bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clozapine, An Atypical Antipsychotic, Reduces The Contribution Of Brown Adipose Tissue (BAT) To Emotional Hyperthermia In Rats
Authors: Mohammed Mazher , Ootsuka Youichirou , Blessing William 
Published: June 2021

Clozapine is an atypical antipsychotic drug used in patients with schizophrenia. Animal models of clozapine's actions are difficult to develop. BAT thermogenesis is increased by 5‐HT2A receptor activation and decreased by 5‐HT1A receptor activation in the CNS. Clozapine's interaction with these receptors predicts that the drug reduces BAT thermogenesis. We tested this in animal model in which BAT thermogenesis is initiated in a resident rat by introduction of an intruder rat confined to a small cage (Mohammed et al., 2012). ) Thermistor probes, connected to a headpiece, were placed in anterior mediastinum and interscapular BAT of anesthetized male Sprague‐Dawley rats (350‐450g. After 1 week the rat was maintained in a quiet, temperature controlled environment with ad libitum food and water. BAT and body temperatures were monitored via a swivel device. Clozapine was administered (0.03, 0.125, 0.5 and 2 mg/kg in 0.5 ml of acidified Ringer via subcutaneous catheter) and 30 min later the caged intruder was introduced for 30 min. At the lowest clozapine dose, the increase in BAT temperature (0.8±0.1C°) was greater (P<0.01) than the increase in body temperature (0.5±0.1C°). Clozapine, in a dose‐responsive manner, reduced the increase in BAT and body temperatures elicited during sudden confrontation with an intruder rat (log‐dose regression P<0001, R2 = 0.52, for BAT and P<0.01, R2 = 0.32 for body). Thus clozapine reduces BAT thermogenesis initiated by salient, threatening environmental events, thereby reducing emotional hyperthermia. BAT thermogenesis occurs in adult humans, possibly excessively in schizophrenics, so that our animal model may illuminate clozapine's therapeutic action and its contribute to obesity.Supported by NHMRC
The Aging Brain
Authors: McCullough Louise 
Published: June 2021

Aging is an important risk factor for the development of many chronic illnesses that increase functional disability and limit survival, including vascular disease, diabetes and dementia. These diseases are becoming increasingly prevalent in the US with the growth of our elderly population. One consistent finding in aging individuals and animals is the evidence of persistent low level elevations in circulating markers of inflammation, a phenomenon known as “inflammaging”. This pro‐inflammatory phenotype contributes to a global reduction in the capability of older individuals to cope with antigenic, toxic, physical and ischemic stressors. Elevated levels of inflammatory markers are strongly associated with increased risk for diabetes, coronary heart disease, frailty, stroke and mortality. Aging not only leads to higher baseline levels of systemic inflammatory markers, but also enhances baseline and stimulus‐induced pro‐inflammatory cytokine levels in the brain.Advanced age increased T cells, dendritic cells (DCs) and myeloid cells (primarily neutrophils) at the site of injury, which contribute to the exacerbated behavioral deficits in the aged. Our work has shown that dramatic age‐related changes are present in the microbiome, contributing to breakdown of the intestinal barrier, loss of bacterial containment, and chronic activation of the immune system with aging. In addition, accumulation of adipose tissue, up‐regulation of vascular adhesion molecules, and thymic involution lead to defects in cellular immunity in aged mice. Age‐related changes that occur in the brain will be reviewed. New research from our laboratory and from that of others suggesting that this age‐associated damage can be reversed will be discussed.
Low‐Fat Diets Differing in Protein and Carbohydrate Content on Cardiometabolic Risk Factors in Adults with Type 2 Diabetes
Authors: Watson Nerylee , Dyer Kathryn , Buckley Jonathon , Brinkworth Grant , Coates Alison , Parfitt Gaynor , Howe Peter , Noakes Manny , Murphy Karen 
Published: June 2021

ObjectiveTo compare the effects of a higher‐protein (HP) diet and a higher‐carbohydrate (HC) diet on cardiometabolic risk factors in type 2 diabetes (T2DM) in phases of weight loss and weight maintenance. MethodsOverweight/obese adults (n = 61, BMI 33.5 ± 4.8kgm2, aged 37 – 67 years) with T2DM were randomized to a hypocaloric HP diet (38% carbohydrate, 30% protein, 29% fat) or an isocaloric HC diet (53%,21%,23%) for 12 weeks, after which energy was adjusted to maintain a stable weight for a further 12 weeks. Outcomes were measured at baseline and the end of each phase. ResultsForty four participants completed the study (HP n=23, HC n=21). Following weight loss, there were significant (p<0.05) reductions in body mass (‐7.7 ± 4.0kg), waist circumference (‐7.6 ± 4.5cm), blood pressure (‐9.6/‐7.2 ± 9.7/6.1mmHg), HbA1c (‐1.4 ± 1.1%), fasting glucose (‐2.5 ± 2.8mmol/L), fasting insulin (‐8.5 ± 10mU/L) and triglycerides (‐0.6 ± 1.1mmol/L). In the weight maintenance phase there were small increases (p<0.05) in total cholesterol (0.2 ± 0.5mmol/L) and HDL (0.1 ± 0.2mmol/L); no other outcomes changed (p>0.05). There were no significant differences between diets in either phase.ConclusionSubstantial improvements in cardiometabolic risk factors were achieved with weight loss in both diets and continued during weight maintenance. Study was funded by a grant from the Pork Co‐operative Research Center.
Index‐based Dietary Patterns and All‐cause and Cause‐specific Mortality Stratified by Body Mass Index and Race/Ethnicity: NIH‐AARP Diet and Health Study
Authors: Schap T , Subar A , Anic G , George S , Krebs‐Smith S , Park Y , Reedy Jill 
Published: June 2021

Objectiveto examine how four diet quality indices– the Healthy Eating Index‐2010 (HEI‐2010), Alternative Healthy Eating Index (AHEI‐2010), alternate Mediterranean Diet Score (aMED), and Dietary Approaches to Stop Hypertension (DASH) Score – are associated with all‐cause, cardiovascular disease (CVD), and cancer mortality when stratified by body mass index (BMI: normal <25 kg/m2, overweight 25‐蠄30 kg/m2, obese 蠅 30kg/m2) and race/ethnicity (white, black) in the NIH‐AARP Diet and Health Study (n=492,823). Data from a 124‐item food frequency questionnaire were used to compute scores; adjusted hazard ratios (HR) and 95% CI were estimated using Cox proportional hazards regression. We documented 86419 deaths. For all BMI categories, higher diet quality index scores were associated with an 8‐30% reduced all‐cause and cancer mortality risk. For CVD mortality, normal and overweight individuals had a 16‐40% significantly reduced risk; reduced risk was not significant for obese individuals, with the exception of AHEI for men, HR = 0.84 (95% CI:0.75,0.92). For whites and blacks, higher scores were associated with an 11‐25% reduced risk for all‐cause mortality. For whites, high adherence for each index was protective for CVD and cancer mortality. For blacks, this relationship was not consistently significant across indices and cause‐specific outcomes. Only aMED (among women) and HEI (among men) were associated with reduced CVD and cancer mortality risk. Sample size may be a factor in non‐significant associations found among blacks. These findings suggest that adherence to healthy diets may lower the risk of mortality even for overweight and obese individuals.
Food Security among Households with Children in Indiana Improved Following a Supplemental Nutrition Assistance Program—Education Intervention
Authors: Rivera Rebecca , Maulding Melissa , Abbott Angela , Eicher‐Miller Heather 
Published: June 2021

ObjectiveThe effects of a Supplemental Nutrition Assistance Program‐Education (SNAP‐Ed) intervention on the food security of households with children in Indiana were determined.MethodsA randomized, controlled, intervention study design using SNAP‐Ed as the intervention was implemented throughout Indiana from 8/2013 to 2/2014. Five hundred sixty SNAP‐Ed eligible participants 蠅18y were recruited and randomly allocated to receive 蠅4 SNAP‐Ed lessons or not during the 4 to 10 week study period, before and after which they also completed the 18‐item US Household Food Security Survey Module to assess food security status and a characteristics questionnaire. Analysis of covariance modeling, adjusted for participant and household characteristics, was used to determine changes in household food security status (p蠄0.05).ResultsThe mean household food security improvement from before compared with after the study period was greater in the intervention (‐1.0, s=3.3) compared with the control group (‐0.4, s=2.7) in simple (p=0.04) and adjusted models (β= ‐0.7, p=0.03).ConclusionThe SNAP‐Ed program is an effective intervention to improve food security in households with children in Indiana over a short‐term period.Funding This project was supported with a grant from the University of Kentucky Center for Poverty Research through funding by the U.S. Department of Agriculture, Food and Nutrition Service, contract number AG‐3198‐S‐12‐0044.
Maternal Metformin Treatment During Obese Pregnancy Reduces Offspring Fatty Liver and Hepatic Inflammation
Authors: Thomas Hugh , Berlanga Alba , Byrne Christopher , Cagampang Felino 
Published: June 2021

Obesity during pregnancy raises offspring risk of non‐alcoholic fatty liver disease (NAFLD) in adulthood. The anti‐diabetic drug metformin (MET) is prescribed for gestational diabetes treatment, yet long term effects of MET during obese pregnancy on offspring NAFLD risk are unknown. We investigated the impact of maternal MET treatment in obese pregnant mice on glucose tolerance (GT), insulin resistance (IR), body fat (BF%) and NAFLD severity in adult offspring.Female C57/BL6J mice were fed control (C) or high fat (HF) diet 6 weeks prior to mating through pregnancy and lactation. Half the pregnant C and HF dams were given MET in drinking water (250mg/kg bodyweight/day) during pregnancy and lactation. Female offspring were weaned onto C or HF diet, giving 8 offspring groups (C/C, C/HF, HF/C, HF/HF and CMET/C, CMET/HF, HFMET/C and HFMET/HF). At 28 weeks GT tests were performed. Offspring were killed at 30 weeks, BF% assessed by μCT scan and livers collected. Expression of hepatic inflammatory genes was measured by RT‐PCR. IR was determined by HOMA‐IR. NAFLD severity was assessed by histological scoring. Data was analysed by mixed effects model.Offspring of HF dam were fatter and had impaired GT and IR compared to offspring of C dam (p<0.05). Offspring of HF dams treated with MET had reduced body fat (mean effect size (ME) 0.8‐fold, p<0.05), improved GT and IR (ME 1.4‐ and 2.3‐fold respectively, both p<0.01), reduced NAFLD severity and lowered expression of inflammatory genes CCL2, TLR2, TLR4 and Osteopontin (p<0.05) vs offspring of untreated HF dams.MET treatment in obese pregnant dams alleviates the developmental priming of metabolic disease in adult offspring.Funded by Diabetes UK
Loss of Slc26a9 induces an early gastric malignancy in mice and is associated with gastric cancer in humans
Authors: Liu Xuemei , Ran Lidan , Li Taolang , Seidler Ursula , Tuo Biguang 
Published: June 2021

BackgroundSlc26a9 deficiency causes a series of precancerous changes in murine stomach at 5 weeks of age (Xu et al., PNAS 2008), suggesting that Slc26a9 may be involved in gastric malignancy with increasing of age. Aim andMethodsTo understand how Slc26a9 deficiency promotes gastric carcinogenesis in mice and humans, histopathological and immunohistochemical analysis were performed in Slc26a9‐/‐ and WT stomach at 15 months of age. Slc26a9 mRNA and protein expression were measured by qPCR and Western‐blot in human normal gastric epithelium, gastric cancer tissues and cell lines.ResultsAbsence of Slc26a9 in the mouse caused epithelial cell aberrations that mimicked most of those seen in progression of human gastric cancer including oxyntic atrophy, chronic inflammation independent of Hp infection, intestinal metaplasia, TFF2‐expressing metaplasia, and ultimately high‐grade intraepithelial neoplasias. Accompanying with stimulated proliferation and suppressed apoptosis in gastric epithelial cells. human gastric cancer tissues and cell lines displayed significantly decreased of Slc26a9 mRNA and protein expression when compared with health control. Immunohistochemical analysis of human superficial gastritis, atrophic gastritis, adenomatous polyp and gastric cancer indicated progressive decrease in Slc26a9 expression.ConclusionsSlc26a9 deficiency leads to spontaneous premalignant and malignant lesions in the gastric epithelia of mice and it can be as a useful model to study gastric cancer. Slc26a9 may be a candidate tumor suppressor gene in development and progression of human gastric cancer.
Persistence of Memory and Prion Mechanisms: A Perspective
Authors: Kandel Eric 
Published: June 2021

Long‐term memory for behavioral sensitization is synapse specific and requires local protein synthesis at the activated synapse. Kausik Si next found that local protein synthesis is regulated by a neuron‐specific isoform of cytoplasmic polyadenylation element binding protein (CPEB). Aplysia CPEB protein is a regulator of protein synthesis that upregulated locally at activated synapses, and it is needed not for the initiation but for the stable maintenance of long‐term facilitation.Recently we have extended this work in two directions:1) We found CPEB‐3 as a homolog of ApCPEB in the mammalian brain and found that CPEB‐3 is activated by Neuralized, an ubiquitin hydrolase.2) We next found for a new class of prions in the mammalian brain, and found a completely new candidate – TIA (T‐cell intracellular antigen). TIA has classic prion properties in yeast and serves as part of the cellular response to systemic stress. TIA serves as a sex‐specific protective factor in PTSD and does so in female mice only.In my talk I will to provide an overall view of the emerging biology of functional prions and the various roles of these prions in brain and behavior.
Therapeutic Strategies for Restoring Neural Circuit Function in Rett Syndrome
Authors: Katz David 
Published: June 2021

Rett syndrome (RTT) is a severe neurodevelopmental disorder with autistic features caused by loss‐of‐function mutations in the gene encoding methyl‐CpG‐binding protein 2 (MeCP2; Amir et al., Nat. Genet., 1999). Evidence from Mecp2 mutant mice indicates that neurological dysfunction in RTT is associated with abnormalities in the structure and function of brain microcircuits, including altered expression of synaptic proteins and dendritic spine defects, resulting in excitatory/inhibitory synaptic imbalance. However, the specific nature of these abnormalities varies considerably among brain regions. For example, forebrain regions exhibit reduced neuronal activity (Kron et al., J. Neuroscience, 2012) associated with decreased excitatory synaptic drive (reviewed in Katz et al., 2012). In contrast, brainstem regions such as the nucleus solitarius exhibit synaptic hyperexcitability (Kline et al., J. Neuroscience, 2010; Kron et al., J. Neuroscience, 2012). Taking this heterogeneity into account will be critical for designing molecular therapies aimed at restoring normal functional connectivity and neurological function in RTT patients.This presentation will focus on preclinical development of potential RTT therapies targeting two different neurotransmitter/neuromodulator systems; glutamatergic signaling through NMDA receptors (Kron et al., J. Neuroscience, 2012) and brain derived neurotrophic factor (BDNF) signaling through the TrkB receptor, respectively (Kron et al., J. Neuroscience, 2014). Our data indicate that both systems can be effectively manipulated to reverse core features of murine RTT in symptomatic Mecp2 mutants. Supported by NINDS, Rett Syndrome Research Trust, Autism Speaks and AstraZeneca.
Effects of Developmental Hyperserotonemia in the Rat Dentate Nucleus Neuronal Morphology
Authors: Hough Lyon , Segal Solomon 
Published: June 2021

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social cognition and disordered communication. Furthermore, abnormalities in basic motor control and motor learning, are common in ASD. These have been attributed to a possible defect in the pre‐ and postnatal development of specific neural networks including the dentate‐thalamo‐cortical pathway, involved in motor learning, automaticity of movements, and higher cognitive functions.The most consistent neurochemical finding reported in autism is an observed 50‐70% increase in platelet serotonin. Occurring in 30% of autistic subjects, developmental hyperserotonemia (DHS) has been implicated in the pathophysiology of ASD. Prior to its role as a neurotransmitter, serotonin functions as a developmental signal, promoting dendritic elaboration, synaptogenesis, cortical organization and autoregulation of the serotonergic system. Accordingly, it has been hypothesized that during the early stages of neural development, the diffusion of abnormally increased amounts of serotonin into the central nervous system, could induce changes in various neural networks relevant to ASD.In the present study, rat pups were exposed to high levels of the serotonergic agonist 5‐methyloxytryptamine both pre‐and postnatally. This exposure produced changes in the dendritic architecture and synaptic connectivity of neurons in the dentate nucleus of the cerebellum. We observed changes in dendritic branching morphology such that DHS groups presented with short reaching, elaborately branched segments, expressing significantly fewer dendritic spines compared with controls. These alterations may be implicated in the neuropathological and behavioral changes observed in ASD.
Lower Prevalence Of Vitamin And Mineral Deficiencies Among Adolescent Users Of Full Spectrum Multivitamin/Multimineral Supplements
Authors: Murphy Rachel , Ciappio Eric , Bird Julia 
Published: June 2021

IntroductionAdequate intake of vitamins and minerals is essential for supporting health, however intakes of several vitamins and minerals from food are below the recommendations in US adolescents. Dietary supplements (DS) and full spectrum multivitamin/multimineral (FSMV) supplements help improve nutrient intakes. We aimed to determine the prevalence of vitamin/mineral deficiency in US adolescents, and associations between DS and FSMV use and the prevalence of vitamin/mineral deficiency.MethodsCross‐sectional analysis of serum vitamins A, B6, B12, folate, C, D, E, and serum minerals iron and iodine in 4637 adolescents aged 9‐18y from the NHANES (2003‐2006) dataset. Deficiencies were defined using standard age and gender‐based cutoffs established by the CDC and the WHO. Supplement use categories were no DS use, DS use other than a FSMV, or use of a FSMV containing 蠅12 vitamins and 6‐14 minerals. Analyses took into account the complex survey design and were weighted to be representative of the US population.ResultsOverall, 26.4% of adolescents had at least 1 vitamin/mineral deficiency. 34.6% of females (14‐18y) were deficient in at least one nutrient. Among non‐DS users 23.3%, 4.98% and 1.21% were deficient in 1, 2, or 蠅3 vitamins/minerals. In comparison, the prevalence of deficiencies for DS and FSMV users was lower, with 18.3%, 2.31%, and 0.34% of DS users and 11.6%, 2.94% and 0.4% of FSMV users, respectively, having deficiencies in 1, 2, or 蠅3 vitamins/minerals. DS and FSMV users had a similar prevalence of vitamin/mineral deficiency, likely reflecting the small number of FSMV users.ConclusionAdolescent users of DS and FSMV have a lower prevalence of vitamin/mineral deficiencies compared to non‐users.
Investigation of the 3‐epimer of 25‐hydroxyvitamin D3 in urban schoolchildren
Authors: Berger Samantha , Van Rompay Maria , Gordon Catherine , Goodman Elizabeth , Economos Christina , Eliasziw Misha , Holick Michael , Sacheck Jennifer 
Published: June 2021

ObjectiveThe biological relevance of the 3‐epimer of 25‐hydroxyvitamin D (25OHD) is not well classified. Our goal was to examine associations between serum 3‐epimer and demographics and blood lipids in diverse school‐aged children.MethodsMultivariate logistic and linear regression models were used to examine relationships between having detectable 3‐epimer, demographics and blood lipids, controlling for age, sex, race, puberty status, BMI z‐score and total 25OHD, in Boston‐area urban schoolchildren (n=687, 8‐15 yrs).Results40% exhibited total 25OHD <20ng/mL and 49% had detectable 3‐epimer. Serum 3‐epimer was correlated with total 25OHD (r=0.36). Being female (OR 0.69, 95%CI: 0.49‐0.96) and race (Asian vs. white, OR 0.24, 95%CI: 0.11‐0.50) were associated with a lower likelihood of having detectable 3‐epimer. Significant interactions between detectable 3‐epimer and sex and puberty status revealed that females with detectable 3‐epimer had higher HDL cholesterol (3.0 mg/dL, p=0.03) and triglycerides (0.90 mg/dL, p=0.02) while pre‐pubertal children with detectable 3‐epimer had higher triglycerides (0.99 mg/dL, p=0.02).ConclusionThis study provides insight into prevalence of detectable 3‐epimer levels in children and variation in the relationship between detectable 3‐epimer and blood lipids by sex and puberty status.
Alternate‐day fasting and daily calorie restriction similarly affect visceral adiposity and circulating inflammatory cytokine concentrations
Authors: Trepanowski John , Kroeger Cynthia , Barnosky Adrienne , Hoddy Kristin , Varady Krista 
Published: June 2021

BackgroundVisceral obesity is associated with dysregulated inflammatory cytokine secretion. We tested the hypothesis that alternate‐day fasting (ADF) would preferentially reduce visceral fat mass and normalize circulating inflammatory cytokines compared to daily calorie restriction (CR).MethodsOverweight and obese subjects (n = 62) were randomized to 1 of 3 groups for 24 weeks: 1) ADF (feed day: 125% of energy needs, alternated with a fast day: 25% of energy needs; all meals provided); 2) CR (75% of energy needs every day; all meals provided); 3) Control (100% of energy needs every day; self‐selected diet).ResultsChanges in visceral fat mass and concentrations of all measured circulating inflammatory cytokines were similar among all three groups (p > 0.05 for all comparisons). After pooling together the data from the dietary intervention groups, C‐reactive protein decreased relative to the control group (0.19 mg/dl; p < 0.02), while insulin‐like growth factor 1 decreased in the control group relative to the dietary intervention groups (24 ng/ml; p < 0.03). There were no changes between the dietary intervention groups and the control group for tumor necrosis factor α, interleukin 6, adiponectin, leptin, or resistin (p > 0.05 for all comparisons).ConclusionADF and CR produce similar changes in C‐reactive protein and insulin‐like growth factor‐1 relative to a control group.