bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intersectin associates with synapsin and regulates its nanoscale localization and function
Authors: Gerth Fabian , Jäpel Maria , Pechstein Arndt , Kochlamazashvili Gaga , Lehmann Martin , Puchkov Dmytro , Onofri Franco , Benfenati Fabio , Nikonenko Alexander G. , Fredrich Kristin , Shupliakov Oleg , Maritzen Tanja , Freund Christian , Haucke Volker 
Published: October 2017

Significance
Mutations in genes regulating neurotransmission in the brain are implicated in neurological disorders and neurodegeneration. Synapsin is a crucial regulator of neurotransmission and allows synapses to maintain a large reserve pool of synaptic vesicles. Human mutations in synapsin genes are linked to epilepsy and autism. How synapsin function is regulated to allow replenishment of synaptic vesicles and sustain neurotransmission is largely unknown. Here we identify a function for the endocytic scaffold protein intersectin, a protein overexpressed in patients with Down syndrome, as a regulator of synapsin nanoscale distribution and function that is controlled by a phosphorylation-dependent autoinhibitory switch. Our results unravel a hitherto unknown molecular connection between the machineries for synaptic vesicle reserve pool organization and endocytosis.
PELI1 functions as a dual modulator of necroptosis and apoptosis by regulating ubiquitination of RIPK1 and mRNA levels of c-FLIP
Authors: Wang Huibing , Meng Huyan , Li Xingyan , Zhu Kezhou , Dong Kangyun , Mookhtiar Adnan K. , Wei Huiting , Li Ying , Sun Shao-Cong , Yuan Junying 
Published: October 2017

Significance
This study demonstrates Pellino 1 (PELI1) as an important modulator that exerts opposite regulatory functions on apoptosis and necroptosis, two distinct forms of regulated cell death mechanisms. K63 ubiquitination of RIPK1 mediated by PELI1 depends on the kinase activity of RIPK1, which provides a mechanism to explain why inhibition of RIPK1 kinase activity by Nec-1s can also reduce its ubiquitination during necroptosis.
What, no rats? The solar bird tradition and its relevance to the Pied Piper legend
Authors: Kline Jim 
Published: October 2017

ABSTRACTFor over seven hundred years, the legend of the Pied Piper has inspired folk tales, poems, songs, and theatrical productions, as well as speculations about whether the legend is based upon actual events that occurred on 26 June 1284, the date given to the incident according to several commemorative documents and monuments found in the town of Hamelin, Germany, where the legend originated. Many scholars who have studied the legend believe it has little to do with a Pied Piper ridding the town of rats and later enticing the town's children to follow him out of town where they all disappear; instead, they believe the incident refers to a military recruiter who either led a troupe of young men to the Baltic or to Transylvania to establish settlements there. However, other scholars put great significance upon the date of the event and how it might be related to a summer solstice celebration gone awry. The following article provides evidence to support the summer solstice theory, presenting information relating to ancient solar bird traditions that link the piper with shamanic rites in which shamans dress as birds and perform bird sacrifices associated with both summer and winter solstice celebrations.
Anchoring Bias in Recall Data: Evidence from Central America
Authors: Godlonton Susan , Hernandez Manuel A , Murphy Mike 
Published: October 2017

AbstractSelf‐reported retrospective survey data is widely used in empirical work but may be subject to cognitive biases, even over relatively short recall periods. This paper examines the role of anchoring bias in self‐reports of objective and subjective outcomes under recall. We use a unique panel‐survey dataset of smallholder farmers from four countries in Central America collected over a period of three years. We exploit differences between recalled and concurrent responses to quantify the degree of mental anchoring in survey recall data. We assess whether respondents use their reported value for the most recent period as a cognitive heuristic when recalling the value from a previous period, while controlling for the value they reported earlier. The results show strong evidence of sizeable anchoring bias in self‐reported retrospective indicators for both objective measures (income, wages, and working hours) and subjective measures (reports of happiness, health, stress, and well‐being). We also generally observe a larger bias in response to negative changes for objective indicators and a larger bias in response to positive changes for subjective indicators.
Iterative reconstruction of rank-one matrices in noise
Authors: Fletcher Alyson K , Rangan Sundeep 
Published: October 2017

AbstractWe consider the problem of estimating a rank-one matrix in Gaussian noise under a probabilistic model for the left and right factors of the matrix. The probabilistic model can impose constraints on the factors including sparsity and positivity that arise commonly in learning problems. We propose a family of algorithms that reduce the problem to a sequence of scalar estimation computations. These algorithms are similar to approximate message-passing techniques based on Gaussian approximations of loopy belief propagation that have been used recently in compressed sensing. Leveraging analysis methods by Bayati and Montanari, we show that the asymptotic behavior of the algorithm is described by a simple scalar equivalent model, where the distribution of the estimates at each iteration is identical to certain scalar estimates of the variables in Gaussian noise. Moreover, the effective Gaussian noise level is described by a set of state evolution equations. The proposed approach to deriving algorithms thus provides a computationally simple and general method for rank-one estimation problems with a precise analysis in certain high-dimensional settings.
NSD1 inactivation defines an immune cold, DNA hypomethylated subtype in squamous cell carcinoma
Authors: Brennan Kevin , Shin June Ho , Tay Joshua K. , Prunello Marcos , Gentles Andrew , Sunwoo John B. , Gevaert Olivier 
Published: October 2017

AbstractChromatin modifying enzymes are frequently mutated in cancer, resulting in a cascade of epigenetic deregulation. Recent reports indicate that inactivating mutations in the histone methyltransferase NSD1 define an intrinsic subtype of head and neck squamous cell carcinoma (HNSC) that features widespread DNA hypomethylation. Here, we describe a similar DNA hypomethylated subtype of lung squamous cell carcinoma (LUSC) that is enriched for both inactivating mutations and deletions inNSD1. The ‘NSD1 subtype’ of HNSC and LUSC are highly correlated at the DNA methylation and gene expression levels, with concordant DNA hypomethylation and overexpression of a strongly overlapping set of genes, a subset of which are also hypomethylated in Sotos syndrome, a congenital growth disorder caused by germlineNSD1mutations. Further, the NSD1 subtype of HNSC displays an ‘immune cold’ phenotype characterized by low infiltration of tumor-associated leukocytes, particularly macrophages and CD8+T cells, as well as low expression of genes encoding the immunotherapy target PD-1 immune checkpoint receptor and its ligands PD-L1 and PD-L2. Using anin vivomodel, we demonstrate that NSD1 inactivation results in a reduction in the degree of T cell infiltration into the tumor microenvironment, implicating NSD1 as a tumor cell-intrinsic driver of an immune cold phenotype. These data have important implications for immunotherapy and reveal a general role of NSD1 in maintaining epigenetic repression.
The ABCE1 capsid assembly pathway is conserved between primate lentiviruses and the non-primate lentivirus feline immunodeficiency virus
Authors: Reed Jonathan C. , Westergreen Nick , Barajas Brook C. , Ressler Dylan , Phuong Daryl , Swain John V. , Lingappa Vishwanath R. , Lingappa Jaisri R. 
Published: October 2017

AbstractDuring immature capsid assembly in cells, the Gag protein of HIV-1 and other primate lentiviruses co-opts a host RNA granule, forming a pathway of assembly intermediates that contains host components, including two cellular enzymes shown to facilitate assembly, ABCE1 and DDX6. Here we asked whether a non-primate lentivirus, feline immunodeficiency virus (FIV), also forms such RNA-granule-derived intracellular capsid assembly intermediates. First, we found that, unlike for HIV-1, the FIV completed immature capsid and the largest putative assembly intermediate are unstable during analysis. Next, we identifiedin situcross-linking conditions that overcame this problem and revealed the presence of FIV Gag complexes that correspond in size to early and late HIV-1 assembly intermediates. Because assembly-defective HIV-1 Gag mutants are arrested at specific intracellular assembly intermediates, we asked if a similar arrest is also observed for FIV. We analyzed four FIV Gag mutants, including three not previously studied that we identified based on sequence and structural similarity to HIV-1 Gag, and found that each is assembly-defective and arrested at the same intermediate as the corresponding HIV-1 mutant. Further evidence that these FIV Gag-containing complexes correspond to assembly intermediates came from co-immunoprecipitation studies demonstrating that FIV Gag is associated with ABCE1 and DDX6, as shown previously for HIV-1. Finally, we validated these co-immunoprecipitations with a proximity ligation assay that revealed co-localization between assembly-competent FIV Gag and ABCE1in situ. Together, these data offer novel structure-function insights and indicate that primate and non-primate lentiviruses form intracellular capsid assembly intermediates derived from ABCE1-containing RNA granules.ImportanceLike HIV-1, FIV Gag assembles into immature capsids; however, it is not known whether FIV Gag progresses through a pathway of immature capsid assembly intermediates derived from host RNA granules, as shown for HIV-1 Gag. Here we asked whether FIV Gag forms complexes similar in size to HIV-1 assembly intermediates and if FIV Gag is associated with ABCE1 and DDX6, two host enzymes that facilitate HIV-1 immature capsid assembly that are found in HIV-1 assembly intermediates. Our studies identified FIV Gag-containing complexes that closely resemble HIV-1 capsid assembly intermediates, showed that known and novel assembly-defective FIV Gag mutants fail to progress past these putative intermediates, and utilized biochemical and imaging approaches to demonstrate association of FIV Gag with ABCE1 and DDX6. Thus, we conclude that viral-host interactions important for immature capsid assembly are conserved between primate and non-primate lentiviruses, and could yield important targets for future antiviral strategies.
Association of a biomarker-based frailty index with telomere length in older US adults: Findings from NHANES 1999-2002
Authors: Bello Ghalib A. , Chiu Yueh-Hsiu M. , Dumancas Gerard G. 
Published: October 2017

ABSTRACTObjectivesTo study the link between frailty and cellular senescence, we examine the association of leukocyte telomere length (LTL) with a recently introduced measure of subclinical frailty that is based entirely on laboratory test biomarkers (FI-LAB).MethodsThis study was conducted on a random sample of 1890 Americans aged 60+. Multiple Linear Regression was used to examine the relationship between FI-LAB and LTL.ResultsA statistically significant association was found between FI-LAB and LTL after adjusting for multiple covariates, indicating that higher FI-LAB scores are associated with shorter telomeres.DiscussionOur study results establish a link between subclinical frailty (FI-LAB) and cellular aging, which may help elucidate the pathophysiological mechanisms giving rise to frailty.
Reduced transmission ofMycobacterium africanumcompared toM. tuberculosisin urban West Africa
Authors: Asare Prince , Asante-Poku Adwoa , Prah Diana Ahu , Borrell Sonia , Osei-Wusu Stephen , Otchere Isaac Darko , Forson Audrey , Adjapong Gloria , Koram Kwadwo Ansah , Gagneux Sebastien , Yeboah-Manu Dorothy 
Published: October 2017

AbstractBackgroundUnderstanding transmission dynamics is useful for tuberculosis (TB) control. We conducted a population-based molecular epidemiological study to understand TB transmission in Ghana.MethodsMycobacterium tuberculosiscomplex (MTBC) isolates obtained from prospectively-sampled pulmonary TB patients between July, 2012 and December, 2015 were confirmed as MTBC using IS6110PCR. MTBC lineages were identified by large sequence polymorphism and single nucleotide polymorphism assays and further characterized using spoligotyping and standard 15-loci MIRU-VNTR typing. We used the n-1 method to estimate recent TB transmission and identified associated risk factors using logistic regression analysis.FindingsOut of 2,309 MTBC isolates, we identified 1,082 (46·9%) single cases with 1,227 (53·1%) isolates belonging to one of 276 clustered cases (clustering range; 2-35). Recent TB transmission rate was estimated to be 41·2%. While we see no significant difference in the recent transmission rates between lineages ofMycobacterium africanum(lineage-5 (31·8%); lineage-6 (24·7%), p=0·118), we found that lineage-4 belonging to theM. tuberculosistransmitted significantly higher (44·9%, p<0·001). Finally, apart from age being significantly associated with recent TB transmission (p=0·007), we additionally identified a significant departure in the male/female ratio among very large clustered cases compared to the general TB patient population (3:1 vs. 2:1, p=0·022).InterpretationsOur findings indicate high recent TB transmission suggesting occurrences of unsuspected outbreaks. The observed reduced transmission rate ofM. africanumsuggests other factor(s) may be responsible for its continuous presence in West Africa.FundingWellcome Trust Intermediate Fellowship Grant 097134/Z/11/Z to Dorothy Yeboah-Manu.
Game theoretic consideration of transgenic bacteria in the human gut microbiota as a pro-biotic prophylactic for metabolic syndrome
Authors: Ibrahim Ahmed M. , Smith James 
Published: October 2017

AbstractA game theoretic treatment is introduced to explore the role of nutrition of the gut bacterial microflora as a potential pro-biotic therapy. Rational design of functional foods and nutraceuticals has far reaching public health and therapeutic benefits. Understanding ecological dynamics and how phenotypic manipulations of microbe-microbe interactions of the gut microbiota can provide direct health benefit is currently a fundamental question in bioengineering and more widely in the food, diet and health industries. This work considers a hypothetical adjustment of the microbiome by introducing a transgenic bacterial species that contributes to increased exposure of omega 3 fats in the gut by converting them from the omega 6 fats, dominant in the Western diet. The ratio of the two fats circulating in blood are risk markers, indicators of metabolic syndrome and related conditions. In this work, we consider nutritional exposure to a pro-biotic, a live culture of transgenic bacteria contributing omega 3 fats from omega 6 in the diet. Maintaining a long-term co-existence between native (indigenous) and transgenic bacteria is a challenge. Game theory is the appropriate tool for handling this conflict. The long-term co-existence is guaranteed if the two strains engage in the Snowdrift game. Our game theoretic treatment provides the basis of a model mechanism for prophylactic nutritional therapy for metabolic syndrome by the transgenic bacteria, providing support of indigenous gut microbiota and additional supplementation of a pro-biotic.
An Observational Study of Ballooning in Large Spiders: Nanoscale Multi-Fibers Enable Large Spiders’ Soaring Flight
Authors: Cho Moonsung , Neubauer Peter , Fahrenson Christoph , Rechenberg Ingo 
Published: October 2017

AbstractThe physical mechanism of aerial dispersal of spiders, “ballooning behavior,” is still unclear because of the lack of serious scientific observations and experiments. Therefore, as a first step in clarifying the phenomenon, we studied the ballooning behavior of relatively large spiders (heavier than 5 mg) in nature. Additional wind tunnel tests to identify ballooning silks were implemented in the laboratory. From our observation, it seems obvious that spiders actively evaluate the condition of the wind with their front leg (leg I) and wait for the preferable wind condition for their ballooning takeoff. In the wind tunnel tests, as yet unknown physical properties of ballooning fibers (length, thickness and number of fibers) were identified. Large spiders, 16–20 mgXysticusspecies, spun 50 to 60 nanoscale fibers, with a diameter of 121 to 323 nm. The length of these threads was 3.22 ± 1.31 m (N = 22). These physical properties of ballooning fibers can explain the ballooning of large spiders with relatively light updrafts, 0.1–0.5 m s-1, which exist in a light breeze of 1.5–3.3 m s-1. Additionally, in line with previous research on turbulence in atmospheric boundary layers and from our wind measurements, it is hypothesized that spiders use the ascending air current for their aerial dispersal, the “ejection” regime, which is induced by hairpin vortices in the atmospheric boundary layer turbulence. This regime is highly correlated with lower wind speeds. This coincides well with the fact that spiders usually balloon when the wind speed is lower than 3 m s-1.
Leveraging heterogeneity across multiple data sets increases accuracy of cell-mixture deconvolution and reduces biological and technical biases
Authors: Vallania Francesco , Tam Andrew , Lofgren Shane , Schaffert Steven , Azad Tej D , Bongen Erika , Alsup Meia , Alonso Michael , Davis Mark , Engleman Edgar , Khatri Purvesh 
Published: October 2017

AbstractIn silico quantification of cell proportions from mixed-cell transcriptomics data (deconvolution) requires a reference expression matrix, called basis matrix. We hypothesized that matrices created using only healthy samples from a single microarray platform would introduce biological and technical biases in deconvolution. We show presence of such biases in two existing matrices, IRIS and LM22, irrespective of the deconvolution method used. Here, we present immunoStates, a basis matrix built using 6160 samples with different disease states across 42 microarray platforms. We found that immunoStates significantly reduced biological and technical biases. We further show that cellular proportion estimates using immunoStates are consistently more correlated with measured proportions than IRIS and LM22, across all methods. Importantly, we found that different methods have virtually no effect once the basis matrix is chosen. Our results demonstrate the need and importance of incorporating biological and technical heterogeneity in a basis matrix for achieving consistently high accuracy.
Machine Learning for Population Genetics: A New Paradigm
Authors: Schrider Daniel R. , Kern Andrew D. 
Published: October 2017

AbstractAs population genomic datasets grow in size, researchers are faced with the daunting task of making sense of a flood of information. To keep pace with this explosion of data, computational methodologies for population genetic inference are rapidly being developed to best utilize genomic sequence data. In this review we discuss a new paradigm that has emerged in computational population genomics: that of supervised machine learning. We review the fundamentals of machine learning, discuss recent applications of supervised machine learning to population genetics that outperform competing methods, and describe promising future directions in this area. Ultimately, we argue that supervised machine learning is an important and underutilized tool that has considerable potential for the world of evolutionary genomics.
Structural lipids enable the formation of functional oligomers of the eukaryotic purine symporter UapA
Authors: Pyle Euan , Kalli Antreas C. , Amillis Sotiris , Hall Zoe , Hanyaloglu Aylin C. , Diallinas George , Byrne Bernadette , Politis Argyris 
Published: October 2017

AbstractThe role of membrane lipids in modulating eukaryotic transporter structure and function remains poorly understood. We used native mass spectrometry in combination with molecular dynamics simulations andin vivoanalyses to investigate the roles of membrane lipids in the structure and transport activity of the purine transporter, UapA, fromAspergillus nidulans. We revealed that UapA exists mainly as a dimer and that two lipid molecules bind per UapA dimer. We identified three classes of phospholipids: phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI) which co-purified with UapA. Delipidation of UapA caused dissociation of the dimer into individual protomers. Subsequent addition of PI or PE rescued the UapA dimer and allowed recovery of bound lipids, suggesting a central role of these lipids in stabilising the dimer. We predicted a putative lipid-binding site near the UapA dimer interface. Mutational analyses established that lipid binding at this site is essential for formation of functional UapA dimers. Our findings reveal unprecedented level of detail into the nature of UapA-lipid interactions and provide a framework for studying similar eukaryotic systems.
SALP, a new single-stranded DNA library preparation method especially useful for the high-throughput characterization of chromatin openness states
Authors: Wu Jian , Dai Wei , Wu Ling , Wang Jinke 
Published: October 2017

AbstractBased on a novel kind of single strand adaptor (SSA), this study developed a new method to construct next-generation sequencing (NGS) library, named as SALP, representing Single strand Adaptor Library Preparation. The key creativity of the method lies in the design and verification of a special adaptor that can be efficiently linked to the 3′ end of single-stranded DNA, which is a double-stranded oligonucleotide with a 3′ overhang of 3 random nucleotides. This method can start with the denatured DNAs or chromatins fragmented by different methods such as Tn5 tagmentation, enzyme digestion and sonication. When applied to Tn5-tagmented chromatin, SALP overcomes the key limitation of the current ATAC-seq method and develops a high-throughput NGS library construction and sequencing approach, SALP-seq, which can be used to comparatively characterize the chromatin openness state of multiple cells simply and unbiasly. In this way, the comparative chromatin openness states of four different cell lines, including GM12878, HepG2, HeLa and 293T, were successfully characterized. This study also demonstrated that SALP-seq could characterize the chromatin openness states with 105to 500 cells, indicating the high sensitivity of SALP-seq in characterizing chromatin state of cells. SALP should have wide applications in the future biological sciences and biomedicine.
Drosophila species learn dialects through communal living
Authors: Kacsoh Balint Z , Bozler Julianna , Bosco Giovanni 
Published: October 2017

ABSTRACTMany species are able to share information about their environment by communicating through auditory, visual, and olfactory cues. In Drosophila melanogaster, exposure to parasitoid wasps leads to a decline in egg laying, and exposed females communicate this threat to naïve flies, which also depress egg laying. We find that species across the genus Drosophila respond to wasps by egg laying reduction, activate cleaved caspase in oocytes, and communicate the presence of wasps to naïve individuals. communication within a species and between closely related species is efficient, while more distantly related species exhibit partial communication. Remarkably, partial communication between some species is enhanced after a cohabitation period that requires exchange of visual and olfactory signals. This interspecies “dialect learning” requires neuronal cAMP signaling in the mushroom body, suggesting neuronal plasticity facilitates dialect learning and memory. These observations establish Drosophila as genetic models for inter-species social communication and evolution of dialects.