bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post‐translational modulations of IL‐6 and oxidative stress networks in the hippocampus after epilepsy induced by pilocarpine in rats.
Authors: DA SILVA RUIZ ÉRICO GUSTAVO , ATUM ALLAN LUÍS BARBOZA , MARQUES DANILA , DOS SANTOS FELICIANO REGIANE , GOUVEIA TELMA LUCIANA FURTADO , NATHANSON LUBOV , MORRIS MARIANA , SILVA JOSE ANTÔNIO 
Published: April 2020

Epilepsy is a prevalent and serious brain condition, characterized by the recurrence of unprovoked seizures. Disturbances on cellular processes, which are controlled by post‐transcriptional gene expression modulations such as microRNAs (miRNAs) can lower multiple proteins expressions within molecular pathways. In order to elucidate the role miRNAs exert in the hippocampus from rats with epilepsy induced by pilocarpine, expression of miRNAs was quantified by NanoString technology. Furthermore, miRNA targets were identified by in silico analysis. We observed strong changes in miRNA expression profiles in hippocampal cells derived from epileptic rats compared to the control. MiRNAs to be related to inflammation and oxidative stress were found differentially expressed in silico analysis. For instance, in hippocampal tissue, miR‐146 emerged, which are known to interact with interleukin‐6, a major player in inflammatory process. Expression change was observed for let‐7, which targets IL‐6 as well. Further differentially expressed miRNAs were related to oxidative stress and generation of reactive oxygen species, such as miR‐30e. Altogether, the data indicate that miRNAs are an interesting starting point for functional and mechanistic epilepsy research.Support or Funding Information1) Universidade Nove de Julho, UNINOVE, São Paulo, Brazil 2) Universidade São Camilo, São Paulo, Brazil 3) Nova Southeastern University, NSU, Florida, USA
ANALYSIS OF RS12976445 VARIANT IN MIR125A AND FEMALE INFERTILITY IN LAGOS, NIGERIA
Authors: Gbenle segun A. , Igwo-Ezikpe Miriam , Taiwo Idowu A. , Salami Fatimah O. , Chukwunonso Chinwedu F. , Ofoma Osita N. , Onawoga Fatimah O. 
Published: April 2020

Micro RNAs play very important roles in maintaining normal human body physiology conditions, meanwhile, abnormal miRNA expressions have been found related to many human diseases including male and female infertility. Reports have indicated that disturbed miRNAs expression contributed to female infertility with reference to a polymorphism (rs12976445) within the miRNA125a sequence. This aim of the study was to investigate the effects of MiRNA125a gene disorders on female infertility and how these can be used in enhancing fertility among women seeking in vitro fertilization (IVF) in Lagos, Nigeria. Ethical approval was obtained from the Lagos University Teaching Hospital Health Research Ethics Committee (LUTHHREC) with number ADM/DCST/HREC/APP/2396. Infertile women (n=50) attending various fertility clinics in Lagos, Nigeria were recruited for this study and structured self‐administered questionnaires were distributed to the subjects to obtain their physiological and demographic parameters. DNA were extracted and amplified from blood samples obtained from subjects using primers specific for miR125a sequencing 5′‐TTTTGGTCTTTCTGTCTCTGG‐3′ and 5′‐TGGAGGAAGGGTATGAGGAGT‐3′. PCR products were analyzed using a BaeGI restriction enzyme specific to the rs12976445 variant. The restriction analysis revealed that 6 out of 50 subjects were TT homozygotes (12%) which were normal, 21 (42%) were TC heterozygotes variants and 23 (46%) were CC homozygotes variants. We hypothesized that rs12976445 may be a potential diagnostic marker of miR125a in female infertility among Nigerian women. Hence, mir125a should be considered in female infertility treatment.Support or Funding InformationNA
Toll‐Like Receptor Expression in the Hypothalamus of Rats Subjected to Chronic Inflammatory Pain Model
Authors: Teel Austin , Winter Lori , Duric Vanja , Clayton Sarah C. 
Published: April 2020

Hypertension is the state of having an abnormally and chronically elevated blood pressure. There are many comorbidities of hypertension, which includes cardiovascular disease, stroke, kidney disease, diabetes mellitus, and psychological disorders, such as chronic pain. Clinical observations suggest that approximately 39% of individuals experiencing chronic pain also have hypertension. While inflammation has been documented in areas of the brain in hypertension and chronic pain, the influence of chronic pain on activation of proinflammatory mechanisms within the cardioregulatory nuclei in the brain has not been evaluated. We speculate that chronic pain leads to inflammation in cardioregulatory brain regions, such as the hypothalamus and brainstem, that leads to dysregulation of autonomic tone and increases in blood pressure. Therefore, in the current study, we evaluated mRNA expression of different members of the Toll‐Like Receptors (TLR) family and associated proteins in the hypothalamus of rats exposed to 21 days of chronic inflammatory pain [i.e., 3 weekly injections of Complete Freund’s Adjuvant (CFA) into the hind paw]. Preliminary results show a decrease in the hypothalamic expression of TLR3 and an increase in the expression of TLR5, TLR7, and TRAM as a result of the pain protocol. These data suggest a relationship between chronic pain and hypothalamic inflammation and may suggest a possible target for probing the intersection of chronic pain and the development of hypertension.Support or Funding InformationDMU IOER and MSBS program
Analysis of Undergraduate Retention Outcomes: What do Students Actually Remember?
Authors: Dvoracek Peter , Balta Joy Y. , Osadjan Mark 
Published: April 2020

As a basic science, anatomy has commonly drawn criticism as a subject material that can be notoriously difficult for undergraduates to learn. Some common reasons for this scrutiny could be due to students’ perception of anatomy as a course that relies heavily on abstract, rote memorization
[1]. Learning through abstract memorization with high intrinsic cognitive load often produces poor retention, compared to more elaborative and meaningful encoding
[2]. In this study, student’s long‐term retention of practical material from a standard 4‐credit undergraduate human anatomy course was reassessed 5‐month past end of term. This data was compared to their continuous practical assessment throughout the semester. Students who had successfully completed this course in the past semester were invited to take part in this study. Informed consent was obtained and participating students attended a single, one hour post‐assessment during their regularly scheduled lab time. This post‐assessment evaluated their retention of lab course material using free recall type questions. Anonymized data were collected and analyzed using Excel. This study was approved by the Institutional Review Board at University of Minnesota.Out of the 156 enrolled students, 94 eligible students participated, yielding a 60% response rate. When comparing post‐assessment results to the practical lab exams, a significant linear moderate positive relationship between the two of them was observed (correlation coefficient=.5971, p<.00001). This suggests that practical lab exams are moderately accurate at predicting students’ performance on the post‐assessment. There is no correlation between student performance and memory retention, as indicated by the linear relationship between the data sets. When comparing written to practical exams, written exam scores stayed relatively constant while students’ practical exam scores were found to have steadily and significantly increased across the semester (p<.00001). This suggests that there was significant development of spatial reasoning skills from the lab material itself. More data, using the same metric, will be collected in the coming years from future cohorts to validate the findings of this study.Support or Funding InformationNone
Differential Protein‐Protein Interactions Driven by the Arg/Gly389 Single Nucleotide Polymorphisms in the Cardiac Beta‐1 Adrenergic Receptor
Authors: Bloomfield Christina , Tran Quang-Kim 
Published: April 2020

Activation of the β1 adrenergic receptor (β1AR) increases electrically induced calcium signals and accelerates sequestration of calcium in the myocardium, promoting contraction and relaxation. In humans, Arg389 and Gly389 are common single nucleotide polymorphisms (SNPs) in β1AR. The Arg389 SNP is associated with higher responses to β agonists in terms of cAMP production and contractile force development; in living subjects, it also is coupled with faster response to b blockers with respect to reductions in heart rate and myocardial contractile force. Nevertheless, it is unknown if calcium signals following β1AR activation affects the receptor’s activities and changes in Ca2+‐dependent regulation of β1AR can explain the difference between these polymorphisms. Calmodulin is the ubiquitous transducer of calcium signals and is a limiting factor in cardiomyocytes. We tested the hypothesis that β1AR directly interacts with calmodulin and that the Arg389 and Gly389 SNPs are associated with disparate β1AR‐calmodulin interactions. Using novel fluorescent biosensors developed for β1AR, we identified a novel calmodulin‐binding domain located at the juxtamembranous region of β1AR that encompasses the Arg/Gly389 SNP. The Arg389 SNP is associated with a biphasic interaction with Ca2+/calmodulin. However, the Gly389 SNP is associated with a monophasic interaction with CaM and a ~12‐fold lower affinity than the Arg389 SNP. These kinetic differences correspond to significant variances in the response of β1AR to physiological calmodulin concentrations, peaking at ~50 nM. We also identified that β1AR‐calmodulin interactions are calcium‐dependent, with higher Ca2+ sensitivity of the Arg389 β1AR–CaM interaction over the entire physiological Ca2+ range. These results suggest that calmodulin binding to β1AR is important for its functions and our observed different biochemical properties of these interactions may explain the different responses in subjects carrying the Arg389 vs the Gly389 SNPs.Support or Funding InformationIOER grant 091707 to Q‐KT.
Lack of muscle p62/SQSTM1 protects against high fat diet‐induced muscle wasting
Authors: Yamada Mami , Okutsu Mitsuharu 
Published: April 2020

Skeletal muscle atrophy is a hallmark of aging and several debilitating diseases (e.g., cancer, congestive heart failure, and type II diabetes) that contribute to morbidity and mortality. Oxidative stress plays an important role in skeletal muscle atrophy in these situations. Therefore, increased antioxidants expression could be a potentially protective measure against oxidative stress and skeletal muscle atrophy. We recently reported that p62/SQSTM1 expression in skeletal muscle contributes to control exercise training‐induced antioxidant enzymes expression with established p62 muscle‐specific knockout mice (p62mKO). However, the role of muscle p62 expression in type II diabetes induced‐muscle wasting was still not understood. Aim of this study was to elucidate the role of muscle p62 in type II diabetes induced‐muscle atrophy. p62mKO and their wild‐type littermates (WT) were fed normal chow (NC) or 45% fat diet (HFD) for 10 weeks. Body weight and food intake were measured every week. Glucose or insulin tolerance test were conducted at the 8 weeks. A grip strength test was performed at the end of HFD feeding. At 10 weeks, mice were sacrificed and harvested soleus (SO), gastrocnemius (GA), tibialis anterior (TA), extensor digitorum longus (EDL), and white vastus lateralis (WV) muscle. These muscles were measured weight and used for evaluation of protein expression. Muscle weight was measured by semi‐micro analytical balances and normalized by tibia length. Carbonylated protein was measures by western blot. Body weight, food intake, glucose and insulin tolerance ability, and grip strength were not significantly different between HFD fed p62mKO (p62mKO‐HFD) mice and HFD fed WT (WT‐HFD) mice. p62mKO‐HFD mice significantly attenuated loss of GA and EDL muscle weight. Carbonylated protein expression in p62mKO‐HFD mice was significantly lower than WT‐HFD mice. These results suggested that lack of muscle p62 protects against high fat diet‐induced muscle wasting via an antioxidants synthesis‐independent pathway.Support or Funding InformationThis study was supported by Grant‐in‐Aid for Research Activity Start‐Up (25882036), Grant‐in‐Aid for Scientific Research (B) (15H03080), Grant‐in‐Aid for Scientific Research (B) (18H03153), The Nakatomi Foundation, and The Uehara Memorial Foundation (to M.O.).
Regulation of the Phenotypic Switch of Vascular Smooth Muscle Cells by Adiponectin
Authors: Cullen Abigail , Centner Ann , Salazar Gloria 
Published: April 2020

Vascular smooth muscle cells (VSMCs) play an essential role in the development and progression of atherosclerosis. The phenotypic switch from contractile to synthetic cells induces excess proliferation and migration of VSMCs into the intima contributing to plaque formation. Adiponectin (Adpn) is an adipokine that regulates glucose metabolism through AMPK and plays beneficial roles in atherosclerosis. We hypothesize that Adpn promotes the contractile phenotype of VSMC reducing proliferation and migration of VSMCs, a process that is protective against plaque formation.Differentiation, proliferation, and signaling through AMPK‐dependent pathways were assessed in VSMCs isolated from aortas of wild type (WT) and Adpn−/− mice. Proliferation markers, including cyclin D1, were increased in Adpn−/− cells, and AMPK activity and differentiation markers were reduced. Cells were analyzed for matrix metalloproteinases (MMPs) which are responsible for extracellular matrix (ECM) remodeling, a contributing factor to the VSMC phenotypic switch. We found that MMP protein expression and activity, measured by zymography, were reduced in Adpn−/− cells. To test whether the phenotypic switch is regulated by AMPK, we treated cells with Metformin, an AMPK activator, or AdipoRon, an activator of Adpn receptors. Metformin and AdipoRon reduced Cyclin D1 and MAPK signaling in Adpn−/− cells, suggesting that AMPK prevents VSMC proliferation; however, none of the treatments yielded an effect on markers of differentiation.These data illustrated that Adpn regulates proliferation through an AMPK‐dependent signaling pathway, while regulating differentiation by an AMPK‐independent mechanism. The role of MMPs in VSMC differentiation in response to Adpn remains to be elucidated.
A Pipeline for Expression, Functionalization, and Characterization of Human Lectins Involved in Innate Immunity
Authors: Dodge Gregory , Bartlett Helen , Isabella Christine , Diehl Roger , Dugan Amanda , Kiessling Laura , Imperiali Barbara 
Published: April 2020

In humans, a collection of diverse proteins known as lectins are responsible for binding to glycan epitopes. Recognition of extracellular glycan epitopes represents a key facet of the innate immune response in eukaryotes. These epitopes can be used to distinguish cell types, self‐from non‐self, and perhaps even pathogenic from commensal bacteria. Understanding human lectin specificity can uncover mechanisms underlying innate immunity. Additionally, lectins represent attractive reagents for the development of glycan‐reading probes. Here, we demonstrate our efforts to develop and deploy a pipeline for recombinant expression, functionalization, and characterization of a subset of human lectins, including C‐type lectins, ficolins, jacalin‐type lectins, galectins, and intelectins. Target lectins can be efficiently expressed and purified, functionalized with either biotin or a fluorophore via sortase‐mediated ligation under flow, and screened for glycan binding. The success of this pipeline has been validated in preliminary studies showing that the recombinant lectins can engage with glycans from mammalian glycan arrays, bacterial glycan arrays, purified mucins, or human biological samples. These experiments highlight the potential of lectins as valuable molecular probes that fill a gap in the current molecular toolkit for glycan analysis.Support or Funding InformationNIH U01 CA231079‐01
Evaluation of melatonin therapy on improving the metabolic disorders associated to obesity in rats
Authors: filali houda , kadil Youness , Ettaqui Soukaina 
Published: April 2020

Obesity is a worldwide epidemic and there are many diseases associated with it. Recent studies suggested that melatonin may be involved in the regulation of body mass and metabolic homeostasis through different mechanisms.To this purpose, we conducted an experimental study on 24 adults male Wistar rats, separated into 2 control groups and 1 test group. Our experimental protocol took place in three phases, an obesity induction phase in which the rats were subjected to a hyper fat diet “Cafeteria diet”. A therapeutic phase in which the control group received NaCl as a placebo, the test group was treated with melatonin at a dose of 5mg/kg/day. The groups were randomized and received treatment intraperitoneally for 6 weeks. A Biological blinded evaluation for lipidic, glucidic, and inflammatory (CRP) assessments were performed for each group.The results of our study showed that the Cafeteria diet significantly increased body weight with a gain of up to 126g (p=0.00). The biological analysis of the blood of rats treated with melatonin showed a decrease in blood glucose levels, triglycerides, LDL, HDL, CRP and total cholesterol compared to the initial values. Plasma analysis results obtained at the end of the therapeutic phase between melatonin and placebo‐treated rats showed a significant decrease in total cholesterol (p=0.002), LDL (p=0.005), HDL (p=0.014) and blood glucose (p=0.013). The difference between the two groups for CRP (p=0.084) and triglycerides (p=0.116) was not significant.Based on our results melatonin seems to have a beneficial effect against metabolic disorders related to obesity.Support or Funding InformationN/A
The role of depressive symptoms on brain blood vessel pulsatility in humans
Authors: Sanjana Faria , Richey Rauchelle E. , DeConne Theodore M. , Saunders Erika F. , Brothers R. Matthew , Martens Christopher R. , Greaney Jody L. 
Published: April 2020

The prevalence of major depression continues to increase, particularly in young women. Depression is associated with increased risk for cardiovascular disease and cognitive impairment later in life. Peripheral vascular dysfunction, including stiffening of the large elastic arteries, is evident in adults with depression and may mediate the relation between depressive and neurocognitive symptoms by exposing the cerebral vasculature to damaging pulsatile pressure waves. We hypothesized that increased depression symptom severity would be associated with more pulsatile blood flow through the middle cerebral artery (MCA) as assessed by the pulsatility index (PI). Transcranial Doppler ultrasound was used to measure MCA cerebral blood velocity (CBV) in 40 young adults (25 F/15 M, mean age: 24±5 y) having a wide range of depressive symptom severity. MCA PI was calculated as the difference between maximum CBV and minimum CBV normalized to the mean CBV. Self‐reported depressive symptom severity was derived using the Patient Reported Outcome Measurement Information System (PROMIS; T‐score). The association between PI and depressive symptom severity was quantified using linear regression; sex differences were assessed using multiple linear regression. PI (mean±SE: 0.8±0.02; range: 0.6–1.0) was negatively correlated with depressive symptom severity (mean±SE: 51.3±1.6; range: 37.1–71.9) (r2=0.12, P=0.03). There was no difference in the relation between depressive symptom severity and PI between men and women (R2=0.09, P=0.39). Lower pulsatility of the cerebral arteries in adults with more severe depressive symptoms may indicate a possible compensatory role to protect the brain from damaging pressure waves. Future studies should examine the mechanisms by which depression contributes to decreased pulsatility of cerebral blood vessels and stiffening of large elastic arteries in young individuals, including the possible role of augmented cerebral autoregulation, and whether this mechanism changes with advancing age.Support or Funding InformationNIH Grant P20GM113125
CHRONIC ALCOHOLISM ASSOCIATED WITH DIABETES INDUCED APOPTOSIS IN THE CORPUS CAVERNOSUM IN RATS
Authors: Cirino Mucio Assis , Schimming Bruno , Novais Paulo Cezar , Lizarte Fermino S. , Melo de Carvalho Camila A. , Fazan Valeria P. S. , Tirapelli Daniela P. C. , Molina Carlos A. F. , Junior Silvio Tucci , Tirapelli Luis F. 
Published: April 2020

The association between diabetes mellitus and erectile dysfunction has been studied for many years. Erectile dysfunction secondary to angiopathic, neuropathic and myopathic damage is one of the main complications of diabetes in men. Other reproductive complications include ejaculatory dysfunction, hypogonadism, modified semen parameters, and delayed puberty. On the other hand, ethanol has various effects too, on male sexual activity, in small amounts improves erection and increases libido because of its vasodilatory effect; however, large amounts can cause central sedation, decreased libido, impaired the penile tumescence, and transient erectile dysfunction. Chronic alcoholism may cause hypogonadism and polineuropathy that may affect penile nerve function. Therefore, chronic alcoholism induced dysfunction of smooth muscle in the corpus cavernosum in rats. Although, effects of ethanol on the ultrastructure of cavernosal smooth muscle cells, elastic fibers and collagen content; and apoptosis in the erectile tissues of diabetic rats has been showed, no studies have been done to analyse the apoptotic effects of the diabetes associated with ethanol in the corpus cavernosum in rats.ObjectivesTo investigate the effects of chronic ethanol consumption and diabetes on apoptotic process in the corpus cavernosum.Material and MethodsMale Wistar rats were divided into four groups: control, diabetic (alloxan injection), ethanol, and ethanol‐diabetic (12 rats in each group). Fragments of corpus cavernosum were obtained and destined to the immunohistochemistry and real‐time PCR to analyze the protein expression of apoptotic genes CASPASE‐3, and CASPASE‐9.ResultsThe immunoreactivity of CASPASE‐3 and CASPASE‐9 was diffuse and higher in the treated groups, however there was no significant difference between the experimental groups, only when compared with the control group. An increase was observed in the gene expression of CASPASE‐3 and CASPASE‐9 in the diabetic and ethanol‐diabetic groups when compared with to control and ethanol groups.ConclusionsThere was an increase in apoptosis in ethanol and ethanol‐diabetic rats. The association of these factors (ethanol and diabetes), jointly with neuropathy and arteriopathy could lead to development of erectile dysfunction.