bluuebunny/crossref_metadata_2025_split huggingface dataset:
picd-1, a gene that encodes CABIN1 domain-containing protein, interacts with pry-1/Axin to regulate multiple processes in Caenorhabditis elegans
Authors: Mallick Avijit , Taylor Shane K. B. , Mehta Sakshi , Gupta Bhagwati P. 
Published: September 2021

ABSTRACTAXIN family members control diverse biological processes in eukaryotes. As a scaffolding protein, AXIN facilitates interactions between cellular components and provides specificity to signaling pathways. Despite its crucial roles in metazoans and discovery of a large number of family members, the mechanism of AXIN function is not very well understood. The C. elegans AXIN homolog PRY-1 provides a powerful tool to identify interacting genes and downstream effectors that function in a conserved manner to regulate AXIN-mediated signaling. Previous work demonstrated pry-1’s essential role in developmental processes such as reproductive system, seam cells, and a P lineage cell P11.p. More recently, our lab carried out a transcriptome profiling of pry-1 mutant and uncovered the essential role of the gene in lipid metabolism, stress response, and aging. In this study, we have extended the work on pry-1 by reporting a novel interacting gene picd-1 (pry-1-interacting CABIN1 domain containing). Our findings have revealed that picd-1 plays an essential role in C. elegans and is involved in several pry-1-mediated processes including regulation of stress response and lifespan maintenance. In support of this, picd-1 expression overlaps with pry-1 in multiple tissues throughout the lifespan of animals. Further experiments showed that picd-1 inhibits CREB-regulated transcriptional coactivator homolog CRTC-1 function, which promotes longevity in a calcineurin-dependent manner. These data provide evidence for an essential role of the CABIN1 domain protein PICD-1 in mediating PRY-1 signaling in C. elegans.
Brain transcriptome analysis reveals gene expression differences associated with dispersal behaviour between range-front and range-core populations of invasive cane toads in Australia
Authors: Yagound Boris , West Andrea J. , Richardson Mark F. , Selechnik Daniel , Shine Richard , Rollins Lee A. 
Published: September 2021

AbstractUnderstanding the mechanisms underlying rapid adaptation of invasive species in novel environments is key to improving our ability to manage these species. Many invaders demonstrate rapid evolution of behavioural traits involved in range expansion such as locomotor activity, exploration and risk-taking. However, the molecular mechanisms that underpin these changes are poorly understood. In 86 years, invasive cane toads (Rhinella marina) in Australia have drastically expanded their geographic range westward from coastal Queensland to Western Australia. During their range expansion, toads have undergone extensive phenotypic changes, particularly in behaviours that enhance the toads’ dispersal ability. Common-garden experiments have shown that some changes in behavioural traits related to dispersal are heritable. However, genetic diversity is greatly reduced across the invasive range due to a strong founder effect, and the genetic basis underlying dispersal-related behavioural changes remains unknown. Here we used RNA-seq to compare the brain transcriptomes of toads from the Hawai’ian source population, as well as three distinct populations from across the Australian invasive range. We found markedly different gene expression profiles between the source population and Australian toads. By contrast, cane toads from across the Australian invasive range had very similar transcriptomic profiles. Yet, key genes with functions putatively related to dispersal behaviour showed differential expression between range-core and range-front populations. These genes could play an important role in the behavioural changes characteristic of range expansion in Australian cane toads.
How well does SARS-CoV-2 spread in hospitals?
Authors: Shirreff George , Zahar Jean-Ralph , Cauchemez Simon , Temime Laura , Opatowski Lulla ,   EMEA-MESuRS working group on the nosocomial modelling of SARS-CoV-2
Published: September 2021

AbstractCovid-19 poses significant risk of nosocomial transmission, and preventing this requires good estimates of the basic reproduction number R0 in hospitals and care facilities, but these are currently lacking. Such estimates are challenging due to small population sizes in these facilities and inconsistent testing practices.We estimate the patient-to-patient R0 and daily transmission rate of SARS-CoV-2 using data from a closely monitored hospital outbreak in Paris 2020 during the first wave. We use a realistic epidemic model which accounts for progressive stages of infection, stochastic effects and a large proportion of asymptomatic infections. Innovatively, we explicitly include changes in testing capacity over time, as well as the evolving sensitivity of PCR testing at different stages of infection. We conduct rigorous statistical inference using iterative particle filtering to fit the model to the observed patient data and validate this methodology using simulation.We provide estimates for R0 across the entire hospital (2.6) and in individual wards (from 3 to 15), possibly reflecting heterogeneity in contact patterns or control measures. An obligatory mask-wearing policy introduced during the outbreak is likely to have changed the R0, and we estimate values before (8.7) and after (1.3) its introduction, corresponding to a policy efficacy of 85%.
Durability of ChAdOx1 nCov-19 (AZD1222) vaccination in people living with HIV - responses to SARS-CoV-2, variants of concern and circulating coronaviruses
Authors: Ogbe Ane , Pace Mathew , Bittaye Mustapha , Tipoe Timothy , Adele Sandra , Alagaratnam Jasmini , Aley Parvinder K , Ansari M. Azim , Bara Anna , Broadhead Samantha , Brown Anthony , Brown Helen , Cappuccini Federica , Cinardo Paola , Dejnirattisai Wanwisa , Ewer Katie J. , Fok Henry , Folegatti Pedro M. , Fowler Jamie , Godfrey Leila , Goodman Anna L. , Jackson Bethany , Jenkin Daniel , Jones Mathew , Longet Stephanie , Makinson Rebecca , Marchevsky Natalie G. , Mathew Moncy , Mazzella Andrea , Mujadidi Yama F. , Parolini Lucia , Petersen Claire , Plested Emma , Pollock Katrina M. , Rajeswaran Thurkka , Ramasamy Maheshi N. , Rhead Sarah , Robinson Hannah , Robinson Nicola , Sanders Helen , Serrano Sonia , Stockmann Helen , Tipton Tom , Waters Anele , Zacharopoulou Panagiota , Barnes Eleanor , Dunachie Susanna , Goulder Philip , Klenerman Paul , Screaton Gavin R. , Winston Alan , Hill Adrian V. S. , Gilbert Sarah C. , Carroll Miles , Pollard Andrew J , Fidler Sarah , Fox Julie , Lambe Teresa , Frater John 
Published: September 2021

AbstractDuration of protection from SARS-CoV-2 infection in people with HIV (PWH) following vaccination is unclear. In a sub-study of the phase 2/3 the COV002 trial (NCT04400838), 54 HIV positive male participants on antiretroviral therapy (undetectable viral loads, CD4+ T cells >350 cells/ul) received two doses of ChAdOx1 nCoV-19 (AZD1222) 4-6 weeks apart and were followed for 6 months. Responses to vaccination were determined by serology (IgG ELISA and MesoScale Discovery (MSD)), neutralisation, ACE-2 inhibition, gamma interferon ELISpot, activation-induced marker (AIM) assay and T cell proliferation. We show that 6 months after vaccination the majority of measurable immune responses were greater than pre-vaccination baseline, but with evidence of a decline in both humoral and cell mediated immunity. There was, however, no significant difference compared to a cohort of HIV-uninfected individuals vaccinated with the same regimen. Responses to the variants of concern were detectable, although were lower than wild type. Pre-existing cross-reactive T cell responses to SARS-CoV-2 spike were associated with greater post-vaccine immunity and correlated with prior exposure to beta coronaviruses. These data support the on-going policy to vaccinate PWH against SARS-CoV-2, and underpin the need for long-term monitoring of responses after vaccination.
Effect of long-term low dose glucocorticoid on children with bronchial asthma
Authors: Du Xueping , Guo Yanjun , Yang Junzheng 
Published: September 2021

AbstractObjectivesTo investigate the clinical efficacy of long-term of low-dose inhaled glucocorticoid (ICS) in the treatment on children with bronchial asthma, and to evaluate its effects on the height, weight and expression of serum insulin-like growth factor of children with bronchial asthma.Methods91 children with bronchial asthma treated in our hospital from January 2017 to December 2017 were chosen, and 31 healthy children without asthma history in our hospital were selected as the control group (Group C); For the different treatment methods comparison, 91 children with bronchial asthma were divided into treatment group A (48 children) and treatment group B (43 children) randomly. In treatment group A, children were treated with low-dose ICS for more than 1 year; in treatment group B, children were treated with low-dose ICS for less than 1 year or received low-dose ICS for less than 2 months/year. For treatment evaluation, the asthma control test (C-ACT) were scored at 0 months, 12 months and 24 months in three groups, and the height and weight of children, the levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in serum in each group were also measured.ResultsIn the control group, the C-ACT scores were increased with time (P<0.01); the C-ACT scores of treatment group A at 12 months and at 24 months was significantly higher than that of treatment group B (P<0.05); there was no significant difference in height and weight between the treatment group and the control group at months, 12 months and 24 months after treatment (P>0.05); there was no significant difference in the expression levels of IGF-1 and IGFBP-3 in serum between treatment group and control group (P>0.05).Compared with the C-ACT scores in treatment group A and treatment group B at 0 month, the C-ACT scores were significantly higher at 12 months and at 24 months, and there was a statistical difference among 0 month, 12 months and at 24 months in treatment group A and treatment group B (P<0.01); The C-ACT score of treatment group A at the 12 month was significantly higher than that in treatment group B at the 12 months(P<0.05), and the C-ACT score in treatment group A at the 24 months was significantly higher than that of treatment group B (P<0.001).ConclusionsTreatment for children with bronchial asthma by long-term use of low-dose ICS is safe and effective, it does not affect health and development of children with bronchial asthma; children with bronchial asthma were treated with low-dose ICS for more than 1 year had a better effective than children were treated with low-dose ICS for less than 1 year or received low-dose ICS for less than 2 months/year.
Counting giraffes: A comparison of abundance estimators on the Ongava Game Reserve, Namibia
Authors: Christophe Bonenfant , Ken Stratford , Stéphanie Périquet 
Published: September 2021

AbstractCamera-traps are a versatile and widely adopted tool for collecting biological data for wildlife conservation and management. While estimating population abundance from camera-trap data is the primarily goal of many projects, the question of which population estimator is suitable for analysing these data needs to be investigated. We took advantage of a 21 day camera-trap monitoring period of giraffes (Giraffa camelopardalis angolensis) on the Ongava Game Reserve (Namibia) to compare capture-recapture (CR), rarefaction curves and N-mixture estimators of population abundance. A marked variation in detection probability of giraffes was observed both in time and between individuals. Giraffes were also less likely to be detected after they were seen at a waterhole (mean daily visit frequency of f = 0.25). We estimated the population size to be 119 giraffes (Cv = 0.10) using the most robust reference estimator (CR). All other estimators deviated from the CR population size by ca. −20 to > +80%. This was due the fact that these models did not account for the temporal and individual variations in detection probability. We found that modelling choice was much less forgiving for N-mixture models than CR estimators because it leads to very variable and inconsistent estimations of abundance. Double counts were problematic for N-mixture models, challenging the use of raw counts (i.e. when individuals are not identified) at waterholes, to monitor the abundance of giraffe or of other species without idiosyncratic coat patterns.
Tumor-Cell Invasion Initiates at Invasion Hotspots, an Epithelial Tissue-Intrinsic Microenvironment
Authors: Kobayashi Rei , Takishima Hiroaki , Deng Sheng , Fujita Yasuyuki , Tamori Yoichiro 
Published: September 2021

SummaryMalignant cancers emerge in epithelial tissues through a progressive process in which a single transformed mutant cell becomes tumorigenic and invasive. Although numerous genes involved in the malignant transformation of cancer cells have been described, how tumor cells launch an invasion into the basal side of epithelial tissues remains elusive. Here, using a Drosophila wing imaginal disc epithelia, we show that genetically mosaic clones of cells mutant for a neoplastic-tumor-suppressor gene (nTSG) in combination with the oncogenic Ras (RasV12) expression initiate invasion into the basal side of the epithelial layer at specific spots in the epithelial tissue. In this “invasion hotspot”, the oncogenic double-mutant cells activate c-Jun N-terminal kinase (JNK) signaling, which causes basal extrusion of the double-mutant cells and destruction of basement membrane through upregulation of a matrix metalloprotease, MMP1. Conversely, in other regions of the epithelial tissue, the double-mutant cells do not strongly activate JNK, deviate from the apical side of the epithelial layer, and show benign tumor growth in the lumen. These data indicate that the onset of tumor-cell invasion is highly dependent on the tissue-intrinsic local microenvironment. Given the conservation of genetic signaling pathways involved in this process, initiation of tumor-cell invasion from invasion hotspots in Drosophila wing imaginal epithelia could help us to understand the developmental mechanisms of invasive cancers.
Defining hierarchical protein interaction networks from spectral analysis of bacterial proteomes
Authors: Zaydman Mark A. , Little Alexander , Haro Fidel , Aksianiuk Valeryia , Buchser William J. , DiAntonio Aaron , Gordon Jeffrey I. , Milbrandt Jeffrey , Raman Arjun S. 
Published: September 2021

AbstractCellular phenotypes emerge from a hierarchy of molecular interactions: proteins interact to form complexes, pathways, and phenotypes. We show that hierarchical networks of protein interactions can be extracted from the statistical pattern of proteome variation as measured across thousands of bacteria and that these hierarchies reflect the emergence of complex bacterial phenotypes. We describe the mathematics underlying our statistical approach and validate our results through gene-set enrichment analysis and comparison to existing experimentally-derived hierarchical databases. We demonstrate the biological utility of our unbiased hierarchical models by creating a model of motility in Pseudomonas aeruginosa and using it to discover a previously unappreciated genetic effector of twitch-based motility. Overall, our approach, SCALES (Spectral Correlation Analysis of Layered Evolutionary Signals), predicts hierarchies of protein interaction networks describing emergent biological function using only the statistical pattern of bacterial proteome variation.
Use of eVLP-based vaccine candidates to broaden immunity against SARS-CoV-2 variants
Authors: Bozic Jasminka , Ahmed Tanvir , Ontsouka Barthelemy , Fluckiger Anne-Catherine , Diress Abebaw , Berthoud Tamara , Yuan Xiaoyang , Yang Lanjian , Diaz-Mitoma Francisco , Anderson David E. , Soare Catalina 
Published: September 2021

AbstractRapid emergence of SARS-CoV-2 variants is a constant threat and a major hurdle to reach heard immunity. We produced VBI-2905a, an enveloped virus-like particle (eVLP)-based vaccine candidate expressing prefusion spike protein from the Beta variant that contains several escape mutations. VBI-2905a protected hamsters against infection with a Beta variant virus and induced high levels of neutralizing antibodies against Beta RBD. In a heterologous vaccination regimen, a single injection of VBI-2905a in animals previously immunized with VBI-2902, a vaccine candidate expressing S from ancestral SARS-CoV-2, hamsters were equally protected against Beta variant infection. As an alternate strategy to broaden immunity, we produced a trivalent vaccine expressing the prefusion spike protein from SARS-CoV-2 together with unmodifed S from SARS-CoV-1 and MERS-CoV. Relative to immunity induced against the ancestral strain, the trivalent vaccine VBI-2901a induced higher and more consistent antibody binding and neutralizing responses against a panel of variants including Beta, Delta, Kappa, and Lambda, with evidence for broadening of immunity rather than just boosting cross-reactive antibodies.
Migrators Within Migrators: Exploring Transposable Element Dynamics in the Monarch Butterfly, Danaus plexippus
Authors: Baril Tobias , Hayward Alexander 
Published: September 2021

AbstractBackgroundLepidoptera (butterflies and moths) are an important model system in ecology and evolution. A high-quality chromosomal genome assembly is available for the monarch butterfly (Danaus plexippus), but it lacks an in-depth transposable element (TE) annotation, presenting an opportunity to explore monarch TE dynamics and the impact of TEs on shaping the monarch genome.ResultsWe find 6.21% of the monarch genome is comprised of TEs, a reduction of 6.85% compared to the original TE annotation performed on the draft genome assembly. Monarch TE content is low compared to two closely related species with available genomes, Danaus chrysippus (33.97% TE) and Danaus melanippus (11.87% TE). The biggest TE contributions to genome size in the monarch are LINEs and Penelope-like elements, and three newly identified families, r2-hero_dPle (LINE), penelope-1_dPle (Penelope-like), and hase2-1_dPle (SINE), collectively contribute 34.92% of total TE content. We find evidence of recent TE activity, with two novel Tc1 families rapidly expanding over recent timescales (tc1-1_dPle, tc1- 2_dPle). LINE fragments show signatures of genomic deletions indicating a high rate of TE turnover. We investigate associations between TEs and wing colouration and immune genes and identify a three-fold increase in TE content around immune genes compared to other host genes.ConclusionsWe provide a detailed TE annotation and analysis for the monarch genome, revealing a considerably smaller TE contribution to genome content compared to two closely related Danaus species with available genome assemblies. We identify highly successful novel DNA TE families rapidly expanding over recent timescales, and ongoing signatures of both TE expansion and removal highlight the dynamic nature of repeat content in the monarch genome. Our findings also suggest that insect immune genes are promising candidates for future interrogation of TE-mediated host adaptation.
Exposure to nitric oxide drives transition to differential culturability inMycobacterium tuberculosis
Authors: Glenn Sarah M. , Gap-Gaupool Brindha , Milburn Emily , Turapov Obolbek , Crosatti Marialuisa , Hincks Jennifer , Stewart Bradley , Bacon Joanna , Kendall Sharon L. , Voskuil Martin I. , Riabova Olga , Monakhova Natalia , Green Jeffrey , Waddell Simon J. , Makarov Vadim A. , Mukamolova Galina V. 
Published: September 2021

ABSTRACTDuring infectionMycobacterium tuberculosis(Mtb) forms differentially culturable (DC) subpopulations that are recalcitrant to treatment and undetectable using standard diagnostic tools. DC Mtb are revealed in liquid media, their revival is often stimulated by resuscitation-promoting factors (Rpfs), secreted peptidoglycan-remodelling enzymes, and prevented by Rpf inhibitors. Here we investigated the role of nitric oxide (NO) in generation of Rpf- dependent DC Mtb, using murine macrophage infection models and treatment with a synthetic NO donor (NOD). Mtb subpopulations were assessed by colony-forming unit counting on agar or by limiting dilution Most Probable Number assays in liquid media with or without Rpf inhibitor. Rpf-dependent DC Mtb were detected following infection of interferon-γ induced macrophages capable of producing NO, but not when iNOS was inactivated. NOD treatment also induced transition to the Rpf-dependent DC phenotype which was accompanied by global transcriptomic changes resulting in the dramatic down-regulation ofrpfA-Egene expression. Furthermore, the DC phenotype was partially reverted by artificial over-expression of Rpfs. This study elucidates molecular mechanisms underlying the generation of DC Mtb, which are the dominant population recovered from clinical tuberculosis samples, with implications for improving both tuberculosis diagnostics and treatments.
HIV-1 Vif protein is stabilized by AKT-mediated phosphorylation to enhance APOBEC3G degradation
Authors: Raja Rameez , Wang Chenyao , Banerjea Akhil C 
Published: September 2021

AbstractHIV-1 virus has to counter anti-viral restriction factors for its successful replication after its entry in the cell. The host-pathogen dynamics operate as soon as HIV-1 interacts with the cell. HIV-1 Vif has been known for its role in degradation of APOBEC3G; a cytosine deaminase which leads to hyper mutations in the viral DNA leading to aberrant viral replication. The cellular proteins regulating the intracellular HIV-1 Vif protein levels can have profound impact on HIV-1 pathogenesis. MDM2 is known to induce degradation of Vif with subsequent effects on APOBEC3G. Here, we have identified AKT/PKB as one of the crucial regulators of HIV-1 Vif protein. The rationale for selecting Vif as a target substrate for AKT was the presence of RMRINT motif in it, which is similar to the AKT phosphorylation motif RxRxxS/T. Immunoprecipitation assay and Kinase assay revealed that AKT and Vif interact strongly with each other and Vif is phosphorylated at T20 position by AKT. This phosphorylation stabilizes HIV-1 Vif while Vif mutant T20A degrades faster. Moreover, use of dominant negative form of AKT (KD-AKT) and AKT inhibitors were found to destabilise Vif and increase its K48-ubiquitination profile. The consequences of this AKT-Vif interplay were also validated on APOBEC3G degradation, a target of Vif. AKT inhibition was found to restore APOBEC3G levels. This process can be interpreted as a strategy used by virus to prevent MDM2 mediated Vif degradation; AKT stabilises Mdm2, which then targets Vif for degradation but at the same time AKT stabilises Vif by phosphorylating it. Thus, AKT mediated stabilization of Vif might compensate for its degradation by MDM2. This study can have significant implications as HIV-1 Tat protein and growth factors like insulin activate PI3-K/AKT Kinase pathway and can potentially affect Vif and APOBEC3G protein levels and hence HIV-1 pathogenesis.