bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short and Long‐term dysfunction induced TLR5 upon intestinal Na+/H+ exchange
Authors: Cabral Jose , Grácio Daniela , Soares‐da‐Silva Patricio , Magro Fernando 
Published: June 2021

It is well known that intestinal microflora play an important role during inflammatory flares in Inflammatory Bowel Disease. However, the cellular mechanisms set in motion are still not completely understood. The immune system relies on Toll‐like receptor (TLR) 5 to detect any pathogenic flagellated microorganisms, as it is activated by flagellin.Aimsevaluate the effect of TLR5 activation by flagellin on activity of Na+/H+ exchanger (NHE) in T84 intestinal epithelial cells as well the signal transduction set in motion.MethodsNHE activity and kinetics were measured using fluorimetric assays and protein expression was determined by western blotanalysis.ResultsShor‐term (st) cell exposure to Flagellin induced NHE1 activity reduction concentration dependent (2.1±2 to ‐14.9±2%). Cell signal set in motion triggered AC3, PKA, PLC and PKC signal molecules. As to the long‐term (lt) exposure, it induced rather opposite effects upon NHE1 and NHE3 activities. NHE1 activity was inhibited (‐1.7±3 to ‐19.1±2%). Whereas, NHE3 activity increased when cells were exposed to Flagellin (~ 10% at 100 ng/ml). Moreover, this NHE3 activity increase was accompanied by a NHE3 expression increase (16.74 ± 2%). During st exposure AC3, PKA, PLC and PKC were recruited while lt exposure to Flagellin activated AC3 and PKA. Flagellin induced an impaired recover of pHi.ConclusionsActivation of TLR5 exerts marked inhibition of NHE1 activity and stimulates NHE3 activity in intestinal epithelial cells. While st Flagellin exposure (that leads to NHE1 inhibition) activates AC3, PKA, PKC and PLC, the lt activation (that leads to NHE3 stimulation) only triggers AC3 and PKA.
The role of radial diagnostics and the endoscopic surgery of diseases of maxillary sinus
Authors: Tulebayev R. , Baimenov A , Azhenov T. , Zhusupov B , Mukhamadieva G. , Papulova N. , Mustafin A 
Published: June 2021

Aim of researchto increase the effectiveness of surgical treatment and diagnostic of chronic sinusitis [CS]Material and methods350 patients were examined, 226 (64,5%) among them with chronic maxillary sinusitis. All patients were undergone complex of laboratorial, clinical and radiological methods of examination. Along with traditional rentgenological methods we used the digital fluorography, computer scan, videoendoscopic examination of sinuses and nasal cavity. 226 patients with nose and maxillary sinus pathology were undergone surgical treatment. Functional examination of mucocilliary transport, anterior active rhinomanometry, pH‐metry and calorifer function investigation were performed. The high resolving ability of digital fluorography allow to diagnose up to 80% true the inflammation of sinuses and to recognize the structural changes, soft tissue mass of nose and sinuses. During diagnostic of chronic rhinosinusitis: purulent, parietal, hyperplastic forms ‐ the effectiveness of digital fluorography is 80,5%. We suggested modified maxillary sinusotomy in case of chronic purulent and parietal‐hyperplastic forms of maxillary sinusitis, effectivity of this method is 86.5%. This method allows providing sanation of sinuses, restoring ventilation, drainage of maxillary sinuses and prevents scarry stricture of osteomyetal complex. Thus, modern examination methods: endoscopy of nasal cavity, digital fluorography, CS and MRT and also functional check up of the nose in pre‐ and postoperative periods prevent complications and allow estimate the effectiveness of treatment.
Circulating RAS in Mice with Prorenin Receptor Gene Deletion Specificly in Adipose Tissue
Authors: Shamansurova Zulaykho , Tan Paul , Ahmed Basma , Michel Catherine , Kajla Sonia , Seda Ondrej , Lavoie Julie 
Published: June 2021

IntroductionAdipose tissue (AT) renin‐angiotensin system (RAS) has been involved in the pathogenesis of obesity, where the role of the prorenin/renin receptor [(P)RR], which acts in an angiotensin‐dependent and ‐independent manner is not clear yet. Our previous results suggest the (P)RR plays a role in the regulation of body weight (BW), fat mass and insulin sensitivity (IS).Material and methodsMice with deletion of the (P)RR gene specificly in AT (KO) created by cre‐loxp technology, were kept either on regular chow (ND) or high‐fat/high‐carbohydrate diet (HF/HC) for 10 weeks. BW measured weekly. Body composition assessed by Echo‐MRI. Glucose homeostasis evaluated by OGTT. At the end of protocol, mice euthanized, subcutaneous, visceral (VF) fat pads separated, weighed, flash frozen. Plasma renin activity (PRA), Angiotensin I (Ang‐I) concentration were measured by immunoassay (DBC, Canada).ResultsMale KO mice had a 20% lower BW compared to wild‐type mice (WT), p0.001, whereas KO female mice had a 4.3% decrease on ND, p<0.01 and 14.12%, p0.001 on HF/HC. The VF mass in KO male mice was lower by 2.4 fold, p0.001 compared to WT, in female KO mice ‐1.3 fold lower on ND, p0.01 and 2.4 folds on HF/HC, p0.001. In addition, although KO and WT mice had similar glycemia during OGTT, fasting and stimulated insulinemia were lower in KO mice which suggests an improved IS. These phenotypes were not associated with any changes in circulating Ang‐I and PRA.ConclusionOur results suggest that AT specific deletion of the (P)RR regulates body weight, fat mass, glucose homeostasis without changing circulating RAS.
NADPH Oxidases Mediate Zinc Deficiency‐Induced Oxidative Stress in Mouse Kidneys
Authors: Li Mirandy , Gooch Jennifer , Hoover Robert , Williams Clintoria 
Published: June 2021

Zn2+ deficiency (ZnD) is common in diabetes. Experimental studies show that ZnD worsens diabetic complications, including diabetic kidney disease. Oxidative stress caused by increased reactive oxygen species (ROS) plays a role in the harmful effects of ZnD. However, the sources of oxidative stress continue to be identified. In diabetes, NADPH oxidases (Nox) are enzymes that promote oxidative stress in the kidneys. This study seeks to determine the role of Nox enzymes in ZnD‐induced oxidative stress in mouse kidneys. WT mice were pair‐fed a ZnD or control diet for 6 weeks. After collecting kidneys and urine, kidney damage (BCA Protein Assay), ROS levels (Amplex Red) and Nox enzymes expression (qRT‐PCR and Western blot) were examined. To further investigate the effect of Zn2+ bioavailability on Nox enzymes, mouse distal convoluted tubule (mDCT) cells were exposed to a Zn2+ chelator (TPEN) or vehicle (DMSO) for 48 hours with or without Zn2+ supplementation for the last 24 hours. Findings show that a Zn2+ restricted diet induces urinary protein that is accompanied by elevated Nox2 expression and ROS levels in mice kidneys. In mDCT cells, inhibition of Nox enzymes with DPI blocks Zn2+ depletion‐induced ROS levels. Zn2+ depletion increases ROS levels and Nox2 and Nox4 expression. Furthermore, Zn2+ supplementation reduces Zn2+ depletion‐induced Nox2 increases. These findings suggest that Nox enzymes mediate ZnD‐induced oxidative stress and kidney damage. Understanding how ZnD causes kidney injury can have an important impact on the treatment of diabetic kidney disease.R25DK101390 (MSL), VA‐MERIT (JLG), R01DK085097 (RSH), T32‐DK00756 (CRW)
Increased ADAM17 Expression in ACE2 Knockout Mice is Associated with Increased Excitability of Paraventricular Nucleus Pre‐sympathetic Neurons
Authors: Mukerjee Snigdha , Sriramula Srinivas , Zsombok Andrea , Lazartigues Eric 
Published: June 2021

We previously reported that ACE2 knockout (KO) mice, like humans, develop age‐dependent hypertension. In addition, a disintegrin and metalloprotease 17 (ADAM17) was recently shown to contribute to neurogenic hypertension. Accordingly, we hypothesized that ADAM17 in the paraventricular nucleus (PVN) of hypothalamus contributes to enhanced sympathetic tone in mice lacking ACE2. Adult 10‐12 week‐old wildtype (WT) and ACE2 KO male mice (n=2‐4/group) were injected in the kidney with a pseudorabies virus encoding a green fluorescent protein, for retrograde labeling of sympathetic neurons. After 4 days, whole‐cell patch‐clamp recordings were conducted from labeled pre‐sympathetic PVN neurons. The resting membrane potential of these PVN neurons in WT mice was ‐59.7 ±1.06 mV, while ‐52.7 ±1.6 mV in ACE2 KO mice, which may suggest an increase threshold for excitability in pre‐sympathetic PVN neurons. In another set of mice, the hypothalamus was dissected from WT and KO animals (n=4/group) for western blot analysis. ADAM17 expression showed a 2‐fold increase in KO compared to WT (P<0.05). Finally, using immunohistochemistry, ADAM17 expression was confirmed in parvocellular neurons. Taken together, our data suggest that enhanced expression of ADAM17 in the parvocellular PVN could be associated with increased excitability of pre‐sympathetic neurons in ACE2 KO mice. This dysregulation in neuronal activity might alter the intricate pressor homeostasis leading to increased blood pressure. These results suggest that ADAM17 could be a potential new target for the reduction of enhanced sympathetic activity in neurogenic hypertension.Support: NIH HL093178
Central Gαi2 proteins facilitate PVN parvocellular neuronal activation during chronic elevated sodium intake to maintain sodium homeostasis
Authors: Carmichael Casey , Carmichael Alana , Vartanyan Philip , Wainford Richard 
Published: June 2021

AimBrain Gαi2 protein‐mediated signal transduction acts as a mechanism to potentiate central sympathoinhibition to maintain fluid and electrolyte homeostasis in settings of chronic high dietary sodium intake. The current study determined if brain Gαi2 proteins impact the pattern of neuronal activation evoked during high‐salt intake to maintain sodium homeostasis.MethodsMale Sprague‐Dawley rats received an ICV miniosmotic‐pump infusion of a scrambled (SCR) or Gαi2 oligodeoxynucleotide (ODN; 25μg/day) and were maintained on a low (LS; 0.03% NaCl), normal (NS; 0.4%), or high salt (HS; 8%) diet for 7 days. 24‐hour metabolic balance measurements were recorded on day 5 and rats were sacrificed on day 7 for FosB/ΔFosB IHC to examine dietary sodium evoked neuronal activation.ResultsFollowing 5‐d of a HS, but not LS or NS, diet ICV Gαi2 ODN infusion reduced 24‐h total sodium excretion compared to SCR ODN‐infused rats (Na+ excretion [meEq/24‐h] SCR HS: 27.0±1.2 vs. Gαi2 HS: 19.6±3.3, P<0.05). Chronic HS, but not LS, diet evoked a significant increase in total PVN FosB in SCR infused rats that was not observed in Gαi2 infused rats (Δ from NS [FosB+ cells] SCR: 11±3 vs. Gαi2: 1±2, P<0.05). Specifically, Gαi2 infusion prevented increases in PVN dorsal, ventrolateral, and lateral parvocellular nuclei that were observed in SCR infused rats (P<0.05). Gαi2 infusion had no effect on sodium‐evoked increases in FosB in PVN magnocellular nuclei, the SON, and MnPO.ConclusionThese data highlight Gαi2 protein signal transduction as a novel CNS mechanism acting to influence neuronal activation, likely at the level of PVN parvocellular neurons, upon chronic HS challenge in a salt‐resistant phenotype.
BDNF Influences the Excitability of Subfornical Organ Neurons
Authors: Black Emily , McIsaac William , Ferguson Alastair 
Published: June 2021

Brain‐derived neurotrophic factor (BDNF) is a peptide known to be involved in several mammalian physiological processes. Expression of BDNF transcripts has been identified in the subfornical organ (SFO), a circumventricular organ involved in fluid balance and energy homeostasis. Microarray analysis has demonstrated that levels of transcript expression in the SFO are differentially regulated by fluid and food deprivation, with levels of BDNF expression increasing significantly in response to dehydration, and decreasing in response to starvation (Hindmarch et al 2008). The current study was therefore undertaken in order to determine the effects of BDNF on the excitability of SFO neurons. We used the whole‐cell patch clamp technique to determine the influence of BDNF on the membrane potential of dissociated SFO neurons as well as that of SFO neurons in slice preparation. We found that 86% of dissociated neurons responded when treated with BDNF (2 nM), all of which depolarized (mean 14 mV). Additionally, 75% of neurons tested in the slice preparation responded when treated with BDNF (2 nM). Of these, 67% showed a depolarization (mean 12 mV) and 33% hyperpolarized (mean ‐18 mV). This study suggests the SFO as a potential central nervous system site at which BDNF may act directly to influence homeostatic regulation.Supported by the Canadian Institutes for Health Research
The Physiological Effect of Fasting the Month of Ramadan on Anthropometrics and Blood Variables
Authors: Alayafi Yahya , Alsulaiman Majed , Aljaloud Khalid , Jabbary Ali , Aljaloud Sulaiman , Aldayel Abdulaziz , Fry Andrew , Vardiman Phillip , Gallagher Philip 
Published: June 2021

Manystudies have beenconducted onfastingduring the monthof Ramadan;however, their resultswerevastly inconsistent.Itis importanttonote thatnone of these studiescontrolledor evenmonitoredphysical activityandfoodintake.PurposeThisstudy willdetermineifintermittentfastingwillaffectbody composition, blood lipid profile,glucose, blood proteins and hormones.MethodsEight healthyathletemales participatedinthisstudy.Weight,height andbody compositionofallsubjectswererecordedatbaselineoneday before Ramadan(D1),after ten daysof fastingRamadan(D10) andtwenty‐eightdaysof fastingRamadan (D28). All data was analyzed using 1x3 repeatedmeasuresANOVA(p<.05).ResultsThere wassignificantdecreasein bodymassandLeanbody masscomparingD28withD1andD10.Vigorousactivityand ModerateactivityweresignificantlydecreaseatD10andD28ofRamadan. Thepercentagewhichrecommendeddietary allowancesof caloriesfromproteinshowedsignificantdecreaseatD10andD28comparetoD1.Inaddition,the percentage of calories fromcarbohydrate showedsignificant increaseatD10andD28comparetoD1.FastedGlucoselevelsweresignificantly increasedat D10compareto D1. Glucagondecreasesignificantly at D10, but not at D28.Inaddition,Albumin levelsweresignificantlyloweratD10andD28compareto D1;however,all measurements were stillwithinnormal/healthrange.ConclusionResultsshowthelevelofphysicalactivity andfoodintakeare majorcontributingfactorsonthereductioninbodyweight.Overall,thesefindingsindicatenohealthriskforfastingthe month of Ramadan.
Attenuated Cerebral Vasodilatory Capacity in Response to Hypercapnia in Young Obese Individuals
Authors: Terwoord Janée , Hurr Chansol , Brothers R Matthew 
Published: June 2021

Obese individuals are at a greater risk for the development of a variety of cardio and cerebral vascular diseases including hypertension, atherosclerosis, coronary artery disease and stroke. Furthermore, obesity is also associated with cognitive impairment and is a risk factor for dementia and Alzheimer's disease. The exact mechanisms of this elevated risk are not fully characterized; however, impaired microvascular function is believed to be a contributor. This study tested the hypothesis that the cerebral vasodilatory capacity in response to hypercapnia is reduced in obese individuals relative to age and sex matched lean counterparts. Cerebral blood velocity (CBFV) was measured using transcranial Doppler before and during rebreathing‐induced hypercapnia in obese (Obese, n=14) and lean (Lean, n=14) subjects. Cerebral vascular conductance (CVCI) was calculated as CBFV / mean arterial pressure (MAP), and a four parameter logistic regression was applied for sigmoidal curve fitting of the relationship between % change in CVCI and end‐tidal CO2 tension (PETCO2). The magnitude of hypercapnia (Δ PETCO2) during rebreathing was similar between groups (Obese 14 ± 3 mmHg vs. Lean: 15 ± 2 mmHg; P = 0.13). The maximum increase in CVCI (Obese: 155 ± 17% vs. Lean: 176 ± 23%; P < 0.05) and the total range of change in CVCI (Obese: 50 ± 15% vs. Lean: 75 ± 22%; P < 0.01) during rebreathing were reduced in the obese relative to the lean individuals. These data indicate that cerebral vasodilatory capacity in response to changes in PETCO2 during hypercapnia is attenuated in obese individuals compared with lean individuals.This study was supported by institutional start‐up funds awarded to R. Matthew Brothers.
Prevalence and Activation of Human Brown Adipose Tissue
Authors: Gifford Aliya , Walker Ronald , Welch E , Towse Theodore 
Published: June 2021

The role of brown adipose tissue (BAT) in human lipid metabolism and whole‐body energy expenditure is not well understood. To study BAT in humans it is necessary to reliably measure the quantitative properties of BAT. The purpose of this study is to assess the volume and activity of BAT prospectively using PET in a cohort of healthy male and female adult humans.Twenty‐five subjects (10 male), aged 21 to 41 years, with a BMI of 20.15 to 31.48 kg/m2 were scanned on a GE Discovery STE PET/CT scanner using the radioactive tracer 18F‐FDG. Each subject underwent two PET‐CT scans on two separate days, once after two hours of cold exposure (16°C) and once after two hours of thermoneutral exposure (24°C). BAT activation was observed on the PET scans of 19 subjects after cold exposure. The PET scans for two representative subjects from this dataset are shown in Fig 1. The resulting PET and CT values (mean ± 95% CI) from the clavicular BAT depots for these two subjects are listed in Table 1.The results of this study show the ability to measure the presence of brown adipose tissue in healthy adults with a variety of ages and BMI levels. Although it is likely this method does not capture the entire volume of BAT or the full degree of activation for a specific subject, this method can detect activated BAT in adult humans in an automated fashion. One advantage of this research over existing studies is that the same subjects are scanned after exposure to both thermoneutral and cold conditions, which enables a comparison of the images between temperatures.Funding1R21DK096282 from NIDDK/NIH & UL1 TR000445 from NCATS/NIHimage

Cold Exposure BAT Values
Thermoneutral Exposure BAT Values

PET Standardized Uptake Value [SUV]
CT Hounsfield Units [HU]
PET Standardized Uptake Value [SUV]
CT Hounsfield Units [HU]
BAT Volume [cm3]

Subject 1
5.2 ± 0.1
‐49.5 ± 0.9
0.6 ± 0.0
‐71.1 ± 1.3
23.7

Subject 2
3.4 ± 0.1
‐64.1 ± 1.7
0.4 ± 0.0
‐93.2 ± 2.4
8.5
Body Mass Index, Serum Adiponectin, leptin, resistin levels, lipid profile in Local Libyan Subjects
Authors: Sheriff dhastagir , Sheriff Sultan 
Published: June 2021

AimThe preliminary study was undertaken to evaluate the serum adiponectin, leptin, resistin levels in local Libyan normal, obese and diabetic subejcts.Materials and MethodsAmong the 1500 patients visiting the Department of Medicine, Faculty of Medicine, Benghazi University hospital for medical check up, 650 subjects were taken for the study. 200 subjects taken as controls( 100 –males; 100‐ females) and 250 (100‐males; 150‐females) subjects formed the obese group and 200 formed the diabetes group(100 males and 100 females).Fasting glucose, total cholesterol (TC), HDL‐cholesterol (HDL‐C), triglyceride (TG) were measured by an enzymatic colorimetric methods.Serum adiponectin levels were measured by enzyme linked immunosorbent assay (ELISA) with a sensitivity of 3 ng/ml. Serum leptin levels were measured by an active human leptin ELISA (DSL, Diagnostic System Laboratories, USA) with a sensitivity of 0.05 ng/ml. Serum resistin levels were measured by ELISA (Linco Research, USA) with a sensitivity of 0.16 ng/ml. Fasting serum insulin levels were measured and homeostatic model assessment (HOMA index) was calculated by HOMA index calculator using fasting blood glucose level and insulin level.Results and DiscussionIn the present study BMI values for control subjects were 29.5, 34.5 for obese subjects and 36.50 for T2DM subjects. WC values for control was 104cm,114 cm for obese subjects and 120 for T2DM subjects. These values clearly indicate that majority of the population are either over‐weight or obese. Serum adiponectin level is comparatively lower in normal Libyan subjects when compared to other Arab and western population. Paradoxically the level of serum adiponectin is found to be higher in diabetic Libyan subjects.The presence of dyslipidemia and insulin resistance in obese and Libyan subjects are observed.The serum level of adiponectin in this population may reflect the pattern of distribution of adipose tissue in local Libyan subjects.
Incidence of Variations in Human Cadaveric Renal Vessels
Authors: Hassan Sherif , Johnson Jane , Youakeem Magdy 
Published: June 2021

ObjectiveKnowledge of vascular variations of the human kidney is essential to avoid complications during operative procedures.MethodsWe examined the renal vasculature in 63 cadavers during routine cadaveric dissection. We recorded the number of renal vasculature and their anomalies. Percentages and exact 95% confidence intervals (CI) were used to estimate the incidence of variations. A 2‐sample t test and Fisher exact tests were used to test for the association of variations with age at death, sex, and cause of death. A McNemar test was used to test whether additional renal vessels were more commonly found on one side or another.ResultsAnomalies of the renal vessels were found in 7 (11%; 95% CI, 5%‐22%) of the 63 cadavers. For the renal arteries, we observed the presence of the additional arteries unilaterally (5%) and arteries attached to both kidney poles (3%) or to the inferior pole only (2%). For the renal veins, we observed the presence of additional veins unilaterally (8%) and veins which drained both kidney poles (3%) or the inferior pole only (5%). Other kidneys showed different anomalies as double inferior vena cava (2%), abnormal gonadal veins (3%), early segmentation of the renal artery (2%), and abnormal common iliac veins (2%). There was no significant difference between those with and without anomalies of the renal vessels on sex (3/7 [43%] males vs. 29/56 [52%] males; P=.71) or age (mean [SD], 73 [15] years vs. 75 [13] years; P=.67).Renal failure was the only cause of death that was significantly different between those with and without anomalies (4/7 [57%] vs. 1/56 [2%]; P<.001).ConclusionThe variation in renal vessels found is a valuable contribution from anatomical knowledge to operative procedures.
Metagenomic Profile of Fecal Samples Generated From Mouse Model Simulating Features of Post‐Traumatic Stress Disorder
Authors: Gautam Aarti , Hoke Allison , Sitta Ramsey , Sowe Bintu , Dimitrov George , Chakraborty Nabarun , Muhie Seid , Kumar Raina , Hammamieh Rasha , Jett Marti 
Published: June 2021

Post‐traumatic stress disorder (PTSD) is an anxiety disorder that can arise due to exposure to a potentially traumatic event (PTE). Using “cage‐within‐cage resident‐intruder” protocol, subject C57BL/6J mice were exposed to aggressor mice for 10 days with 24 hours rest prior to harvesting. The symbiotic influence of microbiota on the nervous system and behavior has been receiving profound interest. In this longitudinal study, we are focusing on the effect of social stress on the microbiome by sequencing for 16S ribosomal RNA (16S rRNA) amplicon on the Illumina MiSeq platform. Fecal samples were collected at 2 day intervals during the 10 day protocol from control as well as subject mice. DNA was isolated using a kit from MO BIO followed by amplification of variable V3 and V4 region of the 16S rRNA amplicon using the Illumina 16S Metagenomics Library Preparation Protocol. The samples were barcoded using Nextera index primers and pooled in preparation for MiSeq sequencing. We will be able to characterize the fecal microbiota in the presence and absence of social stress and also will be able to correlate changes in bacterial communities in our mouse model of PTSD.DISCLAIMERS: Research was conducted in compliance with the Animal Welfare Act and all other Federal Requirements. The views expressed are those of the authors and do not constitute endorsement by the U.S. Army.