bluuebunny/crossref_metadata_2025_split huggingface dataset:
PTEN binding properties for different model membrane morphologies
Authors: Gericke Arne , Ross Alonzo H , King Katrice E. , Neuman Brittany M. , Jiang Zhiping 
Published: June 2021

PTEN acts as an agonist to PI 3‐kinase signaling by removing the phosphate group in the 3 position of PI(3,4,5)P3. PTEN membrane association and activation requires the interaction with PI(4,5)P2 and PS. In biological membranes, these lipids may form upon interaction with other molecular entities domains that exhibit distinct compositional and physicochemical characteristics. It is the objective of this study to elucidate the relationship between lipid bilayer morphologies and the extent of PTEN binding and PTEN membrane association dynamics.MethodsTo characterize lipid morphologies in the absence and presence of PTEN, we used fluorescence microscopy measurements of mixed lipid giant unilamellar vesicles (GUVs). PTEN binding extent is evaluated using SPR and Trp fluorescence measurements. The binding kinetics of PTEN bilayer interaction is elucidated using stopped‐flow experiments.ResultsThe interaction of PTEN with mixed PC/PI(4,5)P2 model membranes results in the formation of PI(4,5)P2 enriched domains. Domain formation in the absence of PTEN is also observed when cholesterol is added when making mixed PC/PI(4,5)P2 vesicles. We find an increased PTEN binding in the presence of PI(4,5)P2 domains, which is probably due to increased local PI(4,5)P2 concentration. This work was supported by NIH R01 NS021716 and NSF CHEM 0922848 and 1058719.
Physiological implications and Haematological indices of Chicks fed on Feed based on Biodegraded Agrowastes
Authors: Babalola Musa Oladayo , Magbagbeola Abiola O , Ebuehi Osaretin A , Okochi Ihuaku Veronica , Okafor Uzoma A 
Published: June 2021

The long‐term benefits of using agrowaste residues as feedstocks will include, reduced potential for water, air, and soil pollution. The study was designed to find out the response of broiler chicks to agrowastes based formulated feed.Aboria sawdust was biodegraded using mixed Aspergillus niger and Penicillium chrysogenum culture. Poultry feed was formulated by replacing 25% (Group A), 50% (Group B), 75% (Group C ) and 100% (Group D)maize in conventional feed with degraded sawdust. The grouping of birds followed the standard procedure for animal care. Feeding was for 28 days, the body weight of chicks was monitored and blood analysis was done.The body weight showed no statistical difference in entire Group. Also, no significant difference in the glucose, Hb, WBC, differential blood count, and PCV (p<0.05) in all the groups as compared to the control. However, there was significant difference in ESR (p<0.05) of Group B and D and no significant difference in Group A and C when compared with the control. There was statistical significant difference in the triglycerides of all the groups except Group D when compared with the control. Cholesterol showed, no statistical significant difference in Group A and B, however, there was a high statistical significant difference in Group C and D. The result indicated the prospect of biodegraded agrowastes utilization for poultry feed formulation.
RGS proteins maintain robustness of GPCR‐GIRK coupling
Authors: Chuang Huai-hu , Chuang Alexander 
Published: June 2021

ObjectiveTo elucidate the mechanism underlying sustained GPCR‐GIRK coupling under RGS actions.ResultsRegulators of G‐protein signaling (RGS) are GTPase activating proteins (GAP) that reduce response amplitudes of activated G‐protein coupled receptors (GPCRs). We discovered that, although RGS proteins drastically accelerate kinetics of GPCR‐coupled K+ currents (GIRK), they actually increased amplitudes of inhibitory neurotransmitter‐evoked GIRK currents. The RGS‐Box domain alone is sufficient for stimulation of transmitter activation of K+ currents, but its membrane association enhances the efficiency of stimulation. Moreover, RGS4 mutants with compromised GAP activity still augment GPCR‐GIRK coupling. Among the pertussis toxin sensitive G‐proteins, we found that RGS4 selectively stimulates Gαo to maintain robustness of GPCR‐GIRK coupling, by accelerating activation kinetics of Gαo.ConclusionOpposing actions of RGS proteins both stimulate and inhibit G‐proteins to modulate ultimate amplitudes of transmitter‐induced GIRK currents and to differentiate signal intensity coupled to various G‐protein isoforms.
MZF‐1 regulates the CTGF gene in the hematopoietic compartment
Authors: Piszczatowski Richard 
Published: June 2021

Connective Tissue Growth Factor (CTGF), an extracellular protein with key roles in wound healing and tissue homeostasis, has recently been shown to be in abundance in thrombocytes. Paradoxically, megakaryocytes, the platelet precursors in the bone marrow, contain no detectable levels of CTGF, and the source of CTGF in platelets is yet to be determined. It has been proposed that cells in the vicinity of the megakaryocyte secrete CTGF upon cellular signaling, at which point it is then internalized by fragmenting platelets entering the vasculature.In this study, we report the discovery of a possible functional binding site for Myeloid Zinc Finger‐1 (MZF‐1), a transcription factor localized in the bone marrow, in the promoter region of the human CTGF gene, using bioinformatics. We further show that, in HeLa, HEK‐293, and select hematopoietic cells, binding of MZF‐1 to the CTGF promoter can be detected with Chromatin Immunoprecipitation (ChIP). Furthermore, we investigated the induction of CTGF by calcitriol (1,25‐ dihydroxyvitamine D3) via MZF‐1, through the PI‐3 kinase pathway in HS‐5 stromal fibroblasts, a possible candidate for the supply of CTGF to platelets entering the bloodstream. Finally, expression of CTGF is attenuated following ablation of MZF1 by miRNA. Taken together, our results argue that MZF‐1 is a key regulator of CTGF in the hematopoietic compartment, and may be a factor in the process of CTGF acquisition by thrombocytes.
MTHFR 1298 A>C gene polymorphism is associated with Non‐Alcoholic Fatty Liver Disease (NAFLD) and Insulin Resistance in well‐nourished patients
Authors: Trovato Guglielmo M , Ragusa Angela , Catalano Daniela , Martines G. Fabio , Tonzuso Antonia , Pirri Clara , Buccheri Maria Antonietta , Trovato Francesca M , Di Nora Concetta 
Published: June 2021

MTHFR gene encodes MethyleneTetraHydroFolate Reductase, a regulatory enzyme whose polymorphisms are associated with higher homocysteine. Among polymorphisms, C677T, a termolabile form, but not A1298C, was associated with fatty liver and insulin resistance.Aimto investigate the influence of A1298C polymorphism on NAFLD in well‐nourished non‐diabetic patients (pts).Patients263 subjects (121 M, 142 F), age 53,19±16,33 years, BMI 28,08±5,92 Kg/m2, on adequate diet. A1298C and C677T polymorphisms were identified by RFLP‐PCR in peripheral blood; 100 C677T polymorphism and 69 double heterozygous pts were excluded by the analysis. Insulin resistance was assessed by HOMA; NAFLD by UltraSound (BLS). Finally 94 subject are included: 26 MTHFR 1298 AA, 35 MTHFR 1298 CC and 33 MTHFR 1298 AC.ResultsThe three groups were not different for age, gender, dietary profile and BMI. Control group (MTHFR 1298 AA, no polymorphism) vs. MTHFR 1298 AC (eterozygotic) pts had more severe NAFLD (BLS: 0,54±0,76 vs. 1,12±1,14; p<0.029), insulin resistance (HOMA 2,12±1,12 vs. 3,20±2,35; p<0.036) and higher ALT/GGT. The MTHFR 1298 CC (omozygotic) pts did not show any difference from MTHFR 1298 AA.ConclusionMTHFR 1298 A>C gene polymorphism confers an increased risk for NAFLD and Insulin resistance, diet‐related conditions, with same level of obesity. Nutritional and omozygotic relationship deserve further investigation.
Effect of polyphenol rich dark chocolate ingestion in SOD2 and IL‐6 expression and plasma total antioxidant capacity
Authors: Verástegui-Tena Luz Maria , Hernández Brianda A , Tolentino Maricruz , Barrera Paloma K , Perez-Lizaur Ana Bertha , Tejero Maria E 
Published: June 2021

BackgroundRecent studies have demonstrated that ingestion of polyphenol rich foods can increase plasma antioxidant status and cause a decrease of inflammatory markers. The aim of this study is to evaluate the effect of the ingestion of a polyphenol rich dark chocolate in plasma total antioxidant capacity and in the expression of SOD2 and IL‐6.MethodsEight healthy volunteers (age 25.75±6.036, BMI 24.9±4.238) were part of a crossover pilot study. Participants were non‐smokers and taking no antioxidant supplements. All volunteers ingested 40 g of a polyphenol rich dark chocolate (70% cacao) and 40 g of a control chocolate (32% cacao). Blood samples were taken at baseline and 2 hours after chocolate ingestion. Total plasma antioxidant capacity was evaluated using the TBARS assay. Expression of mRNA levels of IL‐6 and SOD2 was evaluated in whole blood using Taqman RT‐PCR.ResultsA significant increase in SOD2 expression was observed after dark chocolate ingestion (p=0.031), but not after control intake. No significant difference was found in IL‐6 expression and TBARS levels before and after consumption of each chocolate, or between treatments.ConclusionsDark chocolate ingestion may increase total antioxidant capacity by inducing SOD2 expression. Further studies are required to identify the mechanisms underlying chocolate polyphenols activity.Source of research support Nestlé México.
Effects of antenatal steroid and tracheal occlusion on pulmonary development in the fetal rabbit model of congenital diaphragmatic hernia
Authors: DEMIRBAG Suzi , Ilhami Surer , Yesildaglar Narter , Onguru Onder 
Published: June 2021

ObjectiveCongenital diaphragmatic hernia is one of the life threatening malformations that occurs 1 in 2,400 births. The aim of the study was to investigate the effects of fetal tracheal occlusion (TO) and steroids on pulmonary development in rabbits with surgically‐created diaphragmatic hernia.MethodsThere were four groups in the study: Sham (n=10), tracheal occlusion (n=5), dexamethasone (n=5) and control (n=5) groups. On day 23 of gestation (pseudoglandular stage) CDH was created in 15 fetuses of five time‐mated pregnant New Zealand type white rabbits. TO and fetal intraperitoneal dexamethasone administration (0.25 mg/kg) were performed on day 28. Fetuses were harvested by cesarean section on day 30 of gestation. Pulmonary development was evaluated by lung‐to‐body weight ratio (LBWR).ResultsCongenital diaphragmatic hernia decreased the LBWR in control group. TO and dexamethasone increased the LBWR. There were significant differences between control and TO (0.0289±0.0037vs 0.0348±0.0048, p<0.05), and control and dexamethasone groups (0.0289±0.0037 vs. 0.0301±0.0033, p<0.05) for LBWR.ConclusionBoth tracheal occlusion and fetal intraperitoneal dexamethasone administration can correct pulmonary development in rabbits with surgically created CDH.
A subgroup of lymphangioleiomyomatosis with no TSC mutations identified
Authors: BADRI KAMESWARA RAO , Qin Wei , Gao Ling , Zhe Xiaoning , Gong Can , Schuger Noa , Hyjek Elizabeth , Kwiatkowski David J , Schuger Lucia 
Published: June 2021

Lymphangioleiomyomatosis (LAM) is a rare disease characterized by infiltration of the lungs by neoplastic cells with smooth muscle and melanocytic differentiation. Dissemination of LAM cells cause progressive cystic destruction of the lungs, leading to respiratory insufficiency and death. LAM occurs either sporadically (S‐LAM) or in association with tuberous sclerosis (TSC). TSC is caused by mutations in the genes coding for tuberin (TSC2) and hamartin (TSC1), which dimerize and inhibit the mTOR pathway of cell growth and proliferation. LAM was thus thought to follow a two‐hit model leading to complete inactivation of TSC2 (or TSC1) in LAM cells. In this study, we sequenced TSC2 and TSC1 genes in lung samples from 10 S‐LAM patients. Laser capture microdissection was used to isolate LAM cell clusters, and deep sequencing was performed to detect mutations with greater sensitivity than was previously possible. We identified TSC2 mutations in 8 out of the 10 cases of S‐LAM. Four of these cases bore 2‐hit TSC2 inactivating mutations. Each of the other 4 cases, however, displayed a single mutation which was restricted to a small fraction of LAM cells. More importantly, no TSC2 or TSC1 mutations were identified in 2 of our 10 S‐LAM cases. Our findings are consistent with the existence of a form of S‐LAM unassociated with mutations in TSC2 or TSC1 and that of LAM cells lacking TSC2 mutations.Funded by NHLBI. KB is ALA Dalsemer Scholar
Synergistic effect of Biochanin A on antiproliferative potential of Atorvastatin
Authors: Tadinada Satya Murthy , Lai James C.K. , Bhushan Alok 
Published: June 2021

Pancreatic cancer, with its dismally low survival rate, is one of the most aggressive forms of cancer and is the fourth leading cause of cancer‐related deaths in the United States. Gemcitabine, the first line drug approved by the FDA has not been a huge therapeutic success because it improves the survival by just six months. Epidemiological studies implicated a role for dietary isoflavones in lower incidence of different cancers in the Asian population. Isoflavones such as genistein have been tested for their anti‐cancer potentials in different cancers. Primarily used in management of hyperlipidemia and cardiovascular diseases, statins have been documented to exert anti‐proliferative effects. We have therefore hypothesized a combination treatment with an isoflavone (i.e., biochanin A) and a statin (i.e., atorvastatin) exerts synergistic anti‐cancer effects on pancreatic cancer cells. Our ongoing studies have demonstrated that biochanin A and atorvastatin synergistically lowered survival of AsPC1 and MIAPaCa‐2 pancreatic cancer cells. Concomitant with lowering survival of these cancer cells, biochanin A and atorvastatin combination treatment also induced morphological changes (e.g., shape & cell rounding) in these cells. Our ongoing studies to elucidate signaling mechanisms underlying the combination treatment effects suggested that the PI3K/Akt pathway was unlikely to be implicated in the combination treatment‐induced death of pancreatic cancer cells. Thus, our findings may have therapeutic potential in the design of new combination therapy for pancreatic cancer.Grant support‐ INBRE Program, NIH Grant No. P20 RR016454, Mountain States Tumor and Medical Research Institute and University Research Committee, ISU grant.
Effect of early diabetes on the expression of alpha‐1 adrenoceptors in aorta of Wistar Kyoto and Spontaneously Hypertensive rats
Authors: Rodriguez Jessica Edith Rodriguez , Albor Aldo Arturo Reséndiz , Martínez Ivonne Maciel Arciniega , Chong Enrique Hong , Rodriguez Rafael Campos , Villafaña Santiago 
Published: June 2021

Adrenergic receptors play an important role in the regulation of blood pressure. Diabetes and hypertension affect this mechanism producing changes in vascular responses and exacerbating cardiovascular diseases. Several studies have mentioned that vascular changes are different in the early versus advanced stages of diabetes. For instance, in a recent study by our work group, a decrease in the vasopressor response to noradrenaline was found at 4 weeks of the diabetes evolution in Wistar Kyoto (WKY) and Spontaneously Hypertensive rats (SHR). Among the changes that could take place in the early stages of diabetes to cause this decrease in vascular response is a decrease in the expression of alpha‐1 adrenergic receptors. Therefore, the aim of the present study was to assess the expression of the three subtypes of alpha‐1 adrenergic receptors (alpha‐1A, alpha‐1B, alpha‐1D) in the aorta of WKY and SHR with 4 weeks of the evolution of diabetes. The results showed that whereas the condition of diabetes in WKY rats did not modify significantly the expression of alpha‐1 adrenoceptors, in SHR led to a significative decrease in the expression of both alpha‐1A and alpha‐1B receptors, with no change observed in alpha‐1D expression. In conclusion, the early stages of diabetes produce modifications in the expression of alpha‐1 adrenergic receptors that could explain the decrease found in vascular responses.This work was supported by a CONACYT grant (#82599) and SIP grant (#20110176) COFAA‐ IPN.
ProtoArray® Protein Microarrays: Rapid Identification of PARP Substrates
Authors: Nolan Edward M , Freeman-Cook Lisa 
Published: June 2021

Poly(ADP‐ribose) polymerases (PARPs) play a diverse role in many physiological and pathological pathways, particularly DNA damage repair. To date, ~18 different PARP enzymes have been identified, with PARP1 being the best studied. PARP1 is activated by DNA damage and catalyzes the addition of ADP‐ribose units onto acceptor proteins, setting off the base excision repair pathway.PARP inhibitors have recently garnered attention in cancer treatment as therapeutic adjuvants used in conjunction with DNA damaging chemotherapeutics. Identifying the substrate targets of the various PARP enzymes would better define their function, help identify overlap between different PARP activities, and potentially advance clinical applications for PARP inhibitors.ProtoArray® Human Protein Microarrays contain more than 9,000 purified full‐length human proteins, providing broad coverage of the proteome for a wide range of discovery applications. We report here the development of a rapid and comprehensive assay for PARP substrate identification using ProtoArray® microarrays. Using PARP1 as a model, we identified ~110 known and novel PARP1 substrates.Our results highlight protein microarrays as a platform suitable for the global discovery of PARP substrates, enabling a more detailed understanding of their function and facilitating their potential clinical exploitation as druggable targets.
Influence of exercise on adult hippocampal neurogenic subpopulations and its effects on behaviour
Authors: Gradari Simona , Pérez-Domper Paloma , Ortega Sylvia , Trejo Jose L 
Published: June 2021

The therapeutic interest of the beneficial effects of exercise prompted us to analyze those effects influenced by the duration of the training and the time elapsed between training and evaluation. In particular, the differential sensitivity of learning/memory vs emotional behavior, and of distinct subpopulations of immature neurons depending on their age. To this goal, we have carried out a 2 weeks forced exercise paradigm, either immediately before or 2 months before evaluation; we have also employed a novel analysis of multiple birthdating, behavioral assessment and stereology.We found that exercise effects are significant at different times depending on the type of behavior examined: the anxiolytic effects are detectable immediately after training, and also 2 months after exercise, while the pro‐cognitive effects are discrete and appreciable only immediately after training. Exercise affects adult hippocampal neurogenesis inducing an increase in the number of new neurons, but at least one subpopulation of immature neurons correlated negatively with the anxiolytic effect, opposite to the rest of immature neurons. These data show that although the sensitivity of new neurons to physical exercise is similar, its role on the animal's behavior is different. These results provide new evidences for the involvement of new adult‐borne immature neurons in different behavioral tasks, depending on their age.
Stronger vasoconstrictor response to aspirate from patients undergoing stent implantation into native coronary arteries than into saphenous vein grafts
Authors: Kleinbongard Petra , Baars Theodor , Möhlenkamp Stefan , Konorza Thomas , Kahlert Philipp , Erbel Raimund , Heusch Gerd 
Published: June 2021

BackgroundStent implantation into atherosclerotic coronary arteries releases particulate debris and soluble substances which contribute to impaired microvascular perfusion.MethodsUsing a distal protection/aspiration device, arterial blood was retrieved during stent implantation in 19 patients with a stenosis in native coronary arteries (NA) and in 20 patients with a saphenous vein graft (SVG) stenosis. The constrictor response of rat coronary and mesenteric arteries to aspirate was quantified in a myograph as isometric force development (mN).ResultsAt 80 mmHg, the diameter was 250±28 μm for coronary and 186±16 μm for mesenteric arteries. The KCl (120mM) ‐ induced maximal vasoconstriction was comparable for coronary and mesenteric arteries (6.1±2.3 mN vs. 7.1±1.4 mN; NS). The vasoconstriction provoked by aspirate was greater in coronary than in mesenteric arteries. Aspirate released during stent implantation into NA induced a stronger vasoconstriction than that into SVG (coronary: NA 6.9±0.8*†, SVG 5.2±0.7†, mesenteric: NA 5.6±0.9*, SVG 4.2±0.5 mN; *p<0.05 NA vs. SVG, †p<0.05 coronary vs. mesenteric arteries).ConclusionHuman coronary aspirate released during stenting of NA has a stronger vasoconstrictor potential than that from SVG. The vasoconstrictor response to human coronary aspirate is more profound in rat coronary than in mesenteric arteries.
miR‐1 and miR‐301a Overexpression Impairs Collagen Gel Contraction in Human Mesenchymal Stem Cells
Authors: Klassen Jessica Rae , Neumann Shannon , Guirgis Mina , Ngo Melanie , Li Yun , Dixon Ian , Freed Darren 
Published: June 2021

Previous data in our lab suggests that human mesenchymal stem cells (MSCs) display a myofibroblast phenotype in vitro, coincident with a reduction in miR‐301a expression. We hypothesize that miR‐301a and miR‐1 signalling plays a role in modulating the MSC‐myofibroblast phenotype.The protocol received IRB approval. Human bone marrow derived MSCs were plated on collagen gel substrates and transfected with pre‐miR‐1 and pre‐miR‐301a. The reduction in collagen gel area was analyzed 48 hours post transfection and qRT‐PCR was used to analyze RNA profile and expression of myosin isoforms.MSCs were found to express both non‐muscle myosin (NMM) IIA and IIB, and readily contracted collagen gels in the basal state, which was increased with TGF‐β1. While overexpression of miR‐301a or miR‐1 both resulted in reduced collagen gel contraction, miR‐1 had a greater effect attenuating contractility. Overexpression with both miR‐1 and miR‐301a decreased NMMIIA expression, while no change was observed with NMMIIB expression.Overexpression of miR‐301a and miR‐1 reduced MSC contractility through reduced myosin expression. It is likely that miR‐1 and miR‐301a target additional proteins in these cells.
EFFICACY OF ANTI‐TNF‐ALPHA THERAPY IN PREVENTING UTERINE ADHESION FORMATION IN RATS
Authors: DEMIRBAG Suzi , Uysal Bulent , Surer Ilhami , Oter Sukru , Korkmaz Ahmet 
Published: June 2021

ObjectivePostoperative adhesion formation is a consequence of wound healing and sometimes can result in severe complications. The aim of this study was to evaluate the effect of TNF‐alpha inhibition on the development of postoperative uterine adhesions.MethodsTwenty one female Wistar‐Albino type rats were used in this study. The rats were divided into three groups as sham‐operated, adhesion and adhesion plus the TNF‐alpha inhibitor etanercept. A lower midline abdominal incision was performed and standard uterine lesion was created by electrocautery. Starting immediately after adhesion induction, the treatment group received daily intraperitoneal injections of 2 mg/kg etanercept for a total of 3 days. At day 7, peritoneal washing fluids of rats were obtained for the determination of TNF‐alpha levels. Then all of the rats were sacrificed and uterine adhesions were staged.ResultsThe total adhesion score and tissue malondialdehyde levels were found to be increased whereas superoxide dismutase and glutathione peroxidase activities decreased significantly in the adhesion control group (P<0.05 ). TNF‐alpha inhibition, significantly reversed these findings (P<0.05).ConclusionsAnti‐TNF‐alpha therapy reduces the prevalence of peritoneal and uterine tube adhesion formation in rats possibly by suppressing TNF‐alpha production as well as limiting oxidative stress.