bluuebunny/crossref_metadata_2025_split huggingface dataset:
Yorkie and JNK revert syncytial muscles into myoblasts during Org-1 dependent lineage reprogramming
Authors: Schaub Christoph , Rose Marcel , Frasch Manfred 
Published: April 2019

SummaryLineage reprogramming has become a prominent focus in research since it was demonstrated that lineage restricted transcription factors can be used in vitro for direct reprogramming [1]. Recently, we reported that the ventral longitudinal musculature (VLM) of the adult Drosophila heart arises in vivo by direct lineage reprogramming from alary muscles (AM), a process which starts with dedifferentiation and fragmentation of syncytial alary muscles into mononucleate myoblasts. Central upstream activators of the genetic program regulating the development of VLMs from alary muscles are the T-box factor Org-1 (Drosophila Tbx1) and the LIM homeodomain factor Tup (Drosophila Islet1) [2]. However, the events downstream of Org-1 and Tup that exert dedifferentiation and fragmentation of alary muscles have been unknown. In the present report, we shed light on the initiation of this first step of transdifferentiation and show that AM lineage specific activation of Yorkie (Yki), the transcriptional co-activator of the transcription factor Scalloped (Sd), has a key role in initiating AM lineage reprogramming. An additional necessary input comes from active dJNK signaling, which contributes to the inactivation of the Hippo kinase cascade upstream of Yki and furthermore activates dJun. The synergistic activities of the Yki/Sd and dJun/dFos (AP-1) transcriptional activator complexes in the absence of Hippo activity initiate AM dedifferentiation and lead to the expression of Myc and piwi, which are crucial for different aspects of AM transdifferentiation. Our results provide new insights into the mechanisms that mediate muscle lineage plasticity during a cellular reprogramming process occurring in vivo.HighlightsDirect lineage reprogramming of alary muscles depends on Yorkie and JNKYorkie and JNK mediate reversal of syncytial muscle cell fateYki/Sd and AP-1 induce alary muscle dedifferentiation synergisticallyYki dependent Myc induces and Piwi mediates reprogramming of alary muscles
Mitochondrial architecture rearrangements produce asymmetrical nonadaptive mutational pressures that subvert the phylogenetic reconstruction in Isopoda
Authors: Zhang Dong , Zou Hong , Hua Cong-Jie , Li Wen-Xiang , Mahboob Shahid , Al-Ghanim Khalid Abdullah , Al-Misned Fahad , Jakovlić Ivan , Wang Gui-Tang 
Published: April 2019

AbstractThe phylogeny of Isopoda, a speciose order of crustaceans, remains unresolved, with different datasets often producing starkly incongruent phylogenetic hypotheses. We hypothesised that extreme diversity in their life histories might be causing compositional heterogeneity/heterotachy in their mitochondrial genomes, and compromising the phylogenetic reconstruction. We tested the effects of different datasets (mitochondrial, nuclear, nucleotides, amino acids, concatenated genes, individual genes, gene orders), phylogenetic algorithms (assuming data homogeneity, heterogeneity, and heterotachy), and partitioning; and found that almost all of them produced unique topologies. As we also found that mitogenomes of Asellota and two Cymothoida families (Cymothoidae and Corallanidae) possess inversed base (GC) skew patterns in comparison to other isopods, we concluded that inverted skews cause long-branch attraction phylogenetic artefacts between these taxa. These asymmetrical skews are most likely driven by multiple independent inversions of origin of replication (i.e., nonadaptive mutational pressures). Although the PhyloBayes CAT-GTR algorithm managed to attenuate some of these artefacts (and outperform partitioning), mitochondrial data have limited applicability for reconstructing the phylogeny of Isopoda. Regardless of this, our analyses allowed us to propose solutions to some unresolved phylogenetic debates, and support Asellota are the most likely candidate for the basal isopod branch. As our findings show that architectural rearrangements can produce major compositional biases even on short evolutionary timescales, the implications are that proving the suitability of data via composition skew analyses should be a prerequisite for every study that aims to use mitochondrial data for phylogenetic reconstruction, even among closely related taxa.
Correlation of mRNA delivery timing and protein expression in lipid-based transfection
Authors: Reiser A. , Woschée D. , Mehrotra N. , Krzysztoń R. , Strey H. H. , Rädler J. O. 
Published: April 2019

AbstractNon-viral gene delivery is constrained by the dwell time that most synthetic nucleic acid nanocarriers spend inside endosomal compartments. In order to overcome this endosomal-release bottleneck, methods are required that measure nanocarrier uptake kinetics and transfection efficiency simultaneously. Here, we employ live-cell imaging on single-cell arrays (LISCA) to study the delivery-time distribution of lipid-based mRNA complexes under varied serum conditions. By fitting a translation-maturation model to hundreds of individual eGFP reporter fluorescence time courses, the protein expression onset times and the expression rates after transfection are determined. Using this approach, we find that delivery timing and protein expression rates are not intrinsically correlated at the single-cell level, even though population-averaged values of both parameters conjointly change as a function of increasing external serum protein fraction. Lipofectamine mediated delivery showed decreased transfection efficiency and longer delivery times with increasing serum protein concentration. This is in contrast to ionizable lipid nanoparticles (LNPs) mediated transfer, which showed increased efficiency and faster uptake in the presence of serum. In conclusion, the interdependences of single-cell expression rates and onset timing provide additional clues on uptake and release mechanisms, which are useful for improving nucleic acid delivery.
Targeted sequence capture outperforms RNA-Seq and degenerate-primer PCR cloning for sequencing the largest mammalian multi-gene family
Authors: Yohe Laurel R. , Davies Kalina T. J. , Simmons Nancy B. , Sears Karen E. , Dumont Elizabeth R. , Rossiter Stephen J. , Dávalos Liliana M. 
Published: April 2019

AbstractMultigene families evolve from single-copy ancestral genes via duplication, and typically encode proteins critical to key biological processes. Molecular analyses of these gene families require high-confidence sequences, but the high sequence similarity of the members can create challenges for both sequencing and downstream analyses. Focusing on the common vampire bat,Desmodus rotundus, we evaluated how different sequencing approaches performed in recovering the largest mammalian protein-coding multigene family:olfactory receptors(OR). Using the common vampire bat genome as a reference, we determined the proportion of putatively protein-coding receptors recovered by: 1) amplicons from degenerate primers sequenced via Sanger technology, 2) RNA-Seq of the main olfactory epithelium, and 3) those genes “captured” with probes designed from transcriptomes of closely-related species. Our initial re-annotation of the high-quality vampire bat genome resulted in >400 intactORgenes, more than double the number based on original estimates. Sanger-sequenced amplicons performed the poorest among the three approaches, detecting <33% of receptors in the genome. In contrast, the transcriptome reliably recovered >50% of the annotated genomicORs, and targeted sequence capture recovered nearly 75% of annotated genes. Each sequencing approach assembled high-quality sequences, even if it did not recover all putative receptors in the genome. Therefore, variation among assemblies was caused by low coverage of some receptors, rather than high rates of assembly error. Given this variability, we caution against using the counts of number of intact receptors per species to model the birth-death process of multigene families. Instead, our results support the use of orthologous sequences to explore and model the evolutionary processes shaping these genes.
Shared genetic etiology between obsessive-compulsive disorder, obsessive-compulsive symptoms in the population, and insulin signaling
Authors: Bralten Janita , Widomska Joanna , De Witte Ward , Yu Dongmei , Mathews Carol A. , Scharf Jeremiah M. , Buitelaar Jan , Crosbie Jennifer , Schachar Russell , Arnold Paul , Lemire Mathieu , Burton Christie L. , Franke Barbara , Poelmans Geert 
Published: April 2019

AbstractObjectiveObsessive-compulsive symptoms (OCS) in the population have been linked to obsessive-compulsive disorder (OCD) in genetic and epidemiological studies. Insulin signaling has been implicated in OCD. We extend previous work by assessing genetic overlap between OCD, population-based OCS, and central nervous system (CNS) and peripheral insulin signaling.MethodsWe conducted genome-wide association studies (GWASs) in the population-based Philadelphia Neurodevelopmental Cohort (PNC, 650 children and adolescents) of the total OCS score and six OCS factors from an exploratory factor analysis of 22 questions. Subsequently, we performed polygenic risk score (PRS) analysis to assess shared genetic etiologies between clinical OCD (using GWAS data from the Psychiatric Genomics Consortium), the total OCS score and OCS factors. We then performed gene-set analyses with a set of OCD-linked genes centered around CNS insulin-regulated synaptic function and PRS analyses for five peripheral insulin signaling-related traits. For validation purposes, we explored data from the independent Spit for Science population cohort (5047 children and adolescents).ResultsIn the PNC, we found a shared genetic etiology between OCD and ‘impairment’, ‘contamination/cleaning’ and ‘guilty taboo thoughts’. In the Spit for Science cohort, we were able to validate the finding for ‘contamination/cleaning’, and additionally observed genetic sharing between OCD and ‘symmetry/counting/ordering’. The CNS insulin-linked gene-set associated with ‘symmetry/counting/ordering’. We also identified genetic sharing between peripheral insulin signaling-related traits (type 2 diabetes and the blood levels of HbA1C, fasting insulin and 2 hour glucose) and OCD as well as certain OCS.ConclusionsOCD, OCS in the population and insulin-related traits share genetic risk factors, indicating a common etiological mechanism underlying somatic and psychiatric disorders.
Pericytes enable effective angiogenesis in the presence of pro-inflammatory signals
Authors: Kang Tae-Yun , Bocci Federico , Jolly Mohit Kumar , Levine Herbert , Onuchic José Nelson , Levchenko Andre 
Published: April 2019

AbstractAngiogenesis frequently occurs in the context of acute or persistent inflammation. The complex interplay of pro-inflammatory and pro-angiogenic cues is only partially understood. Using a new experimental model permitting exposure of developing blood vessel sprouts to multiple combinations of diverse biochemical stimuli and juxtacrine cell interactions, we present evidence that a pro-inflammatory cytokine, tumor necrosis factor (TNF), can have both pro- and anti-angiogenic effects, depending on the dose and the presence of pericytes. In particular, we find that pericytes can rescue and enhance angiogenesis in the presence of otherwise inhibitory high TNF doses. This sharp switch from pro- to anti-angiogenic effect of TNF observed with an escalating dose of this cytokine, as well as the effect of pericytes are explained by a mathematical model trained on the biochemical data. Furthermore, this model was predictive of the effects of diverse combinations of pro-and anti-inflammatory cues, and variable pericyte coverage. The mechanism supports the effect of TNF and pericytes as modulating signaling networks impinging in Notch signaling and specification of the Tip and Stalk phenotypes. This integrative analysis elucidates the plasticity of the angiogenic morphogenesis in the presence of diverse and potentially conflicting cues, with immediate implications for many physiological and pathological settings.
PyRates – A Python Framework for rate-based neural Simulations
Authors: Gast Richard , Rose Daniel , Möller Harald E. , Weiskopf Nikolaus , Knösche Thomas R. 
Published: April 2019

AbstractIn neuroscience, computational modeling has become an important source of insight into brain states and dynamics. A basic requirement for computational modeling studies is the availability of efficient software for setting up models and performing numerical simulations. While many such tools exist for different families of neural models, there is a lack of tools allowing for both a generic model definition and efficiently parallelized simulations. In this work, we present PyRates, a Python framework that provides the means to build a large variety of neural models as a graph. PyRates provides intuitive access to and modification of all mathematical operators in a graph, thus allowing for a highly generic model definition. For computational efficiency and parallelization, the model graph is translated into atensorflow-based compute graph. Using the example of two different neural models belonging to the family of rate-based population models, we explain the mathematical formalism, software structure and user interfaces of PyRates. We then show via numerical simulations that the behavior shown by the model implementations in PyRates is consistent with the literature. Finally, we demonstrate the computational capacities and scalability of PyRates via a number of benchmark simulations of neural networks differing in size and connectivity.
Inhibiting fibroblast aggregation in skin wounds unlocks developmental pathway to regeneration
Authors: Seifert Ashley W. , Cook Adam B. , Shaw Douglas 
Published: April 2019

ABSTRACTSalamanders are capable of full-thickness skin regeneration where removal of epidermis, dermis and hypodermis results in scar-free repair. What remains unclear is whether regeneration of these tissues recapitulates the cellular events of skin development or occurs through a process unique to regenerative healing. Unfortunately, information on the post-embryonic development of salamander skin is severely lacking, having focused on compartments or cell types, but never on the skin as a complete organ. By examining coordinated development of the epidermis and dermis in axolotls we establish six distinct stages of skin development (I-VI): I-V for normally paedomorphic adults and a sixth stage following metamorphosis. Raising animals either in isolation (zero density pressure) or in groups (density pressure) we find that skin development progresses as a function of animal size and that density directly effects developmental rate. Using keratins, p63, and proliferative markers, we show that although the epidermis lacks visible stratification at early stages of skin development, when the dermis transforms into the stratum spongiosum and stratum compactum keratinocytes differentiate into at least three distinct phenotypes that reveal a cryptic stratification program uncoupled from metamorphosis. Lastly, comparing skin regeneration to skin development, we find that dermal regeneration occurs through a unique process, relying heavily on remodeling of the wound extracellular matrix, rather than proceeding through direct development of a dermal lamella produced by the epidermis. By preventing fibroblast influx into the wound bed using beryllium nitrate, we show that in the absence of fibroblast generated ECM production skin regeneration occurs through an alternate route that recapitulates development.
Elementary Growth Modes provide a molecular description of cellular self-fabrication
Authors: de Groot Daan H. , Hulshof Josephus , Teusink Bas , Bruggeman Frank J. , Planqué Robert 
Published: April 2019

AbstractA major aim of biology is to predict phenotype from genotype. Here we ask if we can describe all possible molecular states (phenotypes) for a cell that fabricates itself at a constant rate, given its enzyme kinetics and the stoichiometry of all reactions (the genotype). For this, we must understand the autocatalytic process of cellular growth which is inherently nonlinear: steady-state self-fabrication requires a cell to synthesize all of its components, including metabolites, enzymes and ribosomes, in the proportions that exactly match its own composition – the growth demand thus depends on the cellular composition. Simultaneously, the concentrations of these components should be tuned to accomplish this synthesis task – the cellular composition thus depends on the growth demand. We here derive a theory that describes all phenotypes that solve this circular problem; the basic equations show how the concentrations of all cellular components and reaction rates must be balanced to get a constant self-fabrication rate. All phenotypes can be described as a combination of one or more minimal building blocks, which we call Elementary Growth Modes (EGMs). EGMs can be used as the theoretical basis for all models that explicitly model self-fabrication, such as the currently popular Metabolism and Expression models. We then used our theory to make concrete biological predictions: we find that natural selection for maximal growth rate drives microorganisms to states of minimal phenotypic complexity: only one EGM will be active when cellular growth rate is maximised. The phenotype of a cell is only extended with one more EGM whenever growth becomes limited by an additional biophysical constraint, such as a limited solvent capacity of a cellular compartment. Our theory starts from basic biochemical and evolutionary considerations, and describes unicellular life, both in growth-promoting and in stress-inducing environments, in terms of EGMs, the universal building blocks of self-fabrication and a cell’s phenotype.
A generalized framework of AMOVA with any number of hierarchies and any level of ploidies
Authors: Huang Kang , Li Yuli , Dunn Derek W. , Zhang Pei , Li Baoguo 
Published: April 2019

AbstractThe analysis of molecular variance (AMOVA) is a widely used statistical model in the studies of population genetics and molecular ecology. The classical framework of AMOVA only supports haploid and diploid data, in which the number of hierarchies ranges from two to four. In practice, natural populations can be classified into more hierarchies, and polyploidy is frequently observed in contemporary species. The ploidy level may even vary within the same species, even within the same individual. We generalized the framework of AMOVA such that it can be used for any number of hierarchies and any level of ploidy. Based on this framework, we present four methods to account for the multilocus genotypic and allelic phenotypic data. We use simulated datasets and an empirical dataset to evaluate the performance of our framework. We make freely available our methods in a software, POLYGENE, which is freely available athttps://github.com/huangkang1987/.
Spatial clustering of inhibition in mouse primary visual cortex
Authors: Bista Pawan , D’Souza Rinaldo D. , Meier Andrew M. , Ji Weiqing , Burkhalter Andreas 
Published: April 2019

SUMMARYWhether mouse visual cortex contains orderly feature maps is debated. The overlapping pattern of geniculocortical (dLGN) inputs with M2 muscarinic acetylcholine receptor-rich patches in layer 1 (L1) suggests a non-random architecture. Here, we found that L1 inputs from the lateral posterior thalamus (LP) avoid patches and target interpatches. Channelrhodopsin-assisted mapping of EPSCs in L2/3 shows that the relative excitation of parvalbumin-expressing interneurons (PVs) and pyramidal neurons (PNs) by dLGN, LP and cortical feedback are distinct and depend on whether the neurons reside in clusters aligned with patches or interpatches. Paired recordings from PVs and PNs shows that unitary IPSCs are larger in interpatches than patches. The spatial clustering of inhibition is matched by dense clustering of PV-terminals in interpatches. The results show that the excitation/inhibition balance across V1 is organized into patch and interpatch subnetworks which receive distinct long-range inputs and are specialized for the processing of distinct spatiotemporal features.
Effect of Electromagnetic Field (EMF) and Electric Field (EF) on Some Behavior of Honeybees (Apis melliferaL.)
Authors: Erdoğan Yaşar , Cengiz Mahir Murat 
Published: April 2019

ABSTRACTGeomagnetic field can be used by different magnetoreception mechanisms, for navigation and orientation by honeybees. The present study analyzed the effects of magnetic field on honeybees. This study was carried out in 2017 at the Bayburt University Beekeeping Application Station. In this study, the effect of Electro Magnetic field (EMF) and electric field (EF) on the time of finding the source of food of honeybees and the time of staying there were determined. The honeybees behaviors were analyzed in the presence of external magnetic fields generated by Helmholtz coils equipment. The Electro Magnetic field values of the coils were fixed to 0 μT (90mV/m), 50 μT (118 mV/m), 100 μT (151 mV/m), 150 μT (211 mV/m), 200 μT (264 mV/m). Petri dishes filled with sugar syrup were placed in the center of the coils. According to the study, honeybees visited at most U1 (mean =21.0±17.89 bees) and at least U5 (mean =10.82±11.77 bees). Honeybees waited for the longest time in U1 (mean =35.27±6.97 seconds) and at least in U5 (mean =12.28±5.58 seconds). According to the results obtained from this first study showed that honeybees are highly affected by electromagnetic radiation and electric field.SummaryHoneybees uses the magnetic field of the earth to to determine their direction. Nowadays, the rapid spread of electrical devices and mobile towers leads to an increase in man-made EMF. This causes honeybees to lose their orientation and thus lose their hives.
A rapid and automated sample-to-result Candida auris real-time PCR assay for high-throughput testing of surveillance samples with BD MAX™ open system
Authors: Leach L. , Russell A. , Zhu Y. , Chaturvedi S. , Chaturvedi V. 
Published: April 2019

ABSTRACTThe multidrug-resistant yeast pathogen Candida auris continues to cause outbreaks and clusters of clinical cases worldwide. Previously, we developed a real-time PCR assay for the detection of C. auris from surveillance samples (Leach et al. JCM. 2018: 56, e01223-17). The assay played a crucial role in the ongoing investigations of C. auris outbreak in New York City. To ease the implementation of the assay in other laboratories, we developed an automated sample-to-result real-time C. auris PCR assay using BD MAX™ open system. We optimized sample extraction at three different temperatures and four incubation periods. Sensitivity was determined using eight pools of patient samples, and specificity was calculated using four clades of C. auris, and closely and distantly related yeasts. Three independent extractions and testing of two patient sample pools in the quadruplicate yielded assay precision. BD MAX™ optimum assay conditions were: DNA extraction at 75°C for 20 min, and the use of PerfeCTa Multiplex qPCR ToughMix. The limit of detection (LOD) of the assay was one C. auris CFU/PCR reaction. We detected all four clades of C. auris without cross-reactivity to other yeasts. Of the 110 patient surveillance samples tested, 50 were positive for C. auris using the BD MAX™ System with 96% clinical sensitivity and 94% accuracy compared to the manual assay. BD MAX™ assay allows high-throughput C. auris screening of 180 surveillance samples in a 12-hour workday.