bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shear stress increases NO production by thick ascending limb cells
Authors: Garvin Jeffrey L. , Hong Nancy J. 
Published: June 2021

Luminal flow induces NO production in the thick ascending limb (TAL) by activating the enzyme that produces NO, NOS3. Shear stress, cellular stretch and transmural pressure all change when flow increases. Shear stress stimulates NO production in endothelial cells and inner medullary collecting ducts. However, it is unclear whether flow‐induced NO production in TALs is mediated by increases in shear stress, stretch or pressure. We hypothesized that shear stress acts as a mechanical stimulus for NO production in the TAL. We subjected primary cultures of rat TAL cells to shear stresses of 0.02 (low shear stress; LSS) and 0.55 dyne/cm2 (high shear stress; HSS) and measured intracellular NO using the fluorescent dye DAF‐2 DA. The rate of increase in dye fluorescence is indicative of NO production. TAL cells under LSS produced NO at a rate of 55 ± 10 AU/s. NO production increased to 315 ± 93 AU/s at HSS (p < 0.03, n = 7). Pre‐treatment with the NOS inhibitor L‐NAME (5 mM) inhibited the shear stress‐induced increase in NO production (44 ± 24 vs. 48 ± 12 AU/s for LSS and HSS, respectively; n = 6). The PI3‐kinase inhibitor wortmannin (150 nM) also blocked NO production stimulated by increased shear stress (26 ± 9 AU/s for LSS vs.27 ± 8 AU/s for HSS; n = 5). We conclude that increases in shear stress mediate flow‐induced NO production by NOS via the PI3‐kinase pathway. Changes in flow may play an important role in regulation of TAL function by NO.Research support: NIH Grants HL 28982 and HL 70985
Preservation of renal function in the obese Zucker rat by antioxidant diet
Authors: Inman Sharon Ruth , Jackson Edwin , Oshogwemoh Olusayo , Slyvka Yuriy , Nowak Felicia V 
Published: June 2021

Type 2 diabetes accounts for 90–95% of all diabetes mellitus and is the worldwide leading cause of end‐stage renal disease (ESRD). The obese Zucker rat model of Type 2 diabetes was used to determine the gender differences of ESRD and effect of administration of an antioxidant (AO) diet on the progression of ESRD. Male and female obese Zucker rats (fa/fa) were studied at 13 and 20 weeks of age on regular (REG) and AO diets.Disease progression was determined by blood glucose, mean arterial pressure (MAP), and glomerular filtration rate (GFR). The AO diet had effects on GFR, MAP and blood glucose in female rats. GFR in 20 week old females on the AO diet was higher than in rats on the REG diet (0.346 ± 0.098 vs 0.053± 0.031 ml/min, p=0.028). This difference was not observed in males. MAP in females at 20 weeks was lower on the AO diet than on the REG diet (121.5±5.8 vs 146.2±1.7 mm Hg, p=0.02). The data also suggest that the AO diet lowers blood glucose in 13 week female rats (371.3±81.1 vs 688.3±31.9 mg/dl, p=0.005). A sex difference was also observed. MAP was higher in males at 20 weeks than in females, on both AO and REG diets.Conclusion: An AO diet preserves several important parameters in obese Zucker rats, including GFR, MAP and blood glucose. The effect was more significant in females.Supported by NIH R15 DK073066 to SRI and FVN
Evidence that brain L‐arginine availability modulates heat loss during physical exercise in rats
Authors: Wanner Samuel Penna , Leite Laura Hora Rios , Marubayashi Umeko , Coimbra Cândido Celso 
Published: June 2021

We investigated the effects of increased brain L‐arginine (precursor of nitric oxide synthesis) availability on thermoregulatory adjustments and physical performance in rats during exercise (18 m.min‐1 and 5% inclination) until fatigue. Under anesthesia with ketamine and xylazine, male Wistar rats received implants of a guide cannula into the right lateral cerebral ventricle and of a temperature probe into the peritoneal cavity. On the day of the experiments, core (Tb) and tail skin temperatures were measured while the rats were running after injection of 2 μL of either NaCl 0.15 M (Sal, n = 11) or L‐arginine solution (L‐arg: 0.82 M, n = 6; 1.65 M, n = 6, and 3.30 M, n = 5) into the cerebral ventricle. Heat storage rate and threshold Tb for tail vasodilation (TTbV) were calculated. L‐arg injection induced a dose‐dependent reduction in the TTbV and heat storage rate (3.23 ± 0.84 cal.min−1, L‐arg 3.30 M; 6.46 ± 1.12 cal.min−1, L‐arg 1.65 M; 8.59 ± 0.95 cal.min−1, L‐arg 0.82 M; 9.54 ± 0.94 cal.min−1, Sal; p<0.05). Although the lower Tb at fatigue point, treatment with L‐arg failed to change exercise performance (25.7 ± 3.5 min, L‐arg 3.30 M; 25.7 ± 2.4 min, L‐arg 1.65 M; 26.4 ± 2.9 min, L‐arg 0.82 M; 26.9 ± 1.7 min, Sal). These results indicate that brain nitric oxide transmission modulates heat loss during exercise, probably by reducing sympathetic vasoconstrictor tonus to skin vessels.Supported by: CNPq, FAPEMIG e CAPES.
Effect of central application of 17‐β estradiol on thermoregulation during a cold exposure in female rats
Authors: Uchida Yuki , Tokizawa Ken , Nagashima Kei 
Published: June 2021

BACKGROUNDWe reported that, in ovariectomized rats, thermoregulation in the cold was attenuated. However, systemic administration of 17‐β estradiol (E2) restored the response. Moreover, E2 increased cFOS immunoreactive cells in the medial preoptic area (MPO) and dorsomedial hypothalamus (DMH) in the cold.PURPOSETo test the hypothesis that E2 augments central thermosensitivity to the cold, we assessed the effect of the local administration of E2 to the two hypothalamic areas on body temperature (Tb) in the cold.METHODSAdult female rats were ovariectomized, and a stainless steel canula was placed in the MPO, DMH, or horizontal limb diagonal band. At least 7 days after the surgery, E2 or cholesterol was administrated to this brain area through the canula. Forty‐eight hours after the administration, a rat was exposed to 10°C or 25°C environment for 2h, and Tb was measured by telemetry.RESULTSDuring the 10°C exposure, Tb increased only in the group, which was administrated E2 in the MPO. Either cholesterol nor E2 in the other brain area had no effect on Tb.CONCLUSIONThe MPO has abundant estrogen receptors and so‐called thermosensitive neurons, estrogen may modulate thermosensitivity to the cold in the MPO.
Role of human brown adipose tissue in adaptive thermogenesis
Authors: van Marken Lichtenbelt Wouter D , Vanhommerig Joost W , Smulders Nanda M , Teule G J Jaap 
Published: June 2021

Individual variation in cold adaptive thermogenesis can potentially be attributed to sympathetic nervous innervation of brown adipose tissue (BAT). In humans BAT was thought to be present only in infants. Recent results from PET‐CT scans indicate that adults may have significant amounts of active BAT.The objective is to study the relation between presence and activity of BAT and the level of cold induced thermogenesis in humans.Male volunteers (age: 24.3±3.5 y; length: 181±5.5 cm; weight: 75±4.3) were examined for presence and/or activity (standardized uptake value) of BAT during cold exposure by means of 18F‐FDG PET‐CT. In a climate chamber thermoneutral (1 h; 22 °C) condition is compared to mild cold (2 h; 16 °C). Increase in resting metabolic rate (RMR) as measured by indirect calorimetry is compared to the BAT data.Six subjects have currently been measured. RMR (mean 4.07±0.42 kJ/min) increased between 1.5 and 25 %, depending on the subject. Five subjects showed significant amounts of BAT, especially in the supra‐clavicular region. One showed no sign of BAT.This study shows high prevalence of BAT in young adult human males and will relate cold induced thermogenesis to BAT activity.
NAD(P)H oxidase inhibition upregulates anti‐apoptotic BAG‐4 protein expression in the mdx diaphragm
Authors: Kim Jong‐Hee , Kwak Hyo‐Bum , Lawler John M 
Published: June 2021

Duchenne muscular dystrophy (DMD) is the most devastating type of MD resulting in oxidative stress, muscle damage, weakness, and wasting in locomotor and respiratory (e.g., diaphragm) muscle. Previously, we showed that apocynin, a NAD(P)H oxidase inhibitor, protects against reduction in diaphragm mass, oxidative capacity, and apoptosis in 3–4 week old mdx mice. BAG family proteins regulate cell survival and contain a conserved domain binding Bcl‐2, TNF‐R1 and HSP70. We hypothesized that apocynin (1.5mmol/L per day) would upregulate BAG‐1, BAG‐4, and HSP70, while decreasing TNFR1 in the mdx diaphragm. Eight to nine weeks old mdx mice and age‐matched C57BL wild‐types were divided into 4 groups: wild‐type controls + water (WW, n=7); wild‐type controls + apocynin (WA, n=7); mdx mice + water (MW, n=7), and mdx mice + apocynin (MA, n=7). After 7 days of treatment, diaphragm and gastrocnemius muscle were extracted. BAG‐4 levels were significantly higher in MA than MW, whereas BAG‐1 levels remain unchanged both WA and MA. TNFR1 levels were significantly lower in WA compared to WW. HSP70 levels were elevated in mdx mice with and without apocynin. Cleaved caspase‐3 was elevated in the mdx diaphragm, but reduced with apocynin. Our data suggest that apocynin may foster cell protection in the mdx diaphragm via BAG‐4 signaling.Supported by a grant from NIH (AR054084)
D‐Glucose increases the expression and activity of hCAT‐1 and Sp1 binding to SLC7A1 promoter in human umbilical vein endothelium
Authors: González Marcelo , Farías Marcelo , Casanello Paola , Sobrevia Luis 
Published: June 2021

L‐Arginine is mainly transported by the human cationic amino acid transporter 1 (hCAT‐1, protein codified by the gene SLC7A1) in human umbilical vein endothelial cells (HUVEC). hCAT‐1 mediated L‐arginine transport and nitric oxide (NO) synthesis are increased by 25 mM D‐glucose in this cell type. Since Sp1 is a transcription factor activated by NO, we studied whether high D‐glucose effect on transport was due to altered expression of hCAT‐1 and abundance and activity of the transcription factor Sp1 in primary cultures of HUVEC. D‐Glucose (25 mM, 24 hours) increased (~3.2 fold) the maximal velocity (Vmax), without altering the apparent Km, of L‐arginine transport compared with cells in 5 mM D‐glucose. High D‐glucose also increased the hCAT‐1 mRNA number of copies (~5‐fold) and protein abundance (~2‐fold), and Sp1 nuclear abundance and binding to SLC7A1 promoter region (−177 to −103 bp from ATG). Thus, the stimulatory effect of D‐glucose on L‐arginine transport could result from increased expression of hCAT‐1 due to increased activity of Sp1 on the promoter of SLC7A1 in HUVEC.Supported by FONDECYT 1070865, VRAID BM16/2007. MG holds a CONICYT PhD fellowship and PhD Thesis Support grant (CONICYT 23070213).
Essential Role of Cofilin‐1 and mDia1 in Regulating Thrombin‐Induced Actin Dynamics and RelA/p65 Nuclear Translocation in Endothelial Cells
Authors: Fazal Fabeha , Bijli Kaiser M , Minhajuddin Mohammad , Finkelstein Jacob N , Rahman Arshad 
Published: June 2021

Activation of the small GTPase RhoA and associated changes in actin dynamics control thrombin‐induced NF‐κB activation and ICAM‐1 expression in endothelial cells. However, the events acting downstream of RhoA to mediate the changes in actin dynamics required for NF‐κB activation and ICAM‐1 expression remain unclear. Here we show that thrombin engages cofilin 1 and mDia1 downstream of RhoA to regulate these responses in endothelial cells. Stimulation of human umbilical vein endothelial cells with thrombin resulted in Ser‐3 phosphorylation/inactivation of cofilin in a ROCK‐dependent manner. RNAi knockdown of cofilin‐1 stabilized the actin filaments and prevented thrombin‐ and RhoA‐induced NF‐κB activity. In parallel experiments, knockdown of mDia1 destabilized the actin filaments and inhibited thrombin‐ and RhoA‐induced NF‐κB activity. Inhibition of NF‐κB activity and ICAM‐1 expression following stabilization and destabilization of actin filaments by these approaches occurred downstream of IκBα degradation and was associated with impaired RelA/p65 nuclear translocation and consequently, RelA/p65 binding to DNA. These findings support the notion thatspecific alterations in actin dynamics induced by thrombin are mediated by concerted actions ofcofilin‐1 and mDia1 and are necessary for RelA/p65 nuclear localization, and thereby ICAM‐1 expression in endothelial cells.This abstract is funded by: ALA, NIH HL067424.
Scaling of the retinogeniculostriate pathway in mammals
Authors: Willms Jonathan , Heesy Christopher Paul 
Published: June 2021

Studies of the relative sizes of brain components in mammals suggest that areas responsible for sensory processing, including visual processing, are correlated with aspects of ecology. Primate orbit convergence and binocular vision are correlated with overall size of the brain as well as components of the visual pathway, such as the lateral geniculate nucleus. The question remains whether components of the visual pathway (optic tract, lateral geniculate nucleus, and primary visual cortex) are similarly correlated in non‐primate mammals.This study examines the relationship between orbit convergence, binocular field overlap, overall brain size, and the volumes of components of the visual pathway. Data on orbit orientation are combined with those on overall brain size in primates, and non‐primate mammals. In addition, data on brain component volumes were collated for a subset of these taxa. Volumetric data on neural components of the visual pathway are correlated with convergence among the taxa included in this study. Binocular taxa have relatively larger optic tracts, lateral geniculate nuclei and primary visual cortices when brain volume is held constant. Primates are not unique in the relationship between binocularity and brain size; however, since primates are the most binocular of the mammals, they also have the relatively largest components of the visual pathway.
Double tendon of the Human Extensor Indicis Muscle provides “insight' into individual development
Authors: Kumka Myroslava 
Published: June 2021

Methods: This study utilized 16 embalmed cadavers (32 upper limbs) of both sexes and of different ages using traditional anatomical macro‐micro dissections.Summary of results: The variant of the Extensor Indicis (EI) muscle: double tendon to index and middle fingers, was found in one female cadaver, bilaterally. The narrow, elongated muscle belly of EI attached to the posterolateral surface of ulna, the adjacent interosseus membrane and the deep antebrachial fascia. The lateral part of the EI muscle belly became tendonous at the inferior third of the forearm while that of the medial part occurred at the superior border of the extensor retinaculum. Both tendons passed deep to the extensor retinaculum to join with the ulnar sides of the tendons of the extensor digitorum forming the extensor expansion for the index and middle fingers. It was observed that the muscle belly of this anomalous muscle was innervated by branches of the deep radial nerve in the inferior third of forearm. The double EI tendon appears to be a developmental variant of the normal migratory pattern of myogenic cells known to occur during embryogenesis of the upper limb.Conclusion: Our finding supports the hypothesis that the double EI muscle tendon variant may result from early splitting of EI muscle primordium during morphogenesis and may serve to enhance tightness of grip and functional independence to the index and middle fingers.No external support.
Origin and prevalence of allergy to the Asian beetle Harmonia axyridis
Authors: Graue Hayley , Quinn Tim , Barnes Charles , Herndon Betty 
Published: June 2021

The imported Asian lady beetle Harmonia axyridis has been added to the list of allergens derived from insects. These pests hibernate in warm structures during winter, and some exposed humans respond to this beetle antigen with positive skin prick tests and show elevated immunoglobulin E. One report suggests the allergen is a secreted stress chemical, beta caryophyllene.To study occurrence and source of the allergies, lady beetles were collected and stored at ‐70°C. A local allergy clinic provided 48 unselected serum samples without patient data. These sera were tested for IgE and IgG reactivity by ELISA to both beetle protein extract and the purified stress protein caryophyllene.Crude lady beetle protein extract was prepared as a sterile filtrate of homogenized beetles containing 1.5 mg/mL protein. Caryophyllene was diluted to 1 mg/mL. Antibody capture ELISA utilized incubation of serum dilutions on plates coated with the beetle antigens followed by peroxidase coupled anti‐IgG or IgE. Peroxidase substrate (DAB) was read at 450 nm. IgG titers for crude protein vs. stress chemical were unrelated p=0.46, but serum IgE titers of the two antigens showed a correlation (p=0.005). Three samples of the 48 showed IgG and/or IgE reactivity against beetle extract but not caryophyllene, suggesting broad insect protein allergy.Allergy against Asian lady beetles was not high in this urban population; 2% were highly reactive and 6% somewhat reactive, which is lower than agrarian reports. The data overall suggest that insect stress chemical exposure may contribute to the human allergic response to lady beetles over‐wintering in human habitations.
Synthesis of aldosterone in the brain contributes to the hypertension in the Dahl salt sensitive rat
Authors: Gomez Sanchez Elise Peery , Gomez‐Sanchez Clara M , Gomez‐Sanchez Celso E 
Published: June 2021

Despite low or normal plasma aldo levels, the salt‐induced hypertension in Dahl SS rats is mitigated by the same pharmacological maneuvers and brain ablations that prevent mineralocorticoid‐salt excess hypertension. We found that all enzymes required for de novo synthesis of aldo are expressed in rat and human brain and that aldo is synthesized in the normal rat brain in vivo and in vitro in quantities that suggest autocrine or paracrine functions. mRNA for aldo synthase was measured by real time RT‐PCR and aldo by an extraction/ELISA assay in brains. SS rat brains had significantly greater amounts of aldo synthase mRNA in the brain stem, hypothalamus, hippocampus and cerebellum and aldo concentrations compared to control brains, though SS plasma aldo levels tended to be lower. The central infusion of the specific aldo synthase enzyme inhibitor, FAD286, significantly and reversibly lowered the blood pressure of SS rats. Many hypertensive patients benefit from MR antagonists, even though plasma levels of aldo are normal to low. As MR are most abundant in the hippocampus, where they mediate trophic responses necessary for learning and memory, it is important to determine the relevance of this model to human hypertension and devise more specific methods of blood pressure control.This work was supported by Medical Research funds from the Department of Veterans Affairs and NIH grants HL27255 and HL75321.
Serum aldosterone regulation, blood pressure response to high salt intake and renal function and structure in adult female offspring are modified by salt overload during pregnancy
Authors: Rodrigues Edson Nogueira Alves , Oliveira Ivone B. , Furukawa Luzia NS. , Ferreira Daniele N. , Coelho Michella S. , Heimann Joel C. 
Published: June 2021

ObjectiveTo evaluate the effects of high salt intake during pregnancy on blood pressure (BP), renal function and structure and serum aldosterone levels in adult female offspring (off).MethodsFemale Wistar rats were fed normal (NS, 1.3%) or high (HS, 8% NaCl) salt diet during pregnancy. During lactation all dams received NS as well as the off from weaning until the 21st week of age. Starting on the 21st week of age, 50% of each off group was fed high (hs, 4% NaCl) salt diet during 15 weeks.Results (mean ± SEM, p<0.05, n=5‐8/groups)Tail‐cuff BP (TcBP, mmHg) was not different between HS (109±5) and NS (105±2) off groups. However, TcBP was higher in HShs (117±4) compared to NShs (106±2). Kidney weight (g/kg) was higher in HShs (3.7±0.1) compared to HS (3.3±0.1) but not in NShs (3.5±0.1) compared to NS (3.4±0.1). Twenty‐four hour urinary protein excretion (mg/100g/day) was higher in HShs (0.9±0.1) compared to HS (0.5±0.05) but not in NShs (0.7±0.03) compared to NS (0.6±0.09). Serum aldosterone (pg/ml) was lower in NShs (824±62) compared to NS (1128±11) but was not different between HShs (919±60) and HS (988±172) off groups.ConclusionsHS during pregnancy is associated with BP and renal abnormalities in adult female off. Adult off from HS dams are hyperresponsive to salt overload possibly due to an alteration of the regulation of serum aldosterone.Supported by CNPq.
PKC modulation of neurovascular coupling
Authors: Vetri Francesco , Xu Hao Liang , Pelligrino Dale Alan 
Published: June 2021

Protein kinase C (PKC) has been shown to phosphorylate several ion channels involved in neurovascular coupling. Therefore, we sought to assess whether PKC is involved in the regulation of neurally‐evoked pial arteriolar dilation. Using a closed cranial window technique for vessel diameter monitoring, we studied pial arteriolar dilations during sciatic nerve stimulation (SNS) in rats. Topical application of the PKC non‐isoform specific agonist phorbol 12,13‐dibutyrate (PdBu), was able to significantly reduce the dilatory response to SNS. We previously found that a substantial portion of SNS‐induced arteriolar dilation is mediated by the release of K+ from glia limitans large‐conductance Ca2+‐operated K+ (BKCa) channels, which, in turn, activate pial arteriolar smooth muscle inward rectifier K+ (Kir) channels. Both, BKCa and Kir channels can be phosphorylated by PKC. Thus, we compared BKCa and Kir ‐induced vasodilating function in the presence and absence of PdBu. The reactivity to topical applications of the BKCa channel opener, NS1619, and the Kir agonist, KCl, was found to be significantly decreased when the drugs were co‐applied with PdBu. However, responses to adenosine, SNAP, and hypercapnia were not affected by PdBu suffusion, ruling out the possibility of non‐specific effects. These results point to a significant involvement of PKC in regulating the gliovascular mechanisms underlying neurovascular couplingThis work was supported by grant 3‐2008‐462 from Juvenile Diabetes Research Foundation (JDRF) to F.V., NIH grant HL088259 to D.A.P. and American Heart Association grant 0635337N to H.L. Xu
New connections linking sorting & trafficking of VEGFR2 from Golgi with angiogenesis
Authors: Choudhury Amit , Manickam Venkatraman , Tiwari Ajit , Sierra Ana , Bhattacharya Resham , Pagano Richard E. , Mukhopadhyay Debabrata 
Published: June 2021

Vascular endothelial growth factor receptor‐2 (VEGFR2) plays a key role in vasculogenesis and pathophysiological angiogenesis. Cell surface levels of VEGFR2 is regulated by endocytosis and secretory transport of newly synthesized receptors to the plasma membrane. The mechanism of VEGFR2 sorting and trafficking along the secretory pathway is not well defined. In the present study, using human endothelial cells we demonstrate that sorting and trafficking of VEGFR2 from the Golgi is regulated by syntaxin 6, a t‐SNARE involved in intra‐Golgi and post‐Golgi membrane fusion events. Loss of syntaxin 6 function results in altered sorting of VEGFR2 from the Golgi resulting in receptor down regulation. Our data support a model in which syntaxin 6 regulates delivery of VEGFR2 from the Golgi apparatus to the cell surface thereby regulating VEGF‐A‐induced endothelial cell proliferation, migration, and morphogenesis.Grant Funding SourceNIH