bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of viewing distance on object responses in macaque areas 45B, F5a and F5p
Authors: Caprara I , Janssen P
Published: May 2020

To perform real-world tasks like grasping, the primate brain has to process visual object information so that the grip aperture can be adjusted before contact with the object is made. Previous studies have demonstrated that the posterior subsector of the Anterior Intraparietal area (pAIP) is connected to frontal area 45B, and the anterior subsector of AIP (aAIP) to F5a (Premereur et al., 2015). However, the role of area 45B and F5a in visually-guided object grasping is poorly understood. Here, we investigated the role of area 45B, F5a and F5p in visually-guided grasping. If a neuronal response to an object during passive fixation represents the activation of a motor command related to the preshaping of the hand, such neurons should prefer objects presented within reachable distance. Conversely, neurons encoding a pure visual representation of an object should be less affected by viewing distance. Contrary to our expectations, we found that the majority of neurons in area 45B were object- and viewing distance selective, with a clear preference for the near viewing distance. Area F5a showed much weaker object selectivity compared to 45B, with a similar preference for objects presented at the Near position emerging mainly in the late epoch. Finally, F5p neurons were less object selective and frequently preferred objects presented at the Far position. Therefore, contrary to our expectations, neurons in area 45B – but not F5p neurons – prefer objects presented in peripersonal space.

Significance statement

The current experiment provides the first evidence on the neural representation of distance in frontal areas that are active during visually-guided grasping. Area 45B and F5a neurons were object- and distance-selective, and preferred the near viewing distance even for objects with identical retinal size. In area F5p we observed strong visual responses with an unexpected preference for the Far viewing distance, suggesting that the motor-related object representation was still active during the presentation of objects outside reaching distance.
Evaluating the sensitivity of functional connectivity measures to motion artifact in resting-state fMRI data
Authors: Mahadevan Arun S. , Tooley Ursula A. , Bertolero Maxwell A. , Mackey Allyson P. , Bassett Danielle S.
Published: May 2020

Functional connectivity (FC) networks are typically inferred from resting-state fMRI data using the Pearson correlation between BOLD time series from pairs of brain regions. However, alternative methods of estimating functional connectivity have not been systematically tested for their sensitivity or robustness to head motion artifact. Here, we evaluate the sensitivity of six different functional connectivity measures to motion artifact using resting-state data from the Human Connectome Project. We report that FC estimated using full correlation has a relatively high residual distance-dependent relationship with motion compared to partial correlation, coherence and information theory-based measures, even after implementing rigorous methods for motion artifact mitigation. This disadvantage of full correlation, however, may be offset by higher test-retest reliability and system identifiability. FC estimated by partial correlation offers the best of both worlds, with low sensitivity to motion artifact and intermediate system identifiability, with the caveat of low test-retest reliability. We highlight spatial differences in the sub-networks affected by motion with different FC metrics. Further, we report that intra-network edges in the default mode and retrosplenial temporal sub-networks are highly correlated with motion in all FC methods. Our findings indicate that the method of estimating functional connectivity is an important consideration in resting-state fMRI studies and must be chosen carefully based on the parameters of the study.
SMARCB1 loss interacts with neuronal differentiation state to block maturation and impact cell stability
Authors: Parisian Alison D. , Koga Tomoyuki , Miki Shunichiro , Johann Pascal D. , Kool Marcel , Crawford John R. , Furnari Frank B.
Published: May 2020

Atypical teratoid rhabdoid tumors (ATRT) are challenging pediatric brain cancers which are predominantly associated with inactivation of the gene SMARCB1, a conserved subunit of the chromatin remodeling BAF complex, which has known contributions to developmental processes. To identify potential interactions between SMARCB1 loss and the process of neural development, we introduced an inducible SMARCB1 loss of function system into human induced pluripotent stem cells (iPSCs) which were subjected to either directed neuronal differentiation or differentiation into cerebral organoids. Using this system, we have identified substantial differences in the downstream effects of SMARCB1 loss depending on differentiation state and identified an interaction between SMARCB1 loss and neural differentiation pressure which causes a resistance to terminal differentiation and a defect in maintenance of a normal cell state. Our results provide insight into how SMARCB1 loss might interact with neural development in the process of ATRT tumorigenesis.
Direct and specific assessment of axonal injury and spinal cord microenvironments using diffusion correlation imaging
Authors: Benjamini Dan , Hutchinson Elizabeth B. , Komlosh Michal E. , Comrie Courtney J. , Schwerin Susan C. , Zhang Guofeng , Pierpaoli Carlo , Basser Peter J.
Published: May 2020

We describe a practical two-dimensional (2D) diffusion MRI framework to deliver specificity and improve sensitivity to axonal injury in the spinal cord. This approach provides intravoxel distributions of correlations of water mobilities in orthogonal directions, revealing sub-voxel diffusion components. Here we use it to investigate water diffusivities along axial and radial orientations within spinal cord specimens with confirmed, tract-specific axonal injury. First, we show using transmission electron microscopy and immunohistochemistry that tract-specific axonal beading occurs following Wallerian degeneration in the cortico-spinal tract as direct sequelae to closed head injury. We demonstrate that although some voxel-averaged diffusion tensor imaging (DTI) metrics are sensitive to this axonal injury, they are non-specific, i.e., they do not reveal an underlying biophysical mechanism of injury. Then we employ 2D diffusion correlation imaging (DCI) to improve discrimination of different water microenvironments by measuring and mapping the joint water mobility distributions perpendicular and parallel to the spinal cord axis. We determine six distinct diffusion spectral components that differ according to their microscopic anisotropy and mobility. We show that at the injury site a highly anisotropic diffusion component completely disappears and instead becomes more isotropic. Based on these findings, an injury-specific MR image of the spinal cord was generated, and a radiological-pathological correlation with histological silver staining % area was performed. The resulting strong and significant correlation (r= 0.70,p <0.0001) indicates the high specificity with which DCI detects injury-induced tissue alterations. We predict that the ability to selectively image microstructural changes following axonal injury in the spinal cord can be useful in clinical and research applications by enabling specific detection and increased sensitivity to injury-induced microstructural alterations. These results also encourage us to translate DCI to higher spatial dimensions to enable assessment of traumatic axonal injury, and possibly other diseases and disorders in the brain.
Determinants of RNA recognition by the FinO domain of theEscherichia coliProQ protein
Authors: Stein Ewa M. , Kwiatkowska Joanna , Basczok Maciej M. , Gravel Chandra M. , Berry Katherine E. , Olejniczak Mikołaj
Published: May 2020

The regulation of gene expression by small RNAs inEscherichia colidepends on RNA binding proteins Hfq and ProQ, which bind mostly distinct RNA pools. To understand how ProQ discriminates between RNA substrates, we compared its binding to six different RNA molecules. Full-length ProQ bound all six RNAs similarly, while the isolated N-terminal FinO domain (NTD) of ProQ specifically recognized RNAs with Rho-independent terminators. Analysis ofmalM3’-UTR mutants showed that tight RNA binding by the ProQ NTD required a terminator hairpin of at least two base pairs preceding an 3’ oligoU tail of at least four uridine residues. Substitution of an A-rich sequence on the 5’ side of the terminator to uridines strengthened the binding of several ProQ-specific RNAs to the Hfq protein, but not to the ProQ NTD. Substitution of the motif in themalM-3’ andcspE-3’ RNAs also conferred the ability to bind Hfq inE. colicells, as measured using a three-hybrid assay. In summary, these data suggest that the ProQ NTD specifically recognizes 3’ intrinsic terminators of RNA substrates, and that the discrimination between RNA ligands byE. coliProQ and Hfq depends both on positive determinants for binding to ProQ and negative determinants against binding to Hfq.
Subfunctionalization of paralog transcription factors contributes to regulation of alkaloid pathway branch choice inCatharanthus roseus
Authors: Colinas Maite , Pollier Jacob , Vaneechoutte Dries , Malat Deniz G. , Schweizer Fabian , De Milde Liesbeth , De Clercq Rebecca , Guedes Joana G. , Martínez-Cortés Teresa , Molina Hidalgo Francisco J. , Sottomayor Mariana , Vandepoele Klaas , Goossens Alain
Published: May 2020

Catharanthus roseusproduces a diverse range of specialized metabolites of the monoterpenoid indole alkaloid (MIA) class in a heavily branched pathway. Recent great progress in identification of MIA biosynthesis genes revealed that the different pathway branch genes are expressed in a highly cell type- and organ-specific and stress-dependent manner. This implies a complex control by specific transcription factors (TFs), only partly revealed today. We generated and mined a comprehensive compendium of publicly availableC. roseustranscriptome data for MIA pathway branch-specific TFs. Functional analysis was performed through extensive comparative gene expression analysis and profiling of over 40 MIA metabolites in theC. roseusflower petal expression system. We identified additional members of the known BIS and ORCA regulators. Further detailed study of the ORCA TFs suggests subfunctionalization of ORCA paralogs in terms of target gene-specific regulation and synergistic activity with the central jasmonate response regulator MYC2. Moreover, we identified specific amino acid residues within the ORCA DNA-binding domains that contribute to the differential regulation of some MIA pathway branches. Our results advance our understanding of TF paralog specificity for which, despite the common occurrence of closely related paralogs in many species, comparative studies are scarce.

SIGNIFICANCE STATEMENT

A gene discovery program for regulators of monoterpenoid indole alkaloid biosynthesis inCatharanthus roseusadvances our understanding of paralog specificity and subfunctionalization of the renowned class of ORCA transcription factors, particularly in terms of target gene-specificity and synergistic activity with other jasmonate-responsive transcription factors.
A theoretical framework to study the influence of electrical fields on mesenchymal stem cells
Authors: Dawson Jonathan , Lee Poh Soo , van Rienen Ursula , Appali Revathi
Published: May 2020

Mesenchymal stem cell dynamics involves cell proliferation and cell differentiation into cells of distinct functional type, such as osteoblasts, adipocytes, or chondrocytes. Electrically active implants influence these dynamics for the regeneration of the cells in damaged tissues. How applied electric field influences processes of individual stem cells is a problem mostly unaddressed. The mathematical approaches to study stem cell dynamics have focused on the stem cell population as a whole, without resolving individual cells and intracellular processes. In this paper, we present a theoretical framework to describe the dynamics of a population of stem cells, taking into account the processes of the individual cells. We study the influence of the applied electric field on the cellular processes. We test our mean-field theory with the experiments from the literature, involvingin vitroelectrical stimulation of stem cells. We show that a simple model can quantitatively describe the experimentally observed time-course behavior of the total number of cells and the total alkaline phosphate activity in a population of mesenchymal stem cells. Our results show that the stem cell differentiation rate is dependent on the applied electrical field, confirming published experimental findings. Moreover, our analysis supports the cell density-dependent proliferation rate. Since the experimental results are averaged over many cells, our theoretical framework presents a robust and sensitive method for determining the effect of applied electric fields at the scale of the individual cell. These results indicate that the electric field stimulation may be effective in promoting bone regeneration by accelerating osteogenic differentiation.
Independent and Interacting Value Systems for Reward and Information in the Human Brain
Authors: Dezza I. Cogliati , Cleeremens A. , Alexander W.
Published: May 2020

Theories of Prefrontal Cortex (PFC) as optimizingrewardvalue have been widely deployed to explain its activity in a diverse range of contexts, with substantial empirical support in neuroeconomics and decision neuroscience. Theoretical frameworks of brain function, however, suggest the existence of a second, independent value system for optimizinginformationduring decision-making. To date, however, there has been little direct empirical evidence in favor of such frameworks. Here, by using computational modeling, model-based fMRI analysis, and a novel experimental paradigm, we aim at establishing whether independent value systems exist in human PFC. We identify two regions in the human PFC which independently encode distinct value signals. These value signals are then combined in subcortical regions in order to implement choices. Our results provide empirical evidence for PFC as an optimizer of independent value signals during decision-making under realistic scenarios, with potential implications for the interpretation of PFC activity in both healthy and clinical population.

One Sentence Summary

Reward and information value are independently optimized in the Human PFC and are then combined in subcortical regions in order to implement choices.
Impact of formate supplementation on body weight and plasma amino acids
Authors: Dhayade Sandeep , Pietzke Matthias , Wiesheu Robert , Tait-Mulder Jacqueline , Athineos Dimitris , Sumpton David , Coffelt Seth B. , Blyth Karen , Vazquez Alexei
Published: May 2020

Current nutritional recommendations are focused on energy, fat, carbohydrate, protein and vitamins. Less attention has been paid to the nutritional demand of one-carbon units for nucleotide and methionine synthesis. Here we investigate the impact of sodium formate supplementation as a nutritional intervention to increase the dietary intake of one-carbon units. A cohort of six female and six male mice received 125 mM sodium formate in the drinking water for three months. A control group of another six female and six male mice was also followed up for the same period of time. Tail vein blood samples were collected once a month and profiled with a haematology Analyser. At the end of the study blood and tissues were collected for metabolomics analysis and immune cell sorting. Formate supplementation has no significant physiological effect on male mice. Formate supplementation has no significant effect on the immune cell counts during the intervention or at the end of the study in either gender. In female mice however, the body weight and spleen wet-weight were significantly increased by formate supplementation, while the blood plasma levels of amino acids were decreased. Formate supplementation also increased the frequency of probiotic bacteria in the stools of female mice. We conclude that formate supplementation induces physiological changes in female mice.
Spontaneous network coupling enables efficient task performance without local task-induced activations
Authors: Allaman Leslie , Mottaz Anaïs , Kleinschmidt Andreas , Guggisberg Adrian G.
Published: May 2020

Neurobehavioral studies in humans have long concentrated on changes in local activity levels during repetitive executions of a task. Spontaneous neural coupling within extended networks has latterly been found to also influence performance. Here, we intend to uncover the underlying mechanisms and the interaction with task-induced activations. We demonstrate that high performers in visual perception and motor sequence tasks present an absence of classical task-induced activations, but, instead, strong spontaneous network coupling. Activations were thus a compensation mechanism needed only in subjects with lower spontaneous network interactions. This challenges classical models of neural processing and calls for new strategies in attempts to train and enhance performance.
The Digital Mouse: why computational modelling of mouse models of disease can improve translation
Authors: van Riel Natal , Müller Ralph , Dall’Ara Enrico
Published: May 2020

Computational models can be used to study the mechanistic phenomena of disease. Current mechanistic computer simulation models mainly focus on (patho)physiology in humans. However, often data and experimental findings from preclinical studies are used as input to develop such models. Biological processes underlying age-related chronic diseases are studied in animal models. The translation of these observations to clinical applications is not trivial. As part of a group of international scientists working in the COST Action network MouseAGE, we argue that in order to boost the translation of pre-clinical research we need to develop accuratein silicocounterparts of thein vivoanimal models. The Digital Mouse is proposed as framework to support the development of evidence-based medicine, for example to develop geroprotectors, which are drugs that target fundamental mechanisms of ageing.

Highlights

Computational modelling of human (patho)physiology is advancing rapidly, often using and extrapolating experimental findings from preclinical disease models.

The lack ofin silicomodels to supportin vivomodelling in mice is a missing link in current approaches to study complex, chronic diseases.

The development of mechanistic computational models to simulate disease in mice can boost the discovery of novel therapeutic interventions.

The ‘Digital Mouse’ is proposed as a framework to implement this ambition. The development of a Digital Mouse Frailty Index (DM:FI) to study aging and age-related diseases is provided as an example.
An agent-based model clarifies the importance of functional and developmental integration in shaping brain evolution
Authors: Avin Shahar , Currie Adrian , Montgomery Stephen H.
Published: May 2020

Comparisons of vertebrate brain structure suggest a conserved pattern of scaling between components, but also many examples of lineages diverging dramatically from these general trends. Two competing hypotheses of brain evolution seek to explain these patterns of variation by invoking either ‘external’ processes, such as selection driving phenotypic change, or ‘internal’ processes, like developmental coupling among brain regions. Efforts to reconcile these views remain deadlocked, in part due to empirical under-determination and the limitations of ‘relative significance’ debates. We introduce an agent-based model that allows us to simulate brain evolution in a ‘bare-bones’ system and examine the dependencies between variables that may shape brain evolution. Our simulations formalise verbal arguments and interpretations concerning the evolution of brain structure. We illustrate that ‘concerted’ patterns of brain evolution cannot alone be taken as evidence for developmental coupling, or constraint, despite these terms often being treated as synonymous in the literature. Both developmentally coupled and uncoupled brain architectures can represent adaptive mechanisms, depending on the distribution of selection across the brain, life history, and the relative costs of neural tissue. Our model also illustrates how the prevalence of mosaic and concerted patterns of evolution may fluctuate through time in a variable environment, which we argue implies that developmental coupling is unlikely to be a significant evolutionary constraint.
LAMA: Automated image analysis for developmental phenotyping of mouse embryos
Authors: Horner Neil R. , Venkataraman Shanmugasundaram , Casero Ramón , Brown James M. , Johnson Sara , Teboul Lydia , Wells Sara , Brown Steve , Westerberg Henrik , Mallon Ann-Marie
Published: May 2020

Advanced 3D imaging modalities such as micro computed tomography (micro-CT), high resolution episcopic microscopy (HREM), and optical projection tomography (OPT) have been readily incorporated into high-throughput phenotyping pipelines, such as the International Mouse Phenotyping Consortium (IMPC). Such modalities generate large volumes of raw data that cannot be immediately harnessed without significant resources of manpower and expertise. Thus, rapid automated analysis and annotation is critical to ensure that 3D imaging data is able to be integrated with other multi-dimensional phenotyping data. To this end, we present an automated computational mouse phenotyping pipeline called LAMA, based on image registration, which requires minimal technical expertise and human input to use. Designed predominantly for developmental biologists, our software performs image pre-processing, registration, statistical and gene function annotation, and segmentation of 3D micro-CT data. We address several limitations of current methods and create an easy to use, fast solution application for mouse embryo phenotyping. We also present a highly granular, novel anatomical E14.5 (14.5 days post coitus) atlas of a population average that integrates with our pipeline to allow a range of dysmorphologies to be automatically annotated as well as results from the validation of the pipeline.
Global mapping ofSalmonella enterica-host protein-protein interactions during infection
Authors: Walch Philipp , Selkrig Joel , Knodler Leigh A. , Rettel Mandy , Stein Frank , Fernandez Keith , Viéitez Cristina , Potel Clément M. , Scholzen Karoline , Geyer Matthias , Rottner Klemens , Steele-Mortimer Olivia , Savitski Mikhail M. , Holden David W. , Typas Athanasios
Published: May 2020

Intracellular bacterial pathogens inject effector proteins into host cells to hijack diverse cellular processes and promote their survival and proliferation. To systematically map effector-host protein-protein interactions (PPIs) during infection, we generated a library of 32Salmonella entericaserovar Typhimurium (STm) strains expressing chromosomally encoded affinity-tagged effector proteins, and quantified PPIs in macrophages and epithelial cells by Affinity-Purification Quantitative Mass-Spectrometry. Thereby, we identified 25 previously described and 421 novel effector-host PPIs. While effectors converged on the same host cellular processes, most had multiple targets, which often differed between cell types. Using reciprocal co-immunoprecipitations, we validated 13 out of 22 new PPIs. We then used this host-pathogen physical interactome resource to demonstrate that SseJ and SseL collaborate in redirecting cholesterol to theSalmonellaContaining Vacuole (SCV) via NPC1, PipB directly recruits the organelle contact site protein PDZD8 to the SCV, and SteC promotes actin bundling by directly phosphorylating formin-like proteins.
The UCSC SARS-CoV-2 Genome Browser
Authors: Fernandes Jason D. , Hinrichs Angie S. , Clawson Hiram , Navarro Gonzalez Jairo , Lee Brian T. , Nassar Luis R. , Raney Brian J. , Rosenbloom Kate R. , Nerli Santrupti , Rao Arjun , Schmelter Daniel , Zweig Ann S. , Lowe Todd M. , Ares Manuel , Corbet-Detig Russ , Kent W. James , Haussler David , Haeussler Maximilian
Published: May 2020

Background

Researchers are generating molecular data pertaining to the SARS-CoV-2 RNA genome and its proteins at an unprecedented rate during the COVID-19 pandemic. As a result, there is a critical need for rapid and continuously updated access to the latest molecular data in a format in which all data can be quickly cross-referenced and compared. We adapted our genome browser visualization tool to the viral genome for this purpose. Molecular data, curated from published studies or from database submissions, are mapped to the viral genome and grouped together into “annotation tracks” where they can be visualized along the linear map of the viral genome sequence and programmatically downloaded in standard format for analysis.

Results

The UCSC Genome Browser for SARS-CoV-2 (https://genome.ucsc.edu/covid19.html) provides continuously updated access to the mutations in the many thousands of SARS-CoV-2 genomes deposited in GISAID and the international nucleotide sequencing databases, displayed alongside phylogenetic trees. These data are augmented with alignments of bat, pangolin, and other animal and human coronavirus genomes, including per-base evolutionary rate analysis. All available annotations are cross-referenced on the virus genome, including those from major databases (PDB, RFAM, IEDB, UniProt) as well as up-to-date individual results from preprints. Annotated data include predicted and validated immune epitopes, promising antibodies, RT-PCR and sequencing primers, CRISPR guides (from research, diagnostics, vaccines, and therapies), and points of interaction between human and viral genes. As a community resource, any user can add manual annotations which are quality checked and shared publicly on the browser the next day.

Conclusions

We invite all investigators to contribute additional data and annotations to this resource to accelerate research and development activities globally. Contact us atgenome-www@soe.ucsc.eduwith data suggestions or requests for support for adding data. Rapid sharing of data will accelerate SARS-CoV-2 research, especially when researchers take time to integrate their data with those from other labs on a widely-used community browser platform with standardized machine-readable data formats, such as the SARS-CoV-2 Genome Browser.
Phosphorylation and dephosphorylation of Ser852 and Ser889 control clustering, localization, and function of PAR-3
Authors: Yamashita Kazunari , Mizuno Keiko , Furukawa Kana , Hirose Hiroko , Sakurai Natsuki , Masuda-Hirata Maki , Amano Yoshiko , Hirose Tomonori , Suzuki Atsushi , Ohno Shigeo
Published: May 2020

Cell polarity is essential for various asymmetric cellular events, where the partitioning defective (PAR) protein, PAR3, plays a unique role as a cellular landmark to establish polarity. In epithelial cells, PAR3 localizes at the subapical border such as the tight junction in vertebrates and functions as an apical determinant. Although there is much information about the regulators of PAR3 localization, the mechanism involved in PAR3 concentration and localization to the specific membrane domain remains an important question to be clarified. In this study, we demonstrate that ASPP2, a stimulator of PAR3 localization, can link PAR3 and protein phosphatase 1 (PP1). The ASPP2–PP1 complex dephosphorylates a novel phosphorylation site, Ser852, of PAR3. Furthermore, Ser852- or Ser889-unphosphorylatable PAR3 mutants form protein clusters and ectopically localize to the lateral membrane. Concomitance of clustering and ectopic localization suggests that PAR3 localization is a consequence of local clustering. We also demonstrate that unphosphorylatable forms of PAR3 are static in molecular turnover and fail to coordinate rapid reconstruction of the tight junction, supporting that both phosphorylated and dephosphorylated states are essential for the functional integrity of PAR3.

Summary statement

We show that phosphorylation and dephosphorylation regulate clustering of PAR-3, a cell polarity-regulating factor, and how the clustering regulation affects localization of PAR-3 and cell-cell junction formation.
Effects of evolution on niche displacement and emergent population properties, a discussion on optimality
Authors: Rohr Rudolf P. , Loeuille Nicolas
Published: May 2020

Understanding the effects of evolution on emergent population properties such as intrinsic growth rate, species abundance, or dynamical resilience is not only a key theoretical question, but has major empirical implications for conservation, agroecology, invasion ecology among others. In particular, could we classify evolutionary scenarios leading to optimisation of those properties, from the ones who do not. First, we uncover two classes of invasion fitness functions, only the first one allowing optimization of some (but typically not all) population properties. Second, we showed that our two classes are also strongly linked to niche displacement and emergence of polymorphism. Our results indicate that optimization is, in general, incompatible with niche differentiation and, therefore, with emergence of polymorphism through evolutionary branching. Actually, niche displacement between resident and mutant morphs, and potentially polymorphism, only arise when we do not expect optimality to hold. We extensively discuss which biological traits can fall into which class of invasion fitness. Although, it is possible to find traits for which optimality is expected, we argue that for the majority of the cases it does not hold. Finally, we provide practical applications of our results in conservation, agroecology, harvesting and invasion ecology.
A functional genetic toolbox for human tissue-derived organoids
Authors: Sun Dawei , Evans Lewis , Lim Kyungtae , Rawlins Emma L.
Published: May 2020

Human organoid systems recapitulate key features of organs offering platforms for modelling developmental biology and disease. Tissue-derived organoids have been widely used to study the impact of extrinsic niche factors on stem cells. However, they are rarely used to study endogenous gene function due to the lack of efficient gene manipulation tools. We have systematically developed and optimised a complete genetic toolbox for tissue-derived organoids. This includes “Organoid Easytag”, our efficient workflow for targeting all types of gene loci through CRISPR-mediated homologous recombination followed by flow cytometry for enriching correctly-targeted cells. Our toolbox also incorporates conditional gene knock-down, or overexpression, using tightly-inducible CRISPR interference and CRISPR activation; the first efficient application of these techniques to tissue-derived organoids. These tools will facilitate gene perturbation studies in tissue-derived organoids providing a functional counter-part to many on-going descriptive studies, such as the Human Cell Atlas Project.
Nothing better to do? Environment quality and the evolution of cooperation by partner choice
Authors: Ecoffet Paul , Bredeche Nicolas , André Jean-Baptiste
Published: May 2020

The effects of partner choice have been documented in a large number of biological systems such as sexual markets, interspecific mutualisms, or human cooperation. There are, however, a number of situations in which one would expect this mechanism to play a role, but where no such effect has ever been demonstrated. This is the case in particular in many intraspecific interactions, such as collective hunts, in non-human animals. Here we use individual-based simulations to solve this apparent paradox. We show that the conditions for partner choice to operate are in fact restrictive. They entail that individuals can compare social opportunities and choose the best. The challenge is that social opportunities are often rare because they necessitate the co-occurrence of (i) at least one available partner, and (ii) a resource to exploit together with this partner. This has three consequences. First, partner choice cannot lead to the evolution of cooperation when resources are scarce, which explains that this mechanism could never be observed in many cases of intraspecific cooperation in animals. Second, partner choice can operate when partners constitute in themselves a resource, which is the case in sexual interactions and interspecific mutualisms. Third, partner choice can lead to the evolution of cooperation when individuals live in a rich environment, and/or when they are highly efficient at extracting resources from their environment.
SH3KBP1 scaffolds endoplasmic reticulum and controls skeletal myofibers architecture and integrity
Authors: Guiraud Alexandre , Christin Emilie , Couturier Nathalie , Kretz-Remy Carole , Janin Alexandre , Ghasemizadeh Alireza , Durieux Anne-Cécile , Arnould David , Romero Norma Beatriz , Bui Mai Thao , Buchman Vladimir L. , Julien Laura , Bitoun Marc , Gache Vincent
Published: May 2020

The building block of skeletal muscle is the multinucleated muscle fiber, formed by the fusion of hundreds of mononucleated precursor cells, myoblasts. In the normal course of muscle fiber development or regeneration, myonuclei are actively positioned throughout muscular development and adopt special localization in mature fibers: regular spacing along muscle fibers periphery, raising the notion of MyoNuclear Domains (MNDs). There is now growing support for a direct connection between myonuclear positioning and normal function of muscles, but how myonuclei affects muscle function remains poorly characterized.

To identify new factors regulating forces applied on myonuclei in muscles fibers, we performed a siRNA screen and identified SH3KBP1 as a new factor controlling myonuclear positioning in early phases of myofibers formation. Depletion of SH3KBP1 induces a reset of MNDs establishment in mature fibers reflected by a dramatic reduction in pairwise distance between myonuclei. We show that SH3KBP1 scaffolds Endoplasmic Reticulum (ER) in myotubes that in turn controls myonuclei velocity and localization and thus myonuclear domains settings. Additionally, we show that in later phases of muscle maturation, SH3KBP1 contributes to the formation and maintenance of Sarcoplasmic Reticulum (SR) and Transverse-tubules (T-tubules). We also demonstrate that in muscle fibers, GTPase dynamin-2 (DNM2) binds to SH3 domains of SH3KBP1. Interestingly, we observed thatSh3kbp1mRNA is up regulated in a mouse model harboring the most frequent mutation for Autosomal Dominant CentroNuclear Myopathy (AD-CNM):Dnm2+/R465W. SH3KBP1 thus appears as a compensation mechanism in this CNM model since its depletion contributes to an increase of CNM-like phenotypes (reduction of muscle fibers Cross-section Areas (CSA) and increase in slow fibers content).

Altogether our results identify SH3KBP1 as a new regulator of myonuclear domains establishment in the early phase of muscle fibers formation through ER scaffolding and later in myofibers integrity through T-tubules scaffolding/maintenance.

Myonuclei are actively positioned throughout muscular development. Guiraud, Christin, Couturieret alshow that SH3KBP1 scaffolds the ER through Calnexin interaction and controls myonuclei motion during early steps of muscle fibers formation. Besides SH3KBP1 participates in cell fusion and T-tubules formation/maintenance in mature skeletal muscle fibers and contributes to slow-down CNM-like phenotypes.
A Comparative Analysis of Different Feature Extraction Techniques for Palm-print Images
Authors: Pratyasha Prateek , Swarnkar Bharati , Padhy Aditya Prasad
Published: May 2020

In this advanced decade, automatic identification of individuals is a significant achievement due to the high demand of security system. Hence, individual recognition using biometrics data is leading in the field of image processing. Although biometrics data analysis using thumb impression and finger-prints are very popular since many years, sometimes it leads to false acceptance and rejection if any physical change occurs in the finger ridges. There may be a high risk of hacking the biometrics data which is now a big challenge for cyber security employees. This paper captures the palm-print images of individuals as referred biometrics data for individual recognition. The research work is based on one of the prior issue that is feature extraction to extract the features of palm-print image such as principle lines, textures, ridges and pores etc. For this, some of the feature extraction techniques such as Derivatives of Gaussian filter (DoG), Discrete Cosine Transform (DCT), Fast Fourier Transform (FFT) and competitive coding. Two types of filters: Gaussian Filter and Gabor filter are combined with each of the feature extraction scheme for the matching of sampled image with testing image. In the result, the error rates of each of the feature extraction algorithms are compared to recognize the palm image of two different individuals.
Uncovering the genetic blueprint of theC. elegansnervous system
Authors: Kovács István A. , Barabási Dániel L. , Barabási Albert-László
Published: May 2020

Despite rapid advances in connectome mapping and neuronal genetics, we lack theoretical and computational tools to unveil, in an experimentally testable fashion, the genetic mechanisms that govern neuronal wiring. Here we introduce a computational framework to link the adjacency matrix of a connectome to the expression patterns of its neurons, helping us uncover a set of genetic rules that govern the interactions between adjacent neurons. The method incorporates the biological realities of the system, accounting for noise from data collection limitations, as well as spatial restrictions. The resulting methodology allows us to infer a network of 19 innexin interactions that govern the formation of gap junctions inC. elegans, five of which are already supported by experimental data. As advances in single-cell gene expression profiling increase the accuracy and the coverage of the data, the developed framework will allow researchers to systematically infer experimentally testable connection rules, offering mechanistic predictions for synapse and gap junction formation.
Seasonal dynamics of methane cycling microbial communities in Amazonian floodplain sediments
Authors: Gontijo Júlia B. , Venturini Andressa M. , Yoshiura Caio A. , Borges Clovis D. , Moura José Mauro S. , Bohannan Brendan J. M. , Nüsslein Klaus , Rodrigues Jorge L. Mazza , Paula Fabiana S. , Tsai Siu M.
Published: May 2020

The Amazonian floodplain forests are dynamic ecosystems of great importance for the regional hydrological and biogeochemical cycles and provide a significant contribution to the global carbon balance. Unique geochemical factors may drive the microbial community composition and, consequently, affect CH4emissions across floodplain areas. Here we provide the first report of thein situseasonal dynamics of CH4cycling microbial communities in Amazonian floodplains. We asked how abiotic factors may affect both overall and CH4cycling microbial communities and further investigated their responses to seasonal changes. We collected sediment samples during wet and dry seasons from three different types of floodplain forests, along with upland forest soil samples, from the Eastern Amazon, Brazil. We used high-resolution sequencing of archaeal and bacterial 16S rRNA genes combined with real-time PCR to quantify Archaea and Bacteria, as well as key functional genes indicative of the methanogenic (methyl coenzyme-M reductase –mcrA) and methanotrophic (particulate methane monooxygenase –pmoA) metabolisms. Methanogens were found to be present in high abundance in floodplain sediments and they seem to resist to dramatic seasonal environmental changes. Methanotrophs known to use different pathways to oxidise CH4were detected, including anaerobic archaeal and bacterial taxa, indicating that a wide metabolic diversity may be harboured in this highly variable environment. The floodplain environmental variability, which is affected by the river origin, drives not only the sediment chemistry, but also the composition of the microbial communities. The results presented may contribute to the understanding of the current state of CH4cycling in this region.
Where does it go? The fate of thiocyanate in the aquarium water and blood plasma ofAmphiprion clarkiiafter exposure to cyanide
Authors: Bonanno J. Alexander , Breen Nancy E. , Tlusty Michael F. , Andrade Lawrence J. , Rhyne Andrew L.
Published: May 2020

The illegal practice of cyanide fishing continues to damage coral reef ecosystems throughout the Indo-Pacific. To combat this destructive fishing method, a simple, reliable test to detect whether or not a fish has been captured using cyanide (CN) is needed. This study analyzed the toxicokinetics of acute, pulsed CN exposure as well as chronic exposure to thiocyanate (SCN), the major metabolite of CN, in the clownfish species,Amphiprion clarkii. Fish were pulse exposed to 50 ppm CN for 20 or 45 seconds or chronically exposed to 100 ppm SCN for 12 days. Blood plasma levels of SCN were measured following derivatization to SCN-bimane using an Acquity UPLC I-Class and Q-Exactive hybrid Quadrupole-Orbitrap HRAM mass spectrometer or directly by HPLC-UV. After exposure to CN, depending on the duration of exposure, SCN plasma levels reached a maximum concentration (300–470 ppb) 0.13–0.17 days after exposure, had a 0.1 to 1.2 day half-life, and often did not return to baseline levels. The half-life of plasma SCN after direct exposure to SCN was found to be 0.13 days, similar to the CN exposure, and that SCN in the holding water would often drop below detection. Finally, we observed that when a fish, never exposed to SCN, was placed in aquarium water spiked with SCN, there was a steady decrease in aqueous SCN concentration over 24 hours until it could no longer be detected. This pattern was repeated with a second sequential dose. These results demonstrate thatA. clarkiido not excrete SCN after CN exposure, but in fact can absorb low concentrations of SCN from water, refuting several publications. It appears thatA. clarkiiexhibit a classic two compartment model where SCN is rapidly eliminated from the blood plasma and is distributed throughout the tissue but not excreted in their urine. This study demonstrates that SCN may be used as a marker of CN exposure only if fish are tested shortly after exposure. There is species specific variability in response to CN, and studies of other taxa need to be performed before this test can be deployed in the field.
Dexmedetomidine attenuates the injury of H9C2 cardiomyocytes under Hypoxia/reoxygenation condition partly through the inhibition of endoplasmic reticulum stress
Authors: Zhu Zhipeng , Ling Xiaoyan , Zhou Hongmei , Zhang Caijun
Published: May 2020

Background

Myocardial ischemia-reperfusion injury (MIRI) has been confirmed to induce endoplasmic reticulum stress(ERS) during downstream cascade reaction when myocardial cell function keep deteriorating to a certain degree. The fact of matter is the clinical inconsistence with experimental outcomes still exist due to the mechanism has not been entirely clarified. Dexmedetomidine (DEX), a new generation anti-inflammatory and organ protector, has been testified can attenuate the IRI of heart. This study aimed to find out if DEX had the capacity to protect the injured cardiomyocytes under in vitro hypoxia/reoxygenation circumstance and if the ERS was totally or partly intervened.

Methods

H9C2 cells were subjected to cytotoxicity detection for 24h with DEX normally cultivated in several different concentrations. The proper hypoxia/reoxygenation (H/R) model parameter were concluded by the cell viability and injuries by cell counting kit-8(CCK8) and lactate dehydrogenase (LDH) release, when undergoing hypoxic condition for 3 h and reoxygenated for 3h, 6h,12h, and 24h, respectively. Also, the above index was assessed for H/R cardiomyocytes cultivated by various concentrations of DEX. The apoptosis, expression of) Glucose-regulated protein 78(GRP78), C/EBP homologous protein (CHOP), and caspase-12 were also examined in all groups.

Results

1, 5 and 10 μM DEX in normal culture could significantly promote the proliferation of H9C2 (> 80%); the activity of H9c2 cells decreased to 62.67% (P < 0.05) at 3h of reoxygenation and to 36% at 6h of reoxygenation followed by 3h anoxic treatment; The cell viability of H9c2 cells in H/R groups incubated with 1 μM DEX increased 61.3%, and the LDH concentration in the supernatant was effectively lowered (−13.7, P < 0.05); H/R dramatically decreased the proportion of flow cytometry apoptosis and increased the expression of GRP78, CHOP and caspase-12, while both DEX and 4-phenyl butyric acid (4-PBA) could significantly reverse those above indicators. Additionally, DEX could induce deeper alterations than 4-PBA on the basis of H/R.

Conclusion

1 μM DEX can dramatically attended the cell injuries, apoptosis, the expression of GRP78, CHOP and caspase-12 of H9C2 induced by 3h’ hypoxia and 3h’s reoxygenation. moreover, the functions of DEX went beyond the inhibition of ERS under this situation.
Neurocognitive processing efficiency for non-alarm rather than alarm signaling in human scream calls
Authors: Frühholz Sascha , Dietziker Joris , Staib Matthias , Trost Wiebke
Published: May 2020

Across many species, scream calls signal the affective significance of events to other agents. Scream calls were often supposed to be of generic alarming and fearful nature to signal potential threats including their instantaneous, involuntary, and accurate recognition by perceivers. However, scream calls are more diverse in their affective signaling nature than being limited to fearfully alarm a threat, and thus the broader sociobiological relevance of various scream types is unclear. Here we used four different psychoacoustic, perceptual decision-making, and neuroimaging experiments in humans to demonstrate, first, the existence of at least six generic and psycho-acoustically distinctive types of scream calls of both an alarming and a non-alarming nature, rather than being limited to only screams caused by fear or aggression. Second, based on perceptual and processing sensitivity measures for decision-making during scream recognition, we found that alarming screams (with some exceptions) were overall discriminated the worst, were responded to the slowest and were associated with the lower perceptual sensitivity for their recognition compared with non-alarm screams. Third, the neural processing of alarm compared with non-alarm screams during an implicit processing task elicited only minimal neural signal and connectivity in perceivers, contrary to the frequent assumption of a threat processing bias of the primate neural system. These findings show that scream calls are more diverse in their signaling and communicative nature in humans and that especially non-alarming screams, and positive screams in particular, seem to have higher efficiency in the cognitive, neural, and communicative processing in humans.