Primitive Phospholamban- and Sarcolipin-like Peptides Inhibit the Sarcoplasmic Reticulum Calcium Pump SERCA.

Intracellular calcium signaling is essential for all kingdoms of life. An important part of this process is the sarco-endoplasmic reticulum Ca-ATPase (SERCA), which maintains the low cytosolic calcium levels required for intracellular calcium homeostasis. In higher organisms, SERCA is regulated by a series of tissue-specific transmembrane subunits such as phospholamban in cardiac muscles and sarcolipin in skeletal muscles.

The Impact of Internal Medicine Clerkship Characteristics and NBME Subject Exams on USMLE Step 2 Clinical Knowledge Exam Performance.

Background: Residency program directors will likely emphasize the United States Medical Licensing Exam (USMLE) Step 2 clinical knowledge (CK) exam more during residency application given the recent USMLE Step 1 transition to pass/fail scoring. We examined how internal medicine clerkship characteristics and NBME subject exam scores affect USMLE Step 2 CK performance.

Design: The authors used univariable and multivariable generalized estimating equations to determine associations between Step 2 CK performance and internal medicine clerkship characteristics and NBME subject exams.

Disseminated Histiocytic Sarcoma in Two Free-Living Florida Manatees (Trichechus manatus latirostris).

During necropsy of two manatees, masses in multiple organs including liver and spleen were identified. They were composed of neoplastic round to spindle-shaped cells, positive for vimentin, Iba-1, lysozyme, and Mac387, consistent with histiocytic sarcoma. One manatee also had an undifferentiated sarcoma that may have arisen from the histiocytic sarcoma.

Optimized Administration of the M PAM VU0467154 Demonstrates Broad Efficacy, but Limited Effective Concentrations in Mice.

Hypofunction of cholinergic circuits and diminished cholinergic tone have been associated with the neurodevelopmental disorder Rett syndrome (RTT). Specifically, deletion of in cholinergic neurons evokes the same social and cognitive phenotypes in mice seen with global knockout, and decreased choline acetyltransferase activity and vesamicol binding have been reported in RTT autopsy samples. Further, we recently identified significant decreases in muscarinic acetylcholine receptor subtype 4 (M) expression in both the motor cortex and cerebellum of RTT patient autopsies and established proof of concept that an acute dose of the positive allosteric modulator (PAM) VU0467154 (VU154) rescued phenotypes in mice.

Gender-differences of proceduralists in perception of hand-held surgical instrument fit - A cross-sectional survey.

Objective: Determining perception of hand size as it relates to instrument use and ability to perform a procedure in a diverse population of proceduralists across surgical and medical specialties.

Methods: Cross-sectional survey was distributed via electronic format to a convenience sample of surgeons/physicians. Secondary analysis included identified instrument use and choice of/perception of ability to learn and perform procedures.

Inter-domain communication in SARS-CoV-2 spike proteins controls protease-triggered cell entry.

SARS-CoV-2 continues to evolve into variants of concern (VOC), with greatest variability in the multidomain, entry-facilitating spike proteins. To recognize the significance of adaptive spike protein changes, we compare variant SARS-CoV-2 virus particles in several assays reflecting authentic virus-cell entry. Virus particles with adaptive changes in spike amino-terminal domains (NTDs) are hypersensitive to proteolytic activation of membrane fusion, an essential step in virus-cell entry.

Overall and sex-specific risk factors for subjective cognitive decline: findings from the 2015-2018 Behavioral Risk Factor Surveillance System Survey.

Background: Prior research indicates that at least 35% of Alzheimer's disease and related dementia risk may be amenable to prevention. Subjective cognitive decline is often the first indication of preclinical dementia, with the risk of subsequent Alzheimer's disease in such individuals being greater in women than men. We wished to understand how modifiable factors are associated with subjective cognitive decline, and whether differences exist by sex.

Analysis of 3--Sulfated Heparan Sulfate Using Isotopically Labeled Oligosaccharide Calibrants.

The 3--sulfated glucosamine in heparan sulfate (HS) is a low-abundance structural component, but it is a key saccharide unit for the biological activities of HS. A method to determine the level of 3--sulfated HS is lacking. Here, we describe a LC-MS/MS based method to analyze the structural motifs.

SELENOF is a new tumor suppressor in breast cancer.

Epidemiological evidence has indicated an inverse association between selenium status and various types of cancer, including breast cancer. Selenoproteins are the primary mediators of selenium effects in human health. We have previously reported loss of heterozygosity in breast tumor samples of the gene for one of the selenoproteins, SELENOF.

An embedded multiple case study: using CFIR to map clinical food security screening constructs for the development of primary care practice guidelines.

Background: Food insecurity (FI), the limited access to healthy food to live an active and healthy life, is a social determinant of health linked to poor dietary health and difficulty with disease management in the United States (U.S.).

Molecular Activation of the Kv11.1 Channel Reprograms EMT in Colon Cancer by Inhibiting TGFβ Signaling via Activation of Calcineurin.

Control of ionic gradients is critical to maintain cellular homeostasis in both physiological and pathological conditions, but the role of ion channels in cancer cells has not been studied thoroughly. In this work we demonstrated that activity of the Kv11.1 potassium channel plays a vital role in controlling the migration of colon cancer cells by reversing the epithelial-to-mesenchymal transition (EMT) into the mesenchymal-to-epithelial transition (MET).

Loop extrusion promotes an alternate pathway for isotype switching.

Class-switch recombination (CSR) involves replacement of the Cμ constant region with another downstream C region. CSR is initiated by activation-induced cytidine deaminase (AID)-mediated DNA breaks that are targeted to transcriptionally active switch (S) regions. S region promoters (Prs) direct synapsis by associating with the Eμ and 3'Eα enhancers that jointly anchor a chromatin loop.

Loss of SELENOF Induces the Transformed Phenotype in Human Immortalized Prostate Epithelial Cells.

SELENOF is a member of the class of selenoproteins in which the amino acid selenocysteine is co-translationally inserted into the elongating peptide in response to an in-frame UGA codon located in the 3'-untranslated (3'-UTR) region of the SELENOF mRNA. Polymorphisms in the 3'-UTR are associated with an increased risk of dying from prostate cancer and these variations are functional and 10 times more frequent in the genomes of African American men. SELENOF is dramatically reduced in prostate cancer compared to benign adjacent regions.

Vagal neuron expression of the microbiota-derived metabolite receptor, free fatty acid receptor (FFAR3), is necessary for normal feeding behavior.

Objective: The vagus nerve provides a direct line of communication between the gut and the brain for proper regulation of energy balance and glucose homeostasis. Short-chain fatty acids (SCFAs) produced via gut microbiota fermentation of dietary fiber have been proposed to regulate host metabolism and feeding behavior via the vagus nerve, but the molecular mechanisms have not yet been elucidated. We sought to identify the G-protein-coupled receptors within vagal neurons that mediate the physiological and therapeutic benefits of SCFAs.

Homogenization of Continuum-Scale Transport Properties from Molecular Dynamics Simulations: An Application to Aqueous-Phase Methane Diffusion in Silicate Channels.

Silica-based materials including zeolites are commonly used for wide-ranging applications including separations and catalysis. Substrate transport rates in these materials can significantly influence the efficiency of such applications. Two factors that contribute to transport rates include (1) the porosity of the silicate matrix and (2) nonbonding interactions between the diffusing species and the silicate surface.

Non-Canonical Interaction between Calmodulin and Calcineurin Contributes to the Differential Regulation of Plant-Derived Calmodulins on Calcineurin.

Calmodulin (CaM) serves as an important Ca signaling hub that regulates many protein signaling pathways. Recently, it was demonstrated that plant CaM homologues can regulate mammalian targets, often in a manner that opposes the impact of the mammalian CaM (mCaM). However, the molecular basis of how CaM homologue mutations differentially impact target activation is unclear.

The Ile191Val is a partial loss-of-function variant of the TAS1R2 sweet-taste receptor and is associated with reduced glucose excursions in humans.

Objective: Sweet taste receptors (STR) are expressed in the gut and other extra-oral tissues, suggesting that STR-mediated nutrient sensing may contribute to human physiology beyond taste. A common variant (Ile191Val) in the TAS1R2 gene of STR is associated with nutritional and metabolic outcomes independent of changes in taste perception. It is unclear whether this polymorphism directly alters STR function and how it may contribute to metabolic regulation.

Ureterosciatic hernia with concomitant Amyand hernia: Case report and review of the literature.

Ureterosciatic hernias are extremely rare, with fewer than 40 cases reported in the literature. We present a case of a patient with concurrent right ureterosciatic hernia (Lindbom hernia), ipsilateral bladder hernia, and appendix-containing inguinal hernia (Amyand hernia). These findings were discovered incidentally on imaging and the patient had no associated symptoms.

Mechanistic Picture for Chemomechanical Coupling in a Bacterial Proton-Coupled Oligopeptide Transporter from Streptococcus Thermophilus.

Proton-coupled oligopeptide transporters (POTs) use the proton electrochemical gradient to transport peptides across the cell membrane. Despite the significant biological and biomedical relevance of these proteins, a detailed mechanistic picture for chemomechanical couplings involved in substrate/proton transport and protein structural changes is missing. Therefore, we performed microsecond-level molecular dynamics simulations of bacterial POT PepT, which shares ∼80% sequence identity with the human POT, PepT1, in the substrate-binding region.

Study of ultrasound thrombolysis using acoustic bubbles in a microfluidic device.

Thrombosis is a common medical entity associated with many forms of cardiovascular disease including myocardial infarction and stroke. Recently, ultrasound thrombolysis has emerged as a promising technique for thrombosis treatment by delivering acoustic waves onto blood clots. In this study, an ultrasound thrombolysis method is presented using an acoustic bubble-based microfluidic device.

Medical student wellness in the United States during the COVID-19 pandemic: a nationwide survey.

Background: As United States (US) medical students suffer higher rates of depression and anxiety than the general population, the wellness of medical students is particularly salient. One definition describes wellness as having eight dimensions: Intellectual, emotional, physical, social, occupational, financial, environmental, and spiritual. As the coronavirus (COVID-19) pandemic poses unique challenges for medical students, we aimed to compare medical student wellness before and during the COVID-19 pandemic.

Pathognomonic macular ripples are revealed by polarized infrared retinal imaging.

A pathognomonic macular ripple sign has been reported with scanning laser ophthalmoscopy images in patients with foveal hypoplasia, though the optical basis of this sign is presently unknown. Here we present a case series of seven individuals with foveal hypoplasia (based on spectral domain optical coherence tomography). Each patient underwent infrared scanning laser ophthalmoscopy retinal imaging in both eyes, acquired with and without a polarization filter and assessment for a ripple-like effect in the fovea.

Absolute Quantification of Phosphorylated ERβ Amino Acids in the Hippocampus of Women and in A Rat Model of Menopause.

The rapid decline of circulating 17β-estradiol (E2) at menopause leads to negative neurological consequences, although hormone therapy paradoxically has both harmful and positive effects depending on the age at which it is delivered. The inconsistent response to E2 suggests unappreciated regulatory mechanisms for estrogen receptors (ERs), and we predicted it could be due to age-related differences in ERβ phosphorylation. We assessed ERβ phosphorylation using a sensitive mass spectrometry approach that provides absolute quantification (AQUA-MS) of individually phosphorylated residues.