bluuebunny/crossref_metadata_2025_split huggingface dataset:
A neural code for egocentric spatial maps in the human medial temporal lobe
Authors: Kunz Lukas , Brandt Armin , Reinacher Peter C. , Staresina Bernhard P. , Reifenstein Eric T. , Weidemann Christoph T. , Herweg Nora A. , Tsitsiklis Melina , Kempter Richard , Kahana Michael J. , Schulze-Bonhage Andreas , Jacobs Joshua 
Published: March 2020

SummarySpatial navigation relies on neural systems that encode information about places, distances, and directions in relation to the external world or relative to the navigating organism. Since the proposal of cognitive maps, the neuroscience of navigation has focused on allocentric (world-referenced) neural representations including place, grid, and head-direction cells. Here, using single-neuron recordings during virtual navigation, we identify “anchor cells” in the human brain as a neural code for egocentric (self-centered) spatial maps: Anchor cells represent egocentric directions towards “anchor points” located in the environmental center or periphery. Anchor cells were abundant in parahippocampal cortex, supported full vectorial representations of egocentric space, and were integrated into a neural memory network. Neurons encoding allocentric direction complemented anchor-cell activity, potentially assisting anchor cells in transforming percepts into allocentric representations. Anchor cells may facilitate egocentric navigation strategies, may support route planning from egocentric viewpoints, and may underlie the first-person perspective in episodic memories.
Ex-VivoEquine Cartilage Explant Osteoarthritis Model - A Metabolomics and Proteomics Study
Authors: Anderson James R , Phelan Marie M , Foddy Laura , Clegg Peter D , Peffers Mandy J 
Published: March 2020

AbstractOsteoarthritis (OA) is an age-related degenerative musculoskeletal disease characterised by loss of articular cartilage, synovitis, abnormal bone proliferation and subchondral bone sclerosis. Underlying OA pathogenesis is yet to be fully elucidated with no OA specific biomarkers in clinical use.Ex-vivoequine cartilage explants (n=5) were incubated in TNF-α/IL-1β supplemented culture media for 8 days, with media removed and replaced at 2, 5 and 8 days. Acetonitrile metabolite extractions of 8 day cartilage explants and media samples at all time points underwent 1D1H nuclear magnetic resonance metabolomic analysis with media samples also undergoing mass spectrometry proteomic analysis. Within the cartilage, metabolites glucose and lysine were elevated following TNF-α/IL-1β treatment whilst adenosine, alanine, betaine, creatine, myo-inositol and uridine levels decreased. Within the culture media, four, four and six differentially abundant metabolites and 154, 138 and 72 differentially abundant proteins, with > 2 fold change, were identified for 1-2 day, 3-5 day and 6-8 day time points respectively. Nine potential novel OA neopeptides were elevated in treated media. Our innovative study has identified differentially abundant metabolites, proteins and extracellular matrix derived neopeptides, providing insightful information on OA pathogenesis, enabling potential translation for clinical markers and possible new therapeutic targets.
Deletion of Autophagy geneATG1and Glyoxylate cycle Regulator encoding geneUCC1together leads to Synthetic Growth Defects and Sensitivity to Genotoxic agents inSaccharomyces cerevisiae
Authors: Pandita Monika , Sharma Vishali , Sharma Meenu , Shoket Heena , Parvez Sadia , Kumar Prabhat , Bairwa Narendra K 
Published: March 2020

AbstractAtg1 ofS. cerevisiaeis a key component of autophagy encoded byATG1gene, involved in the process of degradation of cytosolic components through autophagy.UCC1, an F-box encoding gene is involved in the negative regulation of glyoxylate pathway via degradation of Cit2 enzyme by ubiquitin proteasome system. We investigated the genetic interaction betweenATG1andUCC1using the gene deletion approach. Theatg1Δucc1Δcells showed the synthetic growth defects with abnormal budding and sensitivity to genotoxic and oxidative stress agents. Based on the observations, we report thatATG1andUCC1interact genetically to regulate the cell growth fitness and function in parallel pathway in cellular response to the genotoxic stress agents. The present investigation also revealed the cross talks among autophagy, ubiquitin proteasome system, and glyoxylate pathways.
Identification of an Aggregation Pheromone from the Small Hive Beetle (Coleoptera: Nitidulidae)
Authors: Stuhl Charles J. , Teal Peter E. A. 
Published: March 2020

AbstractNewly emerged adult small hive beetleAethina tumida(Coleoptera: Nitidulidae) emerge from the soil and seek refuge in honey bee hives. Observations of wild and colony reared populations indicate that the beetles form aggregations of many individuals of both sexes. Volatile collections performed on males and females have identified a male produced aggregation pheromone comprised of 6-methyl-5-hepten-2-one, nonanal and decanal. Synergistic effects of the pheromone and a blend of fruit volatiles provide for an effective attractant for both sexes of the small hive beetle. Laboratory assays were performed with the pheromone blend and kairomone blend tested individually combined. This was done using a synthetic aggregation blend along with a fruit-based attractant containing ethanol, ethyl butyrate, acetic acid, ethyl acetate and acetaldehyde. Our results showed that the synthetic aggregation blend along with a fruit-based attractant captured significantly more beetles than the control. The key to a good trapping system is and effective attractant. Our pheromone/kairomone based attractant shows promise to be used as an effective outside the hive control measure for small hive beetle. The identification of the aggregation pheromone is an important step in the search to provide effective control and monitoring of the small hive beetle.
Analysis of structural brain asymmetries in Attention-Deficit/Hyperactivity Disorder in 39 datasets
Authors: Postema Merel C. , Hoogman Martine ,   ENIGMA ADHD Working Group, Glahn David C. , Jahanshad Neda , Medland Sarah E. , Thompson Paul M. , Fisher Simon E. , Franke Barbara , Francks Clyde 
Published: March 2020

ABSTRACTObjectiveSome studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here we performed the largest-ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.MethodsWe analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,978 people with ADHD and unaffected 1,917 controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modelling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.ResultsThere was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t=2.4,P=0.019). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t=2.4,P=0.007) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen’sdfrom −0.18 to 0.18) and would not survive study-wide correction for multiple testing.ConclusionPrior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.
Variance in within-pair reproductive success influences the opportunity for selection annually and over the lifetimes of males in a multi-brooded songbird
Authors: Germain Ryan R. , Hallworth Michael T. , Kaiser Sara A. , Sillett T. Scott , Webster Michael S. 
Published: March 2020

AbstractIn socially monogamous species, male reproductive success consists of ‘within-pair’ offspring produced with their socially-paired mate(s), and ‘extra-pair’ offspring produced with additional females throughout the population. Both reproductive pathways offer distinct opportunities for selection in wild populations, as each is composed of separate components of mate attraction, female fecundity, and paternity allocation. Identifying key sources of variance and covariance among these components is a crucial step towards understanding the reproductive strategies that males use to maximize fitness both annually and over their lifetimes. We use 16 years of complete reproductive data from a population of black-throated blue warblers (Setophaga caerulescens) to partition variance in male annual and lifetime reproductive success, and thereby identify if the opportunity for selection varies over the lifetimes of individual males and what reproductive strategies likely favor maximum lifetime fitness. The majority of variance in male reproduction was attributable to within-pair success, but the specific effects of individual components of variance differed between total annual and total lifetime reproductive success. Positive overall lifetime covariance between within-pair and extra-pair components indicates that males able to maximize within-pair success, particularly with double-brooding females, likely achieve higher overall lifetime fitness via both within-pair and extra-pair reproductive pathways.
A lineage-tracing tool to map the fate of hypoxic tumour cells
Authors: Vermeer Jenny A.F. , Ient Jonathan , Markelc Bostjan , Kaeppler Jakob , Barbeau Lydie M.O. , Groot Arjan J. , Muschel Ruth J. , Vooijs Marc A. 
Published: March 2020

AbstractIntratumoural hypoxia is a common characteristic of malignant treatment-resistant cancers. However, hypoxia-modification strategies for the clinic remain elusive. To date little is known on the behaviour of individual hypoxic tumour cells in their microenvironment. To explore this issue in a spatial and temporally-controlled manner we developed a genetically encoded sensor by fusing the O2-labile Hypoxia-Inducible Factor 1α to eGFP and a tamoxifen-regulated Cre recombinase. Under normoxic conditions HIF-1α is degraded but under hypoxia, the HIF-1α-GFP-Cre-ERT2fusion protein is stabilised and in the presence of tamoxifen activates a tdTomato reporter gene that is constitutively expressed in hypoxic progeny. We visualise the random distribution of hypoxic tumour cells from hypoxic or necrotic regions and vascularised areas using immunofluorescence and intravital microscopy. Once tdTomato expression is induced, it is stable for at least 4 weeks. Using this system, we could show that the post-hypoxic cells were more proliferativein vivothan non-labelled cells. Our results demonstrate that single-cell lineage tracing of hypoxic tumour cells can allow visualisation of their behaviour in living tumours using intravital microscopy. This tool should prove valuable for the study of dissemination and treatment response of post-hypoxic tumour cellsin vivoat single-cell resolution.Summary StatementHere we developed and characterised a novel HIF-1α-Cre fusion gene to trace the progeny of hypoxic tumour cells in a temporal and spatially resolved manner using intravital microscopy.
Phenotypic and microsite plant individual variation determine the pollination network structure and its functional consequences
Authors: Arroyo-Correa Blanca , Bartomeus Ignasi , Jordano Pedro 
Published: March 2020

AbstractThe biotic and abiotic context of individual plants in animal-pollinated plant populations may influence pollinator foraging behaviour and therefore how the pollen flow occurs. Thus, this variation among conspecifics within a given plant population can ultimately influence the plant reproductive success. Here we used a fine-scale, well characterized population ofHalimium halimifoliumin combination with exponential random graph models (ERGMs) to assess how the intrapopulation variation in intrinsic (i.e. phenotype and phenology) and extrinsic (i.e. microsite) plant attributes configures individual plant-pollinator networks and its functional consequences. We found that pollinator visitation patterns and the emerging network configuration were associated with both intrinsic and extrinsic plant attributes, such as the number of flowers, the flowering synchrony and the cover of intraspecific and interspecific neighbours. Both intrinsic and extrinsic plant attributes also affected the plant female reproductive success directly and indirectly - through its effects on the probability of conspecifics plants to share pollinators. Our study opens up new approaches to assess and predict the functional consequences of context-dependency in plant-pollinator interactions, especially under global change scenarios, where the ecological context of individual plants is likely to change.
CRISPR-mediated Multiplexed Live Cell Imaging of Nonrepetitive Genomic Loci
Authors: Clow Patricia A. , Du Menghan , Jillette Nathaniel , Taghbalout Aziz , Zhu Jacqueline J. , Cheng Albert W. 
Published: March 2020

AbstractThree-dimensional (3D) structures of the genome are dynamic, heterogeneous and functionally important. Live cell imaging has become the leading method for chromatin dynamics tracking. However, existing CRISPR- and TALE-based genomic labeling techniques have been hampered by laborious protocols and are ineffective in labeling non-repetitive sequences. Here, we report a versatile CRISPR/Casilio-based imaging method that allows for a nonrepetitive genomic locus to be labeled using one guide RNA. We construct Casilio dual-color probes to visualize the dynamic interactions of DNA elements in single live cells in the presence or absence of the cohesin subunit RAD21. Using a three-color palette, we track the dynamic 3D locations of multiple reference points along a chromatin loop. Casilio imaging reveals intercellular heterogeneity and interallelic asynchrony in chromatin interaction dynamics, underscoring the importance of studying genome structures in 4D.
Differential impacts of repeated sampling on odor representations by genetically-defined mitral and tufted cell subpopulations in the mouse olfactory bulb
Authors: Eiting Thomas P. , Wachowiak Matt 
Published: March 2020

AbstractSniffing—the active control of breathing beyond passive respiration—is used by mammals to modulate olfactory sampling. Sniffing allows animals to make odor-guided decisions within ~200 ms, but animals routinely engage in bouts of high-frequency sniffing spanning several seconds; the impact of such repeated odorant sampling on odor representations remains unclear. We investigated this question in the mouse olfactory bulb, where mitral and tufted cells (MTCs) form parallel output streams of odor information processing. To test the impact of repeated odorant sampling on MTC responses, we used two-photon imaging in anesthetized male and female mice to record activation of MTCs while precisely varying inhalation frequency. A combination of genetic targeting and viral expression of GCaMP6 reporters allowed us to access mitral (MC) and superficial tufted cell (sTC) subpopulations separately. We found that repeated odorant sampling differentially affected responses in MCs and sTCs, with MCs showing more diversity than sTCs over the same time period. Impacts of repeated sampling among MCs included both increases and decreases in excitation, as well as changes in response polarity. Response patterns across ensembles of simultaneously-imaged MCs reformatted over time, with representations of different odorants becoming more distinct. MCs also responded differentially to changes in inhalation frequency, whereas sTC responses were more uniform over time and across frequency. Our results support the idea that MCs and TCs comprise functionally distinct pathways for odor information processing, and suggest that the reformatting of MC odor representations by high-frequency sniffing may serve to enhance the discrimination of similar odors.
AIDeveloper: deep learning image classification in life science and beyond
Authors: Kräter Martin , Abuhattum Shada , Soteriou Despina , Jacobi Angela , Krüger Thomas , Guck Jochen , Herbig Maik 
Published: March 2020

AbstractPublications on artificial intelligence (AI)-based image analysis have increased drastically in recent years. However, all applications use individual solutions highly specialized for a particular task. Here, we present an easy-to-use, adaptable, open source software, called AIDeveloper (AID) to train neural nets (NN) for image classification without the need for programming. The software provides a variety of NN-architectures that can be simply selected for training. AID allows the user to apply trained models on new data, obtain metrics for classification performance, and export final models to different formats. The working principles of AID are first illustrated by training a convolutional neural net (CNN) on a large dataset consisting of images of different objects (CIFAR-10). We further explore the potential of AID by training a model to distinguish areas of differentiated and non-differentiated mesenchymal stem cells (MSCs) in culture. Additionally, we compare a conventional clinical whole blood cell count with a whole blood cell count performed by an NN-trained, using a dataset of more than 1.2 million images obtained by real-time deformability cytometry, delivering comparable results. Finally, we demonstrate how AID can be used for label-free classification of B- and T-cells derived from human blood, which currently requires costly and time-consuming sample preparation. Thus, AID can empower anyone to develop, train, and apply NNs for image classification. Moreover, models can be generated by non-programmers, exported, and used on different devices, which allows for an interdisciplinary use.
A Comprehensive Analysis of the Phylogenetic Signal in Ramp Sequences in 211 Vertebrates
Authors: McKinnon Lauren M. , Miller Justin B. , Whiting Michael F. , Kauwe John S.K. , Ridge Perry G. 
Published: March 2020

AbstractBackgroundRamp sequences increase translational speed and accuracy when rare, slowly-translated codons are found at the beginnings of genes. Here, the results of the first analysis of ramp sequences in a phylogenetic construct are presented.MethodsRamp sequences were compared from 211 vertebrates (110 Mammalian and 101 non-mammalian). The presence and absence of ramp sequences was analyzed as a binary character in a parsimony and maximum likelihood framework. Additionally, ramp sequences were mapped to the Open Tree of Life taxonomy to determine the number of parallelisms and reversals that occurred, and these results were compared to what would be expected due to random chance. Lastly, aligned nucleotides in ramp sequences were compared to the rest of the sequence in order to examine possible differences in phylogenetic signal between these regions of the gene.ResultsParsimony and maximum likelihood analyses of the presence/absence of ramp sequences recovered phylogenies that are highly congruent with established phylogenies. Additionally, the retention index of ramp sequences is significantly higher than would be expected due to random chance (p-value = 0). A chi-square analysis of completely orthologous ramp sequences resulted in a p-value of approximately zero as compared to random chance.DiscussionRamp sequences recover comparable phylogenies as other phylogenomic methods. Although not all ramp sequences appear to have a phylogenetic signal, more ramp sequences track speciation than expected by random chance. Therefore, ramp sequences may be used in conjunction with other phylogenomic approaches.
GmVTL1 is an iron transporter on the symbiosome membrane of soybean with an important role in nitrogen fixation
Authors: Brear Ella M. , Bedon Frank , Gavrin Aleksandr , Kryvoruchko Igor S. , Torres-Jerez Ivone , Udvardi Michael K. , Day David A. , Smith Penelope M.C. 
Published: March 2020

SummaryLegumes establish symbiotic relationships with soil bacteria (rhizobia), housed in nodules on plant roots. The plant supplies carbon substrates and other nutrients to the bacteria in exchange for fixed nitrogen. The exchange occurs across a plant-derived symbiosome membrane (SM), which encloses rhizobia to form a symbiosome. Iron supplied by the plant is crucial for the rhizobial enzyme nitrogenase that catalyses N2fixation, but the SM iron transporter has not been identified.We use complementation of yeast and plant mutants, real-time PCR, hairy root transformation, microscopy and proteomics to demonstrate the role of soybean GmVTL1 and 2.Both are members of the vacuolar iron transporter family and homologous toLotus japonicusSEN1 (LjSEN1), previously shown to be essential for N2fixation.GmVTL1expression is enhanced in nodule infected cells and both proteins are localised to the SM.GmVTL1 and 2 transport iron in yeast and GmVTL1 restores N2fixation when expressed in theLjsen1mutant.Three GmVTL1 amino acid substitutions that reduce iron transport in yeast also block N2fixation inLjsen1plants.We conclude GmVTL1 is responsible for transport of iron across the SM to bacteroids and plays a crucial role in the N2-fixing symbiosis.
Clinical Features of Patients Infected with the 2019 Novel Coronavirus (COVID-19) in Shanghai, China
Authors: Cao Min , Zhang Dandan , Wang Youhua , Lu Yunfei , Zhu Xiangdong , Li Ying , Xue Honghao , Lin Yunxiao , Zhang Min , Sun Yiguo , Yang Zongguo , Shi Jia , Wang Yi , Zhou Chang , Dong Yidan , Peng Longping , Liu Ping , Dudek Steven M. , Xiao Zhen , Lu Hongzhou 
Published: March 2020

ABSTRACTBackgroundSince mid-December 2019, a cluster of pneumonia-like diseases caused by a novel coronavirus, now designated COVID-19 by the WHO, emerged in Wuhan city and rapidly spread throughout China. Here we identify the clinical characteristics of COVID-19 in a cohort of patients in Shanghai.MethodsCases were confirmed by real-time RT-PCR and were analysed for demographic, clinical, laboratory and radiological features.ResultsOf 198 patients, the median duration from disease onset to hospital admission was 4 days. The mean age of the patients was 50.1 years, and 51.0% patients were male. The most common symptom was fever. Less than half of the patients presented with respiratory systems including cough, sputum production, itchy or sore throat, shortness of breath, and chest congestion. 5.6% patients had diarrhoea. On admission, T lymphocytes were decreased in 45.8% patients. Ground glass opacity was the most common radiological finding on chest computed tomography. 9.6% were admitted to the ICU because of the development of organ dysfunction. Compared with patients not treated in ICU, patients treated in the ICU were older, had longer waiting time to admission, fever over 38.5° C, dyspnoea, reduced T lymphocytes, elevated neutrophils and organ failure.ConclusionsIn this single centre cohort of COVID-19 patients, the most common symptom was fever, and the most common laboratory abnormality was decreased blood T cell counts. Older age, male, fever over 38.5°C, symptoms of dyspnoea, and underlying comorbidity, were the risk factors most associated with severity of disease.