bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced sensitivity to optimistic cues is manifested in brain structure: a voxel-based morphometry study
Authors: Aue Tatjana , Dricu Mihai , Singh Laura , Moser Dominik A , Kotikalapudi Raviteja 
Published: June 2021

Abstract
Recent research shows that congruent outcomes are more rapidly (and incongruent less rapidly) detected when individuals receive optimistic rather than pessimistic cues, an effect that was termed optimism robustness. In the current voxel-based morphometry study, we examined whether optimism robustness has a counterpart in the brain structure. The participants’ task was to detect two different letters (symbolizing monetary gain or loss) in a visual search matrix. Prior to each onset of the search matrix, two different verbal cues informed our participants about a high probability to gain (optimistic expectancy) or lose (pessimistic expectancy) money. The target presented was either congruent or incongruent with these induced expectancies. Optimism robustness revealed in the participants’ reaction times correlated positively with gray matter volume (GMV) in brain regions involved in selective attention (medial visual association area, intraparietal sulcus), emphasizing the strong intertwinement of optimistic expectancies and attention deployment. In addition, GMV in the primary visual cortex diminished with increasing optimism robustness, in line with the interpretation of optimism robustness arising from a global, context-oriented perception. Future studies should address the malleability of these structural correlates of optimism robustness. Our results may assist in the identification of treatment targets in depression.
Crossing Borders: Exploring the Role of School Social Workers in Immigrant-Serving Schools
Authors: Sosa Leticia Villarreal , Roth Benjamin , Rodriguez Sophia 
Published: June 2021

AbstractAnti-immigrant rhetoric increasingly depicts immigrants as undeserving, but schools are social institutions where these perceptions can be challenged and, ideally, where inequities confronting immigrant students can be ameliorated. Existing research suggests that teachers and administrators are central to this task, but it also raises questions about the role of other personnel in immigrant-serving schools. Drawing on the concept of nepantlera, this study examines how school social workers (SSWs) pursue equity for immigrant students by challenging intersecting power structures. The authors present preliminary findings that attest to the importance of nepantleras for SSWs and the importance of SSWs for immigrant-serving schools.
When things go wrong
Authors: Rimmer John 
Published: June 2021

Abstract
Legal arrangements carry their own risks. The courts and legislatures have had centuries to get trust law right, but when foundations were introduced in the Channel Islands and the Isle of Man around ten to twelve years ago, there was a chance to short-cut much of that incremental development, and to use much of the trust and company law experience.
It was planned that foundations, in common law jurisdictions, would not be seen merely as trusts by another name. They were designed closely to resemble the civil law paradigm, in particular having legal personality, and the legislation made clear that they had different characteristics from trusts.
This article looks at the effective oversight of foundations in the Isle of Man, drawing on experiences in Jersey.
Overexpression of cyclin‐dependent kinase (CDK) inhibitors p21 and p27 is a common mechanism of experimental duodenal ulcer and ulcerative colitis
Authors: Paunovic Brankica , Khomenko Tetyana , Deng Xiaoming , Xiong Ximing , Sandor Zsuzsanna , Szabo Sandor 
Published: June 2021

Recently we demonstrated that increased expression of cyclin‐dependent kinase inhibitors p21 and p27 is an early event in duodenal ulceration (DU) induced by cysteamine or mepirizole and in indomethacin‐caused gastric erosions. We hypothesized that overexpression of p21, p27 and p16 may be involved in the mechanisms of mucosal damage in both DU and ulcerative colitis (UC). To compare the effect of chemically‐induced injury in duodenal and colonic mucosa, Sprague‐Dawley rats were treated with cysteamine (85 mg/100 g, intragastrically) or with 6% iodoacetamide (0.1 ml, intracolonically). Animals were euthanized at 0.5, 2, 6, 12, 24 hr after treatment. Mucosal scrapings of proximal duodenum and distal colon were used for RNA isolation; p16, p21 and p27 were detected by Real‐time polymerase chain reaction. The results demonstrated that cysteamine enhanced duodenal p21 and p27 mRNA expression at 2 hr by 2.9‐ and 4.6‐fold, respectively. In colonic mucosa iodoacetamide increased p21 by 4.2‐fold and p27 expression by 1.5‐fold. Expression of p16 changed in neither DU nor UC.Conclusions1) Expressions of p21 and p27 were significantly increased in rat duodenal and colonic mucosa in the early stages of DU and UC formation. 2) Thus, both p21 and p27 but not p16 seem to be a common mechanism involved in the pathogenesis of DU and UC.(This study was supported by Dept of Veterans Affairs, Medical Research Service Merit Reviews)
Diminazene Aceturate Is an ACE2 Activator and a Novel Antihypertensive Drug
Authors: Gjymishka Altin , Kulemina Lidia V , Shenoy Vinayak , Katovich Michael J , Ostrov David A , Raizada Mohan K 
Published: June 2021

Emerging evidence suggests that ACE2 could be a new therapeutic target for cardiovascular disease (CVD) and hypertension. In this study, we used a molecular docking strategy combined with in vitro functional screening to search for novel ACE2 activators in support of this concept. Enzymatic assays with top‐scoring compounds demonstrated that diminazene aceturate (DIZE), a known antiprotozoal drug used in humans, acts as a potent activator of ACE2. DIZE caused a dose‐dependent increase in ACE2 activity and a maximal increase of 2.5 fold (Vmax) was observed with 50 μM. Intravenous administration of DIZE in WKYs and SHRs caused a transient and dose‐dependent decrease in mean arterial pressure (MAP). Although, DIZE decreased MAP in both strains of rats, its efficacy was significantly higher in the SHRs; a dose of 5 mg/kg of DIZE triggered a MAP reduction of 50±9 mmHg in WKY rats (n=6) compared to 85±11 mmHg in SHRs (n=6). In addition, chronic administration of DIZE at 15 mg/kg/day for three weeks in SHRs caused a modest decrease in MAP (from 136±3 to 124±6 mmHg, p<0.05). This was associated with a reduction in the heart weight to body weight ratio (3.8±0.004 in control versus 3.6±0.018 in DIZE treated, p<0.005) and myocardial fibrosis.These data suggest that DIZE may serve as a lead compound for the discovery of next generation of drugs for the treatment of CVD and hypertension.This work was funded by NIH grant HL56921.
Flax seed oil protection from bleomycin‐induced lung vascular damage: a rat model
Authors: Mehrer Aaron , Kamal Afrin , Herndon Betty L , Fibuch Eugene , Quinn Tim , Molteni Agostino , Lawrenz Joshua , Smith Bradford , Nitz Jonathan , Gasper David , Baybutt Richard 
Published: June 2021

Bleomycin, a widely used antineoplastic agent has been associated with severe pulmonary toxicity through production of acute interstitial pneumonia, pulmonary vasculitis and, eventually pulmonary fibrosis. Treatment by omega‐3 fatty acid in flax seed oil may reduce bleomycin induced lung injury. To test this hypothesis 72 rats were equally divided between diets receiving 15% fat as flax seed oil or corn oil (control). These two groups were further divided to receive either 8 units/kg body weight bleomycin or vehicle, intratracheally. Lungs were harvested at 2, 7, or 21 days and tissue was fixed and stained (H&E) for histopathology. Two investigators evaluated the bleomycin induced lung responses particularly the bleomycin‐induced pulmonary vasculitis by photographing five small caliber pulmonary arteries. These arteries were measured for pulmonary lumen patency and the ratio of media diameter/adventitia diameter. At days 7 and 21, bleomycin produced a significant reduction in lumen patency (p=0.01) and of media/adventitial diameter (p=0.02 all days) which was not evident when the rats were treated with the flax seed oil diet. At day 7 the flax seed oil group also showed a delay in edema formation, inflammatory cell infiltrate and reduced pulmonary septal thickness. This model presents a dietary regime which may protect against bleomycin pulmonary toxicity.Support: Wheaton College General Endowment fund.
Racial Disparities in Hypertensive Cardiovascular Disease and Chronic Kidney Disease
Authors: Lea Janice P. 
Published: June 2021

Epidemiologic studies have shown that hypertension (HTN) and its cardiovascular (CV) complications, carry significantly higher morbidity and mortality in African‐Americans (AA) compared with Caucasians. These observations may be partly explained by a higher prevalence of cardiovascular disease (CVD) risk factors, such as HTN, diabetes, and tobacco use among AA.Chronic Kidney Disease (CKD) is not only a major risk factor for End‐Stage Renal Disease, but is a predictor of CVD and death. CVD mortality rates are 10‐fold greater in individuals with CKD. Blacks are disproportionately affected by hypertensive CKD with a 7‐fold higher incidence. Additional risk factors for progressive CKD include level of blood pressure control, proteinuria, low income, and genetic influences.Microalbuminuria and CKD are well‐established risk factors for CV mortality in both diabetic and non‐diabetics and is directly associated with left ventricular hypertrophy and coronary heart disease. The prevalence of microalbuminuria is higher among diabetics and hypertensives as well as among AA compared to Whites.In summary, African‐Americans have a higher burden of HTN, diabetes, CVD and of CKD. However, the pathophysiologic processes underlying this racial predisposition have not been fully elucidated.
Adiponectin mediates leucine‐induced adipocyte‐muscle cross‐talk
Authors: Sun Xiaocun , Zemel Michael B. 
Published: June 2021

We previously showed that leucine modulates energy metabolism in both adipocytes and skeletal muscle cells. We found leucine to stimulate adipocyte‐skeletal muscle cell cross‐talk, resulting in decreased adipocyte lipogenesis and increased fatty acid oxidation and mitochondrial biogenesis in muscle cells. Although these effects appear to be mediated, in part, via multiple adipokines, the effect of leucine on adiponectin production and signaling is unclear. We report here that leucine modulates adiponectin production in a dose‐dependent manner up to 1mM, which increased adipocyte adiponectin production by 78% (p=0.016). These effects are specific to leucine, as other branched chain amino acids exerted no effect. Leucine also stimulated adiponectin type II receptor expression in C2C12 myotubes by 29% (p=0.0071) but had no effect on the more highly expressed type I receptor. Since our previous data suggested that leucine stimulation of mitochondrial biogenesis was mediated by Sirt1, we evaluated leucine effects on Sirt1 activity; leucine exerted no direct effect on muscle Sirt1 activity, but leucine and adiponectin each stimulated ~50% increases in Sirt1 activity in adipocytes and in muscle cell/adipocyte co‐cultures (p<0.005). These data indicate that leucine regulation of adipocyte and muscle energy metabolism is mediated, in part, via adiponectin.Support: TN Agricultural Experiment Station.
Characterization of the orphan human (C‐X‐C) chemokine receptor type 7 receptor (CXCL7) on T lymphocyte cells
Authors: Vu John Peter , Germano Patrizia , Lu Yuxin , Pisegna Joseph 
Published: June 2021

Chemokines function as the main regulators of leukocyte trafficking under inflammatory conditions. Chemokine receptors have a 7 transmembrane structure and belong to the G protein‐coupled receptor subfamily. G‐Protein coupled receptors (GPCRs) mediate cellular responses to a diverse array of signaling molecules such as neurotransmitters, phosophilipds, and peptide hormones. Receptors coupled to G proteins form the largest known family of surface receptors, however despite the identification of hundreds human GPCRs, more than half are termed orphan. Recently, a CXCL7 (RDC1) has been cloned as an orphan GPCR receptor that shares homology with chemokine receptors. Initially, RDC1 was reported as a receptor vasoactive intestinal peptide, however this observation was dismissed when it was shown that RDC1 could not account for calcitonin gene‐related peptide (CGRP) and adrenomedullin (ADM) binding.Here we describe the characterization of the RDC1 receptor expression on T lymphocyte cells. Jurkat cells were stably transfected to overexpress the RDC1 receptor. Gene expression profiles were studied with transfected RDC‐1 and untransfected Jurkat cells 2 and 24 hour conditions in response to either anti‐CD3, CGRP, and ADM with and with out the partial CGRP receptor antagonist CGRP8‐37. Intracellular calcium signaling responded to CGRP, ADM, and slight inhibitory response to CGRP(8–37).Based upon calcium signaling studies, the cells showed a response to anti‐CD3, CGRP and ADM and showed a slight response to CGRP(8–37). These results will permit a more detailed determination as to the localiazation and physiological function of this novel receptor.
Probiotic Lactobacilli Decrease Invasion of Metastatic Human Colon Cancer Cells In Vitro
Authors: Escamilla Juanita , Lane Michelle A , Maitin Vatsala 
Published: June 2021

Colon cancer metastasis involves loss of intercellular junctions and cell invasion through the colonic epithelial basement membrane, a process mediated by matrixmetalloproteinases (MMP). Probiotic bacteria have been shown to improve colonic epithelial barrier function and decrease MMP activity suggesting anti‐metastatic potential. The objective of this study was to explore anti‐metastatic activity of probiotics Lactobacillus casei (L. casei) and Lactobacillus rhamnosus (L. rhamnosus) in terms of decrease in cell invasion. This was assessed by an in vitro assay, measuring the invasion of metastatic human colon cancer cell line HCT‐116 through Matrigel‐coated membranes in Boyden chambers. HCT‐116 cells were plated on top of the membrane with probiotic CFS from either L. casei or L. rhamnosus at 25% (v/v) in DMEM. Bacterial growth medium (MRS) at 25% (v/v) in DMEM was used as the control. Cell invasion was measured after 24 h of treatment; by fixing, staining and counting the cells present on the bottom side of the membrane. Treatment of HCT‐116 cells with CFS from L. casei and L. rhamnosus resulted in a significant decrease in cell invasion by 72% +/− 4.25 and 50% +/− 17.65 respectively, of control. These data indicate that probiotic CFS contain anti‐metastatic bioactive compounds that may be contributing to the decrease in cell invasion in vitro. Funding source: Texas State University Research Enhancement Program.Grant Funding Source: Texas State University Research Enhancement Program
A systematic review of the separate and combined effects of energy restriction and exercise on fat‐free mass in middle‐aged and older adults: Implications for sarcopenic obesity
Authors: Weinheimer Eileen , Sands Laura P , Campbell Wayne W 
Published: June 2021

PurposeThis systematic review assessed the effects of energy restriction (ER) and exercise (EX) on fat‐free mass (FFM) in overweight and obese middle‐aged and older adults.MethodsPubmed was searched using “weight loss or energy restriction” AND “skeletal muscle or body composition” as keywords, with limitations “human” and “middle‐aged and aged.” 52 studies met inclusion criteria that included men and/or postmenopausal women aged ≥ 50 y, BMI > 25 kg/m2, and interventions ≥ 8 wk. Body weight (BW) loss was induced via ER, ER+EX, or EX. ER was achieved by counseling without (n=35) or with (n=7) some food provided, or all food provided (n=3). EX included aerobic (n=31), resistance (n=3), or both (n=5). Results are reported as % of the ER, ER+EX, or EX groups that had a specified change in BW and FFM, since insufficient data were provided to perform a meta‐analysis.Results94% of the ER groups and 89% of the ER+EX groups lost ≥ 5 kg BW. 75% of the ER groups, but only 30% of the ER+EX groups, lost ≥ 1.5 kg FFM. 81% and 39% of the ER and ER+EX groups, respectively, lost ≥ 15% of BW as FFM. The EX groups had modest BW (94% lost < 5 kg) and FFM (100% lost < 1.5 kg) losses.ConclusionExercise is an effective tool to help middle‐aged and older overweight and obese adults preserve FFM after moderate energy restriction‐induced weight loss, and may be effective in combating sarcopenic obesity.Support: T32AG025671; US Whey Protein Research ConsortiumGrant Funding Source: T32AG025671; US Whey Protein Research Consortium
An Irreversible Modification of Histone H3 ‐ Identification and Characterization of Histone H3‐specific Protease from Chicken Liver
Authors: Chaturvedi Madan Mohan , Purohit Jogeswar S , Tomar Raghuvir Singh , Panigrahi Anil K 
Published: June 2021

Regulated removal of N‐terminal tails of histones would constitute an irreversible type of modification. A novel histone H3 specific modifying enzyme from chicken liver nuclei was purified that specifically cleaved histone H3 in vitro and generated a faster migrating histone H3 band. The enzyme named H3ase was sequenced with the help of MALDI‐MS & PSD and was found to align with a known NAD+‐dependent dehydrogenase (NDH). The peptide substrates against the N‐terminus histone H3 could compete with H3ase activity, building the possibility that probably, H3ase modified histone H3 in the N‐terminus. Site of proteolysis was mapped using bacterially expressed recombinant histone H3. The cleaved products corresponded to polypeptides lacking 2, 4 and 8 amino acid residues from the N‐terminus, respectively. The mechanism of proteolysis is still unknown. Efforts are being taken to evaluate the status of H3 proteolysis in chromatin level and to find out its physiological importance.This research work was supported by research grants from Department of Science and Technology, Government of India, New Delhi (Grant no. SR/SO/BB‐38/2002), and University of Delhi, India.
The host is a harsh mistress: role of fatty acid synthesis in trypanosome survival (1001.6)
Authors: Paul Kimberly , McKnight Ciara , Ray Sunayan 
Published: June 2021

Trypanosoma brucei, a protozoan parasite transmitted by the tsetse fly, invades the bloodstream and CNS of humans, causing African sleeping sickness. In addition to antigenic variation of its surface glycoprotein coat, T. brucei employs a second immune evasion tactic: upregulation of endocytosis to clear lytic cell surface immune complexes, a strategy likely involving membrane turnover and fatty acid synthesis (FAS). Acetyl‐CoA carboxylase (ACC) catalyzes the first committed step of FAS and is a regulatory control point. Previous work showed that ACC RNA interference (RNAi) in T. brucei bloodstream forms (BFs) reduced virulence in mice, but had no effect on growth in culture. We hypothesized that ACC is required in BFs for immune evasion via endocytosis upregulation. We examined endocytosis in BF ACC RNAi cells and observed a 90% reduction in fluid phase and receptor‐mediated endocytosis upon ACC RNAi. ACC RNAi also caused a 30% delay in the clearance of surface‐bound antibodies and 40% increase in the susceptibility to complement‐mediated lysis. Because endocytosis upregulation may increase demand for FAS, we examined if ACC is regulated in response to changes in lipid supply. In BFs, we found no change in ACC expression, activity, or phosphorylation upon growth in low or high lipid media. Also, ACC RNAi had similar effects on endocytosis, antibody clearance, and complement‐mediated lysis under low and high lipid conditions. In contrast, insect form cells exhibited a 2X increase in ACC protein and enzymatic activity in low lipid media. Phosphorylation of insect form ACC increased 3X in high lipid media and decreased by 80% in low lipid media. We propose a model whereby T. brucei ACC is up‐regulated in the mammalian host to support increased endocytosis and immune evasion, while in the insect host, ACC is regulated in response to the environmental lipid supply.Grant Funding Source: Supported by NIH R15 AI081207
Sumo‐modification of pxr alters protein cofactor interactions (1062.11)
Authors: Woody Sarah , Staudinger Jeff 
Published: June 2021

Pregnane X Receptor (PXR, NR1I2) is a ligand‐activated nuclear receptor superfamily member expressed at high levels within the entero‐hepatic system in mammals. The primary function of PXR is to regulate the metabolism and transport of xenobiotics and endogenous compounds by controlling the expression of genes encoding major drug metabolizing enzymes and drug transporter proteins. To mediate its function PXR interacts with a plethora of classical co‐regulatory proteins including, but not limited to, Nuclear Receptor Co‐Repressors (NCoR1/NCoR2), Steroid Receptor Co‐activator proteins (SRC‐1/SRC‐2/SRC‐3) and p300/CBP co‐integrator proteins. SUMOylation is a reversible post‐translational modification that plays a central role in regulating multiple cellular activities such as protein‐protein interactions. While direct PXR‐target gene activation programs are currently well characterized, little is known about SUMO‐modification of PXR. Our working hypothesis is that SUMO‐modified PXR alters its protein‐protein interaction profile. Thus, we have created a GAL4‐PXR fusion system that allows us to directly examine SUMO‐PXR interaction with the aforementioned PXR‐binding proteins. Future efforts are focused on developing novel methods for identification of SUMO‐PXR‐binding proteins using non‐biased methods.Grant Funding Source: Supported by NIH DK090558
GAPDH prevents oxidant‐induced apoptosis in smooth muscle cells via upregulation of APE1/Ref‐1 endonuclease (1093.1)
Authors: Sukhanov Sergiy , Yoshida Tadashi , Delafontaine Patrick 
Published: June 2021

We have shown that oxidized low density lipoprotein (OxLDL) co‐localized with apoptotic smooth muscle cells (SMC) in atherosclerotic plaque and that OxLDL downregulated the major glycolytic enzyme glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) in cultured SMC via H2O2‐dependent mechanism. We hypothesized that GAPDH downregulation mediates SMC apoptosis.OxLDL (80 ug/ml) or H2O2 (220 uM, 16h) decreased GAPDH protein (immunoblotting, 78±5% and 55±5% decrease, respectively) and induced TUNEL‐positive DNA fragmentation and apoptosis (Annexin V assay). GAPDH downregulation with siRNA potentiated OxLDL‐ or H2O2‐induced DNA fragmentation (1.9±0.2 and 7.0±0.9‐fold increase, respectively) suggesting that maintenance of sufficient GAPDH levels is critical for DNA integrity and cell survival. GAPDH transient overexpression with pCMV‐GAPDH construct decreased H2O2‐induced cytotoxicity (LDH release assay, 68±5% decrease) and DNA fragmentation (74±4% decrease). SMC constitutively overexpressing GAPDH had increased glycolysis, ATP levels and these cells were resistant to H2O2‐induced cell death (>90% reduction) showing that GAPDH protects SMC against oxidant‐induced apoptosis. We have found that GAPDH was co‐immunoprecipitated and had nuclear co‐localization with APE1/Ref‐1 endonuclease, major DNA repair enzyme. APE1 endonuclease activity was increased in H2O2‐treated GAPDH overexpressing SMC vs.control SMC suggesting that GAPDH preserved APE1 activity under oxidative stress.In summary, GAPDH downregulation mediates oxidant‐induced SMC apoptosis and forced expression of GAPDH protects SMC from oxidant‐induced cell death potentially via stimulation of APE1‐dependent DNA repair. Since SMC apoptosis induces vulnerable plaque phenotype and accelerates atherosclerosis, our data suggest that preservation of GAPDH and APE1 activity in plaque SMC could represent novel therapy to prevent plaque destabilization and atherogenesis.Grant Funding Source: Supported by American Heart Association