bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of cytological alterations and genetic polymorphism in clinically normal oral mucosa of smokers
Authors: Bayoumi Fatehia Ali 
Published: June 2021

BackgroundMany enzymes involved in detoxification of chemical carcinogen metabolism are polymorphically expressed, with the alleles presenting different enzymatic activities and some of them are associated with cancer susceptibility. Genetic polymorphisms may contribute to our understanding of inter‐individual variation in susceptibility to environmental carcinogens and development of neoplasias. Deletion of GSTM1 and GSTT1genes will lead to complete loss of enzymatic activities.Aimto study the relationship between GSTM1 and GSTT1 genes deletion and the rate of cellular proliferation in oral mucosa of smokers among a sample population of United Arab Emirates.Material and MethodsThis cross sectional study consisted of 106 non‐smokers and smokers between the age of30–60. Blood samples and oral smears were collected for DNA extraction and cytologic examination of the silver stained NORs (AgNORs).GSTM1 and GSTT1Gene deletions were analyzed using PCR‐based method. Analysis of data was done by using SPSS program.ResultsThere was significant increased number of Agnors in the cells of oral mucosa of smokers if compared with those of non‐smokers and positive correlation between the number of Agnors in smokers and the age (0.81),Pack‐year(0.93),GSTT1 deletion (0.63) and GSTM1 deletion (0.48).Smokers with deletion of GSTT1 and GSTM1 were at a significant high risk of increased cellular proliferation (OR=0.029, 95%CI= 0.006–0.152)for GSTT1 and 0.060 (0.007–0.504) for GSTM1.There was highly significant difference among the group with deletion when compared to the group of no deletion in both genes(p< 0.001).ConclusionThere is an association between GSTT1 & GSTM1 deletion and the risk of increased cellular proliferation of the oral mucosa of smokers.Source of Fund: the Medical Research Fund, Dubai Medical College (MRF‐DMCG).
RHAMM alters smooth muscle cell (SMC) remodeling of collagen‐hyaluronan (HA) matrix
Authors: MA XUE , BERNISH BRIAN , GEARY RANDOLPH 
Published: June 2021

HA is prominent in ECM at sites of artery injury and alters SMC proliferation and migration by binding receptors CD44 and RHAMM, respectively. HA also enhances contraction of collagen by SMC in vitro but the molecular regulation of this effect is ill defined. Given HA binding of RHAMM induces migration we hypothesize RHAMM also mediates HA‐induced collagen remodeling. To test this hypothesis, rat SMC were pre‐treated with blocking antibody and effects on adhesion, migration, collagen gel contraction determined. Consistent with the literature, HA promoted migration via RHAMM, as blocking antibody inhibited healing of a scratch assay by 84% compared to IgG control (%healing, 48 hr: 8±2 vs 92±2 %, respectively, p=0.008) but without significant effect on initial SMC adhesion to collagen‐coated plates(p=0.08). HA enhanced contraction of collagen‐I gels and contraction was further increased by RHAMM blockade (gel diam, 18hr: 8.5±0.15 vs 5.5±0.1, p=0.01). Gel histology showed increased pericellular collagen with RHAMM blockade (156±7% of control, p<0.05) and reduced cell speading (p=0.015). In summary, RHAMM promoted SMC migration with little effect on initial adhesion. Blocking RHAMM enhanced HA‐induced collagen gel contraction, suggesting RHAMM plays an inhibitory role in collagen remodeling, making RHAMM a potential target for treating constrictive remodeling in vivo.Research Support: NIH R01HL57557
caTissue Suite: An Open‐Access, Feature‐Rich Tool For Biospecimen Annotation And Data Sharing
Authors: McDonald Sandra , Watson Mark , Nagarajan Rakesh , Mulvihill David A , Brink Amy 
Published: June 2021

Advances in molecular technologies and clinical trial design have mandated new requirements for the operation of biorepostories. caTissue Suite is a caBIG(TM) application designed to manage the complexities of biospecimen annotation data.caTissue Suite is a software application developed with requirements gathering and acceptability testing by multiple institutions. caTissue uses a web browser to store and retrieve data from a database. Its open program interface (API) permits customized access to all of the application's features, and data integration from other data systems.caTissue Suite is scalable and configurable for broad deployment across biorepostories of varying size and function. Numerous institutions have adopted the application and are using it in their daily operations. A caBIG(TM) supported, web‐based “Knowledge Center” (https://cabig‐kc.nci.nih.gov/Biospecimen/KC) provides on‐going application support via discussion forums, technical and user guides, training tools, and webinars.caTissue Suite is a freely available, fully supported, open‐access software application for biospecimen data management. Use of caTissue Suite by several NCI Cancer Centers and other biospecimen resource groups is providing a rapid and facilitated path toward standardizing biospecimen informatics and promoting biospecimen data sharing both nationally and globally.
Polymorphisms of heat shock factor‐1: Genetic diversity in an evolutionarily conserved, multifunctional regulator gene
Authors: Bridges Tiffany M. , Singh Ishwar S. , Liggett Stephen B. , Hasday Jeffrey D. 
Published: June 2021

In the present study we analyzed heat shock factor‐1 (HSF‐1) for SNPs by mining the NCBI dbSNP database and directly sequencing the 13 HSF‐1 exons (2152 nt mRNA sequence) from 60 anonymous genomic DNA samples representing 30 Caucasians and 30 African Americans and comparing these with a reference human HSF‐1 sequence (NT_037704).ResultsMining the dbSNP database revealed 6 SNPs (3 in the 3′UTR and 3 in the coding sequence). One of the coding SNPs causes a proline‐to‐threonine missense at amino acid 365 adjacent to LZ3 and one causes a frame‐shift replacement of the 26‐amino acid C‐terminal transactivation domain. Direct sequencing confirmed the P365T SNP, identified a second novel nonsynonymous SNP (L25I) located in the DNA binding domain, 2 novel 5′UTR and 2 novel 3′UTR SNPs. Four of the five 3′UTR SNPs alter predicted miRNA target sequences (MicroSNiPer) and both 5′UTR SNPs alter predicted 5′UTR secondary structure (RNAFOLD).ConclusionsWe have identified several SNPs in both the coding and untranslated regions that are likely to alter HSF‐1 function and expression level, respectively. The functional consequences of these SNPs will be analyzed by overexpressing in MEFs from HSF‐1‐null mice.
Changes in in vivo renal artery hemodynamics after exercise training
Authors: Gurovich Alvaro N , Moningka Natasha , Baylis Chris , Delp Judy M. 
Published: June 2021

Recent studies on the effects of exercise on the kidney have identified strain‐specific responses of shear dependent endothelial enzymes, endothelial nitric oxide synthase (eNOS) and extracellular superoxide dismutase (ECSOD). Here we investigated the effect of 12 weeks voluntary wheel running (VWR) (~3 km/day @wk 12) on in vivo renal artery hemodynamics in male Fisher 344 rat compared to sedentary controls (both n=6). We measured peak and mean flow velocity (PFV and MBV, respectively) using a 10 MHz Doppler probe and workstation 24h after withdrawal from VWR, under isoflurane anesthesia. After Doppler acquisition, the right renal artery diameter (RAD) was measured ex vivo to calculate peak and mean blood flow (PBF and MBF, respectively) and peak and mean shear rate. RAD, PBF, and MBF significantly decreased after ET (0.43±0.08 vs. 0.35±0.05 mm, 4.43±1.47 vs. 2.08±0.87 ml/min, 1.66±0.56 vs. 0.77±0.47 ml/min, respectively, p<0.05). However, despite the fall in PBF/MBF there were no changes observed in PFV, MBV, or shear rate. Thus, 12w of mild exercise (VWR) causes persistent reduction in renal blood flow and vascular remodeling in the renal artery. There was no fall in shear rate entering the kidney, however, which may contribute to the preservation/enhancement of renal cortical eNOS and ECSOD in the F344, which contrasts with the Sprague Dawley, where VWR reduces eNOS/ECSOD.Funded by NIH R01 HL077224 and DK56843
The Effects of Aerobic Exercise Training on Arterial‐Ventricular Coupling in Patients with Metabolic Syndrome: A Pilot Study
Authors: Reger Brian , Donley David , Bonner Daniel , Failinger Conard , Olfert Mark , Chantler Paul 
Published: June 2021

Arterial‐ventricular coupling (EA/Ees) is an important determinant of cardiovascular (CV) function, and can be indexed by the ratio of arterial elastance (EA; net arterial load), to left ventricular (LV) end‐systolic elastance (Ees; LV performance). Metabolic syndrome (MetS) patients have an abnormal CV function, which may be due to a suboptimal EA/Ees.PURPOSETo examine EA/Ees, at rest and peak exercise, in MetS patients before and after 8 weeks of exercise training.METHODSMetS patients (n=13, 46±8) were defined according to ATPIII. Using echocardiography we noninvasively characterized Ees (single beat elastance), and EA (end‐systolic pressure/stroke volume) from which EA/Ees was calculated, and compared to healthy controls (n=4, 48±7). MetS patients were separated into exercise or non‐exercising groups for 8 weeks.RESULTSAt rest, EA/Ees was 21% lower in MetS vs. controls due to a 24% higher Ees in MetS vs. controls. The reduction in EA/Ees during exercise was blunted in MetS (31% vs. 52%, p<.01) because of a blunted increase in Ees in MetS vs. controls (102% vs. 234%, p<.05). 8 weeks of exercise training in MetS increased EA/Ees at rest, and enhanced the reduction in EA/Ees (25%, p=.05) during exercise due to a 61% (p<.05) greater increase in Ees.CONCLUSIONThe abnormal EA/Ees at rest and peak exercise in MetS patients was restored to similar levels noted in healthy controls after 8 weeks of aerobic training
Role of actin cytoskeleton and microtubules in passive diameter and viscoelastic charectistics of rat cremaster arterioles
Authors: Beig Mirza Irfan , Dolan Allison , Zhao Guiling , Hoover Erin , Martinez‐Lemus Luis A 
Published: June 2021

In resistance arteries the role of actin fibers and microtubules on their passive viscoelastic charectistics are not clearly understood. Arterioles were isolated from rat cremaster muscles, and pressurized to 60mmHg and incubated at 34.5 °C. The arterioles were observed under a microscope where vessel diameter was recorded. After vessels developed tone they were washed and incubated in solution containing EGTA but not Ca++ for 30 minutes. After obtaining maximum passive diameter arterioles were subjected to different pressures before and after a 30‐minute incubation with Cytochalasin D, Latrunculin, or Demecolcine alone or in combination.ResultsPressure diameter curves were obtained before and after actin cytoskeleton and microtubule disruption. There was no significant difference in the pressure diameter curve before and after administration of DMSO, Cytochalasin D, Latrunculin or Demecolcine alone or in combinations (p>0.05). We have previously shown that Demecholcine disrupts the microtubular network. Confocal images further indicate that treatment with Cytochalasin D and or Latrunculin successfully disrupts the actin cytoskeleton.DiscussionBased on the above results, it can be considered that the actin fibers and microtubules do not play a major role in the passive viscoelastic characteristics of cremaster arterioles.
Characterizing the effect of long‐range basepairing interactions on translational control of the unfolded protein response transcription factor Hac1
Authors: Bolinger Cheryl G , Dever Thomas E. 
Published: June 2021

Under conditions of ER stress, the unfolded protein response (UPR) induces expression of the transcription factor Hac1. In contrast, under non‐stress conditions the HAC1 mRNA is constitutively expressed, but the protein is not detected. It has been proposed that HAC1 expression is regulated by a basepairing interaction between nucleotides in the mRNA 5′ UTR and intron. The implicit mechanism is that secondary structure created by the interaction blocks scanning ribosomes and that this block is alleviated by removal of the HAC1 intron through a non‐conventional splicing reaction. The goal of the current study is to define the mechanism of HAC1 translational control.A series of HAC1 expression plasmids was created with mutations that disrupt 5′ UTR/intron basepairing. We have found that disruption of a single basepair within the 21 basepairs reported to block HAC1 mRNA translation is sufficient to allow Hac1 synthesis. Whereas the location and identity of the mutation within the 5′ UTR element resulted in varying levels of Hac1 expression, any mutation within the basepairing element in the intron derepressed Hac1 production. Additional studies are examining the association of HAC1 mRNA with ribosomes. The results indicate that Hac1 expression may be regulated through multiple mechanisms in addition to long‐range basepairing interactions.
Protease‐activated receptor ‐3 signals independently to phosphorylate endothelial nitric oxide synthase in human endothelial cells
Authors: Tillery Lakeisha C. , Epperson Tenille , Austin Anita , Motley Evangeline 
Published: June 2021

Protease‐activated receptor‐3 (PAR‐3) is widely recognized as a non‐signaling elusive member of a G protein‐coupled receptor family known to regulate the endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) signaling pathway via phosphorylation of its regulatory sites. Failure of the eNOS/NO pathway leads to endothelial dysfunction, a precursor to cellular induced hypertension and other cardiovascular diseases. Using human umbilical vein endothelial cells (HUVECs) as a model for human endothelium, we demonstrated that PAR‐3 is highly co‐expressed with PAR‐1 and ‐2 and can be activated using a synthetic peptide, SFNGGP‐NH2. Therefore, we hypothesize that PAR‐3 can signal independently of PAR‐1 and ‐2 to regulate eNOS. Immunoblot analysis using eNOS specific antibodies showed that 25uM of SFNGGP lead to the phosphorylation of the positive site of eNOS at ‐Ser1177 and the negative site ‐Thr495 in a time‐dependent manner similar to that observed with thrombin. After HUVECs were pretreated with 10uM of SCH79797, a selective PAR‐1 inhibitor, then stimulated with SFNGGP for 5 minutes, we observed an increase in phosphorylation at both eNOS regulatory sites. Thrombin‐induced phosphorylation of these sites was inhibited in the presence of SCH79797. Our data suggests that PAR‐3 is able to regulate eNOS/NO signaling via site specific phosphorylation that is independent of the activation of PAR‐1. Cardiovascular disease is the leading cause of death among Americans, where hypertension can be a silent aggressor. Studying the signaling pathways responsible for eNOS‐induced NO production will lead to a better understanding of endothelial dysfunction in cardiovascular diseases such as hypertension.NIH‐NIGMS‐SCORE and NIH‐NHLBI‐T32
Association of M3 muscarinic receptors and Kir6.1 with human detrusor caveolae
Authors: Rippe Catarina , Ekman Mari , Dabestani Saeed , Mörgelin Matthias , Karbalaei Mardjaneh , Uvelius Bengt , Swärd Karl 
Published: June 2021

Caveolae are 50–100 nm large membrane invaginations that represent a plasmalemmal sub‐compartment of relevance for cellular signaling. We aimed to assess whether the muscarinic receptor M3 and the K‐ATP channel Kir6.1 are associated with human detrusor caveolae and to probe the functional relevance of this organization. Muscle strips were dissected from human detrusors and used in ultrastructural, biochemical and mechanical studies. Caveolae were ablated by cholesterol desorption with methyl‐β‐cyclodextrin. The subcellular distribution of M3 muscarinic receptors and Kir6.1 was examined using sucrose density fractionation and immunoelectron microscopy. Desorption of cholesterol right‐shifted the concentration‐response curve for the muscarinic receptor agonist carbachol. Using a K‐ATP channel inhibitor (glibenclamide) and activator (levcromakalim), we were able to inhibit and mimic this effect, respectively. Sucrose density fractionation revealed co‐fractionation of detrusor M3 receptors and Kir6.1, in partial overlap with caveolin‐1. Immunoelectron microscopy showed M3 in caveolae and in sub‐plasmalemmal caveolae‐like structures. Thus, M3 receptors are enriched with Kir6.1 in caveolae, and this organization underpins cholinergic detrusor activation in man.Funded by Swedish Research Council (K2009‐65X‐4955‐01‐3), ALF, Crafoord Foundation.
Experience with Sephadex G 50 in Crude Gastrin Purification
Authors: Babatunde Adelaiye Alexander 
Published: June 2021

Animal Crude Gastrin has been a major source of gastrin for gastric acid stimulant in experimental studies. The objective of this study was to evolve a method of crude gastrin purification that could yield a better gastric acid output. The Gastrin was extracted by the standard method of Gregory and tracy(1964) nodified by Adelaiye and Amure(1990)Extraction and purificatio of Crude Gastrin has been a physiological problem since Edkins first extracted Gastrin from the antral mucosa of animals (Edkins 1905) in 1954 Tauber and Medison described a new method for gastrin purification using the cell gel chromotography process. In this experiemnt crude gastrin extract was obtained from the antrum of the Camel, Sheep and Goat and purified using Sephadex G 50. The crdue extract solution was passed through Sephadex G50( Upsala Phamacia) column chromotography. The effluent was then adminsistered to albino rats in at O.5ml. The basal gastric acid output rose from 0.23 meq/lt to 2.32meq/l in 20minutes in sephadex purified crude gastrin as compared to 0.23 to 0.27 meq/lit for the same period. This was found to be statististically significant P<0.02.Sephadex G50 column chromotography purifies crude gastrin extract and improves the gastric stimulant affect.
Low‐Intensity Exercise Training Prevents Muscular Microangiopathy in Non‐obese Type 2 Diabetic Rats
Authors: Fujino Hidemi , Kondo Hiroyo , Murakami Sinichiro , Fujita Naoto , Morifuji Takeshi , Nagatomo Fumiko , Ishihara Akihiko 
Published: June 2021

PURPOSEThe purpose of the present study was to investigate the effects of low‐intensity exercise training on the angiopathy of skeletal muscle by type 2 diabetes.METHODSMale Goto‐Kakizaki (GK) non‐obese type 2 diabetic rats (6 weeks old) and wild‐type Wistar rats (Con) were used. GK rats divided into 2 groups: diabetes (GK) and diabetes plus low‐intensity exercise training (GK+Ex). The low‐intensity exercise training was conducted during 60 min, 5 times per week, for 3 weeks. The three‐dimensional capillary network of soleus muscle was visualized using a confocal laser microscopy. The mRNA expression levels of angiogenic factors (VEGF, KDR, Flt‐1, Ang‐1, Ang‐2, Tie‐2, and HIF‐1 alpha) in the soleus muscle were determined by TaqMan probe‐based real‐time PCR.RESULTSThe capillary volume in the muscle was lower in GK than in Con rats. However, the capillary volume in the muscle of GK+Ex was increased toward to the level of Con rats. Although the expression levels of angiogenic factors in the muscle were lower in GK than in Con, those were increased toward to the levels of those in GK+Ex rats.CONCLUSIONThe present results provide evidence of the effectiveness of endurance exercise training that reduces the muscle circulatory complications associated with type 2 diabetes. Supported by Grants‐in‐Aid for Science Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology, no. 22300189.
Effects of Exercise Preconditioning on Capillary in Soleus Muscle of Type 2 Diabetic Rats
Authors: Murakami Shinichiro , Morifuji Takeshi , Kondo Hiroyo , Takeda Isao , Fujita Naoto , Fujino Hidemi 
Published: June 2021

Type 2 diabetes mellitus is tightly linked to impaired skeletalmuscle glucose uptake and storage. The 3‐D capillarity, myosin heavy chain isoforms (MyHC) transformation and succinatedehydrogenase (SDH) activity in the soleus muscle were different between diabetic and non‐diabetic rats. Aerobic exercise has been known an effective therapy against the diabetes.PURPOSETo clarify the effect of aerobic exercise on capillary architecture in diabetic muscle, the 3‐D capillarity has been investigated.METHODSGoto‐Kakizaki (GK) (36weeks old, n=6) rats, a spontaneous non‐obese type2 diabetes model, and age matched GK rat that performed aerobic exercise preconditioning for 2weeks (GK‐EX), (n=6) were used. The contrast medium‐injected capillaryin the soleus muscle was visualizedusing a confocal laser microscope. The SDH activity and MyHC type were measured.RESULTSThe soleus muscles in GK and GK‐EX were composed of only type I MyHC. The SDH activity in GK‐EX was significantly higher than that in GK. The capillary diameter in the soleus of GK‐EX rat wassmaller than that of GK rat. And the mean capillary volumein GK‐EX was significantly higher than that in GK.CONCLUSIONThe results of the present study indicate that aerobic training improves impaired capillarity in diabetic muscle. This studywas supported by Grants‐in‐Aid for Scientific Research from the Japanese Ministry of Education, Culture,Sports, Science and Technology no. 21700559 and 22300189.
Substance P (SP) Contributes To Rapidly Adapting Receptor (RAR) Activity In High Altitude Pulmonary Edema (HAPE)
Authors: Bhagat Ruchi , Yasir A , Vashisht A , Ravi K 
Published: June 2021

AimsTo investigate whether there is a change in i) basal RAR activity and ii) their responses to SP, in rabbits with HAPE.MethodsExperiments were performed in anesthetized, artificially ventilated and thoracotomized rabbits. After routine cannulations, the RAR activity was recorded from cervical vagus nerve. Increasing doses of SP were administered into the right atrium in control rabbits (C) breathing room air (n= 6) and in rabbits with HAPE (n= 6). To produce HAPE, rabbits were placed in a high altitude simulation chamber ‐ 15,000 feet, 36 hrs. In both the groups, SP doses were repeated after the administration of NK‐1 receptor antagonist, CP‐96345 (400 nmol/kg, Pfizer, Croton, USA).ResultsThe basal RAR activity in C was 6.34±0.46 impulses/breath and it increased to 10.0±0.64 impulses/breath (p<0.001) in HAPE. SP stimulated the RARs in both the groups. However, in HAPE, the RARs were stimulated even by sub‐threshold doses of SP. CP‐96345 attenuated the RAR activity in C but not in HAPE.
RAR response to SP in C and HAPE groups.

RAR activity in %

Groups
After SP (μg/kg)

0.02
0.04
0.08

Before CP‐96345
C
16.22±4.99
28.44±7.00
48.95±9.92

HAPE
51.14±5.10 ***
54.83±3.77**
Not done

After CP‐96345
C
18.10±8.59
24.44±9.27
20.58±4.98

HAPE
38.55±8.87
56.50±6.11*
Not done

RAR activity expressed as a percentage of their respective basal activities.
p<0.05,
p<0.01 and
p<0.001, compared with the corresponding response in C.

Conclusion1.HAPE stimulates RARs. 2. The RARs do not show adaptation to this stimulus. 3. Endogenous SP released during HAPE sensitizes the RARs to exogenous SP. Funded by DIPAS, Delhi.