β-arrestins and G protein-coupled receptor kinases in viral entry: A graphical review.

Viruses rely on host-cell machinery in order to invade host cells and carry out a successful infection. G-protein coupled receptor (GPCR)-mediated signaling pathways are master regulators of cellular physiological processing and are an attractive target for viruses to rewire cells during infection. In particular, the GPCR-associated scaffolding proteins β-arrestins and GPCR signaling effectors G-protein receptor kinases (GRKs) have been identified as key cellular factors that mediate viral entry and orchestrate signaling pathways that reprogram cells for viral replication.

Lipid-laden lung mesenchymal cells foster breast cancer metastasis via metabolic reprogramming of tumor cells and natural killer cells.

While the distant organ environment is known to support metastasis of primary tumors, its metabolic roles in this process remain underdetermined. Here, in breast cancer models, we found lung-resident mesenchymal cells (MCs) accumulating neutral lipids at the pre-metastatic stage. This was partially mediated by interleukin-1β (IL-1β)-induced hypoxia-inducible lipid droplet-associated (HILPDA) that subsequently represses adipose triglyceride lipase (ATGL) activity in lung MCs.

Combined Utility of the Semmes-Weinstein Monofilament and the Timed Vibration Test in the Prediction of Diabetic Foot Ulcers.

Background: Neurologic screening tests are often used to identify and stratify patients at risk for diabetic foot complications such as infections, ulcers, and amputations. Two of the most commonly cited methods are the 5.07 Semmes-Weinstein monofilament (SWM) for loss of protective sensation and vibratory sensation testing.

Thyroid hormone elicits intergenerational epigenetic effects on adult social behavior and fetal brain expression of autism susceptibility genes.

Genetic mutations identified in genome-wide association studies can only explain a small percentage of the cases of complex, highly heritable human conditions, including neurological and neurodevelopmental disorders. This suggests that intergenerational epigenetic effects, possibly triggered by environmental circumstances, may contribute to their etiology. We previously described altered DNA methylation signatures in the sperm of mice that experienced developmental overexposure to thyroid hormones as a result of a genetic defect in hormone clearance (DIO3 deficiency).

A critical bioenergetic switch is regulated by IGF2 during murine cartilage development.

Long bone growth requires the precise control of chondrocyte maturation from proliferation to hypertrophy during endochondral ossification, but the bioenergetic program that ensures normal cartilage development is still largely elusive. We show that chondrocytes have unique glucose metabolism signatures in these stages, and they undergo bioenergetic reprogramming from glycolysis to oxidative phosphorylation during maturation, accompanied by an upregulation of the pentose phosphate pathway. Inhibition of either oxidative phosphorylation or the pentose phosphate pathway in murine chondrocytes and bone organ cultures impaired hypertrophic differentiation, suggesting that the appropriate balance of these pathways is required for cartilage development.

Improved Recovery of Captured Airborne Bacteria and Viruses with Liquid-Coated Air Filters.

The COVID-19 pandemic has revealed the importance of the detection of airborne pathogens. Here, we present composite air filters featuring a bioinspired liquid coating that facilitates the removal of captured aerosolized bacteria and viruses for further analysis. We tested three types of air filters: commercial polytetrafluoroethylene (PTFE), which is well known for creating stable liquid coatings, commercial high-efficiency particulate air (HEPA) filters, which are widely used, and in-house-manufactured cellulose nanofiber mats (CNFMs), which are made from sustainable materials.

Multiscale anisotropy analysis of second-harmonic generation collagen imaging of human pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers with a minority (< 10%) of patients surviving five years past diagnosis. This could be improved with the development of new imaging modalities for early differentiation of benign and cancerous fibrosis. This study intends to explore the application of a two-photon microscopy technique known as second harmonic generation to PDAC using the 2D Wavelet Transform Modulus Maxima (WTMM) Anisotropy method to quantify collagen organization in fibrotic pancreatic tissue.

GLH-1/Vasa represses neuropeptide expression and drives spermiogenesis in the C. elegans germline.

Germ granules harbor processes that maintain germline integrity and germline stem cell capacity. Depleting core germ granule components in C. elegans leads to the reprogramming of germ cells, causing them to express markers of somatic differentiation in day-two adults.

A patient-informed approach to predict iodinated-contrast media enhancement in the liver.

Objective: To devise a patient-informed time series model that predicts liver contrast enhancement, by integrating clinical data and pharmacokinetics models, and to assess its feasibility to improve enhancement consistency in contrast-enhanced liver CT scans.

Methods: The study included 1577 Chest/Abdomen/Pelvis CT scans, with 70-30% training/validation-testing split. A Gaussian function was used to approximate the early arterial, late arterial, and the portal venous phases of the contrast perfusion curve of each patient using their respective bolus tracking and diagnostic scan data.

RGS12 polarizes the GPSM2-GNAI complex to organize and elongate stereocilia in sensory hair cells.

Inhibitory G proteins (GNAI/Gα) bind to the scaffold G protein signaling modulator 2 (GPSM2) to form a conserved polarity complex that regulates cytoskeleton organization. GPSM2 keeps GNAI in a guanosine diphosphate (GDP)-bound state, but how GPSM2-GNAI is generated or relates to heterotrimeric G protein signaling remains unclear. We find that RGS12, a GTPase-activating protein (GAP), is required to polarize GPSM2-GNAI at the hair cell apical membrane and to organize mechanosensory stereocilia in rows of graded heights.

A Missense Variant Causes Degenerative Retinopathy without Myasthenic Syndrome in Mice.

Congenital disorders of glycosylation (CDG) are a heterogenous group of primarily autosomal recessive mendelian diseases caused by disruptions in the synthesis of lipid-linked oligosaccharides and their transfer to proteins. CDGs usually affect multiple organ systems and vary in presentation, even within families. There is currently no cure, and treatment is aimed at ameliorating symptoms and improving quality of life.

Effects of risk factors for ovarian cancer in women with and without endometriosis.

Objective: To evaluate the associations between 10 well-established ovarian cancer risk factors and risk of ovarian cancer among women with vs. without endometriosis.

Design: Pooled analysis of 9 case-control studies in the Ovarian Cancer Association Consortium.

Distinct Tumor Necrosis Factor Alpha Receptors Dictate Stem Cell Fitness versus Lineage Output in Dnmt3a-Mutant Clonal Hematopoiesis.

Unlabelled: Clonal hematopoiesis resulting from the enhanced fitness of mutant hematopoietic stem cells (HSC) associates with both favorable and unfavorable health outcomes related to the types of mature mutant blood cells produced, but how this lineage output is regulated is unclear. Using a mouse model of a clonal hematopoiesis-associated mutation, DNMT3AR882/+ (Dnmt3aR878H/+), we found that aging-induced TNFα signaling promoted the selective advantage of mutant HSCs and stimulated the production of mutant B lymphoid cells. The genetic loss of the TNFα receptor TNFR1 ablated the selective advantage of mutant HSCs without altering their lineage output, whereas the loss of TNFR2 resulted in the overproduction of mutant myeloid cells without altering HSC fitness.

DIO3 protects against thyrotoxicosis-derived cranio-encephalic and cardiac congenital abnormalities.

Maternal hyperthyroidism is associated with an increased incidence of congenital abnormalities at birth, but it is not clear which of these defects arise from a transient developmental excess of thyroid hormone and which depend on pregnancy stage, antithyroid drug choice, or unwanted subsequent fetal hypothyroidism. To address this issue, we studied a mouse model of comprehensive developmental thyrotoxicosis secondary to a lack of type 3 deiodinase (DIO3). Dio3-/- mice exhibited reduced neonatal viability on most genetic backgrounds and perinatal lethality on a C57BL/6 background.

The effect of doxorubicin or cyclophosphamide treatment on auditory brainstem response in mice.

Clinical studies suggest that chemotherapy is associated with long-term cognitive impairment in some patients. Several underlying mechanisms have been proposed; however, the etiology of chemotherapy-related cognitive dysfunction remains relatively unknown. There is evidence that oligodendrocytes and white matter tracts within the CNS may be particularly vulnerable to chemotherapy-related damage and dysfunction.

Curriculum Guidelines for Graduate and Undergraduate Virology Courses.

Curriculum guidelines for virology are needed to best guide student learning due to the continuous and ever-increasing volume of virology information, the need to ensure that undergraduate and graduate students have a foundational understanding of key virology concepts, and the importance in being able to communicate that understanding to both other virologists and nonvirologists. Such guidelines, developed by virology educators and the American Society for Virology Education and Career Development Committee, are described herein.

Sustained Morphine Delivery Suppresses Bone Formation and Alters Metabolic and Circulating miRNA Profiles in Male C57BL/6J Mice.

Opioid use is detrimental to bone health, causing both indirect and direct effects on bone turnover. Although the mechanisms of these effects are not entirely clear, recent studies have linked chronic opioid use to alterations in circulating miRNAs. Here, we developed a model of opioid-induced bone loss to understand bone turnover and identify candidate miRNA-mediated regulatory mechanisms.

The variant in methylenetetrahydrofolate reductase causes morphological and functional cerebrovascular deficits in mice.

Vascular contributions to cognitive impairment and dementia (VCID) particularly Alzheimer's disease and related dementias (ADRDs) are increasing; however, mechanisms driving cerebrovascular decline are poorly understood. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in the folate and methionine cycles. Variants in notably   are associated with dementias, but no mouse model existed to identify mechanisms by which increases risk.

Rapamycin/metformin co-treatment normalizes insulin sensitivity and reduces complications of metabolic syndrome in type 2 diabetic mice.

Rapamycin treatment has positive and negative effects on progression of type 2 diabetes (T2D) in a recombinant inbred polygenic mouse model, male NONcNZO10/LtJ (NcZ10). Here, we show that combination treatment with metformin ameliorates negative effects of rapamycin while maintaining its benefits. From 12 to 30 weeks of age, NcZ10 males were fed a control diet or diets supplemented with rapamycin, metformin, or a combination of both.

Phosphorylation of RGS regulates MAP kinase localization and promotes completion of cytokinesis.

Yeast use the G-protein-coupled receptor signaling pathway to detect and track the mating pheromone. The G-protein-coupled receptor pathway is inhibited by the regulator of G-protein signaling (RGS) Sst2 which induces Gα GTPase activity and inactivation of downstream signaling. G-protein signaling activates the MAPK Fus3, which phosphorylates the RGS; however, the role of this modification is unknown.

Life-long dietary restrictions have negligible or damaging effects on late-life cognitive performance: A key role for genetics in outcomes.

Several studies report that caloric restriction (CR) or intermittent fasting (IF) can improve cognition, while others report limited or no cognitive benefits. Here, we compare the effects of 20% CR, 40% CR, 1-day IF, and 2-day IF feeding paradigms to ad libitum controls on Y-maze working memory (WM) and contextual fear memory (CFM) in a large population of Diversity Outbred mice that model the genetic diversity of humans. While CR and IF interventions improve lifespan, we observed no enhancement of working memory or CFM in mice on these feeding paradigms, and report 40% CR to be damaging to recall of CFM.

Social and maternal behavior in mesoderm specific transcript (Mest)-deficient mice.

Mesoderm specific transcript (Mest)/paternally expressed gene-1 (Peg1) is an imprinted gene expressed predominantly from the paternal allele. Aberrations in maternal behavior were previously reported in a Mest global knockout mouse (Mesttm1Masu). In this study, we performed in-depth social and maternal behavioral testing in a mouse model of Mest inactivation developed in our laboratory (Mesttm1.

The dominoes fall after long-term antibiotic exposure.

Broad-spectrum antibiotics should prevent disease, right? In this issue of Cell Host & Microbe, Drummond et al. turn logic on its head and show they actually drive more deadly invasive fungal-bacterial systemic co-infection. Prophylactic antibiotics increase susceptibility to these infections by targeting the commensal microbes required for gut-derived IL-17-mediated immunity.

Mouse models of NADK2 deficiency analyzed for metabolic and gene expression changes to elucidate pathophysiology.

NADK2 encodes the mitochondrial form of nicotinamide adenine dinucleotide (NAD) kinase, which phosphorylates NAD. Rare recessive mutations in human NADK2 are associated with a syndromic neurological mitochondrial disease that includes metabolic changes, such as hyperlysinemia and 2,4 dienoyl CoA reductase (DECR) deficiency. However, the full pathophysiology resulting from NADK2 deficiency is not known.