bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beyond Bonferroni Revisited: Concerns over inflated false positives in conservation genetics, genetics, and neuroscience
Authors: White Tonya , van der Ende Jan , Nichols Thomas E. 
Published: September 2018

AbstractIn 2006, Narum published a paper in Conservation Genetics that was motivated by the stringent nature of the Bonferroni approach for family wise error correction. That work suggested that the approach of Benjamini and Yekutieli in 2001 provided adequate correction and was more biologically relevant. However, there are crucial differences between the original Benjamini and Yekutieli procedure and that described by Narum. After carefully reviewing both papers, we believe that the Narum procedure is both different than the Benjamini and Yekutieli procedure and does not adequately control for family wise error. We provide an overview of approaches for FWE correction as well as evidence for the faulty implementation of the Benjamini and Yekutieli procedure by Narum using the equations from the respective papers, data from both papers, and the results of simulation.
A cell atlas of the adult Drosophila midgut
Authors: Hung Ruei-Jiun , Hu Yanhui , Kirchner Rory , Li Fangge , Xu Chiwei , Comjean Aram , Tattikota Sudhir Gopal , Song Wei Roc , Sui Shannan Ho , Perrimon Norbert 
Published: September 2018

AbstractStudies of the adult Drosophila midgut have provided a number of insights on cell type diversity, stem cell regeneration, tissue homeostasis and cell fate decision. Advances in single-cell RNA sequencing (scRNA-seq) provide opportunities to identify new cell types and molecular features. We used inDrop to characterize the transcriptome of midgut epithelial cells and identified 12 distinct clusters representing intestinal stem cells (ISCs), enteroblasts (EBs), enteroendocrine cells (EEs), enterocytes (ECs) from different regions, and cardia. This unbiased approach recovered 90% of the known ISCs/EBs markers, highlighting the high quality of the dataset. Gene set enrichment analysis in conjunction with electron micrographs revealed that ISCs are enriched in free ribosomes and possess mitochondria with fewer cristae. We demonstrate that a subset of EEs in the middle region of the midgut expresses the progenitor marker esg and that individual EEs are capable of expressing up to 4 different gut hormone peptides. We also show that the transcription factor klumpfuss (klu) is expressed in EBs and functions to suppress EE formation. Lastly, we provide a web-based resource for visualization of gene expression in single cells. Altogether, our study provides a comprehensive resource for addressing novel functions of genes in the midgut epithelium.
Regulation of KIF1A motility via polyglutamylation of tubulin C-terminal tails
Authors: Lessard Dominique V. , Zinder Oraya J. , Hotta Takashi , Verhey Kristen J. , Ohi Ryoma , Berger Christopher L. 
Published: September 2018

ABSTRACTAxonal transport is a highly regulated cellular process responsible for site-specific neuronal cargo delivery. This process is mediated in part by KIF1A, a member of the kinesin-3 family of molecular motors. It is imperative that KIF1A’s highly efficient, superprocessive motility along microtubules is tightly regulated as misregulation of KIF1A cargo delivery is observed in many neurodegenerative diseases. However, the regulatory mechanisms responsible for KIF1A’s motility, and subsequent proper spatiotemporal cargo delivery, are largely unknown. One potential regulatory mechanism of KIF1A motility is through the posttranslational modifications (PTMs) of axonal microtubules. These PTMs, often occurring on the C-terminal tails of the microtubule tracks, act as molecular “traffic signals” helping to direct kinesin motor cargo delivery. Occurring on neuronal microtubules, C-terminal tail polygutamylation is known to be important for KIF1A cargo transport. KIF1A’s initial interaction with microtubule C-terminal tails is facilitated by the K-loop, a positively charged surface loop of the KIF1A motor domain. However, the K-loop’s role in KIF1A motility and response to perturbations in C-terminal tail polyglutamylation is underexplored. Using single-molecule imaging, we present evidence of KIF1A’s previously unreported pausing behavior on multiple microtubule structures. Further analysis revealed that these pauses link multiple processive segments together, contributing to KIF1A’s characteristic superprocessive run length. We further demonstrate that KIF1A pausing is mediated by a K-loop/polyglutamylated C-terminal tail interaction and is a regulatory mechanism of KIF1A motility. In summary, we introduce a new mechanism of KIF1A motility regulation, providing further insight into KIF1A’s role in axonal transport.
Late greenhouse gas mitigation has heterogeneous effects on European caddisfly diversity patterns
Authors: Januchowski-Hartley Stephanie R , Lauzeral Christine , Schmidt-Kloiber Astrid , Graf Wolfram , Brosse Sebastien 
Published: September 2018

ABSTRACTLittle remains known about how the timing of mitigation of current greenhouse gas emissions will influence freshwater biodiversity patterns. Using three general circulation models, we evaluate the response of 260 broad-ranging European caddisfly species to climate conditions in 2080 under two scenarios: business as usual (A2A) and mitigation (A1B). If implemented effectively, recent government commitments established under COP21, to mitigate current greenhouse gas emissions, would result in future climatic conditions similar to the mitigation scenario we explored. Under the Cgcm circulation model, which we found to be the most conservative model, suitable environmental conditions were predicted to shift 3° more to the east under the mitigation scenario compared to business as usual. The majority of broad-ranging European caddisfly species will benefit from mitigation, but 5 to 15% of species that we evaluated will be bigger losers under the mitigation scenario compared to business as usual. Under the mitigation scenario, caddisfly species that will retain less of their current range and experience lower predicted range expansion are those that currently have relatively limited distributions. Continental-scale assessments such as the ones that we present are needed to identify species at greatest risk of range loss under changing climatic conditions.
OLIVER: A Tool for Visual Data Analysis on Longitudinal Plant Phenomics Data
Authors: Tessmer Oliver L , Kramer David M , Chen Jin 
Published: September 2018

AbstractThere is a critical unmet need for new tools to analyze and understand “big data” in the biological sciences where breakthroughs come from connecting massive genomics data with complex phenomics data. By integrating instant data visualization and statistical hypothesis testing, we have developed a new tool called OLIVER for phenomics visual data analysis with a unique function that any user adjustment will trigger real-time display updates for any affected elements in the workspace. By visualizing and analyzing omics data with OLIVER, biomedical researchers can quickly generate hypotheses and then test their thoughts within the same tool, leading to efficient knowledge discovery from complex, multi-dimensional biological data. The practice of OLIVER on multiple plant phenotyping experiments has shown that OLIVER can facilitate scientific discoveries. In the use case of OLIVER for large-scale plant phenotyping, a quick visualization identified emergent phenotypes that are highly transient and heterogeneous. The unique circular heat map with false-color plant images also indicates that such emergent phenotypes appear in different leaves under different conditions, suggesting that such previously unseen processes are critical for plant responses to dynamic environments.
Optimal features for auditory categorization
Authors: Liu Shi Tong , Montes-Lourido Pilar , Wang Xiaoqin , Sadagopan Srivatsun 
Published: September 2018

AbstractHumans and vocal animals use vocalizations (human speech or animal ‘calls’) to communicate with members of their species. A necessary function of auditory perception is to generalize across the high variability inherent in the production of these sounds and classify them into perceptually distinct categories (‘words’ or ‘call types’). Here, we demonstrate using an information-theoretic approach that production-invariant classification of calls can be achieved by detecting mid-level acoustic features. Starting from randomly chosen marmoset call features, we used a greedy search algorithm to determine the most informative and least redundant set of features necessary for call classification. Call classification at >95% accuracy could be accomplished using only 10 – 20 features per call type. Most importantly, predictions of the tuning properties of putative neurons selective for such features accurately matched some previously observed responses of superficial layer neurons in primary auditory cortex. Such a feature-based approach succeeded in categorizing calls of other species such as guinea pigs and macaque monkeys, and could also solve other complex classification tasks such as caller identification. Our results suggest that high-level neural representations of sounds are based on task-dependent features optimized for specific computational goals.
Deconstructing cell-free extract preparation forin vitroactivation of transcriptional genetic circuitry
Authors: Silverman Adam D. , Kelley-Loughnane Nancy , Lucks Julius B. , Jewett Michael C. 
Published: September 2018

AbstractRecent advances in cell-free gene expression (CFE) systems have enabled their use for a host of synthetic biology applications, particularly for rapid prototyping of genetic circuits designed as biosensors. Despite the proliferation of cell-free protein synthesis platforms, the large number of currently existing protocols for making CFE extracts muddles the collective understanding of how the method by which an extract is prepared affects its functionality. Specifically, a key goal toward developing cell-free biosensors based on native genetic regulators is activating the transcriptional machinery present in bacterial extracts for protein synthesis. However, protein yields from genes transcribedin vitroby the nativeEscherichia coliRNA polymerase are quite low in conventional crude extracts originally optimized for expression by the bacteriophage transcriptional machinery. Here, we show that cell-free expression of genes under bacterial σ70promoters is constrained by the rate of transcription in crude extracts and that processing the extract with a ribosomal run-off reaction and subsequent dialysis can alleviate this constraint. Surprisingly, these processing steps only enhance protein synthesis in genes under native regulation, indicating that the translation rate is unaffected. We further investigate the role of other common process variants on extract performance and demonstrate that bacterial transcription is inhibited by including glucose in the growth culture, but is unaffected by flash-freezing the cell pellet prior to lysis. Our final streamlined protocol for preparing extract by sonication generates extract that facilitates expression from a diverse set of sensing modalities including protein and RNA regulators. We anticipate that this work will clarify the methodology for generating CFE extracts that are active for biosensing and will encourage the further proliferation of cell-free gene expression technology for new applications.
Inhibition of Mycobacterium tuberculosis DosRST two-component regulatory system signaling by targeting response regulator DNA binding and sensor kinase heme
Authors: Zheng Huiqing , Aleiwi Bilal , Ellsworth Edmund , Abramovitch Robert B. 
Published: September 2018

AbstractMycobacterium tuberculosis (Mtb) possesses a two-component regulatory system, DosRST, that enables Mtb to sense host immune cues and establish a state of non-replicating persistence (NRP). NRP bacteria are tolerant to several anti-mycobacterial drugs and are thought to play a role in the long course of tuberculosis (TB) therapy. Therefore, small molecules that inhibit Mtb from establishing or maintaining NRP could reduce the reservoir of drug tolerant bacteria and function as an adjunct therapy to reduce treatment time. Previously, we reported the discovery of six novel chemical inhibitors of DosRST, named HC101A-106A, from a whole cell, reporter-based phenotypic high throughput screen. Here, we report functional and mechanism of action studies of HC104A and HC106A. RNAseq transcriptional profiling shows that the compounds downregulate genes of the DosRST regulon. Both compounds reduce hypoxia-induced triacylglycerol synthesis by ~50%. HC106A inhibits Mtb survival during hypoxia-induced NRP, however, HC104A did not inhibit survival during NRP. An electrophoretic mobility assay shows that HC104A inhibits DosR DNA binding in a dose-dependent manner, indicating that HC104A may function by directly targeting DosR. In contrast, UV-visible spectroscopy studies suggest HC106A directly targets the histidine kinase heme, via a mechanism that is distinct from the oxidation and alkylation of heme previously observed with artemisinin (HC101A). Synergistic interactions were observed when DosRST inhibitors were examined in pair-wise combinations with the strongest potentiation observed between artemisinin paired with HC102A, HC103A, or HC106A. Our data collectively show that the DosRST pathway can be inhibited by multiple distinct mechanisms.
MAPS: model-based analysis of long-range chromatin interactions from PLAC-seq and HiChIP experiments
Authors: Juric Ivan , Yu Miao , Abnousi Armen , Raviram Ramya , Fang Rongxin , Zhao Yuan , Zhang Yanxiao , Yang Yuchen , Li Yun , Ren Bing , Hu Ming 
Published: September 2018

AbstractHi-C and chromatin immunoprecipitation (ChIP) have been combined to identify long-range chromatin interactions genome-wide at reduced cost and enhanced resolution, but extracting the information from the resulting datasets has been challenging. Here we describe a computational method, MAPS, Model-based Analysis of PLAC-seq and HiChIP, to process the data from such experiments and identify long-range chromatin interactions. MAPS adopts a zero-truncated Poisson regression framework to explicitly remove systematic biases in the PLAC-seq and HiChIP datasets, and then uses the normalized chromatin contact frequencies to identify significant chromatin interactions anchored at genomic regions bound by the protein of interest. MAPS shows superior performance over existing software tools in analysis of chromatin interactions centered on cohesin, CTCF and H3K4me3 associated regions in multiple cell types. MAPS is freely available at https://github.com/ijuric/MAPS.
Interpretable Convolution Methods for Learning Genomic Sequence Motifs
Authors: Ploenzke MS , Irizarry RA 
Published: September 2018

AbstractThe first-layer filters employed in convolutional neural networks tend to learn, or extract, spatial features from the data. Within their application to genomic sequence data, these learned features are often visualized and interpreted by converting them to sequence logos; an information-based representation of the consensus nucleotide motif. The process to obtain such motifs, however, is done through post-training procedures which often discard the filter weights themselves and instead rely upon finding those sequences maximally correlated with the given filter. Moreover, the filters collectively learn motifs with high redundancy, often simply shifted representations of the same sequence. We propose a schema to learn sequence motifs directly through weight constraints and transformations such that the individual weights comprising the filter are directly interpretable as either position weight matrices (PWMs) or information gain matrices (IGMs). We additionally leverage regularization to encourage learning highly-representative motifs with low inter-filter redundancy. Through learning PWMs and IGMs directly we present preliminary results showcasing how our method is capable of incorporating previously-annotated database motifs along with learning motifs de novo and then outline a pipeline for how these tools may be used jointly in a data application.
Rapid responses of winter aphid-parasitoid communities to climate warming
Authors: Tougeron K. , Damien M. , Le Lann C. , Brodeur J. , van Baaren J. 
Published: September 2018

AbstractConsequences of environmental fluctuations, including those associated with climate changes, can have a knock-on effect from individual to community scale. In particular, changes in species seasonal phenology can modify the structure and composition of communities, with potential consequences on their functioning and the provision of ecosystem services. In mild climate areas, aphids can be present in cereal fields throughout the winter, which allows aphid parasitoids to remain active. Using a nine-year dataset of aphid-parasitoid winter trophic webs in cereal fields of Western France, we report that the community structure and composition that prevailed before 2011 have recently shifted toward a more diversified community, with the presence of two new braconid parasitoid species (Aphidius erviandAphidius avenae), a few hyperparasitoid species and one aphid species (Metopolophium dirhodum). Increases in minimal winter temperatures and the frequency of frost events across the years partially explain observed community changes. Strong bottom-up effects from the relative abundances of aphid species also determine the relative abundance of parasitoid species each winter. Strong compartmentalization in parasitoid preference for host is reported. We suggest the recent modifications in parasitoid community composition to be linked to shifts in diapause expression (reduction or arrest of the use of winter diapause) and to host availability throughout the year. We highlight the implications for natural biological control in cereal fields. Perspectives are proposed to predict the composition of future host-parasitoid communities in the climate change context.
Numerical optimization of surface texture for improved tribological performance of journal bearing at varying operating conditions
Authors: Usman Ali , Park Cheol Woo 
Published: September 2018

Purpose
Journal bearings are used in numerous rotary machines. The load carrying capacity and friction of a bearing have been major concerns in design. Recent developments in surface texturing have showed potential outcomes to improve the tribological characteristics of mating surfaces. This study aims to investigate surface textures, which are transverse to the sliding direction, for frictional response of the journal bearing.

Design/methodology/approach
A hydrodynamic lubrication model is considered to evaluate the effect of surface texturing on the performance of a journal bearing at varying operating conditions. The two-dimensional generalized Reynolds equation, coupled with mass-conserving Elrod cavitation algorithm, is solved to evaluate texture-induced variations in tribological performance parameters.

Findings
Results have showed remarkable improvements in frictional response. Moreover, micro-textures on the journal surface alter the cavitation response and film-reformation in the hydrodynamic conjunction of the plain bearing.

Originality/value
Operating condition-based comprehensive exhaustive optimization of texture geometry is performed to generate widespread conclusion.
Examining the role of leadership inspiration, rewards and its relationship with contribution to knowledge sharing
Authors: Al Dari Taghreed , Jabeen Fauzia , Papastathopoulos Avraam 
Published: September 2018

Purpose
The purpose of this paper is to examine the impact of leadership and rewards on the contribution to knowledge sharing in public organizations of the United Arab Emirates (UAE).

Design/methodology/approach
Data were collected from 154 employees from various organizational units of a law enforcement organization in the UAE, and structural equation modeling was used to test the proposed hypotheses.

Findings
Leadership inspiration was found to be positively effective in enhancing the contribution of knowledge sharing in terms of solving problems, increasing opportunity and improving the productivity of the workforce. Furthermore, it was found that the reward system had no impact on the contribution to knowledge sharing.

Research limitations
The method of data collection focused on the employees who were attending a training workshop in the department. This survey raises concerns related to non-response bias and common method bias, which describes the measurement error that is compounded by the sociability of the respondents who wanted to provide positive answers.

Practical implications
This research focuses on the implementation of certain practices related to knowledge sharing in public organizations. The model was constructed to assess the impact of leadership and rewards on the contribution to knowledge sharing through knowledge sharing practices as a mediation. The study is a modest attempt to assist the organizational leaders to embark on the right steps to foster knowledge sharing behavior among employees.

Originality/value
The study contributes to the literature on knowledge sharing, particularly on the relationship between leadership inspiration, rewards and contribution to knowledge sharing in the law enforcement organizations in the UAE.
Why modern slavery thrives in multinational corporations’ global value chains
Authors: Stringer Christina , Michailova Snejina 
Published: September 2018

Purpose
Modern slavery, one of the most abhorrent crimes against humanity, is a profitable international business (IB). It often operates in a hidden form in the global value chains (GVCs) governed by multinational corporations (MNCs). The purpose of this paper is to examine why slavery exists in GVCs and what this means for MNCs.

Design/methodology/approach
The paper borrows insights from the GVC literature to conceptually link MNCs and modern slavery. Different from the IB literature that predominantly focusses on the MNC as a single firm, the paper emphasizes the importance of paying attention to the MNC value chains and their complexity and fragmentation.

Findings
Three factors which help explain modern slavery in GVCs are examined: the complexity of GVCs and the challenges this poses to their governance, the business case for slavery and the conditions that enable modern slavery. These factors, taken together, provide an explanation why modern slavery can creep into, persist and thrive in MNCs’ GVCs.

Research limitations/implications
The argument is put forward for the need for IB scholars to borrow from the GVC literature to help understand why slavery can exist in the GVCs of MNCs. This opens the opportunity for examining the MNC in ways not considered by IB scholars so far.

Originality/value
The paper addresses an issue long ignored in IB research and issues a call for IB scholars to study MNCs in a new way, namely, linking MNCs’ activities with modern slavery.