bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of birth order, birth weight, colostrum and serum immunoglobulin G on neonatal piglet survival
Authors: Cabrera Rafael A , Lin Xi , Campbell Joy M , Moeser Adam J , Odle Jack 
Published: December 2012

AbstractBackgroundIntake of colostrum after birth is essential to stimulate intestinal growth and function, and to provide systemic immunological protection via absorption of Immunoglobulin G (IgG). The birth order and weight of 745 piglets (from 75 litters) were recorded during a one-week period of farrowing. Only pigs weighing greater than 0.68 kg birth weight were chosen for the trial. Sow colostrum was collected during parturition, and piglets were bled between 48 and 72 hours post-birth. Piglet serum IgG and colostral IgG concentrations were determined by radial immunodiffusion.ResultsSow parity had a significant (P < 0.001) effect on sow colostral IgG concentration, being 5% higher in multiparous females. Sow colostral IgG concentration explained 6% and piglet birth order accounted for another 4% of the variation observed in piglet serum IgG concentration (P < 0.05); however, birth weight had no detectable effect. Piglet serum IgG concentration had both a linear (P < 0.05) and quadratic effect (P < 0.05) on % survival. Piglets with 1,000 mg/dl serum IgG or less (n=24) had a 67% survival; whereas, piglets with IgG concentrations between 2250 to 2500 mg/dl (n=247) had a 91% survival. Birth order had no detectable effect on survival, but birth weight had a positive linear effect (P < 0.05). Piglets weighing 0.9 kg (n = 107) at birth had a 68% survival rate, and those weighing 1.6 kg (n = 158) had an 89% survival.ConclusionWe found that the combination of sow colostrum IgG concentration and birth order can account for 10% of the variation of piglet serum IgG concentration and that piglets with less than 1,000 mg/dl IgG serum concentration and weight of 0.9 kg at birth had low survival rate when compared to their larger siblings. The effective management of colostrum uptake in neonatal piglets in the first 24 hrs post-birth may potentially improve survival from birth to weaning.
cnvHiTSeq: integrative models for high-resolution copy number variation detection and genotyping using population sequencing data
Authors: Bellos Evangelos , Johnson Michael R , M Coin Lachlan J 
Published: December 2012

AbstractRecent advances in sequencing technologies provide the means for identifying copy number variation (CNV) at an unprecedented resolution. A single next-generation sequencing experiment offers several features that can be used to detect CNV, yet current methods do not incorporate all available signatures into a unified model. cnvHiTSeq is an integrative probabilistic method for CNV discovery and genotyping that jointly analyzes multiple features at the population level. By combining evidence from complementary sources, cnvHiTSeq achieves high genotyping accuracy and a substantial improvement in CNV detection sensitivity over existing methods, while maintaining a low false discovery rate. cnvHiTSeq is available at http://sourceforge.net/projects/cnvhitseq
A microRNA network regulates proliferative timing and extracellular matrix synthesis during cellular quiescence in fibroblasts
Authors: Suh Eric J , Remillard Matthew Y , Legesse-Miller Aster , Johnson Elizabeth L , Lemons Johanna MS , Chapman Talia R , Forman Joshua J , Kojima Mina , Silberman Eric S , Coller Hilary A 
Published: December 2012

Abstract
Background
Although quiescence (reversible cell cycle arrest) is a key part in the life history and fate of many mammalian cell types, the mechanisms of gene regulation in quiescent cells are poorly understood. We sought to clarify the role of microRNAs as regulators of the cellular functions of quiescent human fibroblasts.

Results
Using microarrays, we discovered that the expression of the majority of profiled microRNAs differed between proliferating and quiescent fibroblasts. Fibroblasts induced into quiescence by contact inhibition or serum starvation had similar microRNA profiles, indicating common changes induced by distinct quiescence signals. By analyzing the gene expression patterns of microRNA target genes with quiescence, we discovered a strong regulatory function for miR-29, which is downregulated with quiescence. Using microarrays and immunoblotting, we confirmed that miR-29 targets genes encoding collagen and other extracellular matrix proteins and that those target genes are induced in quiescence. In addition, overexpression of miR-29 resulted in more rapid cell cycle re-entry from quiescence. We also found that let-7 and miR-125 were upregulated in quiescent cells. Overexpression of either one alone resulted in slower cell cycle re-entry from quiescence, while the combination of both together slowed cell cycle re-entry even further.

Conclusions
microRNAs regulate key aspects of fibroblast quiescence including the proliferative state of the cells as well as their gene expression profiles, in particular, the induction of extracellular matrix proteins in quiescent fibroblasts.
Technical Advance: Measurement of iNKT cell responses at the single-cell level against rare HIV-1-infected dendritic cells in a mixed culture
Authors: Andersson Sofia K , Paquin-Proulx Dominic , Kroll Mirko , Sandberg Johan K , Moll Markus 
Published: December 2012

Abstract
A microscopy-based assay to measure iNKT cell responses against rare HIV-1 infected dendritic cells, infected with an eGFP expressing reporter virus.
iNKT cells recognize lipid antigens, such as α-GalCer, presented in complex with CD1d expressed by DCs. Exposure of DCs to HIV-1 can lead to productive infection, and it was demonstrated recently that HIV-1 inhibits CD1d surface expression in an apparent mode of immune evasion. However, studies of the interaction between T cells, including iNKT cells and HIV-infected DCs in vitro, are hampered by the low frequency of productive infection in DCs. Here, we demonstrate the utility of full-length HIV-1 modified to express eGFP to address this problem. This virus allowed identification of single, rare productively infected cells in a mixed DC population by fluorescence microscopy and enabled detailed studies of the interaction of such cells with individual iNKT cells. iNKT cell responses to α-GalCer presented by HIV-1-positive and -negative DCs were quantified by intracellular IFN-γ staining in iNKT cells forming conjugates with DCs. Whereas complex formation was observed between iNKT cells and uninfected and infected DCs, only iNKT cells in contact with uninfected DCs produced IFN-γ. This microscopy assay, based on full-length HIV-1 modified to express eGFP, thus allows detailed evaluation of HIV-1 immune-evasion mechanisms in rare virus-infected live DCs.
Behavioral abnormalities and Parkinson's-like changes resulting from Id2 inactivation in mice
Authors: Havrda Matthew C. , Paolella Brenton R. , Ward Nora M. , Holroyd Kathryn B. 
Published: December 2012

Summary
Characterizing dopaminergic neuronal development and function in novel genetic animal models might uncover strategies for researchers to develop disease-modifying treatments for neurologic disorders. Id2 is a transcription factor expressed in the developing central nervous system. Id2-/- mice have fewer dopaminergic neurons in the olfactory bulb and reduced olfactory discrimination, a pre-clinical marker of Parkinson's disease. Here, we summarize behavioral, histological, and in vitro molecular biological analyses to determine whether midbrain dopaminergic neurons are affected by Id2 loss. Id2-/- mice were hyperactive at 1 and 3 months of age, but by 6 months showed reduced activity. Id2-/- mice showed age-dependent histological alterations in dopaminergic neurons of the substantia nigra pars compacta (SNpC) associated with changes in locomotor activity. Reduced dopamine transporter (DAT) expression was observed at early ages in Id2-/- mice and DAT expression was dependent on Id2 expression in an in vitro dopaminergic differentiation model. Evidence of neurodegeneration, including activated caspase-3 and glial infiltration, were noted in the SNpC of older Id2-/- mice. These findings document a novel role for Id2 in the maintenance of midbrain dopamine neurons. The Id2-/- mouse should provide unique opportunities to study the progression of neurodegenerative disorders involving the dopamine system.
A new and clinically relevant murine model of solid-organ transplant aspergillosis
Authors: Herbst Susanne , Shah Anand , Carby Martin , Chusney Gary , Kikkeri Naresh , Dorling Anthony , Bignell Elaine , Shaunak Sunil , Armstrong-James Darius 
Published: December 2012

Summary
Invasive fungal infections (IFIs) are a major cause of death in organ transplant patients. The murine hydrocortisone-mediated immunosuppression model of pulmonary aspergillosis is commonly used to characterise IFIs in these patients. However, this model does not take into account the effects of calcineurin inhibitors on transplant immunity to IFIs or the fungal calcineurin pathway, which is required for both virulence and antifungal drug resistance. To address these two issues, a new and clinically relevant transplant immunosuppression model of tacrolimus (FK506) and hydrocortisone-associated pulmonary aspergillosis was developed. We first characterised IFIs in 406 patients with a lung transplant. This showed that all of the patients with pulmonary aspergillosis were immunosuppressed with calcineurin inhibitors and steroids. Murine pharmacokinetic studies demonstrated that an ideal dose of 1 mg/kg/day of FK506 intraperitoneally produced blood trough levels in the human therapeutic range (5-12 ng/ml). There was increased mortality from pulmonary aspergillosis in a transplant-relevant immunosuppression model using both FK506 and hydrocortisone as compared with immunosuppression using hydrocortisone only. Lung histopathology showed neutrophil invasion and tracheobronchitis that was associated with reduced lung tumour necrosis factor-α (TNFα), JE (homologue of human MCP-1) and KC (homologue of human IL-8) at 24 hours, but increased lung TNFα, JE and KC at 48 hours when fungal burden was high. Furthermore, FK506 directly impaired fungal killing in alveolar macrophages in vitro, with FK506-mediated inhibition of the radial growth of Aspergillus fumigatus in vitro occurring at the low concentration of 5 ng/ml. Taken together, these findings show that the immunosuppressive activity of FK506 outweighs its antifungal activity in vivo. These observations demonstrate that FK506 impairs innate immune responses and leads to an incremental increase in susceptibility to IFIs when it is combined with steroids. This new and clinically relevant mouse model of invasive aspergillosis is a valuable addition to the further study of both fungal immunity and antifungal therapy in organ transplantation.
Bile-acid-mediated decrease in endoplasmic reticulum stress: a potential contributor to the metabolic benefits of ileal interposition surgery in UCD-T2DM rats
Authors: Cummings Bethany P. , Bettaieb Ahmed , Graham James L. , Kim Jaehyoung , Ma Fangrui , Shibata Noreene , Stanhope Kimber L. , Giulivi Cecilia , Hansen Frederik , Jelsing Jacob , Vrang Niels , Kowala Mark , Chouinard Michael L. , Haj Fawaz G. , Havel Peter J. 
Published: December 2012

Summary
Post-operative increases in circulating bile acids have been suggested to contribute to the metabolic benefits of bariatric surgery; however, their mechanistic contributions remain undefined. We have previously reported that ileal interposition (IT) surgery delays the onset of type 2 diabetes in UCD-T2DM rats and increases circulating bile acids, independently of effects on energy intake or body weight. Therefore, we investigated potential mechanisms by which post-operative increases in circulating bile acids improve glucose homeostasis after IT surgery. IT, sham or no surgery was performed on 2-month-old weight-matched male UCD-T2DM rats. Animals underwent an oral fat tolerance test (OFTT) and serial oral glucose tolerance tests (OGTT). Tissues were collected at 1.5 and 4.5 months after surgery. Cell culture models were used to investigate interactions between bile acids and ER stress. IT-operated animals exhibited marked improvements in glucose and lipid metabolism, with concurrent increases in postprandial glucagon-like peptide-1 (GLP-1) secretion during the OFTT and OGTTs, independently of food intake and body weight. Measurement of circulating bile acid profiles revealed increases in circulating total bile acids in IT-operated animals, with a preferential increase in circulating cholic acid concentrations. Gut microbial populations were assessed as potential contributors to the increases in circulating bile acid concentrations, which revealed proportional increases in Gammaproteobacteria in IT-operated animals. Furthermore, IT surgery decreased all three sub-arms of ER stress signaling in liver, adipose and pancreas tissues. Amelioration of ER stress coincided with improved insulin signaling and preservation of β-cell mass in IT-operated animals. Incubation of hepatocyte, adipocyte and β-cell lines with cholic acid decreased ER stress. These results suggest that post-operative increases in circulating cholic acid concentration contribute to improvements in glucose homeostasis after IT surgery by ameliorating ER stress.
Olfactomedin-1 activity identifies a cell invasion checkpoint during epithelial-mesenchymal transition in the embryonic heart
Authors: Lencinas Alejandro , Chhun Danny C. , Dan Kelvin P. , Ross Kristen D. , Hoover Elizabeth A. , Antin Parker B. , Runyan Raymond 
Published: December 2012

Summary
Endothelia in the atrioventricular (AV) canal of the developing heart undergo a prototypical epithelial mesenchymal transition (EMT) to begin heart valve formation. Using an in vitro invasion assay, an extracellular matrix protein found in the heart, Olfactomedin-1 (OLFM1), increases mesenchymal cell numbers. Both anti-OLFM1 antibody and OLFM1 siRNA treatment inhibit mesenchymal cell formation. OLFM1 does not alter cell proliferation, migration or apoptosis. Dispersion, but lack of invasion in the presence of inhibiting antibody, identifies a specific role for OLFM1 in cell invasion during EMT. This role is conserved in other epithelia, as OLFM1 similarly enhances invasion by MDCK epithelial cells in a trans-well assay. OLFM-1 activity is cooperative with TGFβ, as synergy is observed when TGFβ2 and OLFM1 are added to MDCK cell cultures. Inhibition of both OLFM1 and TGFβ in heart invasion assays shows a similar cooperative role during development. To explore OLFM1 activity during EMT, representative EMT markers were examined. Effects of OLFM1 protein and anti-OLFM1 on transcripts of cell-cell adhesion molecules and the transcription factors, Snail-1, Snail-2, Twist1, and Sox-9, argue that OLFM1 does not initiate EMT. Rather, regulation of transcripts of Zeb1 and Zeb2, secreted proteases and mesenchymal cell markers by both OLFM1 and anti-OLFM1 is consistent with regulation of the cell invasion step of EMT. We conclude that OLFM1 is present and necessary during EMT in the embryonic heart. Its role in cell invasion and mesenchymal cell gene regulation suggests an invasion checkpoint in EMT where OLFM1 acts to promote cell invasion into the three-dimensional matrix.
Pharmacological preconditioning with erythropoietin attenuates the organ injury and dysfunction induced in a rat model of hemorrhagic shock
Authors: Nandra Kiran K. , Collino Massimo , Rogazzo Mara , Fantozzi Roberto , Patel Nimesh S. A. , Thiemermann Christoph 
Published: December 2012

Summary
Pre-treatment with erythropoietin (EPO) has been demonstrated to exert tissue-protective effects against 'ischemia-reperfusion'-type injuries. This protection might be mediated by mobilization of bone marrow endothelial progenitor cells (EPCs), which are thought to secrete paracrine factors. These effects could be exploited to protect against tissue injury induced in cases where hemorrhage is foreseeable, for example, prior to major surgery. Here, we investigate the effects of EPO pre-treatment on the organ injury and dysfunction induced by hemorrhagic shock (HS). Recombinant human EPO (1000 IU/kg/day i.p.) was administered to rats for 3 days. Rats were subjected to HS on day 4 (pre-treatment protocol). Mean arterial pressure was reduced to 35±5 mmHg for 90 minutes, followed by resuscitation with 20 ml/kg Ringer’s lactate for 10 minutes and 50% of the shed blood for 50 minutes. Rats were sacrificed 4 hours after the onset of resuscitation. EPC (CD34+/flk-1+ cell) mobilization was measured following the 3-day pre-treatment with EPO and was significantly increased compared with rats pre-treated with phosphate-buffered saline. EPO pre-treatment significantly attenuated organ injury and dysfunction (renal, hepatic and neuromuscular) caused by HS. In livers from rats subjected to HS, EPO enhanced the phosphorylation of Akt (activation), glycogen synthase kinase-3β (GSK-3β; inhibition) and endothelial nitric oxide synthase (eNOS; activation). In the liver, HS also caused an increase in nuclear translocation of p65 (activation of NF-κB), which was attenuated by EPO. This data suggests that repetitive dosing with EPO prior to injury might protect against the organ injury and dysfunction induced by HS, by a mechanism that might involve mobilization of CD34+/flk-1+ cells, resulting in the activation of the Akt-eNOS survival pathway and inhibition of activation of GSK-3β and NF-κB.
MTR120/KIAA1383, a novel microtubule-associated protein, promotes microtubule stability and ensures cytokinesis
Authors: Fong Ka-wing , Leung Justin Wai-chung , Li Yujing , Wang Wenqi , Feng Lin , Ma Wenbin , Liu Dan , Songyang Zhou , Chen Junjie 
Published: December 2012

Summary
Microtubules (MTs) are the major constituent of the mitotic apparatus. Deregulation of MT dynamics leads to chromosome missegregation, cytokinesis failure and improper inheritance of genetic materials. Here, we describe the identification and characterization of KIAA1383/MTR120 (microtubule regulator 120 kDa) as a novel MT-associated protein. We found that MTR120 localizes to stabilized MTs during interphase and to the mitotic apparatus during mitosis. MTR120 overexpression results in MT bundling and acetylation. In vitro, purified MTR120 protein binds to and bundles preassembled MTs. Moreover, depletion of MTR120 by RNA interference leads to cytokinesis failure and polyploidy. These phenotypes can be rescued by wild-type MTR120 but not by the MT non-binding mutant of MTR120. Together, these data suggest that MTR120 is a novel MT-associated protein that directly stabilizes MTs and hence ensures the fidelity of cell division.
The sugar meal of the African malaria mosquito Anopheles gambiae (Giles) and how deterrent compounds interfere with it: a behavioural and neurophysiological study
Authors: Kessler Sébastien , Vlimant Michèle , Guerin Patrick M. 
Published: December 2012

Summary
In this study, we show that female African malaria mosquitoes Anopheles gambiae (Giles) starved for 3-5 hours start to engorge on sucrose at concentrations between 50 to 75 mM. Half of the feeding response (ED50) is reached at 111 mM and the maximum response (0.4 mg) occurs from 146 mM (5% m/v). Two receptor cells in a trichoid sensillum of the labellum, called the 'sucrose' and the 'water' neurones, are activated by sucrose and water, respectively. The electrophysiological response of the sucrose receptor cell starts well below the level of sugar necessary to induce feeding. An. gambiae is most sensitive to small increments in sucrose concentration up to 10 mM with a response plateau at a maximum frequency of 53 spikes per 2 s from 50 mM, the concentration at which female An. gambiae start to engorge on sucrose. Fructose has a mild phagostimulatory effect on An. gambiae, whereas no significant differences in meal sizes between water and glucose were found. However, when 146 mM fructose plus glucose are mixed, the same engorgement as on 146 mM sucrose is observed. Likewise, even though the sucrose receptor cell is not activated by either fructose or glucose alone, equimolar solutions of fructose plus glucose activate the neurone. We conclude that there is a behavioural and a neurophysiological synergism between fructose and glucose, the two hexose sugars of sucrose. We show that bitter tasting products for humans have a deterrent effect on feeding in An. gambiae. When 1 mM quinidine, quinine or denatonium benzoate is added to 146 mM sucrose, feeding is almost totally inhibited. The effect of berberine is lower and no significant inhibition on engorgement occurs for caffeine. The deterrent effect depends on concentration for both quinine and quinidine. Capillary feeding experiments show that contact chemosensilla on the mouthparts are sufficient for the detection of sucrose and bitter products. The feeding assay findings with deterrents correlate with the neurophysiological responses of the sucrose and the water labellar neurones which are both inhibited by the bitter compounds denatonium benzoate, quinine and berberine between 0.01 and 1 mM, but not by the same concentrations of caffeine which has no effect on feeding. In conclusion, sucrose which stimulates feeding activates the labellar sucrose neurone whereas feeding deterrents inhibit both the sucrose and the water neurones. This study provides an initial understanding of the physiological mechanisms involved in sugar feeding in An. gambiae and shows how some bitter products interfere with it.
The relative contribution of calcium, zinc and oxidation-based cross-links to the stiffness ofArion subfuscusglue
Authors: Braun Melanie , Menges Meghan , Opoku Freda , Smith Andrew M. 
Published: December 2012

SummaryMetal ions are present in many different biological materials, and are capable of forming strong cross-links in aqueous environments. The relative contribution of different metal-based cross-links was measured in the defensive glue produced by the terrestrial slug Arion subfuscus. This glue contains calcium, zinc, manganese, iron and copper. These metals are essential to the integrity of the glue and to gel stiffening. Removal of all metals caused at least a fifteen-fold decrease in the storage modulus of the glue. Selectively disrupting cross-links involving hard Lewis acids such as calcium weakened the glue, while disrupting cross-links involving borderline Lewis acids such as zinc did not. Calcium is the most common cation bound to the glue (40 mmol L-1), and its charge is balanced primarily by sulfate at 82 to 84 mmol L-1. Thus, these ions likely play a primary role in bringing polymers together directly. Imine bonds formed as a result of protein oxidation also contribute substantially to the strength of the glue. Disrupting these bonds with hydroxylamine caused a 33% decrease in storage modulus of the glue, while stabilizing them by reduction with sodium borohydride increased the storage modulus by 40%. Thus, a combination of metal-based bonds operates in this glue. Most likely, cross-links directly involving calcium play a primary role in bringing together and stabilizing the polymer network, followed by imine bond formation and possible iron coordination.