bluuebunny/crossref_metadata_2025_split huggingface dataset:
IMP2 Expression In The Mouse Nervous System
Authors: Chmielewski Sarah Elizabeth , Black Paige E. , Holmes Tiffany , Lau Kelly , Bassell Gary J. , Xu Mei 
Published: June 2021

Insulin‐like growth factor‐II (IGF‐II) mRNA‐binding protein‐2 (IMP2) is one of the three homologs (IMP1–3) that play important roles in the posttranscriptional regulation of gene expression in several tissues. IMP1/ZBP1 (zipcode binding protein) has been shown to play important roles in axon guidance and regeneration by regulating the localization and translation of specific mRNAs. However, the function of IMP2 is least understood, largely because an isoform‐specific antibody is not available, which makes the conventional techniques to locate protein expression not feasible. We custom made an IMP2‐specific antibody. We used Western blot and immunocytochemistry to test its specificity on cultured cells following over expression of IMP 1–3 isoforms, respectively. Using this IMP2‐specific antibody, we examined IMP2 expression in the mouse nervous system. We found that IMP2 expression in the nervous system is sustained postnatally, unlike that of IMP1 and IMP3. Ongoing experiments are aimed at further understanding IMP2 expression patterns during injury and assessment of its role to facilitate mRNA localization during axon regeneration in the adult nervous system.This work is supported by the Department of Anatomy, PCOM and Center for Chronic Disorders of Aging (CCDA).
Impaired muscular force production in a canine model of muscular dystrophin deficiency
Authors: Yang Hsiao Tung , Shin Jin-Hong , Pan Xiufang , Terjung Ronald L , Duan Dongsheng 
Published: June 2021

Loss of muscle force is a salient feature of Duchenne muscular dystrophy (DMD), a fatal disease caused by dystrophin deficiency. Assessment of force production from a single intact muscle has been considered as the gold standard for studying physiological consequences in murine models of DMD. A similar assay has not been established in dystrophic dogs. Therefore, we developed a novel in situ protocol to measure force generated by the extensor carpi ulnaris (ECU) muscle from Normal (n=4) and Affected dog (n=3). Absence of dystrophin resulted in marked histological damage in the ECU muscle. Peak tetanic force was significantly reduced in affected dogs (only 78% of Normal group, p<0.025). The ability to maintain the initial tension during continuous tetanic contractions was similar in both groups. Importantly, eccentric contractions by extending 5% of ECU muscle length while muscle was contracting, induced a much higher magnitude of force loss in the affected dogs (p<0.001). Our data showed that dystrophin‐deficient muscle is sensitive to damage by eccentric contraction. To our knowledge, this is the first convincing demonstration of force deficit in a single intact muscle in the canine DMD model. The method described here will be of great value to study physiological outcome following innovative gene and/or cell therapies.Supported by NIH AR‐49419, MDA, and Jesse's Journey‐the foundation for gene and cell therapy
Efficiency of a controlled physical reconditioning monitored by maximal cardiovascular and metabolic parameters in patients with chronic low back pain
Authors: Duvallet Alain , duvallet Emilie , Lhuissier François , Beaudry Michele , Duque Ivan 
Published: June 2021

Practice physical exercise on a regular basis is admitted to be an important element for health.In patients untrained during a chronic disease, the return is often difficult. A follow‐up is then necessary for reconditioning which will have to be maintained.In 101 patients with chronic low back pain, presenting a physical deconditioning, we have done a programmed physical training. They performed a 5 weeks training with 6 hours of exercise per day, 5 days a week. The exercises comprised endurance, muscledevelopment and limbering‐up. Patients were tested when included in the protocol and at the end of the 5 weeks. The exercise test was performed on a bicycle ergometer by progressive graded exercise from rest to maximal effort. The collected parameters comprised heart rate, followed all along the effort, the maximum work rate, the maximum oxygen consumption, the respiratory exchange ratio and the blood lactate level. The statistical comparison was made by paired t test.Taken together these parameters show a statistically significant improvement after physical reconditioning. These results confirm that physical restoration is a complementary factor of general physical condition as a health factor.
Delineation of the Intestinal Glucose Sensing Pathway in Obese and Diabetic Humans Undergoing RYGB
Authors: BHUTTA HINA YASEEN , DEELMAN TARA , TAVAKKOLIZADEH ALI 
Published: June 2021

Roux‐en‐Y Gastric Bypass (RYGB) surgery for obesity achieves weight loss with additional myriad metabolic benefits. Mechanisms explaining these changes are unknown. We hypothesized that RYGB improves glucose homeostasis by excluding glucose sensors and/or transporters from the enteral pathway.Whilst undergoing RYGB surgery for obesity, jejunal biopsies were taken 40cm (proximal) and 140cm (distal) from the ligament of treitz (Figure 1) of 23 patients (Table 1). mRNA expression of SGLT1, GLUT2, and T1R2 (part of the sweet taste receptor heterodimer) was measured with RT‐PCR. Statistical analysis used paired students’ t‐test.Intestinal expression of transporters SGLT1 and GLUT2 was higher in proximal jejunum forming the biliopancreatic limb (p<0.001 and p<0.05 respectively). Conversely, expression of glucose sensor T1R2 was higher distally towards the common limb (p<0.01) (Figure 2).Glucose transporters and sensors show topographic variation in human jejunum. SGLT1, which accounts for active transport of glucose across the intestinal apical border, and GLUT2, responsible for glucose transport at the basolateral border, are concentrated in jejunum which is bypassed in RYGB surgery, rendering upregulation in response to T1R2 activation redundant post‐RYGB. Replicating exclusion of intestinal glucose transporters in a less invasive manner could provide a valuable way to treat metabolic disease.
Effect of estrogen on molecular and functional characteristics of the rodent vaginal muscularis
Authors: Basha Maureen Elizabeth , Chang Shaohua , Burrows Lara J , Lassmann Jenny , Wein Alan J , Moreland Robert S , Chacko Samuel K 
Published: June 2021

Vaginal atrophy is a consequence of menopause, however little is known concerning the effect of estrogen on vaginal smooth muscle function. The goal of this study was to determine the effect of estrogen on molecular and functional characteristics of the vaginal muscularis using a rodent model of surgical menopause. 3–4 month old Sprague Dawley rats underwent sham laparotomy (Sham) or ovariectomy (Ovx). Two weeks following surgery, animals received a subcutaneous osmotic pump containing vehicle (Sham, Ovx) or 17‐ β estradiol (Ovx). Animals were euthanized one week later and the proximal vagina was collected for molecular and in vitro contractility studies. Measurements were analyzed using one way ANOVA followed by post hoc analysis. Ovariectomy decreased 1) mRNA transcript (P<0.05) and protein (P < 0.001) expression of carboxyl‐terminal myosin heavy chain isoform (MHC), SM1, 2) protein expression of h‐caldesmon (P < 0.01) and 3) peak force of vaginal strips in response to KCl (P < 0.001). Estradiol replacement reversed these changes. No differences were detected in the % vaginal muscularis, amino terminal MHC isoform expression and maximal velocity of shortening. Our results suggest that menopause is associated with changes in the vaginal muscularis which may contribute to the increased incidence of pelvic floor disorders with age.Funding: AUA Research Scholar Award, Maureen Basha
Modulation of Vagus Nerve Stimulation via Ganglionic Plexus activation and Ventricular Ischaemia
Authors: Brack Kieran Eugene , Coote John Haven , Ng G. Andre 
Published: June 2021

Discreet regions in the heart, called ganglionic plexuses (GPs) are a network of integration centres that process afferent and efferent nerve activity to modulate the heart. We aimed to investigate the role of the right atrial GP (RAGP) in controlling heart rate (HR).MethodsThe decentralised innervated Langendorff perfused rabbit heart model was used (n=6). 1) RAGP was stimulated using 0.1–0.4mg nicotine (0.1ml) in 2) the presence of 0.1μm Atropine (At) or 1.8μm Metoprolol (Met), 3) The right vagus nerve was stimulated (VNS, 7H10V) before and after RAGP stimulation and 4) VNS before and following coronary artery occlusion. Data are mean±SEM, repeated measures ANOVA or Students t‐test.Resultsi) RAGP stimulation elicited an initial bradycardia (145±9 to 109±3bpm, P<0.05) and secondary tachycardia (226±12bpm, P<0.001, n=5) ii) At abolished the bradycardia (139±8 to 138±10bpm, P=NS), but not the tachycardia (247±9bpm, P<0.001). Met did not affect the bradycardia (135±7 to 106±4, P<0.05) but abolished the tachycardia (128±6bpm, P=NS, N=5. iii) VNS‐bradycardia was augmented after RAGP stimulation (−81±8 vs 142±9bpm, P<0.01, n=3). iv) Coronary artery occlusion increased VNS‐bradycardia (−45±6 vs −68±8bpm, P<0.05, n‐4).ConclusionThis is the first data representing GP modification in the rabbit showing that RAGP activation elicits a mixed autonomic HR response, via vagal and sympathetic activation that enhanced VNS‐bradycardia. In addition, novel data shows that acute ventricular ischemia augments the HR effect of cervical VNS confirming that the RAGP is important in controlling HR in this species.Research support from the University of Leicester
The efficacy of tart cherry supplementation in the prevention of age‐related bone loss in C57BL/6 mice
Authors: Chongwatpol Pitipa , Rendina Elizabeth , Graef Jennifer L. , Clarke Stephen L. , Lucas Edralin A. , Smith Brenda J. 
Published: June 2021

Osteoporosis continues to be a major health problem and new prevention strategies are needed. This study examined the efficacy of dietary supplementation with tart cherry on age‐related bone loss in female (5 mo) C57BL/6 mice (n=44) assigned to a baseline group or groups receiving 0, 1, 5, or 10% cherry for 90 d. Mice were weighed weekly and bone density and trabecular and cortical bone microarchitecture were assessed at the end of the study. No difference in body weight due to treatment was observed. The groups receiving the 5 and 10% cherry diet had higher (P<0.05) whole body and tibia bone density than the control and baseline groups. The age‐related decrease in trabecular bone volume of the distal femur metaphysis was prevented with cherry supplementation (5 and 10%). In these two treatment groups vertebral trabecular volume and cortical area and thickness of the femoral mid‐diaphysis was increased (P<0.05) compared to the control and baseline cohorts. These findings suggest that tart cherry not only prevented age‐related bone loss, but increased cortical and vertebral trabecular bone above that of baseline which is consistent with an anabolic response.Grant Funding Source: Cherry Marketing Institute
Anthropometric differences and body composition among ethnic minorities in northern Vietnam
Authors: Nguyen P H , Katz B , Lowe A E , Nguyen H , Truong T , Pham H , Nguyen S , Reinhart G A , Harding K B , Neufeld L M , Martorell R , Ramakrishnan U 
Published: June 2021

Little is known about ethnic differences in body size and composition among minority groups in Vietnam. We used data from an ongoing study (PRECONCEPT) of women of reproductive age (WRA) in Thái Nguyên province, Vietnam to 1) compare selected anthropometric measures and body composition indices across ethnic groups; and 2) evaluate cutoff points for mid‐upper‐arm (MUAC) and calf circumference (CC) for screening undernutrition. A battery of anthropometric measurements (weight, height, MUAC, CC, triceps and subscapular skinfold thickness) was obtained for 4918 WRA. Body mass index (BMI), mid upper arm muscle (MUAMA) and fat area were calculated. The prevalence of underweight (BMI < 18.5 kg/m) and overweight (BMI >; 23 kg/m) were 32% and 5%, respectively. Mean (± SD) MUAC for the largest ethnic group, the Kinh (24.3 ± 2.1) was significantly lower than both Tay (24.6 ± 2.2) and San Chi (24.8 ± 2.2). Similar differences were seen for BMI (Kinh: 19.4 ±1.9; Tay :19.6 ±1.9, and San Chi:19.9 ± 2.0). The differences in BMI and MUAMA remained significant after adjusting for age, socioeconomic status, energy intakes, education and food insecurity. ROC analysis showed high predictive strength of MUAC and calf circumference in screening underweight women. Further studies are needed to explain differences in body composition among ethnic minority subpopulations.Funding: The Mathile Inst. and the Micronutrient Initiative
Expert recommendations for consumption frequencies of specific foods
Authors: Chavez Johanna Yvonne Andrews , Konick Jennifer , Davis Charlotte , Marino‐Costello Elizabeth , Connell Patrick , Houser Robert F. 
Published: June 2021

This pilot study was conducted to assess the opinions of a sample of members of the Academy of Nutrition and Dietetics on the ideal consumption frequencies of specific foods and on Academy's policy of promoting a total diet approach to encourage healthy eating. Since the American public lacks sophisticated nutrition knowledge, specific food‐based guidelines could make it easier for consumers to adopt healthier food choices and patterns. An online survey of Massachusetts Dietetic Association members yielded 45 respondents who completed the survey. There appears to be a great deal of support for providing the public with specific food item frequency recommendations. About 50% disagreed with Academy's policy of “no bad foods, only bad diets.” We saw that many of our respondents identified several foods that should never be consumed. These were mostly processed foods. Foods that were considered appropriate for daily consumption were mostly unprocessed fruits and vegetables. Although the total diet approach admirably encourages balance, variety, moderation, and nutrient‐dense foods in the diet, as growing research identifies specific foods as key contributors to the obesity epidemic, nutrition policy should be redirected to provide guidance about what foods should be avoided or limited in the diet. Research support: unfunded.Grant Funding Source: Unfunded
Adaptive thermogenic response to over and underfeeding occurs acutely
Authors: O'Connor Annalouise , Luo Weijun , Galanko Joseph , Brouwer Cory , Swick Andrew G. 
Published: June 2021

Adaptive thermogenesis in response to underfeeding (UF) and overfeeding (OF) may impact an individual's risk of weight gain and ability to lose weight. Studies have reported energy expenditure (EE) changes after 72hrs of UF or OF. However we hypothesize that adaptive responses occur acutely and aimed to determine whether the EE response to UF and OF is detectable within 24hrs. 7 over‐weight post‐menopausal women completed a eucaloric feeding day in the metabolic chamber at UNC NRI to ascertain baseline energy requirements. Subjects were randomized to receive 72hrs of OF (150% of requirements) or UF (50% of requirements) in a cross‐over fashion, each separated by 2 weeks. 24hr EE was measured 3 times during each 72hour period. Macronutrient composition of all test meals was 30%E fat, 55%E carbohydrate and 15%E protein. A repeated regression measures mode with change in EE as the response, and time, treatment order, and pre‐treatment weight and energy intake as predictors was conducted. EE changed significantly within 24‐hours of both OF and UF. 24hr responses did not differ significantly from those at 72hrs. Resting (RMR) and sleeping metabolic rate (SMR) and diet‐induced thermogenesis (DIT) were significantly increased with OF only. That EE response to UF and OF occurs within 24hrs suggests acute energy sensing. Ongoing ‘omics profiling aims to understand mechanisms governing acute EE adaptation.Grant Funding Source: UNC NORC NIH grant #DK056350
A Randomized Double Blind Placebo Controlled Evaluation of MSM for Exercise Induced Discomfort/Pain.
Authors: Kalman Douglas , Feldman Samantha , Samson Adam , Krieger Diane 
Published: June 2021

Methylsulfonylmethane (MSM) has been reported to provide anti‐inflammatory & antioxidant effects in mammals. Resistance exercise is known to induce both inflammation & oxidative stress resulting in muscular discomfort & pain. In a pilot‐proof of concept study, we determined the effects of MSM on markers of exercise recovery & performance.MethodsIn random order 24 moderately exercise‐trained men (25.5±5.6 yrs) received MSM 3.0 gm/d or PLA, for 14 days, with a 17‐day washout between. The study included 3 tests: baseline, no product & the 2nd & 3rd following 14d supplementation with MSM & PLA. Each test consisted of 2 visits. At the 1st visit, subjects performed stressing exercise; 28 total sets of leg extensions, sets 1–25, predetermined weight, 10 reps each, sets 26–28 to muscular failure at 70% 1‐RM (performance). At the 2nd visit (48 hrs later), subjects performed 12 total sets of leg ext, sets 1–9, predetermined weight, sets 10–12 to muscular failure, 70% 1‐RM (performance). Muscle discomfort/pain (10‐point VAS scale), inflammation (hs‐CRP & IL‐6), blood antioxidant status (TEAC & SOD), & homocysteine were measured before the stressing exercise and 2 & 48 hours post exercise. Exercise performance was also measured following 14d supplementation with MSM/PLA (sets 26–28 and sets 10–12). In order to eliminate sequence effects, results are provided on the 1st product as compared to baseline (comparison of the 1st & 2nd tests).ResultsMSM intervention resulted in significantly less pain/discomfort vs. PLA from baseline to 2 hrs (1.55±0.82 vs 3.75±2.58, p=0.012). Change in IL‐6 was significant within the MSM & PLA & between MSM (0.54±0.76) vs PLA (−0.58±0.97) p = 0.006. There were no significant differences between MSM & PLA noted for the other biomarkers.ConclusionMSM may help alleviate the discomfort/pain that can follow a stressful exercise session.
Five days of reduced physical activity selectively impairs endothelial function of the inactive limbs
Authors: Boyle Leryn , Credeur Daniel , Jenkins Nathan , Padilla Jaume , Thyfault John , Fadel Paul 
Published: June 2021

Chronic physical inactivity promotes the development of cardiovascular diseases. However, few data exist on the effects of short‐term reductions in daily ambulatory activity on vascular function, particularly at the cellular level. Thus, we studied popliteal and brachial artery flow mediated dilation (FMD) and measured plasma levels of endothelial microparticles (EMPs) shed from apoptotic and activated endothelial cells (CD31+/CD42b− and CD62E+ EMPs, respectively) at baseline and following 5 days of reduced daily steps (<5,000 steps/day) in 6 healthy, recreationally active men (26±3 yrs). We hypothesized that popliteal FMD would be reduced and concentrations of EMPs would be increased with inactivity. Following inactivity, popliteal FMD decreased (baseline: 5.4±1.2 vs. inactivity: 1.9±1.0%, p=0.05), while brachial artery FMD was unchanged (baseline: 4.2±0.7 vs. inactivity: 5.6±1.0%, p=0.12). CD31+/CD42b− (1.3 ± 0.4 vs. 4.8 ± 2.7 per μL plasma) and CD62E+ (69.2 ± 52.0 vs. 14.7 ± 7.9 per μL plasma) EMPs were not significantly altered following inactivity. These preliminary findings suggest that the vascular consequences of reduced daily steps are primarily localized to the lower (inactive) limbs, although changes in systemic EMPs reflective of endothelial apoptosis (CD31+/CD42b− ) and activation (CD62E+) were not observed.Grants: AHA 12PRE12080242, NIH R01‐HL093167, T32‐AR048523
Poly ADP‐Ribose polymerase (PARP‐1) and DNA damage in pulmonary arterial hypertension
Authors: Meloche Jolyane , Courboulin Audrey , Krietsch Jana , Margaillan Guillaume , Courchesne Antony , Coulombe Yan , Provencher Steeve , Poirier Guy , Masson Jean‐Yves , Bonnet Sebastien 
Published: June 2021

Pulmonary arterial (PA) hypertension (PAH) is characterized by PA obstruction, associated with oxidative stress and inflammation sustained by NFAT (Nuclear factor of activated T‐cells) and HIF‐1 (Hypoxia inducible factor 1) activation. Despite these DNA damaging conditions, PAH‐PA smooth muscle cells (PASMC) are proliferative and apoptosis‐resistant, suggesting DNA repair machinery activation. PARP‐1 is a crucial enzyme implicated single strand DNA breaks (SSB) repair and regulates cell survival and expression of many genes such as NFAT and HIF‐1. We hypothesized that PARP‐1 is activated in PAH‐PASMC, inducing proliferation and survival and thus PA remodeling. Using human lung tissues and PASMC, we demonstrated that increased oxidative stress promotes SSB in PAH‐PASMC. Increased SSB triggers PARP‐1 activation, which promotes NFAT/HIF activation, increasing PAH‐PASMC proliferation and resistance to apoptosis. Finally, we showed that clinically available PARP inhibitor ABT‐888 reverses all these abnormalities both in vitro and in vivo in rats with monocrotaline and Sugen‐induced PAH. In conclusion, we demonstrated the implication of DNA repair machinery PARPs in PAH etiology and that clinically available PARP‐1 inhibitors represent new therapeutic agents for PAH treatment.A Canadian Thoracic Society scholarship to JM and Canadian Institutes of Health Research grants to SB supported this work.
Upregulation of p21 activates the intrinsic apoptotic pathway in pancreatic β cells
Authors: Hernandez Angelina M. , Colvin E. Scott , Fueger Patrick T. 
Published: June 2021

Diabetes results from a loss of functional β cell mass due to decreased β cell function, survival, or proliferation. The cyclin‐dependent kinase inhibitors (CDKI) negatively regulate proliferation; however, their involvement during β cell stress is unclear. Interestingly, p21 (or cdkn1a) was the only CDKI dramatically induced in INS‐1‐derived 832/13 cells and rodent islets by two pharmacologic inducers of β cell stress and death, dexamethasone and thapsigargin. We hypothesized that p21 induction during β cell stress activates the apoptotic pathway. Thus, we adenovirally overexpressed p21 in isolated islets and 832/13 cells. p21 overexpression decreased cell proliferation measured by [3H]‐thymidine incorporation. Flow cytometry analysis revealed that p21 overexpression blocked the G1/S and G2/M transitions and increased the number of annexin‐positive stained apoptotic cells. Further, p21 overexpression increased caspase 3 cleavage. Importantly, p21‐mediated caspase 3 activation was inhibited by either overexpression of the anti‐apoptotic protein Bcl‐2 or siRNA‐mediated suppression of the pro‐apoptotic proteins Bax and Bak. Therefore, our findings indicate that p21 induction during β cell stress triggers the intrinsic apoptotic pathway, thus making p21 a potential target to inhibit for protection of β cell mass.Supported by an APS William Porter Pre‐doctoral Fellowship and NIH grant DK078732.