bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulation of the renin angiotensin system (RAS) in an early stage of life causes sustained hypertension in rats
Authors: Heijnen Bart , van Essen Helma , Debets Jacques , Peutz‐Kootstra Carine , Lijnen Peter , Janssen Ben , Struijker‐Boudier Harry 
Published: June 2021

Transient administration of inhibitors of the renin angiotensin system (RAS) during the prehypertensive period of spontaneously hypertensive rats leads to a long‐lasting lowering of blood pressure (BP) and a reduction of end organ damage. We tested if a transient stimulation of the RAS at young age would exert the opposite effect and permanently increases BP.Studies were performed in Cyp1a1 Ren2 transgenic rats. In this model the production of mouse renin is enhanced when 0.3% Indole‐3 carbinol (I3C) is added to the diet. After withdrawal of I3C the production of mouse renin stops almost immediately. Cyp1a1 Ren2 rats received I3C‐treatment between 4 to 8 weeks of age (WOA) or between 30–34 WOA. Non‐treated rats served as control. BP follow‐up was performed via tailcuff and intra‐arterial BP was determined at 4, 8, 12 and 20 WOA or 34 and 38 WOA. Data are presented as mean ± SEM.At 12 WOA, i.e. 4 weeks after I3C withdrawal, the I3C‐treated rats show a statistically significant increase in BP compared with control rats (156±18 versus 129±6 mmHg). This increase in BP is still present at 20 WOA, i.e. 12 weeks after I3C withdrawal (141±7 versus 125±6mmHg). In the adult rats (30–34 weeks), BP returned immediately to control values after stopping renin activation.This study shows that, at least in rats, sustained hypertension can be induced by a transient stimulation of the RAS in an early stage of life.
8‐CPT‐cAMP is a self‐inhibition reliever for ENaC expressed in Xenopus oocytes
Authors: JI HONG‐LONG , Molina Raul , Han Dong‐Yun , Zhao Run‐Zhen 
Published: June 2021

The epithelial Na+ channels (ENaC) are up‐regulated by cAMP/PKA signal pathway to remove luminal fluid and salt in epithelial tissues. As a specific PKA activator, cell permeable 8‐CPT‐cAMP has been broadly applied to stimulate native ENaC activity in epithelial cells. Recently, it has been proposed that 8‐CPT‐cAMP may act as a ligand of ENaC with unknown mechanisms. To examine whether 8‐CPT‐cAMP stimulates ENaC by eliminating self‐inhibition, both wild type and mutated human αβγ ENaC were expressed in oocytes. Acutely perfusion but not cytosolic microinjection of 8‐CPT‐cAMP activated ENaC current in a dose‐dependent manner with an EC50 value of 49μM (n=5). 8‐CPT‐cAMP reversibly reduced external Na+ self‐inhibition (Ipeak/Isustained ratio, P<0.05). Using Zn2+ ions to modify external histidine residues abolished the eliminating effect of 8‐CPT‐cAMP on self‐inhibition. However, thiol modifying reagent did not exhibit any effect. Furthermore, we identified that γH233R was required for 8‐CPT‐cAMP induced stimulation of ENaC. In addition, 8‐CPT‐cAMP did not increase the channel activity associated with a high opening time mutant, βS520C. Our results suggest that in addition to serve as a key signal molecule of cGMP/PKA signaling pathway, 8‐CPT‐cAMP may be an ENaC opener by relieving self‐inhibition and increasing open probability.Supported by HL087017 and HL095435.
Caloric Restriction Attenuates Many Age‐Related Changes in Skeletal Muscle Mitochondrial Physiology
Authors: Lanza Ian R , Li Eileena , Jakaitis Daniel , Ali Bushra , Nair K. Sreekumaran 
Published: June 2021

Mitochondrial function declines with age but increases with caloric restriction (CR). Mitochondria and muscle fibers were prepared from young (8–11mo) and old (22–24mo) AL‐fed and old CR mice. State 3 respiration was lower in OAL vs. YAL, but preserved in OCR (table). Normalizing to protein content eliminated the age‐effect in AL mice but amplified the effect of CR, indicating that CR enhances the intrinsic mito function. ROS production in isolated fibers increased with age in AL but not CR mice (table). Coupling was reduced in OAL but not OCR. These results indicate that mito capacity declines with age in situ and in vitro, apparently driven largely by decreased mitochondrial protein content. CR increases mito capacity and efficiency independently of mito protein content.

YAL
OAL
OCR

Fibers (pmol/s/m g tiss)
CI
54.0±4.1
38.9±1.6*
50.8±3.0†

CII
44.4±3.4
36.9±1.4*
45.0±2.3†

CI+II
63.4±5.5
51.8±2.5*
67.0±3.4†

Mito (pmol/s/m g tiss)
CI
38.9±1.8
21.5±2.6*
30.7±2.0†

CII
30.6±0.9
19.6±1.2*
24.7±1.4†

CI+II
59.0±1.6
34.0±1.9*
46.7±2.7†

Mito (pmol/s/m g prot)
CI
8350±635
7071±1082
10422±863§

CII
6536±414
6309±506
8408±676§

CI+II
12601±762
11063±1156
15949±1381§

H2O2 (pM/s/mg tiss)
CI
10.0±1.8
30.8±3.7*
15.0±2.0†

CI+II
141.4±20.9
187.2±53.8
101.1±13.6†

P:O
State IV to III
2.94±0.03
2.71±0.02*
2.92±0.05†

Means±SEM.
P<0.05 OAL vs YAL,
P<0.05 OCR vs OAL,
P<0.05 OCR vs. OAL & YAL.
Interaction of GABA and glutamate inputs in the dorsal motor nucleus of the vagus
Authors: Babic Tanja , Browning Kirsteen N , Travagli R Alberto 
Published: June 2021

The dorsal motor nucleus of the vagus (DMV) is pivotal in the regulation of gastric motility. Microinjection of bicuculline (BIC) into the DMV increases gastric motility whereas kynurenic acid (KYN) has no effect unless preceded by microinjection of BIC. The aims of this study were to determine the effects of BIC and KYN on DMV neurons in a slice preparation.Using whole cell patch clamp recordings in 67 DMV neurons, we investigated the effects of BIC and KYN, or their combination, on the firing rate of DMV neurons.Perfusion with BIC increased the firing frequency in 51% of neurons and decreased it in 30%, leaving the remaining neurons unaffected. Following application of BIC, KYN either decreased (60%) or increased (40%) their firing frequency. When KYN was applied first, the firing rate was decreased in 57% and increased 17% neurons. Further perfusion with BIC had no additional effect in most neurons that responded to KYN.These data confirm in vivo studies demonstrating that DMV neurons are under tonic GABAergic control. In contrast to these in vivo studies, though, DMV neurons also responded to KYN, suggesting that they receive tonic glutamatergic input. These data suggest that those DMV neurons regulating gastric motility may be the ones affected by a tonic GABAergic input, whereas the circuits that receive a glutamatergic input may be the ones involved in functions other that gastric motility.Supported by DK 55530
OA/Gpnmb Mutation Impairs Osteoblast and Osteoclast Differentiation and Function
Authors: Belcher Joyce Yvonne , Rico Mario , Ablemagid Samir , Monroy Alexandra , Popoff Steven , Safadi Fayez 
Published: June 2021

Osteoactivin/Gpnmb (OA/Gpnmb) is a glycoprotein identified in bone, and later found to be strongly localized to bone‐forming osteoblasts. There exists in mice a naturally occurring mutation for OA/Gpnmb, which is attributable to premature stop codon resulting in a truncated 150 amino acid OA/Gpnmb protein. Micro‐CT analysis of aged mice show decreased bone volume (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb. Th.) in OA/Gpnmb mutant mice when compared to wild‐type, implying that OA/Gpnmb mutant mice are more osteoporotic. Immunoflourescent analysis has shown OA/Gpnmb protein in mutant osteoblasts (OB) is retained in the peri‐nuclear/cis‐Golgi area. Electron microscopy analysis of osteoblasts showed no morphological differences in mutant osteoblasts versus control, suggesting OA/Gpnmb retention is not cytotoxic. qPCR mRNA and western blot analyses showed increased RANKL expression in OB from OA/Gpnmb mutant. Co‐culture of bone marrow cells showed marked increase in osteoclast (OC) numbers and size in mutant cultures when compared to WT. Treatment of WT and Mutant osteoblasts with recombinant OA/Gpnmb protein resulted in enhanced osteoclast number and size in vitro in WT and but not in mutant OB, suggesting an inherent defect to in mutant compared to WT OC. Collectively, these data suggest OA/Gpnmb acts as a regulator of osteoblast‐osteoclast differentiation and function.Grant Funding Source: NIAMS
Apm‐1 interferes with transcriptional factor MIZ‐1 to repress the p21CIP1 gene
Authors: Lee Kyung‐Mi , Choi Won‐Il , Yoon Jae‐Hyeon , Hur Man‐Wook 
Published: June 2021

The BTB/POZ family proteins have been implicated in many biological processes, including tumorigenesis, DNA damage responses, cell cycle progression and development. We collected the amino acid sequence information of all 183 human BTB‐POZ domain proteins. Among those proteins, MIZ‐1 regulates expression of several genes, and which can be repressed by c‐Myc. Previous studies identified that MIZ‐1 is associated with regulation of p21 and p15INK4B and binds to the two proximal regulatory elements of p21 promoter. We found that MIZ‐1 regulates transcription of not only p21 but also the other genes of p53 pathway, and induced biological functions of p21.To investigate biological functions of particular POZ domain‐POZ domain interaction involving MIZ‐1, we choose Apm‐1, a potentially important protein interaction partner of MIZ‐1. Apm‐1 is a ubiquitously expressed BTB/POZ‐domain class transcription factor and represses transcription of p21 and ARF, which requires p53. Our co‐immunoprecipitation and GST‐fusion protein pull‐down assay showed that MIZ‐1 interacts with Apm‐1 via their POZ domains directly. We also found that Apm‐1 and MIZ‐1 coexist in the proximal p21 promoter by ChIP. Also reporter assay, quantitative PCR analysis, MTT and FACS analysis suggested that Apm‐1 interferes with transcription activator and cellular regulatory functions of MIZ‐1.
The Prediction of The Risk for Hypertension in Carrier of Set of Alleles of Gene Encoding Methylene Tetrahydrofolate Reductase
Authors: Hemimi Neveen Salah , Oda Naglaa Rafaat , Hemedi Samira Ali , Shaafie Ishtiyaq Ahmad 
Published: June 2021

BackgroundMTHFR is a regulatory enzyme of homocysteine metabolism. The genetic polymorphism of the MTHFR gene has been reported to be associated with elevated plasma homocysteine in individual with low folic acid intake.AimTo investigate the influence of the C677T and A1298C polymorphisms of MTHFR gene on the development of hypertension together with the study of other metabolic risk factors for hypertension.Material& Method66 normotensive individual and 60 hypertensive patients were enrolled in the study. The C677T and A1298C polymorphisms of MTHFR were identified by RFLP‐PCR of peripheral blood samples. Analysis of data was done by using SPSS program.ResultsAllele frequency for T allele of C677T polymorphism was higher in the hypertensive group compared to the normotensive group. The carriers of XT genotype (CT and TT) were at high risk of developing hypertension (OR= 1.8; 95% CI = 0.8–3.9) when compared with the carrier of CC genotype. Similarly carries of XC genotype (AC& CC) of A1298C were at high risk of developing hypertension (OR=1.5; 95%CI=0.6–4.1) when compared with AA genotype. The risk for hypertension was increased when the individual was carrier of both alleles (OR= 1.9; 95%CI= 0.6–5.8).ConclusionT and C allele of C677T and A1298C polymorphisms of MTHFR are possible genetic risk factors for hypertension.Source of Fund: Dubai Medical College
Structural properties of the extracellular domain of the synaptic adhesion protein α‐neurexin
Authors: Miller Meghan , Mileni Mauro , Harel Michal , Nakagawa Teru , Taylor Palmer 
Published: June 2021

The neurexin (NRXN) family constitutes a class of membrane proteins ubiquitously expressed at pre‐synaptic glutamatergic and GABAergic terminals. NRXNs help maintain synaptic function and integrity through trans‐synaptic associations with neuroligins. Studies indicate that genomic aberrations play a role in mental disorders, including autism. NRXNs are expressed by 3 genes, each with 2 promoters corresponding to the α‐ or β‐NRXNs. α‐NRXNs differ from β‐NRXNs in their extracellular domain, which contains an additional 5 independently folding LNS domains and 3 EGF domains. Each LNS domain is structurally homologous to the extracellular domain of β‐NRXN. Neuroligins, α‐dystroglycan, neurexophilin, and the spider toxin α‐latrotoxin, are binding partners of 2 of the 6 LNS domains of α‐NRXN. Structural and functional roles of the remaining domains are unknown. By negative‐stain single particle EM we obtained a low resolution (~20 Å) structure of the extracellular domain of α‐ NRXN, providing a description of the conformation and insights into regions of flexibility. These insights enabled us to pursue higher resolution studies. From these data we present a model of the extracellular domain of α‐ NRXN that shows the structural arrangement of the domains, as well as the accessibility of known sites of protein interaction.R37‐GM18360 and PO1‐ES10337
Effect of Giardiasis on Vitamin A Status in Mexican School Children
Authors: Lopez‐Teros Veronica , Valencia‐Juillerat Mauro E , Sotelo‐Cruz Norberto , Vazquez‐Ortiz Francisco , Rascon‐Duran Lucila , Tortoledo‐Ortiz Orlando , Pacheco‐Moreno Bertha Isabel , Mendoza‐Bermudez Diana , Astiazaran‐Garcia Humberto 
Published: June 2021

ObjectiveVitamin A deficiency (VAD) is a nutritional problem affecting the health of people in developing countries because VAD compromises innate and adaptive immunity, increasing a person's predisposition toward infectious diseases. In addition, a high prevalence of infectious diseases continues to be a problem in developing countries, including Giardia lamblia. Giardiasis may be related to VAD because of its ability to change the intestinal architecture, thereby compromising the absorption of vitamin A. The aim of this study was to evaluate the effect of giardiasis on vitamin A status in school children.MethodsThirty Giardia‐infected school children participated in this study. Vitamin A status was evaluated at baseline during active giardiasis and six months after anti‐parasitic treatment was administered. In addition, anthropometric and dietary data were collected.ResultsAccording to anthropometric indicators (age‐appropriate Z scores for weight, height, and body mass index) the children had a normal nutritional status. Although mean dietary vitamin A adequacy was >100%, only 73% (n=22) of subjects had an adequate daily vitamin A intake. There was a significant improvement on serum retinol levels once giardiasis was treated, leading to a 64.6% reduction of subclinical VAD (P<0.02).ConclusionGiardia lamblia has a negative effect on vitamin A status of Mexican school children, increasing their predisposition toward infectious diseases.
Influence of dietary protein on fecal quality and gene expression of apoptosis‐ and immune‐related genes in the colon of Miniature Poodles and German Shepherds
Authors: Nery Joana , Leray Véronique , Biourge Vincent , Martin Lucile , Dumon Henri , Nguyen Patrick 
Published: June 2021

Digestive tolerance vary among dog breeds, which could be partially attributed to higher colonic fermentation. Highly digestible protein sources, such as wheat gluten, could lead to lower colonic protein fermentation. Our aim was to assess the effect of dietary protein on fecal quality, and mRNA expression of genes involved in colonocyte apoptosis and mucosa immune responses.Five Miniature Poodles (MP) and 6 German Shepherds (GS) were fed with diets varying in protein source and level: low‐protein wheat gluten meal (LP) and high‐protein poultry meal (HP). Feces were scored daily (1=dry; 5=liquid) and fecal moisture was analyzed. Colonic biopsies followed each 14‐d trial period. The mRNA expression of proteins involved in apoptosis (Bcl‐2, Casp3), and in mucosa immune responses (IL7, TLR2, TLR4) was analyzed by RT‐real time PCR.Fecal score and moisture were higher in GS than MP, and when feeding HP diet. The expression of IL7 was higher in GS than MP (P < 0.05), and when dogs were fed with HP diet (P = 0.03). The TLR2 mRNA expression was higher in the proximal colon of GS than MP (P = 0.08), and when feeding HP diet to GS (P = 0.03).Up‐regulation of immune‐related proteins could indicate a higher response to commensal bacteria, leading to a lower quality of feces. Diets containing low levels of highly digestible proteins could be an adequate nutritional strategy to improve fecal quality. Research supported by Royal Canin.
Protein source modifies bone health in adult rats
Authors: Thorpe Matthew P , Norton Layne E , Moulton Christopher J , Johnson Amy J Wagoner , Evans Ellen M , Layman Donald K 
Published: June 2021

Studies of protein and bone health report variable results. Differential effects of protein sources may explain incongruities. In particular, portions of sulfur amino acids may impose a bone‐demineralizing acid load while portions of leucine may enhance anabolic balance.We randomized 52 rats, 52d old, to semi‐purified, isonitrogenous diets (16% energy as protein, 54% carb) with protein isolate from soy, egg white, wheat or whey. Animals were sacrificed at 11 wk, and femurs excised for 3 point bend tests of mechanical strength and dual x‐ray absorptiometry.Greater force was required to break the femur midshaft with whey (119±10 N) compared to soy (110±9 N, p=0.02). Bone mineral mass was also greater given whey (480±25 mg) vs. egg (466±14 mg) and soy (456±27 mg); as well as in wheat (478±25 mg) vs. soy animals (p<0.05 for all comparisons).Protein source modified bone health in this animal model independent of total protein and energy intake. These observations are not adequately explained by a negative effect of sulfur in protein sources, which is low in soy (39.8 mEq potential acid per 100g protein) compared to whey (46.2) and wheat (69.4).Supported by National Dairy Council and Egg Nutrition Center.Grant Funding Source: National Dairy Council
Secondary analysis of food group intake in prostate cancer patients undergoing radiotherapy and nutrient supplementation
Authors: Bartalone Rachel L , Brown Jean K , Browne Richard W , Wilding Greg , Tyrpak Donna , Horvath Peter J 
Published: June 2021

Diminished nutritional intake and declining appetite are common in cancer patients during therapy. Prostate cancer patients (53) undergoing radiotherapy had 3‐day diet/activity records taken at baseline (T1), during therapy with supplementation (T3) and post‐therapy with supplementation (T4). Patients were given a Placebo, a multivitamin/mineral Dietary Reference Intake (DRI), or DRI with additional antioxidants (Orthomolecular, OM). As previously reported total sugar, carbohydrate and overall energy intake (EI) decreased significantly with Placebo, not DRI or OM. Food groups and discretionary calories (DC ‐ saturated fat, alcohol and added sugar) were examined to understand the decreased EI. Intakes of milk, vegetable, and grains did not change. DC decreased in the Placebo group during radiation. At T4 oil intake increased in the DRI group, and Placebo vs. DRI. There was a trend for an increase in meat intake at T3 in all groups and for fruit at T4 in OM. In conclusion, the decrease in EI in the Placebo group may be due to DC. Radiation therapy did not affect most food group intakes, regardless of treatment. Supported by a grant from The National Cancer Institute #R21CA102391‐2.Grant Funding Source: The National Cancer Institute #R21CA102391‐2
The Relationship between Breastfeeding and Childhood Leukemia Risk in Oman
Authors: Wali Yasser , Waly Mostafa , Al‐Mukhaini Yahya , Ali Amanat 
Published: June 2021

Recent case‐control studies on breastfeeding and childhood leukemia risk indicated that long duration (>6 months) is associated with decrease risk of the disease. Most of these studies have been conducted in the west and the matched controls were not selected from the same family siblings of the studied cases, this excludes the genetic causes of leukemia.We decided to conduct a case‐control study to investigate the relationship between breastfeeding and childhood leukemia risk in Oman where breastfeeding is culturally favorable for a longer period of time (up to 24 months).All of the recently diagnosed cases and registered cases at the national registry during (1999–2009) has been screened and a total number of 70 cases were recruited for this study. For each case, a matched control for age and sex was selected from the same family siblings and the ratio of cases to controls was 1:1.Data of this study revealed that for breastfeeding duration of (6–12 months), 21% of cases were reported as compared to controls (12%). Meanwhile longer period of (12–24 months) was observed for 75% of cases as compared to controls (81%). For a period of (≥ 24 months) the percentage of cases was 4% as compared to controls (7%). All results were not statistically significant different (Chi‐square, χ2= 3.816), P>0.05.Our study indicates that breastfeeding duration is negatively associated with childhood leukemia risk and other environmental and genetic factors might be synergizing for the disease occurrence in Oman.
Longitudinal associations of physical activity and cancer mortality ‐ the Third National Health and Nutrition Examination Survey
Authors: Parekh Niyati , Lin Yong , Vadiveloo Maya , Fitzgerald Nurgul , Lu‐Yao Grace 
Published: June 2021

BackgroundPrevious studies suggest that physical activity (PA) may afford protection against cancer risk.MethodsThis study evaluated longitudinal associations between PA and cancer mortality in the nationally representative Third National Health and Nutrition Examination Survey (NHANES III; 1988–1994), with an average follow‐up of 8.5y to mortality. Mortality was ascertained using National Death Index certificates. Metabolic equivalents (METS) were calculated from self‐reported PA collected in an in person‐interview. Cox‐proportional hazards models were used to compute hazard ratios (HR) for cancer mortality using SUDAAN in relation with level of PA.ResultsAny mention of PA vs. sedentary lifestyle was protective against cancer mortality (adjusted for age, race, sex, smoking, and BMI)(HR: 0.63, 95% CI: 0.47–0.84). High intensity PA was associated with further risk reduction (HR: 0.46, 95% CI: 0.27 – 0.78). Subjects in the highest vs. lowest tertile of METS had a 43% reduced risk of cancer mortality (HR:0.57, 95%CI: 0.41–0.80), p‐trend = 0.004. Leisure activity (gardening, dancing, yard work, and “other” active hobbies) was also associated with reduced risk of cancer mortality (HR:0.51, 95% CI:0.33–0.78).ConclusionIn these preliminary analyses, all forms of PA confer protection against cancer mortality. PA should be considered as an integral part of cancer management.
Vegetarian diets are associated with a lower risk of metabolic syndrome. The Adventist Health Study 2
Authors: Rizzo Nico Samuel , Sabate Joan , Jaceldo Karen , Fraser Gary 
Published: June 2021

ObjectiveTo compare dietary patterns graded as vegetarian, semi vegetarian and non vegetarian in their relationship with metabolic risk factors and metabolic syndrome (MetS).DesignCross‐sectional analysis of 765 subjects (mean age 60 y) from the Adventist Health Study II calibration sub‐study. Type of diet was categorized based on food‐frequency questionnaire and classified as vegetarian (36%), semi vegetarian (17%) and non vegetarian (47%). ANCOVA was used to determine associations between type of diet and metabolic risk factors. Logistic regression analysis was used to calculate odds ratios (OR) for MetS risk. In all the analyzes adjustments were made for age, sex, ethnicity, socioeconomic status, alcohol intake, smoking, and physical activity.ResultsVegetarians and semi vegetarians had significantly lower levels of fasting blood glucose, total cholesterol, waist circumference and BMI when compared to non vegetarians. Vegetarians had significantly lower levels of triglycerides, systolic and diastolic blood pressure. Vegetarians had the lowest risk for MetS, [OR 0.49, 95% CI 0.29–0.65, P<0.001] and semi vegetarians had a risk of [OR 0.59, 95% CI 0.38–0.94, P=0.025] when compared to non vegetarians.ConclusionsVegetarian and semi vegetarian dietary patterns are associated with more favorable levels of metabolic risk factors and a lower risk for MetS.