bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lung fluid regulation at high‐altitude
Authors: Taylor Bryan , Summerfield Doug , Issa Amine , Kasak Alex , Johnson Bruce 
Published: June 2021

BackgroundWhether lung fluid accumulates in acclimating individuals at high altitude (HA) remains controversial.PurposeTo assess the effect of HA on lung fluid regulation.Methods/ResultsSystolic pulmonary artery pressure (sPAP) (echo), lung diffusing capacity for CO (DLCO), pulmonary capillary blood volume (Vc), alveolar‐capillary conductance (Dm) (single breath method), ultrasound lung comets (ULCs) and pulmonary function (PFTs) were assessed in 8 healthy adults at sea‐level and after 1 and 9 days at Mt. Everest Base Camp (EBC), Nepal (5150 m). Also, after 5 days at EBC, DLCO and PFTs were assessed in 5 subjects pre‐and post‐acute albuterol administration. EBC was reached after an 8 d hike at progressively increasing altitudes starting at 2800 m. Altitude exposure increased sPAP, had no effect on DLCO, increased Dm and decreased Vc with a subsequent increase in Dm/Vc, and decreased the number of ULCs (Table 1). There was no change in FVC or FEV1 but an increase in MEF50. Albuterol administration increased PEF (11.85±1.52 vs. 12.40±1.45 L/s) and MEF50 (4.85±0.77 vs. 6.00±1.30 L/s) but had no effect on DLCO, Dm or Dm/Vc.ConclusionThese data suggest that lung fluid is decreased in acclimating healthy humans at high altitude.Funding:Mayo Clinic & The North Face.
Effect of dietary protein on bone status in US Adults aged 50 years and older; NHANES 1999–2004
Authors: Kim Jung Eun , Zanovec Michael , Fulgoni Victor L , Campbell Wayne W 
Published: June 2021

Dietary protein is an important determinant of bone health, but the effect of dietary total protein intake (Tpro) on bone status of older adults is controversial. We assessed the effect of TPro on bone status using data from the 1999–2004 NHANES. Dietary (24‐h recall) and bone (DXA) data from 6,149 men and women aged 50+ y were analyzed. Subjects were grouped based on TPro (LP (n=1993), <0.8; MP (n=1150), 0.8–1.0; and HP (n=3006), >;1.0 g protein·kg ideal body weight (IBW)−1·d−1). Total‐body bone mineral content (BMC), appendicular BMC (aBMC), total‐body bone mineral density (BMD), and total‐body bone mass index (BoMI) were used as indicators of bone status. Mean protein intakes of LP, MP, and HP were: 0.58±0.004, 0.90±0.002, and 1.45±0.011 g protein·kg IBW−1·d−1, respectively. Compared to the LP, MP and HP had higher BMC (p<0.001), aBMC (p<0.001), and BMD (p<0.001) and HP had higher BoMI (p<0.001). There were no differences between MP and HP for these parameters. After covariate adjustment, HP had higher BMD (1.096 ± 0.003 g/cm2 vs. 1.085 ± 0.004 g/cm2; p < 0.05) than LP, with MP intermediate (1.094 ± 0.005 g/cm2). These results indicate inadequate protein intake adversely affects bone status in older adults. However, among subjects who consumed adequate protein, i.e. greater than 0.8 g protein·kg IBW−1·d−1, bone status was not influenced by higher protein intake.Funding: Dairy Res Inst, Purdue Ingest Behav Res Ctr
Mesenchymal stem cells (MSC) from porcine bone marrow (pBM) of the Os femoris and the Crista iliaca
Authors: Stock Peggy , Brückner Sandra , Tautenhahn Hans‐Michael , Pelz Sandra , Hempel Madlen , Christ Bruno 
Published: June 2021

MSC increasingly gain attention for clinical cell therapy of liver diseases. Before translation into the clinics feasibility must be proven preferably in large animal models.The aim of the study was to demonstrate in the large animal model of the pig whether MSC from bone marrow (pBM‐MSC) of the Crista iliaca and from BM of the femur/shank display differences in regard to their hepatogenic differentiation potential.MSC were isolated either from BM of the Crista iliaca or Os femoris. Mesenchymal features were analysed by flow cytometry. Functional properties like the synthesis of urea and glycogen were compared during hepatogenic differentiation.pBM‐MSC from both sources were negative for hematopoietic markers CD14, CD45 but positive for mesenchymal markers CD44, CD29, CD90, CD105. pBM‐MSC from both sources could be differentiated along the adipocyte, osteocyte and hepatocyte lineage. With differentiation progressing glycogen and urea synthesis increased featuring typical hepatocyte functions. After 21 days of differentiation urea synthesis amounted to 3 nmol/10.000 cells × 24h comparable to the rate in primary pig hepatocytes after 8 days of culture.pBM‐MSC from various sources are not different in respect to their mesenchymal features and their hepatogenic differentiation potential. Hence, hollow bones might be particularly useful to isolate allogeneic bone marrow cell transplants.
Excess postexercise leucine ingestion enhances muscle protein synthesis in skeletal muscle of older men
Authors: Dickinson Jared M , Gundermann David M , Walker Dillon K , Reidy Paul T , Borack Michael , Drummond Micah J , Arora Mohit , Volpi Elena , Rasmussen Blake B 
Published: June 2021

Essential amino acid (EAA) ingestion enhances postexercise muscle protein synthesis, and in particular leucine is thought to promote a greater stimulatory effect. The purpose of this preliminary study was to determine the influence of ingesting excess leucine shortly following resistance exercise (RE) on skeletal muscle mTORC1 signaling and protein synthesis in older adults over a 24h time‐course. During a stable isotope infusion trial, older men performed a bout of RE and at 1h postexercise ingested 10g of EAA containing either a leucine content similar to high quality protein (CTRL, 1.8g leucine, n=6) or excess leucine (LEU, 3.5g leucine, n=6). Muscle biopsies (vastus lateralis) were obtained at rest and at 2, 5, and 24h postexercise to examine mTORC1 signaling and muscle protein synthesis. mTORC1 signaling was increased above rest in both groups at 2 and 5h, however, this increase was more pronounced in LEU at 5h. mTORC1 signaling returned to resting levels at 24h in both groups. Muscle protein synthesis was increased above rest in both groups at 5h, and remained elevated above rest at 24h in both groups. However, the increase in muscle protein synthesis at 5h was more pronounced in LEU. These preliminary data suggest that excess leucine ingestion following RE may enhance the acute anabolic response to resistance exercise in older adults.NIAMS R01AR049877, NIA P30AG024832, NIH T32HD07539, NCATS UL1TR000071
Linoleic acid suppresses cholesterol efflux and ATP‐binding cassette transporters in murine bone marrow‐derived macrophages
Authors: Spartano Nicole L , Lamon‐Fava Stefania , Matthan Nirupa R , Obin Martin S , Greenberg Andrew S , Lichtenstein Alice H 
Published: June 2021

BackgroundIndividuals with diabetes are at increased cardiovascular disease (CVD) risk, possibly associated with elevated plasma free fatty acids (FA). Evidence suggests that elevated unsaturated (U)FA suppress macrophage cholesterol efflux, a mechanism implicated in CVD risk. Murine bone marrow‐derived macrophages (BMDM) were used to explore the relationship between elevated UFA and cholesterol efflux mediated by ATP‐binding cassette transporters (ABCA1 and ABCG1) and transcription factors liver‐x‐receptor‐alpha (LXR‐α) and sterol receptor element binding protein (SREBP)‐1.Methods/ResultsBMDM were stimulated with 100 uM linoleic acid (LA) or palmitic acid (PA) for 16 hrs, and exposed to 25 ug/mL oxidized low density lipoprotein (oxLDL) for 24 hr. LA and PA each suppressed ABCA1 mRNA (60% and 30%, respectively) and ABCG1 mRNA (54% and 29%, respectively) (all p<0.01). LA decreased high density lipoprotein (HDL) mediated cholesterol efflux by 53% and ABCA1 protein by 94% (both p<0.05) with no significant effect on ABCG1, LXR‐α or SREBP‐1 protein.ConclusionThese results suggest that elevated LA attenuates macrophage HDL‐mediated cholesterol efflux through alterations in ABCA1 mRNA and protein but not by regulating LXR‐α or SREBP‐1 expression. This mechanism may contribute to diabetes‐associated CVD.NHLIBI‐T32‐HL069772, USDA 58–1950‐0–0014
Linking obesity with colorectal polyp risk
Authors: Comstock Sarah S. , Hortos Kari , Kovan Bruce , McCaskey Sarah , Pathak Dorothy R. , Fenton Jenifer I. 
Published: June 2021

Obesity is known to increase the risk of colon cancer, and most colorectal cancers develop from adenomatous polyps. However, the effects of obesity on colonic polyp formation are unknown. The aim of this study was to determine if BMI was associated with advanced colon polyps in males. 126 men (48 – 65 yr) were recruited at time of first colonoscopy, and anthropometric measures were collected. Odds ratios were determined using logistic regression for polyp number (0 or ≥ 3) and polytomous logistic regression for polyp severity (no polyp, hyperplastic polyp, tubular adenoma). 41% of the men in our study were obese (BMI ≥ 30). Obese participants were 6.8 (CI: 1.4 – 34.6) times more likely than those who were lean (BMI < 25) to have ≥ 3 polyps than no polyps. For each category increase in BMI (lean, overweight, obese), an individual was 2.5 (CI: 1.2 – 5.4) times more likely to have ≥ 3 polyps than no polyps. Additionally, relative to lean individuals, obese individuals were 7.7 (CI: 2.0 – 29.7) times more likely to have a tubular adenoma then no polyp. As BMI category increased, participants were 2.8 (CI: 1.5 – 5.2) times more likely to have a tubular adenoma than no polyps. Due to the increased number and severity of polyps, earlier screening for polyps in obese individuals may be warranted.Grant Funding Source: NCI 1R03CA142000 and MSU CTSI
Regulation of the Na+,HCO3‐ cotransporter NBCn1 (SLC4A7) by a constitutively active ErbB2 receptor in MCF‐7 breast cancer cells
Authors: Gorbatenko Andrej , Olesen Christina , Valen Eivind , Pedersen Stine Falsig 
Published: June 2021

Net acid production is greatly increased in tumors due to a shift towards glycolytic metabolism. We previously showed that the Na+,HCO3− cotransporter NBCn1 (SLC4A7) is strongly upregulated in MCF‐7 breast cancer cells upon expression of a truncated, constitutively active ErbB2 receptor, ΔNErbB2. Here, we explore the mechanisms involved in this upregulation. NBCn1 mRNA and protein levels were reduced by inhibition of ERK or Src in ΔNErbB2‐, but not vector‐expressing MCF‐7 cells. PI3K‐Akt inhibition reduced NBCn1 expression in both cell types. NBCn1 expression was increased by stimulation of full‐length ErbB receptors. In luciferase promoter assays, the 1.2 kb genomic region upstream of SLC4A7 increased luciferase activity after ΔNErbB2 expression ~2.5 fold. Promoter deletions identified the ΔNErbB2‐ responsive region and putative transcription factor binding sites. NBCn1 expression was increased by expression of dominant‐negative (DN)‐Sp1 or by Sp1 knockdown, and decreased by knockdown of Krüppel‐like factor 4 (KLF4), while DN‐Sp3 or Sp3 knockdown had no effect. Chromatin immunoprecipitation assay (ChIP) demonstrated Sp1, Sp3 and KLF4 binding to the NBCn1 promoter. In conclusion, we identified an NBCn1 promoter and demonstrated that NBCn1 transcriptional regulation involves Sp1 and KLF4, and that ErbB2‐dependent upregulation of NBCn1 is controlled at least in part by ERK‐ and Src signaling.Funding: Danish Cancer Society, Danish Research Council
Francisella bacteria encode genes required for efficient invasion and intracellular replication in hepatocytes
Authors: Law HT , Sriram Aarati , Fevang Charlotte , Guttman Julian Andrew 
Published: June 2021

Francisella tularensis is a bacterium that can cause up to 60% mortality in humans. These microbes carry a cluster of conserved genes present in all F. tularensis subspecies called the Francisella pathogenicity island (FPI). Within the FPI, iglB, iglC, pdpA and vgrG genes are important for intracellular macrophage survival and virulence; yet, their role in epithelial cell infections, a major contributor to the progression of disease, is unclear. Given that F. tularensis uses dissimilar mechanisms to enter different cell types, we hypothesized that FPI genes play a crucial role in bacterial entry into epithelial cells. To test this hypothesis, BNL CL.2 hepatocytes were infected with F. novicida for up to 48 h. Detailed microscopic examination and gentamicin protection assay revealed that ΔiglB, ΔiglC, ΔvgrG, ΔpdpA Francisella mutants were invasion and replication deficient. We showed that gene complementation restored intracellular growth. Our data suggest that IglB, IglC, PdpA and VgrG are important for hepatocyte infections, as they are vital for efficient invasion and intracellular proliferation.Grant Funding Source: NSERC, CIHR
Microarray Studies on the Effects of Palm Fruit Juice in Diabetic Nile Rats
Authors: Leow Soon Sen , Bolsinger Julia , Pronczuk Andrzej , Hayes Kenneth C , Sambanthamurthi Ravigadevi 
Published: June 2021

The Nile rat (NR) models diet‐induced human type 2 diabetes (T2DM). In previous experiments (Brit J Nutr 106:1664, 2011), palm fruit juice (PFJ) blocked T2DM in male NR, while untreated rats exhibited advanced disease stages. The molecular mechanisms whereby PFJ exerts anti‐diabetic effects are unknown, prompting microarray gene expression analysis. Livers were obtained from NR undergoing 4 diet plans: hiCHO alone (diabetic control), 4800ppm resveratrol (RES) in food, 4800ppm PFJ in food, or 1500ppm PFJ in drinking water. Compared to hiCHO (most diabetic), hepatic liver gene expression profiles were enhanced for RES and PFJ‐food, while PFJ‐water gene expression changes were subtler. Random blood glucose was lowered (p<0.05) in both PFJ groups, but only slightly by RES (n.s.). Compared to hiCHO, PFJwater had 17 genes up‐regulated, 29 down‐regulated. PFJ‐food had 71 genes up‐regulated, 108 down‐regulated. RES had 90 genes upregulated, 76 down‐regulated. As a preliminary observation, the insulin signaling pathway, especially phosphatidylinositol (PI) 3‐ kinase, was significantly down‐regulated by PFJ‐food and RES, PFJ‐water being less marked. PI 3‐kinase has been reported to suppress glucose‐stimulated insulin secretion (Diabetes 51:87, 2002), suggesting PFJ and RES may modulate this activity in NRs to favor insulin secretion.Funding source: Foster Biomed Res Lab and the Malaysian Palm Oil Board
Psychopharmacology of a prominent HIV antiretroviral drug
Authors: Schetz John A. , Forster Michael J. , Maeso Javier González 
Published: June 2021

Over half of HIV patients taking the antiretroviral (ARV) drug efavirenz under prescribed dosing conditions experience psychiatric adverse drug reactions, and, despite earlier claims, these side effects can persist. Yet the mechanistic explanation for ARV drug adverse psychiatric events is unknown, prompting us to investigate the psychopharmacology of efavirenz. Profiling the GPCR psychopharmacology of efavirenz pinpointed its interactions with the serotonin 5‐HT2A receptor (5‐HT2AR), a molecular site of action for hallucinogens such as lysergic acid diethylamide (LSD). Efavirenz activates 5‐HT2ARs though its efficacy is comparatively lower than that of LSD. In rodents, an LSD‐like interaction with the 5‐HT2AR appears to dominate efavirenz's behavioral profile. Both LSD and efavirenz depress open field activity in a novel environment. Similar to LSD, efavirenz induces head‐twitch responses in wild type, but not 5‐ HT2AR–knockout mice. We conclude efavirenz has an LSD‐like psychoactivity mediated by the 5‐HT2AR. Our finding correlates with subjective reports from HIV patients experiencing specific dose‐dependent adverse drug reactions to efavirenz, such as hallucinations and night terrors, and also may explain reports of the recreational use of this ARV drug.Support: R01 MH063162, R01 MH084894, UNTHSC RI6015
The in vivo Effects of Glucose and Lipid on the Granulocytes and Monocytes of Type 2 Diabetic Male Subjects
Authors: Horvath Peter , Oliver Stacy R. , Zaldivar Frank P. , Radom‐Aizik Shlomit , Galassetti Pietro R. 
Published: June 2021

Atherosclerosis/cardiovascular disease are major causes of morbidity/mortality in type 2 diabetes (T2D), and have been associated with activation of innate immune cells, their diapedesis to the arterial intima, formation of the atherosclerotic plaque and release of thrombotic factors. While in T2D immune cell activation likely depends on dysregulated metabolic conditions, we have limited knowledge of the interaction between individual metabolic factor typical of T2D (hyperglycemia, hyperlipidemia), innate immune cell activation, and the progression of atherosclerosis. We therefore measured by flow cytometry cell surface expression of CD11b, CD14, CD16, CD62L and CD66b, known markers of granulocyte (Gc) and monocyte (Mc) activation, in 5 T2D subjects, during 4‐h i.v. infusions of glucose and lipids, performed separately or simultaneously. We hypothesized that both glucose and lipids would increase Gc/Mc surface marker expression, and simultaneous infusion would have a synergistic effect. Surprisingly, though, glucose only had little effect, while lipids, alone or combined with glucose, increased expression of several markers (such as CD11b in Gc, see figure, and in Mc). Our results suggest lipids may be stronger acute contributors to innate cell activation than glucose per se, possibly helping shape preventive dietary guidelines in T2D.Supported by NIH Grants P01HD048721 and UL1RR031985
A novel model for ischemic stroke ‐ the ANP gene disrupted (ANP−/−) mouse: molecular effects of hypertension in the development of stroke
Authors: Ventura Nicole Marie , Peterson Nichole T , Tse M Yat , Jin Albert Y , Andrew R David , Pang Stephen C 
Published: June 2021

Cardiovascular disease (CVD) and stroke share many similar risk factors including hypertension. Alterations in the natriuretic peptide system (NPS) have shown to play a protective role in cardiac hypertrophy (CH) and myocardial infarction (MI). Given the similarities between CVD and stroke, these conditions may also share similar molecular mechanisms in their etiologies. The objective of this study is to develop a novel model for stroke using the chronically hypertensive, atrial natriuretic peptide (ANP) gene disrupted (ANP−/ −) mouse to assess the effect of hypertension on stroke development. ANP+/− (salt‐sensitive) mice treated with either high (8%) or normal (0.8%) salt diet for 6 weeks were subjected to left middle cerebral artery occlusion (MCAO) for 30 min and allowed to recover for 24 hr. Results have demonstrated left ventricular (LV) hypertrophy and increased infarct volumes in mice treated with high dietary salt. Furthermore, we have characterized the alterations occurring in four major vasoactive systems in the brain; the NPS, the renin‐angiotensin system (RAS), the nitric oxide system (NOS) and endothelin system (ETS) using real‐time quantitative PCR (qPCR). Since ablation of ANP induces CH, understanding the molecular mechanisms of the above systems in the brain will allow us to assess if ANP plays a protective role for stroke as it does for MI. Support: HSFO and Canadian Foundation for Innovation.Grant Funding Source: Heart and Stroke Foundation of Ontario and Canadian Foundation for Innovation
Skeletal muscle satellite cells are reduced in cigarette smoke exposed mice
Authors: Jackson Jason Matthew , Palau Helena G. , Wagner Peter D. , Breen Ellen C. 
Published: June 2021

Satellite cells (SC) are muscle stem cells important for muscle regeneration. We hypothesized that cigarette smoke (CS) exposure would decrease myofiber associated SCs, in part due to inhibited VEGF expression. SC number per myofiber was measured in wild type (WT), skeletal muscle VEGF gene‐deleted (skmVEGF−/−) and CS exposed mice. Growth of SC colonies in vitro was monitored in myofibers +/− CS extract (CSE) and/or VEGF−/−.MethodsHSA‐Cre‐ ERT2 × VEGFLoxP mice were exposed daily to whole body CS for 4 wks or tamoxifen‐induced skmVEGF−/−. Nes‐GFP+/Pax7+ cells per isolated soleus myofiber were identified by confocal microscopy. Additional fibers were cultured for 4 days in the presence of tamoxifen +/− 2.5% CSE.ResultsGastrocnemius VEGF levels were decreased to the same extent in skmVEGF−/− and smoke exposed mice (17.1 ± 3.9 WT, 5.2 ± 2 skmVEGF−/−, 4.2 ± 1.3 CS, p<0.01). Pax7+/Nes+ cells per soleus fiber were lowest in CS exposed mice but also reduced in the skmVEGF−/− group compared to WT (12 ± 2.2 WT, 7.2 ± 3.3 skmVEGF−/−, 3.5 ± 1.7 CS, p<0.01). Cultured soleus fibers treated with CSE formed long extensions of aggregated SC colonies. In vitro VEGF gene deletion resulted in smaller SC colonies compared to WT mice cultured under control and CSE conditions.ConclusionsCS exposure leads to the loss of SC that may result from inhibited VEGF expression and incorporation into mature myofibers.NIH/NHLBI HL091830‐01A1
The regulation of microRNAs by Brahma‐related gene 1 in smooth muscle cells
Authors: Chen Meng , Herring Paul 
Published: June 2021

MicroRNAs (miRs) regulate the phenotypic switch of smooth muscle cells (SMCs) that occurs under pathological conditions. Little is known about the transcriptional and epigenetic regulation of miR expression in SMCs. To identify miRs that are regulated by the Brahma‐related gene 1 (Brg1)‐containing SWI/SNF chromatin remodeling complex we performed a microRNA array screen of RNA isolated from colonic SMCs of mice harboring a smooth muscle‐specific knockout of Brg1. Quantitative RT‐PCR confirmed changes in expression of several miRs, including miRs‐143/5 and miR‐133. Expression of dominant negative Brg1 in wild‐type SMCs led to decreased expression of miRs‐143/145 but not miR‐133. The dominant negative Brg1 also blocked the myocardin‐mediated induction of miRs‐143/5 in 10T1/2 cells. Knockdown of SRF or myocardin decreased expression of miRs‐143/5 in SMCs, whereas miR‐133 expression was only repressed following SRF knockdown. In Brg1‐null SW13 cells, miRs‐143/5 but not miR‐133 were dramatically induced by myocardin only in the presence of Brg1. Chromatin immunoprecipitation assays revealed that Brg1 was important for myocardin‐mediated SRF binding to the miRs‐143/5 promoter. These data show that Brg1‐dependent chromatin remodeling regulates the expression of miRs‐143/5 and miR‐133 through distinct pathways in SMCs.Supported by NIH DK61130 and AHA predoctoral fellowship.
The MESA Program Advantage in STEM Education
Authors: Bakhiet Raga , Carcia Theresa , Alvarez Rafael 
Published: June 2021

ObjectiveThe objective of our work is to provide a model pathway to Science, Technology, Engineering and Mathematics (STEM) opportunities that students from precollege to community colleges/universities take toward achieving STEM industry positions or graduate school.MethodsThe San Diego MESA Alliance is a student success initiative built on best practices of the Mathematics, Engineering, and Science Achievement (MESA) Program and grant funds. The Alliance team provides essential academic and career development services to students who are interested in STEM fields at the precollege level and who are majoring in STEM fields at the college level. More than 1200 students on the STEM pipeline are served annually. Student support is based on ‘standards’ identified by industry representatives as critical for success. As a result of completing activities that are in line with these standards, students gain career development experience, workforce preparedness, and academic success.ResultsStudents in these programs outperform their peers and standout in job/internship interviews due to their tangible excellence. Evaluation of the standards, implemented by means of student activities, proves that they are effective. The proposed outcomes of our model were either met at or in excess of 100%. These outcomes include the improvement of the retention of STEM students and increase of the number of STEM students graduating with B.S degreesConclusionThe San Diego MESA Alliance model pathway to (STEM) opportunities is a system that works. We recommend it for nationwide adoption in our efforts to maintain a strong STEM presence in the world.