bluuebunny/crossref_metadata_2025 huggingface dataset:
Pattern of early human-to-human transmission of Wuhan 2019-nCoV
Authors: Riou Julien , Althaus Christian L.
Published: January 2020

On December 31, 2019, the World Health Organization was notified about a cluster of pneumonia of unknown aetiology in the city of Wuhan, China. Chinese authorities later identified a new coronavirus (2019-nCoV) as the causative agent of the outbreak. As of January 23, 2020, 655 cases have been confirmed in China and several other countries. Understanding the transmission characteristics and the potential for sustained human-to-human transmission of 2019-nCoV is critically important for coordinating current screening and containment strategies, and determining whether the outbreak constitutes a public health emergency of international concern (PHEIC). We performed stochastic simulations of early outbreak trajectories that are consistent with the epidemiological findings to date. We found the basic reproduction number,R0, to be around 2.2 (90% high density interval 1.4—3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of a similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and the 1918 pandemic influenza. These findings underline the importance of heightened screening, surveillance and control efforts, particularly at airports and other travel hubs, in order to prevent further international spread of 2019-nCoV.
Mineralized collagen scaffolds fabricated with amniotic membrane matrix increase osteogenesis under inflammatory conditions
Authors: Dewey Marley J. , Johnson Eileen M. , Slater Simona T. , Milner Derek J. , Wheeler Matthew B. , Harley Brendan A.C.
Published: January 2020

Defects in craniofacial bones occur congenitally, after high-energy impacts, and during the course of treatment for stroke and cancer. These injuries are difficult to heal due to the overwhelming size of the injury area and the inflammatory environment surrounding the injury. Significant inflammatory response after injury may greatly inhibit regenerative healing. We have developed mineralized collagen scaffolds that can induce osteogenic differentiation and matrix biosynthesis in the absence of osteogenic media or supplemental proteins. The amniotic membrane is derived from placentas and has been recently investigated as an extracellular matrix to prevent chronic inflammation. Herein, we hypothesized that a mineralized collagen-amnion composite scaffold could increase osteogenic activity in the presence of inflammatory cytokines. We report mechanical properties of a mineralized collagen-amnion scaffold and investigated osteogenic differentiation and mineral deposition of porcine adipose derived stem cells within these scaffolds as a function of inflammatory challenge. Incorporation of amniotic membrane matrix promotes osteogenesis similarly to un-modified mineralized collagen scaffolds, and increases in mineralized collagen-amnion scaffolds under inflammatory challenge. Together, these findings suggest that a mineralized collagen-amnion scaffold may provide a beneficial environment to aid craniomaxillofacial bone repair, especially in the course of defects presenting significant inflammatory complications.
Estimation of Full-Length TprK Diversity inTreponema pallidumsubspeciespallidum
Authors: Addetia Amin , Lin Michelle , Phung Quynh , Xie Hong , Huang Meei-Li , Ciccarese Giulia , Dal Conte Ivano , Cusini Marco , Drago Francesco , Giacani Lorenzo , Greninger Alexander L.
Published: January 2020

Immune evasion and disease progression ofTreponema pallidumsubspeciespallidumare associated with sequence diversity in the hypervariable, putative outer membrane protein TprK. Previous attempts to study variation within TprK have sequenced at depths insufficient to fully appreciate the hypervariable nature of the protein, failed to establish linkage between the protein’s 7 variable regions, or were conducted on strains passed through rabbits. As a consequence, a complete profiling oftprKduring infection in the human host is still lacking. Furthermore, prior studies examining howT. pallidumuses its repertoire of genomic donor sites to generate diversity within the V regions of thetprKalso yielded a partial understanding of this process, due to the limited number oftprKalleles examined. In this study, we used short- and long-read deep sequencing to directly characterize full-lengthtprKalleles fromT. pallidumcollected from early lesions of patients attending two STD clinics in Italy. Our data, combined with recent data available on ChineseT. pallidumstrains, show the near complete absence of overlap in TprK sequences among the 41 strains profiled to date. Moreover, our data allowed us to redefine the boundaries oftprKV regions, identify 55 donor sites, and estimate the total number of TprK variants thatT. pallidumcan potentially generate. Altogether, our results support howT. pallidumTprK antigenic variation system is an unsurmountable obstacle for the human immune system to naturally achieve infection eradication, and reiterate the importance of this mechanism for pathogen persistence in the host.

Importance

Syphilis continues to be a significant public health issue in both low- and high-income nations, including the United States, where the number of infectious syphilis cases has increased dramatically over the past five years.T. pallidum, the causative agent of syphilis, encodes an outer membrane protein TprK that undergoes segmental gene conversion to constantly create new sequences. We performed deep TprK profiling to understand full-length TprK diversity inT. pallidum-positive clinical specimens and compared these to all samples for which TprK deep sequencing is available. We found almost no overlap in TprK sequences between different patients. We further estimate that the total baseline junctional diversity of full-length TprK rivals that of current estimates of the human adaptive immune system. These data underscore the immunoevasive ability of TprK that allowsT. pallidumto establish lifelong infection.
Divided Attention in Perception: A Unified Analysis of Dual-Task Deficits and Congruency Effects
Authors: Palmer John , White Alex L. , Moore Cathleen M. , Boynton Geoffrey M.
Published: January 2020

How well can one perceive simultaneous stimuli at two widely spaced visual locations? Are the stimuli processed independently? If not, does the dependency affect perception, disrupt signals in later stages, or both? To address these questions, we measured effects of divided attention using a dual-task paradigm with stimuli presented in noise on either side of fixation. This paradigm was applied to detecting Gabor patches and to the semantic categorization of words. We measureddual-task deficitswhich are a decline in mean performance for a dual task compared to a single task. There was such a deficit for categorizing two words but relatively little deficit for detecting two Gabors. We also measuredcongruency effectswhich are when performance at one location depends on whether the stimulus at the other location requires the same response. There was such a congruency effect for detecting two Gabors but relatively little congruency effect for categorizing two words. Further experiments were consistent with the dual-task deficit in word categorization being perceptual, but the congruency effect in Gabor detection being due to later processes. Results of additional experiments showed that the congruency effect was consistent with either graded selection errors or with all-or-none selection followed by graded interactive processing. To answer our opening question: for Gabor detection, perceptual processes were largely independent but later processes caused congruency effects; for word categorization, perceptual processes had capacity limits but even in combination with later processes caused relatively little congruency effects. In summary, there was evidence for two different kinds of dependency. Such complementary dependencies are inconsistent with theories of divided attention that depend on a single dependency such as a single resource or single source of interactive processing.
Designing Effective small interfering RNA for Post-Transcriptional Silencing of Human GREM1: A Comprehensive Bioinformatics Approach
Authors: Ebenezer Asiedu
Published: January 2020

Human gremlin-1 is a physiologically versatile signaling molecule that has been associated with several human diseases including cancer. The ability of gremlin-1 to induce fibrosis in organs and transduce angiogenesis makes it a target for cancer therapy. RNAi-based therapy has proven to be very efficient and specific in tumor growth inhibition. The efficacy and specificity of siRNA-mediated gene silencing depends on the designing approaches. Here, empirical guidelines for siRNA design and comprehensive target site availability analysis were used to select effective siRNA from a plethora of potential candidates designed using several computation algorithms. Then, the selected siRNA candidates were subjected to stringent similarity searches in order to obtain siRNA candidates with reduced off-target effects (high specificity). The best candidates were compared to experimentally successful gremlin-1 siRNAs in order to predict the silencing potency of the selected siRNAs. siRNA-6 (sense strand: 5’-CCAAGAAAUUCACUACCAU-3’), siRNA-7 (sense strand: 5’-CCAUGAUGGUCACACUCAA-3’) and siRNA-47 (sense strand: 5’-GGCCCAGCACAAUGACUCA-3’) were predicted to be highly effective siRNA candidates for gremlin-1 silencing. These siRNAs can be considered for RNAi-based therapy because off-target effects are predicted to be minimal.
Maternal Anxious Attachment Style is Associated with Reduced Mother-Child Brain-to-Brain Synchrony During Passive TV Viewing
Authors: Azhari Atiqah , Gabrieli Giulio , Bizzego Andrea , Bornstein Marc H. , Esposito Gianluca
Published: January 2020

Synchrony in developmental science reflects the coordination of mother and child to the same mental state. Mentalisation processes are influenced by individual attachment styles. A mother with an anxious-related attachment style tends to engage in emotional mentalisation that relies on her child’s social cues. During an everyday joint activity of watching television shows together, we hypothesised that anxiously-attached mothers are less able to match their mental state to characters in the shows as their attention is likely detracted from the show and directed towards the child. We predict that this mismatch in mother’s and child’s emotional states would be reflected in reduced dyadic brain-to-brain synchrony. To test this hypothesis, we profiled mothers’ Maternal Anxiety score using the Preoccupation and Need for Approval subscales of the Attachment Style Questionnaire (ASQ) and used functional Near-infrared Spectroscopy (fNIRS) hyperscanning with 33 mother-child dyads to measure prefrontal cortex (PFC) synchrony while the dyads watched three 1-min animation videos together. Greater Maternal Anxiety is associated with less synchrony in the medial right prefrontal cluster implicated in mentalisation processes. Anxiously-attached mothers appear to exhibit less brain-to-brain synchrony with their child which suggests differences in intersubjective shared experiences that potentially undermines the quality of bonding during everyday joint activities.
Enhancing CO2-valorization usingClostridium autoethanogenumfor sustainable fuel and chemicals production
Authors: Heffernan James K. , Valgepea Kaspar , de Souza Pinto Lemgruber Renato , Casini Isabella , Plan Manuel , Tappel Ryan , Simpson Sean D. , Köpke Michael , Nielsen Lars K. , Marcellin Esteban
Published: January 2020

Acetogenic bacteria can convert waste gases into fuels and chemicals. Design of bioprocesses for waste carbon valorization requires quantification of steady-state carbon flows. Here, steady-state quantification of autotrophic chemostats containingClostridium autoethanogenumgrown on CO2and H2revealed that captured carbon (460 ± 80 mmol/gDCW/day) had a significant distribution to ethanol (54 ± 3 mol% with a 2.4 ± 0.3 g/L titer). We were impressed with this initial result, but also observed limitations to biomass concentration and growth rate. Metabolic modelling predicted culture performance and indicated significant metabolic adjustments when compared to fermentation with CO as the carbon source. Moreover, modelling highlighted flux to pyruvate, and subsequently reduced ferredoxin, as a target for improving CO2and H2fermentation. Supplementation with a small amount of CO enabled co-utilisation with CO2, and enhanced CO2fermentation performance significantly, while maintaining an industrially relevant product profile. Additionally, the highest specific flux through the Wood-Ljungdahl pathway was observed during co-utilization of CO2and CO. Furthermore, the addition of CO led to superior CO2-valorizing characteristics (9.7 ± 0.4 g/L ethanol with a 66 ± 2 mol% distribution, and 540 ± 20 mmol CO2/gDCW/day). Similar industrial processes are commercial or currently being scaled up, indicating CO-supplemented CO2and H2fermentation has high potential for sustainable fuel and chemical production. This work also provides a reference dataset to advance our understanding of CO2gas fermentation, which can contribute to mitigating climate change.
Analysis of cell-associated DENV RNA by oligo(dT) primed 5’ capture scRNAseq
Authors: Sanborn Mark , Li Tao , Victor Kaitlin , Siegfried Hayden , Fung Christian , Rothman Alan L. , Srikiatkhachorn Anon , Fernandez Stefan , Ellison Damon , Jarman Richard G. , Friberg Heather , Berry Irina Maljkovic , Currier Jeffrey R. , Waickman Adam T
Published: January 2020

Dengue is one of the most widespread vector-borne viral diseases in the world. However, the size, heterogeneity, and temporal dynamics of the cell-associated viral reservoir during acute dengue virus (DENV) infection remains unclear. In this study, we analyzed cells infectedin vitrowith DENV and PBMC from an individual experiencing a natural DENV infection utilizing 5’ capture single cell RNA sequencing (scRNAseq). Both positive- and negative-sense DENV RNA was detected in reactions containing either an oligo(dT) primer alone, or in reactions supplemented with a DENV-specific primer. The addition of a DENV-specific primer did not increase the total amount of DENV RNA captured or the fraction of cells identified as containing DENV RNA. However, inclusion of a DENV-specific cDNA primer did increase the viral genome coverage immediately 5’ to the primer binding site. Furthermore, while the majority of intracellular DENV sequence captured in this analysis mapped to the 5’ end of the viral genome, distinct patterns of enhanced coverage within the DENV polyprotein coding region were observed. The 5’ capture scRNAseq analysis of PBMC not only recapitulated previously published reports by detecting virally infected memory and naïve B cells, but also identified cell-associated genomic variants not observed in contemporaneous serum samples. These results demonstrate that oligo(dT) primed 5’ capture scRNAseq can detect DENV RNA and quantify virus-infected cells in physiologically relevant conditions, and provides insight into viral sequence variability within infected cells.

IMPORTANCE

Dengue is one of the most widespread vector-borne viral diseases in the world. However, it is still unclear which cells harbor virus during DENV infection, and how viral reservoirs in serum and infected cells are related. These results demonstrate for the first time that intracellular DENV RNA can be identified and infected cells quantified by 5’ capture scRNAseq. This strategy provides a significantly greater throughput and higher sensitivity than previously published methods and has the potential to provide additional information on the genomic heterogeneity of intracellular DENV RNA.
Rapid and scalable profiling of nascent RNA with fastGRO
Authors: Barbieri Elisa , Hill Connor , Quesnel-Vallieres Mathieu , Barash Yoseph , Gardini Alessandro
Published: January 2020

Genome-wide profiling of nascent RNA has become a fundamental tool to study transcription regulation. Over the past decade, next-generation sequencing has fostered development of a handful of techniques (i.e. GRO-seq, PRO-seq, TT-seq and NET-seq) that map unprocessed transcripts originating from both the coding and the noncoding portion of the genome. Unlike steady-state RNA sequencing, nascent RNA profiling mirrors the real-time activity of RNA Polymerases and provides an accurate readout of transcriptome-wide variations that occur during short time frames (i.e. response to external stimuli or rapid metabolic changes). Some species of nuclear RNAs, albeit functional, have a short half-life and can only be accurately gauged by nascent RNA techniques (i.e. lincRNAs and eRNAs). Furthermore, these techniques capture uncapped post-cleavage RNA at termination sites or promoter-associated antisense RNAs, providing a unique insight into RNAPII dynamics and processivity.

Here we present a run-on assay with 4s-UTP labelling, followed by reversible biotinylation and affinity purification via streptavidin. Our protocol allows streamlined sample preparation within less than 3 days. We named the technique fastGRO (fast Global Run-On). We show that fastGRO is highly reproducible and yields a more complete and extensive coverage of nascent RNA than comparable techniques. Importantly, we demonstrate that fastGRO is scalable and can be performed with as few as 0.5×10^6 cells.
The dendritic spatial code: branch-specific place tuning and its experience-dependent decoupling
Authors: Rashid Shannon K. , Pedrosa Victor , Dufour Martial A. , Moore Jason J. , Chavlis Spyridon , Delatorre Rodrigo G. , Poirazi Panayiota , Clopath Claudia , Basu Jayeeta
Published: January 2020

Dendrites of pyramidal neurons integrate different sensory inputs, and non-linear dendritic computations drive feature selective tuning and plasticity. Yet little is known about how dendrites themselves represent the environment, the degree to which they are coupled to their soma, and how that coupling is sculpted with experience. In order to answer these questions, we developed a novel preparation in which we image soma and connected dendrites in a single plane across days usingin vivotwo-photon microscopy. Using this preparation, we monitored spatially tuned activity in area CA3 of the hippocampus in head-fixed mice running on a linear track. We identified “place dendrites”, which can stably and precisely represent both familiar and novel spatial environments. Dendrites could display place tuning independent of their connected soma and even their sister dendritic branches, the first evidence for branch-specific tuning in the hippocampus. In a familiar environment, spatially tuned somata were more decoupled from their dendrites as compared to non-tuned somata. This relationship was absent in a novel environment, suggesting an experience dependent selective gating of dendritic spatial inputs. We then built a data-driven multicompartment computational model that could capture the experimentally observed correlations. Our model predicts that place cells exhibiting branch-specific tuning have more flexible place fields, while neurons with homogenous or co-tuned dendritic branches have higher place field stability. These findings demonstrate that spatial representation is organized in a branch-specific manner within dendrites of hippocampal pyramidal cells. Further, spatial inputs from dendrites to soma are selectively and dynamically gated in an experience-dependent manner, endowing both flexibility and stability to the cognitive map of space.

One sentence summary

Hippocampal pyramidal cells show branch-specific tuning for different place fields, and their coupling to their soma changes with experience of an environment.
The allosteric control mechanism of bacterial glycogen biosynthesis disclosed by cryoEM
Authors: Cifuente Javier O. , Comino Natalia , D’Angelo Cecilia , Marina Alberto , Gil-Carton David , Albesa-Jové David , Guerin Marcelo E.
Published: January 2020

Glycogen and starch are the major carbon and energy reserve polysaccharides in nature, providing living organisms with a survival advantage. The evolution of the enzymatic machinery responsible for the biosynthesis and degradation of such polysaccharides, led the development of mechanisms to control the assembly and disassembly rate, to store and recover glucose according to cell energy demands. The tetrameric enzyme ADP-glucose pyrophosphorylase (AGPase) catalyzes and regulates the initial step in the biosynthesis of both α-polyglucans. Importantly, AGPase displays cooperativity and allosteric regulation by sensing metabolites from the cell energy flux. The understanding of the allosteric signal transduction mechanisms in AGPase arises as a long-standing challenge. In this work, we disclose the cryoEM structures of the paradigmatic homotetrameric AGPase fromEscherichia coli(EcAGPase), in complex with either positive or negative physiological allosteric regulators, FBP and AMP respectively, both at 3.0 Å resolution. Strikingly, the structures reveal that FBP binds deeply into the allosteric cleft and overlaps the AMP site. As a consequence, FBP promotes a concerted conformational switch of a regulatory loop, RL2, from a ‘locked’ to a ‘free’ state, modulating ATP binding and activating the enzyme. This notion is strongly supported by our complementary biophysical and bioinformatics evidence, and a careful analysis of vast enzyme kinetics data on single-point mutants ofEcAGPase. The cryoEM structures uncover the residue interaction networks (RIN) between the allosteric and the catalytic components of the enzyme, providing unique details on how the signaling information is transmitted across the tetramer, from which cooperativity emerges. Altogether, the conformational states visualized by cryoEM reveal the regulatory mechanism ofEcAGPase, laying the foundations to understand the allosteric control of bacterial glycogen biosynthesis at the molecular level of detail.
NF90 Modulates Processing of a Subset of Human Pri-miRNAs
Authors: Grasso Giuseppa , Higuchi Takuma , Barbier Jérôme , Helsmoortel Marion , Lorenzi Claudio , Sanchez Gabriel , Bello Maxime , Ritchie William , Sakamoto Shuji , Kiernan Rosemary
Published: January 2020

MicroRNAs are predicted to regulate the expression of more than 60% of mammalian genes and play fundamental roles in most biological processes. Deregulation of miRNA expression is a hallmark of most cancers and further investigation of mechanisms controlling miRNA biogenesis is needed. The dsRNA-binding protein, NF90 has been shown to act as a competitor of Microprocessor for a limited number of pri-miRNAs. Here, we show that NF90 has a more widespread effect on pri-miRNA biogenesis than previously thought. Genome-wide approaches revealed that NF90 is associated with the stem region of 38 pri-miRNAs, in a manner that is largely exclusive of Microprocessor. Following loss of NF90, 22 NF90-bound pri-miRNAs showed increased abundance of mature miRNA products. NF90-targeted pri-miRNAs are highly stable, having a lower free energy and fewer mismatches compared to all pri-miRNAs. Mutations leading to less stable structures reduced NF90 binding while increasing pri-miRNA stability led to acquisition of NF90 association, as determined by RNA EMSA. NF90-bound and modulated pri-miRNAs are embedded in introns of host genes and expression of several host genes is concomitantly modulated. These data suggest that NF90 controls the processing of a subset of highly stable, intronic miRNAs.
Bacterial FtsZ induces mitochondrial fission in human cells
Authors: Spier Anna , Sachse Martin , Tham Nam To , Matondo Mariette , Cossart Pascale , Stavru Fabrizia
Published: January 2020

Mitochondria are key eukaryotic organelles that evolved from an intracellular bacterium, in a process involving bacterial genome rearrangement and streamlining. As mitochondria cannot formde novo, their biogenesis relies on growth and division. In human cells, mitochondrial division plays an important role in processes as diverse as mtDNA distribution, mitochondrial transport and quality control. Consequently, defects in mitochondrial division have been associated with a wide range of human pathologies. While several protists have retained key components of the bacterial division machinery, none have been detected in human mitochondria, where the dynamin-related protein Drp1, a cytosolic GTPase is recruited to the mitochondrial outer membrane, forming helical oligomers that constrict and divide mitochondria. Here, we created a human codon optimized version of FtsZ, the central component of the bacterial division machinery, and fused it to a mitochondrial targeting sequence. Upon expression in human cells, mt-FtsZ was imported into the mitochondrial matrix, specifically localizing at fission sites prior to Drp1 and significantly increasing mitochondrial fission levels. Our data suggests that human mitochondria have an internal, matrix-localized fission machinery, whose structure is sufficiently conserved as to accommodate bacterial FtsZ. We identified interaction partners of mt-FtsZ, and show that expression of PGAM5, FAM210, SFXN3 and MTCH1 induced mitochondrial fission. Our results thus represent an innovative approach for the discovery of novel critical mitochondrial fission components.
Design, optimization, and analysis of large DNA and RNA nanostructures through interactive visualization, editing, and molecular simulation
Authors: Poppleton Erik , Bohlin Joakim , Matthies Michael , Sharma Shuchi , Zhang Fei , Šulc Petr
Published: January 2020

This work seeks to remedy two deficiencies in the current nucleic acid nanotechnology software environment: the lack of both a fast and user-friendly visualization tool and a standard for common structural analyses of simulated systems. We introduce here oxView, a web browser-based visualizer that can load structures with over 1 million nucleotides, create videos from simulation trajectories, and allow users to perform basic edits to DNA and RNA designs. We additionally introduce open-source software tools for extracting common structural parameters to characterize large DNA/RNA nanostructures simulated using the coarse-grained modeling tool, oxDNA, which has grown in popularity in recent years and is frequently used to prototype new nucleic acid nanostructural designs, model biophysics of DNA/RNA processes, and rationalize experimental results. The newly introduced software tools facilitate the computational characterization of DNA/RNA designs by providing multiple analysis scripts, including mean structures and structure flexibility characterization, hydrogen bond fraying, and interduplex angles. The output of these tools can be loaded into oxView, allowing users to interact with the simulated structure in a 3D graphical environment and modify the structures to achieve the required properties. We demonstrate these newly developed tools by applying them toin silicodesign, optimization and analysis of a range of DNA and RNA nanostructures.
METTL4 catalyzes m6Am methylation inU2 snRNAto regulate pre-mRNA splicing
Authors: Goh Yeek Teck , Koh Casslynn W. Q. , Sim Donald Yuhui , Roca Xavier , Goh W. S. Sho
Published: January 2020

N6-methylation of 2’-O-methyladenosine (Am) in RNA occurs in eukaryotic cells to generateN6,2’-O-dimethyladenosine (m6Am). Identification of the methyltransferase responsible for m6Am catalysis has accelerated studies on the function of m6Am in RNA processing. While m6Am is generally found in the first transcribed nucleotide of mRNAs, the modification is also found internally withinU2 snRNA. However, the writer required for catalyzing internal m6Am formation had remained elusive. By sequencing transcriptome-wide RNA methylation at single-base-resolution, we identified human METTL4 as the writer that directly methylates Am atU2 snRNAposition 30 into m6Am. We found that METTL4 localizes to the nucleus and its conserved methyltransferase catalytic site is required forU2 snRNAmethylation. By sequencing human cells with overexpressedMettl4, we determined METTL4’sin vivotarget RNA motif specificity. In the absence ofMettl4in human cells,U2 snRNAlacks m6Am thereby affecting a subset of splicing events that exhibit specific features such as overall 3’ splice-site weakness with certain motif positions more affected than others. This study establishes that METTL4 methylation ofU2 snRNAregulates splicing of specific pre-mRNA transcripts.
Buildup and bistability in auditory streaming as an evidence accumulation process with saturation
Authors: Nguyen Quynh-Anh , Rinzel John , Curtu Rodica
Published: January 2020

A repeating triplet-sequenceABA_ of non-overlapping brief tones,AandB, is a valued paradigm for studying auditory stream formation and the cocktail party problem. The stimulus is “heard” either as a galloping pattern (integration) or as two interleaved streams (segregation); the initial percept is typically integration then followed by spontaneous alternations between segregation and integration, each being dominant for a few seconds. The probability of segregation grows over seconds, from near-zero to a steady value, defining the buildup function, BUF. Its stationary level increases with the difference in tone frequencies,DF, and the BUF rises faster. Percept durations haveDF-dependent means and are gamma-like distributed. Behavioral and computational studies usually characterize triplet streaming either during alternations or during buildup. Here, our experimental design and modeling encompass both. We propose a pseudo-neuromechanistic model that incorporates spiking activity in primary auditory cortex, A1, as input and resolves perception along two network-layers downstream of A1. Our model is straightforward and intuitive. It describes the noisy accumulation of evidence against the current percept which generates switches when reaching a threshold. Accumulation can saturate either above or below threshold; if below, the switching dynamics resemble noise-induced transitions from an attractor state. Our model accounts quantitatively for three key features of data: the BUFs, mean durations, and normalized dominance duration distributions, at variousDFvalues. It describes perceptual alternations without competition per se, and underscores that treating triplets in the sequence independently and averaging across trials, as implemented in earlier widely cited studies, is inadequate.

Author summary

Segregation of auditory objects (auditory streaming) is widely studied using ambiguous stimuli. A sequence of repeating tripletsABA_ of non-overlapping brief pure tones,AandB, frequency-separated, is a valued stimulus. Studies typically focus on one of two behavioral phases: the early (say, ten seconds) buildup of segregation from the default integration or later spontaneous alternations (bistability) between seconds-long integration and segregation percepts. Our experiments and modeling encompass both. Our novel, data-driven, evidence-accumulation model accounts for key features of the observations, taking as input recorded spiking activity from primary auditory cortex (as opposed to most existing, more abstract, models). Our results underscore that assessing individual triplets independently and averaging across trials, as in some earlier studies, is inadequate (lacking neuronal-accountability for percept duration statistics, the underlying basis of buildup). Further, we identify fresh parallels between evidence accumulation and competition as potential dynamic processes for choice in the brain.
Low ribosomal RNA genes copy number provoke genomic instability and chromosomal segment duplication events that modify global gene expression and plant-pathogen response
Authors: Picart-Picolo Ariadna , Grob Stefan , Picault Nathalie , Franek Michal , halter Thierry , Maier Tom R. , Llauro Christel , Jobet Edouard , Zhang Panpan , Vijayapalani Paramasivan , Baum Thomas J. , Navarro Lionel , Dvorackova Martina , Mirouze Marie , Pontvianne Frederic
Published: January 2020

Among the hundreds of ribosomal RNA (rRNA) gene copies organized as tandem repeats in the nucleolus organizer regions (NORs), only a portion is usually actively expressed in the nucleolus and participate in the ribosome biogenesis process. The role of these extra-copies remains elusive, but previous studies suggested their importance in genome stability and global gene expression. Because the nucleolus is also a platform for nuclear organization, we tested the impact of a decreased amount of rRNA gene copies on theArabidopsis thaliana3D genome organization and stability, using anA. thalianaline only containing 20% of rRNA gene copies (20rDNA line). Compared to the wild-type Col-0, the 20rDNA line shows several signs of genomic instability, such as variations in 3D genome organization, spontaneous double-strand breaks accumulation, transcriptomic changes, and higher DNA methylation level. Strikingly, using genomic and microscopic approaches, we identified seven large tandem duplications in direct orientation (TDDOs) ranging from 60 kb to 1.44 Mb. As a consequence, more than 600 genes were duplicated, often associated with an increase in their expression level. Among them, we found several upregulated genes involved in plant-pathogen response, which could explain why the 20rDNA line is hyper-resistant to both bacterial and nematode infections. Finally, we show that the TDDOs create gene fusions and/or truncations and we discuss their potential implications on plant genome evolution.
Can Intestinal Absorption of Dietary Protein Be Improved Through Early Exposure to Plant-Based Diet?
Authors: Molinari Giovanni S. , McCracken Vance J. , Wojno Michal , Rimoldi Simona , Terova Genciana , Kwasek Karolina
Published: January 2020

Nutritional Programming (NP) has been studied as a means of mitigating the negative effects of dietary plant protein (PP), but the optimal timing and mechanism behind NP are still unknown. The objectives of this study were: 1) To determine whether zebrafish (Danio rerio) can be programmed to soybean meal (SBM) through early feeding and broodstock exposure to improve SBM utilization; 2) To determine if NP in zebrafish affects expression of genes associated with intestinal nutrient uptake; 3) To determine if early stage NP and/or broodstock affects gene expression associated with intestinal inflammation or any morphological changes in the intestinal tract that might improve dietary SBM utilization. Two broodstocks were used to form the six experimental groups. One broodstock group received fishmeal (FM) diet (FMBS), while the other was fed (“programmed with”) SBM diet (PPBS). The first ((+) Control) and the second group ((-) Control) received FM and SBM diet for the entire study, respectively, and were progeny of FMBS. The last four groups consisted of a non-programmed(FMBS-X-PPandPPBS-X-PP)and a programmed group(FMBS-NP-PPandPPBS-NP-PP)from each of the broodstocks. The programming occurred through feeding with SBM diet during 13-23 dph. The non-control groups underwent a PP-Challenge, receiving SBM diet during 36-60 dph. During the PP-Challenge, both PPBS groups experienced significantly lower weight gains than the (+) Control group. NP in early life stages significantly increased the expression of PepT1 in PPBS-NP-PP, compared to PPBS-X-PP. NP also tended to increase the expression offabp2in the programmed vs. non-programmed groups of both broodstocks. The highest distal villus length-to-width ratio was observed in the dual-programmed group, suggesting an increase in surface area for nutrient absorption within the intestine. The results of this study suggest that NP during early life stages may increase intestinal absorption of nutrients from PP-based feeds.
A systematic review of scientific research focused on farmers in agricultural adaptation to climate change (2008-2017)
Authors: Yang Yao , Seyler Barnabas C. , Feng Miao , Tang Ya
Published: January 2020

Due to the severe consequences of climate change, associated risks to global food security, and the contribution of agriculture to greenhouse gas emissions, agriculture must necessarily adapt to meet these challenges. Many studies have therefore sought to investigate agricultural adaptation to climate change, and as key stakeholders in agriculture, farmers play a vital role in this process. There is a rapidly increasing corpus of scholarship on agricultural adaptation to climate change, with many studies beginning to incorporate survey methods to examine farmer perceptions and adaptation responses. Nevertheless, in-depth understanding of farmers worldwide is inadequate due to insufficiently robust methodologies, socio-economic disparities, and unequal geographic distribution. In this study, we searched and reviewed the existing peer-reviewed, English-language scientific articles published between 2008 and 2017 on agricultural adaptation to climate change that have incorporated farmers into their research methodologies. The main findings include the following: (1) a small but increasing number of studies focus on farmers in climate change adaptation; (2) the global geographic distribution of the reviewed studies is uneven, and many of the most vulnerable nations (e.g., lower-income/agricultural-dependent economies) have no representation at all; (3) there were diverse rationales and methods for incorporating farmers into the studies, and many of the methodological differences were due to practical and logistical limitations in lower-income/agricultural-dependent nations; and (4) studies were from multiple academic fields, indicating the need for more interdisciplinary collaboration moving forward because agricultural adaptation to climate change is too complex for a single discipline to fully explore. Although English is increasingly recognized as the “international language of science,” due to the challenge of language segmentation limiting broader understanding of global scholarship whenever possible, future reviews should be jointly conducted in both English and non-English languages.
Isolation and characterization of bovine herpes virus 5 (BHV5) from cattle in India
Authors: Kumar Naveen , Chander Yogesh , Riyesh Thachamvally , Khandelwal Nitin , Kumar Ram , Kumar Harish , Tripathi Bhupendra N. , Barua Sanjay
Published: January 2020

Bovine herpesvirus 1 (BHV1) and 5 (BHV5) are genetically and antigenically related alphaherpesviruses. Infection with one virus induces protective immunity against the other. However, disease associated with BHV1 and BHV5 varies significantly; whereas BHV1 infection is usually associated with rhinotracheitis and abortion, BHV5 causes encephalitis in cattle. BHV5 outbreaks are sporadic and mainly restricted to the South American countries. We report BHV5 infection for the first time from aborted cattle in India. Based on the characteristic cytopathic effects in MDBK cells, amplification of the viral genome in PCR, differential PCR for BHV1/BHV5, nucleotide sequencing and restriction endonuclease patterns, identity of the virus was confirmed as BHV5 subtype A. Serum samples from the aborted cattle strongly neutralized both BHV1 and BHV5 suggesting an active viral infection in the herd. UponUL27, UL44andUL54gene-based sequence and phylogenetic analysis, the isolated virus clustered with BHV5 strains and showed highest similarity with the Brazilian BHV5 strains.

Author Summary

BHV5 causes fatal meningoencephalitis that may result in a mortality rate of up to 100% in cattle. BHV5 is rarely associated with abortion and its distribution is restricted to South American countries. Only a few cases of this disease have been reported from other countries. For the first time, we provide a strong evidence of BHV5 infection from aborted cattle in India. The finding may necessitate inclusion of BHV5 test protocol in testing of semen for sexually transmitted diseases. Also, the isolated virus would be useful for developing diagnostic, prophylactic and therapeutic agents to combat BHV5 disease in the country.
Regulation of olfactory-based sex behaviors in the silkworm by genes in the sex-determination cascade
Authors: Xu Jun , Liu Wei , Yang Dehong , Chen Shuqing , Chen Kai , Liu Zulian , Yang Xu , Meng Jing , Zhu Guanheng , Dong Shuanglin , Zhang Yong , Zhan Shuai , Wang Guirong , Huang Yongping
Published: January 2020

Insect courtship and mating depend on integration of olfactory, visual, and tactile cues. Compared to other insects,Bombyx mori, the domesticated silkworm, has relatively simple sexual behaviors as it cannot fly. Here by using CRISPR/Cas and electrophysiological techniques we found that courtship and mating behaviors are regulated in male silk moths by mutating genes in the sex determination cascade belonging to two conserved pathways. Loss ofBmdsxgene expression significantly reduced the peripheral perception of the major pheromone component bombykol by reducing expression of the product of theBmOR1gene which completely blocked courtship in adult males. Interestingly, we found that mating behavior was regulated independently by another sexual differentiation gene,Bmfru.Loss ofBmfrucompletely blocked mating, but males displayed normal courtship behavior. Lack ofBmfruexpression significantly reduced the perception of the minor pheromone component bombykal due to the down regulation ofBmOR3expression; further, functional analysis revealed that loss of the product ofBmOR3played a key role in terminating male mating behavior. Our results suggest thatBmdsxandBmfruare at the base of the two primary pathways that regulate olfactory-based sexual behavior.

Author Summary

The fundamental insect sexual behaviors, courtship and mating, result from successful integration of olfactory, vision, tactile and other complex innate behaviors. In the widely used insect model,Drosophila melanogaster, the sex determination cascade genesfruitlessanddoublesexare involved in the regulation of courtship and mating behaviors; however, little is known about the function of these sexual differentiation genes in regulating sex behaviors of Lepidoptera. Here we combine genetics and electrophysiology to investigate regulation pathway of sexual behaviors in the model lepidopteran insect, the domesticated silk moth,Bombyx mori. Our results support the presence of two genetic pathways inB. mori, namedBmdsx-BmOR1-bombykol andBmfru-BmOR3-bombykal, which control distinct aspects of male sexual behavior that are modulated by olfaction. This is the first comprehensive report about the role of sex differentiation genes in the male sexual behavior in the silk moth.
Pesticides and transgenerational inheritance of pathologies: Designing, analysing and reporting rodent studies
Authors: Plewis Ian
Published: January 2020

The evidence for transgenerational transmission of pathologies in rodents exposed to pesticides is largely based on studies with weaknesses in design and analysis and a lack of transparency in reporting the results. This paper examines these methodological and statistical issues in detail. Its particular focus is on the estimation of ‘litter effects’: the tendency for rodents within a litter to be more alike than rodents in different litters. Appropriate statistical models were fitted to published data from a series of widely reported studies carried out at Washington State University. These studies were amalgamated into a single dataset in order to estimate these litter effects and the associated treatment effects. Litter effects varied by outcome and were often substantial. Consequently, the effective sample size was often substantially less than the number of observations with implications for the power of the studies. Moreover, the reported precision of the estimates of treatment effects was too low. These problems are exacerbated by unexplained missing data across generations. Researchers in the life sciences could be more cognisant of the guidelines established in medicine for reporting randomised controlled trials, particularly cluster randomised trials. More attention should be paid to the design and analysis of multi-generational rodent studies; their imperfections have important implications for assessments of the evidence relating to the risks of pesticides for public health.
Ameliorative effect of a quinazoline-based bromodomain inhibitor, CN210, on experimentally-induced Crohn’s disease-like murine ileitis via inhibition of inflammatory cytokine expression
Authors: Noguchi Takehisa , Hidaka Kyosuke , Kobayashi Satsuki , Matsumoto Kenjiro , Yoshioka Makoto , Yang Shyh-Ming , Maloney David J. , Kato Shinichi
Published: January 2020

Inhibitors of bromodomain and extra-terminal motif proteins (“BET inhibitors”) are emerging epigenetic therapeutics that exert their effects by suppressing the expression of genes that drive cancer and inflammation. The present study examined the anti-inflammatory effects of a quinazoline-based BET inhibitor, CN210, which also inhibits bromodomains of two paralogous histone acetyltransferases (HATs), such as cAMP-responsive element binding protein-binding protein (CBP) and p300. To assess its effectiveness against inflammatory bowel disease (IBD), CN210 was tested in an experimentally-induced murine Crohn’s disease (CD)-like ileitis model. Ileitis was induced in mice by subcutaneous administration of indomethacin and CN210 was given orally 30 min before and 24 h after the indomethacin administration. Whilst indomethacin produced severe ileitis accompanied by an increase in ileal mucosal myeloperoxidase (MPO) activity, administration of CN210 reduced the severity of ileitis in a dose-dependent manner and suppressed the MPO activity. Similarly, upregulation of inflammatory cytokines was observed in ileitis mucosa after indomethacin injection but this response was significantly attenuated by CN210 administration. To further characterize the effects of CN210 on inflammatory pathways, monocyte/macrophage-like cell line RAW264 treated with lipopolysaccharide (LPS) was exposed to CN210. CN210 significantly attenuated the expression of inflammatory cytokines and reversed the activation of NF-κB and MAP kinases induced by LPS. These findings suggest that CN210 ameliorates indomethacin-induced ileitis due at least in part to the inhibition of inflammatory cytokine expressionviaattenuation of NF-κB and MAP kinase pathways, thus representing a new mode of therapy for CD.
Structural and Functional NIR-II Fluorescence Bioimaging in Urinary System via Clinically Approved Dye Methylene Blue
Authors: Xue Dingwei , Wu Di , Lu Zeyi , Zebibula Abudureheman , Feng Zhe , Qian Jun , Li Gonghui
Published: January 2020

Accurate structural and functional imaging is vital for the diagnosis and prognosis of the urinary system diseases. Near-infrared region (NIR) II fluorescence imaging has shown advantages of high sensitivity, high safety, and fast feedback compared to the conventional imaging methods but limited to its clinical applicability. Herein, we first report that in vivo NIR-II fluorescence imaging of the urinary system enabled by clinically approved and renal-clearable NIR dye methylene blue, which can not only achieve clear invasive/non-invasive urography but also noninvasively detect renal function. These results demonstrate that MB assisted NIR-II fluorescence imaging holds great promise for invasive/noninvasive structural imaging of the urinary system clinically and investigation of renal function in animal models preclinically.