bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blockade of P2X purinergic receptors of the lateral parabrachial nucleus reduces hypoxia‐induced tachypnea
Authors: Menezes Miguel Furtado , Menani José Vanderlei , De Paula Patrícia Maria 
Published: June 2021

In the present study, we investigated the involvement of the purinergic receptors of the lateral parabrachial nucleus (LPBN) on cardiorespiratory responses induced by hypoxia (HYP) in awake rats. Male Holtzman rats (290–310 g, n=9) with cannulas implanted in the LPBN were used. Mean arterial pressure (MAP), heart rate (HR) and ventilation (VE) were recorded before and after bilateral injections of saline (SAL) or PPADS (a selective P2X purinergic receptor antagonist) into the LPBN under normoxia (NORM, 21% O2) or HYP (7% O2). HYP reduced MAP (95±2 mmHg, vs. NORM: 100±1 mmHg, p<0.05) and increased HR (438±10 bpm, vs. NORM: 396±6 bpm, p<0.05) and VE (1026±84 ml/min/kg, vs. NORM: 620±62 ml/min/kg, p<0.05). Bilateral injections of PPADS (4 nmol/200 nl) into the LPBN in HYP reduced the increase of respiratory frequency (fR, 10±6 cpm, vs. SAL: 28±5, p<0.05) and slightly increased tidal volume (VT, 2.3±0.5 ml/kg, vs. SAL: 1.7±0.6 ml/kg, p>0.05), without changing VE (896±96 ml/kg/min, vs. SAL: 795±74 ml/kg/min). Bilateral injections of PPADS into the LPBN did not change MAP and HR in HYP and VE, MAP and HR in NORM. The results suggest that the reduction of HYP‐induced tachypnea by the blockade of purinergic receptors into the LPBN is counterbalanced by the increase in VT and, therefore, HYP‐induced hyperventilation is not affected, suggesting that activation of purinergic receptors in the LPBN facilitate HYP‐induced tachypnea.Supported by FAPESP, CAPES and CNPq
Quantifying the ellipticalness of the lateral femoral condyle in Gorilla, Pan and Homo
Authors: Sylvester Adam David 
Published: June 2021

Articular surfaces of limb bones are thought to be informative for understanding animal locomotion because their size and shape are related to habitual postures and movements. Here I present a method for quantifying an aspect of the shape of femoral condyles, applying this technique to hominid femora.Three‐dimensional surface models were created for 50 modern human, 30 chimpanzee and 29 gorilla femora. Software was developed that fit separate cylinders to each of the femoral condyles. These cylinders were constrained to have a single longitudinal axis, but could have different radii. The cylinder fit to the lateral condyle was allowed to assume an elliptical cross‐section. The shape of the elliptical cylinder (ratio of the axes of the ellipse) and the angle between the major axis of the ellipse and the femoral shaft were measured. Species were compared using ANOVA and post hoc multiple comparisons tests.Human lateral femora condyles are more elliptical than those of chimpanzees (p<0.01) and gorillas (p<0.01), however the latter two do not differ. Human femora exhibit a narrow range of the angle between the elliptical cylinder and the femoral shaft (80–110 degrees). Most chimpanzee femora fall in two categories for this angle (25–60 and 90–140 degrees), while gorilla show no preferred angle. This suggests that, unlike gorilla, human and chimpanzee femoral condyles have functionally distinct regions.Grant Funding Source: N/A
Cariogenic bacteria and diet according to nutritional status in pre‐school children
Authors: Argentieri Angela , Mateo María , Iglesias María , Manto María , Friedman Silvia , Lifshitz Fima , Molgatini Susana , Rodriguez Patricia 
Published: June 2021

Dental caries is a multifactorial disease, and diet, closely associated with nutritional status (NS), plays an essential role. However, the relation between these factors has not been thoroughly studied to date. To clarify the relationship between NS and cariogenic bacteria, eighty four children aged 59.2 ± 12.8 months, attending a day care center, were examined. They were classified by Body Mass Index Z‐scores (WHO, 2007) in adequate (A), overweight (OW) or obese (O). Carbohydrate consumption frequency between meals/day (CH), cariogenic risk (CR), and colony‐forming unit/ml saliva (CFU) of streptococci and lactobacilli were assessed.NS showed 46% of children A, 30% OW and 18% O. Although CH did not differ significantly among groups (p>0.05), O presented less children with high CR (A:62, OW:77 and O:50%, p<0.05). The number of CFU of Streptococcus mutans group did not differ significantly, but CFU of Lactobacillus acidophilus was reduced in O (O:2241±1586 vs A:3700±1710 and OW:2715±1793, p<0.05).Thus, these results suggest an association among NS, diet and microbiology composition of dental biofilm that leads to a negative relationship between obesity and caries risk.
Ways of educating, informing and networking with health professionals about nutritional sciences: The Nestlé Nutrition Institute
Authors: Klassen Petra , Haschke Ferdinand 
Published: June 2021

The aim of the Nestlé Nutrition Institute (NNI) is to deliver latest scientific information in the area of nutrition and health and to provide training for capacity building and continuous medical education. The NNI is a not‐for‐profit organization which is run separately from the business.The information provided is based on educational needs which were identified by consumer research. Results led to restructuring the content of the NNI website by nutrition topics. Consequently traffic to the site doubled over a 6 months period. All information and training is prepared by independent experts in their fields. Global distribution of information is achieved via the website, distribution of materials by a global NNI network reaching out to tens of thousands of health professionals. E.g. a recently published practical guide book for pediatric nutrition (Pediatric Nutrition in Practice) has been distributed over 60’000 times.The NNI plays a role in education of health professionals by organizing nutrition trainings in the field of clinical nutrition and mother and child nutrition, a global scholarship program and accredited continuous medical education. Since the NNI supports these activities in conjunctions with renowned institutions and societies (e.g ESPGHAN or NASPGHAN) it can be an important partner to lever and foster ongoing efforts in nutritional education in the academic and public health sector globally.
Underserved minority children are not meeting the moderate‐to‐vigorous physical activity (MVPA) recommendation
Authors: Wong William W. , Ortiz Christina L. , Lathan Debra , Moore Louis A. , Konzelmann Karen L. , Adolph Anne L. , Stuff Janice E. , Mikhail Carmen , Smith E. OˈBrian , Butte Nancy F. 
Published: June 2021

Childhood obesity is more prevalent among underserved minority children. It is recommended that children should spend a minimal of 60 min/d in MVPA in order to maintain a healthy body weight. Based on a minimal of 5 days of Actical measurements, we quantified the amount of MVPA in 483 underserved minority children (10.3±1.0 y; 51.1% male; 31.1% Black/68.9% Hispanic; 66% overweight or obese) who took part in our community childhood obesity intervention program (Healthy Kids‐Houston). The majority of children (89.4%) were in the reduced cost/free meal program and 71.1% had no health insurance or were insured under programs for low‐income families. The children spent more time on MVPA (p<0.01) on weekdays (46.8±1.2 min/d, mean±SE) than on weekend days (41.0±1.6 min/d). Time spent on MVPA decreased with age (−5 min/d per y, p< 0.01) with boys spending more time (12.6 min/d, p<0.01) in MVPA than girls. Black children also spent more time on MVPA (6 min/d, p=0.03) than Hispanic children. MVPA also decreased with BMI z‐score (p<0.01). Most alarmingly, the majority of children (76.4%) spent less than 60 min/d on MVPA. Therefore, to combat childhood obesity, public and private resources should be invested to promote MVPA and to enhance the environment for underserved, minority children.National Research Initiative of the USDA National Institute of Food and Agriculture grant #2008‐55215‐18875 and USDA/ARS grant #6250‐51000‐053. Clinical trial: NCT00994084.
REEPs, an ER adapter protein family, have differential effects on GPCR expression
Authors: Angelotti Timothy , Ho Vincent , Hurt Carl 
Published: June 2021

IntroductionREEPs are members of a growing class of proteins termed ER morphogens or adapter proteins. REEP1 mutations have been implicated in Hereditary Spastic Paraplegia (HSP). To further understand the role of REEPs in ER membrane trafficking and HSP, we have examined their role using two model proteins, alpha2A and alpha2C adrenergic receptors (ARs).MethodsTransiently transfected HEK293 cells expressing individual Flag‐REEP proteins and HA‐alpha2A&C ARs were examined by FACS analysis to determine REEP effects on receptor expression, correlated with ligand binding and deglycosylation analysis.ResultsAnalysis of individual cells expressing both REEPs and ARs revealed a complex effect. Co‐expression of alpha2A ARs with REEP1, REEP2, and REEP6 caused a small increase in plasma membrane AR expression (1.0×, 1.0×, and 0.5× respectively), however there was a larger increase in total AR expression within the cell (1.8×, 1.8×, and 1.2× respectively). A similar analysis of alpha2C AR expression showed a larger REEP effect on surface expression (1.3×, 1.4×, and 1.9× respectively) coupled with a smaller increase in total AR expression (1.2×, 1.2×, and 1.5× respectively). Ligand binding of total membranes showed a similar pattern. Lastly, deglycosylation analysis of ARs revealed that co‐expression of REEPs led to an increase in a minimally glycosylated form of alpha2C ARs.ConclusionsREEPs were originally identified by their ability to enhance GPCR surface expression; however, their effects cannot be generalized. REEPs appear to enhance the production or stability of a minimally glycosylated alpha2C AR. Lastly, co‐IP analysis has revealed that REEPs interact preferentially with alpha2C, but not alpha2A ARs.
Elucidation of the phosphorylation profiles of the long and short isoforms of the omega‐3 fatty acid receptor‐1 (GPR120)
Authors: Burns Rebecca N. , Moniri Nader H. 
Published: June 2021

The omega‐3 fatty acid receptor‐1 (O3FAR1), formally termed GPR120, is a G protein‐coupled receptor that has been thrust to the forefront of diabetes research due to its ability to stimulate release of the insulin secretagogue glucagon‐like peptide‐1 (GLP‐1) upon agonism by the family of omega‐3 fatty acids. We have identified long and short splice variants of human O3FAR1 and demonstrated that the long variant contains additional amino acids within the third intracellular loop, a GPCR region typically associated with signaling and desensitization. Our previous work also showed four additional phosphorylation sites within this region of the long isoform, suggesting varied desensitization between the two variants. While we did not detect notable differences in agonist‐induced phosphorylation of either isoform, basal phosphorylation was significantly higher for the shorter variant, evoking the possibility that O3FAR1‐long and short are differentially regulated by receptor phosphorylation. Here, we present data investigating the phosphorylation profiles of both O3FAR1 isoforms. Our results are the first to reveal the molecular mechanisms of agonist‐induced and agonist‐independent phosphorylation of O3FAR1.This project was funded by a grant from the Diabetes Action Research and Education Foundation. Mrs. Burns is supported by a fellowship from the American Foundation for Pharmaceutical Education.
Systemic adenosine‐induced impairment of endothelial glycocalyx barrier properties is associated with a reduction in functional capillary density in hindlimb skeletal muscle of rats
Authors: van Haare Judith , Vink Hans , Eskens Bart , Cleutjens Jack , Cobelens Hanneke , van Teeffelen Jurgen 
Published: June 2021

ObjectiveTo determine the effect of systemic adenosine infusion on dextran accessibility in capillaries of rat skeletal muscle.MethodsA bolus of fluorescently‐labeled small (40 kDa) dextrans (Dex40) and large (2000 kDa) dextrans (Dex2000) was i.v. infused in anesthetized rats. This was done in control rats (N=4) and in rats that received continuous adenosine infusion (2 mg/ml; 1.5 ml/h) (N=3) for 15 minutes. 3 minutes after dextran infusion, calf muscles were removed and sectioned. Images were captured using fluorescence microscopy. For both tracers, the number as well as the diameter of tracer‐filled capillaries was determined.ResultsIn control rats the diameter of Dex2000 filling in capillaries was smaller compared to Dex40, 3.27 ± 0.05 μm versus 3.48 ± 0.08 μm (MEAN ± SEM). During adenosine infusion, diameters for both tracers did not differ anymore, 3.24 ± 0.24 (Dex40) versus 3.34 ± 0.27 μm (Dex2000). The number of dextran perfused capillaries in control animals was smaller for Dex2000 than for Dex40, 357 ± 31 versus 658 ± 51 and decreased more for Dex2000 (270 ± 22, P<0.05) than for Dex40 (572 ± 60, NS) during adenosine infusion.ConclusionGlycocalyx recruitment during systemic adenosine infusion in rats is associated with a decrease in vascular anatomic volume in resting hindlimb muscle.Sponsored by Dutch Heart Foundation (NHS2009B56)
Capillary pericytes in cochlear lateral wall express strong Kir current and electrical coupling suggest its role in K+‐mediated local blood flow regulation
Authors: Yang Yu-Qin , Nuttall Alfred L , Jiang Zhi-Gen 
Published: June 2021

Microvessels in spiral ligament (SL) and strial vascularis (SV) are densely populated with pericytes (PC) but their functioning mechanisms are not well understood. Using capillary segments isolated from guinea pig cochlear lateral wall and whole‐cell recording techniques, we found the PCs showed a robust inward K+‐current, which would play a key role in regulation of local blood flow.Results1) With physiological solutions, the PCs, but not the endothelial cells (EC), showed a Ba2+‐sensitive inward rectification in I/V domain <‐60 mV. [K+]o 20 mM enhanced the rectification and induced a ~15 mV hyperpolarization. 2) The PCs’ input conductance and capacitance indicated an 18β‐glycyrrhetinic acid‐sensitive electrical coupling. 3) TEA and 4‐AP showed little effect on IV relations. 4) La3+ and niflumic acid (0.1 mM) slightly reduced I/V slope with a net current reversal potential ~−15 and 0 mV, respectively. 5) Acetylcholine, norepinephrine, nitrendipine and glipizide caused no significant change in I/Vs or membrane potentials in the PCs. We conclude that local physio‐pathological [K+]o fluctuation can act on Kir and regulates PC's membrane potential and thus its motor tone. By this mechanism and the spreading effect of gap junction coupling, the PCs may sense the level of K+ recycling driven by hair cell acoustic transduction thus to adjust the vasotone and lateral wall blood flow. In addition, cholinergic and adrenergic neuro factors may play little role in the microcirculation control at PC level. Supported by NIH grants R01 DC004716 (ZGJ) and DC00105 (ALN).
Endothelial bioeffects from acoustic droplet vaporization for gas embolotherapy
Authors: Bull Joseph L , Seda Robinson , Samuel Stan , Fowlkes J. Brian 
Published: June 2021

The dynamics of vascular microbubbles within the microcirculation is examined using a combination of experiments and theoretical analyses. This work is motivated by a developmental gas embolotherapy technique for cancer treatment by infarction of tumors with selectively formed gas bubbles. Additionally, the transport component of this work is relevant to air embolism. The bioeffects resulting from acoustic droplet vaporization (ADV) of a superheated dodecafluoropentane microdroplet is investigated using endothelial cells cultured in Opticells and in vivo in the rat cremaster muscle. The subsequent transport and lodging of microbubbles are examined in the cremaster. Acoustic pressures sufficient for ADV, but below the threshold for inertial cavitation of the resulting bubbles results in smaller damage regions in the Opticell experiments. The onset of inertial cavitation results in a larger region of endothelial bioeffects. The occurrence of bioeffects in the in vivo studies is found to depend on the size vessel in which the droplets are vaporized, with smaller vessels (relative to the initial droplet radius) leading to larger bioeffects. The subsequent lodging of the bubbles agrees with predictions from our mathematical models.This work is supported by NIH grant R01EB006476.
Erythrocytes from Older Healthy Humans Fail to Release ATP during Hemoglobin Deoxygenation
Authors: Kirby Brett S , Garcia Leora J , Crecelius Anne R , Richards Jennifer C , Luckasen Gary J , Larson Dennis G , Dinenno Frank A 
Published: June 2021

Deoxygenation of human erythrocytes (red blood cells; RBCs) from young healthy adults stimulates the release of vasoactive ATP in proportion to the number of unoccupied hemoglobin (Hb) binding sites. Aging humans have diminished plasma [ATP] and impaired skeletal muscle vasodilation to stimuli in which RBCs become deoxygenated (systemic hypoxia and exercise). Therefore, we tested the hypothesis that RBCs from older vs young adults release less ATP during Hb deoxygenation. RBCs from young (n=8, age=27±1 yrs, BMI=23±1 kg/m2, HbA1c=5.1±0.1%) and older (n=8, age=66±3, BMI=26±1, HbA1c=5.1±0.1) subjects were exposed to 16% O2 (NORM) and two levels of low O2 (HYP1 = 3% O2 and HYP2 = 1.5% O2) to facilitate Hb deoxygenation. No difference across age was observed for the variables of pH, pO2, pCO2, and the fraction of oxyHb (FO2Hb) within each condition. ATP (nmol/4•108 RBCs) release from RBCs of young adults increased by 71% during HYP1 (FO2Hb = ~71%) and by 205% during HYP2 (FO2Hb = ~43%) from NORM (FO2Hb = ~95%). In contrast, RBCs from older adults did not significantly release ATP during either HYP condition (Δ 35% and 43%; P<0.05 vs young). Intracellular ATP was not different with subject age. We conclude that RBCs from humans of advanced age fail to release ATP during Hb deoxygenation, and thus may explain the impaired plasma [ATP] and vasodilation during hypoxemia with age.Support: HL102720
Functional analysis of CLCN5 mutations in patients with Dent's disease
Authors: Grand Teddy , Teulon Jacques , Lourdel Stéphane 
Published: June 2021

Dent's disease is an X‐linked renal disease characterized by low molecular weight proteinuria, hypercalciuria and nephrolithiasis, which can be due to loss‐of‐function mutations in the CLCN5 gene encoding the ClC‐5 2Cl−/H+ exchanger. Here, we investigated three published CLCN5 mutations: E267A, S270G and S270R (Hoopes et al., Kidney Int., 2004; Igarashi et al., Kidney Int., 1998).We studied wild‐type (WT) and ClC‐5 mutants in X. laevis oocytes using two‐electrode voltage‐clamp for measuring currents and chemiluminescence for evaluating surface expression. Protein expression and subcellular localization was investigated in HEK293 cells using western blots and immunocytochemistry.No significant current was recorded with the S270R mutant. The E267A and S270G mutants produced 20–50% lower currents as compared to WT. We found no difference between these mutants and WT ClC‐5 in terms of subcellular targeting and protein expression levels. They trafficked normally to the cell surface and to the early endosomes and displayed complex N‐glycosylation like WT ClC‐5.Our study shows that these CLCN5 mutations considerably alter electrical activity of ClC‐5.
Neuronal uptake and subcellular localization of functional nanoformulated copper/zinc superoxide dismutase (SOD nano)
Authors: Rosenbaugh Erin G , Manickam Devika S. , Batrakova Elena V , Kabanov Alexander V , Zimmerman Matthew C 
Published: June 2021

Dysregulation of angiotensin II (AngII) signaling and elevated superoxide (O2 •−) in the brain are associated with cardiovascular diseases, such as hypertension. To improve brain delivery of the O2 •− scavenging enzyme SOD1, we developed SOD nano, a polyion complex composed of a polyethylene glycol corona and polyethyleneimine core that electrostatically binds SOD1 protein. We hypothesized that SOD nano delivers functional SOD to neurons via active endocytosis. Using fluorescently‐labeled SOD1 and CATH.a neurons, we observed a significant increase in the neuronal uptake of SOD nano (70 ± 1 arbitrary fluorescent units, AFU) versus free SOD (22 ± 1 AFU, P<0.05) with 6 h incubation. SOD nano uptake was inhibited by chloropromazine, a clathrin endocytosis inhibitor (14 ± 0.6 AFU, P<0.05 vs. SOD nano), and nystatin, a caveolae endocytosis inhibitor (28 ± 1 AFU, P<0.05 vs. SOD nano). SOD nano co‐localized in lysosomes (38.5%), endosomes (17.1%), mitochondria (9.8%), golgi (7.8%) and ER (5.2%). Electron paramagnetic resonance (EPR) studies show that the AngII‐induced O2 •− in neurons (88 ± 10 EPR arbitrary units, EAU) was attenuated to pre‐AngII levels with 6 h SOD nano (66 ± 11 EAU) but not free SOD protein incubation (73 ± 13 EAU). These data indicate that SOD nano is internalized by neurons through clathrin and caveolae endocytosis and localizes to various organelles where it scavenges AngII‐generated O2 •−.NIH F31 NS073398
Identification of a regulatory region within the EMX2 locus that is active in the neural tube
Authors: Schober Jared P. , Pira Charmaine U. , Oberg Kerby C. 
Published: June 2021

Development requires regulation of essential genes to ensure functional morphology. Conservation of the developmental pathways across species suggests retention of regulatory mechanisms. Thus, conserved non‐coding regions (CNR) may play a role in the genetic regulatory process. EMX2 is a homeodomain transcription factor critical to the development of the central nervous system (CNS). We have previously identified EMX2 as a target of LMX1B, a transcription factor required for brain development and. We report on a CNR ~ 335 kb downstream of EMX2 (CNRZ1), that is highly conserved across species and that also contains putative Lmx1b binding sites (FLAT sequences). We hypothesize that CNRZ1 may play a role in regulating EMX2, possibly mediated by LMX1B binding. To test enhancer function, we isolated CNRZ1 by PCR and ligated it into a plasmid containing a thymidine kinase minimal promoter linked to a GFP reporter. The plasmid was introduced into chick embryos by electroporation (EP). Whole embryo EP was performed on Hamburger and Hamilton (HH) stage 4 chick embryos for CNS evaluation. Fluorescence was visible by microscopy in the neural tube beginning at 12 hrs post‐EP (stage 6), with the strongest signal observed at 48 hrs (stage 10–11). Co‐localization of CNRZ1 enhancer activity with EMX2 and LMX1B expression in the neural tube implicates CNRZ1 as an enhancer for EMX2 that is potentially regulated by LMX1B.Grant Funding Source : National Institutes of Child Health and Human Development