bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 Epidemic Outside China: 34 Founders and Exponential Growth
Authors: Li Yi , Liang Meng , Yin Xianhong , Liu Xiaoyu , Hao Meng , Hu Zixin , Wang Yi , Jin Li
Published: March 2020

Background

In December 2019, pneumonia infected with a novel coronavirus burst in Wuhan, China. Now the situation is almost controlled in China but is worse outside China. We aimed to build a mathematical model to capture the global trend of epidemics outside China.

Methods

In this retrospective, outside-China diagnosis number reported from Jan 21 to Feb 28, 2020 was downloaded from WHO website. We develop a simple regression model on these numbers:where Ntis the total diagnosed patient till theith day, t=1 at Feb 1.

Findings

Based on this model, we estimate that there have been about 34 unobserved founder patients at the beginning of spread outside China. The global trend is approximately exponential, with the rate of 10 folds every 19 days.

Research in context

Evidence before this study

In December 2019, pneumonia infected with a novel coronavirus burst in Wuhan, China. Now the situation is almost controlled in China but is worse outside China. Now there are 4,691 patients across 51 countries and territories outside China. We searched PubMed and the China National Knowledge Infrastructure database for articles published up to Feb 28, 2020, using the keywords “COVID”, “novel coronavirus”, “2019-nCoV” or “2019 novel coronavirus”. No published work about the global trend of epidemics outside China could be identified.

Added value of this study

We built a simple “log-plus” linear model to capture the global trend of epidemics outside China. We estimate that there have been about 34 unobserved founder patients at the beginning of spread outside China. The global trend is approximately exponential, with the rate of 10 folds every 19 days.

Implications of all the available evidence

With the limited number of data points and the complexity of the real situation, a straightforward model is expected to work better. Our model suggests that the COVID-19 disease follows an approximate exponential growth model stably at the very beginning. We predict that the number of confirmed patients outside China will increase ten folds in every 19 days without strong intervention by applying our model. Powerful actions on public health should be taken to combat this epidemic all over the world.
Interspecific Hybrids Show a Reduced Adaptive Potential Under DNA Damaging Conditions
Authors: Bautista Carla , Marsit Souhir , Landry Christian R
Published: March 2020

Hybridization may increase the probability of adaptation to extreme stresses. This advantage could be caused by an increased genome plasticity in hybrids, which could accelerate the search for adaptive mutations. High ultraviolet (UV) radiation is a particular challenge in terms of adaptation because it affects the viability of organisms by directly damaging DNA, while also challenging future generations by increasing mutation rate. Here we test if hybridization accelerates adaptive evolution in response to DNA damage, using yeast as a model. We exposed 180 populations of hybrids between species (Saccharomyces cerevisiaeandSaccharomyces paradoxus) and their parental strains to UV mimetic and control conditions for approximately 100 generations. Although we found that adaptation occurs in both hybrids and parents, hybrids achieved a lower rate of adaptation, contrary to our expectations. Adaptation to DNA damage conditions comes with a large and similar cost for parents and hybrids, suggesting that this cost is not responsible for the lower adaptability of hybrids. We suggest that the lower adaptive potential of hybrids in this condition may result from the interaction between DNA damage and the inherent genetic instability of hybrids.
Automatic encoding of a view-centered background image in the macaque temporal lobe
Authors: Chen He , Naya Yuji
Published: March 2020

Perceptual processing along the ventral visual pathway to the hippocampus is hypothesized to be substantiated by signal transformation from retinotopic space to relational space, which represents interrelations among constituent visual elements. However, our visual perception necessarily reflects the first person’s perspective based on the retinotopic space. To investigate this two-facedness of visual perception, we compared neural activities in the temporal lobe (anterior inferotemporal cortex, perirhinal and parahippocampal cortices, and hippocampus) between when monkeys gazed on an object and when they fixated on the screen center with an object in their peripheral vision. We found that in addition to the spatially invariant object signal, the temporal lobe areas automatically represent a large-scale background image, which specify the subject’s viewing location. These results suggest that a combination of two distinct visual signals on relational space and retinotopic space may provide the first person’s perspective serving for perception and presumably subsequent episodic memory.
Spatial organization of the kelp microbiome at micron scales
Authors: Ramirez-Puebla S. Tabita , Weigel Brooke L. , Jack Loretha , Schlundt Cathleen , Pfister Catherine A. , Mark Welch Jessica L.
Published: March 2020

Macroalgae are colonized by complex and diverse microbial communities that are distinct from those on inert substrates, suggesting intimate symbioses that likely play key roles in both macroalgal and bacterial biology. Canopy-forming kelp fix teragrams of carbon per year in coastal kelp forest ecosystems, yet little is known about the structure and development of their associated microbial communities. We characterized the spatial organization of bacterial communities on blades of the canopy-forming kelpNereocystis luetkeanausing fluorescencein situhybridization and spectral imaging with a probe set combining phylum, class and genus-level probes to target >90% of the microbial community. We show that kelp blades host a dense microbial biofilm, generally less than 20 μm thick, in which disparate microbial taxa live in close contact with one another. The biofilm is spatially differentiated, with tightly clustered cells of the dominant symbiontGranulosicoccus sp. (Gammaproteobacteria) close to the kelp surface and filamentousBacteroidetesand Alphaproteobacteria relatively more abundant near the biofilm-seawater interface. Further, a community rich inBacteroidetescolonized the interior of kelp tissues. Microbial community structure and cell density increased along the length of the kelp blade, from sparse microbial colonization of newly produced tissues at the meristematic base of the blade to an abundant microbial biofilm on older tissues at the blade tip. Finally, kelp from a declining population hosted fewer microbial cells compared to kelp from a stable population, indicating that biofilms are characteristic of health and that biofilm loss may be related to the condition of the host.

Importance

The microbial community coating the surfaces of macroalgae may play a key but underexplored role both in the biology of the macroalgal host and in the biogeochemistry of the coastal ocean. We show that photosynthetic blades of the canopy-forming kelpNereocystis luetkeanahost a complex microbial biofilm that is both dense and spatially differentiated. Microbes of different taxa are in intimate cell-to-cell contact with one another; microbial cells invade the interior of kelp cells as well as cover their external surfaces; and a subset of the surface microbiota projects into the water column. These results highlight the potential for metabolic interactions between key members of the kelp microbiome as well as between microbes and their host. The dense layer of microbes coating the surface of the kelp blade is well-positioned to mediate interactions between the host and surrounding organisms and to modulate the chemistry of the surrounding water column.
Development of locomotion in low water exposure using sturgeon
Authors: Asano-Hoshino Anshin. , Tanaka Hideyuki. , Nakakura Takashi. , Tsuji Toshiaki. , Mizukami Takuo.
Published: March 2020

The evolution of early land vertebrates from aquatic forms of life was a biological milestone. The transition to land was accompanied with expectedly challenging physiological and morphological evolutionary hurdles. So far, fossil records have provided substantial information on the origin of quadrupedal locomotion. However, fossil evidence alone is insufficient to understand how the soft-tissue-dependent motor functions and locomotion were acquired and developed. In the present study, we focus on locomotion of the sturgeon, an extant primitive fish, as a new experimental model, to investigate behavioural plasticity. Their locomotion in low-water-level conditions was similar to an escape response in water, the C-start escape response, which is used by most fish and amphibian juveniles to avoid predation. Sturgeons were also found to have mastered rolling-over in response to low water levels, resulting in the improvement of their trunk-twisting action. Sturgeons acquired an efficient shift in their centroid, thereby improving their mobility. We hypothesise that the escape response triggered by environmental hazards drove the development of locomotion, which was accompanied by a variety of behaviours.
Revised annotation and characterization of novelAedes albopictusmiRNAs and their potential functions in dengue virus infection
Authors: Azlan Azali , Yunus Muhammad Amir , Azzam Ghows
Published: March 2020

The Asian tiger mosquito,Aedes albopictus(Ae. albopictus), is a highly invasive species that transmit several arboviruses including dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV). Although several studies have identified microRNAs (miRNAs) inAe. albopictus, it is crucial to extend and improve current annotations with the newly improved genome assembly, and the increase number of small RNA-sequencing data. We combined our high-depth sequence data and 26 public datasets to re-annotateAe. albopictusmiRNAs, and found a total of 110 novel mature miRNAs. We discovered that the expression of novel miRNAs was lower than known miRNAs. Furthermore, compared to known miRNAs, novel miRNAs are prone to be expressed in stage-specific manner. Upon DENV infection, a total of 59 novel miRNAs were differentially expressed, and target prediction analysis revealed that miRNA-target genes were involved in lipid metabolism and protein processing in endoplasmic reticulum. Taken together, miRNA annotation profile provided here is the most comprehensive to date, and we believed that this will facilitate future research in understanding virus-host interactions particularly on the role of miRNAs.
Drug-induced resistance in micrometastases: analysis of spatio-temporal cell lineages
Authors: Pérez-Velázquez Judith , Rejniak Katarzyna A.
Published: March 2020

Resistance to anti-cancer drugs is a major cause of treatment failure. While several intracellular mechanisms of resistance have been postulated, the role of extrinsic factors in the development of resistance in individual tumor cells is still not fully understood. Here we used a hybrid agent-based model to investigate how sensitive tumor cells develop drug resistance in the heterogeneous tumor microenvironment. We characterized the spatio-temporal evolution of lineages of the resistant cells and examined how resistance at the single-cell level contributes to the overall tumor resistance. We also developed new methods to track tumor cell adaptation, to trace cell viability trajectories and to examine the three-dimensional spatio-temporal lineage trees. Our findings indicate that drug-induced resistance can result from cells adaptation to the changes in drug distribution. Two modes of cell adaptation were identified that coincide with microenvironmental niches—areas sheltered by cell micro-communities (protectorates) or regions with limited drug penetration (refuga or sanctuaries). We also recognized that certain cells gave rise to lineages of resistant cells (precursors of resistance) and pinpointed three temporal periods and spatial locations at which such cells emerged. This supports the hypothesis that tumor micrometastases do not need to harbor cell populations with pre-existing resistance, but that individual tumor cells can adapt and develop resistance induced by the drug during the treatment.
Meta-analysis of the effects of sleep deprivation on depression in patients and animals
Authors: Hu Baiqi , Ye Mengfei , Feng Dan , Ying Jianghua , Mou Tingting , Luo Fangyi , Lv Tingting , Jiang Liya , Qian Chao , Ding Zhinan , Yu Chaoyang , Gao Hui , Zhang Jian , Liu Zheng
Published: March 2020

Objective

Research on the antidepressant effects of sleep deprivation (SD) is lagging and has not produced completely uniform results in humans and animals. The present study aimed to reassess the effect of SD on patients and animals by meta-analysis based on updated research.

Methods

We searched PubMed, Embase and Cochrane Library for articles since the first relevant literature published up to June 10th, 2019. Data on sample characteristics, features of SD, and tests for depression were extracted.

Results

Fourteen articles were included, eight on humans and six on animals. We found that when the duration of SD in patients was 7–14 days, it reflected antidepression [-1.52 (−2.07, −0.97); I2=19.6%]. In animals, the results of sucrose consumption experiments showed that SD has depressogenic effects [-1.06 (−1.63, −0.49); I2=81.1%], while the results of forced swimming experiments showed that SD treated depression [-1.17 (−2.19, −0.16); I2=80.1%], regardless of the duration of sleep deprivation.

Conclusion

SD can be an effective antidepressant measure when the duration is 7–14 days in patients. In animal studies, SD has shown more antidepressant effects when measured by forced swimming experiments, whereas using sucrose consumption tests had the effect of worsening depression.
Enrichment of disease-associated genes in cortical areas defined by transcriptome-based parcellation
Authors: Gregor Gryglewski , Matej Murgaš , Paul Michenthaler , Manfred Klöbl , Bruce Reed Murray , Jakob Unterholzner , Rupert Lanzenberger
Published: March 2020

The parcellation of the cerebral cortex serves the investigation of the emergence of uniquely human brain functions and disorders. We employed hierarchical clustering based on comprehensive transcriptomic data of the human cortex in order to delineate areas with distinct gene expression profiles. These profiles were analyzed for the enrichment of gene sets associated with brain disorders by genome-wide studies (GWAS) and expert curation. This suggested new roles of specific cortical areas in psychiatric, neurodegenerative, congenital and other neurological disorders while reproducing some well-established links for movement disorders and dementias. GWAS-derived gene sets for psychiatric disorders exhibited similar enrichment patterns in the posterior fusiform gyrus and inferior parietal lobule driven by pleiotropic genes. This implies that the effects of risk variants shared between neuropsychiatric disorders might converge in these areas. For several diseases, specific genes were highlighted, which may aid the discovery of novel disease mechanisms and urgently needed treatments.
Streptococcus pyogenesM1T1 variants activate caspase-1 and induce an inflammatory neutrophil phenotype
Authors: Williams Jonathan G. , Ly Diane , Geraghty Nicholas J. , McArthur Jason D. , Vyas Heema K. N. , Gorman Jody , Tsatsaronis James A. , Sluyter Ronald , Sanderson-Smith Martina L.
Published: March 2020

Invasive infections due to Group AStreptococcus(GAS) advance rapidly causing tissue degradation and unregulated inflammation. Neutrophils are the primary immune cells that respond to GAS. The neutrophil response to GAS was characterised in response to two M1T1 isolates; 5448 and animal passaged variant 5448AP. Neutrophil co-incubation with 5448AP allowed proliferation of GAS while it also lowered the production of reactive oxygen species by neutrophils when compared with 5448. Infection with both strains invoked neutrophil death, however apoptosis was reduced in response to 5448AP. Both strains induced neutrophil caspase-1 activation and caspase-4 expressionin vitro, with caspase-1 activation detectedin vivo. Thus, GAS infection of neutrophils corresponds to increased caspase-1 activity and caspase-4 expression, consistent with inflammasome activation and pyroptosis. GAS infections that promote an inflammatory neutrophil phenotype may contribute to increased inflammation yet ineffective bacterial eradication, contributing to the speed and severity of invasive GAS infections.
Transferrin-dependent crosstalk between the intestinal tract and commensal microbes contributes for immune tolerance
Authors: Tang Xiaopeng , Fang Mingqian , Xu Kuanhong , Cheng Ruomei , Wang Gan , Liao Zhiyi , Zhang Zhiye , Mwangi James , Lu Qiumin , Lai Ren
Published: March 2020

Crosstalks between gastrointestinal tract and commensal microbes regulate immune tolerance and maintain host intestinal homeostasis. However, molecular events that regulate the crosstalks remain poorly understood. Here, we show that microbial products (lipopolysaccharide, lipoteichoic acid and DNA) up-regulate host transferrin, an iron supplier of commensal bacteria, to induce host’s immune tolerance by negatively regulating toll-like receptor (TLR) signaling. Transferrin level in germ-free and broad-spectrum antibiotics-treated mice is much less than that in normal mice. Transferrin is found to silence TLR signaling complex by directly interacting with CD14, a co-receptor of many TLRs. Transferrin knock-down impaired host tolerogenic responses as well as broad-spectrum antibiotics treatment. Our findings reveal that commensal bacteria up-regulate and beneficially use host transferrin as a negative regulator of TLR signaling to shape host immunity and contribute for intestinal tolerance.
The transcription and export complex THO/TREX contributes to transcription termination in plants
Authors: Khan Ghazanfar Abbas , Deforges Jules , Reis Rodrigo S. , Hsieh Yi-Fang , Montpetit Jonatan , Antosz Wojciech , Santuari Luca , Hardtke Christian S , Grasser Klaus , Poirier Yves
Published: March 2020

Transcription termination has important regulatory functions, impacting mRNA stability, localization and translation potential. Failure to appropriately terminate transcription can also lead to read-through transcription and the synthesis of antisense RNAs which can have profound impact on gene expression. The Transcription-Export (THO/TREX) protein complex plays an important role in coupling transcription with splicing and export of mRNA. However, little is known about the role of the THO/TREX complex in the control of transcription termination. In this work, we show that two proteins of the THO/TREX complex, namely TREX COMPONENT 1 (TEX1 or THO3) and HYPER RECOMBINATION1 (HPR1 or THO1) contribute to the correct transcription termination at several loci inArabidopsis thaliana. We first demonstrate this by showing defective termination intex1andhpr1mutants at the nopaline synthase (NOS) terminator present in a T-DNA inserted between exon 1 and 3 of thePHO1locus in thepho1-7mutant. Read-through transcription beyond the NOS terminator and splicing-out of the T-DNA resulted in the generation of a near full-lengthPHO1mRNA (minus exon 2) in thetex1 pho1-7andhpr1 pho1-7double mutants, with enhanced production of a truncated PHO1 protein that retained phosphate export activity. Consequently, the strong reduction of shoot growth associated with the severe phosphate deficiency of thepho1-7mutant was alleviated in thetex1 pho1-7andhpr1 pho1-7double mutants. Additionally, we show that RNA termination defects intex1andhpr1mutants leads to 3’UTR extensions in several plant genes. These results demonstrate that THO/TREX complex contributes to the regulation of transcription termination.

Author summary

Production of messenger RNAs (mRNAs) involves numerous steps including initiation of transcription, elongation, splicing, termination, as well as export out of the nucleus. All these steps are highly coordinated and failure in any steps has a profound impact on the level and identity of mRNAs produced. The THO/TREX protein complex is associated with nascent RNAs and contributes to several mRNA biogenesis steps, including splicing and export. However, the contribution of the THO/TREX complex to mRNA termination was poorly defined. We have identified a role for two components of the THO/TREX complex, namely the proteins TEX1 and HPR1, in the control of transcription termination in the plantArabidopsis thaliana. We show that thetex1andhpr1mutants have defects in terminating mRNA at the nopaline synthase (NOS) terminator found in T-DNA insertion mutants leading to the transcriptional read-through pass the NOS terminator. We also show thattex1andhpr1mutants have defects in mRNA termination at several endogenous genes, leading to the production of 3’UTR extensions. Together, these results highlight a role for the THO/TREX complex in mRNA termination.
Isolation and characterization of SARS-CoV-2 from the first US COVID-19 patient
Authors: Harcourt Jennifer , Tamin Azaibi , Lu Xiaoyan , Kamili Shifaq , Sakthivel Senthil Kumar. , Murray Janna , Queen Krista , Tao Ying , Paden Clinton R. , Zhang Jing , Li Yan , Uehara Anna , Wang Haibin , Goldsmith Cynthia , Bullock Hannah A. , Wang Lijuan , Whitaker Brett , Lynch Brian , Gautam Rashi , Schindewolf Craig , Lokugamage Kumari G. , Scharton Dionna , Plante Jessica A. , Mirchandani Divya , Widen Steven G. , Narayanan Krishna , Makino Shinji , Ksiazek Thomas G. , Plante Kenneth S. , Weaver Scott C. , Lindstrom Stephen , Tong Suxiang , Menachery Vineet D. , Thornburg Natalie J.
Published: March 2020

The etiologic agent of the outbreak of pneumonia in Wuhan China was identified as severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) in January, 2020. The first US patient was diagnosed by the State of Washington and the US Centers for Disease Control and Prevention on January 20, 2020. We isolated virus from nasopharyngeal and oropharyngeal specimens, and characterized the viral sequence, replication properties, and cell culture tropism. We found that the virus replicates to high titer in Vero-CCL81 cells and Vero E6 cells in the absence of trypsin. We also deposited the virus into two virus repositories, making it broadly available to the public health and research communities. We hope that open access to this important reagent will expedite development of medical countermeasures.

Article Summary

Scientists have isolated virus from the first US COVID-19 patient. The isolation and reagents described here will serve as the US reference strain used in research, drug discovery and vaccine testing.
Identification and Optimization of cell active 4-anilino-quin(az)oline Inhibitors for Protein Kinase Novel 3 (PKN3)
Authors: Asquith Christopher R. M. , Temme Louisa , Laitinen Tuomo , Pickett Julie , Kwarcinski Frank E. , Sinha Parvathi , Wells Carrow I. , Tizzard Graham J. , Zutshi Reena , Drewry David H.
Published: March 2020

The development of a small library of 4-anilinoquinolines led to the identification of 7-iodo-N-(3,4,5-trimethoxyphenyl)quinolin-4-amine16as a potent inhibitor of Protein Kinase Novel 3 (PKN3) with an IC50of 1.3 μM in cells. Compound16presents a useful potential tool compound to study the biology of PKN3 including links to pancreatic and prostate cancer, along with T-cell acute lymphoblastic leukemia. These compounds may be useful tools to explore the therapeutic potential of PKN3 inhibition in prevention of a broad range of infectious and systemic diseases.
Optogenetic activation of afferent pathways in brain slices and modulation of responses by volatile anesthetics
Authors: Murphy Caitlin A. , Raz Aeyal , Banks Matthew I.
Published: March 2020

Anesthetics influence consciousness in part via their actions on thalamocortical circuits. However, the extent to which volatile anesthetics affect distinct cellular and network components of these circuits remains unclear.Ex vivobrain slices provide a means by which investigators may probe discrete components of complex networks and disentangle potential mechanisms underlying the effects of volatile anesthetics on evoked responses. To isolate potential cell type- and pathway-specific drug effects in brain slices, investigators must be able to independently activate afferent fiber pathways, identify non-overlapping populations of cells, and apply volatile anesthetics to tissue in aqueous solution. In this protocol, we describe methods to measure optogenetically-evoked responses to two independent afferent pathways to neocortex inex vivobrain slices. We record extracellular responses to assay network activity and conduct targeted whole-cell patch clamp recordings in somatostatin- and parvalbumin-positive interneurons. We also describe a means by which to deliver physiologically relevant concentrations of isoflurane via artificial cerebral spinal fluid to modulate cellular and network responses.

Ex vivobrain slices can be used to study the effects of volatile anesthetics on evoked responses to afferent inputs. We employ optogenetics to independently activate thalamocortical and corticocortical afferents to non-primary neocortex, and we modulate synaptic and network responses with isoflurane.
AHistoplasma capsulatumlipid metabolic map identifies antifungal targets
Authors: Zamith-Miranda Daniel , Heyman Heino M. , Burnet Meagan C. , Couvillion Sneha P. , Zheng Xueyun , Munoz Nathalie , Nelson William C. , Kyle Jennifer E. , Zink Erika M. , Weitz Karl K. , Bloodsworth Kent J. , Clair Geremy , Zucker Jeremy D. , Teuton Jeremy R. , Payne Samuel H. , Kim Young-Mo , Gil Morayma Reyes , Baker Erin S. , Bredeweg Erin L. , Nosanchuk Joshua D. , Nakayasu Ernesto S.
Published: March 2020

Lipids play a fundamental role in fungal cell biology, being essential cell membrane components and major targets of antifungal drugs. A deeper knowledge of lipid metabolism is key for developing new drugs and a better understanding of fungal pathogenesis. Here we built a comprehensive map of theHistoplasma capsulatumlipid metabolic pathway by incorporating proteomic and lipidomic analyses. We performed genetic complementation and overexpression ofH. capsulatumgenes inSaccharomyces cerevisiaeto validate reactions identified in the map and to determine enzymes responsible for catalyzing orphan reactions. The map led to the identification of both the fatty acid desaturation and the sphingolipid biosynthesis pathways as targets for drug development. We found that the sphingolipid biosynthesis inhibitor myriocin, the fatty acid desaturase inhibitor thiocarlide and the fatty acid analog 10-thiastearic acid inhibitH. capsulatumgrowth in nanomolar to low micromolar concentrations. These compounds also reduced the intracellular infection in an alveolar macrophage cell line. Overall, this lipid metabolic map revealed pathways that can be targeted for drug development.
Phylogenomics of piranhas and pacus (Serrasalmidae) uncovers how convergent diets obfuscate traditional morphological taxonomy
Authors: Kolmann M.A. , Hughes L.C. , Hernandez L.P. , Arcila D. , Betancur R. , Sabaj M.H. , López-Fernández H. , Ortí G.
Published: March 2020

The Amazon and neighboring South American river basins harbor the world’s most diverse assemblages of freshwater fishes. One of the most prominent South American fish families are the Serrasalmidae (pacus and piranhas), found in nearly every continental basin. Serrasalmids are keystone ecological taxa, being some of the top riverine predators as well as the primary seed dispersers in the flooded forest. Despite their widespread occurrence and notable ecologies, serrasalmid evolutionary history and systematics are controversial. For example, the sister taxon to serrasalmids is contentious, the relationships of major clades within the family are obfuscated by different methodologies, and half of the extant serrasalmid genera are suggested to be non-monophyletic. We used exon capture to explore the evolutionary relationships among 64 (of 99) species across all 16 serrasalmid genera and their nearest outgroups, including multiple individuals per species in order to account for cryptic lineages. To reconstruct the timeline of serrasalmid diversification, we time-calibrated this phylogeny using two different fossil-calibration schemes to account for uncertainty in taxonomy with respect to fossil teeth. Finally, we analyzed diet evolution across the family and comment on associated changes in dentition, highlighting the ecomorphological diversity within serrasalmids. We document widespread non-monophyly within Myleinae, as well as betweenSerrasalmusandPristobrycon, and propose that reliance on traits like teeth to distinguish among genera is confounded by ecological convergence, especially among herbivorous and omnivorous taxa. We clarify the relationships among all serrasalmid genera, propose new subfamily affiliations, and support hemiodontids as the sister taxon to Serrasalmidae.
Intragenic Complementation ofCellulose Synthase-Like D1alleles in Root Hair Development
Authors: Karas Bogumil J. , Ross Loretta , Novero Mara , Amyot Lisa , Inada Sayaka , Nakano Michiharu , Sakai Tatsuya , Sato Sushei , Murray Jeremy Dale , Bonfante Paola , Szczyglowski Krzysztof
Published: March 2020

Root hair cells form the primary interface of plants with the soil environment, playing key roles in nutrient uptake and plant defense. In addition, they are typically the first cells infected by nitrogen-fixing soil bacteria during the root nodule symbiosis. Here we report a role for theCellulose Synthase-Like D1(CSLD1) gene in root hair development inLotus japonicus. CSLD1 belongs to the cellulose synthase protein family that includes cellulose synthases, and cellulose synthase-like proteins, the latter thought to be involved in the biosynthesis of hemicellulose. We describe 11csld1mutant alleles that have either short (Ljcsld1-1) or variable length roots hairs (Ljcsld1-2to11). Examination ofLjcsld1-1and one variable-length root hair mutant,Ljcsld1-6showed increased root hair cell wall thickness, which inLjcsld1-1was more pronounced, suggesting a possible link with the defect in root nodule symbiosis. In addition,Ljcsld1-1heterozygotes had intermediate root hair lengths, between those of wild type and the homozygotes. Intragenic complementation was observed between alleles with mutations in the N-terminal domain and other alleles, suggesting modularity of CSLD1 function and that it may operate as a homodimer or multimer.

One sentence summary

This research describes novel gain- and loss-of-function mutations at theLotus japonicus CELLULOSE SYNTHASE-LIKE D1locus and analyzes their impact on root hair development.
Minimally invasive brain injections for viral-mediated transgenesis: New tools for behavioral genetics in sticklebacks
Authors: James Noelle , Bell Alison
Published: March 2020

Behavioral genetics in non-model organisms is currently gated by technological limitations. However, with the growing availability of genome editing and functional genomic tools, complex behavioral traits such as social behavior can now be explored in diverse organisms. Here we present a minimally invasive neurosurgical procedure for a classic behavioral, ecological and evolutionary system: threespine stickleback (Gasterosteus aculeatus). This method of direct brain injection enables viral-mediated transgenesis and pharmaceutical delivery which bypasses the blood-brain barrier. This method is flexible, fast, and amenable to statistically powerful within-subject experimental designs, making it well-suited for use in genetically diverse animals such as those collected from natural populations.

Viral-mediated transgenesis in the brain allows for a direct examination of the genetic mechanisms underlying behavior in wild-caught animals from natural populations. Using this method, we were able to detect changes in aggression from the knockdown of either of two different genes, arginine vasopressin (AVP) and monoamine oxidase (MAOA), in outbred animals in less than one month. In addition, we demonstrate that widely available mammalian plasmids work with this method, lowering the barrier of entry to the technique.
Bayesian Structural Time Series for Biomedical Sensor Data: A Flexible Modeling Framework for Evaluating Interventions
Authors: Liu Jason , Spakowicz Daniel J. , Ash Garrett I. , Hoyd Rebecca , Zhang Andrew , Lou Shaoke , Lee Donghoon , Zhang Jing , Presley Carolyn , Greene Ann , Stults-Kolehmainen Matthew , Nally Laura , Baker Julien S. , Fucito Lisa M. , Weinzimer Stuart A. , Papachristos Andrew V , Gerstein Mark
Published: March 2020

The development of mobile-health technology has the potential to revolutionize personalized medicine. Biomedical sensors (e.g. wearables) can assist with determining treatment plans for individuals, provide quantitative information to healthcare providers, and give objective measurements of health, leading to the goal of precise phenotypic correlates for genotypes. Even though treatments and interventions are becoming more specific and datasets more abundant, measuring the causal impact of health interventions requires careful considerations of complex covariate structures as well as knowledge of the temporal and spatial properties of the data. Thus, biomedical sensor data need to make use of specialized statistical models. Here, we show how the Bayesian structural time series framework, widely used in economics, can be applied to these data. We further show how this framework corrects for covariates to provide accurate assessments of interventions. Furthermore, it allows for a time-dependent confidence interval of impact, which is useful for considering individualized assessments of intervention efficacy. We provide a customized biomedical adaptor tool around a specific Google implementation of the Bayesian structural time series framework that uniformly processes, prepares, and registers diverse biomedical data. We apply the resulting software implementation to a structured set of examples in biomedicine to showcase the ability of the framework to evaluate interventions with varying levels of data richness and covariate complexity. In particular, we show how the framework is able to evaluate an exercise intervention’s effect on stabilizing blood glucose in a diabetes dataset. We also provide a future-anticipating illustration from a behavioral dataset showcasing how the framework integrates complex spatial covariates. Overall, we show the robustness of the Bayesian structural time series framework when applied to biomedical sensor data, highlighting its increasing value for current and future datasets.
CO2reduction driven by a pH gradient
Authors: Hudson Reuben , de Graaf Ruvan , Rodin Mari Strandoo , Ohno Aya , Lane Nick , McGlynn Shawn E. , Yamada Yoichi M.A. , Nakamura Ryuhei , Barge Laura M. , Braun Dieter , Sojo Victor
Published: March 2020

All life on Earth is built of organic molecules, so the primordial sources of reduced carbon are a major open question in studies of the origin of life. A variant of the alkaline-vent theory suggests that organics could have been produced by the reduction of CO2via H2oxidation, facilitated by geologically sustained pH gradients. The process would be an abiotic analog—and proposed evolutionary predecessor—of the modern Wood-Ljungdahl acetyl-Co-A pathway of extant archaea and bacteria. The first energetic bottleneck of the pathway involves the endergonic reduction of CO2with H2to formate, which has proven elusive in low-temperature abiotic settings. Here we show the reduction of CO2with H2at moderate pressures (1.5 bar), driven by microfluidic pH gradients across inorganic Fe(Ni)S precipitates. Isotopic labelling with13C confirmed production of formate. Separately, deuterium (2H) labelling indicated that electron transfer to CO2did not occur via direct hydrogenation with H2. Instead, freshly deposited Fe(Ni)S precipitates appear to facilitate electron transfer in an electrochemical-cell mechanism with two distinct half-reactions. Decreasing the pH gradient significantly, or removing either H2or the precipitate, yielded no detectable product. Our work demonstrates the feasibility of spatially separated, yet electrically coupled geochemical reactions as drivers of otherwise endergonic processes. Beyond corroborating the ability of early-Earth alkaline hydrothermal systems to couple carbon reduction to hydrogen oxidation through geologically plausible and biologically relevant mechanisms, these results may also be of significance for industrial and environmental applications, where other redox reactions could be facilitated using similarly mild approaches.
Overlapping neural representations for the position of visible and imagined objects
Authors: Robinson Amanda K. , Grootswagers Tijl , Shatek Sophia M. , Gerboni Jack , Holcombe Alex O. , Carlson Thomas A.
Published: March 2020

Humans can covertly track the position of an object, even if the object is temporarily occluded. What are the neural mechanisms underlying our capacity to track moving objects when there is no physical stimulus for the brain to track? One possibility is that the brain “fills-in” information about imagined objects using internally generated representations similar to those generated by feed-forward perceptual mechanisms. Alternatively, the brain might deploy a higher order mechanism, for example using an object tracking model that integrates visual signals and motion dynamics (Kwon et al., 2015). In the present study, we used electroencephalography (EEG) and time-resolved multivariate pattern analyses to investigate the spatial processing of visible and imagined objects. Participants tracked an object that moved in discrete steps around fixation, occupying six consecutive locations. They were asked to imagine that the object continued on the same trajectory after it disappeared and move their attention to the corresponding positions. Time-resolved decoding of EEG data revealed that the location of the visible stimuli could be decoded shortly after image onset, consistent with early retinotopic visual processes. For processing of unseen/imagined positions, the patterns of neural activity resembled stimulus-driven mid-level visual processes, but were detected earlier than perceptual mechanisms, implicating an anticipatory and more variable tracking mechanism. Encoding models revealed that spatial representations were much weaker for imagined than visible stimuli. Monitoring the position of imagined objects thus utilises similar perceptual and attentional processes as monitoring objects that are actually present, but with different temporal dynamics. These results indicate that internally generated representations rely on top-down processes, and their timing is influenced by the predictability of the stimulus. All data and analysis code for this study are available athttps://osf.io/8v47t/.
Development of nascent focal adhesions in spreading cells
Authors: Ibata Neil , Terentjev Eugene M.
Published: March 2020

Cell spreading provides one of the simplest configurations in which eukaryotic cells develop angular symmetry-breaking assemblies of mechanosensing and mechanotransducive organelles in preparation for cell differentiation and movement. By identifying the edge of the cell-ECM adhesion area as having an important role in mechanosensor complex aggregation, we consider the spatial patterns arising on this edge, within a 1D lattice model of the nearest-neighbour interaction between individual integrin-mediated mechanosensors. We obtain the Ginzburg-Landau free energy for this model and analyse the spectrum of spatial modes as the cell spreads and increases the contact area. We test the plausibility of our model by comparing its predictions for the azimuthal angular frequency of aggregation of mechanosensors into nascent focal adhesions (FAs) to observations of the paxillin distribution in spreading fibroblasts.

STATEMENT OF SIGNIFICANCE

The topic of cell adhesion on substrates is very active, with numerous theoretical, experimental and computer simulation studies probing the mechanisms and signalling pathways of cell response to interacting with substrate. Integrin-based adhesion complexes are known to be the individual units of this process, and their dense aggregation into focal adhesions leads to cells developing asymmetry, polarity, and eventually - locomotion. Here we develop a theoretical model that suggests that physical interactions between individual adhesion complexes is the factor that defines the initial breaking of symmetry of the cell spreading on substrate, and predicts the characteristic wavelength of modulation above the critical size of adhesion area.
Out-of-register parallel β-sheets and antiparallel β-sheets coexist in 150 kDa oligomers formed by Aβ(1-42)
Authors: Gao Yuan , Guo Cong , Watzlawik Jens O. , Lee Elizabeth J. , Huang Danting , Zhou Huan-Xiang , Rosenberry Terrone L. , Paravastu Anant K.
Published: March 2020

We present solid-state NMR measurements of β-strand secondary structure and inter-strand organization within a 150 kDa oligomeric aggregate of the 42-residue variant of the Alzheimer’s amyloid-β peptide (Aβ(1-42)). This oligomer is characterized by a structure that cannot be explained by any previously proposed model for aggregated Aβ. We build upon our previous report of a β-strand spanned by residues 30-42, which arranges into an antiparallel β-sheet. New results presented here indicate that there is a second β-strand formed by residues 11-24. We show negative results for NMR experiments designed to reveal antiparallel β-sheets formed by this β-strand. Remarkably, we show that this strand is organized into a parallel β-sheet despite the co-existence of an antiparallel β-sheet in the same structure. In addition, the in-register parallel β-sheet commonly observed for amyloid fibril structure does not apply to residues 11-24 in the 150 kDa oligomer. Rather, we present evidence for an inter-strand registry shift of 3 residues that alternates in direction between adjacent molecules along the β-sheet. We corroborated this unexpected scheme for β-strand organization using multiple 2-dimensional NMR and13C-13C dipolar recoupling experiments. Our findings indicate a previously unknown assembly pathway and inspire a suggestion as to why this aggregate does not grow to larger sizes.
Auditory Countermeasures for Sleep Inertia: An Ecological Study Examining the Influence of Melody and Rhythm
Authors: McFarlane Stuart J. , Garcia Jair E. , Verhagen Darrin S. , Dyer Adrian G.
Published: March 2020

Sleep inertia is the potentially harmful decline in cognition that occurs upon and following awakening. Sound has been shown to counteract the negative symptoms of sleep inertia, with a recent study revealing that an alarm perceived as melodic by participants displayed a significant relationship to reports of reductions in perceived sleep inertia. This current research builds on these findings by specifically testing the effect melodic and rhythmic stimuli exhibit on sleep inertia for subjects awakening in their habitual environments. Two test Groups (A & B;N= 10 equally) completed an online psychomotor experiment and questionnaire in two separate test sessions immediately following awakening from nocturnal sleep epochs. Both groups responded to a Control stimulus in the first session, while in the second session, Group A experienced a Melodic treatment, and Group B the Rhythmic. The results show that the melodic treatment significantly decreased attentional Lapses, False Starts and had a significantly improved PVT Performance Score than the Control. There was no significant result for Reaction Time or Response Speed. Additionally, no significant difference was observed for all PVT metrics between the Control – Rhythmic conditions. The results support melodies potential to counteract symptoms of sleep inertia by the observed increase in participant vigilance following waking. Specifically, a melodically rhythmic contour is highlighted as a significant musical treatment noteworthy of consideration when designing alarm compositions for the reduction of sleep inertia. As auditory assisted awakening is a common within modern society, improvements in alarm sound design may have advantages in domestic and commercial settings.
Green Fabricated Zinc Oxide Nanoformulated Media Enhanced Callus Induction and Regeneration Dynamics ofPanicum virgatumL.
Authors: Shafique Saima , Jabeen Nyla , Ahmad Khawaja Shafique , Irum Samra , Anwaar Sadaf , Ahmad Naeem , Alam Sadia , Ilyas Muhammad , Khan Talha Farooq , Hussain Syed Zaheer
Published: March 2020

The current study was focused on the usage of bio synthesized zinc oxide nanoparticles to increase the tissue culture efficiency of important forage grassPanicum virgatum. Zinc being a micronutrient enhanced the callogenesis and regeneration efficiency ofPanicum virgatumat different concentrations. Here, we synthesized zinc oxide nanoparticles throughCymbopogon citratusleaves extract to evaluate the influence of zinc oxide nanoparticles on the quality of plant regeneration in switchgrass. X-ray diffraction (XRD) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) validate phase purity of green synthesize Zinc oxide nanoparticles whereas, electron microscopy (SEM) has illustrated the average size of particle 50±4 nm with hexagonal rod like shape. Energy dispersive Xray (EDS) spectra depict major peaks of Zn (92.68%) while minor peaks refer to Oxygen (7.32%). ZnO NPs demonstrate the incredibly promising results against callogenesis. Biosynthesized ZnO NPs at optimum concentration showed very promising effect on plant regeneration ability. Both the explants, seeds and nodes used in study showed dose dependent response and upon high doses exceeding 40 mg/L the results were recorded negative, whereas at 30 mg/L both explants demonstrate 70 % and 76 % regeneration frequency. The results conclude that zinc oxide nanoparticles enhance plant growth and development. Being one of the essential plant nutrients, ZnO has greatly tailored the nutritive properties at nano-scale.
Compartmentalization of the replication fork by single-stranded DNA binding protein regulates translesion synthesis
Authors: Chang Seungwoo , Thrall Elizabeth S. , Laureti Luisa , Pagès Vincent , Loparo Joseph J.
Published: March 2020

DNA replication is mediated by the coordinated actions of multiple enzymes within replisomes. Processivity clamps tether many of these enzymes to DNA, allowing access to the primer/template junction. Many clamp-interacting proteins (CLIPs) are involved in genome maintenance pathways including translesion synthesis (TLS). Despite their abundance, DNA replication in bacteria is not perturbed by these CLIPs. Here we show that while the TLS polymerase Pol IV is largely excluded from moving replisomes, the remodeling of ssDNA binding protein (SSB) upon replisome stalling enriches Pol IV at replication forks. This enrichment is indispensable for Pol IV-mediated TLS on both the leading and lagging strands as it enables Pol IV-processivity clamp binding by overcoming the gatekeeping role of the Pol III epsilon subunit. As we have demonstrated for the Pol IV-SSB interaction, we propose that the binding of CLIPs to the processivity clamp must be preceded by interactions with factors that serve as localization markers for their site of action.