bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asymmetric Control of Food Intake by Left and Right Vagal Sensory Neurons
Authors: de Araujo Alan , Singh Arashdeep , McDougle Molly , Braga Isadora , Leme Gabriel , de Lartigue Guillaume 
Published: May 2022

Gut‐innervating vagal sensory neurons residing in the nodose ganglia (NG) conveys meal‐borne signals and control food intake, however, the underlying gut‐brain neurocircuit is unclear. The neuropeptide cocaine‐ and amphetamine‐regulated transcript (CART) is expressed in a subpopulation of vagal sensory neurons (~40%) that innervate the whole length of the gut and its release in the NTS is sufficient for meal termination. Thus, it can be an excellent target to understand the role of sensory neurons in feeding. Emerging evidence suggests that right or left NG (LNG or RNG) neurons recruit different downstream central circuits to control feeding, but the mechanisms remain poorly understood. Our hypothesis is that LNGCART and RNGCART neurons sense different meal‐related signals and are necessary and sufficient to modulate feeding.MethodsIn vivo calcium imaging, viral neuronal tracing, and feeding behaviors were assessed in response to chemo‐ and opto‐genetic stimulation of gut‐innervating vagal sensory neurons using CARTcre mice.ResultsAnatomical tracing revealed that LNGCART and RNGCART neurons innervate different regions of the duodenum (n=3). LNGCART innervate the muscular layer, while RNGCART innervate the villi. Importantly, 2‐photon calcium imaging highlighted real time increased activity in LNGCART in response to stretch, while intraduodenal fat infusions preferentially increased RNGCART neuron activity (n=7/group). Mice with LNGCART neurons ablation consumed higher volumes of liquid meal indicative of attenuated response to gastric and intestinal distension (n=6‐7/group). Furthermore, chemogenetic stimulation of LNGCART, but not RNGCART, caused pronounced and sustained hypophagia (n=7/group). Interestingly, mice with chemogenetic activation of RNGCART, but not LNGCART, increased flavor conditioning (n=7/group), while ablation of RNGCART neurons abolished the conditioned flavor preference that was paired with intragastric fat infusion (n=7/group) supporting their role in reward. In addition, optogenetic stimulation of RNGCART promoted self‐stimulation in a nose poke task (n=4). Lastly, dopaminergic neurons of the substantia nigra increased their firing rate in response to intraduodenal fat infusion, but not duodenal distension (n=2/group).ConclusionLeft and right vagus nerves provide different sensory information about a meal to the brain. Both anatomical and behavioral feeding studies support the necessity and sufficiency LNGCART neurons as food quantity detectors and RNGCART neurons as food reward mediators ‐ which has less influence on how much is consumed but rather plays a role in the decision‐making process about which foods to consume. Our findings on asymmetrical vagal innervation of the gut provides new mechanistic insight for how feeding decisions are made in response to vast and complex meal‐related signals.
Study on changes of cardiac function and peripheral vascular resistance in elderly patients with hypertension
Authors: Hao Chunyan , Yang Shuang , Li Mingli , Duan Hubin 
Published: May 2022

ObjectiveTo investigate the changes of cardiac function and peripheral vascular resistance in elderly patiants with hypertention and their correlation with homocysteine (Hcy) and lipid levels.Methods126 hypertensive patients aged ≥60 years in the department of geriatrics, the first hospital of shanxi medical university from October 2017 to March 2019 were selected as the hypertension group, and 107 healthy patients aged ≥60 years in the same period were selected as the control group(The clinical study has passed ethical review). Serum Hcy and lipid levels in the two groups were measured, and parameters of cardiac function and peripheral vascular resistance were recorded by non‐invasive hemodynamic detector. The changes of Hcy, lipid profile, cardiac function and peripheral vascular resistance parameters in the two groups were compared, and the correlation between cardiac function and peripheral vascular resistance parameters and Hcy and lipid profile was analyzed.ResultsHcy, total cholesterol (TC), triglyceride (TG) and low‐density lipoprotein cholesterol (LDL‐C) in the hypertension group were higher than those in the control group (P<0.05), while high‐density lipoprotein cholesterol (HDL‐C) was lower than those in the control group (P<0.05). Peripheral vascular resistance (SSVR) and systemic resistance (SVR) in the hypertensive group were higher than those in the control group (P<0.05), and cardiac function parameters (CO), SV, LSW and LVET were lower than those in the control group (P<0.05). Pearson correlation analysis showed that hypertension group CO and Hcy in cardiac output, and negatively correlated with TC, LDL‐C, stroke volume SV and negatively correlated with Hcy, left ventricular stroke work LSW and negatively correlated with Hcy, LDL‐C, left ventricular ejection time (LVET)and negatively correlated with Hcy, peripheral vascular resistance index SSVR, SVR and Hcy, TC, TG, LDL‐C were positively correlated, and negatively correlated with the SVR and HDL‐C.ConclusionIn elderly patients with hypertension, cardiac function, including cardiac displacement and myocardial contractility, was significantly reduced, and peripheral vascular resistance was significantly increased. Moreover, such hemodynamic disorder was associated with Hcy and lipid levels.
The Effect of Curricular Reform on Gross Anatomy Laboratory Examination Performance: A Retrospective Analysis
Authors: Taylor Melissa , Nichols Richard A. , Herr Michael , Loder Danielle 
Published: May 2022

IntroductionMedical education in the United States has changed dramatically in the last few decades. Medical schools have moved away from a traditional, didactic, and discipline‐based curriculum to a more integrative, active, and student‐centered curriculum. Another common change has been the shift from a graded curriculum to a pass‐fail curriculum. While much research has documented overall performance, especially on high stakes examinations, little research has been conducted on gross anatomy laboratory performance.AimThis study examines the effects of curricular change, including decreased contact hours and shift to a pass‐fail curriculum, on gross anatomy laboratory performance.MethodologyGross anatomy laboratory examinations were reviewed retrospectively in two cohorts: one cohort that was in the previous, nonintegrated curriculum with a graded (i.e., A, B, F) curriculum; and a second cohort that was part of the first integrated class with a pass‐fail curriculum. For the pass‐fail curriculum in particular, the standard for passing was notably lower than that for the graded curriculum. Each of the students’ examinations were de‐identified. Only identification questions (i.e., ones that asked “Identify the tagged structure”) were reviewed. Questions that were common between the two cohorts were used for analysis. An independent samples t‐test was performed on the data, and Cohen’s d effect size was calculated. Significance was ascribed for p<0.05.ResultsThere were 69 questions that were similar between all the laboratory examinations from the pre‐curricular reform and post‐curricular reform cohorts. There was an approximately even number of questions from muscles, nerves, vessels, and additional structures on the cadaveric specimens and plastic models used on the examinations. It was found that the post‐curricular reform cohort scored significantly lower (mean = 67.05 ± 22.35) than the pre‐curricular reform cohort (mean = 79.89 ± 19.56) p<0.001, d = 0.61.Discussion and ConclusionThe results of the study demonstrate that students within the new curriculum, with reduced contact hours and a pass‐fail curriculum, performed significantly poorer than students in the non‐integrated curriculum. Students may have felt that the gross anatomy laboratory experience was lower stakes compared to their other coursework, especially since the passing standard for the post‐curricular reform cohort was markedly lower than the that of the pre‐curricular reform cohort.
Development of highly potent and selective GRK5 inhibitors
Authors: Chen Yueyi 
Published: May 2022

G protein‐coupled receptor kinases (GRKs) regulate cell signaling by triggering receptor desensitization via phosphorylation on G protein‐coupled receptors (GPCRs). (1) The seven human GRKs (GRK1−GRK7) are classified into three subfamilies: GRK1 (GRK1 and GRK7), GRK2 (GRK2 and GRK3), and GRK4 (GRK4, GRK5, and GRK6). GRK2 and GRK5 are the most abundant in cardiovascular tissue, where they are potential targets for treatment of cardiovascular disease. GRK5 also undergoes Ca2+/calmodulin‐dependent nuclear localization, where it phosphorylates histone deacetylase 5 (HDAC5), inducing an increase in transcription of cardiac hypertrophy‐related genes. In GRK5‐knockdown mice, cardiomyocytes are protected from hypertrophy; however, the specific roles of GRK5 in heart failure and hypertrophic cardiomyopathy are still unclear. Furthermore, GRK5 is required for cancer progression in various cancer types. Depletion of GRK5 has been shown to suppress prostate cancer, breast cancer, and non‐small‐cell lung cancer. (2) Therefore, targeting GRK5 can also be a chemotherapeutic strategy. Here we are testing a series of inhibitors for GRK5/6 derived from the indolinone scaffold, utilizing Cys474 residue unique in GRK5/6 to enhance selectivity by covalent capture. An immediate goal is to facilitate the development of more selective inhibitors via rational design by determining x‐ray crystal structures of inhibitor complexes with GRK5. Recently, we have crystallized a hyper‐phosphorylated GRK5, and the active site structure suggested the possibility for compound soaking. Overall, discovery of the inhibitors can significantly facilitate understanding and treatment of cardiovascular diseases and cancer.1. Z. Yang et al., Phosphorylation of G Protein‐Coupled Receptors: From the Barcode Hypothesis to the Flute Model. Molecular Pharmacology 92, 201‐210 (2017).2. L.‐P. Jiang et al., GRK5 functions as an oncogenic factor in non‐small‐cell lung cancer. Cell Death Dis 9, 295 (2018).
Enhanced confidence and ultrasound‐performance skills of medical students: A comparative study with and without prior videographic ultrasound exposure
Authors: Li Jeffrey J. , Kim Jane J. , Tan Shirley , Young Corey , Park Claire , Haney Megan , Nausheen Fauzia 
Published: May 2022

INTRODUCTIONPoint‐of‐care ultrasonography (POCUS) is commonly used in many modalities of medicine. However, there is a lack of standardized protocol for integrating POCUS into preclinical medical education. Previous literature has detailed the benefits of POCUS in clinical diagnoses and reasoning, but many medical students still lack exposure to POCUS. At California University of Science and Medicine (CUSM), medical students will be exposed to POCUS in their preclinical years. We aim to compare the confidence levels and ultrasound‐performance skills of medical students with and without prior videographic ultrasound exposure.HypothesisPrior videographic ultrasound exposure will improve the confidence and ultrasound‐performance skills of medical students during a live ultrasound workshop compared to those without videographic exposure.MethodsParticipants will be divided into two groups. One group will watch a 5–10‐minute procedural video about ultrasound‐guided peripheral intravenous (IV) access prior to ultrasound training, while the other group will be ultrasound‐naive prior to ultrasound training. Ultrasound training will be led by three other medical students who are trained and approved by ultrasound physicians. After demonstrations, participants will practice ultrasound‐guided IV access on a practice pad. Instructors will grade students on the spot on their ability to perform ultrasound‐guided IV access correctly. The parameters measured will be proper positioning of the ultrasound probe, insertion of the needle, ultrasound probe movement, puncturing of the vein, and overall technique. The two study groups will then take surveys on their perceived performance and overall confidence levels.ResultsResults from participants will be scored using two measures. Firstly, their self‐reflection surveys will measure their level of confidence and perceived ultrasound‐performance skills. Secondly, on‐the‐spot grading by instructors will provide information on participants’ actual ultrasound‐performance skills. A standardized grading scheme will ensure fairness among different instructors and participants.ConclusionComparison of the effectiveness of an additional videographic ultrasound component prior to live demonstration will be elucidated. This study will help create elements within existing ultrasound curriculae that will enhance the confidence and ultrasound‐performance skills of preclinical medical students.
Marsupsin Isolated from Polyherbal Product ABPA Rejuvenates Insulin Resistance in L6 Skeletal Muscle Cell Line via IRS1‐PI3K‐AKT‐GLUT4 Signaling Pathway
Authors: Balachandran Abbirami , Okechukwu Patrick N. , Gunasekaran Baskaran , Nalweyiso Jacinta , Sapra Sameer , Stanslas Johnson , Froemming Gabriele R. A. , Rajendran Salini D. 
Published: May 2022

BackgroundInsulin resistance (IR) is one of the key characteristics of type 2 diabetes mellitus (T2DM) which impairs the insulin signal transduction pathway. It is typically caused by many factors including hyperglycemia, accumulation of advanced glycation end products (AGEs), chronic oxidative stress and hyperlipidemia. Hence, complementary medicine such as herbal medications have been widely used as a complement to allopathic medicine to facilitate its efficacy while minimizing its potential adverse effects. ABPA is a polyherbal formulation that consists several powerful antidiabetic agents such as Pterocarpus marsupium. Our previous study showed that ABPA exhibited strong antidiabetic effect and detected high expression of marsupsin through HPLC studies.ObjectiveThe current study aims to elucidate the effect of marsupsin in rejuvenating insulin resistance through the IRS1‐PI3K‐AKT‐GLUT4 insulin signaling pathway.MethodL6 skeletal muscle cells were cultured and differentiated into L6 myotubes under standard conditions. The differentiated L6 myotubes were induced with high insulin to mimic insulin resistance and treated. Glucose uptake assay was also conducted to evaluate the effect of marsupsin on the rate of glucose uptake in the L6 cells. The cells were then lysed to extract the protein and RNA where the protein and differential gene expression of IRS1, PI3K, AKT and GLUT4 were analyzed using ELISA, qPCR, and Western Blot respectively.ResultsThe rate of glucose uptake was higher in MAR‐treated cells as compared to the negative control. This was further confirmed in the ELISA, qPCR and Western Blot analysis where MAR‐treated cells showed an upregulation of IRS1, PI3K, AKT and GLUT4 proteins as compared to the vehicle control.ConclusionMarsupsin rejuvenates insulin resistance in skeletal muscle cells by increasing the rate of glucose uptake through the activation of the IRS1‐PI3K‐AKT‐GLUT4 pathway.
Transcriptional regulation of primary and specialized metabolism
Authors: Brady Siobhan 
Published: May 2022

Michelle Tang1, Allison Gaudinier1, Baohua Li1, Lifang Zhang2, Christophe Liseron‐Monfils2, Joel Rodriguez‐Medina1, Anne‐Maarit Bagman1, Andrew Olsen2, Doreen Ware2,3, Mary Frank4, Bo Shen4, Daniel J. Kliebenstein1, Siobhan M. Brady11UC Davis, Davis, CA2Cold Spring Harbor Laboratory, Cold Spring Harbor, NY3USDA‐ARS, Albany, NY4DuPont Pioneer, Johnston, IARegulation of plant development requires intricate communication with both primary and specialized metabolism in order to fuel growth. While transcriptional regulation of metabolism is evident from myriad whole genome‐expression analyses, our understanding of which transcriptional regulators are responsible for these changes as well as their underlying mode of action is unclear. I will highlight our efforts on systematic mapping of transcriptional regulators of primary metabolism (nitrogen and central carbon) as well as specialized metabolism (glucosinolates). Network analyses incorporating protein‐DNA interaction data, gene expression and connectivity were used to identify critical regulators, most of which were shown to regulate metabolism via developmental‐ and stress‐conditional processes that coordinate across primary and specialized metabolism. These analyses demonstrate distinct design principles responsible for metabolism between microbes and this multicellular eukaryote.
Roles for inter‐organelle contacts in organizing metabolism
Authors: Henne W. M. 
Published: May 2022

When faced with nutrient shortage, cells adapt by remodeling their metabolic pathways and organelles. I will discuss our work using budding yeast to dissect how nutrient shortage impacts the spatial organization of metabolism and lipid droplets. We find that in response to glucose restriction, yeast remodel their mevalonate pathway by spatially compartmentalizing its rate‐limiting enzyme, HMG‐CoA Reductase (HMGCR). HMGCR spatial compartmentalization occurs at a unique inter‐organelle contact site called the nucleus‐vacuole junction (NVJ). This spatial partitioning enhances HMGCR activity, driving mevalonate synthesis to enable cellular adaptation. Our work suggests a new use for an inter‐organelle contact site in the fine‐tuning of mevalonate metabolism during nutrient stress.Remarkably, we also find that glucose restriction drives the phase transition of lipids within lipid droplets (LDs), causing them to convert from a disordered to liquid‐crystalline phase. Mechanistically, we find that these liquid crystalline lattices (LCLs) within LDs require triglyceride lipolysis. We also find that LCL‐LDs exhibit changes to the LD surface proteome. Several known LD proteins redistribute from LDs to the ER network, whereas others remain on LCL‐LDs, suggesting phase transitions of LD lipids influences LD protein targeting. Global proteomics also reveals that triglycerides harvested from LDs fuel cellular energetics at peroxisomes and mitochondria. This indicates that glucose starvation induces inter‐organelle lipid flux while promoting lipid phase transitions within LDs.
Building the microtubule cytoskeleton via phase transitions
Authors: Petry Sabine 
Published: May 2022

How does a cell construct its microtubule cytoskeleton? According to Feynman’s principle “what I cannot create, I do not understand”, my lab pursues this question by building the chromosome segregation machinery from scratch. I will first tell you how the microtubule framework is generated in a cell. Upon deciphering the function of the most important microtubule accessory proteins, I will present how we use those building blocks to reconstitute a spindle substructure in vitro and determine its building plan. Surprisingly, the spindle substructure relies on a protein condensate, which forms on the surface of a microtubule and arranges into a droplet pattern like a fluid.By studying how the MT cytoskeleton is built, I hope to help explain how hundreds of proteins can self‐assemble on the nm scale into a complex molecular machine 1000‐fold larger than its constituents, a challenge for the biochemistry of the 21st century.
Epigenetic Mediators of Risk for Metabolic Disease Across Generations
Authors: Patti Mary E. 
Published: May 2022

Obesity and type 2 diabetes (T2D) are leading global health threats and innovative multi‐pronged approaches are needed to combat both epidemics. Many risk factors for obesity and T2D – beyond genetics – are present before birth, reflecting the influence of environmental factors on germ cells and on the developing infant. For example, parental obesity or diabetes, prenatal undernutrition, and both low and high birth weight, are linked to offspring’s obesity and T2D risk later in life. Such prenatal exposures increase obesity risk not only in the individual exposed to the stressor, but also in their offspring. The result is a vicious cycle of risk to subsequent generations.The concept that the maternal perinatal environment shapes childhood chronic diseases is well‐recognized. However, mounting evidence demonstrates that fathers can also contribute to obesity and diabetes risk to their offspring. While genetic factors are important, additional non‐genetic impacts of paternal metabolism have been demonstrated both in rodent models and in humans. Paternal metabolism can influence epigenetic signals in sperm, including DNA methylation, histone modification, and/or noncoding RNA (ncRNA), which can impact gene expression and development in the offspring. We and others have shown that epigenetic marks are altered in sperm from rodents exposed to prenatal undernutrition, postnatal overnutrition, and other stimuli. While human data are more limited, paternal BMI at the time of conception is associated with infant birth weight and DNA methylation of infant cord blood; differential DNA methylation at some loci persisted to age 7. Our new preliminary data demonstrate that T2D also modifies the sperm methylome.Given that sperm epigenetic marks may be modifiable, this suggests a potential novel approach and untapped opportunity for multigenerational prevention of metabolic disease. We demonstrate that interventions in male mice, including exercise and pharmacological lowering of glucose levels, result in amelioration of obesity, glucose tolerance and metabolic syndrome in offspring.
Reprogramming T cells to target glycans and overcome glycan‐mediated immunosuppression for cancer therapy
Authors: Posey Avery D. 
Published: May 2022

T‐lymphocytes (or T‐cells) exhibit rapid proliferation and cytotoxicity after immune recognition of foreign or non‐self antigens. Cancerous cells can often display mutated peptides that can be recognized as non‐self by the immune system, but a frequent mechanism of tumor escape is loss of the antigen display complexes. Chimeric antigen receptor (CAR) technology allows T‐cells to be genetically engineered with a novel immune receptor (as well as additional pro‐inflammatory or effector molecules) that redirect T‐cell specificity based on the targets of monoclonal antibodies. This genetic engineering allows the manufacturing of billions of T‐cells specific for one tumor‐associated antigen.Previously, we designed a CAR T‐cell therapy that targets the glycopeptide epitope Tn‐MUC1 and demonstrated anti‐tumor efficacy against a variety of tumor histotypes, including T‐cell lymphoma, pancreatic cancer, breast cancer, prostate cancer, and other cancer histotypes. Now, we extend the targeting of Tn‐glycopeptides to an oncofetal form of fibronectin, recognized by the antibody FDC‐6. Tn‐fibronectin‐targeting CAR T‐cells exhibit similar efficacy against PC3 prostate tumors as CAR T‐cells targeting cell surface antigens; however, the mechanism of action of cytotoxicity appears to be different, suggesting that T‐cells targeting extracellular antigens may represent a novel platform for inducing anti‐tumor efficacy. Additionally, CAR T‐cell activity against tumors can be improved through additional engineering approaches, such as the use of enzymatic activity, the generation of immunomodulatory fusion proteins, and secretion of large molecules, such as cytokines and antibodies.