bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heparinox, a generic version of low molecular weight heparin enoxaparin, is bioequivalent to the branded version
Authors: Qneibi Dalia , Ramacciotti Eduardo , Kouta Ahmed , Hoppensteadt Debra , Daravath Bharathi , Jeske Walter , Iqbal Omer , Fareed Jawed 
Published: April 2020

IntroductionEnoxaparin is the most widely used low molecular weight heparin. Several generic versions of enoxaparin have also become available for clinical use in the indications for which this product is approved. The regulatory bodies require the generic products to conform with the product specifications in terms of biological and structural equivalence. Heparinox (Cristália, São Paulo, Brazil) represents a new generic version of enoxaparin which has become available in the South American continent recently. The purpose of this investigation is to compare the branded enoxaparin (Sanofi Aventis, Paris, France) with heparinox using validated biologic and physico‐chemical assays to demonstrate the similarities of this low molecular weight heparin with its branded version.Materials and methodsHeparinox brand of enoxaparin was obtained in commercial syringes containing 20 and 40 mg doses. Branded enoxaparin was commercially obtained in syringes containing 100 mg. The molecular weight profiling was carried out by gel permeation chromatography using a narrow range calibrator method. The anticoagulant activities were measured in whole blood and plasma based assays. The antiprotease activities were measured using anti‐Xa and IIa chromogenic substrate methods. USP compliant assays were used to calculate potency relative to the NIBSC low molecular weight heparin standard (NIBSC, London, England). Protamine titration studies were carried out to compare the extent of neutralization of the generic and branded products.ResultsThe molecular weight of 2 batches of heparinox was comparable to that of the branded enoxaparin (4.1 kDa vs. 4.1 kDa). In the ACT, APTT and thrombin time assays the concentration curves for heparinox and branded enoxaparin were superimposable. Similarly, the antiprotease activities of the branded and generic products were comparable. There was no difference in the USP potency of the heparinox (96 anti‐Xa units/mg, 32 anti‐IIa units/mg) in comparison to the branded product (97 anti‐Xa units/mg, 32 anti‐IIa units/mg). The protamine titration studies revealed similar neutralization profiles for both the generic and branded products.ConclusionsThese studies demonstrate that the newly introduced generic low molecular weight heparinox exhibits similar molecular weight and functional profiles in comparison to the branded enoxaparin. Additional structural studies using NMR and oligosaccharide analysis, and pharmacological profiling in terms of antithrombotic, bleeding and PK/PD parameters are currently in progress.
Gender Differential Upregulation of 15‐Hydroxyprostaglandin Dehydrogenase Associates with Aspirin Decreasing Intracranial Aneurysm (IA) Rupture in Mice
Authors: Lu Yongjun , Ishii Daizo , Hasan David M. 
Published: April 2020

Previously we showed 1) that aspirin decreased the risk of IA rupture significantly more in male than in female in the International Study of Unruptured Intracranial Aneurysms (ISUIA) and 2) the presence of sex‐differential plasma level of 15‐hydroxyprostaglandin dehydrogenase (15‐PGDH) in the lumen of human IAs. These observations were confirmed in our animal experiments using established mouse model of IAs. However, the aspirin dose used in these experiments was high (25 mg/kg/d).In the present study, we used a lower dose of aspirin 5 mg/kg/d (comparable to 325 mg for human) in our mouse‐model experiments to examine the protective effect of aspirin at lower doses and to test whether such sex differential response still exists in response to lower dose of aspirin.Aneurysms were induced with hypertension using Angiotensin II infusion (1000ng/kg/min for 21 days) and elastase (35m Units, single injection into mice basal cisterns). When grouping males and females together (n=30), aspirin decreased significantly the incidence of aneurysm when compared to control (60% vs 87%, p=0.0164), and the incidence of aneurysm rupture (43% vs 68%, p=0.0480). When analyzing the incidence of aneurysm rupture by gender (n=15), the incidence of aneurysm formation was significantly lower in male versus female mice on aspirin (40% vs 80%, p=0.0302), and the incidence of aneurysm rupture was lower in male mice (33% vs 53%, p=0.2311).qPCR analysis from individual mouse cerebral arteries showed significantly higher wall tissue of 15‐PGDH mRNA in male than in female mice at baseline (before administering aspirin) (1.69±0.12 vs 1.10±0.14, p=0.027). Administering aspirin upregulated this expression and maintained the sex difference (2.37±0.30 vs 1.25±0.12, p=0.012).These observations further validate the previous findings that aspirin protect against IA rupture significantly more in males than in females, potentially via 15‐PGDH pathway, which may provide a new promising therapeutic target for decreasing risk of aneurysm ruptures.Support or Funding InformationNIH, 1R01NS107293‐01A1
Protective Effects of Magnesium Biotinate on Propionic Acid‐Induced Autistic Features in Rats
Authors: Komorowski James , Ojalvo Sara Perez , Orhan Cemal , Erten Fusun , Sahna Engin , Kılıc Ertugrul , Sahin Kazim 
Published: April 2020

ObjectiveThis study investigated the protective effects of magnesium biotinate (MgB) on propionic acid (PPA)‐induced autistic features in rats.BackgroundBiotin is involved in energy metabolism and various immune and nerve functions. MgB is a novel biotin complex that has enhanced absorption. Compared to D‐Biotin, MgB has superior tissue uptake and anti‐inflammatory effects. Neurological problems can occur in biotin‐deficient individuals. Supplementation with MgB may prevent or reduce neurodevelopmental disorders such as those seen in autism spectrum disorder.Design/MethodsThirty‐five male Wistar rats (3 weeks old) were randomized into the following five groups; 1: Control (received saline), 2: PPA alone, 3: PPA + 10 mg human equivalent dose (HED) MgB, 4: PPA + 100 mg HED MgB, 5: PPA + 500 mg HED MgB. Animals were fed a standard diet, with or without MgB, for 35 days and on day 30, rats were administered PPA (500 mg/kg BW/day) by subcutaneous injection for 5 days. Neurobehavioral tests were then performed for two days. Serum and tissue samples were then collected for analysis.ResultsSocial interaction deficits and signs of brain toxicity, including higher brain levels of inflammatory and oxidative stress markers, were observed in PPA alone rats. Brain levels of inflammatory markers were lower in all MgB groups compared to PPA alone (p<0.05). Oxidative stress markers were lower and antioxidant markers were higher in the 100 mg and 500 mg HED MgB groups compared to PPA alone (p<0.05). These effects were most significant in the 500 mg HED MgB group. Sociability and social preference scores were greater in the 100 and 500 mg HED MgB treatment groups compared to PPA alone (p<0.05). The 500 mg HED MgB dose improved social preference score to the extent that it did not differ from normal controls.ConclusionsPre‐treatment with MgB significantly reduced brain toxicity and improved autistic features induced by PPA.Support or Funding InformationThis study was conducted at Firat University and funded by JDS Therapeutics, LLC.
Evaluation of Tumor Necrosis Factor Alpha (TNF‐α) in Sleep‐Deprived Menopausal‐Induced Rats and the Impact on Bone Health
Authors: Ellsworth Nicole Lynn , Frisch Frank 
Published: April 2020

Post‐menopausal osteoporosis as a consequence of estrogen depletion is a growing concern for women in the United States. As more women take on executive positions and experience sleep deprivation, there is the potential for up regulation of pro‐inflammatory cytokines, such as tumor necrosis factor alpha. It follows that the homeostatic imbalance of osteoclastic and osteoblastic activity leads to a greater risk of disease. Bisphosphonates generally, and Zoledronate specifically works by decreasing the number of osteoclasts. This current study investigated the impact of Zoledronate on the concentrations of tumor necrosis factor alpha‐type (TNF‐α) in 32 ovariectomized Wistar rats that were ovariectomized to simulate post‐menopausal estrogen‐deficiency. After one week of surgical recovery, rats were separated into 4 groups. The control group (C, n=4) was given an intraperitoneal (IP) injection of 0.45 mL of 0.9% saline, were housed in standard conditions permitting 12 hours light and 12 hours dark. The Zoledronate group (Z, n=8) were given an IP injection of 50 ug/kg of 10% Zoledronate and housed in standard conditions with a 12 hour light/dark cycle. The sleep‐deprived group (SD, n=8) were given the same IP injection as the rats in C, but were housed in chambers that did not permit sleep for 18 hours, then moved to sleep chambers for 6 hours. The sleep‐deprived Zoledronate group experienced the same sleep deprivation as the SD group, but received an IP injection of 50ug/kg body weight of 10% Zoledronate. Throughout the five‐week period of sleep deprivation cycles, the concentrations of TNF‐α were collected and examined. It was originally hypothesized that the sleep‐deprived group of rats would have the highest concentration of TNF‐α due to the biological stress associated with insomnia. However, TNF‐α levels were significantly higher in the Zoledronate group than both the control and sleep‐deprived groups, as well as the sleep‐deprived with Zoledronate groups (p<0.01). We ascribe this to bisphosphonate induced transient fever seen in Zoledronate usage in previous studies (Dicuonzo, 2003). It is also suspected that the low concentrations of TNF‐α in the sleep‐deprived groups are seen due to the short time frame of this experiment along with a challenged immune system in the animals. With a longer period of sleep deprivation, it is possible that the hypothesized cytokine levels would be reached.Support or Funding InformationThis study was supported in part by Novartis, Basel, Switzerland
Identification of Predictors Underlying the Attitude of Medical Students towards Medical Biochemistry in their Pre‐clinical Years and its Influence on Students’ Learning Outcome
Authors: Sengupta Anamika 
Published: April 2020

BackgroundThe importance of positive attitude in the learning process of students has been acknowledged in numerous educational studies (Reiss 2004; Berg 2005; Banya 2005; Trumper 2006). The frequently observed negative attitude of medical students towards Biochemistry among pre‐clinical students in US medical schools served as the motivation for this study. It aims at identifying predictors underlying the attitude of 150 participating medical students (1st, 2nd, and 3rd semesters at Ross University School of Medicine) towards medical biochemistry (a basic science subject that they are exposed to in their pre‐clinical years) and explores the relationship between the possible predictors, attitudes and learning outcomes.MethodsA 7‐item questionnaire paper survey with questions (related to students’ demography (age, sex, marital status, first language), their familiarity with the subject matter, and a 1–7 Likert scale rating of their attitude & confidence levels towards biochemistry was distributed in class at the start of the semester. MCAT scores and GPAs were obtained from the University database. Correlation and Multiple Regression models were used for data analysis.ResultsPreliminary results indicated students’ attitude towards Biochemistry was positively correlated with their levels of confidence for the subject. Multiple Regression analysis identified Confidence and Age as predictors of attitude. However, MCAT Biology scores and familiarity with the subject matter were the best predictors of students’ confidence levels. Learning outcomes were directly influenced by gender and first language, none of which predicted their attitude towards biochemistry.ConclusionAlthough students’ prior exposure to the subject matter determines their approach to medical biochemistry in the pre‐clinical years (in addition to their MCAT scores and ages), the ultimate performance outcomes in the subject are notably higher in males with English as a first language.
Comparisons of catalytic efficiency during the reduction of lignocellulosic substrates between free enzyme versus enzyme bound to mobile enzyme sequestration platforms (mESP)
Authors: Fatema Nour , Moore Blakely , Wangnai Chinnapong , Ceballos Ruben Michael 
Published: April 2020

Plants represent a vast, renewable source of biomass. Plant biomass serves as a major substrate for sustainable biofuel production. However, to overcome the food‐versus‐fuel dilemma, effective use of plant residues for cellulosic (versus corn‐ or sugarcane‐based) ethanol must be realized. Effective deconstruction of lignocellulosic matrix and efficiently accessing and reducing cellulose to fermentable sugars (i.e., glucose) would overcome current constraints that prevent cellulosic ethanol from becoming an economically viable alternative for liquid/transportation fuel. Cellulosic feedstocks consist of cellulose (20–50%), hemicellulose (15–35%), and lignin (5–30%). In previous work, we demonstrated that the use of thermotolerant and acidotolerant engineered mobile enzyme sequestration platforms (mESP) could enhance lignocellulosic deconstruction of two acid pretreated (and alkaline pretreated) feedstocks. Specifically, acid‐pretreated wheat straw and corn pericarp were subjected to a suite of cellulases, an enzyme cocktail, under two conditions: (a) pretreated substrate plus enzymes free in solution (experimental control); and, (b) pretreated substrate plus enzymes bound to a prototype mESP. The mESP‐bound enzymes showed enhanced ability to convert complex carbohydrates to glucose (i.e., sugar reduction) when compared to the free enzyme in solution control (at equimolar enzyme concentrations). Although the mESP was known to be thermotolerant and acidotolerant, enhancement of sugar reduction efficiency was also observed with alkaline pretreated substrate. Still, these preliminary experiments only demonstrated a 2‐ to 3‐fold increase in enzymatic efficiency over controls. Indeed, with some enzyme ‘cocktails’, sugar reduction efficiency actually decreased when employing mESPs. It was suggested that steric interference between enzymes due to the close proximity of enzyme attachment points on the platform and the use of enzymes with different target points (exo‐versus endo‐) on the substrate (i.e., cellulose) may limit the magnitude of enhancement that can be achieved. After re‐engineering the mESP system to separate attachment points and strategic development of free enzyme cocktails and enzyme composition on charged mESPs, this study demonstrates that next‐generation mESPs can improve catalytic efficiency more than 3‐fold. In addition, alternative substrates have been tested (e.g., rice straw) with similar results. These results and implications for mESP technology are discussed in detail.Support or Funding InformationU.S. National Science Foundation Molecular and Cellular Biosciences (MCB) grant (Award No. 1818346; PI‐Ceballos); U.S. National Science Foundation Research Coordination Network (RCN) grant (Award No. 1624171; PI‐Ceballos)
Assessment of the Alveolar Bones’ Unique Structure and Impact on Periodontology
Authors: Shah Kushal , Lacin Nursima , Sun Lu , Naveh Gili 
Published: April 2020

The composition and structure of bones is important to the function of the periodontal ligament (PDL) in particular and to tooth movement overall. One bone crucial to the arrangement of teeth is the alveolar process, which connects teeth to the jawbone through intramembranous bone formation housing the cementum. Comprising of both cortical bone and cancellous bone, the alveolar process is unique in function as it is able to endure tension during mastication by working with the PDLSeeing that alveolar bone can endure tension and compression forces provokes question towards how the composition and structure influences this bone.Using immunohistochemistry (IHC) staining, collagen II, IX, and XI, have all been found in the alveolar bone; these are a set of tissue specific collagens that are found at low levels in intramembranous bone. Identifying this type of collagen in the alveolar bone is unusual as it is mainly found in cartilage and the vitreous humor in the eye.These observations will provide insights into the connection between collagen in the alveolar process and basic structure‐function relations of the tooth‐PDL‐bone system, while establishing a better understanding of tooth movement reactivity and the development of treatments to periodontal diseases.Support or Funding InformationHarvard School of Dental Medicine AFM project
Identifying species‐specific Hfq‐RNA Interactions using a bacterial three‐hybrid assay
Authors: Tran Anh M. , Chambers Kelly M. , Berry Katherine E. 
Published: April 2020

Bacteria use non‐coding small RNAs (sRNAs) to regulate expression of target mRNAs, often with the help of protein chaperones. About half of bacterial species possess a well‐characterized globally‐acting RNA‐binding protein, a hexameric protein called Hfq, which contributes to virulence in many pathogenic species. While much is known about the mechanism of RNA interactions by Hfq proteins in certain well‐studied model bacteria, there are significant gaps in our understanding of how conserved the RNA‐binding behavior of Hfq homologs from diverse bacterial organisms. Here, we use a recently developed bacterial three‐hybrid (B3H) assay to further define the interactions between Hfq and its RNA substrates. This assay connects the interaction between a DNA‐bound RNA and a RNA polymerase (RNAP)‐bound protein Hfq to the expression of a reporter gene, providing a genetic route to the analysis of RNA interactions from a heterologously expressed RNA‐binding protein. This provides a facile route to study the behavior of diverse RNA‐binding proteins in an innocuous laboratory strain of E. coli. Here we present data collected using the B3H assay to compare the RNA interactions of Hfq from several bacterial species, including Listeria monocytogenes, Caulobacter crescentus, and Escherichia coli. We have observed distinct RNA‐binding profiles between these Hfq proteins. Sequence alignments of these three proteins led to a hypothesis that charged residues along the rim surface of Hfq may underlie the differences in binding preferences for different sRNAs. Data will be presented that test this model using both chimeric and site‐directed mutants. Our long‐term goal is to gain a better understanding of what structural elements of an RNA‐binding protein such as Hfq determine its RNA binding and function in driving bacterial gene regulation.Support or Funding InformationThis work was supported by National Institutes of Health [R15GM135878], Mount Holyoke College and the Henry Luce foundation.
Astrocytic modulation of IKA, NMDA and AMPA currents in NTS neurons of rats is affected by sustained hypoxia
Authors: Machado Benedito H. , Bonagamba Leni G.H. , Accorsi-Mendonça Daniela 
Published: April 2020

Short term sustained hypoxia (SH, FiO2 0.1, 24 h) produces cardiovascular and respiratory changes mainly due to peripheral chemoreflex activation. SH alters the electrophysiological properties of neurons in the NTS, where the first synapses of chemoreflex afferents are located. In the present study we evaluated alterations produced by SH on neuronal excitability and excitatory synaptic transmission in the NTS neurons integral to chemoreflex pathways. After SH protocol, brainstem slices were obtained for electrophysiological recordings using whole cell patch–clamp and fluoracetate (FAC) was used to produce metabolic inhibition of astrocytes. SH increased the action potential discharge in response to positive injected current into NTS neurons (p=0.0048). The presence of A‐type potassium current (IKA) was observed and its peak amplitude was larger in neurons from control [Vm = 10 mV, 1428 ± 600 pA (n=10)] than in SH rats [Vm = 10 mV, 334 ± 76 pA (n=10)]. Inhibition of astrocytes with FAC decreased the IKA amplitude in neurons from control rats [1227 ± 129 pA vs 605 ± 210 pA (n=7)], but not in SH rats [475 ± 110 pA vs 427 ± 114 pA (n=6)]. With respect to excitatory neurotransmission, SH increased AMPA/kainate [−183 ± 122 pA (n=10) vs −353 ± 101 pA (n=10)] and NMDA currents amplitude [61 ± 10 pA (n=7) vs 102 ± 37 pA (n=10)]. Astrocytic modulation on AMPA [aCSF: −353 ± 101 pA vs aCSF + FAC: −369 ± 76 pA, (n=10)] and NMDA currents [aCSF: 102 ± 37 pA vs aCSF + FAC: 108 ± 32 pA, (n=10)] was blunted by SH. In addition, SH increased AMPA current density [control: −6 ± 3.5 pA/pF (n=6) vs SH: −20 ± 12 pA/pF (n=7)]. The data shows that astrocyte modulation of synaptic transmission in NTS neurons integral to the chemoreflex pathways is reduced by SH, which may contribute to the observed increase in the chemoreflex responsiveness on this experimental model.Support or Funding InformationFAPESP, CAPES and CNPq
Intermittent but not Chronic Access to Western Diet Selectively Induced Binge‐like Eating and Risk‐taking Behavior in Rats.
Authors: Shaw Cemilia , Patterson Sasha , Shah Krishna , Longley Megan , Sirohi Sunil 
Published: April 2020

Binge eating disorder (BED), the most common eating disorder in the US, has a lifetime prevalence of 2.8% and has been associated with many other psychological and metabolic disorders. Several preclinical models developed to study binge‐eating disorder and related pathologies use stress, food restriction, or limited access conditions to induce binge‐like intake. Using limited access model, Corwin and colleague, demonstrated that limited‐short (2 hr Mon, Wed and Fri) access to vegetable shortening induced a binge‐compensate feeding pattern which was not present in limited‐regular (2 hr every day) access conditions. Similar findings were reported when a nutritionally complete high‐fat diet was utilized either every day (HFD‐ED) or every‐third day (HFD‐3D). Using this model, we have recently shown that both HFD‐ED and HFD‐3D groups of rats undergo similar binge‐compensate eating patterns and display compulsive feeding/risk‐taking behavior, suggesting the frequency instead of presence/absence of binge‐like feeding episodes as a major difference between HFD‐3D and HFD‐ED. It was also unclear if the intermittent availability or the HFD itself triggered compulsive feeding. Therefore, in the present study, we evaluated the impact of ad libitum chow and western diet (WD; rich in both sugar and fat) consumed in a binge manner in relation to the same diet consumed in a non‐binge manner. Male Long Evans rats received chronic (every day) or intermittent (Mon, Wed, and Fri) 24 hr access to Western Diet for six weeks. The control group received normal rodents chow. All the animals had ad libitum access to chow and water throughout the experiment. We observed that intermittent access‐group significantly overconsumed on WD‐access days and under‐consumed on chow‐access days as compared to both chow controls and chronic access group. Chronic access group, on the other hand, significantly overconsumed every day as compared to chow controls but not in a binge/compensate manner. Only intermittent access‐group showed elevated food intake than their baseline during the first two hours of WD‐access days. Finally, only the intermittent access‐group showed risk‐taking behavior when tested in the light/dark box. These data demonstrate selective induction of risk‐taking behavior following binge‐like eating but not when the same diet was consumed in a non‐binge manner.Support or Funding InformationResearch reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number TL4GM118968 and RL5GM118966. This publication was also made possible by funding, in part, by NIMHD‐RCMI # G12MD007595‐10, NIGMS‐BUILD # UL1GM118967 and NIGMS‐SCORE # 1SC3GM127173‐01A1 to SS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.