bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell specific expression of Sphingosine‐1‐Phosphate receptors in endothelial cells and smooth muscle cells
Authors: Hudson Nicola K , Speake Paul F , Robinson Nicola J , Baker Philip N , Taggart Michael J 
Published: June 2021

Much attention has recently been given to a vasoactive role for the lipid metabolite sphingosine‐1‐phosphate (S1P). We have previously shown S1P to control net tone of human maternal and placental arteries. These data suggest S1P actions may be mediated by cell‐specific receptor expressions with potentially vasoconstrictory actions on smooth muscle cells (SMCs) and dilatory actions on endothelial cells (ECs).In the absence of efficacious antibodies, the first step in validating this hypothesis was to establish expression of mRNA encoding S1P receptors (S1PR) 1–3 in purified cell populations. Human reference RNA was used to construct standard curves and 18s as an internal calibrator. We used human primary SMC's from myometrium and cultured umbilical vein EC's numbering from 1250 to 1 in order to assess cellular heterogeneous expression patterns, another possible contributor to net functional vasoactive action of S1P.Results show S1PR 1–3 to be expressed in both ECs and SMCs. S1PR 1 is the predominant receptor in ECs, whereas SMCs express S1PR 3 to a greater extent than the other two sub‐types. We found similar expression patterns to be independent of cell number suggesting homogenous expression.Future work will characterize cell‐specific expression of these receptors in native blood vessel cells in order to further elucidate the role of S1P in regulation of human vascular tone.Research supported by Ardana PLC.
Real time measurement of hydrogen peroxide (H2O2) and nitric oxide (NO) release in the renal vein: The effects of Protein Kinase C beta II inhibitor (PKC β ‐) on rat kidneys exposed to extracorporeal shock wave lithotripsy (ESWL)
Authors: Krass Samuel , Zambrano Christopher , Thomas Shawn , Chen Qian , Young Lindon H 
Published: June 2021

ESWL clinically treats kidney stones. However, studies have suggested that hypertension and decreased renal function are long term effects of ESWL therapy. ESWL induced renal injury results from free radical production and microvascular injury in the kidney. ESWL causes vasoconstriction, which results in renal injury analogous to an ischemia/reperfusion (I/R) injury. I/R injury is characterized by decreased endothelial nitric oxide. This is mediated by the NO scavenger, superoxide, which results in the formation of peroxynitrite, a potent oxidant. Endothelial NO synthase (eNOS) produces NO when activated. PKC is a key enzyme in the regulation of eNOS. The effects of PKC β‐ (0.055 − 0.55mg/kg) were examined in the renal veins in kidneys exposed to ESWL. PKC β‐was injected through the tail vein immediately post ESWL. NO and H2O2 were directly measured by inserting either NO or H2O2 microsensors (100 μm diameter) into the left renal vein in the anesthetized rat. Preliminary data suggests that PKC β‐attenuates H2O2 in the renal vein 20 minutes post ESWL, which may be related to an NO mechanism. In saline treated controls, NO decreases throughout 20 min post ESWL. The preliminary data thus far support our hypothesis that ESWL increases oxidative stress whereas PKC β‐attenuates oxidative stress.This study is supported by PCOM, department of neuroscience, physiology, & pharmacology.
Comparison of lower extremity strength, power and muscle area between healthy subjects and mobility‐limited elders
Authors: Reid Kieran F. , Doros Gheorghe , Cloutier Gregory J. , Clark David J. , Carabello Robert J. , Phillips Edward M. , Frontera Walter R. , Fielding Roger A. 
Published: June 2021

This study compared muscle strength, power and cross sectional area (CSA) in healthy middle‐aged adults (mean age: 47.3 ± 5 yrs, n = 26), healthy older adults (73.8 ± 4 yrs, n = 21), and older adults with mobility limitations (77.1 ± 5 yrs, n = 21). One repetition maximum strength (1RM) and peak power output (PP) were estimated using the bilateral leg press exercise. Total thigh muscle CSA was assessed using computated tomography. Mobility‐limited elders had significantly reduced muscle strength, PP and CSA compared to both healthy groups (table). There were no significant differences for any of these measures between the healthy‐middle aged or healthy‐older participants. These data suggest that preservation of strength, power and muscle mass in healthy older adults attenuates the age‐related decline in lower extremity functional performance. Additional studies should assess the efficacy of exercise and therapeutic interventions designed to increase muscle quality in older adults with compromised physical functioning.NIA AG‐18844 and the USDA 58‐1950‐7‐707
Treadmill training does not prevent loss of muscle mass or contractile properties in senescence
Authors: Thomas Melissa M , Betik Andrew C , Wright Kathryn J , Riel Caitlin , Hepple Russell T 
Published: June 2021

With aging there is a decline in muscle mass and strength. This study was designed to examine the impact of treadmill training, beginning in late‐middle age and continuing across a 7 mo period when muscle atrophy and functional decline markedly accelerates. 29 mo old rats were divided into 2 groups: half of the animals were exercised on a treadmill for 5 (34T) or 7 mo (36T), while the others maintained normal cage activity (34C and 36C). In situ contractile properties were measured in the Gastrocnemius/plantaris (GAS) and Soleus (SOL) muscles via sciatic nerve stimulation. Mass of the GAS and SOL was lower than young adult (YA) in 34C and 36C. Training had no affect on mass in 34T but decreased mass in 36T vs 36C. GAS tetanic force was lower than YA (12.1 ± 0.9 N/g) in 34T (8.8 ± 0.9 N/g) and 34C (7.1± 1.0 N/g), with no further decline with aging. SOL tetanic force was lower than YA (14.9 ± 0.8 N/g) in 34T (5.4 ± 0.7 N/g) and 34C (5.8 ± 1.0 N/g), with no further decline at 36 mo. In addition, training did not prevent the increase in time to peak force and time to half relaxation seen with aging in controls. In conclusion, treadmill training did not attenuate declining muscle contractile function with aging and may even exacerbate muscle mass decline in senescence.Supported by CIHR and NSERC (Canada).
Isolation of resistance vessels and detection of Vasopressin receptor (V1a) from different vascular beds in Spontaneous Hypertensive Rat (SHR).
Authors: Samsøe Elisabeth Vaagen , Gharehnia Behzad , Jonassen Anne Kristine , Vågnes Øyvind Brune , Iversen Bjarne Magnus 
Published: June 2021

The arginine vasopressin receptor (V1a) is up‐regulated in renal resistance vessels from 4 wk old SHR compared to age matched normotensive Wistar Kyoto rats (WKY). At the age of 20 weeks, the receptor level is not different between the strains. V1a expression in renal resistance vessels seems to be up‐regulated during the development of hypertension.In the present study we investigated the expression of the V1a in resistance vessels from different organs in SHR and WKY. Resistance vessels were isolated from heart, aorta, small intestine, tail and lower limb using magnetic iron oxide. In addition, the effect of vasopressin injection on coronary blood flow (CBF) was studied in isolated hearts. V1a expression was analysed by western blot and real time PCR.Results: V1a protein expression was increased in resistance vessels from the heart of young SHR. In resistance vessels from tail, intestine and lower limbs, no difference in expression was found. In 20 wk old rats no difference in CBF response to vasopressin was found between the strains, in 4 wk old rats the situation is not yet clear. In conclusion the V1a expression was upregulated in heart resistance vessels isolated from young SHR compared to age matched control WKY rats. This may indicate involvement in the development of genetic hypertension. No upregulation was found in resistance vessels from other tissues.
Rescue of mechanical function, muscle morphology and signaling by desmin plasmid transfection
Authors: Lieber Richard Louis , Palmisano Michelle , Shah Sameer , Hornberger Troy , Ryan Allen F. 
Published: June 2021

The muscle‐specific intermediate filament desmin has been described as the “mechanical integrator” of the muscle cell. We probed this function by transfecting adult desmin knockout (DKO) muscle with plasmid DNA encoding desmin and measuring the resulting structural and functional changes. Mice were transfected by electroporation and, after 7 days, when protein expression peaked, we measured the regularity of the myofibrillar lattice and several responses to mechanical stretch including the deformability of nuclei, stress production, injury and c‐Jun‐kinase (JNK) phosphorylation. Desmin transfection reversed essentially all of the knockout phenotype in a quantitative manner—Z‐disks were re‐aligned, myonuclear deformability was restored, and stress production and the resulting injury response was also returned to near‐wildtype levels in a dose‐dependent, although nonlinear manner. Furthermore, the stretch‐induced activation of JNK phosphorylation, which was not detectable in the DKO muscles, was restored. These results demonstrate that the desmin intermediate filament is primarily responsible for the spatial alignment of Z‐disks and plays a central role in transducing mechanical stress: (1) from the force‐generating cytoskeletal network to the surrounding tissue and (2) to the intracellular signaling apparatus.Supported by NIH and Department of Veterans Affairs.
Physiopathological characterization of the venom of the freshwater stingray Potamotrygon sp C
Authors: dos Santos Juliane Monteiro , Santos Janaina C. , Lopes Monica F. , Marques Elineide E. , Seibert Carla S. 
Published: June 2021

Freshwater stingrays are benthic animals that almost always behave passively and preferentially inhabit shallow water. Their tail barb is rigid and serrated, and is covered by glandular epithelium. Injury from the barb is followed by local symptoms such as bleeding, intense throbbing pain, and edema in the affected member. Nausea, salivation, convulsion, and tachycardia are reported systemic changes. The Potamotrygon sp. C is stingray species most often encountered in rivers of the state of Tocantins, Brazil.ObjectiveTo evaluate the physiopathological changes induced by poisoning caused by Potamotrygon sp. C.MethodsMucus was removed from the epithelial tissue at the barb and from the disc of the animal (far from the barb), and an extract was prepared from the glandular epithelium that covers the barb and analized. Different concentrations of this material (25, 50, 100 μg/ml) were used to evaluate the edematogenic, nociceptive, hemorrhagic, and necrotic effects in male and female Swiss mice.ResultsThe nociceptive and edematogenic activity was dose‐dependent, with the most intense response observed for the mucus collected from the disc. No hemorrhagy was observed, and necrosis was limited to small dots on the tissue evaluated.ConclusionIt was evident that the greatest changes caused by poisoning with Potamotrygon sp. C are related to contact of the barb‐injured tissue with the mucus that covers the animal.
Development of a sleeve gastrectomy weight‐loss surgical model in obese Zucker rats
Authors: Lopez Peter P , Nicholson Susannah E , Burkhardt Gabriel E , Johnson Robert A , Johnson Fruzsina K 
Published: June 2021

Obesity promotes the development of diabetes and cardiovascular disease. The most effective weight‐loss treatment is bariatric surgery, but results greatly vary by procedure. Recently, sleeve gastrectomy (SG) has emerged as a safe weight‐loss procedure for super obese patients. However, the mechanism of weight‐loss by SG and its effects on obesity‐induced complications are yet to be determined. Our goal was to develop an experimental model of SG in genetically obese rats. Male obese Zucker rats (400–500g, leptin‐insensitive) were anesthetized with isoflurane. After a midline laparotomy, the stomach was clamped, the greater curvature was excised and a triple suture line was used to close the gastric remnant. Sham rats underwent laparotomy only. Metabolic parameters were followed for 14 days after surgery. Caloric intake (SG: 136.0±4.4 to 29.2±8.2 vs sham: 134.5±4.9 to 102.5±2.6kcal/day) and body weight (Δmax SG: −88±14 vs sham: +63±5g) decreased in SG rats over 14 days. Blood total and LDL cholesterol levels were lower in rats that lost weight (total SG: 120±10 vs sham: 214±23mg/dL) (LDL SG: 67±9 vs sham: 169±17mg/dL). Furthermore, blood glucose (SG: 145±20 vs sham: 246±23mg/dL) and insulin (SG: 4.1±0.4 vs sham: 5.8±1.0ng/mL) levels were lower in rats that lost weight. These results show that SG promotes weight‐loss in obese Zucker rats. Furthermore, SG‐induced weight‐loss is accompanied by improved plasma cholesterol and glucose/insulin profile. These results suggest that SG is an effective weight‐loss procedure in leptin‐insensitivity to improve the lipid profile and decrease insulin resistance.Supported by NIH grant HL64577 (RAJ) and in‐house funds (PPL).
Resuscitation with hydroxyethyl starch 130/0.4 versus lactated Ringer on hemorrhage following a liver trauma in swine
Authors: Zaar Morten , Lauritzen Brian , Secher Niels H. , Krantz Torben , Johansson Pär I. 
Published: June 2021

Background: The effect of resuscitation fluids on hemorrhage remains disputed. This study evaluated the effect of resuscitation with hydroxyethyl starch 130/0.4 versus lactated Ringer on hemorrhage in a pig liver trauma model.Methods: A grade III crush and avulsion liver injury was inflicted on the left lateral lobe and, to simulate a pre‐hospital setting, resuscitation began after 7 min: phase 1, 0.7 mL kg−1 min−1 for 10 min; phase 2, 1.65 mL kg−1 min−1 for 20 min; and phase 3, according to the blood loss. Initial resuscitation was with hydroxyethyl starch 130/0.4 or lactated Ringer while in phase 3 it was with hydroxyethyl starch 130/0.4, and lactated Ringer was also evaluated for a grade IV laceration liver injury.Results: With a grade III liver injury, initial resuscitation with hydroxyethyl starch 130/0.4 (n=5) caused progressive bleeding and exsanguination after ~75 min, while lactated Ringer (n=5) elicited a slow bleeding that ceased after ~45 min. With a grade IV injury (n=5), initial resuscitation with lactated Ringer caused exsanguination after ~75 min.Conclusion: For a mild liver injury, initial resuscitation with hydroxyethyl starch 130/0.4 appeared to provoke uncontrolled hemorrhage, while hemostasis was achieved in animals resuscitated with lactated Ringer. In contrast, hemostasis was not achieved in animals with a severe liver trauma and resuscitated with lactated Ringer.
Impact of natural and industrial trans fatty acids consumption on HDL metabolism
Authors: Grenier Geneviève , Motard‐Bélanger Annie , Charest Amélie , Clerc Élise , Paquin Paul , Chouinard Yvan , Lemieux Simone , Couture Patrick , Lamarche Benoit 
Published: June 2021

Unlike dietary industrial trans fatty acids (iTFA), which are known to increase the risk of cardiovascular disease (CVD) through adverse modifications of blood lipids, the impact of dietary trans fatty acids from ruminants (rTFA) remains unknown. The purpose of the present study was to compare the effects of iTFA and rTFA on in vivo HDL metabolism. According to a double‐blind, randomized crossover controlled study design, 9 healthy men were fed each of 3 experimental 5‐week isoenergetic diets: 1‐ high in iTFA (10.2 g/2500 kcal), 2‐ high in rTFA (10.2 g/2500 kcal) and 3‐ a control diet low in TFA (2.2 g/2500 kcal). Apolipoprotein (apo) A‐I kinetic was investigated after each diet after administration of D3‐Leucine in the fasted state. The fractional catabolic rate (FCR) and production rate (PR) of apo A‐I were significantly higher after the diet rich in iTFA than after the control diet (+12.9% and +12.6% respectively, p=0.03). No significant change in apo A‐I FCR and PR were observed after the diet rich in rTFA. When analysing all 3 diets, the apo A‐I FCR was a strong correlate of on‐diet plasma HDL‐C concentrations (r=−0.50, p=0.008). This kinetic study of apo A‐I suggested that a high consumption of rTFA may not significantly modify HDL in vivo kinetics.Supported by grants from the Dairy farmers of Canada, Novalait and the Canada Research Chair in nutrition and Cardiovascular Health.
Use of Dietary Supplements at Baseline is Similar across Ethnic Groups: Results from the SURE Study
Authors: Monroe Kristine Robinson , Wilkens Lynne , Yonemori Kim , Morimoto Yukiko , Steffen Alana , Shen Lucy , Murphy Suzanne 
Published: June 2021

Errors in reporting supplement intake in nutritional epidemiology studies have not been evaluated. The Supplement Reporting (SURE) Study is evaluating the most common methods of collecting dietary supplement use data. We present here cross‐sectional data reported on a supplement frequency questionnaire in the five racial/ethnic populations participating in the study: Caucasians, Japanese Americans, Native Hawaiians, African Americans, and Latinos divided into two comparison groups (US‐born and non‐US‐born) to study the effect of acculturation on supplement use practices. The questionnaire asked about the different types of multiple vitamin preparations and the common single vitamins including selenium, iron, zinc, fish oil and garlic.Subjects are members of the Multiethnic Cohort who reported regular use of at least one dietary supplement (n =1,109). In general, baseline supplement use practices were similar across ethnic groups. A multivitamin with minerals was reported most often (55% of subjects) followed by calcium, vitamin C, and vitamin E. Significantly fewer Caucasians and Japanese Americans reported use of iron and significantly more African Americans and non‐US‐born Latinos report use of garlic.Future analyses, using more detailed instruments, will compare supplement use across ethnic groups to determine if the homogeneity of use persists. Supported by NCI, grant # R01 CA106744.
mRNA control: PUF repressors and GLD2 activators
Authors: Wickens Marvin 
Published: June 2021

Eukaryotic mRNAs often are controlled by regulatory elements in their 3’UTRs. Repressors bind those elements and turn down expression, either by affecting mRNA stability, translation, or both. Other proteins bind to the 3’UTR and enhance expression. The two families of proteins we will focus on – PUF protein repressors and GLD2 activators – have key biological roles, both in stem cells and in the nervous system.Among repressors, we will focus on the PUF proteins. We will discuss how these proteins interact with RNA and exclusively bind to their cognate sites. The modularity of the interaction and the key role of spacer nucleotides in recognition are key features of these RNA‐protein interaction. PUF proteins achieve repression via their interaction with POP2, indirectly recruiting factors involved in decay, repression and deadenylation. Multiple PUF proteins regulate a single mRNA, providing versatility in control.Among activators, we will focus the GLD2 family of poly(A) polymerase. Initially discovered in C. elegans, we have now identified members in many eukaryotic species, including mammals. Members of this family activate expression by extending the poly(A) tail. We will emphasize new biological roles of these enzymes, and their interactions with members of the PUF protein system.
Transition state analogues, purine salvage, cancer and malaria
Authors: Schramm Vern L. 
Published: June 2021

Transition state theory proposes that chemically stable mimics of the transition state will bind more tightly than substrates by the rate acceleration factor imposed by the enzyme, typically 1010 to 1015 fold. Transition state structures of enzymatic targets for cancer and malaria have been explored by the systematic application of kinetic isotope effects and computational chemistry. Analogues of the transition states deduced by these methods bind up to 107 times tighter than substrate. Using these methods, three generations of transition state analogues have been produced for human purine nucleoside phosphorylase (PNP) and two of these are in clinical trials. Transition state analogues of human 5′‐methylthioadenosine phosphorylase show promise as anticancer agents in mouse xenografts. Inhibition of S‐adenosylmethionine recycling and DNA methylation are implicated in the anti‐cancer effect. Malaria parasites are purine auxotrophs and require parasite‐specific PNP and adenosine deaminase in the purine salvage pathway. Powerful and parasite‐specific transition state analogues were designed against both malarial PNP and adenosine deaminases. These inhibitors cause purine starvation (purine‐less death) in parasites cultured in human erythrocytes. Application of kinetic isotope effects and transition state have permitted synthesis of some of the most powerful enzymatic inhibitors.Supported by GM41916 and AI49512.
Relations of dietary type of protein, glutamine, and glutamate to the incidence of type 2 diabetes mellitus among middle‐aged women
Authors: Lenders Carine , HU Frank B , Willett Walter C , Douglas Wilmore W , Sampson Laura , Dougherty Lauren , Spiegelman Donna , Liu Simin 
Published: June 2021

Objective: To examine the relations of types of protein, glutamine, and glutamate to the incidence of diabetes (T2DM) among middle‐aged women.Methods: We identified incident cases of T2DM among 70,356 nurses free of T2DM and major chronic diseases at baseline, 1984–2002. Dietary habits were assessed using food frequency questionnaires. Cox proportional hazard models were used. Risk was considered significant at p for trend value<0.05.Results: During the 18‐years follow‐up (1,115,620 person‐years), we documented 3,804 new cases of T2DM. After adjusting for demographic and lifestyle variables, T2DM was not associated with total protein RR=0.88[0.78;1.00], p =0.14), animal protein (RR=0.96[0.85;1.09], p=0.77), and glutamate (RR=0.88[0.77;1.00], p=0.10). Although plant protein was inversely associated with T2DM in the multivariate model (RR=0.88 [0.78;1.00], p=0.03), this relationship appeared to be explained by cereal fiber (RR=0.97[0.85;1.11], p=0.64).Glutamine was also inversely associated with T2DM in the multivariate model (RR=0.81[0.72;0.91], p<0.001). In further analysis, glutamine was inversely related to T2DM independent of cereal fiber (RR=0.87 [0.77;0.99], p=0.02) and total protein (RR=0.79 [0.69;0.90], p=0.0002).Conclusions: Study findings suggest a significant modest inverse relation of glutamine with T2DM independent of total protein.
These spaces have great potential: teaching students about anatomical potential spaces.
Authors: Dalley Arthur F. 
Published: June 2021

Potential anatomical spaces are vital to normal, pain free function of the heart, lungs, and locomotor system. They are also the basis for extraluminal endoscopic procedures. However, understanding potential spaces can be challenging. In dissection, potential spaces such as bursae and tendon sheaths are usually unnoticed. Others, such as the pleural and pericardial sacs, are viewed only after they have been opened, making them into realized spaces more representative of pathological states.Difficult concepts include: (1) an “empty space,” containing only a capillary layer of lubricating fluid, (2) a structure being surrounded by (but not within) a potential space, (3) the ability of moist potential spaces to provide adherence and enable low‐friction movement at the same time, in the presence of positive or negative pressure, (4) parietal and visceral layers that are continuous layers of the same sac, and (5) the effect of actualization (interruption of surface tension), as in atelectasis.Illustrations are helpful but require misleading exaggeration. Simple tools for better demonstrating concepts include large balloons, plastic bags, calculator paper, glass slides, “water wiggler” toys, and–for dissections–a syringe with injectable colored fluid.