bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reproducible Tract Profiles (RTP2): from diffusion MRI acquisition to clinical practice and research
Authors: Lerma-Usabiaga Garikoitz , Liu Mengxing , Paz-Alonso Pedro M. , Wandell Brian A. 
Published: March 2022

SummaryDiffusion MRI is a complex technique, where new discoveries and implementations occur at a fast pace. The expertise needed for data analyses and accurate and reproducible results is increasingly demanding and requires multidisciplinary collaborations. In the present work we introduce Reproducible Tract Profiles (RTP2): a set of flexible and automated methods to analyze anatomical MRI and diffusion weighted imaging (DWI) data for reproducible tractography. The tools read structural MRI data and process them through a succession of serialized containerized analyses. We describe the DWI algorithms used to identify white-matter tracts and their summary metrics, the flexible architecture of the platform, and the tools to programmatically access and control the computations. The combination of these three components provides an easy-to-use automatized tool developed and tested over 20 years, to obtain usable and reliable state-of-the-art diffusion metrics at the individual and group levels for basic research and clinical practice.HighlightsAutomated, flexible and reproducible protocol for white-matter tractography and tractometry.High computational (same data, different computations) and test-retest reproducibility (data from different sessions, different computations).Open-source code and publicly available containers.
Using a combination of CRISPR/Cas9, behavioural experiments and functional analysis to characterise taste receptors in honeybees
Authors: Değirmenci Laura , Ferreira Fábio Luiz Rogé , Vukosavljevic Adrian , Heindl Cornelia , Keller Alexander , Geiger Dietmar , Scheiner Ricarda 
Published: March 2022

AbstractHoneybees (Apis mellifera) need their fine sense of taste to evaluate nectar and pollen sources. Gustatory receptors (Grs) translate taste signals into electrical responses. In vivo experiments primarily demonstrate collective responses of the whole Gr-set, but little is known about the individual impact of receptors. Here, we disentangle for the first time the contributions of three gustatory receptors (AmGr1-3) in sugar sensing of honeybees by combining CRISPR/Cas9 mediated genetic knock-out, electrophysiology and behaviour. AmGr1 responds to multiple sugars. Bees lacking this receptor have a reduced response to sucrose and glucose but not to fructose. AmGr2 acts as co-receptor of AmGr1 in a heterologous expression system, but honeybee knock-out mutants perform normally. Eliminating AmGr3 while preserving AmGr1 and AmGr2 abolishes the perception of fructose but not of sucrose. We thus dissociate the roles of AmGr1, AmGr2 and AmGr3 in honeybee taste perception.
Ratiometric Sensing of Redox Environments Inside Individual Carboxysomes Trapped in Solution
Authors: Carpenter William B. , Lavania Abhijit A. , Borden Julia S. , Oltrogge Luke M. , Perez Davis D. , Dahlberg Peter D. , Savage David F. , Moerner W. E. 
Published: March 2022

AbstractDiffusion of biological nanoparticles in solution impedes our ability to continuously monitor individuals and measure their physical and chemical properties. To overcome this, we previously developed the Interferometric Scattering Anti-Brownian ELectrokinetic (ISABEL) trap, which uses scattering to localize a particle and applies electrokinetic forces which counteract Brownian motion, thus enabling extended observation. Here, we present an improved ISABEL trap that incorporates a near-infrared scatter illumination beam and rapidly interleaves 405 and 488 nm fluorescence excitation reporter beams. With the ISABEL trap, we monitor the internal redox environment of individual carboxysomes labeled with the ratiometric redox reporter roGFP2. Carboxysomes widely vary in scattering contrast (reporting on size) and redox-dependent ratiometric fluorescence. Further, we used redox sensing to explore the chemical kinetics within intact carboxysomes, where bulk measurements may contain unwanted contributions from aggregates or interfering fluorescent proteins. Overall, we demonstrate the ISABEL trap’s ability to sensitively monitor nanoscale biological objects, enabling new experiments on these systems.TOC Graphic
What Happens After an Error?
Authors: Adkins Tyler J , Zhang Han , Lee Taraz G 
Published: March 2022

AbstractHumans tend to slow down after making an error. A longstanding account of this post-error slowing is that people are simply more cautious. However, accuracy typically does not improve following an error leading some researchers to suggest that an initial ‘orienting’ response may initially impair performance immediately following error. Unfortunately, characterizing the nature of this error-based impairment remains a challenge in standard tasks that use free response times. Using a new experimental approach, we exert tight control over the timing of responses to reveal the time course of stimulus-response processing. Participants are less accurate after an error even when given ample time to make a response. A computational model of response preparation rules out the possibility that errors lead to slower cognitive processing. Instead, we find that the “efficacy” of cognitive processing in producing an intended response is impaired following errors. Participants commit more perseverative slips of action following an error. Rather than a strategic shift along a single speed-accuracy tradeoff function, post-error slowing observed in free response time tasks may be an adaptive response to impaired cognitive processing that reflects a fundamentally altered relationship between the speed and accuracy of responses.
Dynamic intestinal stem cell plasticity and lineage remodeling by a nutritional environment relevant to human risk for tumorigenesis
Authors: Choi Jiahn , Zhang Xusheng , Li Wenge , Houston Michele , Peregrina Karina , Dubin Robert , Ye Kenny , Augenlicht Leonard H. 
Published: March 2022

AbstractNWD1, a purified rodent diet establishing mouse exposure to key nutrients recapitulating levels that increase risk for intestinal cancer, reproducibly causessporadicintestinal and colonic tumors in the mouse, reflecting human etiology, incidence, frequency and lag with developmental age. Complex NWD1 reprogramming of stem cells and lineages was deconvolved by bulk and scRNAseq, scATACseq, functional genomics and imaging. NWD1 extensively, rapidly, and reversibly reprogrammed Lgr5histem cells, epigenetically down-regulatingPpargc1aexpression, altering mitochondrial structure and function. This suppressed Lgr5histem cell functions and developmental maturation of Lgr5hicell progeny as cells progressed through progenitor cell compartments, recapitulated byPpargc1agenetic inactivation in Lgr5hicellsin vivo. MobilizedBmi1+, Ascl2hicells adapted lineages to the nutritional environment and elevated antigen processing and presentation pathways, especially in mature enterocytes, causing chronic, pro-tumorigenic low-level inflammation. There were multiple parallels between NWD1 remodeling of stem cells and lineages with pathogenic mechanisms in human inflammatory bowel disease, also pro-tumorigenic. Moreover, the shift to alternate stem cells reflects that the balance between Lg5 positive and negative stem cells in supporting human colon tumors is determined by environmental influences. Stem cell and lineage plasticity in response to nutrients supports historic concepts of homeostasis as a continual adaptation to environment, with the human mucosa likely in constant flux in response to changing nutrient exposures. Thus, although oncogenic mutations provide a competitive advantage to intestinal epithelial cells in clonal expansion, the competition is on a playing field dynamically sculpted by the nutritional environment, influencing which cells dominate in mucosal maintenance and tumorigenesis.
Emotional intensity can enrich or degrade memories: impact of the amygdalar pathway on hippocampus through inhibitory neurons
Authors: John Yohan J. , Wang Jingyi , Bullock Daniel , Barbas Helen 
Published: March 2022

AbstractThe brain’s emotional system powerfully modulates processing of context and episodic memory. A key pathway that mediates these effects is the projection from the amygdala to the hippocampus. Wang and Barbas (1) uncovered a distinctive pattern in the pathways from amygdala to hippocampus in primates. In hippocampal CA3, a pathway from the amygdala innervated excitatory pyramidal neurons as well as parvalbumin (PV) and calretinin (CR) inhibitory neurons. In hippocampal CA1, amygdalar projections also innervated pyramidal neurons and CR interneurons, but not PV interneurons. The effects of these complex circuits can best be probed using computational simulations. We developed a model of spiking neurons to investigate the implications and significance of these amygdala-hippocampal circuits for affective influence on processing mnemonic context, and to test their effects as input from the amygdala gradually increased. Our simulations revealed that moderate input from the amygdala can enhance detail in CA3 representations that can correctly sort out contexts and episodes from memory. However, high amygdalar input suppressed CA3 responses to non-amygdalar inputs through powerful inhibitory neurons, leading to memory representations that lack detail. Moreover, high amygdalar input prematurely hastened the timing of responses in CA1 occurring when the current situation broadly and non-specifically matched a remembered context. Amygdalar pathways to hippocampus enable a mechanism whereby affective signaling appropriately enhances hippocampal representations of remembered context. However, when amygdalar input is excessive in high emotional arousal, there is loss of memory detail and overgeneralization, as seen in post-traumatic stress disorder or pathologic phobias.
The DC1 domain protein BINUCLEATE POLLEN is required for pollen development in Arabidopsis thaliana
Authors: Arias Leonardo A. , D’Ippolito Sebastián , Frik Jésica , Amigo Natalia L. , Marchetti Fernanda , Casalongué Claudia A. , Pagnussat Gabriela C. , Fiol Diego F. 
Published: March 2022

AbstractDevelopment of the male gametophyte is a tightly regulated process that requires precise control of cell division and gene expression. A relevant aspect to understand the events underlying pollen development regulation constitutes the identification and characterization of the genes required for this process. In this work we showed that the DC1 domain protein BINUCLEATE POLLEN (BNP) is essential for pollen development and germination. Pollen grains carrying the defective BNP allele failed to complete mitosis II and are impaired in pollen germination. By yeast two-hybrid analysis and bimolecular fluorescence complementation assays, we identified a set of BNP-interacting proteins. Among confirmed interactors we found NAC family transcriptional regulators Vascular Plant One-Zinc Finger 1 (VOZ1) and VOZ2. VOZ1 localization changes during pollen development, moving to the vegetative nucleus at the tricellular stage. We observed that this relocalization requires BNP, as in the absence of BNP in pollen from bnp/BNP plants, VOZ1 nuclear localization is impaired. As voz1voz2 double mutants showed the same developmental defect observed in bnp pollen grains, we propose that BNP requirement to complete microgametogenesis could be linked to its interaction with VOZ1/2 proteins. BNP could have a role of scaffold protein, recruiting VOZ1/2 to the endosomal system into assemblies that are required for their further translocation to the nucleus, where they act as transcriptional regulators.
Hyper-adaptation in the Human Brain: Functional and structural changes in the foot section of the primary motor cortex in a top wheelchair racing Paralympian
Authors: Morita Tomoyo , Hirose Satoshi , Kimura Nodoka , Takemura Hiromasa , Asada Minoru , Naito Eiichi 
Published: March 2022

AbstractThe human brain has the capacity to drastically alter its somatotopic representations in response to congenital or acquired limb deficiencies and dysfunctions. The main purpose of the present study was to elucidate such extreme adaptability in the brain of an active top wheelchair racing Paralympian (participant P1) who has congenital paraplegia (dysfunction of bilateral lower limbs). Participant P1 has undergone long-term wheelchair racing training using bilateral upper limbs and has won a total of 19 medals in six consecutive summer Paralympic games as of 2021. We examined the functional and structural changes in the foot section of the primary motor cortex (M1) in participant P1 as compared to able-bodied control participants. We also examined the functional and structural changes in three other individuals (participants P2, P3, and P4) with acquired paraplegia, who also had long-term non-use period of the lower limbs and had undergone long-term training for wheelchair sports (but not top athletes at the level of participant P1). We measured brain activity in all the participants using functional magnetic resonance imaging (MRI) when bimanual wrist extension-flexion movement was performed, and the structural MRI images were collected. Compared to 37 control participants, participant P1 showed significantly greater activity in the M1 foot section during the bimanual task, and significant local GM expansion in this section. Significantly greater activity in the M1 foot section was also observed in participant P4, but not in P2 and P3, and the significant local GM expansion was observed in participant P2, but not in P3 and P4. Thus, functional or structural change was observed in an acquired paraplegic participant, but was not observed in all the paraplegic participants. The functional and structural changes typically observed in participant P1 may represent extreme adaptability of the human brain. We discuss the results in terms of a new idea of hyper-adaptation.
Phenotype to genotype mapping using supervised and unsupervised learning
Authors: Pastore Vito Paolo , Oke Ashwini , Capponi Sara , Elnatan Daniel , Fung Jennifer , Bianco Simone 
Published: March 2022

AbstractThe relationship between the genotype, the genetic instructions encoded into a genome, and phenotype, the macroscopic realization of such instructions, remains mostly uncharted. In addition, tools able to uncover the connection between the phenotype with a specific set of responsible genes are still under definition. In this work, we focus on yeast organelles called vacuoles, which are cell membrane compartments that vary size and shape in response to various stimuli, and we develop a framework relating changes of cellular morphology to genetic modification. The method is a combination of convolutional neural network (CNN) and an unsupervised learning pipeline, which employs a deep-learning based segmentation, classification, and anomaly detection algorithm. From the live 3D fluorescence vacuole images, we observe that different genetic mutations generate distinct vacuole phenotypes and that the same mutation might correspond to more than one vacuole morphology. We trained a Unet architecture to segment our cellular images and obtain precise, quantitative information in 2D depth-encoded images. We then used an unsupervised learning approach to cluster the vacuole types and to establish a correlation between genotype and vacuole morphology. Using this procedure, we obtained 4 phenotypic groups. We extracted a set of 131 morphological features from the segmented vacuoles images, reduced to 50 after a tree-based feature selection. We obtained a purity of 85% adopting a Fuzzy K-Means based algorithm on a random subset of 880 images, containing all the detected phenotypic groups. Finally, we trained a CNN on the labels assigned during clustering. The CNN has been used for prediction of a large dataset (6942 images) with high accuracy (80%). Our approach can be applied extensively for live fluorescence image analysis and most importantly can unveil the basic principles relating genotype to vacuole phenotype in yeast cell, which can be thought as a first step for inferring cell designing principles to generate organelles with a specific, desired morphology.
Reference values for amplitude-integrated EEGs in children from 1 month to 17 years of age
Authors: Greve Sandra , Löffelhardt Verena Tamara , Della-Marina Adela , Felderhoff-Müser Ursula , Dohna-Schwake Christian , Bruns Nora 
Published: March 2022

AbstractAimAmplitude-integrated electroencephalography (aEEG) is used to monitor electrocortical activity in critically ill children, but reference values are lacking for patients older than 3.5 months. We aimed to derive reference values for paediatric aEEGs from neurologically healthy children.MethodsNormal EEGs from awake children aged 1 month to 17 years (213 female, 237 male) without neurological disease or neuroactive medication were retrospectively converted into aEEGs. Two observers manually measured the upper and lower amplitude borders of the C3 – P3, C4 – P4, C3 – C4, P3 – P4, and Fp1 – Fp2 channels of the 10 – 20 system. Percentiles (10th, 25th, 50th, 75th, 90th) were calculated for each age group (< 1 year, 1 year, 2 – 5 years, 6 – 9 years, 10 – 13 years, 14 – 17 years).ResultsAmplitude heights and curves differed between channels without sex-specific differences. During the first 2 years of life, upper and lower amplitudes of all but the Fp1 – Fp2 channel increased and then declined until 17 years. The decline of the upper Fp1 – Fp2 amplitude began at four years, while the lower amplitude declined from the first year of life.InterpretationaEEG interpretation must account for age and electrode positions but not for sex in infants and children.What this paper adds-aEEG amplitudes increase in the first years of life and then decline.-aEEG amplitudes depend on electrode positions but not on sex.-aEEG interpretation must account for age and electrode positions.
Wochenende - modular and flexible alignment-based shotgun metagenome analysis
Authors: Rosenboom Ilona , Scheithauer Tobias , Friedrich Fabian C. , Pörtner Sophia , Hollstein Lisa , Pust Marie-Madlen , Sifakis Konstantinos , Wehrbein Tom , Rosenhahn Bodo , Wiehlmann Lutz , Chhatwal Patrick , Tümmler Burkhard , Davenport Colin F. 
Published: March 2022

AbstractBackgroundShotgun metagenome analysis provides a robust and verifiable method for comprehensive microbiome analysis of fungal, viral, archaeal and bacterial taxonomy, particularly with regard to visualization of read mapping location, normalization options, growth dynamics and functional gene repertoires. Current read classification tools use non-standard output formats, or do not fully show information on mapping location. As reference datasets are not perfect, portrayal of mapping information is critical for judging results effectively.ResultsOur alignment-based pipeline, Wochenende, incorporates flexible quality control, trimming, mapping, various filters and normalization. We observe stringent filtering of mismatches and use of mapping quality sharply reduces the number of false positives. Further modules allow genomic visualization, as well as integration and subsequent plotting of pipeline results. Our novel normalization approach additionally allows calculation of absolute abundance profiles by comparison with reads assigned to the human host genome.ConclusionWochenende has the ability to find and filter alignments to all kingdoms of life using both short and long reads, and requires only good quality reference genomes. Wochenende automatically combines multiple available modules ranging from quality control and normalization to taxonomic visualization. Wochenende is available at https://github.com/MHH-RCUG/nf_wochenende.
The genetic and biochemical determinants of mRNA degradation rates in mammals
Authors: Agarwal Vikram , Kelley David 
Published: March 2022

ABSTRACTBackgroundDegradation rate is a fundamental aspect of mRNA metabolism, and the factors governing it remain poorly characterized. Understanding the genetic and biochemical determinants of mRNA half-life would enable a more precise identification of variants that perturb gene expression through post-transcriptional gene regulatory mechanisms.ResultsHere, we establish a compendium of 54 human and 27 mouse transcriptome-wide mRNA decay rate datasets. A meta-analysis of these data identified a prevalence of technical noise and measurement bias, induced partially by the underlying experimental strategy. Correcting for these biases allowed us to derive more precise, consensus measurements of half-life which exhibit enhanced consistency between species. We trained substantially improved statistical models based upon genetic and biochemical features to better predict half-life and characterize the factors molding it. Our state-of-the-art model, Saluki, is a hybrid convolutional and recurrent deep neural network which relies only upon an mRNA sequence annotated with coding frame and splice sites to predict half-life (r=0.77). Saluki predicts the impact of RNA sequences and genetic mutations therein on mRNA stability, in agreement with functional measurements derived from massively parallel reporter assays.ConclusionsOur work produces a more robust “ground truth” with regards to transcriptome-wide mRNA half-lives in mammalian cells. Using these consolidated measurements, we trained a model that is over 50% more accurate in predicting half-life from sequence than existing models. Our best model, Saluki, succinctly captures many of the known determinants of mRNA half-life and can be rapidly deployed to predict the functional consequences of arbitrary mutations in the transcriptome.
High resolution species assignment of Anopheles mosquitoes using k-mer distances on targeted sequences
Authors: Boddé Marilou , Makunin Alex , Ayala Diego , Bouafa Lemonde , Diabaté Abdoulaye , Ekpo Uwem Friday , Kientega Mahamadi , Goff Gilbert Le , Makanga Boris K. , Ngangue Marc F. , Omitola Olaitan Olamide , Rahola Nil , Tripet Frederic , Durbin Richard , Lawniczak Mara K. N. 
Published: March 2022

AbstractThe ANOSPP amplicon panel is a genus-wide targeted sequencing panel to facilitate large-scale monitoring of Anopheles species diversity. Combining information from the 62 nuclear amplicons present in the ANOSPP panel allows for a more nuanced species assignment than single gene (e.g. COI) barcoding, which is desirable in the light of permeable species boundaries. Here, we present NNoVAE, a method using Nearest Neighbours (NN) and Variational Autoencoders (VAE), which we apply to k-mers resulting from the ANOSPP amplicon sequences in order to hierarchically assign species identity. The NN step assigns a sample to a species-group by comparing the k-mers arising from each haplotype’s amplicon sequence to a reference database. The VAE step is required to distinguish between closely related species, and also has sufficient resolution to reveal population structure within species. In tests on independent samples with over 80% amplicon coverage, NNoVAE correctly classifies to species level 98% of samples within the An. gambiae complex and 89% of samples outside the complex. We apply NNoVAE to over two thousand new samples from Burkina Faso and Gabon, identifying unexpected species in Gabon. NNoVAE presents an approach that may be of value to other targeted sequencing panels, and is a method that will be used to survey Anopheles species diversity and Plasmodium transmission patterns through space and time on a large scale, with plans to analyse half a million mosquitoes in the next five years.