bluuebunny/crossref_metadata_2025_split huggingface dataset:
The neural code for face memory
Authors: She Liang , Benna Marcus K. , Shi Yuelin , Fusi Stefano , Tsao Doris Y. 
Published: March 2021

AbstractThe ability to recognize familiar visual objects is critical to survival. A central assumption of neuroscience is that long-term memories are represented by the same brain areas that encode sensory stimuli (1). Neurons in inferotemporal (IT) cortex represent the sensory percept of visual objects using a distributed axis code (2–4). Whether and how the same IT neural population represents the long-term memory of visual objects remains unclear. Here, we examined how familiar faces are encoded in face patch AM and perirhinal cortex. We found that familiar faces were represented in a distinct subspace from unfamiliar faces. The familiar face subspace was shifted relative to the unfamiliar face subspace at short latency and then distorted to increase neural distances between familiar faces at long latency. This distortion enabled markedly improved discrimination of familiar faces in both AM and PR. Inactivation of PR did not affect these memory traces in AM, suggesting that the memory traces arise from intrinsic recurrent processes within IT cortex or interactions with downstream regions outside the medial temporal lobe (5, 6). Overall, our results reveal that memories of familiar faces are represented in IT and perirhinal cortex by a distinct long-latency code that is optimized to distinguish familiar identities.
Deep learning from multiple experts improves identification of amyloid neuropathologies
Authors: Wong Daniel R. , Tang Ziqi , Mew Nicholas C. , Das Sakshi , Athey Justin , McAleese Kirsty E. , Kofler Julia K. , Flanagan Margaret E. , Borys Ewa , White Charles L. , Butte Atul J. , Dugger Brittany N. , Keiser Michael J. 
Published: March 2021

AbstractPathologists can label pathologies differently, making it challenging to yield consistent assessments in the absence of one ground truth. To address this problem, we present a DL approach that draws on a cohort of experts, weighs each contribution, and is robust to noisy labels. We collected 100,495 annotations on 20,099 candidate amyloid beta neuropathologies (cerebral amyloid angiopathy (CAA), and cored and diffuse plaques) from three institutions, independently annotated by five experts. DL methods trained on a consensus-of-two strategy yielded 12.6-26% improvements by area under the precision recall curve (AUPRC) when compared to those that learned individualized annotations. This strategy surpassed individual-expert models, even when unfairly assessed on benchmarks favoring them. Moreover, ensembling over individual models was robust to hidden random annotators. In blind prospective tests of 52,555 subsequent expert-annotated images, the models labeled pathologies like their human counterparts (consensus model AUPRC=0.74 cored; 0.69 CAA). This study demonstrates a means to combine multiple ground truths into a common-ground DL model that yields consistent diagnoses informed by multiple and potentially variable expert opinion.
Wrack enhancement of post-hurricane vegetation and geomorphological recovery in a coastal dune
Authors: Joyce Matthew A. , Crotty Sinead M. , Angelini Christine , Cordero Orlando , Ortals Collin , de Battisti Davide , Griffin John N 
Published: March 2021

ABSTRACTCoastal ecosystems such as sand dunes, mangrove forests, and salt marshes provide natural storm protection for vulnerable shorelines. At the same time, storms erode and redistribute biological materials among coastal systems via wrack. Yet how such cross-ecosystem subsidies affect post-storm recovery is not well understood. Here, we report an experimental investigation into the effect of storm wrack on eco-geomorphological recovery of a coastal embryo dune in north-eastern Florida, USA, following hurricane Irma. We contrasted replicated 100-m2wrack-removal and unmanipulated (control) plots, measuring vegetation and geomorphological responses over 21 months. Relative to controls, grass cover was reduced 4-fold where diverse storm wrack, including seagrass rhizomes, seaweed, and wood, was removed. Wrack removal was also associated with a reduction in mean elevation, which persisted until the end of the experiment when removal plots had a 14% lower mean elevation compared to control plots. These results suggest that subsides of wrack re-distributed from other ecosystem types (e.g. seagrasses, macroalgae, uplands): i) enhances the growth of certain dune-building grasses; and ii) boosts the geomorphological recovery of coastal dunes. Our study also indicates that the practice of post-storm beach cleaning to remove wrack – a practice widespread outside of protected areas – may undermine the resilience of coastal dunes and their services.
SweepCluster: A SNP clustering tool for detecting gene-specific sweeps in prokaryotes
Authors: Qiu Junhui , Zhou Qi , Ye Weicai , Chen Qianjun , Bao Yun-Juan 
Published: March 2021

AbstractBackgroundThe gene-specific sweep is a selection process where an advantageous mutation along with the nearby neutral sites in a gene region increases the frequency in the population. It has been demonstrated to play important roles in ecological differentiation or phenotypic divergence in microbial populations. Therefore, identifying gene-specific sweeps in microorganisms will not only provide insights into the evolutionary mechanisms, but also unravel potential genetic markers associated with biological phenotypes. However, current methods were mainly developed for detecting selective sweeps in eukaryotic data of sparse genotypes and are not readily applicable to prokaryotic data. Furthermore, some challenges have not been sufficiently addressed by the methods, such as the low spatial resolution of sweep regions and lack of consideration of the spatial distribution of mutations.ResultsWe proposed a novel gene-centric and spatial-aware approach for identifying gene-specific sweeps in prokaryotes and implemented it in a python tool SweepCluster. Our method searches for gene regions with a high level of spatial clustering of pre-selected polymorphisms in genotype datasets assuming a null distribution model of neutral selection. The pre-selection of polymorphisms is based on their genetic signatures, such as elevated population subdivision, excessive linkage disequilibrium, or significant phenotype association. Performance evaluation using simulation data showed that the accuracy and sensitivity of the clustering algorithm in SweepCluster is above 90%. The application of SweepCluster in two real datasets from the bacteriaStreptococcus pyogenesandStreptococcus suisshowed that the impact of pre-selection was dramatic and significantly reduced the uninformative signals. We validated our method using the genotype data fromVibrio cyclitrophicus, the only available dataset of gene-specific sweeps in bacteria, and obtained a concordance rate of 78%. We noted that the concordance rate could be underestimated due to distinct reference genomes and clustering strategies. The application to the human genotype datasets showed that SweepCluster is also applicable to eukaryotic data and recovered the known sweep regions in a wide dynamic range of pre-selection parameters.ConclusionsSweepCluster is applicable to a broad category of datasets. It will be valuable for detecting gene-specific sweeps in diverse genotypic data and provide novel insights on adaptive evolution.
Affinity selection in germinal centers: Cautionary tales and new opportunities
Authors: Faro Jose , Castro Mario 
Published: March 2021

AbstractOur current quantitative knowledge of the kinetics of antibody-mediated immunity is partly based on idealized experiments throughout the last decades. However, new experimental techniques often render contradictory quantitative outcomes that shake previously uncontroversial assumptions. This has been the case in the field of T-cell receptors, where recent techniques for measuring the 2-dimensional rate constants of T-cell receptor-ligand interactions exposed contradictory results to those obtained with techniques measuring 3-dimensional interactions. Recently, we have developed a mathematical framework to rationalize those discrepancies focusing on the proper fine-grained description of the underlying kinetic steps involved in the immune synapse. In this perspective article, we apply this approach to unveil potential blind spots in the case of B-cell receptors (BCR) and to rethink the interactions between B cells and follicular dendritic cells (FDC) during the germinal center (GC) reaction. Also, we elaborate on the concept of “catch bonds” and on the recent observations that B-cell synapses retract and pull antigen generating a “retracting force”, and propose some testable predictions that can lead to future research.
A specialist flea beetle manipulates and tolerates the activated chemical defense in its host plant
Authors: Sporer Theresa , Körnig Johannes , Wielsch Natalie , Gebauer-Jung Steffi , Reichelt Michael , Hupfer Yvonne , Beran Franziska 
Published: March 2021

AbstractGlucosinolates, the characteristic secondary metabolites of Brassicales, are hydrolyzed upon herbivory by myrosinases to toxic and deterrent defense metabolites. The specialist flea beetle,Phyllotreta armoraciae, sequesters glucosinolates in the body despite myrosinase activity, but it is unknown whether plant myrosinase activity influences sequestration and how beetles prevent the hydrolysis of ingested glucosinolates. In feeding experiments performed with the myrosinase-deficientArabidopsis thaliana tgg1×tgg2(tgg) mutant and the corresponding wild type, we found that plant myrosinases reduced the glucosinolate sequestration rate by up to 50% and hydrolyzed a fraction of ingested glucosinolates in adult beetles. Although these results show thatP. armoraciaecannot fully prevent glucosinolate hydrolysis, we observed no negative influence on beetle performance. To understand howP. armoraciaecan avoid the hydrolysis of some ingested glucosinolates, we analyzed their fate directly after ingestion.P. armoraciaerapidly absorbed glucosinolates across the gut epithelium, a strategy that has been proposed to prevent hydrolysis in the gut lumen of sequestering insects. Moreover, beetle gut content suppressedin vitromyrosinase activity, and almost no myrosinase activity was detectable in the feces, which indicates that ingested myrosinases are inactivated in the beetle gut. In summary, we show thatP. armoraciaeuses several strategies to prevent the hydrolysis of ingested glucosinolates but can also tolerate the formation of glucosinolate hydrolysis products.
An ancient route towards salicylic acid and its implications for the perpetualTrichormus–Azollasymbiosis
Authors: de Vries Sophie , Herrfurth Cornelia , Li Fay-Wei , Feussner Ivo , de Vries Jan 
Published: March 2021

ABSTRACTDespite its small size, the water fernAzollais a giant among plant symbioses. Within each of its leaflets, a specialized leaf cavity is home to a population of nitrogen-fixing cyanobacteria (cyanobionts). While examples of nitrogen fixing cyanobionts are found across the land plant tree of life,Azollais unique in that its symbiosis is perpetual: the cyanobionts are inherited during sexual and vegetative propagation of the fern. What underpins the communication between the two partners? In angiosperms, the phytohormone salicylic acid (SA) is a well-known regulator of plant–microbe interactions. Using HPLC-MS/MS, we pinpoint the presence of SA in the fern; using comparative genomics and phylogenetics, we mined homologs of SA biosynthesis genes across Chloroplastida (Viridiplantae). While canonical isochorismate synthase (ICS) sequences are largely limited to angiosperms, homologs for the entire Phenylalanine ammonia-lyase (PAL)-dependent pathway likely existed in the last common ancestor of land plants. Indeed,A. filiculoidessecondarily lost its ICS, but has the genetic competence to derive SA from benzoic acid. Global gene expression data from cyanobiont-containing and -freeA. filiculoidesunveil a putative feedback loop: SA appears to induce cyanobacterial proliferation, which in turn down-regulates genes in SA biosynthesis and its responses.
Paper-and-pencil questionnaires analysis: a new automated technique to reduce analysis time and errors
Authors: Chabert Clovis , Collado Aurélie , Cheval Boris , Hue Olivier 
Published: March 2021

AbstractBackground and ObjectiveQuestionnaires are essential tools in many scientific fields, including health and medicine. However, the analysis of paper-and-pencil questionnaires is time consuming, source of errors and expensive, limiting its use in large cohort studies. Computer-based questionnaires might be a valuable alternative but they may introduce bias, especially for sensitive questions, and they require programming skills. The aim of this study is to develop a reliable and adaptable open-source technique (i.e. LightQuest) to automatically analyse various types of scanned paper-and-pencil questionnaires with closed questions, including those with inverted scale.MethodsTo evaluate the usefulness of LightQuest, the time needed for 7 experimenters for manually code 10 sets of 4 frequently used questionnaires and the number of errors (i.e. reliability) were compared with the time and errors their made using LightQuest.ResultsLightQuest was twice as fast as the manual analysis, even though the time to create the reference model was taken into account (933s vs. 1935s, t(2)=8.81, p<0.001). Without model creation, the reduced analysis time was more pronounced, with an average of 2.77s.question-1for the manual technique versus 0.55s.question-1for LightQuest (t(2)=22.5, p<0.001). Moreover, during correction of the 5180 questions performed by the 7 experimenters, LightQuest made a total of 2 errors versus 46 with the manual technique (q(2)=4.53, p<0.05).ConclusionLightQuest demonstrated clear superiority both in terms of time and reliability. The script of this first open-source technique, which does not require programming skills, is downloadable in supplemental data and may become an asset for all studies using questionnaires.
Systems analysis of gut microbiome influence on metabolic disease in HIV and high-risk populations
Authors: Armstrong Abigail J.S. , Quinn Kevin , Fouquier Jennifer , Li Sam X. , Schneider Jennifer M. , Nusbacher Nichole M. , Doenges Katrina A. , Fiorillo Suzanne , Marden Tyson J. , Higgins Janine , Reisdorph Nichole , Campbell Thomas B. , Palmer Brent E. , Lozupone Catherine A. 
Published: March 2021

AbstractPoor metabolic health, characterized by insulin resistance and dyslipidemia, is higher in people living with HIV and has been linked with inflammation, anti-retroviral therapy (ART) drugs, and ART-associated lipodystrophy (LD). Metabolic disease is associated with gut microbiome composition outside the context of HIV but has not been deeply explored in HIV infection nor in high-risk men who have sex with men (HR-MSM), who have a highly altered gut microbiome composition. Furthermore, the contribution of increased bacterial translocation and associated systemic inflammation that has been described in HIV-positive and HR-MSM individuals has not been explored. We used a multi-omic approach to explore relationships between impaired metabolic health, defined using fasting blood markers, gut microbes, immune phenotypes and diet. Our cohort included ART-treated HIV positive MSM with and without LD, untreated HIV positive MSM, and HR-MSM. For HIV positive MSM on ART, we further explored associations with the plasma metabolome. We found that elevated plasma lipopolysaccharide binding protein (LBP) was the most important predictor of impaired metabolic health and network analysis showed that LBP formed a hub joining correlated microbial and immune predictors of metabolic disease. Taken together, our results suggest the role of inflammatory processes linked with bacterial translocation and interaction with the gut microbiome in metabolic disease among HIV positive and negative MSM.Importance StatementThe gut microbiome in people living with HIV (PLWH) is of interest as chronic infection often results in long term comorbidities. Metabolic disease is prevalent in PLWH even in well-controlled infection and has been linked with the gut microbiome in previous studies, but little attention has been given to PLWH. Furthermore, integrated analyses that consider gut microbiome together with diet, systemic immune activation, metabolites, and demographics have been lacking. In a systems-level analysis of predictors of metabolic disease in PLWH and men who are at high risk of acquiring HIV, we found that increased LBP, an inflammatory marker indicative of compromised intestinal barrier function, was associated with worse metabolic health. We also found impaired metabolic health associated with specific dietary components, gut microbes, and host and microbial metabolites. This work lays the framework for mechanistic studies aimed at targeting the microbiome to prevent or treat metabolic endotoxemia in HIV-infected individuals.
Multi-compartment analysis of the complex gradient-echo signal quantifies myelin breakdown in premanifest Huntington’s disease
Authors: Casella Chiara , Kleban Elena , Rosser Anne E. , Coulthard Elizabeth , Rickards Hugh , Fasano Fabrizio , Metzler-Baddeley Claudia , Jones Derek K. 
Published: March 2021

AbstractWhite matter (WM) alterations have been identified as a relevant pathological feature of Huntington’s disease (HD). Increasing evidence suggests that WM changes in this disorder are due to alterations in myelin-associated biological processes. Multi-compartmental analysis of the complex gradient-echo MRI signal evolution in WM has been shown to quantify myelinin vivo, therefore pointing to the potential of this technique for the study of WM myelin changes in health and disease. This study first characterized the reproducibility of metrics derived from the complex multi-echo gradient-recalled echo (mGRE) signal across the corpus callosum in healthy participants, finding highest reproducibility in the posterior callosal segment. Subsequently, the same analysis pipeline was applied in this callosal region in a sample of premanifest HD patients (n = 19) and age, sex and education matched healthy controls (n = 21). In particular, we focused on two myelin-associated derivatives: i. the myelin water signal fraction (fm), a parameter dependent on myelin content; and ii. the difference in frequency between myelin and intra-axonal water pools (Δω), a parameter dependent on the ratio between the inner and the outer axonal radii. fmwas found to be lower in HD patients (β = −0.13, p = 0.03), while Δω did not show a group effect. Performance in tests of working memory, executive function, social cognition and movement was also assessed, and a greater age-related decline in executive function was detected in HD patients (β = −0.06, p = 0.006), replicating previous evidence of executive dysfunction in HD. Finally, the correlation between fm, executive function, and proximity to disease onset was explored in patients, and a positive correlation between executive function and fmwas detected (r = 0.542; p = 0.02). This study emphasises the potential of complex mGRE signal analysis for aiding understanding of HD pathogenesis and progression. Moreover, expanding on evidence from pathology and animal studies, it provides novelin vivoevidence supporting myelin breakdown as an early feature of HD.
Cell-intrinsic functions of the transcription factor Bhlhe40 in activated B cells and T follicular helper cells restrain the germinal center reaction and prevent lymphomagenesis
Authors: Rauschmeier René , Reinhardt Annika , Gustafsson Charlotte , Glaros Vassilis , Artemov Artem V. , Taneja Reshma , Adameyko Igor , Månsson Robert , Busslinger Meinrad , Kreslavsky Taras 
Published: March 2021

ABSTRACTThe generation of high-affinity antibodies against pathogens and vaccines requires the germinal center (GC) reaction – a process that relies on a complex interplay between specialized effector subsets of B and CD4 T lymphocytes – GC B cells and T follicular helper (TFH) cells. Intriguingly, several key positive regulators of the GC reaction are common for both cell types. Here, we report that the transcription factor Bhlhe40 is a crucial cell-intrinsic negative regulator affecting both the B and T cell sides of the GC reaction. In activated CD4 T cells, Bhlhe40 was required to restrain proliferation thus limiting the number of TFHcells. In B cells, Bhlhe40 executed its function in the first days after immunization by selectively restricting the generation of the earliest GC B cells but not of early memory B cells or plasmablasts. Conditional Bhlhe40 inactivation confirmed cell-autonomous functions of Bhlhe40 in both GC B and TFHcells, while the GC phenotype was further enhanced upon loss of Bhlhe40 in both cell types. This negative regulation of the GC reaction by Bhlhe40 was of crucial importance, as Bhlhe40-deficient mice with progressing age succumbed to a B cell lymphoma characterized by accumulation of monoclonal GC B-like cells and polyclonal TFHcells in various tissues.
The GT factor ZmGT-3b mediates growth–defense tradeoff by regulating photosynthesis and defense response1
Authors: Zhang Qianqian , Lizhu E , Dai Weixing , Xu Mingliang , Ye Jianrong 
Published: March 2021

AbstractPlant growth and development face constant threat from various environmental stresses. Transcription factors (TFs) are crucial for maintaining balance between plant growth and defense. Trihelix TFs display multifaceted functions in plant growth, development, and responses to various biotic and abiotic stresses. Here, we explore the role of a trihelix TF, ZmGT-3b, in regulating the growth–defense tradeoff in maize (Zea mays).ZmGT-3bis primed for instant response toFusarium graminearumchallenge by implementing a rapid and significant reduction of its expression to suppress seedling growth and enhance disease resistance.ZmGT-3bknockdown led to diminished growth, but improved disease resistance and drought tolerance in maize seedlings. InZmGT-3bknockdown seedlings, the chlorophyll content and net photosynthetic rate were strongly reduced, whereas the contents of major cell wall components, such as lignin, were synchronically increased. Correspondingly,ZmGT-3bknockdown specifically downregulated photosynthesis-related genes, especiallyZmHY5(encoding a conserved central regulator of seedling development and light responses), but synchronically upregulated genes associated with secondary metabolite biosynthesis and defense-related functions.ZmGT-3bknockdown induced defense-related transcriptional reprogramming and increased biosynthesis of lignin without immune activation. These data suggest that ZmGT-3b is a regulator of plant growth–defense tradeoff that coordinates metabolism during growth-to-defense transitions by optimizing the temporal and spatial expression of photosynthesis- and defense-related genes.One-sentence summaryZmGT-3b regulates photosynthesis activity and synchronically suppresses defense response.