bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a novel missense variant inSPDL1associated with idiopathic pulmonary fibrosis
Authors: Dhindsa Ryan S. , Mattsson Johan , Nag Abhishek , Wang Quanli , Wain Louise V. , Allen Richard , Wigmore Eleanor M. , Ibanez Kristina , Vitsios Dimitrios , Deevi Sri VV. , Wasilewski Sebastian , Karlsson Maria , Lassi Glenda , Olsson Henric , Muthas Daniel , Mackay Alex , Murray Lynne , Young Simon , Haefliger Carolina ,   FinnGen Consortium, Maher Toby M. , Belvisi Maria G. , Jenkins Gisli , Molyneaux Philip , Platt Adam , Petrovski Slavé 
Published: June 2020

AbstractIdiopathic pulmonary fibrosis (IPF) is a fatal disorder characterised by progressive, destructive lung scarring. Despite significant progress, the genetic determinants of this disease remain incompletely defined. Using next generation sequencing data from 752 individuals with sporadic IPF and 119,055 controls, we performed both variant- and gene-level analyses to identify novel IPF genetic risk factors. Our variant-level analysis revealed a novel rare missense variant inSPDL1(NM_017785.5 p.Arg20Gln;p= 2.4 × 10−7, odds ratio = 2.87). This signal was independently replicated in the FinnGen cohort (combinedp= 2.2 × 10−20), firmly associating this variant as a novel IPF risk allele.SPDL1encodes Spindly, a protein involved in mitotic checkpoint signalling during cell division that has not been previously described in fibrosis. Our results highlight a novel mechanism underlying IPF, providing the potential for new therapeutic discoveries in a disease of great unmet need.
Local thermal environment and warming influence supercooling and drive widespread shifts in the metabolome of diapausingPieris rapaebutterflies
Authors: Mikucki Emily E. , Lockwood Brent L. 
Published: June 2020

ABSTRACTGlobal climate change has the potential to negatively impact biological systems as organisms are exposed to novel temperature regimes. Increases in annual mean temperature have been accompanied by disproportionate rates of change in temperature across seasons, and winter is the season warming most rapidly. Yet, we know relatively little about how warming will alter the physiology of overwintering organisms. Here, we simulated future warming conditions by comparing diapausingPieris rapaebutterfly pupae collected from disparate thermal environments and by exposingP. rapaepupae to acute and chronic increases in temperature. First, we compared internal freezing temperatures (supercooling points) of diapausing pupae that were developed in common-garden conditions but whose parents were collected from northern Vermont, USA, or North Carolina, USA. Matching the warmer winter climate of North Carolina, North Carolina pupae had significantly higher supercooling points than Vermont pupae. Next, we measured the effects of acute and chronic warming exposure in Vermont pupae and found that warming induced higher supercooling points. We further characterized the effects of chronic warming by profiling the metabolomes of Vermont pupae via untargeted LC-MS metabolomics. Warming caused significant changes in abundance of hundreds of metabolites across the metabolome. Notably, there were warming-induced shifts in key biochemical pathways, such as pyruvate metabolism, fructose and mannose metabolism, and beta-alanine metabolism, suggesting shifts in energy metabolism and cryoprotection. These results suggest that warming affects various aspects of overwintering physiology inP. rapaeand may be detrimental depending on the frequency and variation of winter warming events. Future research is needed to ascertain the extent to which the effects of warming are felt among a broader set of populations ofP. rapae, and among other species, in order to better predict how insects may respond to changes in winter thermal environments.
Heh2/Man1 may be an evolutionarily conserved sensor of NPC assembly state
Authors: Borah Sapan , Thaller David J. , Hakhverdyan Zhanna , Rodriguez Elisa C. , Rout Michael P. , King Megan C. , Lusk C. Patrick 
Published: June 2020

AbstractIntegral membrane proteins of the Lap2-emerin-MAN1 (LEM) family have emerged as important components of the inner nuclear membrane (INM) required for the functional and physical integrity of the nuclear envelope. However, like many INM proteins, there is limited understanding of the biochemical interaction networks that enable LEM protein function. Here, we show that Heh2/Man1 can be affinity purified with major scaffold components of the nuclear pore complex (NPC), specifically the inner ring complex, in evolutionarily distant yeasts. Interactions between Heh2 and nucleoporins is mediated by its C-terminal winged-helix (WH) domain and are distinct from interactions required for INM targeting. Disrupting interactions between Heh2 and the NPC leads to NPC clustering. Interestingly, Heh2’s association with NPCs can also be broken by knocking out Nup133, a component of the outer ring that does not physically interact with Heh2. Thus, Heh2’s association with NPCs depends on the structural integrity of both major NPC scaffold complexes. We propose a model in which Heh2 acts as a sensor of NPC assembly state, which may be important for NPC quality control mechanisms and the segregation of NPCs during cell division.
In situhumoral selection in human lupus tubulointerstitial inflammation
Authors: Kinloch Andrew J , Asano Yuta , Mohsin Azam , Henry Carole J , Abraham Rebecca , Chang Anthony , Labno Christine , Wilson Patrick C , Clark Marcus R 
Published: June 2020

ABSTRACTIn human lupus nephritis, tubulointerstitial inflammation (TII) is associated within situexpansion of B cells expressing anti-vimentin antibodies (AVAs). The mechanism by which AVAs are selected is unclear. Herein, we demonstrate that AVA somatic hypermutation and selection increase affinity for vimentin. However, enzyme-linked immunosorbent assays (ELISAs) suggested that affinity maturation might be a non-specific consequence of increasing polyreactivity. Subsequent multi-color confocal microscopy studies indicated that while TII AVAs often appeared polyreactive by ELISA, they bound selectively to vimentin fibrils in whole cells or inflamed renal tissue. Using a novel machine learning pipeline (CytoSkaler) to quantify the cellular distribution of antibody staining, we demonstrated that TII AVAs were selected for both enhanced binding and specificityin situ. These data suggest a new approach to assess and define antibody polyreactivity based on quantifying the distribution of binding to native and contextually relevant antigens.
Valproic Acid-Induced Changes of 4D Nuclear Morphology in Astrocyte Cells
Authors: Kalinin Alexandr A. , Hou Xinhai , Ade Alex S. , Fon Gordon-Victor , Meixner Walter , Higgins Gerald A. , Sexton Jonathan Z. , Wan Xiang , Dinov Ivo D. , O’Meara Matthew J. , Athey Brian D. 
Published: June 2020

AbstractHistone deacetylase inhibitors, such as valproic acid (VPA), have important clinical therapeutic and cellular reprogramming applications. They induce chromatin re-organization that is associated with altered cellular morphology. However, there is a lack of comprehensive characterization of VPA-induced changes of nuclear size and shape. Here, we quantify 3D nuclear morphology of primary human astrocyte cells treated with VPA over time (hence, 4D). We compared volumetric and surface-based representations and identified seven features that jointly discriminate between normal and treated cells with 85% accuracy on day 7. From day 3, treated nuclei were more elongated and flattened and then continued to morphologically diverge from controls over time, becoming larger and more irregular. On day 7, most of the size and shape descriptors demonstrated significant differences between treated and untreated cells, including a 24% increase in volume and 6% reduction in extent (shape regularity) for treated nuclei. Overall, we show that 4D morphometry can capture how chromatin re-organization modulates the size and shape of the nucleus over time. These nuclear structural alterations may serve as a biomarker for histone (de-)acetylation events and provide insights into mechanisms of astrocytes-to-neurons reprogramming.
Chemical convergence between a guild of facultative myrmecophilous caterpillars and host plants
Authors: Lima Luan Dias , Roberto Trigo José , Kaminski Lucas Augusto 
Published: June 2020

AbstractAnts exert a strong selective pressure on herbivorous insects, although some caterpillars can live in symbiosis with them using chemical defensive strategies.We investigated the adaptive resemblance of cuticular hydrocarbons (CHCs) in multitrophic systems involving a guild of facultative myrmecophilous caterpillar species (Lepidoptera: Lycaenidae), tending ants (Hymenoptera: Formicidae) and host plants from three families. We hypothesized that the CHCs of the caterpillars would resemble those of their host plants (chemical camouflage).We analyzed CHCs using gas chromatography/mass spectrometry. Morisita’s similarity index (SI) was used to compare CHC profiles of caterpillar species with different types of ant associations (commensal or mutualistic), ants and host plants.We found strong convergence between caterpillars’ CHCs and plants, especially for commensal species that do not provide secretion rewards for ants. Moreover, we found unexpected chemical convergence among mutualistic caterpillar species that offer nectar reward secretions to ants.These results show that the studied caterpillars acquire CHCs through their diet and that they vary according to host plant species and type of ant association (commensalism or mutualism). This ‘chemical camouflage’ of myrmecophilous caterpillars may have arisen as a defensive strategy allowing coexistence with ants on plants, whereas ‘chemical conspicuousness’ may have evolved in the context of honest signaling between true mutualistic partners.We suggest the existence of both Müllerian and Batesian chemical mimicry rings among myrmecophilous caterpillar species. Cuticular chemical mixtures can play a key adaptive role in decreasing ant attacks and increasing caterpillar survival in multimodal systems.Graphical abstractChemical camouflage can be a defensive strategy of myrmecophilous caterpillars against ants.‘Chemical conspicuousness’ is proposed as a new strategy mediated by cuticular hydrocarbons in myrmecophilous caterpillars.Chemical mimicry rings can occur between myrmecophilous caterpillars and especially between mutualistic species that produce nectar rewards for ants.
Multiple Imputation Approaches Applied to the Missing Value Problem in Bottom-up Proteomics
Authors: Gardner Miranda L. , Freitas Michael A. 
Published: June 2020

ABSTRACTAnalysis of differential abundance in proteomics data sets requires careful application of missing value imputation. Missing abundance values vary widely when performing comparisons across different sample treatments. For example, one would expect a consistent rate of “missing at random” (MAR) across batches of samples and varying rates of “missing not at random” (MNAR) depending on inherent difference in sample treatments within the study. The missing value imputation strategy must thus be selected that best accounts for both MAR and MNAR simultaneously. Several important issues must be considered when deciding the appropriate missing value imputation strategy: (1) when it is appropriate to impute data, (2) how to choose a method that reflects the combinatorial manner of MAR and MNAR that occurs in an experiment. This paper provides an evaluation of missing value imputation strategies used in proteomics and presents a case for the use of hybrid left-censored missing value imputation approaches that can handle the MNAR problem common to proteomics data.
Quorum sensing provides a molecular mechanism for evolution to tune and maintain investment in cooperation
Authors: Bruger Eric L. , Synder Daniel J. , Cooper Vaughn S. , Waters Christopher M. 
Published: June 2020

AbstractAs selection frequently favors non-cooperating defectors in mixed populations with cooperators, mechanisms that promote cooperation stability clearly exist. One potential mechanism is bacterial cell-to-cell communication, quorum sensing (QS), which can allow cooperators to prevent invasion by defectors. However, the impact of QS on widespread maintenance of cooperation in well-mixed conditions has not been experimentally demonstrated over extended evolutionary timescales. Here, we use wild-type (‘WT’)Vibrio harveyithat regulates cooperation with QS and an unconditionally cooperating (‘UC’) mutant to examine the evolutionary origins and subsequent dynamics of novel defectors during a long-term evolution experiment. We found that UC lineages were completely outcompeted by defectors, whereas functioning QS enabled the maintenance of cooperative variants in most WT populations. Sequencing of evolved populations revealed multipleluxRmutations that swept the UC lineages. However, the evolution of mutant lineages with reduced levels of bioluminescence (‘dims’) occurred in many WT lineages. These dim variants also decreased other cooperative phenotypes regulated by QS, such as protease production, indicating they result from changes to QS regulation. This diminished investment phenotype optimizes a trade-off between cooperative input and growth output, allowing cooperation to be maintained under QS control even in the presence of evolved defectors.
CoRINs: A tool to compare residue interaction networks from homologous proteins and conformers
Authors: da Fonseca Felipe V. , Souza Júnior Romildo O. , de Almeida Marília V. A. , Soares Thiago D. , Morais Diego A. A. , Dalmolin Rodrigo J. S. , Lima João Paulo M. S. 
Published: June 2020

ABSTRACTMotivationA useful approach to evaluate protein structure and quickly visualize crucial physicochemical interactions related to protein function is to construct Residue Interactions Networks (RINs). By using this application of graphs theory, the amino acid residues constitute the nodes, and the edges represent their interactions with other structural elements. Although several tools that construct RINs are available, many of them do not compare RINs from distinct protein structures. This comparison can give valuable insights into the understanding of conformational changes and the effects of amino acid substitutions in protein structure and function. With that in mind, we present CoRINs (Comparator of Residue Interaction Networks), a software tool that extensively compares RINs. The program has an accessible and user-friendly web interface, which summarizes the differences in several network parameters using interactive plots and tables. As a usage example of CoRINs, we compared RINs from conformers of two cancer-associated proteins.AvailabilityThe program is available athttps://github.com/LasisUFRN/CoRINs.
Structural Dynamics of DNA Depending on Methylation Pattern
Authors: Kameda Takeru , Suzuki Miho M. , Awazu Akinori , Togashi Yuichi 
Published: June 2020

AbstractDNA methylation is associated with a number of biological phenomena, and plays crucial roles in epigenetic regulation of eukaryotic gene expression. It is also suggested that DNA methylation alters the mechanical properties of DNA molecules, which is likely to affect epigenetic regulation. However, it has not been systematically investigated how methylation changes the structural and dynamic features of DNA. In this research, to elucidate the effects of methylation on DNA mechanics, a fully atomic molecular dynamics simulation of double-stranded DNA with several methylation patterns was performed. Through the analysis of the relative positioning of the nucleotides (base-step variables), characteristic changes in terms of local flexibility were observed, which further affected the overall DNA geometry and stiffness. These findings may serve as a basis for a discussion on methylation-dependent DNA dynamics in physiological conditions.
Approximation of Indel Evolution by Differential Calculus of Finite State Automata
Authors: Holmes Ian 
Published: June 2020

AbstractWe introduce a systematic method of approximating finite-time transition probabilities for continuous-time insertion-deletion models on sequences. The method uses automata theory to describe the action of an infinitesimal evolutionary generator on a probability distribution over alignments, where both the generator and the alignment distribution can be represented by Pair Hidden Markov Models (Pair HMMs). In general, combining HMMs in this way induces a multiplication of their state spaces; to control this, we introduce a coarse-graining operation to keep the state space at a constant size. This leads naturally to ordinary differential equations for the evolution of the transition probabilities of the approximating Pair HMM. The TKF model emerges as an exact solution to these equations for the special case of single-residue indels. For the general case, the equations can be solved by numerical integration. Using simulated data we show that the resulting distribution over alignments, when compared to previous approximations, is a better fit over a broader range of parameters. We also propose a related approach to develop differential equations for sufficient statistics to estimate the underlying instantaneous indel rates by Expectation-Maximization. Our code and data are available athttps://github.com/ihh/trajectory-likelihood.
The third coiled coil domain of Atg11 is required for shaping mitophagy initiation sites
Authors: Margolis Hannah K. , Katzenell Sarah , Leary Kelsie A. , Ragusa Michael J. 
Published: June 2020

AbstractSelective autophagy is the capture of specific cytosolic contents in double membrane vesicles that subsequently fuse with the vacuole or lysosome, thereby delivering cargo for degradation. Selective autophagy receptors (SARs) mark the cargo for degradation and, in yeast, recruit Atg11, the scaffolding protein for selective autophagy initiation. The mitochondrial protein Atg32 is the yeast SAR that mediates mitophagy, the selective autophagic capture of mitochondria. Atg11- Atg32 interactions concentrate Atg32 into puncta that are thought to represent sites of mitophagy initiation. However, it is unclear how Atg11 concentrates Atg32 to generate mitophagy initiation sites. We show here that the coiled coil 3 (CC3) domain of Atg11 is required for concentrating Atg32 into puncta. We determined the structure of the majority of the CC3, demonstrating that the CC3 forms a parallel homodimer whose dimer interface is formed by a small number of hydrophobic residues. We further show that the CC3 dimerization interface is required for shaping Atg32 into functional mitophagy initiation sites and for delivery of mitochondria to the vacuole. Our findings suggest that Atg11 self-interactions help concentrate SARs as a necessary precondition for cargo capture.
Optoacoustic skin mesoscopy opens a window to systemic effects of diabetes
Authors: He Hailong , Fasoula Nikolina-Alexia , Karlas Angelos , Omar Murad , Aguirre Juan , Lutz Jessica , Kallmayer Michael , Füchtenbusch Martin , Eckstein Hans-Henning , Ziegler Anette-Gabriele , Ntziachristos Vasilis 
Published: June 2020

AbstractDiabetes mellitus affects the microvasculature of several organs, including the eyes, heart, brain, kidneys and skin. The skin is the most accessible organ and could offer a window for detecting diabetes-related systemic effects on the microvasculature. However, assessment of skin microvasculature is typically performed based on invasive histological analysis, which is a method that is not well suited for disease monitoring and application to large populations. We introduce ultra-wide band raster-scan optoacoustic mesoscopy (RSOM) for precise, non-invasive assessment of diabetes-related changes in the dermal microvasculature and skin micro-anatomy, resolved with unprecedented sensitivity and detail without the need of contrast agents. Based on this novel contrast, we investigated whether RSOM could impart a new concept in diabetes healthcare, offering characterization of systemic effects of the disease. We applied pretibial RSOM to 72 patients with diabetes, grouped according to disease complications, and 20 age-matched healthy volunteers. We extracted six label-free optoacoustic biomarkers, including dermal microvasculature density, total dermal blood volume and epidermal parameters. We study the effects of diabetes on these parameters as a function of disease severity and find strong statistically significant differences between microvasculature parameters and diabetes progression. We discuss how RSOM label-free biomarkers can lead to a quantitative assessment of the systemic effects of diabetes, complementing the qualitative assessment allowed by current clinical metrics and possibly, in the future, enable a more precise scoring system capturing the gradual evolution of disease.
Forecasting the Number of Coronavirus (COVID-19) Cases in Ethiopia Using Exponential Smoothing Times Series Model
Authors: Abebe Teshome Hailemeskel 
Published: June 2020

AbstractThe main objective of this study is to forecast COVID-19 case in Ethiopiausing the best-fitted model. The time series data of COVID-19 case in Ethiopia from March 14, 2020 to June 05, 2020 were used.To this end, exponential growth, single exponential smoothing method, and doubleexponential smoothing methodwere used. To evaluate the forecasting performance of the model, root mean sum of square error was used. The study showed that double exponential smoothing methods was appropriate in forecasting the future number ofCOVID-19 cases in Ethiopia as dictated by lowest value of root mean sum of square error. The forecasting model shows that the number of coronavirus cases in Ethiopia grows exponentially. The finding of the results would help the concerned stakeholders to make the right decisions based on the information given on forecasts.
Citywide Nucleic Acid Screening of SARS-CoV-2 Infections in Post-lockdown Wuhan, China: Results and Implications
Authors: Cao Shiyi , Gan Yong , Wang Chao , Bachmann Max , Huang Yuchai , Wang Tiantian , Li Liqing , Lu Kai , Jiang Heng , Gong Yanhong , Xv Hongbin , Shen Xin , Tian Qingfeng , Lv Chuanzhu , Song Fujian , Yin Xiaoxv , Lu Zuxun 
Published: June 2020

AbstractBackgroundAfter the outbreak of Coronavirus disease in 2019 (COVID-19), stringent lockdown measures were imposed in Wuhan between January 23, 2020 and April 8, 2020. To provide evidence on the post-lockdown risk of COVID-19 epidemic in Wuhan, the city government conducted a citywide nucleic acid screening of SARS-CoV-2 infection between May 14 and June 1, 2020.MethodsAll city residents aged ≥6 years were potentially eligible to participate the screening programme. The rate of detection of asymptomatic infected cases was calculated, and their demographic and geographic distributions were investigated. ArcGIS 10.0 was used to draw a geographic distribution of asymptomatic infected persons.ResultsThe screening programme recruited a total of 9,899,828 persons (response rate, 92.9%). The screening found no newly confirmed patients with COVID-19, and identified 300 asymptomatic infected cases (detection rate 0.303/10,000). In addition, 107 of 34,424 previously recovered patients with a history of COVID-19 diagnosis were tested positive (relapse rate, 0.31%). Virus culture of SARS-CoV-2 was negative for all 300 asymptomatic cases and all 107 recovered COVID-19 patients. A total of 1,174 close contacts of asymptomatic cases were traced and all of them had a negative nucleic acid testing result.ConclusionsPrevalence of COVID-19 nucleic acid test positivity was very low in the Wuhan general population, in recovered cases and in contacts of asymptomatic cases, five to eight weeks after the end of lockdown. These findings help resolve concerns about the post-lockdown risk of COVID-19 epidemic, and promote the recovery of economy and normal social life in Wuhan.