bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the post-glacial spread of human commensal Arabidopsis thaliana: journey to the east
Authors: Hsu Che-Wei , Lo Cheng-Yu , Lee Cheng-Ruei 
Published: September 2018

AbstractWith the availability of more sequenced genomes, our understanding of the evolution and demographic history of the model plant Arabidopsis thaliana is rapidly expanding. Here we compile previously published data to investigate global patterns of genetic variation. While the Southeast African accessions were reported to be the most divergent among worldwide populations, we found accessions from Yunnan, China to be genetically close to the sub-Saharan accessions. Our further investigation of worldwide chloroplast genomes identified several deeply diverged haplogroups existing only in Eurasia, and the African populations have lower variation in many haplogroups they shared with the Eurasian populations. Bayesian inferences of chloroplast demography showed that representative haplogroups of Africa exhibited long-term stable population size, suggesting recent selective sweep or bottleneck is not able to explain the lower chloroplast variation in Africa. Taken together, these patterns cannot be easily explained by a single out-of-Africa event. Several Eurasian chloroplast haplogroups had rapid population growth since 10 kya, presumably reflecting the recent expansion of the weedy non-relicts across Eurasia. Our demographic analysis on a chromosomal region un-affected by relict introgression also suggested the European, Central Asian, and Chinese Yangtze populations diverged no earlier than 15 kya, in contrast to previous estimates of 45 kya inferred from whole genome that likely contains relict admixture. The most recent expansion is observed in the Yangtze population of China less than 2000 years ago. Similar to Iberia, the western end of non-relict expansion reported in our previous study, in this eastern end of Eurasia we find clear traces of gene flow between the Yangtze non-relicts and the Yunnan relicts. Genes under strong selection and previously suggested to contribute to adaptation in the Yangtze valley are enriched for traces of relict introgression, especially those related with biotic and immune responses. The results suggest the ability of non-relicts to obtain locally adaptive alleles through admixture with relicts is an important factor contributing to the rapid expansion across the environmental gradients spanning the eastern to the western coast of Eurasia.
Tau filaments from multiple cases of sporadic and inherited Alzheimer’s disease adopt a common fold
Authors: Falcon Benjamin , Zhang Wenjuan , Schweighauser Manuel , Murzin Alexey G. , Vidal Ruben , Garringer Holly J. , Ghetti Bernardino , Scheres Sjors H.W. , Goedert Michel 
Published: September 2018

AbstractThe ordered assembly of tau protein into abnormal filaments is a defining characteristic of Alzheimer’s disease (AD) and other neurodegenerative disorders. It is not known if the structures of tau filaments vary within, or between, the brains of individuals with AD. We used a combination of electron cryo-microscopy (cryo-EM) and immuno-gold negative-stain electron microscopy (immuno-EM) to determine the structures of paired helical filaments (PHFs) and straight filaments (SFs) from the frontal cortex of 17 cases of typical AD (15 sporadic and 2 inherited) and 2 cases of atypical AD (posterior cortical atrophy). The high-resolution structures of PHFs and SFs from the frontal cortex of 3 cases of typical AD, 2 sporadic and 1 inherited, were determined by cryo-EM. We also used immuno-EM to study the PHFs and SFs from a number of cortical and subcortical brain regions. PHFs outnumbered SFs in all AD cases. By cryo-EM, PHFs and SFs were made of two C-shaped protofilaments with a combined cross-β/β-helix structure, as described previously for a case of AD. The higher resolution structures obtained here showed two additional amino acids at each end of the protofilament structure. The immuno-EM findings, which established the presence of repeats 3 and 4, but not repeats 1 and 2, of tau in the filament cores of all AD cases and brain regions thereof, were consistent with the cryo-EM results. These findings show that there is no significant variation in tau filament structures between individuals with AD. This knowledge will be crucial for understanding the mechanisms that underlie tau filament formation and for developing novel diagnostics and therapies.
Karyopherin Kap114p regulates TATA-binding protein-mediated transcription
Authors: Liao Chung-Chi , Shankar Sahana , Ahmed Golam Rizvee , Hsia Kuo-Chiang 
Published: September 2018

SUMMARYGene expression is regulated by nuclear accessibility of transcription factors controlled by transport receptors and competitive inhibitors. Multiple karyopherin-βs (Kap-βs) facilitate nuclear import of yeast TATA-binding protein (yTBP). However, only Kap114p suppresses temperature-sensitive yTBP mutations, suggesting Kap114p executes undefined non-transport functions. We show that yTBP preferably binds Kap114p with an affinity three orders of magnitude higher than other Kap-βs facilitating yTBP nuclear import. Our crystal structure of Kap114p reveals an extensively negatively-charged concave surface, accounting for high-affinity basic-protein binding. Furthermore, we biochemically demonstrate that two intra-HEAT-repeat inserts act as regulatory TBP-binding domains carried by TBP-associated factor 1 (TAF1-TAND), suppressing binding of yTBP with DNA and the transcription factor IIA. Remarkably, dual-knockout of Kap114 and TAF1-TAND in yeast synergistically suppresses cell growth. Our study reveals that Kap114p has a dual function that modulates the nuclear localization and activity of yTBP, illuminating how the nuclear transport machinery regulates yTBP-mediated transcription.
SCDT: Detecting somatic CNVs of low chimeric ratio in cf-DNA
Authors: Qian Zhaoyang , Wang Xiaofeng , Shi Chang , Han Rui , Wang Yaoshen , Zhu Hongmei 
Published: September 2018

AbstractMotivationSequencing of cell-free DNA (cf-DNA) has enabled Noninvasive Prenatal Testing (NIPT) and”liquid biopsy” of cancers. However, while the aneuploidy and point mutations were focused on by most of NITP and liquid biopsy studies, detecting sub-chromosome CNVs that affect a few to dozens of megabases was rarely reported, likely attributable to the difficulty in accurately identifying them, especially for those present in a small fraction of cf-DNA.ResultsWe developed a somatic CNV detection tool (SCDT), for detecting sub-chromosome CNVs in cf-DNA using whole genome sequencing (WGS) data or off-target reads in target sequencing data. Additional to using control samples for correcting genome position specific bias, two GC correction steps were performed, which regressed GC content of DNA fragments and that of genome bins, respectively. After GC correction, the coefficients of variation of copy ratios approximated the lower boundary of theoretical values, suggesting removing of almost all systematic errors. Finally, CNVs were detected by a piecewise least squares fitting based segmentation algorithm, which outperformed other segmentation methods. We applied SCDT on simulated and real maternal plasma samples, and target cf-DNA sequencing of 118 normal individuals and 240 cancer patients, and demonstrated high sensitivity and specificity.AvailabilitySCDT is available at https://github.com/Martiantian/Somatic_cnv_detect_tool.Contactzhuhongmei@genomics.cnSupplementary InformationSupplementary data are available at Bioinformatics online
Computational mechanisms of curiosity and goal-directed exploration
Authors: Schwartenbeck Philipp , Passecker Johannes , Hauser Tobias U , FitzGerald Thomas H B , Kronbichler Martin , Friston Karl 
Published: September 2018

AbstractSuccessful behaviour depends on the right balance between maximising reward and soliciting information about the world. Here, we show how different types of information-gain emerge when casting behaviour as surprise minimisation. We present two distinct mechanisms for goal-directed exploration that express separable profiles of active sampling to reduce uncertainty. ‘Hidden state’ exploration motivates agents to sample unambiguous observations to accurately infer the (hidden) state of the world. Conversely, ‘model parameter’ exploration, compels agents to sample outcomes associated with high uncertainty, if they are informative for their representation of the task structure. We illustrate the emergence of these types of information-gain, termed active inference and active learning, and show how these forms of exploration induce distinct patterns of ‘Bayes-optimal’ behaviour. Our findings provide a computational framework to understand how distinct levels of uncertainty induce different modes of information-gain in decision-making.
Tissue self-organization based on collective cell migration by contact activation of locomotion and chemotaxis
Authors: Fujimori Taihei , Nakajima Akihiko , Shimada Nao , Sawai Satoshi 
Published: September 2018

AbstractDespite their central role in multicellular organization, navigation rules that dictate cell rearrangement remain much to be elucidated. Contact between neighboring cells and diffusive attractant molecules are two of the major determinants of tissue-level patterning, however in most cases, molecular and developmental complexity hinders one from decoding the exact governing rules of individual cell movement. A primordial example of tissue patterning by cell rearrangement is found in the social amoebaDictyostelium discoideumwhere the organizing center or the ‘tip’ self-organize as a result of sorting of differentiating prestalk and prespore cells. Due to its relatively simple and conditional multicellularity, the system provides a rare case where the process can be fully dissected into individual cell behavior. By employing microfluidics and microsphere-based manipulation of navigational cues at the single-cell level, here we uncovered a previously overlooked mode ofDictyosteliumcell migration that is strictly directed by cell-cell contact. The cell-cell contact signal is mediated by E-set Ig-like domain containing heterophilic adhesion molecules TgrB1/TgrC1 that act in trans to induce plasma membrane recruitment of SCAR complex and formation of dendritic actin networks, and the resulting cell protrusion competes with those induced by chemoattractant cAMP. Furthermore, we demonstrate that both prestalk and prespore cells can protrude towards the contact signal as well as to chemotax towards cAMP, however when given both signals, prestalk cells orient towards the chemoattractant whereas prespore cells choose the contact signal. These data suggest a new model of cell sorting by competing juxtacrine and diffusive cues each with potential to drive its own mode of collective cell migration. The present findings not only resolve the long standing question of how cells sort inDictyosteliumbut also cast light on the remarkable parallels in collective cell migration that evolved independently in metazoa and amoebozoa.
Influenza incidence prediction for the United States: an update for the 2018-2019 season
Authors: Du Xiangjun , Peng Yousong , Liu Mi , Pascual Mercedes 
Published: September 2018

AbstractIntroduction:Seasonal influenza causes a high disease burden every year in the United States and worldwide. Anticipating epidemic size ahead of season can contribute to preparedness and more targetted control and prevention of seasonal influenza.Methods:A recently developed process-based epidemiological model that incorporates evolutionary change of the virus and generates incidence forecasts for the H3N2 subtype ahead of the season, was previously validated by several statistical criteria, including an accurate real-time prediction for the 2016-2017 influenza season. With this model, a new forecast is generated here for the upcoming 2018-2019 season. The accuracy of predictions published for the 2017-2018 season is also retrospectively evaluated.Results:For 2017-2018, the model correctly predicted the dominance of the H3N2 subtype and its higher than average incidence. Based on surveillance and sequence data up to June 2018, the new forecast for the upcoming 2018-2019 season indicates low levels for H3N2, and suggests an H1N1 dominant season with low incidence of influenza B.Discussion:Real-time forecasts, those generated with a model that was parameterized based on data preceding the predicted season, allows valuable evaluation of the approach. Anticipating the dominant subtype and the size of the upcoming epidemic ahead of season informs disease control. Further studies are needed to promote more accurate ahead-of-season forecasts and extend the approach to multiple subtypes.
Systematically improved in vitro culture conditions reveal new insights into the reproductive biology of the human parasite Schistosoma mansoni
Authors: Wang Jipeng , Chen Rui , Collins James J. 
Published: September 2018

ABSTRACTSchistosomes infect over 200 million people. The prodigious egg output of these parasites is the sole driver of pathology due to infection, yet our understanding of their sexual reproduction is limited because egg production is not sustained for more than a few days in vitro. Here, we describe culture conditions that support schistosome sexual development and sustained egg production in vitro. Female schistosomes rely on continuous pairing with male worms to fuel the maturation of their reproductive organs. Exploiting these new culture conditions, we explore the process of male-stimulated female maturation and demonstrate that physical contact with a male worm, and not insemination, is sufficient to induce female development and the production of viable parthenogenetic haploid embryos. We further report the characterization of a novel nuclear receptor, that we call vitellogenic factor 1, that is essential for female sexual development following pairing with a male worm. Taken together, these results provide a platform to study the fascinating sexual biology of these parasites on a molecular level, illuminating new strategies to control schistosome egg production.
Neuroanatomical correlates of food addiction and obesity in the general population
Authors: Beyer F. , García-García I. , Heinrich M. , Scholz M. , Schroeter ML , Sacher J. , Luck T. , Riedel-Heller S.G. , Stumvoll M. , Villringer A. , Witte A.V. 
Published: September 2018

AbstractThe food addiction model suggests neurobiological similarities between substance-related and addictive disorders and obesity. While structural brain differences have been consistently reported in these conditions, little is known about the neuroanatomical correlates of food addiction. We therefore assessed whether food addiction, assessed with the Yale Food Addiction Scale (YFAS), related to obesity, personality and brain structure in a large population-based sample (n=625; 20-59 years old, 45% women). A higher YFAS symptom score correlated with obesity and disinhibited eating. In a whole-brain analysis, YFAS symptom score was not associated with cortical thickness nor subcortical gray matter volumes. Higher body mass index (BMI) correlated with reduced thickness of (pre)frontal, temporal and occipital cortex. Bayes factor analysis suggested that BMI and - to a smaller extent - YFAS symptom score contributed independently to right lateral orbitofrontal cortex thickness. Our study shows that food addiction is not associated with neuroanatomical differences in a large population-based sample, and does not account for the major part of obesity-associated gray matter alterations. Yet, food addiction might explain additional variance in orbitofrontal cortex, a hub area of the reward network. Longitudinal studies implementing both anatomical and functional MRI could further disentangle the neural mechanisms of addictive eating behaviors.
Enhancing the cell-free expression of native membrane proteins by in-silico optimization of the coding sequence – an experimental study of the human voltage-dependent anion channel
Authors: Zayni Sonja , Damiati Samar , Moreno-Flores Susana , Amman Fabian , Hofacker Ivo , Ehmoser Eva-Kathrin 
Published: September 2018

AbstractThe investigation of membrane proteins, key constituents of cells, is hampered by the difficulty and complexity of their in vitro synthesis, of unpredictable yield. Cell-free synthesis is herein employed to unravel the impact of the expression construct on gene transcription and translation, without the complex regulatory mechanisms of cellular systems. Through the systematic design of plasmids in the immediacy of the start of the target gene, it was possible to identify translation initiation and the conformation of mRNA as the main factors governing the cell-free expression efficiency of the human voltage dependent anion channel (VDAC), a relevant membrane protein in drug-based therapy. A simple translation initiation model was developed to quantitatively assess the expression potential for the designed constructs. A scoring function is proposed that quantifies the feasibility of formation of the translation initiation complex through the ribosome-mRNA hybridization energy and the accessibility of the mRNA segment binding to the ribosome. The scoring function enables to optimize plasmid sequences and semi-quantitatively predict protein expression efficiencies.
Rodent-borne bacterial infections in Gwangju, Korea
Authors: Bang Mi Seon , Kim Choon-Mee , Kim Dong-Min , Yun Na Ra 
Published: September 2018

AbstractBackgroundThis study investigated the prevalence ofOrientia tsutsugamushi, Anaplasma phagocytophilum,andLeptospira interroganin wild rodents through molecular detection in organ samples collected from two distinct sites in Gwangju Metropolitan City, Republic of Korea.Methodology/Principal FindingsA total of 47 wild rodents, identified asApodemus agrarius (A. agrarius), were captured from June to August 2016. The seroprevalence of antibodies against bacterial pathogens in rodent sera was analyzed; 17.4% (8/46) were identified asO. tsutsugamushithrough indirect immunofluorescence assay and 2.2% (1/46) were identified asLeptospiraspp. through passive hemagglutination assay. Using molecular methods, the spleen, kidney, and blood samples were evaluated for the presence ofO. tsutsugamushi, A. phagocytophilum, andL. interrogans. Out of 47 wild rodents, 25.5% (12/47) were positive for bacterial pathogens by PCR, where 19.1% (9/47) were positive forA. phagocytophilumand 6.4% (3/47) were positive forL. interrogans, while none were positive forO. tsutsugamushi. In addition, testing for bacterial infection in different tissues indicated that 8.7% (4/46) were positive forA. phagocytophilumin the blood, 13.3% (6/45) were positive forA. phagocytophilumin the spleen, and 6.4% (3/47) and 2.1% (1/47) were positive forL.interrogansandA. phagocytophilum, respectively, in the kidney.Conclusions/SignificanceIn this study, tropisms forA. phagocytophilumin the spleen andL. interrogansin the kidney were identified. Notably,A. phagocytophilumandL. interroganswere detected in wild rodents living in close proximity to humans in the metropolitan suburban areas. Results of the present study indicate that rodent-borne bacteria may be present in wild rodents in the metropolitan suburban area of Republic of Korea.Author SummaryMany zoonotic diseases are spreading not only in the Republic of Korea (ROK), but also worldwide. Scrub typhus, anaplasmosis, and leptospirosis are well known diseases that are considered common, widespread rodent-borne infectious diseases. Rodents serve as important reservoirs for zoonotic pathogens such asO. tsutsugamushi, A. phagocytophilum, andL. interrogans,which may be fatal to humans. Our study demonstrated the prevalence of these pathogens in wild rodents, through molecular assays and seroprevalence in organ samples. We captured 47 wild rodents in the Gwangju metropolitan city area of ROK. All were identified asA. agrarius. The prevalence of rodent-borne bacteria was 17.4% in the sera, where 25.5% was positively detected as bacterial pathogens via polymerase chain reaction. Our results indicate the importance of detecting rodent-borne bacteria in wild rodents living close to humans in suburban areas of ROK. Our data was limited to only a few samples of rodents in two regions. More samples may have to be collected over longer periods of time, to investigate the infectious nature of these pathogens in detail.
Impact of agricultural credit on farm income under the Savanna and Transitional zones of Ghana
Authors: Abdallah Abdul-Hanan , Ayamga Micheal , Awuni Joseph A. 
Published: September 2018

PurposeThe purpose of this paper is twofold: to determine the factors contributing to farm income in the Transitional and Savanna zones of Ghana and to ascertain variations between in the same and across the two locations; and to determine the impact of credit on farm income in each of the two zones and to ascertain the variation in impact of credit across the two locations.Design/methodology/approachIn order to address endogeneity and sample selection bias, the authors draw from the theory of impact evaluation in nonrandom experiment, employing the endogenous switching regression (ESR) while using the propensity score matching (PSM) to check for robustness of the results.FindingsThe results show significant mean differences between some characteristics of households that have access to credit and those that did not have access. Further, the results revealed farm size, labor; gender, age, literacy, wealth and group membership as the significant determinants of both credit access and income in the two zones. With the ESR, credit access increases households farm income by GH¢206.56/ha and GH¢39.74/ha in the Transitional and Savanna zones, respectively, but with the PSM, credit increases farm income by GH¢201.50 and GH¢45.69 and in the Transitional and Savanna, respectively.Research limitations/implicationsThe mean differences in characteristics of the households revealed the presence of selection bias in the distribution of household’s covariates in the two zones. The results further indicate the importance of productive resources, information and household characteristics in improved access to credit and farm income. Also, the results from both methods indicate that credit access leads to significant gains in farm income for households in both zones. However, differences exist in the results of PSM and that of the ESR results.Practical implicationsThe presence of selection bias in the samples suggests that the use of ESR and PSM techniques is appropriate. Further, the results suggesting that enhanced credit access and farm income could be attained through improved access to household resources and information. The results also suggest the need for establishing and expanding credit programs to cover more households in both zones. The differential impact of credit between the two methods employed in each zone revealed the weakness of each model. The low values from PSM could indicate the presence of selection bias resulting from unobservable factors whiles the high values from the ESR could stem from the restrictive assumption of the model. This reinforces the importance of combining mixed methods to check robustness of results and to explore the weakness of each method employed.Originality/valueThe novelty of this study lies in the use of a very extensive and unique data set to decompose the determinants of credit access and farm income and as well as the impacts of credit into zones.