bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased basal ganglia activation in Chronic Fatigue Syndrome subjects is associated with increased fatigue
Authors: Unger Elizabeth R. , Miller Andrew H. , Jones James F. , Drake Daniel F. , Tian Hao , Pagnoni Giuseppe 
Published: June 2021

ObjectivesConduct a functional magnetic resonance (fMRI) study using a monetary win‐lose gambling task that strongly activates basal ganglia to test hypothesis of decreased basal ganglia function in chronic fatigue syndrome (CFS).MethodsParticipants included 18 CFS subjects (1994 case definition) and 41 non‐fatigued controls matched on age, sex and race who were free of psychotropic medications and significant depression (Zung Depression score <60). The general activation pattern for win‐lose contrast across all subjects was determined. The resulting statistical parametric brain map thresholded at p<0.05, corrected for multiple comparisons, was intersected with basal ganglia regions of interest (ROIs). For each subject, the average value of win‐lose activation contrast in each ROI was extracted.ResultsCFS subjects showed decreased right caudate (p=0.01) and right globus pallidus (p=0.02) activation compared to controls. The decreased globus pallidus activation correlated with increased mental fatigue (r2=0.49, p=0.001), general fatigue (r2=0.34, p=0.01) and reduced activity (r2=0.29, p=0.02) Multidimensional Fatigue Inventory scores of CFS subjects but not controls.ConclusionReduced basal ganglia activation may contribute to symptoms of fatigue in CFS subjects.The findings in this report are those of the authors and do not necessarily reflect the views of the funding agency (CDC).
Protein expression of myostatin and follistatin in the myocardium of spontaneously hypertensive rats with heart failure
Authors: Damatto Ricardo Luiz , Martinez Paula , Guizoni Daniele , Lima Aline , Cezar Marcelo , Bonomo Camila , Nakatani Bruno , Campana Alvaro , Okoshi Katashi , Okoshi Marina 
Published: June 2021

The aim of this study was to evaluate myocardial myostatin and follistatin protein expression in spontaneously hypertensive rats (SHR) with heart failure (HF).Methods18‐month‐old SHR's were evaluated to identify clinical features of HF: tachypnea/labored respiration and weight loss. After HF was detected, rats were subjected to transthoracic echocardiogram and euthanized. During euthanasia, we evaluated pathological evidence of HF such as pulmonary congestion and right ventricular hypertrophy. Wistar‐Kyoto (WKY) rats were used as controls. Myostatin and follistatin protein expression was assessed by Western blotting.ResultsAll SHR's (n=8) presented tachypnea, lung congestion and right ventricular hypertrophy. No WKY rat (n=8) presented any feature of HF. Echocardiographic evaluation showed left chambers dilation (left atrial diameter: WKY 5.73±0.59; SHR 7.28±1.17 mm; p=0.004; left ventricular diastolic diameter/body weight ratio: WKY 19.6±3.1; SHR 27.7±4.7 mm/kg; p=0.001), and left ventricular systolic (fractional shortening: WKY 54.6±6.3; SHR 42.2±7.1 %; p=0.003) and diastolic dysfunction in SHR. Myostatin (WKY 1.00±0.16; SHR 0.77±0.23 arbitrary units; p=0.035) and follistatin (WKY 1.00±0.35; SHR 0.49±0.18 arbitrary units; p=0.002) protein expression was lower in SHR.ConclusionMyostatin and follistatin protein expression is reduced in myocardium of SHR with heart failure.
Insulin ameliorates collagen remodeling after myocardial infarction
Authors: Tian Na , Zhang Yuan , Fu Feng , Yan Wenli , Gao Feng 
Published: June 2021

AimTo investigate whether insulin treatment ameliorates collagen remodeling after myocardial infarction (MI).MethodsAdult male rats were subjected to the ligation of anterior descending coronary artery and randomized to receive one of the following treatments: Sham, MI+saline or MI+insulin. Myocardial collagen remodeling environment was simulated by TGF‐beta in cultured neonatal rat cardiac fibroblasts.ResultsInsulin significantly improved cardiac function by increased left ventricular ejection fraction after ischemia. Cardiac collagen contents were decreased post‐MI as evidenced by reduced hydroxyproline and collagen volume fraction (P<0.05). Meanwhile, immunohistochemistry staining and Western blot showed that the ratios of myocardial collagen I/III of 1 wk and 4 wk post‐MI were significantly higher than those in the sham hearts (P<0.05). Insulin treatment significantly reduced the ratios of collagen I/III compared with those in saline hearts 1 wk post‐MI (P<0.05), while there were no differences in the ratios of collagen I/III 4 wk post‐MI (P>0.05). Moreover, insulin reduced TGF‐beta induced a‐SMA expression and the phosphorylation of JNK in cardiac fibroblasts.ConclusionInsulin ameliorates cardiac collagen remodeling in post‐MI hearts via insulin‐suppressed JNK activation.Supported by the State Key Program of National Natural Science Foundation of China (No. 81030005).
The NHE3 interacting PDZ protein NHERF2 determines the lipid raft association of the apical Na+/H+ exchanger NHE3 in murine small intestine
Authors: Sultan Ayesha , Riederer Brigitte , Xia Weiliang , Chen Mingmin , Lamprecht Georg , Lissner Simone , Yun Chris , de Jonge Hugo , Donowitz Mark , Gessner Johannes , Seidler Ursula 
Published: June 2021

BackgroundIntestinal NHE3 is scaffolded and differentially regulated by Na+/H+Exchanger Regulatory Factor (NHERF) PDZ‐adaptors. NHE3 partially resides in lipid rafts of the Brush Border Membrane (BBM).AimTo investigate if there is a cross talk between NHERFs and membrane rafts, specifically if NHERFs associate differentially with the raft and non‐raft fraction of NHE3, and whether they influence the function and distribution of NHE3 in these microdomains.Methods and ResultsMurine BBM was detergent‐solubilised and lipid rafts isolated by density gradient floatation. NHE3 was partially, NHERF2 strongly and NHERF1 weakly raft‐associated, and NHERF3 exclusively in the non‐raft fraction. In absence of NHERF2, raft‐associated NHE3 was strongly decreased. Increasing the membrane sphingomyelin/ceramide ratio, increased NHE3‐dependent small intestinal fluid absorption in vivo, as well as overall NHE3 in the lipid rafts, suggesting a positive correlation between NHE3 function and raft association.ConclusionsIn murine small intestinal BBM, NHE3 differentially associates with the different NHERFs in the raft and non‐raft fraction. NHE3 raft‐association is NHERF2‐dependent. NHE3 and NHERF raft‐association and function are modulated by changes in the lipidic environment. This suggests that PDZ‐scaffolding proteins are involved in the retention of membrane proteins within lipid raft platforms.
Role of cysteine residues for the function of the human sodium‐dependent multivitamin transporter (hSMVT)
Authors: Ghosal Abhisek , Said Hamid M 
Published: June 2021

The hSMVT plays an important role in biotin uptake. While significant knowledge has been gained for regulation and cell biology of SMVT, there is little known about its structure‐functional activity relationship. Using site‐directed mutagenesis we examined the role of each of the ten conserved cysteine residues in the function of hSMVT. The results showed that mutation at Cys294 only (but not at the other conserved cysteine residues) significantly impairs biotin transport and the effect is not related to polar status of substituting amino acids. Kinetic studies showed the inhibition to be mediated via a significant reduction in the Vmax, but not the apparent Km, of the biotin uptake process, suggesting a decrease in the number (and/or activity) of hSMVT but not its affinity. Biotinylation assay confirmed the latter observation by showing a marked reduction in the level of expression of the mutated hSMVT protein at the cell membrane. Mutation of non conserved Cys at position 628 also showed inhibition in biotin uptake suggesting possible interaction with Cys294. These results show an important role for Cys294 in the function and cell biology of hSMVT.(Supported by grants from the DVA and the NIH)
Renal hemodynamics in the anesthetized giraffe
Authors: Bie Peter , Grøndahl Carsten , Bertelsen Mads Frost , Hørlyck Arne , Hasenkam J. Michael , Wang Tobias , Brøndum Emil Toft , Candy Geoffrey , Kristensen Bodil Aarup 
Published: June 2021

In the giraffe, the brain is located some two meters above the heart most of the time and the central mean arterial blood pressure is twice that of mammals of similar mass. Consequently, the heart perfuses the kidney at a mean pressure of some 200 mmHg. The renal capsule is thick and non‐translucent.Nine giraffes (mean body mass 493 kg) were anaesthetized and instrumented. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by conventional clearance techniques using continuous infusions of inulin and p‐aminohippurate. Renal interstitial hydrostatic pressure (RIHP) was measured by a 22G needle inserted in the renal parenchyma. The intrarenal artery resistance index (AI) was determined by Doppler ultrasound. Hormone immunoactivities in plasma were measured by conventional radioimmunoassays.GFR was 342 ± 99 ml/min and ERPF 1252 ± 305 ml/min. AI was median 0.27 (max. 0.49, min. 0) and RIHP 142 ± 6 mmHg. Plasma renin concentration was 17 ± 4 mIU/l, peptide levels were 6.3 ± 0.9 pg/ml for AngII, 135 ± 23 pg/ml for atrial natriuretic peptide, and highly variable for vasopressin.The data show low values of GFR, ERPF and resistance index, yet the RIHP is >20 fold higher than in other mammals. The results suggest that a strong renal capsule allows for a high RIHP reducing the net arterial driving pressure and effectively protecting the kidney against organ damage.
Deficiency of p47phox subunit of NADPH oxidase protects skeletal muscle from depression of force stimulated by sphingomyelinase
Authors: Bost Elaina Reid , Ferreira Leonardo 
Published: June 2021

Chronic diseases (e.g., heart failure) increase sphingomyelinase (SMase) activity in the serum and skeletal muscle. SMase forms ceramide, which activates reactive oxygen species production by mitochondria and NADPH oxidase. Reactive oxygen species contribute to depression of force stimulated by SMase. p47phox is a subunit required for activation of NOX2 isoform of NADPH oxidase. We hypothesized that mice lacking p47phox would be protected from depression of force when treated with SMase. We exposed diaphragm bundles from genetic controls (C57BL/6J; n = 16) and p47phox knockout mice (C57BL/6J; n = 11) to vehicle (glycerol) or SMase (0.5 U/ml). Maximal tetanic force decreased in genetic controls (in N/cm2: Vehicle 20 ± 0.6, SMase 16 ± 0.7, P < 0.05), but was unchanged in p47phox knockout (in N/cm2: Vehicle 20 ± 1.0, SMase 19 ± 1.1). Our results suggest that SMase‐induced depression of force requires signaling through the p47phox subunit of NADPH oxidase. It appears that SMase increases reactive oxygen species production by NADPH oxidase, which leads to depression of force.Funding support: NIH 1K99HL098453‐01, 4R00HL098453‐02
GABA‐A receptor inhibition reverses autoresuscitation defects in serotonin (5‐HT)‐deficient Pet‐1−/− mice
Authors: Cummings Kevin James , Li Aihua , Nattie Eugene 
Published: June 2021

Autoresuscitation is compromised in serotonin (5‐HT)‐deficient Pet‐1−/− mice during a critical developmental period (P7‐10). We hypothesized that the autoresuscitation defects of Pet‐1−/− mice can be restored by antagonizing GABAA receptors. We gave an intracerebroventricular injection of either gabazine (2 uL of 20uM) or saline to Pet‐1−/− pups (n=5 and 7, respectively) and wild‐type littermates (WT; n=14 and 7) at P8. We tested autoresuscitation over 10 asphyxic episodes. We determined survival, delay to gasping, and time required for the recovery of heart rate and normal breathing. ~60% of WT animals survived all 10 episodes, while no Pet‐1−/− animals survived beyond 4 episodes (median=2). Lower survival in Pet‐1−/− was associated with a 7‐fold increase in the delay to the first gasp and a 3‐fold increase in the time required to restore heart rate upon return to room air. Gabazine completely reversed the autoresuscitation defects of Pet‐1−/− mice (P<0.001 for gasp delay and cardio‐respiratory recovery). The median number of asphyxic episodes survived by gabazine‐treated Pet‐1−/− mice was 4, with 2 of 5 surviving to the 8th episode. Based on these data we suggest that pharmacological inhibition of the GABA system could help reduce SIDS in infants that can be identified as being 5‐HT deficient.This research was supported by a Parker B. Francis Fellowship (KJC) and NIH grant HL28066, (PI, E. E. Nattie)
Peripheral Cardiac Sympathetic dysfunction in the prehypertensive Spontaneously Hypertensive Rat
Authors: Shanks Julia , Manou-Stathopoulou Sotiria , Lu Chieh-Ju , Li Dan , Paterson David J , Herring Neil 
Published: June 2021

The spontaneously hypertensive rat (SHR) has increased peripheral cardiac sympathetic activity compared to Wistar Kyoto (WKY) controls. However, it is not clear whether this precedes the development of hypertension. We therefore compared peripheral cardiac sympathetic responsiveness in the SHR to the WKY at 4 weeks of age. Ventricular weight/body weight ratios and mean arterial pressure measured via the left carotid artery demonstrated that SHRs (n=8) were without left ventricular hypertrophy and were normotensive at this age compared to WKYs (n=7). In isolated cultured neurons from stellate ganglia, the magnitude of the calcium transient in response to high extracellular potassium depolarization was significantly (p<0.05) larger in SHRs (n=10) compared to WKYs (n=8). There was also a significantly greater release of [3H]‐norepinephrine (NE) to field stimulation (5Hz) of right atria (n=7 for both groups) and higher plasma levels of the sympathetic co‐transmitter neuropeptide Y (NPY) (n=12 for both groups). In an isolated organ bath atrial preparation with intact right stellate ganglion there was a greater heart rate response to right stellate stimulation at 5 and 7Hz in SHRs (n=9) compared to WKYs (n=7). Increased cardiac sympathetic neurotransmission may therefore represent an early marker in the development of hypertension driven by larger calcium transients.Supported by the British Heart Foundation
Assessment of HD‐X11 Transmitter (DSI) for Telemetric Measurement of Arterial Pressure, Electrocardiogram, Heart Rate and Autonomic Function in Conscious Mice
Authors: Sabharwal Rasna , Chapleau Mark W 
Published: June 2021

The small size of mice limits the number of variables that can be measured simultaneously by telemetry. The goal of this study was to evaluate the performance of the recently released HD‐X11 transmitter (DSI®) capable of recording blood pressure (BP), electrocardiogram (ECG), locomotor activity and body temperature. C57BL6 mice and mice deficient in the antioxidant enzyme methionine sulfoxide reductase (MsrA−/−) were studied before and during infusion (2wks) of angiotensin II (AngII) (1000 ng/kg/min). Measurements were compared with those obtained using the PA‐C10 transmitter capable of recording BP and activity only. Catheters/transmitters were chronically implanted under ketamine/xylazine anesthesia. Body weight, BP, heart rate (HR), and derived variables did not differ in mice implanted with HD‐X11 (n=4) vs. PA‐C10 (n=4) transmitters, before and during AngII infusion. Activity was lower in mice with the HD‐X11 probe (P<0.05). Both transmitters detected hypertension and decreased baroreflex sensitivity (BRS, sequence method) in MsrA−/− and AngII‐infused mice (Table). HR variability (SD) calculated from pulse intervals and R‐R intervals were strongly correlated (slope=1.17, r=0.97, P<.001), and reduced in MsrA−/− and AngII‐infused mice (P<0.05). We conclude: 1) HD‐X11 and PA‐C10 transmitters provide equivalent cardiovascular and autonomic data in normotensive and hypertensive mice; 2) Locomotor activity is lower in mice implanted with the HD‐X11, perhaps due to increased size/weight of the probe; and 3) Recording of both ECG and BP with the HD‐X11 can assure accurate measurements of HR variability and BRS, and define relationships between autonomic function and arrhythmias. (HL14388, DS1)

PA‐C10
HD‐X11

24hr BP (mmHg)
Baseline
AngII
Baseline
AngII

C57BL6
106±1
147±11
105±3
144±3

MsrA−/−
115±13
168±3
119±1
161±7

BRS(ms/mmHg)

C57BL6
2.0±0.0
1.5±0.1
2.0±0.1
1.1±0.1

MsrA−/−
1.1±0.0
0.7±0.2
1.0±0.1
0.6±0.1
Behavioral assessments of mouse Strain differences in response to social stress
Authors: Jibitu Meskerem , Meyerhoff James , Chakraborty Nabarun , De Lima Thereza Christina Monteiro , Jett Marti , Hammamieh Rasha 
Published: June 2021

In this study a mouse model is set up with a potentially unbiased platform to address the strain differences in response to social stress. Three different mouse strains of C57, BALB/c and DBA were submitted to 5 day and 10 day social stress (SS). Mice were kept inside an aggressor (AGG) home cage and randomly exposed to the AGG three times a day for one minute or for up to ten attacks in less than one minute, while control mice never experienced AGG proximity.Behavioral assessments were performed using the partition/barrier test. Behaviors were recorded and analyzed using Etho Vision software. Subject mice were kept in the aggressor cage separated from the aggressor by a perforated divider.Socially stressed mice persistently avoided the partition area that separated them from the aggressor mouse. C57 mice exhibited significant behavioral changes in response to stress. DBA strain mice showed lower susceptibility to SS than C57. When BABL/c mice were evaluated on the same scale of behavioral parameters, they showed intermediate levels of (SS) responses that were between the C57 and BALB/c responses.Genomic and epigenetic studies are underway to understand these differences in stress response.
Genetic Background (C57BL/6J Versus FVB/N) Influence in Global Gene Expression Profile to High Fat Diet
Authors: Christoffolete Marcelo Augusto , do Nascimento-Sales Michelle , Mendes Adriane Cecília Borges , da Silva Melo Suzane , Prata Rodrigo Ferreira , Ribeiro Miriam Oliveira 
Published: June 2021

Genetic Background is a key player in metabolic phenotypes, however, gene modulation evoked by dietary interventions are still poorly understood.ObjectiveSubmit C57BL/6J (C57) and FVB/N (FVB) mice to high fat diet and determine pattern of gene expression.MethodsAnimals were on chow diet (16,8% protein, 73,5% carb and 4,8% fat) or High Fat Diet ‐ HFD (23% protein, 35,5% carb and 35,9% fat) for 68 days. At the end, animals were euthanized and tissues collected. Total RNA was extracted and submitted to microarray analysis.ResultsFVB mice gained ~5 and ~9g on chow and HFD, respectively. C57 mice gained ~0.5 and ~13g on chow and HFD, respectively. Liver shows ~700 genes up and ~900 genes down‐regulated in FVB compared to C57. HFD evokes up‐regulation of ~215 genes and ~200 genes while ~170 genes and ~240 genes were down‐regulated, in FVB and C57, respectively. WAT shows ~1050 genes up and ~1350 genes down‐regulated in FVB compared to C57. High Fat diet evokes in this tissue the up‐regulation of ~1900 and ~1300 genes while ~1200 and ~1000 genes were down‐regulated, in FVB and C57, respectively.ConclusionLiver gene expression is severely affected by genetic background.
CNS Gαi2subunit proteins – the origin of impaired fluid and electrolyte homeostasis and blood pressure regulation in a saltsensitive phenotype?
Authors: Wainford Richard David , Pascale Crissey L 
Published: June 2021

AimWe examined the role of hypothalamic paraventricular nucleus (PVN) Gαi2 proteins, which we have shown are upregulated to mediate renal sympathoinhibitory pathways to prevent body fluid imbalance and salt‐sensitive hypertension in Sprague‐Dawley rats, in the Dahl Salt‐Sensitive (DSS) vs. ‐Resistant (DSR) rat phenotypes.MethodsDSR, DSS, or DSS rats receiving an i.c.v. infusion of a scrambled (S) or Gαi2 oligodeoxynucleotide (ODN; 25 μg/day) were fed a normal 0.4% (NS) or high 8% NaCl (HS) diet for 3‐ wks. On day 21 MAP (via DSI radiotelemetry probes), 24h metabolic balance, plasma norepinephrine (NE), plasma renin activity (PRA) & PVN Gαi2 protein levels were determined (N=6/gp).ResultsPVN Gαi2 protein levels significantly increased in response to HS intake in DSR but not DSS rats. In DSS rats CNS Gαi2 down‐regulation significantly exacerbated renal sodium retention, global sympathoexcitation & hypertension.ConclusionThe failure to endogenously up‐regulate PVN Gαi2‐proteins in the DSS, but not DSR phenotype, is a likely origin of impaired fluid & electrolyte homeostasis and blood pressure regulation in the DSS rat. This is supported by increased dysregulation of sympathetically driven sodium retaining mechanisms and the exacerbated hypertension following CNS Gαi2‐protein down‐regulation in DSS rats ‐ HL107330.

DSR
DSS

NS
HS
NS
HS
HS+ S ODN
HS + Gαi2 ODN

MAP (mmHg)
122±3
126±3
129±4
161±4*
155±2*
178±3*≠

24h H2O balance (ml/day)
15±1
17±21
13±2
34±3*
32±2*
37±2*

24h Na+ balance (meq/day)
0.6±0.1
1.2±0.3
0.4±0.1
3.3±0.4*
3.5±0.2*
5.4±0.4*≠

PVN Gαi2 protein levels (normalized to GAPDH)
2.4±0.2
11.1±1.3*
0.64±0.1
0.54±0.1
0.8±0.1
0.1±0.1*≠

Index of salt‐sensitivity (slope)
4.8±0.4
0.6±0.3
0.55±0.2
0.3±0.1≠

Plasma NE (nmol/L)
49±3
36±2*
47±5
87±7*
84±8*
116±9*≠

PRA activity (Ang I generation ng/ml/h)
4.9±0.5
1.4±0.1*
5.2±0.5
1.7±0.2*
1.5±0.3*
1.6±0.4*

p<0.05 vs. respective NS gp,
p<0.05 vs. HS + S ODN gp.
Chitosan oligosaccharides ameliorate inflammation in two experimental models of colitis through inhibition of intestinal epithelial cell NF‐kB signaling and apoptosis
Authors: Muanprasat Chatchai , Yousef Mohammad , Pichyangkura Rath , Chatsudthipong Varanuj 
Published: June 2021

Dysregulated mucosal immune response and intestinal epithelial barrier defect contribute to pathogenesis of inflammatory bowel disease (IBD). Chitosan oligosaccharide (COS), a biodegradation product of chitosan, has been recently shown to have anti‐inflammatory properties in vitro. We aimed to evaluate the therapeutic potential of COS in the treatment of IBD and to elucidate its mechanism of action. Anti‐inflammatory effects of COS were investigated both in mice and in human colonic epithelial cell line (T84 cells). In dextran sulphate sodium (DSS)‐induced colitis model, COS treatment significantly rescued dead rate and protected against inflammatory intestinal damage with the most effective dose being 10–20 mg/kg/day. In addition, COS treatment suppressed NF‐κB activation and decreased colonic tissue levels of TNF‐α and IL‐6. Similar protective effect was also observed in acetic acid induced colitis models. In T84 cells, COS suppressed NF‐κB activation and production of TNF‐α and IL‐6 under both LPS and TNF‐α‐stimulated conditions. Furthermore, TNF‐α and H2O2‐induced T84 apoptosis was significantly prevented by COS treatment. COS represents a promising therapeutic option in the treatment of IBD, which may preserve the intestinal epithelial barrier integrity and prevent initiation and progression of IBD.This work was supported by the Thailand Research Fund and the Office of the Higher Education Commission and Mahidol University under the National Research Universities Initiative.