bluuebunny/crossref_metadata_2025 huggingface dataset:
A robustness comparison of two market network models
Authors: Semenov D P , Koldanov A P , Koldanov P A , Pardalos P M
Published: January 2021

Two market network models are investigated. One of them is based on the classical Pearson correlation as the measure of association between stocks returns, whereas the second one is based on the sign similarity measure of association between stocks returns. We study the uncertainty of identification procedures for the following market network characteristics: distribution of weights of edges, vertex degree distribution in the market graph (MG), cliques and independent sets in the MG and the vertex degree distribution of the maximum spanning tree. We define the true network characteristics, the losses from the error of its identification by observations and the uncertainty of identification procedures as the expected value of losses. We use an elliptically contoured distribution as a model of the multivariate stocks returns distribution. It is shown that identification of statistical procedures based on the sign similarity are statistically robust in contrast to the procedures based on the classical Pearson correlation.
Dose–response and functional role of whey permeate as a source of lactose and milk oligosaccharides on intestinal health and growth of nursery pigs
Authors: Jang Ki Beom , Purvis Jerry M , Kim Sung W
Published: January 2021

Two experiments were conducted to evaluate dose–response and supplemental effects of whey permeate on growth performance and intestinal health of nursery pigs. In experiment (exp.) 1, 1,080 pigs weaned at 6.24 kg body weight (BW) were allotted to five treatments (eight pens/treatment) with increasing levels of whey permeate in three phases (from 10% to 30%, 3% to 23%, and 0% to 9% for phase 1, 2, and 3, respectively) fed until 11 kg BW and then fed a common phase 4 diet (0% whey permeate) until 25 kg BW in a 48-d feeding trial. Feed intake and BW were measured at the end of each phase. In exp. 2, 1,200 nursery pigs at 7.50 kg BW were allotted to six treatments (10 pens/treatment) with increasing levels of whey permeate from 0% to 18.75% fed until 11 kg BW. Feed intake and BW were measured during 11 d. Six pigs per treatment (1 per pens) were euthanized to collect the jejunum to evaluate tumor necrosis factor-alpha, interleukin-8 (IL-8), transforming growth factor-beta 1, mucin 2, histomorphology, digestive enzyme activity, crypt cell proliferation rate, and jejunal mucosa-associated microbiota. Data were analyzed using contrasts in the MIXED procedure and a broken-line analysis using the NLIN procedure of SAS. In exp. 1, increasing whey permeate had a quadratic effect (P < 0.05) on feed efficiency (G:F; maximum: 1.35 at 18.3%) in phase 1. Increasing whey permeate linearly increased (P < 0.05) average daily gain (ADG; 292 to 327 g/d) and G:F (0.96 to 1.04) of pigs in phase 2. In exp. 2, increasing whey permeate linearly increased (P < 0.05) ADG (349 to 414 g/d) and G:F (0.78 to 0.85) and linearly increased (P < 0.05) crypt cell proliferation rate (27.8% to 37.0%). The breakpoint from a broken-line analysis was obtained at 13.6% whey permeate for maximal G:F. Increasing whey permeate tended to change IL-8 (quadratic, P = 0.052; maximum: 223 pg/mg at 10.9%), to decrease Firmicutes:Bacteroidetes (P = 0.073, 1.59 to 1.13), to increase (P = 0.089) Bifidobacteriaceae (0.73% to 1.11%), and to decrease Enterobacteriaceae (P = 0.091, 1.04% to 0.52%) and Streptococcaceae (P = 0.094, 1.50% to 0.71%) in the jejunal mucosa. In conclusion, dietary inclusion of whey permeate increased the growth of nursery pigs from 7 to 11 kg BW. Pigs grew most efficiently with 13.6% whey permeate. Improvement in growth performance is partly attributed to stimulating intestinal immune response and enterocyte proliferation with positive changes in jejunal mucosa-associated microbiota in nursery pigs.
Geographical stratification of urban green areas in European cities
Authors: Picard Pierre M , Tran Huyen T T
Published: January 2021

This article studies the provision of urban green areas in cities where residents have preferences for the size of and access to those areas. At the optimum, the number of urban green spaces is a nonmonotone function of distance to the city center, while the sizes and distances to other urban green areas increase as one moves to the urban fringe. This article empirically investigates those properties for the 300 largest European cities by using the Global Monitoring Environment Services Urban Atlas database (European Environmental Agency). The empirical analysis confirms the nonmonotone relationship between the number of urban green spaces and the distance to the city center. The distance between two parks also increases as one moves toward the urban fringe.
A low CO2-responsive mutant of Setaria viridis reveals that reduced carbonic anhydrase limits C4 photosynthesis
Authors: Chatterjee Jolly , Coe Robert A , Acebron Kelvin , Thakur Vivek , Yennamalli Ragothaman M , Danila Florence , Lin Hsiang-Chun , Balahadia Christian Paolo , Bagunu Efren , Padhma Preiya P O S , Bala Soumi , Yin Xiaojia , Rizal Govinda , Dionora Jacqueline , Furbank Robert T , von Caemmerer Susanne , Quick William Paul
Published: January 2021

In C4 species, β-carbonic anhydrase (CA), localized to the cytosol of the mesophyll cells, accelerates the interconversion of CO2 to HCO3–, the substrate used by phosphoenolpyruvate carboxylase (PEPC) in the first step of C4 photosynthesis. Here we describe the identification and characterization of low CO2-responsive mutant 1 (lcr1) isolated from an N-nitroso-N-methylurea- (NMU) treated Setaria viridis mutant population. Forward genetic investigation revealed that the mutated gene Sevir.5G247800 of lcr1 possessed a single nucleotide transition from cytosine to thymine in a β-CA gene causing an amino acid change from leucine to phenylalanine. This resulted in severe reduction in growth and photosynthesis in the mutant. Both the CO2 compensation point and carbon isotope discrimination values of the mutant were significantly increased. Growth of the mutants was stunted when grown under ambient pCO2 but recovered at elevated pCO2. Further bioinformatics analyses revealed that the mutation has led to functional changes in one of the conserved residues of the protein, situated near the catalytic site. CA transcript accumulation in the mutant was 80% lower, CA protein accumulation 30% lower, and CA activity ~98% lower compared with the wild type. Changes in the abundance of other primary C4 pathway enzymes were observed; accumulation of PEPC protein was significantly increased and accumulation of malate dehydrogenase and malic enzyme decreased. The reduction of CA protein activity and abundance in lcr1 restricts the supply of bicarbonate to PEPC, limiting C4 photosynthesis and growth. This study establishes Sevir.5G247800 as the major CA allele in Setaria for C4 photosynthesis and provides important insights into the function of CA in C4 photosynthesis that would be required to generate a rice plant with a functional C4 biochemical pathway.
Wedlock or Wed-Lockup? A Case for Abolishing Restitution of Conjugal Rights in India
Authors: Uma Saumya
Published: January 2021

Colonialism in India consisted of a “civilizing mission” when the British rulers sought to initiate reforms in India, by projecting themselves to be the forerunners of modernity. Ironically, restitution of conjugal rights (RCR) runs contrary to any claims of modernity. Through an RCR, an unwilling spouse could be directed by the coercive machinery of the law to cohabit with his/her spouse, in recognition of the right of married persons to conjugality and consortium. Although couched in gender neutral terms, the remedy had and continues to have grave ramifications for women. This was applied by British judges to family law cases in India in the 1800s, and incorporated in family law statutes in post-independent India. RCR remains in force and is a legal remedy sought in the Indian courts till date, although it was abolished in England in 1970. This article critically examines RCR through historical, legal, feminist and comparative law perspectives. It analyses the impact of the English remedy on the norms of marriage and family in India, which are sites of oppression of, violence against and subordination of women. It argues for the repeal of RCR from the Indian statute books as it undermines bodily integrity and sexual autonomy of women in intimate relationships, and is incongruent with constitutional principles and India’s international human rights obligations.
Searching for wide-orbit gravitational instability protoplanets with ALMA in the dust continuum
Authors: Humphries J , Hall C , Haworth T J , Nayakshin S
Published: January 2021

Searches for young gas giant planets at wide separations have so far focused on techniques appropriate for compact (Jupiter-sized) planets. Here, we point out that protoplanets born through gravitational instability (GI) may remain in an initial pre-collapse phase for as long as the first 105–107 yr after formation. These objects are hundreds of times larger than Jupiter and their atmospheres are too cold (T ∼ tens of K) to emit in the near-infrared or Hα via accretion shocks. However, it is possible that their dust emission can be detected with Atacama Large Millimeter/submillimeter Array (ALMA), even around Classes I and II protoplanetary discs. In this paper, we produce synthetic observations of these protoplanets. We find that making a detection in a disc at 140 pc would require a few hundred minutes of ALMA band 6 observation time. Protoplanets with masses of 3–5 MJ have the highest chance of being detected; less massive objects require unreasonably long observation times (1000 min), while more massive ones collapse into giant planets before 105 yr. We propose that high-resolution surveys of young (105–106 yr), massive and face on discs offer the best chance for observing protoplanets. Such a detection would help to place constraints on the protoplanet mass spectrum, explain the turnover in the occurrence frequency of gas giants with system metallicity and constrain the prevalence of GI as a planet formation mechanism. Consistent lack of detection would be evidence against GI as a common planet formation mechanism.
Music Use in Adult Patients with Sickle Cell Disease: A Pilot Survey Study
Authors: Rodgers-Melnick Samuel N , Gam Kristina , Debanne Sara , Little Jane A
Published: January 2021

Sickle cell disease (SCD) is a group of genetic disorders primarily affecting individuals of African descent. Adults with SCD experience both acute and chronic pain. Data on music preferences, resources, and music-based pain strategies of adults with SCD are needed to tailor future music therapy interventions to the unique needs of adults with SCD. The purpose of this study was to (1) gather descriptive data related to music use in adults with SCD and (2) explore associations between participants’ music use, pain interference, and perceived helpfulness of music for reducing pain. In total, 100 adults with SCD participated in this survey during outpatient clinic visits. Results indicate a population that: (1) faces significant challenges related to pain interference (M = 61.13, SE = 0.76); (2) perceives music as being helpful for managing challenges, including mood (57%), sleep (48%), stress (47%), and pain (37%); (3) purposefully engages in music listening to manage pain (74%); and (4) would be interested in participating in music therapy services in inpatient (88%) and outpatient (81%) settings. Participants selected songs in genres, such as Hip-Hop/Rap and R&B/Soul, that contrast with previously reported characteristics of music for pain management. There was a moderate positive correlation (rs = 0.516, p < .001) between the number of strategies used alongside music and the perceived helpfulness of music for reducing pain. Findings inform the clinical use of music therapy and support future music therapy research with this population to address quality of life.
Interplay of folded domains and the disordered low-complexity domain in mediating hnRNPA1 phase separation
Authors: Martin Erik W , Thomasen F Emil , Milkovic Nicole M , Cuneo Matthew J , Grace Christy R , Nourse Amanda , Lindorff-Larsen Kresten , Mittag Tanja
Published: January 2021

Liquid–liquid phase separation underlies the membrane-less compartmentalization of cells. Intrinsically disordered low-complexity domains (LCDs) often mediate phase separation, but how their phase behavior is modulated by folded domains is incompletely understood. Here, we interrogate the interplay between folded and disordered domains of the RNA-binding protein hnRNPA1. The LCD of hnRNPA1 is sufficient for mediating phase separation in vitro. However, we show that the folded RRM domains and a folded solubility-tag modify the phase behavior, even in the absence of RNA. Notably, the presence of the folded domains reverses the salt dependence of the driving force for phase separation relative to the LCD alone. Small-angle X-ray scattering experiments and coarse-grained MD simulations show that the LCD interacts transiently with the RRMs and/or the solubility-tag in a salt-sensitive manner, providing a mechanistic explanation for the observed salt-dependent phase separation. These data point to two effects from the folded domains: (i) electrostatically-mediated interactions that compact hnRNPA1 and contribute to phase separation and (ii) increased solubility at higher ionic strengths mediated by the folded domains. The interplay between disordered and folded domains can modify the dependence of phase behavior on solution conditions and can obscure signatures of physicochemical interactions underlying phase separation.
A case series of pediatric survivors of anaplastic pleomorphic xanthoastrocytoma
Authors: Ronsley Rebecca , Dunham Christopher , Yip Stephen , Brown Lindsay , Zuccato Jeffrey A , Karimi Shirin , Zadeh Gelareh , Goddard Karen , Singhal Ash , Hukin Juliette , Cheng Sylvia
Published: January 2021

Background

Anaplastic pleomorphic xanthoastrocytoma (APXA) is a rare subtype of CNS astrocytoma. They are generally treated as high-grade gliomas; however, uncertainty exists regarding the optimal therapy. Here, we report on 3 pediatric cases of APXA.

Methods

Our institutional database was queried for cases of APXA and 3 cases were identified. Surgical samples were processed for methylation profiling and chromosomal microarray analysis. Methylation data were uploaded to the online CNS tumor classifier to determine methylation-based diagnoses to determine copy number variations (CNVs).

Results

Two patients were male, 1 female, and all were aged 12 years at diagnosis. All underwent a gross total resection (GTR) and were diagnosed with an APXA. Immunohistochemical analysis demonstrated that 2 cases were BRAF V600E positive. Methylation-based tumor classification supported the APXA diagnosis in all cases. CNV analyses revealed homozygous CKDN2A deletions in all and chromosome 9p loss in 2 cases. All patients received radiation therapy (54 Gy in 30 fractions) with concurrent temozolomide. Two patients received maintenance chemotherapy with temozolomide and lomustine for 6 cycles as per the Children’s Oncology Group ACNS0423. The third patient recurred and went on to receive a second GTR and 6 cycles of lomustine, vincristine, and procarbazine. All are alive with no evidence of disease >4 years post-treatment completion (overall survival = 100%, event free survival = 67%).

Conclusions

The natural history and optimal treatment of this rare pediatric tumor are not well understood. This case series supports the use of adjuvant chemoradiotherapy in the treatment of APXA. The genetic landscape may be informative for optimizing treatment and prognosis.
Small-Area Estimation of Smoke-Free Workplace Policies and Home Rules in US Counties
Authors: Liu Benmei , Dompreh Isaac , Hartman Anne M
Published: January 2021

Introduction

The workplace and home are sources of exposure to secondhand smoke, a serious health hazard for nonsmoking adults and children. Smoke-free workplace policies and home rules protect nonsmoking individuals from secondhand smoke and help individuals who smoke to quit smoking. However, estimated population coverages of smoke-free workplace policies and home rules are not typically available at small geographic levels such as counties. Model-based small-area estimation techniques are needed to produce such estimates.

Methods

Self-reported smoke-free workplace policies and home rules data came from the 2014–2015 Tobacco Use Supplement to the Current Population Survey. County-level design-based estimates of the two measures were computed and linked to county-level relevant covariates obtained from external sources. Hierarchical Bayesian models were then built and implemented through Markov Chain Monte Carlo methods.

Results

Model-based estimates of smoke-free workplace policies and home rules were produced for 3134 (of 3143) US counties. In 2014–2015, nearly 80% of US adult workers were covered by smoke-free workplace policies, and more than 85% of US adults were covered by smoke-free home rules. We found large variations within and between states in the coverage of smoke-free workplace policies and home rules.

Conclusions

The small-area modeling approach efficiently reduced the variability that was attributable to small sample size in the direct estimates for counties with data and predicted estimates for counties without data by borrowing strength from covariates and other counties with similar profiles. The county-level modeled estimates can serve as a useful resource for tobacco control research and intervention.

Implications

Detailed county- and state-level estimates of smoke-free workplace policies and home rules can help identify coverage disparities and differential impact of smoke-free legislation and related social norms. Moreover, this estimation framework can be useful for modeling different tobacco control variables and applied elsewhere, for example, to other behavioral, policy, or health related topics.
Membrane voltage as a dynamic platform for spatiotemporal signaling, physiological, and developmental regulation
Authors: Klejchova Martina , Silva-Alvim Fernanda A L , Blatt Michael R , Alvim Jonas Chaves
Published: January 2021

Membrane voltage arises from the transport of ions through ion-translocating ATPases, ion-coupled transport of solutes, and ion channels, and is an integral part of the bioenergetic “currency” of the membrane. The dynamics of membrane voltage—so-called action, systemic, and variation potentials—have also led to a recognition of their contributions to signal transduction, both within cells and across tissues. Here, we review the origins of our understanding of membrane voltage and its place as a central element in regulating transport and signal transmission. We stress the importance of understanding voltage as a common intermediate that acts both as a driving force for transport—an electrical “substrate”—and as a product of charge flux across the membrane, thereby interconnecting all charge-carrying transport across the membrane. The voltage interconnection is vital to signaling via second messengers that rely on ion flux, including cytosolic free Ca2+, H+, and the synthesis of reactive oxygen species generated by integral membrane, respiratory burst oxidases. These characteristics inform on the ways in which long-distance voltage signals and voltage oscillations give rise to unique gene expression patterns and influence physiological, developmental, and adaptive responses such as systemic acquired resistance to pathogens and to insect herbivory.
Brexit, Terrorist Attacks, and Hate Crime: A Longitudinal Analysis
Authors: Piatkowska Sylwia J , Stults Brian J
Published: January 2021

Drawing on theories of intergroup conflict and research on political legitimization of prejudice and crime motivated by bias, this study examines the temporal clustering of hate crimes in the aftermath of triggering events in the UK. In addition to domestic and nondomestic terrorist attacks, we consider the effects of the EU referendum widely known as Brexit. Consistent with previous work, the results reveal sharp increases of hate crimes in the aftermath of the antecedent events. However, we found that the effects of the EU referendum were more prolonged and more intense than the effects of the other triggering events. Moreover, the effects of domestic events are generally significant and stronger in magnitude than nondomestic events. Finally, the results show that the duration and decay of the effects of terrorist attacks on hate crimes generally mirror the severity of the galvanizing event. Taken together, our findings underscore the role of the EU referendum in explaining dramatic increases in crime motivated by bias. Accordingly, they are of particular importance to politicians and policy makers and have implications that go beyond the case of Brexit.
Humoral response to COVID-19 infection in immunosuppressed patients with inflammatory bowel disease
Authors: Scharrer Susanna , Kutschera Maximilian , Weseslindtner Lukas , Primas Christian , Vogelsang Harald
Published: January 2021

The course of coronavirus 19 (COVID-19) might be determined by certain comorbidities (e.g. diabetes, hypertension and other cardiovascular diseases) and advanced age. Because the impact of immunosuppression on disease severity is not entirely clear, management of patients under immunosuppressive treatment remains controversial. Six cases of inflammatory bowel disease (IBD) patients with COVID-19 on immunosuppressive medication are presented. The aim of this study was to describe patients’ clinical manifestation and chronologic development of virus-specific antibodies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection before and after restart with immunosuppressive/biological therapy as an indicator for a specific immune response. All patients were tested for the presence of SARS-CoV-2-RNA with PCR, were in clinical remission prior to COVID-19 and only one patient continued his immunosuppressive treatment during the COVID-19 infection. Initial symptoms of COVID-19 were pyrexia, diarrhea, cephalea, and dysgeusia and anosmia. No patient needed admission to hospital or ICU. The SARS-CoV-2 antibody development was described to be late in three of the six patients. Late antibody development seems to be more frequent in older patients and in patients with combined immunosuppressive treatment. In this scenario, SARS-CoV-2 antibody testing could be useful prior to restarting immunosuppressive therapy.
An optic ray theory for durotactic axon guidance
Authors: Oliveri Hadrien , Franze Kristian , Goriely Alain
Published: January 2021

During the development of the nervous system, neurons extend bundles of axons that grow and meet other neurons to form the neuronal network. Robust guidance mechanisms are needed for these bundles to migrate and reach their functional target. Directional information depends on external cues such as chemical or mechanical gradients. Unlike chemotaxis that has been extensively studied, the role and mechanism of durotaxis, the directed response to variations in substrate rigidity, remain unclear. We model bundle migration and guidance by rigidity gradients by using the theory of morphoelastic rods. We show that at a rigidity interface, the motion of axon bundles follows a simple behavior analogous to optic ray theory and obeys Snell’s law for refraction and reflection. We use this powerful analogy to demonstrate that axons can be guided by the equivalent of optical lenses and fibers created by regions of different stiffnesses.
P. falciparumK13 mutations present varying degrees of artemisinin resistance and reduced fitness in African parasites
Authors: Stokes Barbara H. , Rubiano Kelly , Dhingra Satish K. , Mok Sachel , Straimer Judith , Gnädig Nina F. , Bath Jade R. , Deni Ioanna , Ward Kurt E. , Striepen Josefine , Yeo Tomas , Ross Leila S. , Legrand Eric , Ariey Frédéric , Cunningham Clark H. , Souleymane Issa M. , Gansané Adama , Nzoumbou-Boko Romaric , Ndayikunda Claudette , Kabanywanyi Abdunoor M. , Uwimana Aline , Smith Samuel J. , Kolley Olimatou , Ndounga Mathieu , Warsame Marian , Leang Rithea , Nosten François , Anderson Timothy J.C. , Rosenthal Philip J. , Ménard Didier , Fidock David A.
Published: January 2021

The emergence of artemisinin (ART) resistance inPlasmodium falciparumparasites, driven by K13 mutations, has led to widespread antimalarial treatment failure in Southeast Asia. In Africa, our genotyping of 3,299 isolates confirms the emergence of the K13 R561H variant in Rwanda and reveals the continuing dominance of wild-type K13 across 11 countries. We show that this mutation, along with M579I and C580Y, confers varying degrees ofin vitroART resistance in African parasites. C580Y and M579I cause substantial fitness costs, which may counter-select against their dissemination in high-transmission settings. We also define the impact of multiple K13 mutations on ART resistance and fitness in multiple Southeast Asian strains. ART susceptibility is unaltered upon editing point mutations in ferrodoxin or mdr2, earlier resistance markers. These data point to the lack of an evident biological barrier to mutant K13 mediating ART resistance in Africa, while identifying their detrimental impact on parasite growth.
The imprintedZdbf2gene finely tunes feeding and growth in neonates
Authors: Glaser Juliane , Iranzo Julian , Borensztein Maud , Marinucci Mattia , Gualtieri Angelica , Jouhanneau Colin , Teissandier Aurelie , Gaston-Massuet Carles , Bourc’his Deborah
Published: January 2021

Genomic imprinting refers to the mono-allelic and parent-specific expression of a subset of genes. While long recognized for their role in embryonic development, imprinted genes have recently emerged as important modulators of postnatal physiology, notably through hypothalamus-driven functions. Here, using mouse models of loss, gain and parental inversion of expression, we report that the paternally expressedZdbf2gene controls neonatal growth in mice, in a dose-sensitive but parent-of-origin-independent manner. We further found thatZdbf2-KO neonates failed to fully activate hypothalamic circuits that stimulate appetite, and suffered milk deprivation and diminished circulating Insulin Growth Factor 1 (IGF-1). Consequently, only half ofZdbf2-KO pups survived the first days after birth and those surviving were smaller. This study demonstrates that precise imprinted gene dosage is essential for vital physiological functions at the transition from intra- to extra-uterine life, here the adaptation to oral feeding and optimized body weight gain.
A synthetic switch based on orange carotenoid protein to control blue light responses in chloroplasts
Authors: Piccinini Luca , Cazzaniga Stefano , Iacopino Sergio , Ballottari Matteo , Giuntoli Beatrice , Licausi Francesco
Published: January 2021

Synthetic biology approaches to engineer light‐responsive system are widely used, but their applications in plants are still limited, due to the interference with endogenous photoreceptors. Cyanobacteria, such asSynechocystis spp., possess a soluble carotenoid associated protein named Orange Carotenoid binding Protein (OCP) that, when activated by blue‐green light, undergoes reversible conformational changes that enable photoprotection of the phycobilisomes. Exploiting this system, we developed a new chloroplast‐localized synthetic photoswitch based on a photoreceptor‐associated protein‐fragment complementation assay (PCA). SinceArabidopsis thalianadoes not possess the prosthetic group needed for the assembly of the OCP2 protein, we implemented the carotenoid biosynthetic pathway with a bacterial β‐carotene ketolase enzyme (crtW), to generate keto‐carotenoids producing plants. The novel photoswitch was tested and characterized in Arabidopsis protoplasts with experiments aimed to uncover its regulation by light intensity, wavelength, and its conversion dynamics. We believe that this pioneer study establishes the basis for future implementation of plastid optogenetics to regulate organelle responses, such as gene transcription or enzymatic activity, upon exposure to specific light spectra.

One-sentence summary

Inspired by the light-driven conformational transitions of orange carotenoid proteins of cyanobacteria, we generated a molecular device able to switch its dimeric state in response to blue light.
Loss of the Long Non-coding RNA OIP5-AS1 Exacerbates Heart Failure in a Sex-Specific Manner
Authors: Zhuang Aowen , Calkin Anna C. , Lau Shannen , Kiriazis Helen , Donner Daniel G. , Liu Yingying , Bond Simon T. , Moody Sarah C. , Gould Eleanor A.M. , Colgan Timothy D. , Carmona Sergio Ruiz , Inouye Michael , de Aguiar Vallim Thomas Q. , Tarling Elizabeth J. , Quaife-Ryan Gregory A. , Hudson James E. , Porrello Enzo R. , Gregorevic Paul , Gao Xiao-Ming , Du Xiao-Jun , McMullen Julie R. , Drew Brian G.
Published: January 2021

Background

Long ncRNAs (lncRNAs) are known to influence numerous biological processes including cellular differentiation and tissue development. They are also implicated in the maintenance, health and physiological function of many tissues including the heart. Indeed, manipulating the expression of specific lncRNAs has been shown to improve pathological cardiac phenotypes such as heart failure. One lncRNA studied in various settings is OIP5-AS1 (also known as1700020I14RikandCyrano), however its role in cardiac pathologies remains mostly uncharacterised.

Methods

We used data generated from FACS sorted murine cardiomyocytes, human iPSC derived cardiomyocytes, as well as heart tissue from various animal models to investigate OIP5-AS1 expression in health and disease. Using CRISPR we engineered a global OIP5-AS1 knock out (KO) mouse model and performed cardiac pressure overload experiments to study heart failure in these animals. RNA-sequencing of left ventricles provided mechanistic insight between WT and KO mice.

Results

We demonstrate that OIP5-AS1 expression is regulated during cardiac development and cardiac specific pathologies in both rodent and human models. Moreover, we demonstrate that global female OIP5-AS1 KO mice develop exacerbated heart failure, but male mice do not. Transcriptomics and gene set enrichment analysis suggests that OIP5-AS1 may regulate pathways that impact mitochondrial function.

Conclusions

OIP5-AS1 is regulated in cardiac tissue and its deletion leads to worsening heart function under pressure overload in female mice. This may be due to impairments in mitochondrial function, highlighting OIP5-AS1 as a gene of interest in sex-specific differences in heart failure.
An agnostic study of associations between ABO and RhD blood group and phenome-wide disease risk
Authors: Dahlén Torsten , Clements Mark , Zhao Jingcheng , Olsson Martin L , Edgren Gustaf
Published: January 2021

There are multiple known associations between the ABO and RhD blood groups and disease. However, no systematic population-based studies elucidating associations between a large number of disease states and blood group have been conducted. Using SCANDAT3-S, a comprehensive nationwide blood donation-transfusion database, we modelled outcomes for 1,217 disease categories including 70 million person-years of follow-up, accruing from 5.1 million unique individuals. We discovered 49 and 1 associations between a disease and ABO and RhD blood group, respectively, after adjustment for multiple testing. We identified new associations such as kidney stones and blood group B as compared to O. We also expanded previous knowledge on other associations such as pregnancy-induced hypertension and blood group A and AB as compared to O and RhD positive as compared to negative. Our findings generate strong further support for previously known associations, but also indicate new interesting relations.
Dynamic dichotomy of accumbal population activity underlies cocaine sensitization
Authors: van Zessen Ruud , Flakowski Jérôme , Lüscher Christian
Published: January 2021

Locomotor sensitization (LS) is an early behavioral adaptation to addictive drugs, driven by the increase of dopamine in the Nucleus Accumbens (NAc). However, the effect on accumbal population activity remains elusive. Here we used single cell calcium imaging to record the activity of dopamine-1-receptor (D1R) and dopamine-2-receptor (D2R) expressing spiny projection neurons (SPNs) during cocaine LS. Acute exposure to cocaine elevated D1R SPN activity and reduced D2R SPN activity, albeit with high variability between neurons. During LS, the number of D1R and D2R neurons responding in opposite directions increased. Moreover, preventing LS by inhibition of the ERK signalling pathway decreased the number of cocaine-responsive D1R SPNs, but had little effect on D2R SPNs. These results indicate that accumbal population dichotomy is dynamic and contains a subgroup of D1R SPNs that eventually drives LS. Insights into the drug-related activity dynamics provides a foundation for understanding the circuit-level addiction pathogenesis.
Biodiversity Image Quality Metadata Augments Convolutional Neural Network Classification of Fish Species
Authors: Leipzig Jeremy , Bakis Yasin , Wang Xiaojun , Elhamod Mohannad , Diamond Kelly , Dahdul Wasila , Karpatne Anuj , Maga Murat , Mabee Paula , Bart Henry L. , Greenberg Jane
Published: January 2021

Biodiversity image repositories are crucial sources of training data for machine learning approaches to biological research. Metadata, specifically metadata about object quality, is putatively an important prerequisite to selecting sample subsets for these experiments. This study demonstrates the importance ofimage quality metadatato a species classification experiment involving a corpus of 1935 fish specimen images which were annotated with 22 metadata quality properties. A small subset of high quality images produced an F1 accuracy of 0.41 compared to 0.35 for a taxonomically matched subset of low quality images when used by a convolutional neural network approach to species identification. Using the full corpus of images revealed that image quality differed between correctly classified and misclassified images. We found the visibility of all anatomical features was the most important quality feature for classification accuracy. We suggest biodiversity image repositories consider adopting a minimal set of image quality metadata to support future machine learning projects.
Directed Functional and Structural Connectivity in a Large-Scale Model for the Mouse Cortex
Authors: Nunes Ronaldo V. , Reyes Marcelo Bussotti , Mejias Jorge F. , de Camargo Raphael Y.
Published: January 2021

Abstract

Inferring the structural connectivity from electrophysiological measurements is a fundamental challenge in systems neuroscience. Directed functional connectivity measures, such as the Generalized Partial Directed Coherence (GPDC), provide estimates of the causal influence between areas. However, the relation between causality estimates and structural connectivity is still not clear. We analyzed this problem by evaluating the effectiveness of GPDC to estimate the connectivity of a ground-truth, data-constrained computational model of a large-scale network model of the mouse cortex. The model contains 19 cortical areas comprised of spiking neurons, with areas connected by long-range projections with weights obtained from a tract-tracing cortical connectome. We show that GPDC values provide a reasonable estimate of structural connectivity, with an average Pearson correlation over simulations of 0.74. Moreover, even in a typical electrophysiological recording scenario containing five areas, the mean correlation was above 0.6. These results suggest that it may be possible to empirically estimate structural connectivity from functional connectivity even when detailed whole-brain recordings are not achievable.
The evolution of interdependence in a four-way mealybug symbiosis
Authors: Garber Arkadiy I. , Kupper Maria , Laetsch Dominik R. , Weldon Stephanie R. , Ladinsky Mark S. , Bjorkman Pamela J. , McCutcheon John P.
Published: January 2021

Mealybugs are insects that maintain intracellular bacterial symbionts to supplement their nutrientpoor plant sap diets. Some mealybugs have a single betaproteobacterial endosymbiont, aCandidatusTremblaya species (hereafterTremblaya) that alone provides the insect with its required nutrients. Other mealybugs have two nutritional endosymbionts that together provide these nutrients, whereTremblayahas gained a gammaproteobacterial partner that resides in the cytoplasm ofTremblaya. Previous work had established thatPseudococcus longispinusmealybugs maintain not one but two species of gammaproteobacterial endosymbionts along withTremblaya. Preliminary genomic analyses suggested that these two gammaproteobacterial endosymbionts have large genomes with features consistent with a relatively recent origin as insect endosymbionts, but the patterns of genomic complementarity between members of the symbiosis and their relative cellular locations were unknown. Here, using long-read sequencing and various types of microscopy, we show that the two gammaproteobacterial symbionts ofP. longispinusare mixed together withinTremblayacells, and that their genomes are somewhat reduced in size compared to their closest non-endosymbiotic relatives. Both gammaproteobacterial genomes contain thousands of pseudogenes, consistent with a relatively recent shift from a free-living to endosymbiotic lifestyle. Biosynthetic pathways of key metabolites are partitioned in complex interdependent patterns among the two gammaproteobacterial genomes, theTremblayagenome, and horizontally acquired bacterial genes that are encoded on the mealybug nuclear genome. Although these two gammaproteobacterial endosymbionts have been acquired recently in evolutionary time, they have already evolved co-dependencies with each other,Tremblaya, and their insect host.

Significance

Mealybugs are sap-feeding insects that house between one and three bacterial endosymbionts to supplement their nutritionally poor diets. Many mealybug-bacteria relationships were established tens or hundreds of millions of years ago, and these ancient examples show high levels host-endosymbiont genomic and metabolic integration. Here, we describe the complete genomes and cellular locations for two bacterial endosymbiont which have recently transitioned from a free-living to an intracellular state. Our work reveals the rapid emergence of metabolic interdependence between these two nascent endosymbionts, their partner bacterial co-symbiont in whose cytoplasm they reside, and their insect host cell. Our work confirms that intracellular bacteria rapidly adapt to a host-restricted lifestyle through breakage or loss of redundant genes.
Resequencing 250 soybean accessions: new insights into genes associated with agronomic traits and genetic networks
Authors: Yang Chunming , Yan Jun , Jiang Shuqin , Li Xia , Min Haowei , Wang Xiangfeng , Hao Dongyun
Published: January 2021

Limited knowledge on genomic diversity and the functional genes associated with soybean variety traits has resulted in slow breeding progress. We sequenced the genome of 250 soybean landraces and cultivars from China, America and Europe, and investigated their population structure, genetic diversity and architecture and selective sweep regions of accessions. We identified five novel agronomically important genes and studied the effects of functional mutations in respective genes. We found candidate genes GSTT1, GL3 and GSTL3 associated with isoflavone content, CKX3 associated with yield traits, and CYP85A2 associated with both architecture and yield traits. Our phenotype-gene network analysis revealed that hub nodes play a role in complex phenotypic associations. In this work, we describe novel agronomic trait associated genes and a complex genetic network, providing a valuable resource for future soybean molecular breeding.
The genomes of precision edited cloned calves show no evidence for off-target events or increasedde novomutagenesis
Authors: Jivanji Swati , Harland Chad , Cole Sally , Brophy Brigid , Garrick Dorian , Snell Russell , Littlejohn Mathew , Laible Götz
Published: January 2021

Animal health and welfare are at the forefront of public concern and the agricultural sector is responding by prioritising the selection of welfare-relevant traits in their breeding schemes. In some cases, welfare-enhancing traits such as horn-status (i.e., polled) or diluted coat colour, which could enhance heat tolerance, may not segregate in breeds of primary interest, highlighting gene-editing tools such as the CRISPR-Cas9 technology as an approach to rapidly introduce variation into these populations. A major limitation preventing the acceptance of CRISPR-Cas9 mediated gene-editing, however, is the potential for off-target mutagenesis, which has raised concerns about the safety and ultimate applicability of this technology. Here, we present a clone-based study design that has allowed a detailed investigation of off-target andde novomutagenesis in a cattle line bearing edits in thePMELgene for diluted coat-colour. No off-target events were detected from high depth whole genome sequencing performed in precursor cell-lines and resultant calves cloned from those edited and non-edited cell lines. Long molecule sequencing at the edited site and plasmid-specific PCRs did not reveal structural variations and/or plasmid integration events in edited samples. Furthermore, an in-depth analysis ofde novomutations across samples revealed that the mutation frequency and spectra were unaffected by editing status. Cells in culture, however, had a distinct mutation signature wherede novomutations were predominantly C>A mutations, and in cloned calves they were predominantly T>G mutations, deviating from the expected excess of C>T mutations. We conclude that the gene-edited cells and calves in this study did not present a higher mutation load than unedited controls. Cell culture and somatic cell nuclear transfer cloning processes contributed the major source of contrast in mutational profile between samples.
Spatial Variability in Streambed Microbial Community Structure Across Two Watersheds
Authors: Akinwole Philips O. , Kan Jinjun , Kaplan Louis A. , Findlay Robert H.
Published: January 2021

The spatial patterns of microbial communities are largely unknown compared to those of macro-fauna and flora. We investigated patterns of microbial community structure on streambed sediments from two watersheds across spatial scales spanning < 1m within a single stream to several hundred km between watersheds. Analyses of phospholipid fatty acids (PLFA) profiles indicated that the variations in microbial community structure were driven by increases in the relative abundance of microeukaryotic photoautotrophs and their contribution to total microbial biomass. Furthermore, streams within watersheds had similar microbial community structure, underscoring within-watershed controls of microbial communities. Moreover, bacterial community structure assayed as either polymerase chain reaction-denaturing gradient gelelectrophoresis (PCR-DGGE) fingerprints or PLFA profiles edited to remove microeukaryotes indicated a distinct watershed-level biogeography. No distinct stream order-level distributions were identified although DGGE analysis clearly indicated that there was greater variability in community structure among 1st-order streams compared to 2nd- and 3rd-order streams into which they flowed. Longitudinal gradients in microbial biomass and structure showed that the greatest variations were associated with 1st order streams within a watershed and 68% of the variation in total microbial biomass was explained by sediment C:N mass ratio, percent Carbon, sediment surface area, and percent water content. This study confirms a distinct microbial biogeography for headwater stream communities driven by environmental heterogeneity across distant watersheds and suggests that eukaryotic photoautotrophs play a key role in structuring sediment microbial communities.

IMPORTANCE

Microorganisms in streams drive many biogeochemical reactions of global significance, including nutrient cycling and energy flow, yet the mechanisms responsible for the distribution and composition of streambed microbial communities are not well known. We sampled sediments from multiple streams in two watersheds; Neversink River (New York) and White Clay Creek (Pennsylvania) watersheds and measured microbial biomass, total microbial and bacterial community structures using phospholipid and molecular methods. Microbial and bacterial community structures displayed a distinct watershed-level biogeography. The smallest headwater streams within a watershed showed the greatest variation in microbial biomass, and C:N ratio, percent carbon, sediment surface area and percent water content explained 68% of the variations in microbial biomass. This study indicates a non-random distribution of microbial communities in streambeds, and that microeukaryotic photoautotrophs, environmental heterogeneity and geographical distance influence microbial composition and spatial distribution.
Movements ofMycoplasma mobilegliding machinery detected by high-speed atomic force microscopy
Authors: Kobayashi Kohei , Kodera Noriyuki , Kasai Taishi , Tahara Yuhei O , Toyonaga Takuma , Mizutani Masaki , Fujiwara Ikuko , Ando Toshio , Miyata Makoto
Published: January 2021

Mycoplasma mobile, a parasitic bacterium, glides on solid surfaces, such as animal cells and glass by a special mechanism. This process is driven by the force generated through ATP hydrolysis on an internal structure. However, the spatial and temporal behaviors of the internal structures in living cells are unclear. In this study, we detected the movements of the internal structure by scanning cells immobilized on a glass substrate using high-speed atomic force microscopy (HS-AFM). By scanning the surface of a cell, we succeeded in visualizing particles, 2 nm in hight and aligned mostly along the cell axis with a pitch of 31.5 nm, consistent with previously reported features based on electron microscopy. Movements of individual particles were then analyzed by HS-AFM. In the presence of sodium azide, the average speed of particle movements was reduced, suggesting that movement is linked to ATP hydrolysis. Partial inhibition of the reaction by sodium azide enabled us to analyze particle behavior in detail, showing that the particles move 9 nm right, relative to the gliding direction, and 2 nm into the cell interior in 330 ms, then return to their original position, based on ATP hydrolysis.

IMPORTANCE

TheMycoplasmagenus contains bacteria generally parasitic to animals and plants. SomeMycoplasmaspecies form a protrusion at a pole, bind to solid surfaces, and glide by a special mechanism linked to their infection and survival. The special machinery for gliding can be divided into surface and internal structures that have evolved from rotary motors represented by ATP synthases. This study succeeded in visualizing the real-time movements of the internal structure by scanning from the outside of the cell using an innovative high-speed atomic force microscope, and then analyzing their behaviors.