'Clarifying', 'assuming', and 'reducing' stigma: a commentary on stigma in genetics.

The concept of stigma has been applied across many disciplines. Within the context of health and illness, research on stigma tells familiar stories about the impact of a diagnosis on the lives of individuals and their families, and the perceived negative effects of stigma on them and their relationships. This can result in public and private efforts to 'reduce' stigma for certain social groups by raising awareness and sharing more positive stories about their lives.

Structure and stability of an apo thermophilic esterase that hydrolyzes polyhydroxybutyrate.

Pollution from plastics is a global problem that threatens the biosphere for a host of reasons, including the time scale that it takes for most plastics to degrade. Biodegradation is an ideal solution for remediating bioplastic waste as it does not require the high temperatures necessary for thermal degradation and does not introduce additional pollutants into the environment. Numerous organisms can scavenge for bioplastics, such as polylactic acid (PLA) or poly-(R)-hydroxybutyrate (PHB), which they can use as an energy source.

Recruitment, regulation, and release: Control of signaling enzyme localization and function by reversible S-acylation.

An ever-growing number of studies highlight the importance of S-acylation, a reversible protein-lipid modification, for diverse aspects of intracellular signaling. In this review, we summarize the current understanding of how S-acylation regulates perhaps the best-known class of signaling enzymes, protein kinases. We describe how S-acylation acts as a membrane targeting signal that localizes certain kinases to specific membranes, and how such membrane localization in turn facilitates the assembly of signaling hubs consisting of an S-acylated kinase's upstream activators and/or downstream targets.

The CCT chaperonin and actin modulate the ER and RNA-binding protein condensation during oogenesis and maintain translational repression of maternal mRNA and oocyte quality.

The regulation of maternal mRNAs is essential for proper oogenesis, the production of viable gametes, and to avoid birth defects and infertility. Many oogenic RNA-binding proteins have been identified with roles in mRNA metabolism, some of which localize to dynamic ribonucleoprotein granules and others that appear dispersed. Here, we use a combination of in vitro condensation assays and the in vivo oogenesis model to characterize the properties of the conserved KH-domain MEX-3 protein and to identify novel regulators of MEX-3 and three other translational regulators.

The CCT chaperonin and actin modulate the ER and RNA-binding protein condensation during oogenesis to maintain translational repression of maternal mRNA and oocyte quality.

Unlabelled: The regulation of maternal mRNAs is essential for proper oogenesis, the production of viable gametes, and to avoid birth defects and infertility. Many oogenic RNA-binding proteins have been identified with roles in mRNA metabolism, some of which localize to dynamic ribonucleoprotein granules and others that appear dispersed. Here, we use a combination of condensation assays and the oogenesis model to determine the intrinsic properties of the conserved KH-domain MEX-3 protein and to identify novel regulators of MEX-3 and the Lsm protein, CAR-1.

SANS reveals lipid-dependent oligomerization of an intramembrane aspartyl protease from H. volcanii.

Reactions that occur within the lipid membrane involve, at minimum, ternary complexes among the enzyme, substrate, and lipid. For many systems, the impact of the lipid in regulating activity or oligomerization state is poorly understood. Here, we used small-angle neutron scattering (SANS) to structurally characterize an intramembrane aspartyl protease (IAP), a class of membrane-bound enzymes that use membrane-embedded aspartate residues to hydrolyze transmembrane segments of biologically relevant substrates.

Novel inhibitors of acute, axonal DLK palmitoylation are neuroprotective and avoid the deleterious side effects of cell-wide DLK inhibition.

Dual leucine-zipper kinase (DLK) drives acute and chronic forms of neurodegeneration, suggesting that inhibiting DLK signaling could ameliorate diverse neuropathological conditions. However, direct inhibition of DLK's kinase domain in human patients and conditional knockout of DLK in mice both cause unintended side effects, including elevated plasma neurofilament levels, indicative of neuronal cytoskeletal disruption. Indeed, we found that a DLK kinase domain inhibitor acutely disrupted the axonal cytoskeleton and caused vesicle aggregation in cultured dorsal root ganglion (DRG) neurons, further cautioning against this therapeutic strategy.

Utilizing a Paper-Based Platform for Oilfield Applications: Time-Resolved Fluorescence Imaging and Detection of Interwell Chemical Tracers.

Chemical tracers are indispensable tools for enhancing reservoir characterization and optimizing production processes in the oil and gas industry. Particularly, interwell water tracers provide key data for efficient water flood management and the improvement of production rates. However, the analysis of these water tracers within reservoir fluids is challenging, requiring laborious separation and extraction steps that often rely on complex instruments and skilled operators.

Lipid environment modulates processivity and kinetics of a presenilin homolog acting on multiple substrates in vitro.

Intramembrane proteases (IPs) hydrolyze peptides in the lipid membrane. IPs participate in a number of cellular pathways including immune response and surveillance, and cholesterol biosynthesis, and they are exploited by viruses for replication. Despite their broad importance across biology, how activity is regulated in the cell to control protein maturation and release of specific bioactive peptides at the right place and right time remains largely unanswered, particularly for the intramembrane aspartyl protease (IAP) subtype.

Palmitoylation-dependent control of JAK1 kinase signaling governs responses to neuropoietic cytokines and survival in DRG neurons.

Janus Kinase-1 (JAK1) plays key roles during neurodevelopment and following neuronal injury, while activatory JAK1 mutations are linked to leukemia. In mice, Jak1 genetic deletion results in perinatal lethality, suggesting non-redundant roles and/or regulation of JAK1 for which other JAKs cannot compensate. Proteomic studies reveal that JAK1 is more likely palmitoylated compared to other JAKs, implicating palmitoylation as a possible JAK1-specific regulatory mechanism.

Dalbavancin vs standard of care for Staphylococcus aureus bacteraemia in patients unable to receive outpatient parenteral antimicrobial therapy.

Background: This study compared dalbavancin with standard of care (SOC) for patients with Staphylococcus aureus bacteraemia (SAB) who were unable to receive outpatient parenteral antimicrobial therapy (OPAT).

Methods: This retrospective cohort compared re-admission rates related to the index infection between patients treated with dalbavancin or SOC for SAB. Patients aged ≥18 years seen by the infectious diseases consult service who had received at least one dose of dalbavancin or at least 1 week of SOC parenteral antibacterials as directed therapy for SAB at the time of discharge were included.

Deep Learning Applied to Raman Spectroscopy for the Detection of Microsatellite Instability/MMR Deficient Colorectal Cancer.

Defective DNA mismatch repair is one pathogenic pathway to colorectal cancer. It is characterised by microsatellite instability which provides a molecular biomarker for its detection. Clinical guidelines for universal testing of this biomarker are not met due to resource limitations; thus, there is interest in developing novel methods for its detection.

Palmitoylation controls the stability of 190 kDa ankyrin-G in dendritic spines and is regulated by ZDHHC8 and lithium.

Introduction: AnkG, encoded by the gene, is a multifunctional scaffold protein with complex isoform expression: the 480 and 270 kDa isoforms have roles at the axon initial segment and node of Ranvier, whereas the 190 kDa isoform (AnkG-190) has an emerging role in the dendritic shaft and spine heads. All isoforms of AnkG undergo palmitoylation, a post-translational modification regulating protein attachment to lipid membranes. However, palmitoylation of AnkG-190 has not been investigated in dendritic spines.

Influence of Surgeon Specialty on 30-day Outcomes Following Single-Level Cervical Disc Arthroplasty: A Propensity-Matched Analysis.

Study Design: Retrospective, propensity-matched analysis.

Objectives: Cervical disc arthroplasty (CDA) is being increasingly utilized for cervical disc generation. Surgeon specialty has been shown to influence the risk for postoperative complications in spine surgery, but this has not yet been explored for CDA.

Bioplastic degradation by a polyhydroxybutyrate depolymerase from a thermophilic soil bacterium.

As the epidemic of single-use plastic worsens, it has become critical to identify fully renewable plastics such as those that can be degraded using enzymes. Here we describe the structure and biochemistry of an alkaline poly[(R)-3-hydroxybutyric acid] (PHB) depolymerase from the soil thermophile Lihuaxuella thermophila. Like other PHB depolymerases or PHBases, the Lihuaxuella enzyme is active against several different polyhydroxyalkanoates, including homo- and heteropolymers, but L.

Shoulder, upper arm and elbow injuries in high school men's American football.

In order to reduce shoulder, upper arm and elbow injury rates in American football, identifying injury risk factors and any underlying associations is needed. No prior study has done such characterization at the high school level. A descriptive epidemiology study was performed using data from the National Athletic Treatment, Injury, and Outcomes Network Surveillance Program (NATION-SP) from the years 2011/12 to 2013/14 on high school football athletes.

Preventable operating room delays in robotic-assisted thoracic surgery: Identifying opportunities for cost reduction.

Background: This study aimed to characterize the types of intraoperative delays during robotic-assisted thoracic surgery, operating room staff awareness/perceptions of delays, and cost impact of delays on overall operative costs.

Methods: Robotic-assisted thoracic surgery cases from May to August 2019 were attended by 3 third-party observers to record intraoperative delays. The postoperative surveys were given to operating room staff to elicit perceived delays.

Anti-cardiolipin IgG autoantibodies associate with circulating extracellular DNA in severe COVID-19.

Whereas the detection of antiphospholipid autoantibodies (aPL) in COVID-19 is of increasing interest, their role is still unclear. We analyzed a large aPL panel in 157 patients with COVID-19 according to the disease severity. We also investigated a potential association between aPL and extracellular DNA (exDNA, n = 85) or circulating markers of neutrophil extracellular traps (NET) such as citrullinated histones H3 (CitH3, n = 49).

Machine Learning of Raman Spectroscopy Data for Classifying Cancers: A Review of the Recent Literature.

Raman Spectroscopy has long been anticipated to augment clinical decision making, such as classifying oncological samples. Unfortunately, the complexity of Raman data has thus far inhibited their routine use in clinical settings. Traditional machine learning models have been used to help exploit this information, but recent advances in deep learning have the potential to improve the field.

Clinical Severity on Hospital Admission for COVID-19: An Analysis of Social Determinants of Health From an Early Hot Spot in the Southeastern U.S.

Introduction: Disparities in COVID-19 infection, illness severity, hospitalization, and death are often attributed to age and comorbidities, which fails to recognize the contribution of social, environmental, and financial factors on health. The purpose of this study was to examine relationships between social determinants of health (SDOH) and COVID-19 severity.

Methods: This multicenter retrospective study included adult patients hospitalized with COVID-19 in Southwest Georgia, U.

Palmitoylation couples the kinases DLK and JNK3 to facilitate prodegenerative axon-to-soma signaling.

Dual leucine-zipper kinase (DLK; a MAP3K) mediates neuronal responses to diverse injuries and insults through the c-Jun N-terminal kinase (JNK) family of mitogen-activated protein kinases (MAPKs). Here, we identified two ways through which DLK is coupled to the neural-specific isoform JNK3 to control prodegenerative signaling. JNK3 catalyzed positive feedback phosphorylation of DLK that further activated DLK and locked the DLK-JNK3 module in a highly active state.

Missed opportunities to identify cryptococcosis in COVID-19 patients: a case report and literature review.

SARS-CoV-2 may activate both innate and adaptive immune responses ultimately leading to a dysregulated immune response prompting the use of immunomodulatory therapy. Although viral pneumonia increases the risk of invasive fungal infections, it remains unclear whether SARS-CoV-2 infection, immunomodulatory therapy, or a combination of both are responsible for the increased recognition of opportunistic infections in COVID-19 patients. Cases of cryptococcosis have previously been reported following treatment with corticosteroids, interleukin (IL)-6 inhibitors, and Janus kinase (JAK) inhibitors, for patients with autoimmune diseases, but their effect on the immunologic response in patients with COVID-19 remains unknown.

Crystal Packing-Driven Selective Hg(II) Ion Sensing Using Thiazolothiazole-Based Water-Stable Zinc Metal-Organic Framework.

A soft acid-soft base interaction is highly predictable. However, we demonstrate how the crystal packing of the newly synthesized zinc framework [Zn(5-AIA)(DPTTZ)]·DMF (where 5-AIA = 5-aminoisophthalic acid, DPTTZ = -di(4-pyridyl)thiazolo-[5,4-]thiazole, DMF = -dimethylformamide) directs an unexpected interaction between the soft acid Hg(II) and the hard base oxygen instead of having a soft center like nitrogen and sulfur in the system attributed to a strong solvent interaction and a favorable ionic radius of Hg(II) ion for oxygen chelation. This engenders selective Hg(II) ion sensing through a "turn-off" emission quenching in water (limit of detection = (2.

A legacy of silence: the intersections of medical sociology and disability studies.

Disability remains on the margins of the social sciences. Even where disability is foregrounded as a category of analysis, accounts regularly emerge in silos, with little interdisciplinary dialogue acknowledging the potential intersections and points of convergence. This discord is particularly acute within medical sociology and disability studies, yet there is mostly a legacy of silence about the relationship between the two disciplines.

The Development of an Assessment Rubric for the Core and Contingency Team Interaction Among Rapid Response Teams.

Introduction: Teamwork training is critical in the development of high-functioning rapid response teams (RRT). Rapid response teams involve interactions between a patient's core care team and a hospital contingency team, which can lead to disorganized and unsafe resuscitations, largely due to problems with communication and information dissemination. An extensive literature search found no assessment tools specific to the unique communicative challenges of an RRT, and thus, this study sought to develop an assessment rubric validated for training RRTs.