bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosomal-level genome assembly of the scimitar-horned oryx: insights into diversity and demography of a species extinct in the wild
Authors: Humble Emily , Dobrynin Pavel , Senn Helen , Chuven Justin , Scott Alan F. , Mohr David W. , Dudchenko Olga , Omer Arina D. , Colaric Zane , Aiden Erez Lieberman , Wildt David , Oliaji Shireen , Tamazian Gaik , Pukazhenthi Budhan , Ogden Rob , Koepfli Klaus-Peter 
Published: December 2019

AbstractCaptive populations provide a valuable insurance against extinctions in the wild. However, they are also vulnerable to the negative impacts of inbreeding, selection and drift. Genetic information is therefore considered a critical aspect of conservation management planning. Recent developments in sequencing technologies have the potential to improve the outcomes of management programmes however, the transfer of these approaches to applied conservation has been slow. The scimitar-horned oryx (Oryx dammah)is a North African antelope that has been extinct in the wild since the early 1980s and is the focus of a long-term reintroduction project. To enable the selection of suitable founder individuals, facilitate post-release monitoring and improve captive breeding management, comprehensive genomic resources are required. Here, we used 10X Chromium sequencing together with Hi-C contact mapping to develop a chromosomal-level genome assembly for the species. The resulting assembly contained 29 chromosomes with a scaffold N50 of 100.4 Mb, and displayed strong chromosomal synteny with the cattle genome. Using resequencing data from six additional individuals, we demonstrated relatively high genetic diversity in the scimitar-horned oryx compared to other mammals, despite it having experienced a strong founding event in captivity. Additionally, the level of diversity across populations varied according to management strategy. Finally, we uncovered a dynamic demographic history that coincided with periods of climate variation during the Pleistocene. Overall, our study provides a clear example of how genomic data can uncover valuable insights into captive populations and contributes important resources to guide future management decisions of an endangered species.
Akt1-associated actomyosin remodelling is required for nuclear lamina dispersal and nuclear shrinkage in epidermal terminal differentiation
Authors: Rogerson Clare , Wotherspoon Duncan , O’Shaughnessy Ryan F L 
Published: December 2019

AbstractKeratinocyte cornification and epidermal barrier formation are tightly controlled processes, which require complete degradation of intracellular organelles, including removal of keratinocyte nuclei. Keratinocyte nuclear destruction requires Akt1-dependent phosphorylation and degradation of the nuclear lamina protein, Lamin A/C, essential for nuclear integrity. However, the molecular mechanisms that result in complete nuclear removal and their regulation are not well defined. Post-confluent cultures of rat epidermal keratinocytes (REKs) undergo spontaneous and complete differentiation, allowing visualisation and perturbation of the differentiation process in vitro. We demonstrate that there is dispersal of phosphorylated Lamin A/C to structures throughout the cytoplasm in differentiating keratinocytes. We show that the dispersal of phosphorylated Lamin A/C is Akt1-dependent and these structures are specific for the removal of Lamin A/C from the nuclear lamina; nuclear contents and Lamin B were not present in these structures. Immunoprecipitation identified a group of functionally related Akt1 target proteins involved in Lamin A/C dispersal, including actin, which forms cytoskeletal microfilaments, Arp3, required for actin filament nucleation, and Myh9, a component of myosin IIa, a molecular motor that can translocate along actin filaments. Disruption of actin filament polymerisation, nucleation or myosin IIa activity prevented formation and dispersal of cytoplasmic Lamin A/C structures. Live imaging of keratinocytes expressing fluorescently tagged nuclear proteins showed a nuclear volume reduction step taking less than 40 minutes precedes final nuclear destruction. Preventing Akt1-dependent Lamin A/C phosphorylation and disrupting cytoskeletal Akt1-associated proteins prevented nuclear volume reduction. Single cell RNA sequencing of differentiating keratinocytes identified gene changes correlated with lamin dispersal, which we propose are due to changes in lamina-associated domains upon Lamin A/C dispersal. We propose keratinocyte nuclear destruction and differentiation requires myosin II activity and the actin cytoskeleton for two intermediate processes: Lamin A/C dispersal and rapid nuclear volume reduction.
PPARγ is a tumor suppressor in basal bladder tumors offering new potential therapeutic opportunities
Authors: Coutos-Thévenot Laure , Beji Syrine , Neyret-Kahn Hélène , Pippo Quentin , Fontugne Jacqueline , Osz Judith , Krucker Clémentine , Groeneveld Clarice Dos Santos , Dufour Florent , Kamoun Aurélie , Ley Marie , Chapeaublanc Elodie , Reynies Aurélien de , Lebret Thierry , Allory Yves , Cianférani Sarah , Radvanyi François , Rochel Natacha , Bernard-Pierrot Isabelle 
Published: December 2019

AbstractPPARγ activation is a critical event in luminal muscle-invasive bladder cancer (MIBC) tumorigenesis, favoring both tumor cell growth and microenvironment modulation toward tumor immune escape. Conversely, the down-regulation of PPARγ activity in basal MIBC suggests tumor suppressive effects in this subgroup. Here, we report genetic, epigenetic and functional evidence to support the tumor suppressor role for PPARγ in basal bladder tumors. We identified hemizygous deletions, DNA hyper-methylation and loss-of-function mutations of PPARγ in basal MIBC, associated with PPARγ under-expression and its decreased activity. Re-expression of PPARγ in basal tumor cells resulted in the activation of PPARγ -dependent transcription program that modulated fatty acid metabolism and cell differentiation and decreased cell growth, which could partly rely on EGFR down-regulation. Structure-function studies of two PPARγ mutant revealed a destabilization of a region important for coactivator recruitment and should help develop potent molecules to activate PPARγ as a therapeutic strategy for basal MIBC. The identification of this subtype-dependent dual role of PPARγ in MIBC strengthens the critical role of PPARγ in bladder tumorigenesis and reinforces the interest in stratified medicine based on tumor molecular subtyping.One sentence summaryGenetic, epigenetic and functional evidence of a tumor suppressor role for PPARγ in basal bladder tumors offer new therapeutic opportunities for this subgroup.
In situ SAXS of protein deposits in Alzheimer’s disease
Authors: Solvas Biel Roig , Hyman Bradley T. , Makowski Lee 
Published: December 2019

AbstractDeposits of Aβ peptides (plaques) and tau protein (neurofibrillary tangles (NFTs)) are ubiquitous features of brain tissue in Alzheimer’s disease. Their contribution to disease etiology remains controversial. The molecular-to-nano-scale organization of fibrillar species in these protein aggregates remains uncertain, but may contain clues as to the contributions of these structures to disease. Whether or not all plaques are the same structure, and all tangles are the same, has implications for current hypotheses about polymorphic templated misfolding of their constituent proteins, Aβ and tau. Here we use x-ray microdiffraction in the small-angle regime (SAXS) to probe the molecular organization of these deposits. Using unstained histological sections of human brain tissue, we demonstrate that SAXS can characterize Aβ fibrils and tau filaments in situ. Aβ fibrils have a cross-sectional radius of gyration (Rxc) of ~45 Å, and larger (Rxc >150 Å) aggregates appear to represent Aβ fibrils that have coalesced side-to-side with one another to create fibrillar bundles or macrofibrillar aggregates. Tau fibrils exhibit an Rxc of ~55 Å with little sign of coalescence into larger structure. The in situ mapping of these structures revealed subtle variation in Aβ structure across different brain areas and different cases.
The dynamic transmission of positional information in stau- mutants during Drosophila embryogenesis
Authors: Yang Zhe , Zhu Hongcun , Kong KaKit , Chen Jiayi , Wu Xiaxuan , Li Peiyao , Jiang Jialong , Zhao Jingchao , Liu Feng 
Published: December 2019

AbstractIntriguingly, the developmental patterning during Drosophila embryogenesis is highly accurate and robust despite its dynamic changes and constant fluctuations. It has been suggested that Staufen (Stau) is key in controlling the boundary variability of the gap protein Hunchback (Hb). However, its underlying mechanism is still elusive. Here, we have developed methods to quantify the dynamic 3D expression of segmentation genes in Drosophila embryos. With improved control of measurement errors, our results reveal that the posterior boundary of the Hb anterior domain (xHb) of stau- mutants shows comparable variability to that of the wild type (WT) and shifts posteriorly by nearly 12% of the embryo length (EL) to the WT position in the nuclear cycle (nc) 14. This observed large shift might contribute significantly to the apparent large variability of xHb in previous studies. Moreover, for stau- mutants, the upstream Bicoid (Bcd) gradients show equivalent gradient noise to that of the WT in nc12-nc14, and the downstream Even-skipped (Eve) and cephalic furrow (CF) show the same positional errors as the WT. Our results indicate that threshold-dependent activation and self-organized filtering are not mutually exclusive but could both be implemented in early Drosophila embryogenesis.
Toxicity, transfer and depuration of anatoxin-a (cyanobacterial neurotoxin) in medaka fish exposed by single-dose gavage
Authors: Colas Simon , Duval Charlotte , Marie Benjamin 
Published: December 2019

AbstractThe proliferations of cyanobacteria are increasingly prevalent in warm and nutrient-enriched waters and occur in many rivers and water bodies due especially to eutrophication. The aim of this work is to study in female medaka fish the toxicity, the transfer and the depuration of the anatoxin-a, a neurotoxin produced by benthic cyanobacterial biofilms. This work will provide answers regarding acute toxicity induced by single gavage by anatoxin-a and to the risks of exposure by ingestion of contaminated fish flesh, considering that data on these aspects remain particularly limited.The oral LD50 of a single dose of (±)-anatoxin-a was determined at 11.50 µg.g−1. First of all, lethal dose (100% from 20 µg.g−1) provokes rapid respiratory paralysis (in 1-2 min) of the fish inducing the death by asphyxia. Noticeably, no death nor apparent neurotoxicologic effect occurred during the experimentation period for the 45 fish exposed to a single sub-acute dose of (±)-anatoxin-a corresponding to the no observable adverse effect level (NOAEL = 6.67 µg.g−1). Subsequently, the toxico-kinetics of the (±)-anatoxin-a was observed in the guts, the livers and the muscles of female medaka fish for 10 days.In parallel, a protocol for extraction of anatoxin-a has been optimized beforehand by testing 3 different solvents on several matrices, the extraction with 75% methanol + 0.1% formic acid appearing to be the most efficient. Anatoxin-a was quantified by high-resolution qTOF mass spectrometry coupled upstream to a UHPLC chromatographic chain. The toxin could not be detected in the liver after 12 h, and in the gut and muscle after 3 days. The mean clearance rates of (±)-anatoxin-a calculated after 12 h are above 58%, 100% and 90% for the guts, the livers and the muscles, respectively. Non-targeted metabolomics investigations performed on the fish liver indicates that the single sub-acute exposure by gavage induces noticeable metabolome dysregulations, including important phospholipid decreases, with an organism recovery period of above 12-24h. Overall, the medaka fish do not appear to accumulate (±)-anatoxin-a and to largely recover after 24h following a single sub-acute oral liquid exposure at the NOAEL.
Evaluating the consequences of common assumptions in run reconstructions on Pacific-salmon biological status assessments
Authors: Peacock Stephanie J. , Hertz Eric , Holt Carrie A. , Connors Brendan , Freshwater Cameron , Connors Katrina 
Published: December 2019

AbstractInformation on biological status is essential for designing, implementing, and evaluating management strategies and recovery plans for threatened or exploited species. However, the data required to quantify status are often limited, and it is important to understand how assessments of status may be biased by assumptions in data analysis. For Pacific salmon, biological status assessments based on spawner abundances and spawner-recruitment (SR) analyses often involve “run reconstructions” that impute missing spawner data, expand observed spawner abundance to account for unmonitored streams, assign catch to individual stocks, and quantify age-at-return. Using a stochastic simulation approach, we quantified how common assumptions in run reconstructions biased assessments of biological status based on spawner abundance. We found that status assessments were robust to most common assumptions in run reconstructions, even in the face of declining monitoring coverage, but that overestimating catch tended to increase rates of status misclassification. Our results lend confidence to biological status assessments based on spawner abundances and SR analyses, even in the face of incomplete data.
Cryo-EM Structure of the Human Mitochondrial Translocase TIM22 Complex
Authors: Qi Liangbo , Wang Qiang , Guan Zeyuan , Wu Yan , Cao Jianbo , Zhang Xing , Yan Chuangye , Yin Ping 
Published: December 2019

AbstractMitochondria play vital functions in cellular metabolism, homeostasis, and apoptosis1-3. Most of the mitochondrial proteins are synthesized as precursors in the cytosol and imported into mitochondria for folding or maturation4,5. The translocase TIM22 complex is responsible for the import of multiple hydrophobic carrier proteins that are then folded in the inner membrane of mitochondria6-8. In mammalian cells, the TIM22 complex consists of at least six components, Tim22, Tim29, AGK, and three Tim chaperones (Tim9, Tim10a and Tim10b)9-14. Here, we report the cryo-EM structure of the human translocase TIM22 complex at an overall resolution of 3.7 angstrom. The core subunit, Tim22, contains four transmembrane helices, forming a partial pore that is open to the lipid bilayer. Tim29 is a single transmembrane protein that provides an N-terminal helix to stabilize Tim22 and a C-terminal intermembrane space (IMS) domain to connect AGK and two TIM chaperone hexamers to maintain complex integrity. One TIM hexamer comprises Tim9 and Tim10a in a 3:3 molar ratio, and the other consists of two Tim9 units, three Tim10a units, and one Tim10b unit. The latter hexamer faces the intramembrane region of Tim22, likely providing the dock to load the precursors to the partial pore of Tim22. Our structure serves as a molecular basis for the mechanistic understanding of TIM22 complex function.
SEMA3F-deficient colorectal cancer cells Promote lymphangiogenesis: fatty acid metabolism replace glycolysis for energy supply during lymphatic endothelial cells proliferation in tumor hypoxia microenvironment
Authors: Fu Xiaoyuan , Tao Miaomiao , Ma Hongbo , Wang Cancan , Li Yanyan , Hu Xiaoqiao , Qin Xiurong , Lv Renming , Zhou Gengdou , Wang Jun , Zhou Meiyu , Xu Guofa , Wang Zexin , Chen Min , Zhou Qi 
Published: December 2019

Abstractlymphangiogenesis as a process is colorectal cancer first metastasis via lymphatic vessels to proximal lymph nodes. The fuel metabolism in mitochondrial and support proliferation of lymphatic endothelial cells (LECs) remain elusive during lymphangiogenesis in tumor hypoxic microenvironment. Recent studies report that loss of SEMA3F critically contributes to lymphangiogenesis of the CRCs. Here, we silenced SEMA3F expression of CRCs and co-culture with hLECs, the tubulogenesis capacity and hLECs migration were escalated in the hypoxia, the hLECs mainly relied on fatty acid metabolism not aerobic glycolysis during lymphangiogenesis. SEMA3F-deficient CRCs up-regulated PMAKP expression and phosphorylation of hLECs, and activated its peroxisome proliferator-activated receptor (PPARs) and Peroxisome proliferator–activated receptor gamma coactivator-1 alpha (PGC-1a) facilitated their switched toward fatty acids (FA) catabolism. Furthermore, we observed that activation of the PGCI-PPAR lipid oxidation signaling pathway in hLECs was caused by the secretion of interleukin-6 by tumor cells.Taken together, this study indicates that CRCs with SEMA3F expression depletion significantly promotes lymphangiogenesis in hypoxia and faciliates the secretion of IL-6 in tumor cell, and activates mitochondria fatty acids oxidation (FAO) reaction in the hLECs by PGCI-PPAR signaling pathways to support its growth.
4D Bridge Information Modelling for management of bridge projects: a case study from India
Authors: Vilventhan Aneetha , Rajadurai R. 
Published: December 2019

Purpose
The rapid development of the construction industry requires effective ways to monitor and control the project, and the use of 4D BIM is found to be very efficient. The purpose of this paper is to consider development, application and evaluation of 4D Bridge Information Modelling (BrIM) models for an ongoing bridge project.

Design/methodology/approach
An ethnographic action-based case study research methodology is adopted in this study. An ongoing bridge construction project in India is chosen and the 4D BrIM application is evaluated both quantitatively and qualitatively using planned percentage complete (PPC) measurements and semi-structured interviews, respectively.

Findings
The evaluation of the case study shows an increase in PPC values from 26.5 to 56.4 per cent after implementation of 4D BrIM in the project. The application of 4D BrIM in the construction phase benefits the project team in material delivery planning, project monitoring and control, construction schedule improvement, documentation and coordination.

Practical implications
The developed models are practically applied to the ongoing project and the positive benefits are observed. It is shown that 4D BrIM has the potential to improve the construction of bridge projects.

Originality/value
Studies have contributed towards the development and implementation of 3D BrIM models for bridge projects. Limited efforts have been taken to analyse how 4D BrIM models help in the overall management of bridge projects. This study adds value to the existing literature through development, implementation and systematic qualitative and quantitative evaluation of 4D BrIM models.
Friends with benefits
Authors: Wiese Melanie , Akareem Husain Salilul 
Published: December 2019

Purpose
This two-country comparative study’s purpose is to investigate antecedents to, and the consequences of a sense of belonging to a firm’s Facebook community.

Design/methodology/approach
The model was grounded in the theory of sense of community and tested through structural equation modelling. Consumer panels were used via online surveys.

Findings
Of the three antecedents hypothesised to influence an individual’s sense of belonging, enjoyment is a very strong predictor in both countries; while the credibility of posts was also a significant predictor for Australia, but not for South Africa. The findings also show no direct relationship between a sense of belonging and continuing behaviour. However, for both countries, there is a strong relationship between a sense of belonging and the involvement with firm offerings in Facebook; and that involvement is significant for the intention to continue engaging with firms through this social media environment.

Research limitations/implications
The findings support the framing of the study, in the sense of community theory and enhance researchers’ understanding of the role of a sense of belonging in moving visitors from simply clicking “like” to a deeper sense of engagement with the firm’s social media community and the flow-on effect to managerial relevant outcomes.

Originality/value
The model is developed from the theory of sense of belonging, thus providing a fresh perspective to this research context. Additionally, there is limited research into the psycho-social antecedents and the outcomes of consumers’ sense of belonging to a firm’s Facebook community.
Using latent commitment profile analysis to segment bank customers
Authors: Fullerton Gordon 
Published: December 2019

Purpose
Allen and Meyer’s (1990) three component model of organizational commitment is now well accepted in the study of consumer–service provider relationships (Keiningham et al., 2015). Commitment profiling is a “person-centered approach” to commitment (Meyer et al., 2012) which examines groups of individuals who share similar commitment mindsets. The purpose of this paper is to apply commitment profile methodology to the analysis of customer–firm relationships in the context of financial services.

Design/methodology/approach
This method was applied with customer data collected as part of a nation-wide panel study of consumer financial service relationships in Canada. In total, 428 banking customers participated in this study.

Findings
This study identified five distinct bank customer commitment profiles (fully committed, affective commitment dominant, continuance commitment dominant, moderately committed and uncommitted) that varied in both size and behaviors and intentions.

Research limitations/implications
This is an exploration of commitment profiling as a technique to understand the ways in which consumers differ in terms of their commitment mindsets and behavior. It has application to a wide range of service relationships beyond financial services.

Practical implications
This has applications for market segmentation on the basis of customer commitment mindsets in many service sectors, but banking in particular. Since financial institutions have adopted various techniques to measure customer lifetime value (CLV), it would be appropriate to understand how various commitment profiles (segments) are linked to CLV.

Originality/value
While commitment profiling is a well-developed approach in understanding the nature of the firm–employee employment relationships, this is an early and exploratory attempt at applying this method in the context of a customer–financial service provider marketing relationship. This is a novel way of understanding bank customer segments in terms of their felt commitment to the financial institution with which they do business.