bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel polymorphisms in TICAM2 and NOD1 associated with tuberculosis progression phenotypes in Ethiopian populations
Authors: Mekonnen E. , Bekele E. , Stein C. M. 
Published: January 2018

BackgroundInfection by Mycobacterium tuberculosis (Mtb) is a necessary but not sufficient cause for tuberculosis (TB). Although numerous studies suggest human genetic variation may influence TB pathogenesis, there is a conspicuous lack of replication, likely due to imprecise phenotype definition. We aimed to replicate novel findings from a Ugandan cohort in Ethiopian populations.MethodWe ascertained TB cases and household controls (n = 292) from three different ethnic groups. Latent Mtb infection was determined using Quantiferon to develop reliable TB progression phenotypes. We sequenced exonic regions of TICAM2 and NOD1.ResultSignificant novel associations were observed between two variants in NOD1 and TB: rs751770147 [unadjusted p = 7.28 × 10−5] and chr7:30477156(T), a novel variant, [unadjusted p = 1.04 × 10−4]. Two SNPs in TICAM2 were nominally associated with TB, including rs2288384 [unadjusted p = 0.003]. Haplotype-based association tests supported the SNP-based results.ConclusionWe replicated the association of TICAM2 and NOD1 with TB and identified novel genetic associations with TB in Ethiopian populations.
Miniaturization and morphological evolution in Paleozoic relatives of living amphibians: a quantitative approach
Authors: Pérez-Ben Celeste M. , Schoch Rainer R. , Báez Ana M. 
Published: January 2018

AbstractMiniaturization has been defined as the evolution of extremely small adult size in a lineage. It does not simply imply the decrease of the body size but also involves structural modifications to maintain functional efficiency at a strongly reduced size. Miniaturization has been proposed as a key factor in the origin of several major tetrapod clades. Current hypotheses propose that the living amphibians (lissamphibians) originated within a clade of Paleozoic dwarfed dissorophoid temnospondyls. Morphological traits shared by these small dissorophoids have been interpreted as resulting from constraints imposed by the extreme size reduction, but these statements were based only on qualitative observations. Herein, we assess quantitatively morphological changes in the skull previously associated with miniaturization in the lissamphibian stem lineage by comparing evolutionary and ontogenetic allometries in dissorophoids. Our results show that these features are not comparable to the morphological consequences of extreme size reduction as documented in extant miniature amphibians, but instead they resemble immature conditions of larger temnospondyls. We conclude that the truncation of the ancestral ontogeny, and not constraints related to miniaturization, might have been the factor that played a major role in the morphological evolution of small dissorophoids. Based on our results, we discuss the putative role of miniaturization in the origin of lissamphibians within Dissorophoidea.
Making a Brazilian New Deal: Oliveira Vianna and the Transnational Sources of Brazil's Corporatist Experiment
Authors: TEIXEIRA MELISSA 
Published: January 2018

AbstractThis article explores the legal writings of Brazilian sociologist and jurist Francisco José de Oliveira Vianna to reveal the global context that shaped Brazil's corporatist experiment in the 1930s. From the Labour Ministry, Oliveira Vianna was at the forefront of legal and political debates over how to create corporatist laws and institutions. He was often cast as an authoritarian and retrograde thinker, yet this article looks beyond those categories to examine how his engagement with the US New Deal inserted corporatism into global debates over the role of the state in economic recovery and social welfare.
Sex- and age patterns in incidence of infectious diseases in Germany: analyses of surveillance records over a 13-year period (2001–2013)
Authors: Walter F. , Ott J. J. , Claus H. , Krause G. 
Published: January 2018

AbstractSex differences in the incidence of infections may indicate different risk factors and behaviour but have not been analysed across pathogens. Based on 3.96 million records of 33 pathogens in Germany, notified from 2001 to 2013, we applied Poisson regression to generate age-standardised incidence rate ratios and assessed their distribution across age and sex. The following trends became apparent: (a) pathogens with male incidence preponderance at infant and child age (meningococcal disease (incidence rate ratio (IRR) = 1.19, 95% CI 1.03–1.38, age = 0–4); influenza (IRR = 1.09, 95% CI 1.06–1.13, age = 0–4)), (b) pathogens with sex-switch in incidence preponderance at puberty (e.g. norovirus (IRR = 1.10, 95% CI 1.02–1.19 in age = 5–14, IRR = 0.96, 95% CI 0.93–0.99, age ⩾ 60), (c) pathogens with general male incidence preponderance (bacterial/parasitic infections with campylobacter, Yersinia and Giardia), (d) pathogens with male incidence preponderance at juvenile and adult age (sexually transmitted or vector-borne infections (combined-IRR = 2.53, 95% CI 2.36–2.71, age = 15–59), (e) pathogens with male preponderance at older age (tick-borne encephalitis - IRR = 2.75, 95% CI 1.21–6.24, listeriosis - IRR = 2.06, 95% CI 1.38–3.06, age ⩾ 60). Risk factor concepts only partly serve to interpret similarities of grouped infections, i.e. transmission-related explanations and sex-specific exposures not consistently explain the pattern of food-borne infections (b). Sex-specific differences in infectious disease incidence are well acknowledged regarding the sexually transmitted diseases. This has led to designing gender-specific prevention strategies. Our data suggest that for infections with other transmission routes, gender-specific approaches can also be of benefit and importance.
Maternal and neonatal micronutrient levels in newborns with CHD
Authors: Dilli Dilek , Doğan Nazan Neslihan , Örün Utku Arman , Koç Murat , Zenciroğlu Ayşegül , Karademir Selmin , Akduman Hasan 
Published: January 2018

AbstractObjectiveIt is suggested that folic acid and/or multivitamins, taken periconceptionally, have a role in the prevention of many congenital anomalies. The aim of this study was to determine the serum micronutrient levels in mother–infant pairs with CHD compared with those with healthy newborns and their mothers.MethodsSerum levels of folic acid, homocysteine, zinc, vitamin A, vitamin D, and vitamin B12were measured from 108 newborns with CHD (study group) and 103 healthy newborns (control group). The mothers’ micronutrient levels were also measured simultaneously.ResultsWhen compared with healthy newborns, for both maternal and neonatal data, homocysteine and zinc levels were higher and vitamin D levels were lower in the study group. In multivariate analysis, only maternal high zinc levels were associated with CHD in the newborns (p=0.02, OR: 0.9, 95% CI 0.8–0.9). The results did not change when analysed for truncal anomalies including truncus arteriosus, tetralogy of Fallot, and d-transposition of great arteries. There were positive correlations between maternal and neonatal levels of micronutrients, except vitamin B12.ConclusionWe thought that high homocysteine and zinc levels and low vitamin D levels in mother–infant pairs might have a role in the aetiopathogenesis of CHD. Large-scale, prospective studies are needed to clarify the role of micronutrients in CHDs.
Inorganic carbon addition stimulates snow algae primary productivity
Authors: Hamilton Trinity L , Havig Jeff R 
Published: January 2018

Abstract
Earth has experienced glacial/interglacial oscillations accompanied by changes in atmospheric CO2 throughout much of its history. Today over 15 million square kilometers of Earth’s land surface is covered in ice including glaciers, ice caps, and ice sheets. Glaciers are teeming with life and supraglacial snow and ice surfaces are often darkened by the presence of photoautotrophic snow algae, resulting in accelerated melt due to lowered albedo. Few studies report the productivity of snow algal communities and the parameters which constrain their growth on supraglacial surfaces—key factors for quantifying biologically induced albedo effects (bio-albedo). We demonstrate that snow algae primary productivity is stimulated by the addition of inorganic carbon. Our results indicate a positive feedback between increasing CO2 and snow algal primary productivity, underscoring the need for robust climate models of past and present glacial/interglacial oscillations to include feedbacks between supraglacial primary productivity, albedo, and atmospheric CO2.
Arsenic trioxide promoting ETosis in acute promyelocytic leukemia through mTOR-regulated autophagy
Authors: Li Tao , Ma Ruishuang , Zhang Yan , Mo Hongdan , Yang Xiaoyan , Hu Shaoshan , Wang Lixiu , Novakovic Valerie A , Chen He , Kou Junjie , Bi Yayan , Yu Bo , Fang Shaohong , Wang Jinghua , Zhou Jin , Shi Jialan 
Published: January 2018

AbstractDespite the high efficacy and safety of arsenic trioxide (ATO) in treating acute promyelocytic leukemia (APL) and eradicating APL leukemia-initiating cells (LICs), the mechanism underlying its selective cytotoxicity remains elusive. We have recently demonstrated that APL cells undergo a novel cell death program, termed ETosis, through autophagy. However, the role of ETosis in ATO-induced APL LIC eradication remains unclear. For this study, we evaluated the effects of ATO on ETosis and the contributions of drug-induced ETosis to APL LIC eradication. In NB4 cells, ATO primarily increased ETosis at moderate concentrations (0.5–0.75 μM) and stimulated apoptosis at higher doses (1.0–2.0 μM). Furthermore, ATO induced ETosis through mammalian target of rapamycin (mTOR)-dependent autophagy, which was partially regulated by reactive oxygen species. Additionally, rapamycin-enhanced ATO-induced ETosis in NB4 cells and APL cells from newly diagnosed and relapsed patients. In contrast, rapamycin had no effect on apoptosis in these cells. We also noted that PML/RARA oncoprotein was effectively cleared with this combination. Intriguingly, activation of autophagy with rapamycin-enhanced APL LIC eradication clearance by ATO in vitro and in a xenograft APL model, while inhibition of autophagy spared clonogenic cells. Our current results show that ATO exerts antileukemic effects at least partially through ETosis and targets LICs primarily through ETosis. Addition of drugs that target the ETotic pathway could be a promising therapeutic strategy to further eradicate LICs and reduce relapse.
MicroRNA miR-4779 suppresses tumor growth by inducing apoptosis and cell cycle arrest through direct targeting of PAK2 and CCND3
Authors: Koo Kyung Hee , Kwon Heechung 
Published: January 2018

AbstractDepending on the function of their target genes, microRNAs (miRNAs) act as either tumor suppressors or oncogenes. Therefore, miRNAs represent a novel therapeutic strategy for prevention and management of cancer by targeting of onco-miRNAs or mimicking of tumor suppressor miRNAs. Herein, we identified novel tumor suppressor miRNAs and investigated their molecular mechanisms. To identify novel tumor suppressor miRNAs, we used 532 human miRNA mimic libraries and measured cell viability using MTS assays. The function of miR-4779 was then analyzed using cell cycle analyses and apoptosis, colony forming, and soft agar assays. Target genes of miR-4779 were predicted using TargetScan and miRDB databases and were confirmed using luciferase assays. Levels of miR-4779 and target genes in colon cancer tissue samples from patients were evaluated using qRT-PCR and western blotting analyses. Finally, in vivo tumor suppressive effects of miR-4779 were evaluated in HCT116 xenografts. In this study, miR-4779 inhibited cancer cell growth by inducing apoptosis and cell cycle arrest, and the putative survival factors PAK2 and CCND3 were identified as direct targets of miR-4779. In subsequent experiments, PAK2 knockdown induced cell cycle arrest and CCND3 knockdown induced cell cycle arrest and apoptosis. In addition, miR-4779 suppressed tumor growth and tumorigenesis in an in vivo HCT116 xenograft model. Finally, miR-4779 expression was low in 9 of 10 colon cancer tissues, whereas PAK2 and CCND3 expressions were significantly high in colon cancer tissues. The novel tumor suppressor miR-4779 inhibits cancer cell growth via cell cycle arrest and apoptosis by directly targeting PAK2 and CCND3. The present data indicate the potential of miR-4779 as a therapeutic target for miRNA-based cancer therapy.
Control of primary metabolism by a virulence regulatory network promotes robustness in a plant pathogen
Authors: Peyraud Rémi , Cottret Ludovic , Marmiesse Lucas , Genin Stéphane 
Published: January 2018

AbstractRobustness is a key system-level property of living organisms to maintain their functions while tolerating perturbations. We investigate here how a regulatory network controlling multiple virulence factors impacts phenotypic robustness of a bacterial plant pathogen. We reconstruct a cell-scale model of Ralstonia solanacearum connecting a genome-scale metabolic network, a virulence macromolecule network, and a virulence regulatory network, which includes 63 regulatory components. We develop in silico methods to quantify phenotypic robustness under a broad set of conditions in high-throughput simulation analyses. This approach reveals that the virulence regulatory network exerts a control of the primary metabolism to promote robustness upon infection. The virulence regulatory network plugs into the primary metabolism mainly through the control of genes likely acquired via horizontal gene transfer, which results in a functional overlay with ancestral genes. These results support the view that robustness may be a selected trait that promotes pathogenic fitness upon infection.
Dual catalysis for enantioselective convergent synthesis of enantiopure vicinal amino alcohols
Authors: Ye Chen-Xi , Melcamu Yared Yohannes , Li Heng-Hui , Cheng Jiang-Tao , Zhang Tian-Tian , Ruan Yuan-Ping , Zheng Xiao , Lu Xin , Huang Pei-Qiang 
Published: January 2018

AbstractEnantiopure vicinal amino alcohols and derivatives are essential structural motifs in natural products and pharmaceutically active molecules, and serve as main chiral sources in asymmetric synthesis. Currently known asymmetric catalytic protocols for this class of compounds are still rare and often suffer from limited scope of substrates, relatively low regio- or stereoselectivities, thus prompting the development of more effective methodologies. Herein we report a dual catalytic strategy for the convergent enantioselective synthesis of vicinal amino alcohols. The method features a radical-type Zimmerman–Traxler transition state formed from a rare earth metal with a nitrone and an aromatic ketyl radical in the presence of chiral N,N′-dioxide ligands. In addition to high level of enantio- and diastereoselectivities, our synthetic protocol affords advantages of simple operation, mild conditions, high-yielding, and a broad scope of substrates. Furthermore, this protocol has been successfully applied to the concise synthesis of pharmaceutically valuable compounds (e.g., ephedrine and selegiline).
Molecular basis for the specific and multivariant recognitions of RNA substrates by human hnRNP A2/B1
Authors: Wu Baixing , Su Shichen , Patil Deepak P. , Liu Hehua , Gan Jianhua , Jaffrey Samie R. , Ma Jinbiao 
Published: January 2018

AbstractHuman hnRNP A2/B1 is an RNA-binding protein that plays important roles in many biological processes, including maturation, transport, and metabolism of mRNA, and gene regulation of long noncoding RNAs. hnRNP A2/B1 was reported to control the microRNAs sorting to exosomes and promote primary microRNA processing as a potential m6A “reader.” hnRNP A2/B1 contains two RNA recognition motifs that provide sequence-specific recognition of RNA substrates. Here, we determine crystal structures of tandem RRM domains of hnRNP A2/B1 in complex with various RNA substrates, elucidating specific recognitions of AGG and UAG motifs by RRM1 and RRM2 domains, respectively. Further structural and biochemical results demonstrate multivariant binding modes for sequence-diversified RNA substrates, supporting a RNA matchmaker mechanism in hnRNP A2/B1 function. Moreover, our studies in combination with bioinformatic analysis suggest that hnRNP A2/B1 may mediate effects of m6A through a “m6A switch” mechanism, instead of acting as a direct “reader” of m6A modification.
RASSF1A uncouples Wnt from Hippo signalling and promotes YAP mediated differentiation via p73
Authors: Papaspyropoulos Angelos , Bradley Leanne , Thapa Asmita , Leung Chuen Yan , Toskas Konstantinos , Koennig Delia , Pefani Dafni-Eleftheria , Raso Cinzia , Grou Claudia , Hamilton Garth , Vlahov Nikola , Grawenda Anna , Haider Syed , Chauhan Jagat , Buti Ludovico , Kanapin Alexander , Lu Xin , Buffa Francesca , Dianov Grigory , von Kriegsheim Alex , Matallanas David , Samsonova Anastasia , Zernicka-Goetz Magdalena , O’Neill Eric 
Published: January 2018

AbstractTransition from pluripotency to differentiation is a pivotal yet poorly understood developmental step. Here, we show that the tumour suppressor RASSF1A is a key player driving the early specification of cell fate. RASSF1A acts as a natural barrier to stem cell self-renewal and iPS cell generation, by switching YAP from an integral component in the β-catenin-TCF pluripotency network to a key factor that promotes differentiation. We demonstrate that epigenetic regulation of the Rassf1A promoter maintains stemness by allowing a quaternary association of YAP–TEAD and β-catenin–TCF3 complexes on the Oct4 distal enhancer. However, during differentiation, promoter demethylation allows GATA1-mediated RASSF1A expression which prevents YAP from contributing to the TEAD/β-catenin–TCF3 complex. Simultaneously, we find that RASSF1A promotes a YAP–p73 transcriptional programme that enables differentiation. Together, our findings demonstrate that RASSF1A mediates transcription factor selection of YAP in stem cells, thereby acting as a functional “switch” between pluripotency and initiation of differentiation.
Dopamine genes are linked to Extraversion and Neuroticism personality traits, but only in demanding climates
Authors: Fischer Ronald , Lee Anna , Verzijden Machteld N. 
Published: January 2018

AbstractCross-national differences in personality have long been recognized in the behavioural sciences. However, the origins of such differences are debated. Building on reinforcement sensitivity theories and gene-by-environment interactions, we predict that personality trait phenotypes linked to dopaminergic brain functions (centrally involved in reward processing) diverge most strongly in climatically stressful environments, due to shifts in perceived rewards vs risks. Individuals from populations with a highly efficient dopamine system are biased towards behavioural approach traits (Extraversion and Emotional Stability) due to higher perceived reward values, whereas individuals from populations with a less efficient dopaminergic system are biased towards risk avoidance. In temperate climates, we predict smaller phenotypic differences due to overall weakened reward and risk ratios. We calculated a population-level index of dopamine functioning using 9 commonly investigated genetic polymorphisms encoding dopamine transporters and receptors, derived from a meta-analysis with data from 805 independent samples involving 127,685 participants across 73 societies or territories. We found strong support for the dopamine gene by climatic stress interaction: Population genetic differences in dopamine predicted personality traits at the population level in demanding climates, but not in temperate, less demanding climates, even when controlling for known correlates of personality including wealth and parasite stress.
The motilin agonist erythromycin increases hunger by modulating homeostatic and hedonic brain circuits in healthy women: a randomized, placebo-controlled study
Authors: Zhao Dongxing , Meyer-Gerspach Anne Christin , Deloose Eveline , Iven Julie , Weltens Nathalie , Depoortere Inge , O’daly Owen , Tack Jan , Van Oudenhove Lukas 
Published: January 2018

AbstractThe motilin agonist, erythromycin, induces gastric phase III of the migrating motor complex, which in turn generates hunger peaks. To identify the brain mechanisms underlying these orexigenic effects, 14 healthy women participated in a randomized, placebo-controlled crossover study. Functional magnetic resonance brain images were acquired for 50 minutes interprandially. Intravenous infusion of erythromycin (40 mg) or saline started 10 minutes after the start of scanning. Blood samples (for glucose and hormone levels) and hunger ratings were collected at fixed timepoints. Thirteen volunteers completed the study, without any adverse events. Brain regions involved in homeostatic and hedonic control of appetite and food intake responded to erythromycin, including pregenual anterior cingulate cortex, anterior insula cortex, orbitofrontal cortex, amygdala, caudate, pallidum and putamen bilaterally, right accumbens, hypothalamus, and midbrain. Octanoylated ghrelin levels decreased, whereas both glucose and insulin increased after erythromycin. Hunger were higher after erythromycin, and these differences covaried with the brain response in most of the abovementioned regions. The motilin agonist erythromycin increases hunger by modulating neurocircuitry related to homeostatic and hedonic control of appetite and feeding. These results confirm recent behavioural findings identifying motilin as a key orexigenic hormone in humans, and identify the brain mechanisms underlying its effect.
Chemotherapy drugs cyclophosphamide, cisplatin and doxorubicin induce germ cell loss in an in vitro model of the prepubertal testis
Authors: Smart Ellie , Lopes Federica , Rice Siobhan , Nagy Boglarka , Anderson Richard A. , Mitchell Rod T. , Spears Norah 
Published: January 2018

AbstractLong term survival rates for childhood cancers is steadily increasing, however cancer survivors can experience fertility problems as a consequence of chemotherapy treatment. This is particularly problematic for young boys, for whom no fertility preservation treatment is yet established. Here, we have determined the effects on prepubertal mouse testis of three commonly used chemotherapy drugs; cyclophosphamide (using its active metabolite phosphoramide mustard), cisplatin and doxorubicin, exposing testicular fragments to a clinically relevant range of concentrations in vitro. All three drugs induced a specific and highly significant loss of germ cells, including spermatogonial stem cells. In contrast, there was no significant effect on somatic cells, for either Sertoli or interstitial cells. Time course analysis of cleaved Caspase-3 expression showed a significant increase in apoptosis eight hours prior to a detectable decrease in germ cell numbers following exposure to phosphoramide mustard or cisplatin, although this pattern was not seen following doxorubicin-exposure. Moreover, analysis of DNA damage at 16 h showed increased γH2AX expression in response to all three drugs. Overall, results show that cisplatin, doxorubicin and cyclophosphamide all specifically induce loss of germ cells, including of spermatogonial stem cells, in the prepubertal mouse testis at concentrations relevant to human therapeutic exposures.