bluuebunny/crossref_metadata_2025_split huggingface dataset:
Change in sexual signaling traits outruns morphological divergence in a recent avian radiation across an ecological gradient
Authors: Friis Guillermo , Milá Borja 
Published: September 2018

AbstractThe relative roles of natural and sexual selection in promoting evolutionary lineage divergence remains controversial and difficult to assess in natural systems. Local adaptation through natural selection is known to play a central role in adaptive radiations, yet secondary sexual traits can vary widely among species in recent radiations, suggesting that sexual selection may also be important in the early stages of speciation. Here we compare rates of divergence in ecologically relevant traits (morphology) and sexually selected signaling traits (coloration) relative to neutral structure in genome-wide molecular markers, and examine patterns of variation in sexual dichromatism to understand the roles of natural and sexual selection in the diversification of the songbird genusJunco(Aves: Passerellidae). Juncos include divergent lineages in Central America and several dark-eyed junco (J. hyemalis) lineages that diversified recently as the group recolonized North America following the last glacial maximum (c.a. 18,000 years ago). We found an accelerated rate of divergence in sexually selected characters relative to ecologically relevant traits. Moreover, a synthetic index of sexual dichromatism comparable across lineages revealed a positive relationship between the degree of color divergence and the strength of sexual selection, especially when controlling for neutral genetic distance. We also found a positive correlation between dichromatism and latitude, which coincides with the latitudinal pattern of decreasing lineage age but also with a steep ecological gradient. Finally, we detected an association between outlier loci potentially under selection and both sexual dichromatism and latitude of breeding range. These results suggest that the joint effects of sexual and ecological selection have played a role in the junco radiation and can be important in the early stages of lineage formation.
Bacteria: A novel source for potent mosquito feeding – deterrents
Authors: Kajla Mayur K. , Barrett-Wilt Gregory A. , Paskewitz Susan M. 
Published: September 2018

AbstractAntibiotic and insecticidal bioactivities of the extracellular secondary metabolites produced by entomopathogenic bacteria belonging to genus Xenorhabdus have been identified; however, their novel applications such as mosquito feeding-deterrence have not been reported. Here, we show that a mixture of compounds isolated fromXenorhabdus budapestensis in vitrocultures exhibits potent feeding-deterrent activity against three deadly mosquito vectors:Aedes aegypti, Anopheles gambiaeandCulex pipiens. We further demonstrate that the deterrent-active fraction isolated from replicate bacterial cultures is consistently highly enriched in two modified peptides identical to the previously described fabclavines, strongly suggesting that these are molecular species responsible for feeding-deterrence. The mosquito feeding-deterrent activity in the fabclavines-rich fraction is comparable to or better than that of N, N-diethyl-3-methylbenzamide (also known as Deet) or picaridin in side-by-side assays. Our unique discovery lays the groundwork for research into biologically derived, peptide-based low molecular weight compounds isolated from bacteria for exploitation as mosquito repellents and feeding-deterrents.
Novel deleterious nsSNPs withinMEFVgene that could be used as Diagnostic Markers to Predict Hereditary Familial Mediterranean Fever: Using bioinformatics analysis
Authors: Mustafa Mujahed I. , Abdelhameed Tebyan A , Abdelrhman Fatima A. , Osman Soada Ahmed , Hassan Mohamed A. 
Published: September 2018

AbstractBackgroundFamilial Mediterranean Fever (FMF) is the most common auto inflammatory disease (AID) affecting mainly the ethnic groups originating from Mediterranean basin, we aimed to identify the pathogenic SNPs in MEFV by computational analysis software.MethodsWe carried out in silico prediction of structural effect of each SNP using different bioinformatics tools to predict substitution influence on protein structure and function.Result23 novel mutations out of 857 nsSNPs that are found to be deleterious effect on the MEFV structure and function.ConclusionThis is the first in silico analysis in MEFV gene to prioritize SNPs for further genetic mapping studies. After using multiple bioinformatics tools to compare and rely on the results predicted, we found 23 novel mutations that may cause FMF disease and it could be used as diagnostic markers for Mediterranean basin populations.
The origin and evolution of acetylcholine signaling through AchRs in metazoans
Authors: Faltine-Gonzalez Dylan Z. , Layden Michael J 
Published: September 2018

ABSTRACTBackgroundAcetylcholine is a cell signaling molecule that has been identified in plants, bacteria, and metazoans to play multiple roles in cells and as a neurotransmitter capable of exciting both neurons and muscle. While cell-cell communication activity has been reported in all phyla that have been investigated, its role as a neurotransmitter is less clear. Work within cnidarians implies that neurotransmitter activity emerged within or prior to the emergence of the cnidarian-bilaterian ancestor, but whether or not it is able to excite both muscles and neurons has not been addressed.ResultsTo investigate the evolution of acetylcholine signaling we characterized the expression pattern of acetylcholine receptors (AchRs) and the neurotransmitter activity of acetylcholine in Nematostella vectensis. Expression patterns for 13 of the 21 known NvAchRs are consistent with acetylcholine acting as a cell signaling molecule and a neurotransmitter in neurons, muscles, or both. To dissect neurotransmitter activity we investigated the mechanism by which acetylcholine activates tentacular contractions in Nematostella. Tentacular contractions induced by application of acetylcholine are suppressed by inactivating voltage gated sodium channels with lidocaine indicating that acetylcholine specifically activates neurons in the tentacular contractile circuit.ConclusionOur results verify that acetylcholine’s neurotransmitter activity emerged prior to cnidarian-bilaterian divergence and that non-neuronal roles were likely retained in Nematostella. Additionally, we found no evidence to support a muscle activating role for acetylcholine indicating that its role in muscle excitability evolved during bilaterian evolution.
The oxysterol synthesizing enzyme CH25H contributes to the development of intestinal fibrosis
Authors: Raselli T. , Wyss A. , Gonzalez Alvarado M.N. , Weder B. , Mamie C. , Spalinger M.R. , van Haaften W. T. , Dijkstra G. , Sailer A.W. , Imenez Silva P.H. , Wagner C.A. , Tosevski V. , Leibl Sebastian , Scharl M. , Rogler G. , Hausmann M. , Misselwitz B. 
Published: September 2018

AbstractIntestinal fibrosis and stenosis are common complications of Crohn’s disease (CD), frequently requiring surgery. Anti-inflammatory strategies can only partially prevent fibrosis; hence, anti-fibrotic therapies remain an unmet clinical need. Oxysterols are oxidized cholesterol derivatives, with important roles in various biological processes. The enzyme cholesterol 25-hydroxylase (CH25H) converts cholesterol to 25-hydroxycholesterol (25-HC), which modulates immune responses and oxidative stress. In human intestinal samples from CD patients we found a strong correlation of CH25H mRNA expression with the expression of fibrosis markers. We demonstrate reduced intestinal fibrosis in mice deficient for the CH25H enzyme using the sodium dextran sulfate (DSS)-induced chronic colitis model. Additionally, using a heterotopic transplantation model of intestinal fibrosis, we demonstrate reduced collagen deposition and lower concentrations of hydroxyproline in CH25H knockouts. In the heterotopic transplant model, CH25H was expressed in fibroblasts. Taken together, our findings indicate an involvement of oxysterol synthesis in the pathogenesis of intestinal fibrosis.
An Amyloid beta-derived Septapeptide has hMCP-1 Chemokine Activity
Authors: Van Alstyne Diane 
Published: September 2018

AbstractSeptapeptides (“septas”), previously identified as meningitis-specific antigens, defined by a rubella virus (RV) monoclonal antibody, were found in human Monocyte Chemoattractant Protein (hMCP-1) and on the surface of meningitis-causing bacteria, viruses and spirochetes. Some bacterial septas were tested for Ca+2 mobilization through receptor-associated heterotrimeric G-protein binding on THP-1 cells, progenitor cells of circulating peripheral macrophages. Certain of the free septas acted on their own as mild agonist of Ca+2 mobilization. Their signal transduction activity may be mediated through a single, or a single class, of receptor, but the data do not link this with the MCP-1 receptor on THP-1 cells. These data support the proposals that (1) the septas represent muteins of the MCP-1 active site for stem cell activation to macrophages and (2) infectious organisms may conserve and employ these sequences in order to facilitate their transport through the Blood Brain Barrier (BBB) to infect the Central Nervous System (CNS). Other MCP muteins have since been identified in the Alzheimer’s Disease (AD)-associated agents, amyloid beta (Abeta) and prions, as well as in viruses like HIV, known to establish chronic infections in the CNS. Rat glial progenitor cells in tissue culture were used to test for hMCP-1 activity in septas derived from amyloid beta. Nanomolar concentrations of the amyloid beta septa 13HHQKLVF19 were found to transform more than 60% of the progenitor cells into microglia in tissue culture. Taken together, these data support the hypothesis that amyloid beta may accumulate to increase the number of microglia available to combat chronic infection in the CNS. A new paradigm for neurodegenerative disease is presented.
Towards Zero-Latency Neurofeedback
Authors: Smetanin Nikolai , Lebedev Mikhail A. , Ossadtchi Alexei 
Published: September 2018

ABSTRACTNeurofeedback (NFB) is a real-time paradigm, where subjects monitor their own brain activity presented to them via one of the sensory modalities: visual, auditory or tactile. NFB has been proposed as an approach to treat neurological conditions and augment brain functions. In many applications, especially in the automatic learning scenario it is important to decrease NFB latency, so that appropriate brain mechanisms can be efficiently engaged. To this end, we propose a novel algorithm that significantly reduces feedback signal presentation in the electroencephalographic (EEG) NFB paradigm. The algorithm is based on the least squares optimization of the finite impulse response (FIR) filter weights and analytic signal reconstruction. In this approach, the trade-off between NFB latency and the accuracy of EEG envelope estimation can be achieved depending on the application needs. Moreover, the algorithm allows to implement predictive NFB by setting latency to negative values while maintaining acceptable envelope estimation accuracy. As such, our algorithm offers significant improvements in cases where subjects need to detect neural events as soon as possible and even in advance.
Muscle mechanics and energy expenditure of the triceps surae during rearfoot and forefoot running
Authors: Gruber Allison H. , Umberger Brian R. , Miller Ross H. , Hamill Joseph 
Published: September 2018

ABSTRACTForefoot running is advocated to improve running economy because of increased elastic energy storage than rearfoot running. This claim has not been assessed with methods that predict the elastic energy contribution to positive work or estimate muscle metabolic cost. The purpose of this study was to compare the mechanical work and metabolic cost of the gastrocnemius and soleus between rearfoot and forefoot running. Seventeen rearfoot and seventeen forefoot runners ran over-ground with their habitual footfall pattern (3.33-3.68m•s−1) while collecting motion capture and ground reaction force data. Ankle and knee joint angles and ankle joint moments served as inputs into a musculoskeletal model that calculated the mechanical work and metabolic energy expenditure of each muscle using Hill-based muscle models with contractile (CE) and series elastic (SEE) elements. A mixed-factor ANOVA assessed the difference between footfall patterns and groups (α=0.05). Forefoot running resulted in greater SEE mechanical work in the gastrocnemius than rearfoot running but no differences were found in CE mechanical work or CE metabolic energy expenditure. Forefoot running resulted in greater soleus SEE and CE mechanical work and CE metabolic energy expenditure than rearfoot running. The metabolic cost associated with greater CE velocity, force production, and activation during forefoot running may outweigh any metabolic energy savings associated with greater SEE mechanical work. Therefore, there was no energetic benefit at the triceps surae for one footfall pattern or the other. The complex CE-SEE interactions must be considered when assessing muscle metabolic cost, not just the amount of SEE strain energy.
Time and space dimensions of gene dosage imbalance of aneuploidies revealed by single cell transcriptomes
Authors: Stamoulis Georgios , Garieri Marco , Makrythanasis Periklis , Letourneau Audrey , Guipponi Michel , Panousis Nikolaos , Sloan-Béna Frédérique , Falconnet Emilie , Ribaux Pascale , Borel Christelle , Santoni Federico , Antonarakis Stylianos E 
Published: September 2018

AbstractThe mechanisms underlying cellular and organismal phenotypes due to copy number alterations (CNA) are not fully understood. Aneuploidy is a major source of gene dosage imbalance due to CNA and viable human trisomies are model disorders of altered gene expression. To understand the cellular impact of gene dosage imbalance, we studied gene and allele specific expression (ASE) of 9668 single-cell fibroblasts in trisomies T21, T18, T13 and T8. To limit the bias of interindividual noise, all comparisons between euploid and trisomic single-cells were performed on an isogenic setting for all trisomies studied. Initially we examined 928 single cells with deep RNA-Seq. For T21 we used fibroblasts from one pair of monozygotic twins discordant for T21 and from mosaic T21. For T18, T13 and T8 we analyzed single cells from mosaic individuals. Single-cell analyses revealed inconsistencies concerning the overexpression of some genes observed in differential trisomic vs euploid bulk RNAseq while this imbalance was not detectable in trisomic vs. euploid single cells. Moreover, ASE profiling of all single cells uncovered a substantial monoallelic pattern of expression in the trisomic fraction of the genome. By classifying genes according to the level of mono and bi-allelic transcription, we have observed that, for genes with monoallelic and low-to-average expression, the altered gene dosage is mainly due to the higher fraction of cells simultaneously expressing these genes in the trisomic samples. These results were confirmed in a further experiment of 8740 single fibroblasts from the monozygotic twins discordant for T21 samples. We conclude that gene dosage imbalance is of bidimensional nature: over time (simultaneous expression of all alleles resulting in increased accumulation of RNA of copy altered genes in each single cell) as previously stated, and over space (increased fraction of cells simultaneously expressing copy altered genes). These results strongly suggest that each class of genes contributes to the phenotypic variability of trisomies according to its temporal and spatial behavior and propose an improved model to understand the effects of copy number alterations.
Vision using multiple distinct rod opsins in deep-sea fishes
Authors: Musilova Zuzana , Cortesi Fabio , Matschiner Michael , Davies Wayne I. L. , Stieb Sara M. , de Busserolles Fanny , Malmstrøm Martin , Tørresen Ole K. , Mountford Jessica K. , Hanel Reinhold , Jakobsen Kjetill S. , Carleton Karen L. , Jentoft Sissel , Marshall Justin , Salzburger Walter 
Published: September 2018

AbstractVertebrate vision is accomplished through a set of light-sensitive photopigments, which are located in the photoreceptors of the retina and consist of a visual opsin protein bound to a chromophore. In dim-light, vertebrates generally rely upon a single rod opsin (RH1) for obtaining visual information. By inspecting 101 fish genomes, we found that three deep-sea teleost lineages have independently expanded theirRH1gene repertoires. Amongst these, the silver spinyfin (Diretmus argenteusJohnson 1863) stands out as having the highest number of visual opsins known for animals to date (2 cone and 38 rod opsins). Spinyfins simultaneously express up to 14RH1sencoding for photopigments with different peak spectral sensitivities (λmax=448-513 nm) that cover the range of the residual daylight, as well as the bioluminescence spectrum present in the deep-sea. Our findings present novel molecular and functional evidence for the recurrent evolution of multiple rod opsin-based vision in vertebrates.SHORT ABSTRACTContrary to the single rod opsin used by most vertebrates, some fishes use multiple rod opsins for vision in the dimly lit deep-sea.
Optimization of Energy State Transition Trajectory Supports the Development of Executive Function During Youth
Authors: Cui Zaixu , Stiso Jennifer , Baum Graham L. , Kim Jason Z. , Roalf David R. , Betzel Richard F. , Gu Shi , Lu Zhixin , Xia Cedric H. , Ciric Rastko , Moore Tyler M. , Shinohara Russell T. , Ruparel Kosha , Davatzikos Christos , Pasqualetti Fabio , Gur Raquel E. , Gur Ruben C. , Bassett Danielle S. , Satterthwaite Theodore D. 
Published: September 2018

ABSTRACTExecutive function develops rapidly during adolescence, and failures of executive function are associated with both risk-taking behaviors and psychopathology. However, it remains relatively unknown how structural brain networks mature during this critical period to facilitate energetically demanding transitions to activate the frontoparietal system, which is critical for executive function. In a sample of 946 human youths (ages 8-23 yr) who completed diffusion imaging as part of the Philadelphia Neurodevelopment Cohort, we capitalized upon recent advances in network control theory in order to calculate the control energy necessary to activate the frontoparietal system given the existing structural network topology. We found that the control energy required to activate the frontoparietal system declined with development. Moreover, we found that this control energy pattern contains sufficient information to make accurate predictions about individuals’ brain maturity. Finally, the control energy costs of the cingulate cortex were negatively correlated with executive performance, and partially mediated the development of executive performance with age. These results could not be explained by changes in general network control properties or in network modularity. Taken together, our results reveal a mechanism by which structural networks develop during adolescence to facilitate the instantiation of activation states necessary for executive function.SIGNIFICANCE STATEMENTExecutive function undergoes protracted development during youth, but it is unknown how structural brain networks mature to facilitate the activation of the frontoparietal cortex that is critical for executive processes. Here, we leverage recent advances in network control theory to establish that structural brain networks evolve in adolescence to lower the energetic cost of activating the frontoparietal system. Our results suggest a new mechanistic framework for understanding how brain network maturation supports cognition, with clear implications for disorders marked by executive dysfunction, such as ADHD and psychosis.
5-Hydroxymethylcytosines from Circulating Cell-free DNA as Diagnostic and Prognostic Markers for Hepatocellular Carcinoma
Authors: Cai Jiabin , Chen Lei , Zhang Zhou , Zhang Xinyu , Lu Xingyu , Liu Weiwei , Shi Guoming , Ge Yang , Gao Pingting , Yang Yuan , Ke Aiwu , Xiao Linlin , Dong Ruizhao , Zhu Yanjing , Yang Xuan , Wang Jiefei , Zhu Tongyu , Yang Deping , Huang Xiaowu , Sui Chengjun , Qiu Shuangjian , Shen Feng , Sun Huichuan , Zhou Weiping , Zhou Jian , Nie Ji , Zhang Xu , C-H.Chiu Brian , Lau Wan Yee , He Chuan , Wang Hongyang , Zhang Wei , Fan Jia 
Published: September 2018

AbstractThe lack of highly sensitive and specific diagnostic biomarkers is a major contributor to the poor outcomes of patients with hepatocellular carcinoma (HCC), the second-most common cause of cancer deaths worldwide. We sought to develop a clinically convenient and minimally-invasive approach that can be deployed at scale for the sensitive, specific, and highly reliable diagnosis of HCC, and to evaluate the potential prognostic value of this approach. The study cohort comprised of 2,728 subjects, including HCC patients (n = 1,208), controls (n = 965) (572 healthy individuals and 393 patients with benign lesions), as well as patients with chronic hepatitis B infection (CHB) (n =291), liver cirrhosis (LC) (n = 110), and cholangiocarcinoma (CCC) (n = 154), was recruited from three major liver cancer hospitals in Shanghai, China, from July 2016 to November 2017. Circulating cell-free DNA (cfDNA) were collected from plasma samples from these individuals before surgery or any radical treatment. Applying our 5hmC-Seal technique, the summarized 5-hydroxymethylcytosine (5hmC) profiles in cfDNA were obtained. Molecular annotation analysis suggested that the profiled 5hmC loci in cfDNA were enriched with liver tissue-derived regulatory markers (e.g., H3K4me1). We showed that a weighted diagnostic score (wd-score) based on 117 genes detected using the summarized 5hmC profiles in cfDNA accurately distinguished HCC patients from controls (AUC = 95.1%; 95% CI, 93.6-96.5%) in the validation set, markedly outperformed α-fetoprotein (AFP) with superior sensitivity. The wd-scores, which not only detected early BCLC stages (e.g., Stage 0: AUC = 96.2%; 95% CI,94.1-98.4%) and small tumors (e.g., < 2 cm: AUC = 95.7%; 95% CI: 93.6-97.7%), also showed high capacity for distinguishing HCC from non-cancer patients with CHB/LC (AUC = 80.2%; 95% CI, 75.8-84.6%). Moreover, the prognostic value of 5hmC markers in cfDNA was evaluated for HCC recurrence, showing that a weighted prognostic score (wp-score) based on 16 marker genes predicted the recurrence risk (HR = 6.67; 95% CI, 2.81-15.82, p < 0.0001) in 555 patients who have been followed up after surgery. In conclusion, we have developed and validated a robust 5hmC-based diagnostic model that can be applied routinely with clinically feasible amount of cfDNA (e.g., from ~2-5 mL of plasma). Applying this new approach in the clinic could significantly improve the clinical outcomes of HCC patients, for example by early detection of those patients with surgically resectable tumors or as a convenient disease surveillance tool for recurrence.