bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eco-epidemiological assessment of the COVID-19 epidemic in China, January-February 2020
Authors: Byass Peter 
Published: March 2020

AbstractBackgroundThe outbreak of COVID-19 in China in early 2020 provides a rich data source for exploring the ecological determinants of this new infection, which may be of relevance elsewhere.ObjectivesAssessing the spread of the COVID-19 across China, in relation to associations between cases and ecological factors including population density, temperature, solar radiation and precipitation.MethodsOpen-access COVID-19 case data include 18,069 geo-located cases in China during January and February 2020, which were mapped onto a 0.25° latitude/longitude grid together with population and weather data (temperature, solar radiation and precipitation). Of 15,539 grid cells, 559 (3.6%) contained at least one case, and these were used to construct a Poisson regression model of cell-weeks. Weather parameters were taken for the preceding week given the established 5-7 day incubation period for COVID-19. The dependent variable in the Poisson model was incident cases per cell-week and exposure was cell population, allowing for clustering of cells over weeks, to give incidence rate ratios.ResultsThe overall COVID-19 incidence rate in cells with confirmed cases was 0.12 per 1,000. There was a single case in 113/559 (20.2%) of cells, while two grid cells recorded over 1,000 cases. Weekly means of maximum daily temperature varied from −28.0 to 30.1 °C, minimum daily temperature from −42.4 to 23.0 °C, maximum solar radiation from 0.04 to 2.74 MJm−2 and total precipitation from 0 to 72.6 mm. Adjusted incidence rate ratios suggested brighter, warmer and drier conditions were associated with lower incidence.ConclusionThough not demonstrating cause and effect, there were appreciable associations between weather and COVID-19 incidence during the epidemic in China. This does not mean the pandemic will go away with summer weather but demonstrates the importance of using weather conditions in understanding and forecasting the spread of COVID-19.
Access to Scientific Literature by the Conservation Community
Authors: Larios Daisy , Brooks Thomas M. , Macfarlane Nicholas B.W. , Roy Sugoto 
Published: March 2020

AbstractAccess to the scientific literature is perceived to be a challenge to the biodiversity conservation community, but actual level of literature access relative to needs has never been assessed globally. We examined this question by surveying the constituency of the International Union for Conservation of Nature (IUCN) as a proxy for the conservation community, generating 2,285 responses. Of these respondents, ∼97% need to use the scientific literature in order to support their IUCN-related conservation work, with ∼50% needing to do so at least once per week. The crux of the survey revolved around the question, “How easy is it for you currently to obtain the scientific literature you need to carry out your IUCN-related work?” and revealed that roughly half (49%) of the respondents find itnot easyornot at all easyto access scientific literature. We fitted a binary logistic regression model to explore factors predicting ease of literature access. Whether the respondent had institutional literature access (55% do) is the strongest predictor, with region (Western Europe, the United States, Canada, Australia and New Zealand) and gender (male) also significant predictors. Approximately 60% of respondents from Western Europe, the United States, Canada, Australia and New Zealand have institutional access compared to ∼50% in Asia and Latin America, and ∼40% in Eastern Europe and in Africa. Nevertheless, accessing free online material is a popular means of accessing literature for both those with and without institutional access. The four journals most frequently mentioned when asked which journal access would deliver the greatest improvements to the respondent’s IUCN-related work wereConservation Biology, Biological Conservation, Nature, andScience. The majority prefer to read journal articles on screen but prefer to read books in hard copy. Overall, it is apparent that access to the literature is a challenge facing roughly half of the conservation community worldwide.
HIFα regulates developmental myelination independent of autocrine Wnt signaling
Authors: Zhang Sheng , Wang Yan , Xu Jie , Deng Wenbin , Guo Fuzheng 
Published: March 2020

AbstractThe developing CNS is exposed to physiological hypoxia, under which hypoxia inducible factor alpha (HIFα) is stabilized and plays a crucial role in regulating neural development. The cellular and molecular mechanisms of HIFα in developmental myelination remain incompletely understood. Previous concept proposes that HIFα regulates CNS developmental myelination by activating the autocrine Wnt/β-catenin signaling in oligodendrocyte progenitor cells (OPCs). Here, by analyzing a battery of genetic mice of both sexes, we presentedin vivoevidences supporting an alternative understanding of oligodendroglial HIFα-regulated developmental myelination. At the cellular level, we found that HIFα was required for developmental myelination by transiently controlling upstream OPC differentiation but not downstream oligodendrocyte maturation and that HIFα dysregulation in OPCs but not oligodendrocytes disturbed normal developmental myelination. We demonstrated that HIFα played a minor, if any, role in regulating canonical Wnt signaling in the oligodendroglial lineage or in the CNS. At the molecular level, blocking autocrine Wnt signaling did not affect HIFα-regulated OPC differentiation and myelination. We further identified HIFα-Sox9 regulatory axis as an underlying molecular mechanism in HIFα-regulated OPC differentiation. Our findings support a concept shift in our mechanistic understanding of HIFα-regulated CNS myelination from the previous Wnt-dependent view to a Wnt-independent one and unveil a previously unappreciated HIFα-Sox9 pathway in regulating OPC differentiation.
Two new coral fluorescent proteins of distinct colors for sharp visualization of cell-cycle progression
Authors: Ando Ryoko , Sakaue-Sawano Asako , Shoda Keiko , Miyawaki Atsushi 
Published: March 2020

SummaryWe cloned and characterized two new coral fluorescent proteins: h2-3 and 1-41. h2-3 formed an obligate dimeric complex and exhibited bright fluorescence. On the other hand, 1-41 formed a highly multimeric complex and exhibited dim red fluorescence. We engineered 1-41 into AzaleaB5, a practically useful red-emitting fluorescent protein for cellular labeling applications. We fused h2-3 and AzaleaB5 to the ubiquitination domains of human Geminin and Cdt1, respectively, to generate a new color variant of Fucci (Fluorescent Ubiquitination-based Cell-Cycle Indicator): Fucci5. We found Fucci5 provided brighter nuclear labeling for monitoring cell cycle progression than the 1stand 2ndgenerations that used mAG/mKO2 and mVenus/mCherry, respectively.
Identification of the associated expression patterns as potential predictive markers for cancer prognosis
Authors: Liang Han , Lin Cong , Hou Yong , Li Fuqiang , Wu Kui 
Published: March 2020

AbstractDysregulated gene expression can develop as a consequence of uncontrolled alterations of tumor cells. Analysis of these abnormal alterations will improve our understanding of the tumor development and reveal the corresponding clinical associations. It is well known that multiple genetic abnormalities could be observed in the same tumor, however, the interactions between those abnormal events are rarely analyzed. To address this problem, we constructed a novel gene expression correlation network by integrating the transcriptomes of 5,001 cancer patients from 22 cancer types. We investigated how the change of associated expression pattern (AEP), which describe certain associations between gene expression, could affect the cancer patient’s prognosis. Consequently, we identified an AEP composed of mitosis-related gene expressions, which is significantly correlated with overall survival in most cancer types. In particular, the AEPs could present the association between gene expressions and show distinct effects on prognosis prediction for cancer patients, suggesting that AEP analysis is indispensable to uncover the complex interactions of abnormal gene expressions in tumor development.
Folliculin variants linked to Birt-Hogg-Dubé syndrome are targeted for proteasomal degradation
Authors: Clausen Lene , Stein Amelie , Grønbæk-Thygesen Martin , Nygaard Lasse , Søltoft Cecilie L. , Nielsen Sofie V. , Lisby Michael , Ravid Tommer , Lindorff-Larsen Kresten , Hartmann-Petersen Rasmus 
Published: March 2020

AbstractGermline mutations in the folliculin (FLCN) tumor suppressor gene are linked to Birt-Hogg-Dubé (BHD) syndrome, a dominantly inherited genetic disease characterized by predisposition to fibrofolliculomas, lung cysts, and renal cancer. Most BHD-linkedFLCNvariants include large deletions and splice site aberrations predicted to cause loss of function. The mechanisms by which missense variants and short in-frame deletions inFLCNtrigger disease are unknown. Here, we present computational and experimental studies showing that the majority of such disease-causingFLCNvariants cause loss of function due to proteasomal degradation of the encoded FLCN protein, rather than directly ablating FLCN function. Accordingly, several different single-site FLCN variants are present at strongly reduced levels in cells. In line with our finding that FLCN variants are protein quality control targets, several are also highly insoluble and fail to associate with the FLCN-binding partners FNIP1 and FNIP2. The lack of FLCN binding leads to rapid proteasomal degradation of FNIP1 and FNIP2. Half of the tested FLCN variants are mislocalized in cells, and one variant (ΔE510) forms perinuclear protein aggregates. A yeast-based screen revealed that the deubiquitylating enzyme Ubp15/USP7 and molecular chaperones regulate the turnover of the FLCN variants. Lowering the temperature to 29 °C led to a stabilization of two FLCN missense proteins, and for one variant (R362C), FLCN function was re-established at low temperature. In conclusion, we propose that most BHD-linkedFLCNmissense variants and small in-frame deletions operate by causing misfolding and degradation of the FLCN protein, and that stabilization of certain disease-linked variants may hold therapeutic potential.
Isobaric matching between runs and novel PSM-level normalization in MaxQuant strongly improve reporter ion-based quantification
Authors: Yu Sung-Huan , Kiriakidou Pelagia , Cox Jürgen 
Published: March 2020

ABSTRACTIsobaric labeling has the promise of combining high sample multiplexing with precise quantification. However, normalization issues and the missing value problem of complete n-plexes hamper quantification across more than one n-plex. Here we introduce two novel algorithms implemented in MaxQuant that substantially improve the data analysis with multiple n-plexes. First, isobaric matching between runs (IMBR) makes use of the three-dimensional MS1 features to transfer identifications from identified to unidentified MS/MS spectra between LC-MS runs in order to utilize reporter ion intensities in unidentified spectra for quantification. On typical datasets, we observe a significant gain in quantifiable n-plexes. Second, we introduce a novel PSM-level normalization, applicable to data with and without common reference channel. It is a weighted median-based method, in which the weights reflect the number of ions that were used for fragmentation. On a typical dataset, we observe complete removal of batch effects and dominance of the biological sample grouping after normalization. Furthermore, we provide many novel processing and normalization options in Perseus, the companion software for the downstream analysis of quantitative proteomics results. All novel tools and algorithms are available with the regular MaxQuant and Perseus releases, which are downloadable athttp://maxquant.org.
Assessing the impact of the threatened crucian carp (Carassius carassius) on pond invertebrate diversity - a comparison of conventional and molecular tools
Authors: Harper Lynsey R. , Handley Lori Lawson , Sayer Carl D. , Read Daniel S. , Benucci Marco , Blackman Rosetta C. , Hill Matthew J. , Hänfling Bernd 
Published: March 2020

AbstractFishes stocked for recreation and angling can damage freshwater habitats and negatively impact biodiversity. The pond-associated crucian carp (Carassius carassius) is rare across Europe and stocked for conservation management in England, but impacts on pond biota are understudied. Freshwater invertebrates contribute substantially to aquatic biodiversity, encompassing many rare and endemic species, but their small size and high abundance complicates their assessment. Practitioners have employed sweep-netting and kick-sampling with microscopy (morphotaxonomy), but specimen size/quality and experience can bias identification. DNA and eDNA metabarcoding offer alternative means of invertebrate assessment. We compared invertebrate diversity in ponds (N= 18) with and without crucian carp using morphotaxonomic identification, DNA metabarcoding, and eDNA metabarcoding. Five 2-L water samples and 3-minute sweep-net samples were collected at each pond. Inventories produced by morphotaxonomic identification of netted samples, DNA metabarcoding of bulk tissue samples, and eDNA metabarcoding of water samples were compared. Alpha diversity was greatest with DNA or eDNA metabarcoding, depending on whether standard or unbiased methods were considered. DNA metabarcoding reflected morphotaxonomic identification, whereas eDNA metabarcoding produced markedly different communities. These complementary tools should be combined for comprehensive invertebrate assessment. Crucian carp presence minimally reduced alpha diversity in ponds, but positively influenced beta diversity through taxon turnover (i.e. ponds with crucian carp contained different invertebrates to fishless ponds). Crucian carp presence contributes to landscape-scale invertebrate diversity, supporting continued conservation management in England. Our results show that molecular tools can enhance freshwater invertebrate assessment and facilitate development of more accurate and ecologically effective pond management strategies.
PDE-constrained optimization for estimating population dynamics over cell cycle from static single cell measurements
Authors: Kuritz Karsten , Bonny Alain R , Fonseca João Pedro , Allgöwer Frank 
Published: March 2020

AbstractMotivationUnderstanding how cell cycle responds and adapts dynamically to a broad range of stresses and changes in the cellular environment is crucial for the treatment of various pathologies, including cancer. However, measuring changes in cell cycle progression is experimentally challenging, and model inference computationally expensive.ResultsHere, we introduce a computational framework that allows the inference of changes in cell cycle progression from static single-cell measurements. We modeled population dynamics with partial differential equations (PDE), and derive parameter gradients to estimate time- and cell cycle position-dependent progression changes efficiently. Additionally, we show that computing parameter sensitivities for the optimization problem by solving a system of PDEs is computationally feasible and allows efficient and exact estimation of parameters. We showcase our framework by estimating the changes in cell cycle progression in K562 cells treated with Nocodazole and identify an arrest in M-phase transition that matches the expected behavior of microtubule polymerization inhibition.ConclusionsOur results have two major implications: First, this framework can be scaled to high-throughput compound screens, providing a fast, stable, and efficient protocol to generate new insights into changes in cell cycle progression. Second, knowledge of the cell cycle stage- and time-dependent progression function allows transformation from pseudotime to real-time thereby enabling real-time analysis of molecular rates in response to treatments.AvailabilityMAPiT toolbox (Karsten Kuritz 2020) is available at github:https://github.com/karstenkuritz/MAPiT.
Hypergravity affects Cell Traction Forces of Fibroblasts
Authors: Eckert J. , van Loon J. J.W.A. , Eng L. M. , Schmidt T. 
Published: March 2020

ABSTRACTCells sense and react on changes of the mechanical properties of their environment, and likewise respond to external mechanical stress applied to them. Whether the gravitational field, as overall body force, modulates cellular behavior is however unclear. Different studies demonstrated that micro- and hypergravity influences the shape and elasticity of cells, initiate cytoskeleton reorganization, and influence cell motility. All these cellular properties are interconnected, and contribute to forces that cells apply on their surrounding microenvironment. Yet, studies that investigated changes of cell traction forces under hypergravity conditions are scarce. Here we performed hypergravity experiments on 3T3 fibroblast cells using the Large Diameter Centrifuge at the European Space and Technology Centre (ESA-ESTEC). cells were exposed to hypergravity of up to 19.5gfor 16 h in both the upright and the inverted orientation with respect to the g-force vector. We observed a decrease in cellular traction forces when the gravitational field was increased up to 5.4g, followed by an increase of traction forces for higher gravity fields up to 19.5gindependent of the orientation of the gravity vector. We attribute the switch in cellular response to shear-thinning at low g-forces, followed by significant rearrangement and enforcement of the cytoskeleton at high g-forces.SIGNIFICANCEThe behavior of cells critically depend on the mechanical properties of their environment. For example external stresses and strains lead to decisions in cell differentiation as well as to collective-migration in metastasis. Gravity, as a permanently acting body force, is one of those externs stresses. We demonstrate the impact of gravitational challenges on forces that cells apply to their environment. We observed a switch in cellular response with a decrease in cell traction forces for low bypgrarayiv. conditions, followed by a significant increase in cell traction forces at higher g-level. This particular cellular response reflects a switch in croskeletal organization, similar to that observed for cells in fluids where shear forces act.
Diutina (Candida) rugosacomplex: The biofilm ultrastructure, extracellular matrix, cell wall component and antifungal susceptibility to amphotericin B, caspofungin, fluconazole and voriconazole
Authors: Mahalingam Sri Raja Rajeswari , Madhavan Priya , Pei Chong Pei 
Published: March 2020

AbstractThe genusCandidais the most common etiological factor of opportunistic fungal infections in humans. The virulence ofCandidaspecies is due to a wide repertoire of factors, specifically, the ability to form biofilms. Medical devices such as intravenous catheters, prosthetic heart valves and surgical interventions provide pathogenic microorganisms with a surface to adhere to form biofilm. The objectives of this study were to investigate the biofilm ultrastructure ofDiutina(Candida) rugosa(D. rugosa) at different developmental phases using Confocal scanning laser microscopy (CSLM) and scanning electron microscopy (SEM), quantify β-glucan, total carbohydrate and total protein in the extracellular matrix (ECM) using enzymatic β-glucan kit, phenol-sulfuric acid method and Bradford’s method, respectively, and to identify Sessile Minimum Inhibition Concentrations (SMICs) of amphotericin B, caspofungin, fluconazole, and voriconazole using serial doubling dilution. From the SEM micrographs,D. rugosabiofilms were composed of adherent yeast cells and blastospores with hyphal elements. The ultrastructure of the yeast cells was collapsed and disfigured upon exposure to amphotericin B, fluconazole and voriconazole and the biofilms presented with punctured yeast morphology upon exposure to caspofungin at their respective SMICs. The matrix thickness of embedded yeast cells from CLSM micrographs was 3.9µm at 48h. However, there was reduction in the thickness of the biofilms upon antifungal exposure. The antifungal exposed biofilms exhibit bright, diffuse, green-yellow fluorescence that were not seen in the control.D. rugosabiofilm matrices revealed 172.57µg/mL of carbohydrate, and 27.11µg/mL of protein content. The β-glucan yield inD. rugosacomplex planktonic cells were in the range of 2.5 to 4.38%, on the contrary, β-glucan was not detected in the ECM. The SMICs ofDiutinabiofilm for amphotericin B is 1024μg/mL, caspofungin is 512 μg/mL, whereas fluconazole and voriconazole is 2048 μg/mL, respectively.
ActuAtor, a molecular tool for generating force in living cells: Controlled deformation of intracellular structures
Authors: Nakamura Hideki , Rho Elmer , Deng Daqi , Razavi Shiva , Matsubayashi Hideaki T. , Inoue Takanari 
Published: March 2020

SummaryMechanical force underlies fundamental cell functions such as division, migration and differentiation. While physical probes and devices revealed cellular mechano-responses, how force is translated inside cells to exert output functions remains largely unknown, due to the limited techniques to manipulate force intracellularly. By engineering an ActA protein, an actin nucleation promoting factor derived fromListeria monocytogenes, and implementing this in protein dimerization paradigms, we developed a molecular tool termed ActuAtor, with which actin polymerization can be triggered at intended subcellular locations to generate constrictive force in a rapidly inducible manner. The ActuAtor operation led to striking deformation of target intracellular structures including mitochondria, Golgi apparatus, nucleus, and non-membrane-bound RNA granules. Based on functional analysis before and after organelle deformation, we found the form-function relationship of mitochondria to be generally marginal. The modular design and genetically-encoded nature enable wide applications of ActuAtor for studies of intracellular mechanobiology processes.
Inferring Timing of Infection Using Within-host SARS-CoV-2 Infection Dynamics Model: Are “Imported Cases” Truly Imported?
Authors: Ejima Keisuke , Kim Kwang Su , Ito Yusuke , Iwanami Shoya , Ohashi Hirofumi , Koizumi Yoshiki , Watashi Koichi , Bento Ana I. , Aihara Kazuyuki , Iwami Shingo 
Published: March 2020

AbstractIn countries/communities at risk of future outbreaks of COVID-19, ascertaining whether cases are imported or the result of local secondary transmission is important for government to shape appropriate public health strategies. In this study, we propose a novel approach to identify the timing of infection, whereby we developed a within-host model to capture viral load dynamics post-symptom onset. We submit our approach allow us to differentiate imported cases from local secondary cases. To illustrate our method, we use the initial reported cases in Singapore, where the first reported 18 cases were considered imported, as these individuals had recent travel history to Wuhan, China, which is a hotspot of COVID-19 outbreak. With additional information regarding day of entrance in Singapore, we were able to infer whether these were infected locally or prior to arriving in Singapore. Of all the cases, we identified 6 as likely evidence of ongoing secondary transmission within Singapore. In an early phase of outbreaks, collecting viral load data over time from cases from symptom onset is highly recommended.