital in-line holographic microscope to provide a synoptic diversity survey of eukaryotic plankton along the Newfoundland Shelf (Canada) during the winter transition phase of the North Atlantic bloom phenomenon.

Microbiomes: How a gut bacterium promotes healthier living in a nematode.

A new study finds that a bacterium from the microbiome of the nematode Pristionchus pacificus can promote rapid growth, increased body size, and increased fecundity by inducing neuronal expression of TGF-β ligands. This is an intriguing example of how the microbiota induces systemic effects in the host by stimulating neuroendocrine signaling.

The Alberta Newborn Screening Approach for Sickle Cell Disease: The Advantages of Molecular Testing.

Sickle cell disease (SCD), a group of inherited red blood cell (RBC) disorders caused by pathogenic variants in the beta-globin gene (), can cause lifelong disabilities and/or early mortality. If diagnosed early, preventative measures significantly reduce adverse outcomes related to SCD. In Alberta, Canada, SCD was added to the newborn screening (NBS) panel in April 2019.

Plankton classification with high-throughput submersible holographic microscopy and transfer learning.

Background: Plankton are foundational to marine food webs and an important feature for characterizing ocean health. Recent developments in quantitative imaging devices provide in-flow high-throughput sampling from bulk volumes-opening new ecological challenges exploring microbial eukaryotic variation and diversity, alongside technical hurdles to automate classification from large datasets. However, a limited number of deployable imaging instruments have been coupled with the most prominent classification algorithms-effectively limiting the extraction of curated observations from field deployments.

A compact filtered x-ray diode array spectrometer for the National Ignition Facility: SENTINEL.

Sentinel is a 16-channel, filtered x-ray diode array spectrometer that has been developed to measure ∼1 keV-20 keV x-ray emission generated by the National Ignition Facility (NIF) laser. Unlike the large, fixed-port versions of this diagnostic that currently exist on the NIF (known as Dante), Sentinel is a Diagnostic Instrument Manipulator compatible such that it can be fielded along the polar or equatorial lines-of-sight-an essential new capability for characterizing the often anisotropic x-ray emission from laser-driven sources. We present the diagnostic design along with preliminary diode calibrations and performance results.

Acute, Exercise-Induced Alterations in Cytokines and Chemokines in the Blood Distinguish Physically Active and Sedentary Aging.

Aging results in a chronic, proinflammatory state which can promote and exacerbate age-associated diseases. In contrast, physical activity in older adults improves whole body health, protects against disease, and reduces inflammation, but the elderly are less active making it difficult to disentangle the effects of aging from a sedentary lifestyle. To interrogate this interaction, we analyzed peripheral blood collected at rest and postexercise from 68 healthy younger and older donors that were either physically active aerobic exercisers or chronically sedentary.

Urine creatine metabolite panel as a screening test in neurodevelopmental disorders.

Background: Cerebral creatine deficiency disorders (CCDD) are inherited metabolic disorders of creatine synthesis and transport. Urine creatine metabolite panel is helpful to identify these disorders.

Methods: We reviewed electronic patient charts for all patients that underwent urine creatine metabolite panel testing in the metabolic laboratory at our institution.

Sickle cell trait newborn screen results: disclosure and management.

This study aims to evaluate the notification process of sickle cell trait (SCT) identified by newborn screening in Alberta. On April 1, 2019, Alberta began newborn screening for sickle cell disease (SCD) and elected to report sickle cell trait (SCT). For 1 year, healthcare providers (HCPs) were sent a questionnaire which addressed the perceived importance of disclosing the SCT results, whether HCPs felt competent in disclosing the result, knowledge of available resources, and comfort with coordinating and interpreting testing for the newborn's parents.

Evaluating the relationship between health information technology and safer-prescribing in the long-term care setting: A systematic review.

Background: The prevalence of health information technology (HIT) as an adjunct to increase safety and quality in healthcare applications is well known. There is a relationship between the use of HIT and safer-prescribing practices in long-term care.

Objective: The objective of this systematic review is to determine an association between the use of HIT and the improvement of prescription administration in long-term care facilities.

Homozygous GLUL deletion is embryonically viable and leads to glutamine synthetase deficiency.

Glutamine synthetase (GS) is the enzyme responsible for the biosynthesis of glutamine, providing the only source of endogenous glutamine necessary for several critical metabolic and developmental pathways. GS deficiency, caused by pathogenic variants in the glutamate-ammonia ligase (GLUL) gene, is a rare autosomal recessive inborn error of metabolism characterized by systemic glutamine deficiency, persistent moderate hyperammonemia, and clinically devastating seizures and multi-organ failure shortly after birth. The four cases reported thus far were caused by homozygous GLUL missense variants.

Cuticle Collagen Expression Is Regulated in Response to Environmental Stimuli by the GATA Transcription Factor ELT-3 in .

The nematode is protected from the environment by the cuticle, an extracellular collagen-based matrix that encloses the animal. Over 170 cuticular collagens are predicted in the genome, but the role of each individual collagen is unclear. Stage-specific specialization of the cuticle explains the need for some collagens; however, the large number of collagens suggests that specialization of the cuticle may also occur in response to other environmental triggers.

Nutrient Sensing and Response Drive Developmental Progression in Caenorhabditis elegans.

In response to nutrient limitation, many animals, including Caenorhabditis elegans, slow or arrest their development. This process requires mechanisms that sense essential nutrients and induce appropriate responses. When faced with nutrient limitation, C.

Whole-exome sequencing identifies a homozygous pathogenic variant in in a girl with palmoplantar keratoderma.

Palmoplantar keratoderma (PPK) is a defect in cornification that is characterized by progressive hyperkeratosis of palms and soles. Many phenotypes are linked with PPK, making exome-based diagnosis increasingly efficient. In this report, we identified tyrosinemia type II on whole-exome sequencing in a 7-year-old Syrian refugee that presented with PPK.

Homozygous pathogenic variant in associated with nonprogressive cerebellar ataxia.

Objective: To investigate the pathogenicity of a novel homozygous variant in 2 siblings with nonprogressive cerebellar ataxia (NPCA) through functional studies on primary and immortalized patient cell lines.

Methods: BRAT1 protein levels and ataxia-telangiectasia mutated (ATM) kinase activity in patient-derived and control cell lines were assessed by Western blotting. The impact of the novel variants on mitochondrial function was also assessed, by comparing patient and control cell lines for rates of oxygen consumption and for phosphorylation (S293) of the E1⍺ subunit of pyruvate dehydrogenase (PDH).

Expanding the Clinical Spectrum of -Related Mitochondrial Cytopathy.

Pathogenic variants in the gene have been associated with CODAS syndrome (Cerebral, Ocular, Dental, uricular, and keletal Anomalies Syndrome). A recent report identified the first newborn case with -related mitochondrial cytopathy due to a compound heterozygous pathogenic variant in without features of CODAS. The proband had manifested with severe congenital lactic acidosis and profound multiple respiratory chain complex activity deficiencies associated with the quantitative loss of mtDNA copy number in muscle.