bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulator of G Protein Signaling Protein 6 (RGS6) Protects the Heart from Ischemic Injury
Authors: Rorabaugh Boyd , Mabe Nathaniel , Seeley Sarah , Bui Albert , Yang Jianqi , Neubig Richard , Fisher Rory 
Published: June 2021

BackgroundRegulator of G protein signaling (RGS) proteins are important modulators of cardiac function. We previously reported that disruption of interactions between RGS proteins and Gαi2 protects the heart from ischemic injury. However, the ability of specific members of the RGS protein family to influence cardiac sensitivity to ischemic injury has not been previously explored. The goal of the present study was to determine how genetic deletion of specific RGS proteins influences myocardial sensitivity to ischemic injury.MethodsHearts from RGS1 knockout (RGS1‐/‐), RGS2‐/‐, RGS2‐/‐ RGS4‐/‐ double knockout, RGS5‐/‐, and RGS6‐/‐ mice, and their respective wildtype (+/+) littermates were subjected to 30 min ischemia and 2 hours reperfusion using the Langendorff isolated heart model. Infarct sizes were measured by triphenyltetrazolium chloride staining.ResultsRGS6‐/‐ hearts had significantly larger infarcts than RGS6+/+ hearts (51 ± 2 % and 34 ± 5 % area at risk, respectively). Importantly, deletion of RGS1, RGS2, RGS4, or RGS5 had no effect on infarct size indicating that this effect was specific for RGS6. We also found that RGS6 expression was significantly decreased in ventricles (but not atria) of RGS6+/+ hearts subjected to ischemia / reperfusion injury.ConclusionThese data demonstrate that expression of RGS6 protects the heart from ischemic injury. Modulating RGS6 may provide a novel therapeutic approach for the treatment of ischemic heart disease.
Extended Biomimetic Culture and Functional Assessment of Recellularized Human Lungs
Authors: Gilpin Sarah , Charest Jonathan , Tapias Luis , Ren Xi , Wu Tong , Ott Harald 
Published: June 2021

RationaleNative lung scaffolds prepared by decellularization provide a novel platform for organ engineering. Recellularization with specific cell types requires ex vivo culture for evaluation and restoration of organ function prior to transplantation.MethodsHuman lung‐derived epithelial and endothelial cells were isolated and expanded in vitro. Immunostaining, flow cytometery, and qPCR confirmed cell identity. Epithelial and endothelial cells were delivered to lung scaffold airways and vasculature respectively (>350x106).Constructs were cultured for 10 days in a custom automated, closed‐circuit bioreactor, providing physiologic perfusion and negative pressure ventilation. Perfusate was analyzed daily by iSTAT. Tissue was analyzed by histology and qPCR.ResultsDonor‐derived epithelium was a population of primarily basal‐cell phenotype (70% p63+), with 20% CC10+, and minor pneumocytes (<10% SP‐B/C) by flow cytometry. Basal cell ciliogenesis was confirmed by ALI. Endothelium was sorted to CD31 purity.Biocompatibility to lung matrix confirmed maintenance of cell phenotype, viability, and proliferation (Ki67+) in slice co‐culture.Recellularized constructs were cultured for 6 days with constant perfusion, plus 4 days with additional fluid or air ventilation. Increasing rate of glucose metabolism and lactate production in the perfusate was quantified over time. Measured pO2, pCO2, and pH remained consistent.Cell distribution and viability was confirmed by Resazurin metabolism, and by histology/qPCR of serial tissue biopsies.ConclusionIntact acellular lung scaffolds can be repopulated with primary tissue‐derived cells and maintained in extended ex‐vivo biomimetic culture, supporting cell viability and function.image
Substrate Utilization Effects on Shortening Properties in Aging Cardiac Myocytes
Authors: Barton Greg , Aiken Judd , Diffee Gary 
Published: June 2021

Aging is associated with declining cardiac contractile function as well as changes in substrate metabolism and mitochondrial function. The relationship between age‐related changes in cardiac metabolism and declining cardiac contractile function has not been determined. We explored the role of alterations in substrate metabolism on age‐related changes in contractile function of isolated left ventricular myocytes from Young (Y) and Old (O) FBN rats. Single, intact myocytes were stimulated for ten minutes of continuous contraction at either2Hz or 4Hz while being perfused with Ringers solution containing either Glucose (11mM) or Oleate (0.4mM) as the fuel substrate. Properties of shortening (% and rate of shortening) were measured at the onset (T0) and after 10 minutes (T10) of continuous contraction, and the decline in shortening over time (T10/T0) was determined at each workload. Myocytes from Y hearts generally had better contractile function when glucose was the substrate, with a smaller workload‐dependent decline in function, compared to when oleate was the substrate. In aged myocytes, the opposite was true, with O myocytes showing less workload‐dependent decline in percent shortening and rate of shortening when oleate was the substrate. This data suggests that when forced to use only one substrate, myocytes from young hearts are better able to use glucose, while cells from old hearts are better able to metabolize oleate.Supported by NIH AG030423
Metaboreflex Activation Delays Heart Rate Recovery after Aerobic Exercise
Authors: Peçanha Tiago , Brito Leandro , Fecchio Rafael , Sousa Patricia , Silva‐Júnior Natan , Forjaz Cláudia 
Published: June 2021

The role of metaboreflex on heart rate recovery after exercise (HRR) is controversial. It is speculated that this mechanism is active in exercises with larger muscle masses, however it has not been tested after a typical aerobic exercise. The aim of this study was to evaluate the influence of metaboreflex on HRR. 12 healthy middle‐aged men randomly underwent 2 sessions consisting of an exercise (cycle ergometer, 70% VO2peak, 30 min) followed by 5 min of recovery. In each session, the recovery was performed with (occlusion) or without (control) leg circulatory occlusion (cuffs at the hips inflated to supra‐systolic pressure). ECG was registered and HRR was assessed by: heart rate reduction after 60 (HRR60s) and 300s (HRR300s) of recovery; short‐term time constant of HRR (T30); time constant of the HRR after exponential fitting (HRRτ); and mean values of HR in segments of 30s (HR30s). Heart rate variability (HRV) was assessed by the root mean square residual (RMS) and square root of mean squared differences of successive R–R intervals (rMSSD) on subsequent 30‐s segments. Paired T‐test, Wilcoxon test and ANOVA were employed. HRR60s (25 ± 7 vs. 22 ± 12 beats.min‐1, p = 0.69), T30 (284 ± 155 vs. 309 ± 253 s, p = 0.89) and HRRτ (120 ± 45 vs. 107 ± 103 s, p = 0.75) were similar between control and occlusion sessions, respectively. HRR300s was significantly lower in occlusion session (30 ± 13 vs. 38 ± 14, p = 0.05). There was no session vs. time interaction for the rMSSD index (p = 0.46), while HR30s and RMS had significant time vs. session interactions (p = 0.00 and 0.01, respectively), showing slower decrease of HR30s and slower increase of RMS in the occlusion session. In conclusion, metaboreflex activation delays HRR, particularly at the slower phase of HRR.Funding: FAPESP 2013/044997‐0 and 2013/05519‐4; CAPES PROEX
Exercise Mitigates Hyperhomocysteinemia Induced Vascular Dysfunction and Adverse Skeletal Muscle Remodeling
Authors: Winchester Lee , Veeranki Sudhakar , Pushpakumar Sathnur , Givvimani Srikanth , Tyagi Suresh 
Published: June 2021

IntroHyperhomocysteinemia (HHcy) is associated with vascular and skeletal muscle dysfunction. HHcy induces MMP‐9 activity, myostatin release, systemic inflammation and may increase M1 macrophages. Previous reports suggest that exercise reduces HHcy and myostatin levels, however the effects of exercise on macrophages and myostatin during HHcy are unclear. We hypothesize that exercise decreases HHcy induced inflammation and muscular dysfunction by decreasing MMP‐9, myostatin and M1 macrophages.MethodsC57 WT, FVB, MMP‐9‐/‐, CBS‐/+ (HHcy), and CBS‐/+/MMP‐9‐/‐ (Double KO) mice were administered 4 weeks of treadmill running, swimming, or no exercise for controls. Ultrasonography and laser Doppler were used to measure wall to lumen ratio, blood flow and perfusion rate of the femoral artery. Western Blotting, IHC, Histology and PCR were used to analyze mouse tissue samples.ResultsBlood flow rates in control CBS‐/+ mice were approximately 23.9% lower than in control C57 WT mice. This rate was increased by 1.89 fold with exercise. Wall to Lumen ratio was approximately 4.14 fold higher in the CBS‐/+ control mice compared with WT, but became similar to WT after exercise. Laser Perfusion imaging demonstrated a 12.5% lower femoral artery red blood cell flux in CBS‐/+ mice when compared with WT, but was increased by 1.35 fold after exercise. Collagen staining reveals higher collagen deposition in the gastrocnemius of CBS‐/+ mice compared with WT, but was completely reversed with exercise.ConclusionsWe conclude that Exercise Mitigates HHcy Induced Vascular Dysfunction and Adverse Skeletal Muscle Remodeling.
The Effects of Perinatal Androgen Deprivation on Sexual Motivation in Male Rats
Authors: Khan Talha , Yn Alicia , Fickes Dane , Vang Pakou , Jeong KumHwa , Shah Binita , Yousaf Faeeq , Taylor George , Gopalan Chaya 
Published: June 2021

Testosterone and its metabolites—estrogen and dihydrotestosterone— are involved in the brain sex differentiation during the perinatal period by binding to androgen receptors (AR) or estrogen receptors (ER). However, in the presence of flutamide (FLU), testosterone that is metabolized to estrogen will only bind to ER. Blockade of AR using FLU during the perinatal period could alter the levels of estrogen, which in turn, may modulate the sex differentiation of the brain. This study tested perinatal androgen deprivation on estrogen levels and in turn, its effects on sexual motivation paradigm in male rats.Animals (N=37) were divided into two groups: Group 1 received FLU (20 mg/kg; SC) during perinatal period (prenatal day 4 ‐ postnatal day 4) and Group 2 served as control. On postnatal day 65, these groups were divided into 3 subgroups (injected 5 days/week x 7 weeks): A. finasteride (20 mg/kg, SC), an α‐reductase inhibitor, B. letrozole (2 mg/kg, SC), an aromatase inhibitor and C. vehicle. Each male rat had a choice of approaching a cage containing a gonadally‐intact female or an ovariectomized (OVX) rat for 20 minutes. The movement of the male rat was video‐tracked by Any‐Maze. In addition, serum estrogen levels were measured using ELISA.Animals receiving FLU not only had high serum estrogen levels, but also exhibited no preference for the gonadally‐intact or the OVX female. On the other hand, the control‐vehicle group spent more time with the gonadally‐intact than the OVX rat. These results suggest that perinatal androgen deprivation in male rats results in high levels of estrogen and lack of sexual motivation towards gonadally‐intact female rats.
Characterizing household food shopping behavior using novel receipt‐based geospatial measures
Authors: Barnes Timothy , French Simone , Mitchell Nathan , Van Riper David 
Published: June 2021

BackgroundIn efforts to better understand how geographic food access measures influences dietary behaviors, researchers are developing second‐generation methodologies to explore and track how individuals behave within their food environment.MethodsUsing receipt‐based data collected over four weeks in 90 households in Minneapolis/St. Paul, MN and geographic information systems (GIS), we created two geospatial measures to characterize households' shopping spaces via minimum bounding geometry. Thus, a spatial ‘footprint’ representing the geographic areas households purchased food at supermarkets and restaurants was determined. Statistical correlation with traditional measures of shopping behavior (frequency and distance traveled) were assessed along with associations with food purchasing (in dollars) and dietary intake of fruit, vegetables, and sugar‐sweetened beverages.ResultsOn average, households' shopping space for supermarkets and restaurants were 15.9 and 41.8 square miles, respectively. Shopping space was significantly correlated with both frequency of shopping and distance traveled for supermarkets (r=0.59 and r=0.54) and restaurants (r=0.74 and r=0.45). Neither shopping space for supermarkets or restaurants were significantly associated with purchases of fruits and vegetables, however, restaurant shopping space was significantly associated with expenditures for sugar‐sweetened beverages (β=0.06, p=0.004) and vegetable intake (cup servings) during the past 7 days (β=‐0.01, p=0.015).ConclusionsFindings suggest that household shopping space may capture shopping and purchasing behaviors of interest to researchers examining the relationship between the food environment and dietary intake.
Imaging IGF‐I Uptake in Growth Plate Cartilage Using in vivo Multiphoton Microscopy
Authors: Serrat Maria , Ion Gabriela 
Published: June 2021

Bone elongation occurs in cartilaginous growth plates located at the ends of the principal long bones. Linear growth is driven by a cascade of cellular signals initiated by endocrine and paracrine regulators acting on growth plate chondrocytes. Relative to our knowledge of their signaling mechanisms, surprisingly little is known about how these molecules physically reach avascular cartilage (which lacks a penetrating blood supply) or how they are transported from surrounding blood vessels through the dense extracellular matrix. In vivo multiphoton microscopy is a powerful imaging modality that enables the study of intact growth plates with cellular level resolution. This imaging approach has potential to fundamentally advance our understanding of bone lengthening processes by allowing us to track molecular delivery to cartilage in real time. We developed quantitative methods for measuring the uptake of biologically active IGF‐I into tibial growth plates of live 5‐week old mice. We demonstrate that fluorescently‐labeled IGF‐I is readily taken up in growth plate cartilage and localizes to chondrocytes. In vitro bioactivity tests confirmed that the labeled protein is functional, assessed by phosphorylation of its downstream targets. These results are relevant for understanding mechanisms of growth plate regulation and for developing strategies to modulate limb elongation rate through growth factor delivery to cartilage.Supported by ASBMR GAP, UK‐CCTS (NIH UL1TR000117), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R15AR067451‐01).
Comparing arginine flux, catabolism and availability for NO synthesis in American, Indian, and Jamaican women
Authors: Hsu Jean , Kao Christina , Dwarkanath Pratibha , Karnes Jeffrey , Baker Tameka , Bohren Kurt , Badaloo Asha , Thame Minerva , Kurpad Anura , Jahoor Farook 
Published: June 2021

We have reported that Indian women do not have increased Arg production during pregnancy like their American or Jamaican counterparts. There has not been a direct comparison of Arg flux, catabolism, and availability for NO synthesis in non‐pregnant American, Indian, and Jamaican women. The objective of this study was to determine whether Indian women are producing less Arg and/or catabolizing more Arg to Orn and therefore have less Arg available for anabolic pathways than their Jamaican and American counterparts. Ten healthy women of childbearing age from each country were given 6h primed, constant intravenous infusions of 15N2‐Arg, 2H2‐Cit, 15N2‐Orn, and 2H5‐Phe in both the fasted and fed states to measure Arg flux, hydrolysis, bioavailability, NO synthesis and Phe flux, an index of protein breakdown.

USA
India
Jamaica
P Value

μmol/kg FFM/h
μmol/kg FFM/h
μmol/kg FFM/h

Fasted

Arg flux
56.1 ± 2.1a
54.2 ± 3.1a
66.1 ± 3.1 b
0.01

Arg hydrolysis
17.6 ± 1.5 a
23.7 ± 1.5 b
23.4 ± 1.6 b
0.01

Arg bioavailability
49.9 ± 1.3 ab
42.0 ± 2.6 a
55.5 ± 3.5 b
0.004

NO Synthesis
0.18 ± 0.01a
0.15 ± 0.01 b
0.21 ± 0.02 a
0.002

Phe flux
39.7 ± 0.9
39.0 ± 2.2
43.8 ± 2.3
0.17

Fed

Arg flux
79.1 ± 3.3 a
80.3 ± 4.9 a
95.9 ± 2.9 b
0.008

Arg hydrolysis
27.3 ± 2.5 a
39.6 ± 3.7 b
37.2 ± 2.0 b
0.01

Arg bioavailability
51.8 ± 1.2 a
40.7 ± 3.5 b
57.5 ± 3.2 a
&lt;0.001

NO Synthesis
0.20 ± 0.01a
0.21 ± 0.03a
0.34 ± 0.04 b
&lt; 0.0001

Phe flux
58.8 ± 1.6
59.4 ± 3.0
63.3 ± 2.7
0.39

Means with different superscript letters are significantly different, P < 0.05 (post‐hoc Tukey's multiple comparison test).In conclusion, Indian women had increased Arg hydrolysis without a compensatory increase in Arg flux resulting in decreased bioavailability of Arg for the synthesis of proteins and other Arg‐derived biomolecules, including NO synthesis. Though American women also had slower Arg flux compared to Jamaican women, they were able to conserve Arg bioavailability because of decreased Arg hydrolysis. The results suggest that Indian women may need a higher dietary Arg intake.Supported by the Bill and Melinda Gates Foundation
Mechanism of Liver Injury Caused by Autophagy Deficiency
Authors: Khambu Bilon , Zhang Hao , Li Yong , Chen Xiaoyun , Yin Xiao‐Ming 
Published: June 2021

Autophagy is a vital intracellular degradation process which is required for many physiological & pathological processes. Deficiency of autophagy in the liver causes severe injury characterized by increased liver function enzymes in serum & hepatocyte hyperplasia & degeneration. Mice lacking one of the key autophagy genes, such as Atg7, could also be subjected to a high mortality due to liver failure. However it is not clear how autophagy deficiency causes liver injury. The goal of this study is thus to investigate the potential mechanism of injury. A careful examination of the liver histology of the Atg7‐deficient mice indicates that there was inflammation, cell death, & significant ductular reaction. We hypothesized that there was a notable level of cholestasis, which can cause cholestatic hepatitis & thus liver injury. Indeed, further blood chemistry analysis indicated a raised level of total bile acids, cholesterol, & alkaline phosphatase. This exciting new finding suggests a molecular linker from autophagy to cholestasis regulation. Previously it has been reported that anti‐oxidative stress master gene, Nrf2, is involved in autophagy deficiency‐induced liver injury. Indeed, deletion of Nrf2 in Atg7 or Atg5‐deficient mice reversed the liver condition & corrected the injury phenotype, indicating that Nrf2 participates in the pathological changes caused by autophagy deficiency. Remarkably, co‐deletion of Nrf2 in Atg7‐deficient mice also significantly tamed the cholestatic features. These observations support the notion that Nrf2 over‐activation is the key factor in the development of cholestasis, which then cause hepatocyte apoptosis & liver injury.Autophagy deficiency can cause cholestasis, which could be responsible for the liver injury seen in the autophagy‐deficient mice.
Moving in and Renovating: Invasion and Remodeling of The Human Erythrocyte by The Malaria Parasite
Authors: Cowman Alan 
Published: June 2021

Moving in and renovating: invasion and remodeling of the human erythrocyte by the malaria parasiteAlan F. CowmanThe Walter and Eliza Hall Institute of Medical ResearchIn humans the most severe form of malaria is caused by Plasmodium falciparum. With a third of the world's population at risk of infection, with 300 million people infected and over 800,000 deaths annually malaria is still a huge problem. Entry of P. falciparum into erythrocytes involves a complex cascade of protein‐protein interactions using several specific ligand‐receptor interactions, that activate penetration and generation of a vacuole that the parasite resides in for subsequent development. Inside the parasite exports hundreds of its own proteins into the host erythrocyte remodelling these terminally differentiated host cells into one in which the parasite can harvest growth nutrients, while providing a protective niche allowing escape from host responses. Such exported proteins must traverse biological barriers including parasite, vacuole and erythrocyte membranes. Understanding function of the proteins involved in parasite invasion and host cell remodelling is important for development of a vaccine and new treatments required to treat and control disease. Malaria has been a companion of humans throughout history and numerous attempts to control it have been defeated by a combination of the ability of the parasite and mosquito vector to adapt. Recently, hope has arisen with strengthening political will to combat this including initiatives funded by the Bill and Melinda Gates Foundation. It is hoped that increased commitment to malaria together with exploitation of the scientific advances, together with our increased knowledge of the P. falciparum genome will bring this enemy under control.
You Need a Game Plan
Authors: Clifford Philip 
Published: June 2021

The Merriam Webster dictionary defines a game plan as a strategy for achieving an objective. If sports teams go through the effort to make detailed plans to win trivial competitions, doesn't it make sense for you to have a game plan for something as consequential as your career‾ To advance in a scientific career you need a game plan ‐ a strategy for how you will prepare for success in a highly competitive environment. Industry and government agencies have long used individual development plans (IDPs) to help employees navigate their careers and now the idea has caught on among PhD scientists.Constructing an IDP is a four‐step process: self‐assessment, exploring careers, setting goals, and implementing your plan. myIDP (myidp.sciencecareers.org) is a free website designed to help guide early career scientists through these steps. It includes exercises to assist you with the self‐assessment process and it will help you determine how well your skills and interests match 20 different scientific career paths. For each career path, there is an extensive list of resources in the form of articles, books, and professional organizations, which can be used to gain a better understanding about unfamiliar careers. Finally, there is a tool to assist you in setting and achieving your goals.An IDP will help you develop professionally by creating a game plan for a successful career. This session will briefly cover the why and how of creating an IDP.
Sphingolipids of Commensals Modulate Host Immunity through Regulation of iNKT Cells
Authors: Kasper Dennis 
Published: June 2021

The microbiota modulate invariant natural killer T (iNKT) cell numbers in the colon. SInce iNKT cells recognize glycosphingolipids presented by CD1d and the Bacteroidetes are among the few microbial phyla with sphingolipids contributing to membrane architecture, we sought to find a molecule within the Bacteroidetes involved in modulating iNKT cell homeostasis.In Bacteroides fragilis, we generated a mutant deleted of serine palmitoyl transferase (del SPT) that does not produce any sphingolipids in the microbial membranes. After monocolonization of germ‐free (GF) mice with either the wild‐type or the del SPT mutant, we found that the wild‐type B. fragilis colonized mice had significantly lower colonic iNKT cell numbers than the del SPT mutant mono‐colonized mice. Interestingly colonic iNKT cell numbers were very low in the wild type colonized mice as we had previously reported in conventionally colonized mice. In contrast, the del SPT mutant colonized mice had high iNKT cell numbers as we reported in GF mice. We purified and chemically identified a microbial sphingolipid molecule that when administered to the del SPT colonized mice, re‐capitulates the colonic iNKT phenotype seen in the WT mice. Sphingolipids have been reported previously to stimulate iNKT cell numbers, but the sphingolipid we have isolated from Bacteroides fragilis actually inhibits iNKT cell numbers in the colon, simulating the observation reported with the entire microbiota.Our study revealed a previously unknown pathway by which the microbiota modulate the host immune system. It also points to a new direction for therapeutic intervention of diseases mediated by proinflammatory iNKT cells.