bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Modeling Suggests Homologous 2-APB Binding Sites in Connexins 26 and 32
Authors: Comollo Thomas W. 
Published: March 2018

ABSTRACTConnexins are the transmembrane pore forming proteins that participate in gap junctions; connections between cells that certain nutrients and other molecules can pass through. There are several kinds of connexins (Cx) named based on their weight in kilodaltons. 2-aminoethoxydiphenyl borate (2-APB) is a small molecule inhibitor (SMI) of Cx26 and Cx32. Knock out of Cx32 and also blockage of Cx32 by 2-aminoethoxydiphenyl (2-APB) has been suspected to be beneficial in not only, drug induced liver toxicity, but also in blocking the propagation of an inflammatory signal. If the binding site of 2-APB can be determined, virtual screening for additional, perhaps more specific Cx26 and Cx32 blocking SMI can be carried out. Our modeling suggests that 2-APB binds to similar sites inside the pores of Cx26 and Cx32. Here 2-APB interacts with the conserved ILE82 and THR86. These residues hold the same numbering in both CX26 and CX32. This suggests these residues have a high level of conservation and importance Further virtual screening results imply molecules with similar activity on Cx26 and Cx32 as 2-APB can be found.Background2-APB has been shown to block Cx26 and Cx32.ResultsDocking of 2-APB to Cx26 and CX32 finds conserved binding site in pore. Suggestive that 2-APB has conserved homologous binding site on Cx26 and Cx32.ConclusionMutational studies of 2APB and ILE82 and THR86 in Cx26 and Cx32 appear warranted. Additional virtual screening could yield 2-APB analogs that act on Cx26 and Cx32.SignificancePotential for developing gap junction blocking compounds.
Altered function of the glutamate aspartate transporter GLAST in glioblastoma
Authors: Corbetta Cristina , Di Ianni Natalia , Bruzzone Maria Grazia , Patanè Monica , Pollo Bianca , Cantini Gabriele , Cominelli Manuela , Zucca Ileana , Pisati Federica , Poliani Pietro Luigi , Finocchiaro Gaetano , Pellegatta Serena 
Published: March 2018

AbstractIn glioma patients, high levels of glutamate can cause brain edema and seizures. GLAST, a glutamate-aspartate transporter expressed by astrocytes with a role in glutamate uptake, is highly expressed on the plasma membrane of glioblastoma (GBM) cells, and its expression significantly correlates with shortened patient survival. Here, it was demonstrated that inhibition of GLAST expression limited the progression and invasion of GBM xenografts. Magnetic resonance spectroscopy was used to measure glutamate in GLAST-expressing gliomas showing that these tumors exhibit increased glutamate concentration. Despite their GLAST expression, GBM stem-like cells (GSCs) released rather than took up glutamate due to their lack of Na+/K+-ATPase. Overexpression of Na+/K+-ATPase in these cells restored glutamate uptake and induced apoptosis. The therapeutic relevance of targeting GLAST in gliomas was assessed using the inhibitor UCPH-101. In glioma-bearing mice, a single intratumoral injection of UCPH-101 significantly increased survival by decreasing GLAST expression and inducing apoptosis. Thus, GLAST has a novel role in GBM that appears to have crucial relevance in glutamate trafficking and may thus be a new therapeutic target.
Impact of Sex and APOE Status on Spatial Navigation in Pre-symptomatic Alzheimer’s disease
Authors: Coughlan G. , Coutrot A. , Khondoker M. , Minihane A. , Spiers H. , Hornberger M. 
Published: March 2018

INTRODUCTIONSpatial navigation is emerging as a critical factor in identifying pre-symptomatic Alzheimer pathophysiology, with the impact of sex and APOE status on spatial navigation yet to be established.METHODSWe estimate the effects of sex on navigation performance in 27,308 individuals (50-70 years [benchmark population]) by employing a novel game-based approach to cognitive assessment using Sea Hero Quest. The effects of APOE genotype and sex on game performance was further examined in a smaller lab-based cohort (n = 44).RESULTSBenchmark data showed an effect of sex on wayfinding distance, duration and path integration. Importantly in the lab cohort, performance on allocentric wayfinding levels was reduced in ε4 carriers compared to ε3 carriers, and effect of sex became negligible when APOE status was controlled for. To demonstrate the robustness of this effect and to ensure the quality of data obtained through unmonitored at-home use of the Sea Hero Quest game, post-hoc analysis was carried out to compare performance by the benchmark population to the monitored lab-cohort.DISCUSSIONAPOE ε4 midlife carriers exhibit changes in navigation pattern before any symptom onset. This supports the move towards spatial navigation as an early cognitive marker and demonstrates for the first time how the utility of large-scale digital cognitive assessment may hold future promise for the early detection of Alzheimer’s disease. Finally, benchmark findings suggest that gender differences may need to be considered when determining the classification criteria for spatial navigational deficits in midlife adults.
Thrombospondins 1 and 2 affect lysyl oxidase protein and collagen matrix maturation in cortical bone of growing male and female mice via non-redundant pathways
Authors: Shearer Dylan , Mervis Madison O , Manley Eugene , Reddy Anita B , Alford Andrea I 
Published: March 2018

AbstractThrombospondin-2-deficiency is associated with impaired matrix maturation in osteoblasts and cortical bone of growing mice. Here we addressed the possibility that lysyl oxidase (LOX) contributes to this phenotype. After overnight serum starvation, pro-LOX levels were elevated compared to wild-type in marrow-derived osteoblasts from male and female TSP2−/− mice. The liberated LOX pro-peptide (LOPP) was faintly visible in serum-starved cultures. When serum was maintained, pro-LOX content was not affected by TSP2 status, but relative LOPP levels were elevated in cultures from female TSP2−/− mice. Two isoforms of pro-LOX at 75 kDa and 50 kDa were detected in detergent soluble protein extracts of diaphyseal tissue from growing mice. In female mice, TSP2 status did not affect detergent soluble pro-LOX content or the relative contribution of each band to the total signal. Instead, levels of the 50 kDa band were reduced in female TSP1−/− samples. In male diaphyseal tissue, total pro-LOX content and the contribution each isoform made to the total signal was not affected by TSP1 or TSP2 status. We did not detect 32 kDa mature LOX in detergent soluble preparations of cells or whole bone tissue. Detergent insoluble hydroxyproline content was reduced in diaphyseal tissue obtained from female TSP1−/− and TSP2−/− mice. In male diaphyseal cortical samples, TSP2 but not TSP1 deficiency was associated with reduced insoluble hydroxyproline content. Our data suggest that the trimeric thrombospondins contribute to bone matrix quality via non-redundant mechanisms that are dependent on the unique tissue milieu of the male and female skeleton.
Lipid utilization in skeletal muscle cells is modulated in vitro and in vivo by specific miRNAs
Authors: Chemello Francesco , Grespi Francesca , Zulian Alessandra , Cancellara Pasqua , Hebert-Chatelain Etienne , Martini Paolo , Bean Camilla , Alessio Enrico , Ferrazza Ruggero , Laveder Paolo , Guella Graziano , Reggiani Carlo , Romualdi Chiara , Bernardi Paolo , Scorrano Luca , Cagnin Stefano , Lanfranchi Gerolamo 
Published: March 2018

SUMMARYSkeletal muscle is composed by different myofiber types that can preferentially use glycolysis or lipids for ATP production. How fuel preference is specified in these post-mitotic cells is unknown. Here we show that miRNAs are important players in defining the myofiber metabolic profile. mRNA and miRNA signatures of all myofiber types obtained at single cell level unveiled fiber-specific regulatory networks and identified two master miRNAs that coordinately control myofiber fuel preference and mitochondrial morphology. Our work provides a complete and integrated myofiber type-specific catalogue of genes and miRNAs expressed and establishes miR-27a-3p and miR-142-3p as key regulators of lipid utilization in skeletal muscle.HIGHLIGHTSTranscriptional networking in single cells distinguished myofibers based on glycolytic or oxidative metabolism, regulated by specific miRNAsmiR-27a-3p and −142-3p influence mitochondrial morphologymiR-27a-3p improves lipid utilization and increases glycogen storage both in vitro and in vivomiR-142-3p reduces lipid utilization both in vitro and in vivo
Children with cochlear implants in infancy: predictors of early vocabulary
Authors: Bavin Edith L. , Sarant Julia , Leigh Greg , Prendergast Luke , Busby Peter , Peterson Candida 
Published: March 2018

AbstractBackgroundLanguage outcomes for children with cochlear implants (CIs) vary widely, even for those implanted before 2 years of age. Identifying the main influencing factors that account for some of the variability is important in order to provide information to guide appropriate clinical and intervention services for young children with CIs. However, there is limited research focusing on the predictors of early vocabulary development for children implanted in infancy.AimsTo identify significant predictors of vocabulary (12–15 months post‐implant) for a sample of 33 children with CIs, the majority implanted between 6 and 10 months of age, drawing on predictors of vocabulary reported for children with normal hearing. Of particular interest was the impact of pre‐implant development and use of gestures.Methods & ProceduresChildren with severe to profound hearing loss, and no other known disabilities, were recruited from CI clinics in Australia before receiving their CIs. Subscales from the Bayley Scales‐III (receptive and expressive communication, gross and fine motor, and cognition) were used to assess their development at that time. Using the Macarthur–Bates Communicative Development Inventory (Words and Gestures) we documented the children's (1) use of gestures at six data‐collection times 3 months apart; and (2) vocabulary at the last three time points. Time since implant and time to consistent use of the CIs were also included as potential predictors. Data were analysed using generalized linear models, assuming a negative binomial response with a log‐link function. Stepwise variables selection was followed to retain a smaller number of the covariates.Outcomes & ResultsA year after implantation, the significant predictors identified for vocabulary were pre‐implant receptive communication and early gesture use. Together with fine motor and cognitive skills, these two variables were also significant predictors of vocabulary 3 months later. With maternal education entered into the models, higher vocabulary scores were significantly associated with higher maternal education 12 months post‐implantation, but not 15 months.Conclusions & ImplicationsPre‐implant abilities are important in explaining some variability in the early vocabulary of infants with CIs, together with their use of early gestures post‐implantation. That is, having a non‐verbal means to express a concept can assist in their development of oral vocabulary. Identifying strategies to help develop fine motor skills for infants with CIs, and encouraging their use of gestures to communicate their needs/intentions, are likely to be of benefit.
Speculative futures at the bottom of the pyramid
Authors: Dolan Catherine , Rajak Dinah 
Published: March 2018

AbstractCelebrated as creative, flexible catalysts of inclusive capitalism, urban youth are central to bottom‐of‐the‐pyramid (BoP) models of development, which set out to repurpose the jobless as entrepreneurs in the making. We explore the multiple (at times conflicting) temporalities – the practices, technologies, and representations of time – which figure in a BoP initiative offering entrepreneurial opportunities to unemployed youth in Nairobi's slums: from the invocation of clock‐time discipline to the professional time of entrepreneurial subjectivities and the enchantments of the not‐yet. But the appeal of BoP, we suggest, does not turn either on the here‐and‐now of survival or on an impossible pipe dream of prosperity, but rather resides firmly in the medium term: a foreseeable future of modest desires, which nonetheless remain tantalizingly just out of reach for most. By examining how these temporal conflicts play out in attempts to fashion a cadre of self‐willed, aspiring entrepreneurs, we reveal the limits to entrepreneurial agency, and the contradictions inherent in the mission of (self‐)empowerment through enterprise upon which the ideology of inclusive markets is built.
A ‘kinship anthropology of politics’? Interest, the collective self, and kinship in Argentine unions★
Authors: Lazar Sian 
Published: March 2018

AbstractIn this article I argue for a kinship anthropology of politics, understood as a focus on the day‐to‐day imbrications of kinship and politics in a given political space, and the implications of that for the construction of political subjects. I describe kinship within shop‐floor‐level trade union delegations of state employees in Argentina in three different ways: first, languages of kinship mobilized to describe political allegiance and dispositions, especially inheritance; second, family connections in recruitment and activism; and, third, practices of kinning as relatedness. The combination of these three kinship modes creates the union as kin group, and enables it to act on the world politically in order to transform it.
The (ir)relevance of unemployment for labour market policy attitudes and welfare state attitudes
Authors: WEHL NADJA 
Published: March 2018

AbstractTypically, associations between being unemployed and policy attitudes are explained with reference to economic self‐interest considerations of the unemployed. Preferences for labour market policies (LMP) and egalitarian preferences are the prime example and the focus of this study. Its aim is to challenge this causal self‐interest argument: self‐interest consistent associations of unemployment with policy preferences are neither necessarily driven by self‐interest nor necessarily causal. To that end, this article first confronts the self‐interest argument with a broader perspective on attitudes. Given that predispositions (e.g., value orientations) are stable and influence more specific policy attitudes, it is at least questionable whether people change their policy attitudes simply because they get laid off. Second, the article derives a non‐causal argument behind associations between unemployment and policy attitudes, arguing that these might be spurious associations driven by individuals’ socioeconomic background. After all, the entire socioeconomic background of a person is simultaneously related to both the risk of getting unemployed (‘selection into unemployment’) and distinct political socialisation experiences from early childhood onwards. Third, this article uses methods inspired by a counterfactual account on causality to test the non‐causal claims. Analyses are carried out using the fourth wave of the European Social Survey and applying entropy balancing to control for selection bias. In only two of the 31 analysed countries do unemployment effects on egalitarian orientations remain significant after controlling for selection bias. The same holds for effects on active LMP attitudes with the exception of six countries. Attitudes towards passive LMP are to some degree an exception since effects remain in a third of the countries. Robustness checks and Bayes factor replications showing evidence for the absence of unemployment effects support the general impression from these initial analyses. After discussing this article's results and limitations, its broader implications are considered. On the one hand, the article offers a new perspective on the conceptualisation and measurement of unemployment risk. On the other hand, its theoretical argument, as well as its treatment of the resulting selection bias, can be broadly applied. Thus, this article can contribute to many other research questions regarding the (ir)relevance of individual life events for political attitudes and political behaviour.
Chemical Imaging of Cyanoacrylate‐Fumed Fingerprints by Matrix‐assisted Laser Desorption/Ionization Mass Spectrometry Imaging,
Authors: O'Neill Kelly C. , Hinners Paige , Lee Young Jin 
Published: March 2018

AbstractFor new techniques to be incorporated into forensic science, they must be compatible with current practices. Here, cyanoacrylate fuming, a common development technique for latent fingerprints, is studied for its compatibility with matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) for chemical imaging of latent fingerprints. Half of a fingerprint was fumed while the other half was not; then, the changes in chemical composition and signal intensity were compared with MALDI‐MS imaging. No evidence was found that fingerprint compounds are chemically altered by fuming or their signal intensities affected. The only exceptions were significant signal loss for quaternary ammonium compounds from hygiene products and moderate signal loss for tertiary amine compounds. This result is in striking contrast with the previous attempts by others, which is attributed to the difference in instrumentation.
Developmental inhibition of Drosophila suzukii by ionizing radiation
Authors: Kim Junheon , Kim Jeongmin , Lee Yeon Jeong , Park Chung Gyoo 
Published: March 2018

AbstractSpotted wing drosophila (SWD) has emerged as a major invasive insect pest of small berry fruits in the Americas and Europe since the late 2000s. Thus, phytosanitary treatment of commodities for export is imperative to prevent the movement of viable SWD to newer areas. In the present study, all developmental stages of SWD were irradiated with different doses of gamma and electron beam radiation to assess developmental inhibition to identify potential quarantine doses of the radiations. Ionizing radiation induced developmental inhibition of all stages of SWD. The effective doses for 99% inhibition (ED99) of hatching, pupariation, and adult emergence from irradiated eggs for gamma radiation were 882, 395 and 39 Gy, respectively, compared with 2849, 687, and 41 Gy, respectively, for electron beam radiation. The ED99 for inhibition of pupariation and adult emergence in irradiated larvae were 703 and 47 Gy, respectively, for gamma radiation, and 619 and 33 Gy, respectively, for electron beam radiation. Pupal irradiation did not completely inhibit adult emergence, even at 300 Gy. However, irradiation with ≥100 Gy of puparia induced adult sterility, with no egg production at all. The ED99 for inhibition of F1 egg hatchability from adults irradiated with gamma radiation and electron beam radiation was estimated to be 424 and 125 Gy, respectively. The results of the present study suggest that gamma radiation and electron beam radiation are alternatives for phytosanitary treatment. Irradiation with 100 Gy could be suggested as a potential dose for egg, larval, and pupal quarantine treatment of SWD.
Activity of glutathione S‐transferase and esterase enzymes in Helicoverpa armigera (Hübner) after exposure to entomopathogenic fungi
Authors: Bilal Muhammad , Freed Shoaib , Muhammad Saleh , Ashraf Muhammad Zubair , Khan Muhammad Bismillah 
Published: March 2018

AbstractHelicoverpa armigera, a polyphagous insect of crops and vegetables, is acquiring resistance against many commercial insecticides. The present study shows variations in the activity of two detoxification enzymes, namely esterase and glutathione S‐transferase (GST), in H. armigera after exposure to different isolates of entomopathogenic fungi. After treatment of larvae with the different isolates (Day 0), samples were collected on three days (Days 3, 5 and 7) for enzyme analysis. High GST activity was found in samples of hemolymph, intestine and fat bodies of H. armigera following treatment with Beauveria bassiana (isolate Bb‐08), Metarhizium anisopliae (isolates Ma‐11.1 and Ma‐4.1), and Isaria fumosorosea (isolates If‐02 and If‐2.3). High esterase activity was recorded in samples of the intestine and fat bodies on various days after treatment, whereas increased esterase activity in hemolymph was noted only in samples from Day 5 after treatment with M. anisopliae (Ma‐4.1). The detection of high GST and esterase activity demonstrates the possibility of the development of resistance against these microbial control agents in H. armigera.
An independent validation study of loci associated with nematode resistance in sheep
Authors: Keane O. M. , Hanrahan J. P. , McRae K. M. , Good B. 
Published: March 2018

SummaryGastrointestinal nematode infection is a constraint on sheep production worldwide. Selective breeding programmes to enhance resistance to nematode infection are currently being implemented in a number of countries. Identification of loci associated with resistance to infection or causative mutations for resistance would enable more effective selection. Loci associated with indicator traits for nematode resistance has been identified in previous studies. In this study, Scottish Blackface, Texel and Suffolk lambs were used to validate the effects at eight genomic regions previously associated with nematode resistance (OAR3, 4, 5, 7, 12, 13, 14, 21). No SNP was significantly associated with nematode resistance at the region‐wide level but seven SNPs in three of the regions (OAR4, 12, 14) were nominally associated with trichostrongyle egg count in this study and six of these were also significant when fitted as single SNP effects. Nematodirus egg count was nominally associated with SNPs on OAR3, 4, 7 and 12.
Analysis of genetic relatedness among Indian cattle (Bos indicus) using genotyping‐by‐sequencing markers
Authors: Malik A. A. , Sharma R. , Ahlawat S. , Deb R. , Negi M. S. , Tripathi S. B. 
Published: March 2018

SummaryGenetic relatedness of 24 animals belonging to seven Indian cattle breeds was studied using high throughput genotyping‐by‐sequencing (GBS) markers.GBSproduced 93.6 million reads with an average of about 3.9 million reads per animal. A total of 107 488SNPs were identified in these individuals. When only oneSNPper read was considered, a total of 60 261SNPs representing independent reads were identified with an averageSNP‐to‐SNPdistance of 45 kb across the bovine reference genome. About 24% of theGBS‐SNPmarkers were more than 100 kb apart. Of these, 58 322SNPs mapped to autosomes, 1645 to the X chromosome and 28 to the Y chromosome. The averageSNP‐to‐SNPdistance on the X chromosome was 91.3 kb, whereas on the Y chromosome it was 1546.4 kb. The minor allele frequency within the Indian cattle varied from 0.103 (Ongole) to 0.177 (Siri), whereas Holstein cattle had the lowest value of 0.089. This is the first application ofGBSin cattle of South Asia. The baseline information generated in this study might prompt implementation ofGBSin breeding of cattle belonging to this region.