bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Generic Neural Network Approach to Infer Segmenting Classifiers for Disease-Associated Regions in Medical Images
Authors: Schuhmacher David , Gerwert Klaus , Mosig Axel 
Published: February 2020

AbstractIn many settings in digital pathology or radiology, it is of predominant importance to train classifiers that can segment disease-associated regions in medical images. While numerous deep learning approaches, most notably U-Nets, exist to learn segmentations, these approaches typically require reference segmentations as training data. As a consequence, obtaining pixel level annotations of histopathological samples has become a major bottleneck to establish segmentation learning approaches. Our contribution introduces a neural network approach to avoid the annotation bottleneck in the first place: our approach requires two-class labels such as cancer vs. healthy at the sample level only. Using these sample-labels, a meta-network is trained that infers a segmenting neural network which will segment the disease-associated region (e.g. tumor) that is present in the cancer samples, but not in the healthy samples. This process results in a network, e.g. a U-Net, that can segment tumor regions in arbitrary further samples of the same type.We establish and validate our approach in the context of digital label-free pathology, where hyperspectral infrared microscopy is used to segment and characterize the disease status of histopathological samples. Trained on a data set comprising infrared microscopic images of 100 tissue microarray spots labelled as either cancerous or cancer-free, the approach yields a U-Net that reliably identifies tumor regions or the absence of tumor in an independent test set involving 40 samples.While our present work is focused on training a U-Net for infrared microscopic images, the approach is generic in the sense that it can be adapted to other image modalities and essentially arbitrary segmenting network topologies.
The abundant-centre is not all that abundant: a comment to Osorio-Olvera et al. 2020
Authors: Dallas Tad , Pironon Samuel , Santini Luca 
Published: February 2020

AbstractSpecies abundance is expected to decrease from the centre towards the edge of their ecological niches (abundant niche-centre hypothesis). Recently, Osorio-Olveraet al. (2020) reported strong support for the abundant niche-centre relationship in North American birds. We demonstrate here that methodological decisions strongly affected perceived support. Avoiding these issues casts doubt on conclusions by Osorio-Olvera et al. and the putative support for the abundant nichecentre hypothesis in North American birds.
High-content screening for rare respiratory diseases: readthrough therapy in primary ciliary dyskinesia
Authors: Lee Dani Do Hyang , Cardinale Daniela , Nigro Ersilia , Butler Colin R. , Rutman Andrew , Fassad Mahmoud R. , Hirst Robert A. , Moulding Dale , Agrotis Alexander , Forsythe Elisabeth , Peckham Daniel , Robson Evie , Smith Claire M. , Somavarapu Satyanarayana , Beales Philip L. , Hart Stephen L. , Janes Sam M. , Mitchison Hannah M. , Ketteler Robin , Hynds Robert E. , O’Callaghan Christopher 
Published: February 2020

AbstractDevelopment of therapeutic approaches for rare respiratory diseases is hampered by the lack of systems that allow medium-to-high-throughput screening of fully differentiated respiratory epithelium from affected patients. This is a particular problem for primary ciliary dyskinesia (PCD), a rare genetic disease caused by mutations in genes that adversely affect ciliary movement and consequently mucociliary transport. Primary cell culture of basal epithelial cells from nasal brush biopsies, followed by ciliated differentiation at air-liquid interface (ALI) has proven to be a useful tool in PCD diagnostics but the technique’s broader utility, including in pre-clinical PCD research, has been limited by the number of basal cells that it is possible to expand from such biopsies. Here, we describe a high-content, imaging-based screening method, enabled by extensive expansion of PCD patient basal cells and their culture into differentiated human respiratory epithelium in miniaturised 96-well transwell format ALI cultures. Analyses of ciliary beat pattern, beat frequency and ultrastructure indicate that a range of different PCD defects are retained in these cultures. We perform a proof-of-principle personalized investigation in reduced generation of motile cilia (RGMC), a rare and very severe form of PCD, in this case caused by a homozygous nonsense mutation (c.441C>A; p.Cys147*) in theMCIDASgene. The screening system allowed multiple drugs inducing translational readthrough to be evaluated alone or in combination with inhibitors of nonsense-mediated decay. Restoration of basal body formation in the patient’s nasal epithelial cells was seenin vitro, suggesting a novel avenue for drug evaluation and development in PCD.SummaryWe describe primary cell culture of nasal epithelial cells from patients with primary ciliary dyskinesia including differentiatiation of these to a ciliary phenotype and high-content screening in miniaturised air-liquid interface cultures.
Massive windborne migration of Sahelian insects: Diversity, seasonality, altitude, and direction
Authors: Florio J , Verú L , Dao A , Yaro AS , Diallo M , Sanogo ZL , Samaké D , Huestis DL , Yossi O , Talamas E , Chomorro L , Frank JH , Biondi M , Morkel C , Bartlett C , Linton Y-M , Strobach E , Chapman JW , Reynolds DR , Faiman R , Krajacich BJ , Smith CS , Lehmann T 
Published: February 2020

AbstractKnowledge on long-distance migration of insects is especially important for food security, public health, and conservation–issues that are especially significant in Africa. During the wet season, the Sahel nourishes diverse life forms which are soon purged by the long dry season. Windborne migration is a key strategy enabling exploitation of such ephemeral havens. However, our knowledge of these large-scale movements remains sparse due to the virtual invisibility of insects flying at altitude. In this first cross-season investigation (3 years) of the aerial insect fauna over Africa, we sampled crepuscular and nocturnal insects flying 40–290 m above ground in four Sahelian villages in Mali, using sticky nets mounted on tethered helium-filled balloons. Nearly half a million insects were caught, representing at least thirteen insect orders following preliminary sorting of the collections. At least 100 insect families were determined to have been captured at altitude in samples collected on 222 nets, obtained in 125 collections over 96 nights. Control nets (raised momentarily to >40 m during system launch and retrieval) confirmed that the insects were captured at altitude, not near the ground. Thirteen ecologically and phylogenetically diverse species were studied in detail. The flight activity of all species peaked during the wet season every year across localities up to ~100 km apart, and occurred over multiple nights, suggesting regular migrations. Species differed in flight altitude, seasonality, and correlations with aerial temperatures, humidity, and wind speed. All taxa exhibited frequent migrations on southerly winds, accounting for the recolonization of the Sahel from southern source populations. “Return” southward movement at the end of the wet season occurred in most taxa but no selectivity for such winds was detected. Extrapolation of aerial density to estimate the seasonal number of migrants crossing Mali at latitude 14°N suggested numbers in the trillions, even for the modestly abundant taxa. Assuming 2–10 hours of flight, the nightly distances traversed exceed tens and even hundreds of kilometers. Two migration strategies were proposed: “residential Sahelian migration” and “round trip migration”. The unprecedented magnitude and diversity of long-range windborne insect migrations highlight the importance of this life strategy in their impact on Sahelian and neighboring ecosystems.
Redefining CD4 T cell residency: Helper T cells orchestrate protective humoral immunity in the lung
Authors: Swarnalekha Nivedya , Schreiner David , Litzler Ludivine C , Iftikhar Saadia , Kirchmeier Daniel , Künzli Marco , King Carolyn G 
Published: February 2020

AbstractInfluenza is a severe and acute respiratory pathogen, and a significant cause for morbidity, particularly in young children and the elderly. Following influenza infection, clonally expanded T cells take up permanent residence in the lung where they are poised to rapidly respond to challenge infection. The non-circulating status of these tissue resident memory (TRM) cells makes them an attractive target for vaccination. While many studies have characterized CD8 TRM cells, less is known about the heterogeneity and protective capacity of CD4 TRM cells. Here we characterized the dynamics and transcriptional regulation of lung resident CD4 T cells to define a non-lymphoid signature that removes the bias created by the prevalence of Th1 helper cells during viral infection. We identified a novel population of long-lived T resident helper (TRH) cells that requires intrinsic Bcl6 expression for their differentiation. Although TRH cells also depend on B cells, they are generated independently of T follicular helper effector cells in the lymph node. In contrast to lung resident Th1 cells, TRH cells are tightly co-localized with B cells in inducible Bronchus Associated Lymphoid Tissue (iBALT). Deletion of Bcl6 in CD4 T cells prior to heterotypic challenge infection results in redistribution of CD4 T cells outside of iBALT areas and impaired local antibody production. These data highlight lung iBALT as a niche for the homeostasis and survival of TRH cells, and further suggest that vaccination strategies to selectively induce TRH cells can improve protective immunity in the tissue.
In search of the RNA world on Mars
Authors: Mojarro Angel , Jin Lin , Szostak Jack W. , Head James W. , Zuber Maria T. 
Published: February 2020

AbstractAdvances in origins of life research and prebiotic chemistry suggest that life as we know it may have emerged from an earlier RNA World. However, it has been difficult to reconcile the conditions used in laboratory experiments with real-world geochemical environments that may have existed on the early Earth and hosted the origin(s) of life. This challenge is in part due to geologic resurfacing and recycling that have erased the overwhelming majority of the Earth’s prebiotic history. We therefore propose that Mars, a planet frozen in time, comprised of many surfaces that have remained relatively unchanged since their formation >4 Gya, is the best alternative to search for environments consistent with geochemical requirements imposed by the RNA world. In this study we synthesizein situand orbital observations of Mars and modeling of its early atmosphere into solutions containing a range of pHs and concentrations of prebiotically relevant metals (Fe2+, Mg2+, and Mn2+), spanning various candidate aqueous environments. We then experimentally determine RNA degradation kinetics due to metal-catalyzed hydrolysis and evaluate whether early Mars could have been permissive towards the accumulation of long-lived RNA polymers. Our results indicate that a Mg2+-rich basalt sourcing metals to a slightly acidic (pH 5.4) aqueous environment mediates the slowest rates of metal-catalyzed RNA hydrolysis, though geologic evidence and modeling of basalt weathering suggest that aquifers on Mars would be near neutral (pH ∼7). Moreover, oxidizing conditions on Mars have major consequences regarding the availability oxygen-sensitive prebiotic metals (i.e., Fe2+and Mn2+) very early in its history due to increased RNA degradation rates and precipitation. Overall, 1) low pH better preserves RNA than basic conditions at high concentrations; 2) acidic to neutral pH environments with Fe2+or Mn2+will hydrolyze more RNA; and 3) alkaline environments with Mg2+dramatically hydrolyze more RNA.
Conserved regulation of omptin proteases by the PhoPQ two-component regulatory system in Enterobacteriaceae
Authors: Cho Youn Hee , Aziz Monir Riasad Fadle , Sutradhar Tanuja , Bashal Jasika , Cojocari Veronica , McPhee Joseph B. 
Published: February 2020

AbstractBacteria that colonize eukaryotic surfaces interact with numerous host-produced molecules that have antimicrobial activity. Bacteria have evolved numerous strategies to both detect and resist these molecules, and in gram-negative bacteria these include alterations of the cell surface lipopolysaccharide structure and/or charge and the production of proteases that can degrade these antimicrobial molecules. Many of the lipopolysaccharide alterations found in enteric bacteria are controlled by the PhoPQ and PmrAB two-component regulatory systems. Here, we show that omptin family proteases fromEscherichia coliandCitrobacter rodentiumare induced by growth in low Mg2+. We further show that deletion of PhoP eliminates omptin protease activity, transcriptional regulation and protein levels. We identify conserved PhoP-binding sites in the promoters of theE. coliomptin genes,ompT,ompPandarlCas well as incroPofCitrobacter rodentiumand show that mutation of the putative PhoP-binding site in theompTpromoter abrogates PhoP-dependent expression. Finally, we show that despite the conserved PhoP-dependent regulation, each of theE. coliomptin proteins has differential activity toward a particular substrate, suggesting that each omptin may contribute to resistance to a particular repertoire of host-defense peptides, depending on the particular environment in which each evolved.
POU6F2 Positive Retinal Ganglion Cells a Novel Group of ON-OFF Directionally Selective Subtypes in the Mouse Retina
Authors: Li Ying , Wang Jiaxing , King Rebecca , Geisert Eldon E. 
Published: February 2020

AbstractPurposePreviously we identified POU6F2 as a genetic link between central corneal thickness (CCT) and risk of open-angle glaucoma. The present study is designed to characterize the POU6F2-positive retinal ganglion cells (RGCs).MethodsThe Thy1-YFP-H mouse was used to identify the structure of POU6F2-positive RGCs in the retina. In the retina of the Thy1-YFP-H mouse approximately 3% of the RGCs were labeled with yellow fluorescent protein. These retinas were stained for POU6F2 to identify the morphology of the POU6F2 subtypes in 3D reconstructions of the labeled RGCs. Multiple retinal cell markers were also co-stained with POU6F2 to characterize the molecular signature of the POU6F2-positive RGCs. DBA/2J glaucoma models were used to test the role of POU6F2 in injury.ResultsIn the retina POU6F2 labels 32.9% of the RGCs in the DBA/2J retina (16.1% heavily and 16.8% lightly labeled). In 3D constructions of Thy1-YFP-H positive RGCs, the heavily labeled POU6F2-positive cells had dendrites in the inner plexiform layer that were bistratified and appeared to be ON-OFF directionally selective cells. The lightly labeled POU6F2 RGCs displayed 3 different dendritic distributions, with dendrites in the ON sublaminae only, OFF sublaminae only, or bistratified. The POU6F2-positive cells partially co-stained withCdh6. The POU6F2-positive cells do not co-stain with CART and SATB2 (markers for ON-OFF directionally selective RGC), SMI32 (a marker for alpha RGCs), or ChAT and GAD67(markers for amacrine cells). The POU6F2-positive cells were sensitive to injury. In DBA/2J glaucoma model, at 8 months of age there was a 22% loss of RGCs (labeled with RBPMS) while there was 73% loss of the heavily labeled POU6F2 RGCs.ConclusionsPOU6F2 is a marker for a novel group of RGC subtypes that are ON-OFF directionally selective RGCs that are sensitive to glaucomatous injury.
Metabolic multi-stability and hysteresis in a model aerobe-anaerobe microbiome community
Authors: Khazaei Tahmineh , Williams Rory L. , Bogatyrev Said R. , Doyle John C. , Henry Christopher S. , Ismagilov Rustem F. 
Published: February 2020

AbstractChanges in the composition of the human microbiome are associated with health and disease. Some microbiome states persist in seemingly unfavorable conditions, e.g., the proliferation of aerobe-anaerobe communities in oxygen-exposed environments in wounds or small intestinal bacterial overgrowth. However, it remains unclear how different stable microbiome states can exist under the same conditions, or why some states persist under seemingly unfavorable conditions. Here, using two microbes relevant to the human microbiome, we combine genome-scale mathematical modeling, bioreactor experiments, transcriptomics, and dynamical systems theory, to show that multi-stability and hysteresis (MSH) is a mechanism that can describe the shift from an aerobe-dominated state to a resilient, paradoxically persistent aerobe-anaerobe state. We examine the impact of changing oxygen and nutrient regimes and identify factors, including changes in metabolism and gene expression, that lead to MSH. When analyzing the transitions between the two states in this system, the familiar conceptual connection between causation and correlation is broken and MSH must be used to interpret the dynamics. Using MSH to analyze microbiome dynamics will improve our conceptual understanding of the stability of microbiome states and the transitions among microbiome states.One sentence summaryMulti-stability and hysteresis (MSH) is a potential mechanism to describe shifts to and persistence of aerobe-anaerobe communities in the microbiome.
Neglected Quaternary legacy on biodiversity in the Mountains of Southwest China
Authors: Wan Tao , Huang Huateng , Oaks Jamie R. , Jiang Xuelong , Knowles L. Lacey 
Published: February 2020

AbstractMountains of Southwest China (MSWC) is a biodiversity hotspot with a very unique and highly complex terrain. However, with the majority of studies focusing on the biogeographic consequences of massive mountain building, the Quaternary legacy of biodiversity for the MSWC has long been overlooked. Here, we took a comparative phylogeography approach to examine factors that shaped community-wide diversification. With data from 30 vertebrate species, the results reveal spatially concordant genetic structure, with temporally clustered divergence events during severe glacial cycles, indicating the importance of riverine barriers in the phylogeographic history of the vertebrate community. We conclude that the repeated glacial cycles are associated with temporal synchrony of divergence patterns that are themselves structured by the heterogeneity of the montane landscape has of the MSWC. This orderly process of diversifications has profound implications for conservation by highlighting the relative independence of different geographic areas in which communities have responded similarly to climate changes and calls for further comparative phylogeographic investigations to reveal the extent to which these findings might apply more broadly to other taxa in this biodiversity hotspot.
More than a feeling: central amygdala mediates social transfer of information about proximity of danger
Authors: Andraka K. , Kondrakiewicz K. , Rojek-Sito K. , Ziegart-Sadowska K. , Meyza K. , Nikolaev T. , Hamed A. , Kursa M. , Wójcik M. , Danielewski K. , Wiatrowska M. , Kublik E. , Bekisz M. , Lebitko T. , Duque D. , Jaworski T. , Madej H. , Konopka W. , Boguszewski P. M. , Knapska E. 
Published: February 2020

AbstractTo survive, an animal must adequately respond to challenges presented by the environment. Social animals can learn about danger from fear of conspecifics which allows them to avoid predation and other threats without costly, first-hand experience. However, it remains unclear as to whether animals can transmit specific information that helps an individual avoid harm or whether the transmitted social signals simply increase vigilance in a non-specific manner. Here we demonstrate that animals can select appropriate defensive strategies in a novel environment depending on cues from the conspecific and, using opsins targeted to behaviorally activated neurons, identify distinct neuronal circuits in the central amygdala (CeA) that are crucial for choosing a context-appropriate reaction. The identified circuits differ in molecular markers and patterns of connectivity. Thus, we show that social signals carry explicit information about proximity of danger, necessary for choosing a context-appropriate reaction, and that the choosing process is mediated by the CeA circuits.
Multithreaded two-pass connected components labelling and particle analysis in ImageJ
Authors: Doube Michael 
Published: February 2020

AbstractSequential region labelling, also known as connected components labelling, is a standard image segmentation problem that joins contiguous foreground pixels into blobs. Despite its long development history and widespread use across diverse domains such as bone biology, materials science, and geology, connected components labelling can still form a bottleneck in image processing pipelines. Here, I describe a multithreaded implementation of classical two-pass sequential region labelling and introduce an efficient collision resolution step, ‘bucket fountain’. Code was validated on test images and against commercial software (Avizo). It was performance tested on images from 2 MB (161 particles) to 6.5 GB (437,508 particles) to determine whether theoretical linear scaling (O(n)) had been achieved, and on 1 – 40 CPU threads to measure speed improvements due to multithreading. The new implementation achieves linear scaling (b= 0.905 – 1.052,time∝pixelsb;R2 = 0.985 – 0.996), which improves with increasing thread number up to 8-10 threads, suggesting that it is memory bandwidth limited. This new implementation of sequential region labelling reduces the time required from hours to a few tens of seconds for images of several GB, and is limited only by hardware scale. It is available open source and free of charge in BoneJ.