bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Activism to Get Nurses on Boards
Authors: Disch Joanne , Kingston Mary Beth
Published: June 2021

Over the past 15 years, there has been a growing call for nurses to be placed on boards of hospitals and health systems. Rationale for this action includes the changing nature of health care; a greater emphasis on person and family-centered care; nurses' background and experience in health care delivery; and that boards with a more diverse composition are associated with better organizational performance. Several national organizations have come forward to support this, among them the Robert Wood Johnson Foundation, American Hospital Association, the Institute of Medicine, and several industry leaders in health care. While progress has been made, however, nurses still occupy only 4% of board seats. This article reviews some of the myths and barriers that have prevented nurses from serving on boards, as well as offering 3 major recommendations for action that reflect not only long-term efforts but also short-term activism.
Is it Noise? Factors Linked With Sleep Interruption in Hospitalized Patients
Authors: Mori Candace , Boss Karrie , Indermuhle Patty , Stahl Erica , Chiu Sheau-Huey , Shanks Linda
Published: June 2021

Purpose/Aim

The aim of this study was to explore the perceived quality of sleep and sleep disturbances in hospitalized patients.

Design

A prospective descriptive, exploratory, cross-sectional study was conducted at a 172-bed community hospital in Northeast Ohio. A convenient sample of 100 hospitalized patients was recruited from medical/surgical, progressive care, and intensive care units.

Methods

Participants used the Richards-Campbell Sleep Questionnaire to report sleep. A quality of sleep assessment survey was used to collect information regarding 17 factors leading to decreased quality of sleep.

Results

Mean sleep score was 47.92 for each question regarding sleep depth, latency, awakenings, time spent awake, and overall sleep quality. Pearson's correlation showed a significantly positive correlation between measure of noise and sleep score. Five environmental factors were identified as most disruptive to sleep: pain, laboratory draws, staff, blood pressure checks, and intravenous alarms.

Conclusion

The positive correlation between sleeping well and higher noise levels is noteworthy. Raising awareness about the importance of sleep in the hospital setting and introducing interventions to promote a quiet environment and minimize sleep-disturbing factors may increase patient satisfaction scores and improve healing.
College Students’ COVID-19 Vaccine Beliefs and Intentions: Implications for interventions
Authors: Small Meg L. , Lennon Robert P. , Dziak John J. , Smith Rachel A. , Sommerville Gillian , Bharti Nita
Published: June 2021

On college campuses, effective management of vaccine-preventable transmissible pathogens requires understanding student vaccination intentions. This is necessary for developing and tailoring health messaging to maximize uptake of health information and vaccines. The current study explored students’ beliefs and attitudes about vaccines in general, and the new COVID-19 vaccines specifically. This study provides insights into effective health messaging needed to rapidly increase COVID-19 vaccination on college campuses—information that will continue to be informative in future academic years across a broad scope of pathogens. Data were collected via an online cohort survey of college students aged 18 years and older residing on or near the campus of a large public university during fall 2020. Overall, we found COVID-19 vaccine hesitancy in college students correlated strongly with some concerns about vaccines in general as well as with concerns specific to COVID-19 vaccines. Taken together, these results provide further insight for message development and delivery, and can inform more effective interventions to advance critical public health outcomes on college campuses beyond the current pandemic.
IgG index and not serum 25-hydroxyvitamin D is associated with age at onset of multiple sclerosis
Authors: Stridh Pernilla , Kockum Ingrid , Huang Jesse
Published: June 2021

Background

Vitamin D deficiency is associated with an increased risk of multiple sclerosis (MS). However, its effect on the age of disease onset remains unclear. This study examines the relationship between serum 25 hydroxyvitamin D (25(OH)D) levels and age of first symptom onset among recently diagnosed MS patients.

Method

Serum 25(OH)D was measured from forty MS patients sampled near disease onset. After correcting seasonal variability, a multivariable linear regression was used to examine associations to age at onset.

Results

Serum 25(OH)D was not correlated with age at onset (P>0.5). However, CSF IgG index was lower among patients with later disease onset (β=-5.35, P=0.028). Furthermore, we observed bias resulting from non-random distribution of sampling by season, which after correcting indicates a higher 25(OH)D level among patients sampled at relapse compared to remission, instead of lower as previously reported.

Conclusion

In summary, serum 25(OH)D was not associated with the age at onset.
Favorable outcome on viral load and culture viability using Ivermectin in early treatment of non-hospitalized patients with mild COVID-19 – A double-blind, randomized placebo-controlled trial
Authors: Biber Asaf , Mandelboim Michal , Harmelin Geva , Lev Dana , Ram Li , Shaham Amit , Nemet Ital , Kliker Limor , Erster Oran , Schwartz Eli
Published: June 2021

Background

Ivermectin, an anti-parasitic agent, also has anti-viral properties. Our aim was to assess whether ivermectin can shorten the viral shedding in patients at an early-stage of COVID-19 infection.

Methods

The double-blinded trial compared patients receiving ivermectin 0·2 mg/kg for 3 days vs. placebo in non-hospitalized COVID-19 patients. RT-PCR from a nasopharyngeal swab was obtained at recruitment and then every two days. Primary endpoint was reduction of viral-load on the 6thday (third day after termination of treatment) as reflected by Ct level>30 (non-infectious level). The primary outcome was supported by determination of viral culture viability.

Results

Eighty-nine patients were eligible (47 in ivermectin and 42 in placebo arm). Their median age was 35 years. Females accounted for 21·6%, and 16·8% were asymptomatic at recruitment. Median time from symptom onset was 4 days. There were no statistical differences in these parameters between the two groups.

On day 6, 34 out of 47 (72%) patients in the ivermectin arm reached the endpoint, compared to 21/ 42 (50%) in the placebo arm (OR 2·62; 95% CI: 1·09-6·31). In a multivariable logistic-regression model, the odds of a negative test at day 6 was 2.62 time higher in the ivermectin group (95% CI: 1·06–6·45). Cultures at days 2 to 6 were positive in 3/23 (13·0%) of ivermectin samples vs. 14/29 (48·2%) in the placebo group (p=0·008).

Conclusions

There were significantly lower viral loads and viable cultures in the ivermectin group, which could lead to shortening isolation time in these patients.

The study is registered atClinicalTrials.govNCT 044297411.
Revealing the host antiviral protein ZAP-S as an inhibitor of SARS-CoV-2 programmed ribosomal frameshifting
Authors: Zimmer Matthias M. , Kibe Anuja , Rand Ulfert , Pekarek Lukas , Cicin-Sain Luka , Caliskan Neva
Published: June 2021

Programmed ribosomal frameshifting (PRF) is a fundamental gene expression event in many viruses including SARS-CoV-2, which allows production of essential structural and replicative enzymes from an alternative reading frame. Despite the importance of PRF for the viral life cycle, it is still largely unknown how and to what extent cellular factors alter mechanical properties of frameshifting RNA molecules and thereby impact virulence. This prompted us to comprehensively dissect the interplay between the host proteome and the SARS-CoV-2 frameshift element. Here, we reveal that zinc-finger antiviral protein (ZAP-S) is a direct and specific regulator of PRF in SARS-CoV-2 infected cells. ZAP-S overexpression strongly impairs frameshifting and viral replication. Using in vitro ensemble and single-molecule techniques, we further demonstrate that ZAP-S directly interacts with the SARS-CoV-2 RNA and ribosomes and interferes with the folding of the frameshift RNA. Together these data illuminate ZAP-S as de novo host-encoded specific inhibitor of SARS-CoV-2 frameshifting and expand our understanding of RNA-based gene regulation.
Balanced mitochondrial and cytosolic translatomes underlie the biogenesis of human respiratory complexes
Authors: Soto Iliana , Couvillion Mary , McShane Erik , Hansen Katja G. , Moran J. Conor , Barrientos Antoni , Churchman L. Stirling
Published: June 2021

Oxidative phosphorylation (OXPHOS) complexes consist of nuclear and mitochondrial DNA-encoded subunits. Their biogenesis requires cross-compartment gene regulation to mitigate the accumulation of disproportionate subunits. To determine how human cells coordinate mitochondrial and nuclear gene expression processes, we established an optimized ribosome profiling approach tailored for the unique features of the human mitoribosome. Analysis of ribosome footprints in five cell types revealed that average mitochondrial synthesis rates corresponded precisely to cytosolic rates across OXPHOS complexes. Balanced mitochondrial and cytosolic synthesis did not rely on rapid feedback between the two translation systems. Rather, LRPPRC, a gene associated with Leigh’s syndrome, is required for the reciprocal translatomes and maintains cellular proteostasis. Based on our findings, we propose that human mitonuclear balance is enabled by matching OXPHOS subunit synthesis rates across cellular compartments, which may represent a vulnerability for cellular proteostasis.
Hematologic and systemic metabolic alterations due to Mediterranean type II G6PD deficiency in mice
Authors: D’Alessandro Angelo , Howie Heather L , Hay Ariel M. , Dziewulska Karolina H. , Brown Benjamin , Wither Matthew J , Karafin Matthew , Stone Elizabeth F. , Spitalnik Steven L , Hod Eldad A , Francis Richard O , Fu Xiaoyun , Thomas Tiffany , Zimring James C
Published: June 2021

Deficiency of Glucose 6 phosphate dehydrogenase (G6PD) is the single most common enzymopathy, present in approximately 400 million humans (e.g. 5% of humans). Its prevalence is hypothesized to be due to conferring resistance to malaria. However, G6PD deficiency also results in hemolytic sequelae from oxidant stress. Moreover, G6PD deficiency is associated with kidney disease, diabetes, pulmonary hypertension, immunological defects, and neurodegenerative diseases. To date, the only available mouse models have decreased levels of G6PD due to promoter mutations, but with stable G6PD. However, human G6PD mutations are missense mutations that result in decreased enzymatic stability. As such, this results in very low activity in red blood cells and platelets that cannot synthesize new protein. To generate a more accurate model, the human sequence for a severe form of G6PD deficiency (Med -) was knocked into the murine G6PD locus. As predicted, G6PD levels were extremely low in RBCs and deficient mice have increased hemolytic sequalae to oxidant stress. G6PD levels were mildly decreased in non-erythroid organs, consistent with what has been observed in humans. Juxtaposition of G6PD deficient and wild-type mice revealed altered lipid metabolism in multiple organ systems. Together, these findings both establish a new mouse model of G6PD deficiency that more accurately reflects human G6PD deficiency and also advance our basic understanding of altered metabolism in this setting.
Resurrected Rubisco suggests uniform carbon isotope signatures over geologic time
Authors: Kedzior Mateusz , Garcia Amanda K. , Li Meng , Taton Arnaud , Adam Zachary R. , Young Jodi N. , Kacar Betul
Published: June 2021

The earliest geochemical indicators of microbes—and the enzymes that powered them—extend back almost 3.8 billion years on our planet. Paleobiologists often attempt to understand these indicators by assuming that the behaviors of modern microbes and enzymes are consistent (uniform) with those of their predecessors. A uniformitarian assumption (i.e., the idea that fundamental geobiological processes have occurred in much the same manner over Earth history) seems at odds with our understanding of the inherent variability of living systems. Here, we examine whether a uniformitarian assumption for an enzyme thought to generate carbon isotope indicators of biological activity, RuBisCO, can be corroborated by independently studying the history of changes recorded within RuBisCO’s genetic sequences. Specifically, we resurrected a Precambrian-age, ancient RuBisCO by engineering its ancient DNA inside a modern cyanobacterium genome and measured the engineered organism’s fitness and carbon-isotope-discrimination profile. The envelope of ancestral RuBisCO isotopic fractionation observed here indicates that uniformitarian assumptions may be warranted, but with important caveats. Our results suggest that further inquiries that link molecule-level evolutionary changes with planet-level geochemical conditions are needed to discern whether enzyme-affected isotope fractionation trends extend deeper into the early Precambrian. Experimental studies illuminating life’s early molecular innovations are crucial to explore the foundations of Precambrian uniformitarian assumptions.
Center-surround interactions underlie bipolar cell motion sensing in the mouse retina
Authors: Strauss Sarah , Korympidou Maria M , Ran Yanli , Franke Katrin , Schubert Timm , Baden Tom , Berens Philipp , Euler Thomas , Vlasits Anna L
Published: June 2021

Motion is a critical aspect of vision. We studied the representation of motion in mouse retinal bipolar cells and found, surprisingly, that some bipolar cells possess motion-sensing capabilities that rely on their center-surround receptive fields. Using a glutamate sensor, we directly observed motion-sensitive bipolar cell synaptic output, which was strongest for local motion and dependent on the motion’s origin. We characterized bipolar cell receptive fields and found that there are motion and non-motion sensitive bipolar cell types, the majority being motion sensitive. Next, we used these bipolar cell receptive fields along with connectomics to design biophysical models of downstream cells. The models and experiments demonstrated that bipolar cells pass motion-sensitive excitation to starburst amacrine cells through direction-specific signals mediated by bipolar cells’ center-surround receptive field structure. As bipolar cells provide excitation to most amacrine and ganglion cells, their motion sensitivity may contribute to motion processing throughout the visual system.
Differential microRNA expression analyses across two brain regions in Alzheimer’s disease
Authors: Dobricic Valerija , Schilling Marcel , Schulz Jessica , Zhu Ling-Shuang , Zhou Chao-Wen , Fuß Janina , Franzenburg Sören , Zhu Ling-Qiang , Parkkinen Laura , Lill Christina M. , Bertram Lars
Published: June 2021

Background

Dysregulation of microRNAs (miRNAs) is involved in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD). Hitherto, sample sizes from differential miRNA expression studies in AD are exceedingly small aggravating any biological inference. To overcome this limitation, we investigated six candidate miRNAs in a large collection of brain samples.

Methods

Brain tissue was derived from superior temporal gyrus (STG) and entorhinal cortex (EC) from 99 AD patients and 91 controls. Expression of six miRNAs was examined by qPCR (STG) or small RNA sequencing (EC). Brain region-dependent differential miRNA expression was investigated in a transgenic AD mouse model using qPCR and FISH. Total RNA sequencing was used to assess differential expression of miRNA target genes.

Results

MiR-129-5p, miR-132-5p, and miR-138-5p were significantly downregulated in AD vs. controls both in STG and EC, while miR-125b-5p and miR-501-3p showed no evidence for differential expression in this dataset. In addition, miR-195-5p was significantly upregulated in EC but not STG in AD patients. The brain region-specific pattern of miR-195-5p expression was corroboratedin vivoin transgenic AD mice. Total RNA sequencing identified several novel and functionally interesting target genes of these miRNAs involved in synaptic transmission (GABRB1), the immune-system response (HCFC2) or AD-associated differential methylation (SLC16A3).

Conclusions

Using two different methods (qPCR and small RNA-seq) in two separate brain regions in 190 individuals we more than doubled the available sample size for most miRNAs tested. Differential gene expression analyses confirm the likely involvement of miR-129-5p, miR-132-5p, miR-138-5p, and miR-195-5p in AD pathogenesis and highlight several novel potentially relevant target mRNAs.

Funding

This work was supported by the Deutsche Forschungsgemeinschaft (DFG) and the National Science Foundation China (NSFC) as a Joint Sino-German research project (“MiRNet-AD”, #391523883). Additional support was provided by the DFG Research Infrastructure NGS_CC (project 407495230) as part of the Next Generation Sequencing Competence Network (#423957469) and the Cure Alzheimer’ s Fund (CAF) as part of the CIRCUITS consortium project.
Nuclear and plastid phylogenomic analyses provide insights into the reticulate evolution, species delimitation and biogeography of the Sino-Japanese disjunctive Diabelia (Caprifoliaceae)
Authors: Ke Xiu-Rong , Morales-Briones Diego F. , Wang Hong-Xin , Sun Qing-Hui , Landis Jacob B. , Wen Jun , Wang Hua-Feng
Published: June 2021

Understanding biological diversity and the mechanisms of the Sino-Japanese disjunctions are major challenges in eastern Asia biogeography. The Sino-Japanese flora has been broadly studied as an ideal model for plant phylogeography. Diabelia (Caprifoliaceae) is an East Asian genus, with a disjunctive distribution across the Sino-Japanese region. However, relationships within Diabelia remain elusive. In this study, we reconstructed the phylogeny of Diabelia and inferred historical biogeography and evolutionary patterns based on nuclear and plastid sequences from target enrichment and genome skimming approaches, respectively. We found that the main clades within Diabelia were discordant between nuclear and plastid trees. Both nuclear and plastid phylogenetic analyses supported five main clades: D. serrata, D. tetrasepala, D. sanguinea, D. spathulata var. stenophylla and D. spathulata var. spathulata. Species network analyses revealed that Diabelia tetrasepala is likely the result of a hybridization event. Divergence time estimation and ancestral area reconstructions showed that Diabelia originated in Japan during the early Miocene, with subsequent vicariance and dispersal events between Japan and Korea, and between Japan and China. Overall, our results support the division of Diabelia into five main clades and the recognition of five species in the genus. This research provides new insights in the species delimitation and speciation processes of taxonomically complex lineages such as Diabelia.
Putative role of PV and SOM interneuron subtypes in working memory
Authors: Patil Pritish , Katkov Mikhail , Yizhar Ofer , Tsodyks Misha
Published: June 2021

Working memory is an essential human trait required for all cognitive activities. Our previous model from Mongillo et al. (1), Mi et al. (2) uses synaptic facilitation to store traces of working memory. Thus memories can be maintained without persistent neural activity. A critical component of this model is a central inhibition which prevents multiple item representations from being active at the same time. We know from experimental studies that multiple genetically-defined interneuron subtypes (e.g. PV, SOM) with different excitability and connectivity properties mediate inhibition in the cortex. The role of these sub-types in working memory however is not known. Here we develop a modified model with these interneuron subtypes, and propose their functional roles in working memory. We make concrete testable predictions about the roles of these groups.
Serial Dependence in Temporal Perception Reveals the Dynamics of Constructing an Internal Reference Frame
Authors: Wang Tianhe , Luo Yingrui , Pöppel Ernst , Bao Yan
Published: June 2021

Temporal perception is crucial to cognitive functions. To better estimate temporal durations, the observers need to construct an internal reference frame based on past experience and apply it to guide future perception. However, how this internal reference frame is constructed remains largely unclear. Here we showed the dynamics of the internal reference construction from the perspective of serial dependence in temporal reproduction tasks. We found the current duration estimation is biased towards both perceived and reproduced durations in previous trials. Moreover, this effect is regulated by the variability of sample durations. The influence of previous trials was stronger when the observers were exposed to context with more variable durations, which is inconsistent with previous theories that the similarity between successive stimuli induces serial dependence. We proposed a Bayesian model with an adaptive reference updated continuously after each observation, which can better explain the serial dependence observed in temporal perception.
Anatomical Structures, Cell Types, and Biomarkers Tables Plus 3D Reference Organs in Support of a Human Reference Atlas
Authors: Börner Katy , Teichmann Sarah A. , Quardokus Ellen M. , Gee James , Browne Kristen , Osumi-Sutherland David , Herr Bruce W. , Bueckle Andreas , Paul Hrishikesh , Haniffa Muzlifah A. , Jardine Laura , Bernard Amy , Ding Song-Lin , Miller Jeremy A. , Lin Shin , Halushka Marc , Boppana Avinash , Longacre Teri A. , Hickey John , Lin Yiing , Valerius M. Todd , He Yongqun , Pryhuber Gloria , Sun Xin , Jorgensen Marda , Radtke Andrea J. , Wasserfall Clive , Ginty Fiona , Ho Jonhan , Sunshine Joel , Beuschel Rebecca T. , Brusko Maigan , Lee Sujin , Malhotra Rajeev , Jain Sanjay , Weber Griffin
Published: June 2021

1.

This paper reviews efforts across 16 international consortia to construct human anatomical structures, cell types, and biomarkers (ASCT+B) tables and three-dimensional reference organs in support of a Human Reference Atlas. We detail the ontological descriptions and spatial three-dimensional anatomical representations together with user interfaces that support the registration and exploration of human tissue data. Four use cases are presented to demonstrate the utility of ASCT+B tables for advancing biomedical research and improving health.
Lessons from 20 years of plant genome sequencing: an unprecedented resource in need of more diverse representation
Authors: Marks Rose A. , Hotaling Scott , Frandsen Paul B. , VanBuren Robert
Published: June 2021

The field of plant genomics has grown rapidly in the past 20 years, leading to dramatic increases in both the quantity and quality of publicly available genomic resources. With this ever-expanding wealth of genomic data from an increasingly diverse set of taxa, unprecedented potential exists to better understand the genome biology and evolution of plants. Here, we provide a contemporary view of plant genomics, including analyses on the quality of existing plant genome assemblies, the taxonomic distribution of sequenced species, and how national participation has influenced the field’s development. We show that genome quality has increased dramatically in recent years, that substantial taxonomic gaps exist, and that the field has been dominated by affluent nations in the Global North and China, despite a wide geographic distribution of sequenced species. We identify multiple disconnects between the native range of focal species and the national affiliation of the researchers studying the plants, which we argue are rooted in colonialism--both past and present. However, falling sequencing costs paired with widening availability of analytical tools and an increasingly connected scientific community provide key opportunities to improve existing assemblies, fill sampling gaps, and, most importantly, empower a more global plant genomics community.
Phylogenetic context using phylogenetic outlines
Authors: Bagci Caner , Bryant David , Cetinkaya Banu , Huson Daniel H.
Published: June 2021

Abstract

Microbial studies typically involve the sequencing and assembly of draft genomes for individual microbes or whole microbiomes. Given a draft genome, one first task is to determine its phylogenetic context, that is, to place it relative to the set of related reference genomes. We provide a new interactive graphical tool that addresses this task using Mash sketches to compare against all bacterial and archaeal representative genomes in the GTDB taxonomy, all within the framework of SplitsTree5. The phylogenetic context of the query sequences is then displayed as a phylogenetic outline, a new type of phylogenetic network that is more general that a phylogenetic tree, but significantly less complex than other types of phylogenetic networks. We propose to use such networks, rather than trees, to represent phylogenetic context, because they can express uncertainty in the placement of taxa, whereas a tree must always commit to a specific branching pattern. We illustrate the new method using a number of draft genomes of different assembly quality.
Cryo-EM structures of human RNA polymerase I
Authors: Misiaszek Agata D. , Girbig Mathias , Grötsch Helga , Baudin Florence , Lafita Aleix , Murciano Brice , Müller Christoph W.
Published: June 2021

RNA polymerase I (Pol I) specifically synthesizes ribosomal RNA. Pol I upregulation is linked to cancer, while mutations in the Pol I machinery lead to developmental disorders. Here, we report the cryo-EM structure of elongating human Pol I at 2.7 Å resolution. In the exit tunnel, we observe a double-stranded RNA helix that may support Pol I processivity. Our structure confirms that human Pol I consists of 13 subunits with only one subunit forming the Pol I stalk. Additionally, the structure of human Pol I in complex with the initiation factor RRN3 at 3.1 Å resolution reveals stalk flipping upon RRN3 binding. We also observe an inactivated state of human Pol I bound to an open DNA scaffold at 3.3 Å resolution. Lastly, the high-resolution structure of human Pol I allows mapping of disease-related mutations that can aid understanding of disease etiology.
EnTrance: Exploration of Entropy Scaling Ball Cover Search in Protein Sequences
Authors: Kim Yoonjin , Guo Zhen , Robertson Jeffrey A. , Reidys Benjamin , Zhang Ziyan , Heath Lenwood S.
Published: June 2021

Biological sequence alignment using computational power has received increasing attention as technology develops. It is important to predict if a novel DNA sequence is potentially dangerous by determining its taxonomic identity and functional characteristics through sequence identification. This task can be facilitated by the rapidly increasing amounts of biological data in DNA and protein databases thanks to the corresponding increase in computational and storage costs. Unfortunately, the growth in biological databases has caused difficulty in exploiting this information. EnTrance presents an approach that can expedite the analysis of this large database by employing entropy scaling. This allows scaling with the amount of entropy in the database instead of scaling with the absolute size of the database. Since DNA and protein sequences are biologically meaningful, the space of biological sequences demonstrates the structure exploited by entropy scaling. As biological sequence databases grow, taking advantage of this structure can be extremely beneficial for reducing query times. EnTrance, the entropy scaling search algorithm introduced here, accelerates the biological sequence search exemplified by tools such as BLAST. EnTrance does this by utilizing a two step search approach. In this fashion, EnTrance quickly reduces the number of potential matches before more exhaustively searching the remaining sequences. Tests of EnTrance show that this approach can lead to improved query times. However, constructing the required entropy scaling indices beforehand can be challenging. To improve performance, EnTrance investigates several ideas for accelerating index build time that supports entropy scaling searches. In particular, EnTrance makes full use of the concurrency features of Go language greatly reducing the index build time. Our results identify key tradeoffs and demonstrate that there is potential in using these techniques for sequence similarity searches. Finally, EnTrance returns more matches and higher percentage identity matches when compared with existing tools.
Functional organization of frontoparietal cortex in the marmoset investigated with awake resting-state fMRI
Authors: Hori Yuki , Cléry Justine C. , Schaeffer David J. , Menon Ravi S. , Everling Stefan
Published: June 2021

Frontoparietal networks contribute to complex cognitive functions in humans and macaques such as working memory, attention, task-switching, response suppression, grasping, reaching, and eye movement control. However, little is known about the organization of frontoparietal networks in the New World common marmoset monkey (Callithrix jacchus) which is now widely recognized as a powerful nonhuman primate experimental animal. In this study, we employed hierarchical clustering of interareal BOLD signals to investigate the hypothesis that the organization of the frontoparietal cortex in the marmoset follows the organizational principles of the macaque frontoparietal system. We found that the posterior part of the lateral frontal cortex (premotor regions) was functionally connected to the anterior parietal areas while more anterior frontal regions (frontal eye field (FEF)) were connected to more posterior parietal areas (the area around lateral intraparietal area (LIP)). These overarching patterns of inter-areal organization are consistent with a recent macaque study. These findings demonstrate parallel frontoparietal processing streams in marmosets and support the functional homologies of FEF-LIP and premotor-anterior parietal pathways between marmoset and macaque.

Significant Statement

Frontoparietal networks contribute to many cognitive functions in humans and macaques, but little is known about the organization of frontoparietal networks in the New World common marmoset monkey. Here, we investigated the hypothesis that the organization of the frontoparietal cortex in the marmoset follows the organizational principles of the macaque frontoparietal system. These frontoparietal connection showed overarching pattern of interareal organization consistent with Old world monkeys. These findings demonstrate parallel frontoparietal processing streams in marmosets.
Genome characterization of ‘Candidatus Phytoplasma meliae’ (isolate ChTYXIII)
Authors: Fernández Franco Daniel , Conci Luis Rogelio
Published: June 2021

‘Candidatus Phytoplasma meliae’ (subgroups 16SrXIII-G and XIII-C) has been reported in association to chinaberry yellowing disease in Argentina, Bolivia and Paraguay. In Argentina, this disease constitutes a major phytosanitary problem for chinaberry forestry production. To date, no genome information of this phytoplasma and others from 16SrXIII-group has been published, hindered its characterization at genomic level. Here we analyze the draft genome of ‘Candidatus Phytoplasma meliae’ strain ChTYXIII obtained from a chinaberry-infected plant using a metagenomics approach. The draft assembly consists of twenty-one contigs with a total length of 751.949 bp. The annotation contains 669 CDSs, 34tRNA and one set of rRNA operons. Metabolic pathways analysis indicated that the ChTYXIII contains the complete core genes for glycolysis and functional sec system for translocation of proteins. The phylogenetic relationships inferred 132 single copy genes (orthologues core) analysis revealed that ‘Ca. P. meliae’ constitutes a clade closely related to the ‘Ca. australiense’ and ‘Ca. P. solani’. Thirty-one putative effectors were identified, among which a homologue to SAP11 was found and others that have only been described in this pathogen. This work provides relevant genomic information for ‘Ca. P. meliae’ and constitutes the first genome described for the group 16SrXIII (MPV).
Genomic evidence for a chemical link between redox conditions and microbial community composition
Authors: Dick Jeffrey M. , Tan Jingqiang
Published: June 2021

Environmental influences on community structure are often assessed through multivariate analyses in order to relate microbial abundances to separately measured physicochemical variables. However, genes and proteins are themselves chemical entities; in combination with genome databases, differences in microbial abundances directly encode for chemical variability. We predicted that the carbon oxidation state of inferred community proteomes, obtained by combining taxonomic abundances from published 16S rRNA gene sequencing datasets with predicted microbial proteomes from the NCBI Reference Sequence (RefSeq) database, would reflect environmental oxidation-reduction conditions in various natural and engineered settings including shale gas wells. Our analysis confirms the geobiochemical predictions for environmental redox gradients within and between hydrothermal systems and stratified lakes and marine environments. Where they are present, a common set of taxonomic groups (Gamma- and Deltaproteobacteria and Clostridia) act as drivers of the community-level differences in oxidation state, whereas Flavobacteria most often oppose the overall changes. The geobiochemical signal is largest for the steep redox gradients associated with hydrothermal systems and between surface water and produced fluids from shale gas wells, demonstrating the ability to determine the magnitude of redox effects on microbial communities from 16S sequencing alone.
Enhanced negative emotional processing limits behavioral flexibility in a mouse model of autism spectrum disorder
Authors: Yun Miru , Kim Eunjoon , Jung Min Whan
Published: June 2021

Impaired behavioral flexibility might underlie some of the symptoms associated with autism spectrum disorder (ASD). We investigated whether and how behavioral flexibility is impaired in a mouse model of ASD by testing Shank2-knockout (Shank2-KO) mice in reversal learning. Shank2-KO mice were trained in probabilistic classical conditioning with two odor cues paired with water and air puff. Upon the reversal of cue-outcome contingency, Shank2-KO mice were significantly slower than wild-type mice in reversing their anticipatory licking responses. Shank2-KO mice also showed stronger anticipatory eye closure responses than wild-type mice to the air puff, raising a possibility that the impairment might be because of enhanced negative emotional processing. Indeed, Shank2-KO mice showed intact reversal learning when the strong air puff was replaced with a mild air puff. Shank2-KO mice also showed intact reversal learning between two odor cues predicting rewards with different probabilities. These results indicate that enhanced negative emotional processing suppresses reversal learning despite of intact capability to learn cue-outcome contingency changes in Shank2-KO mice in our behavioral settings. Our findings suggest that behavioral flexibility may be seriously limited by abnormal emotional processing in ASD.
The role of obesity in female reproductive conditions: A Mendelian Randomisation study
Authors: Venkatesh Samvida S. , Ferreira Teresa , Benonisdottir Stefania , Rahmioglu Nilufer , Becker Christian M. , Granne Ingrid , Zondervan Krina T. , Holmes Michael V. , Lindgren Cecilia M. , Wittemans Laura B. L.
Published: June 2021

Background

Obesity is observationally associated with altered risk of many female reproductive conditions. These include polycystic ovary syndrome (PCOS), abnormal uterine bleeding, endometriosis, infertility, and pregnancy-related disorders. However, the roles and mechanisms of obesity in the aetiology of reproductive disorders remain unclear.

Methods and Findings

We estimated observational and genetically predicted causal associations between obesity, metabolic hormones, and female reproductive conditions using logistic regression, generalised additive models, and Mendelian randomisation (two-sample, non-linear, and multivariable) applied to data from UK Biobank and publicly available genome-wide association studies (GWAS).

Body mass index (BMI), waist-hip ratio (WHR), and WHR adjusted for BMI (WHRadjBMI) were observationally (odds ratios (ORs) = 1.02 – 1.87 per 1 S.D. obesity trait) and causally (ORs = 1.06 – 2.09) associated with uterine fibroids (UF), PCOS, heavy menstrual bleeding (HMB), and pre-eclampsia. Causal effect estimates of WHR and WHRadjBMI, but not BMI, were attenuated compared to their observational counterparts. Genetically predicted visceral adipose tissue mass was causal for the development of HMB, PCOS, and pre-eclampsia (ORs = 1.01 - 3.38). Increased waist circumference also posed a higher causal risk (ORs = 1.16 – 1.93) for the development of these disorders and UF than did increased hip circumference (ORs = 1.06 – 1.10). Leptin, fasting insulin, and insulin resistance each mediated between 20% -50% of the total causal effect of obesity on pre-eclampsia. Reproductive conditions clustered based on shared genetic components of their aetiological relationships with obesity.

Conclusions

In this first systematic, large-scale, genetics-based analysis of the aetiological relationships between obesity and female reproductive conditions, we found that common indices of overall and central obesity increased risk of reproductive disorders to heterogenous extents, mediated by metabolic hormones. Our results suggest exploring the mechanisms mediating the causal effects of overweight and obesity on gynaecological health to identify targets for disease prevention and treatment.
Arousal-dependent auditory responses in the brain of Bengalese finches measured by gene expression
Authors: Iizuka Takafumi , Mori Chihiro , Okanoya Kazuo
Published: June 2021

Songbirds use auditory feedback to maintain their own songs. Juveniles also memorize a tutor song and use memory as a template to make up their own songs through auditory feedback. A recent electrophysiological study revealed that HVC neurons respond to BOS playback only in low arousal, sleeping, or anesthetized conditions. One outstanding question is how does auditory suppression occur in the brain? Here, we determined how arousal affects auditory responses simultaneously in the whole brain and over the song neural circuit in Bengalese finches, using the immediate early gene egr-1 as a marker of neural activity. Our results showed that auditory responses in the low-arousal state were less susceptible to gating, which was also confirmed by gene expression, and that the suppression may be weaker than observed in previous zebra finch studies. This may be because the Bengalese finch is a domesticated species. In addition, our results suggest that information may flow from the MLd.I of the midbrain to higher auditory regions. Altogether, this study presents a new attempt to explore the auditory suppression network by simultaneously investigating the whole brain using molecular biology methods.
Distinct spatiotemporal contribution of morphogenetic events and mechanical tissue coupling during Xenopus neural tube closure
Authors: Christodoulou Neophytos , Skourides Paris A.
Published: June 2021

Neural tube closure (NTC) is a fundamental process during vertebrate embryonic development and is indispensable for the formation of the central nervous system. Here, using Xenopus laevis embryos, live imaging, single cell tracking, optogenetics and loss of function experiments we examine the contribution of convergent extension (CE) and apical constriction (AC) and we define the role of the surface ectoderm (SE) during NTC. We show that NTC is a two-stage process and that CE and AC do not overlap temporally while their spatial activity is distinct. PCP driven CE is restricted to the caudal part of the neural plate (NP) and takes place during the first stage. CE is essential for correct positioning of the NP rostral most region in the midline of the dorsoventral axis. AC occurs after CE throughout the NP and is the sole contributor of anterior NTC. We go on to show that the SE is mechanically coupled with the NP providing resistive forces during NTC. Its movement towards the midline is passive and driven by forces generated through NP morphogenesis. Last, we show that increase of SE resistive forces is detrimental for NP morphogenesis, showing that correct SE development is permissive for NTC.
Brief exposure of neuronal cells to levels of short chain fatty acids observed in human systemic circulation impair the cell lipid metabolism resulting in associated cell death by apoptosis
Authors: Fillier Tiffany A. , Shah Shrushti , Doody Karen M. , Pham Thu H. , Aubry Isabelle , Tremblay Michel L. , Cheema Sukhinder K. , Blundell Jacqueline , Thomas Raymond H.
Published: June 2021

Communication between gut microbiota and the brain is an enigma. Alterations in the gut microbial community affects enteric metabolite levels, such as SCFAs. SCFAs have been proposed as a possible mechanism through which the gut microbiome modulate brain health and function. This study analyzed for the first time the effects of SCFAs at levels reported in human systemic circulation on human neuronal cell energy metabolism, viability, survival and the brain lipidome. Cell and rat brain lipidomics was done using UHPLC-HESI-HRAMS/MS. Neuronal cells viability, survival and energy metabolism were analyzed via flow cytometer, immunofluorescence, and SeahorseXF platform. Lipidomics analysis demonstrated that SCFAs significantly remodeled the brain lipidome in vivo and in vitro. The most notable remodulation was observed in the metabolism of phosphatidylethanolamine plasmalogens, and mitochondrial lipids carnitine and cardiolipin. Increased mitochondrial mass, fragmentation, and hyperfusion occurred concomitant with the altered mitochondrial lipid metabolism resulting in decreased neuronal cell respiration, ATP production, and increased cell death. This suggests SCFAs at levels observed in human systemic circulation can adversely alter the brain lipidome and neuronal cell function potentially negatively impacting brain health outcomes.
Discovery, diversity and functional associations of crAss-like phages in human gut metagenomes from four Dutch cohorts
Authors: Gulyaeva Anastasia , Garmaeva Sanzhima , Ruigrok Renate A.A.A. , Wang Daoming , Riksen Niels P. , Netea Mihai G. , Wijmenga Cisca , Weersma Rinse K. , Fu Jingyuan , Vila Arnau Vich , Kurilshikov Alexander , Zhernakova Alexandra
Published: June 2021

The crAss-like phages are a diverse group of related viruses that includes one of the most abundant viruses of the human gut. To explore their diversity and functional role in human population and clinical cohorts, we analyzed gut metagenomic data collected from more than 2000 individuals from the Netherlands. We discovered 125 novel species-level and 32 novel genus-level clusters of crAss-like phages, all belonging to five previously recognized groups associated with the human gut. Analysis of their genomic features revealed that closely related crAss-like phages can possess strikingly divergent regions responsible for transcription, presumably acquired through recombination. Prediction of crAss-like phage hosts pointed primarily to bacteria of the phylum Bacteroidetes, consistent with previous reports. Finally, we explored the temporal stability of crAss-like phages over a 4-year period and identified associations between the abundance of crAss-like phages and several human phenotypes, including depletion of crAss-like phages in inflammatory bowel disease patients.

Highlights

125 tentative new species of crAss-like phages were discovered

Closely related crAss-like phages often possess highly divergent transcription gene modules possibly acquired via recombination

CrAss-like fraction of the human gut virome remains relatively stable over the period of 4 years

Prevalence of crAss-like phages in the human gut is associated with several metabolic, dietary and health phenotypes

Gut crAss-like phages are depleted in inflammatory bowel disease patients
The draft chromosome-level genome assembly of tetraploid ground cherry (Prunus fruticosa Pall.) from long reads
Authors: Wöhner Thomas W. , Emeriewen Ofere F. , Wittenberg Alexander H.J. , Schneiders Harrie , Vrijenhoek Ilse , Halász Júlia , Hrotkó Károly , Hoff Katharina J. , Gabriel Lars , Keilwagen Jens , Berner Thomas , Schuster Mirko , Peil Andreas , Wünsche Jens , Kropop Stephan , Flachowsky Henryk
Published: June 2021

Background

Cherries are stone fruits and belong to the economically important plant family of Rosaceae with worldwide cultivation of different species. The ground cherry, Prunus fruticosa Pall. is one ancestor of cultivated sour cherry, an important tetraploid cherry species. Here, we present a long read chromosome-level draft genome assembly and related plastid sequences using the Oxford Nanopore Technology PromethION platform and R10.3 pore type.

Finding

The final assemblies obtained from 117.3 Gb cleaned reads representing 97x coverage of expected 1.2 Gb tetraploid (2n=4x=32) and 0.3 Gb haploid (1n=8) genome sequence of P. fruticosa were calculated. The N50 contig length ranged between 0.3 and 0.5 Mb with the longest contig being ∼6 Mb. BUSCO estimated a completeness between 98.7 % for the 4n and 96.1 % for the 1n datasets.

Using a homology and reference based scaffolding method, we generated a final consensus genome sequence of 366 Mb comprising eight chromosomes. The N50 scaffold was ∼44 Mb with the longest chromosome being 66.5 Mb.

The repeat content was estimated to ∼190 Mb (52 %) and 58,880 protein-coding genes were annotated. The chloroplast and mitochondrial genomes were 158,217 bp and 383,281 bp long, which is in accordance with previously published plastid sequences.

Conclusion

This is the first report of the genome of ground cherry (P. fruticosa) sequenced by long read technology only. The datasets obtained from this study provide a foundation for future breeding, molecular and evolutionary analysis in Prunus studies.