bluuebunny/crossref_metadata_2025_split huggingface dataset:
N-terminal modification of actin by acetylation and arginylation determines the architecture and assembly rate of linear and branched actin networks
Authors: Chin Samantha M. , Hatano Tomoyuki , Sivashanmugam Lavanya , Suchenko Andrejus , Kashina Anna S. , Balasubramanian Mohan K. , Jansen Silvia 
Published: June 2020

AbstractThe great diversity in actin network architectures and dynamics is exploited by cells to drive fundamental biological processes, including cell migration, endocytosis and cell division. While it is known that this versatility is the result of the many actin-remodeling activities of actin-binding proteins, recent work implicates post-translational modification of the actin N-terminus by either acetylation or arginylation itself as an equally important regulatory mechanism. However, the molecular mechanisms by which acetylation and arginylation alter the properties of actin are not well understood. Here, we directly compare how processing, and modification of the N-terminus of actin affects its intrinsic polymerization dynamics and its remodeling by actin-binding proteins that are essential for cell migration. We find that in comparison to acetylated actin, arginylated actin reduces intrinsic as well as formin-mediated elongation and Arp2/3-mediated nucleation. By contrast, there are no significant differences in Cofilin-mediated severing. Taken together, these results suggest that cells can employ the differently modified actins to precisely regulate actin dynamics. In addition, unprocessed, or non-acetylated actin show very different effects on formin-mediated-elongation, Arp2/3-mediated nucleation, and severing by Cofilin. Altogether, this study shows that the nature of the N-terminus of actin can induce distinct actin network dynamics, which can be differentially used by cells to locally finetune actin dynamics at distinct cellular locations, such as at the leading edge.
An unbiased, quantitative and versatile method for determining misaligned and lagging chromosome during mitosis
Authors: Braga Luciano Gama , Prifti Diogjena Katerina , Garand Chantal , Saini Pawan Kumar , Elowe Sabine 
Published: June 2020

ABSTRACTAccurate chromosome alignment at metaphase facilitates the equal segregation of sister chromatids to each of the nascent daughter cells. Lack of proper metaphase alignment is an indicator of defective chromosome congression and aberrant kinetochore-microtubule attachments which in turn promotes chromosome missegregation and aneuploidy, hallmarks of cancer. Therefore, tools to sensitively and quantitatively measure chromosome alignment at metaphase will facilitate understanding of how changes in the composition and regulation of the microtubule attachment machinery impinge on this process. In this work, we have developed and validated a method based on analytical geometry to measure several indicators of chromosome misalignment. We generated semi-automated and flexible ImageJ2/Fiji pipelines to quantify kinetochore misalignment at metaphase plates as well as lagging chromosomes at anaphase. These tools will ultimately allow sensitive, unbiased, and systematic quantitation of these chromosome segregation defects in cells undergoing mitosis.
Resource optimization in COVID-19 diagnosis
Authors: Taniwaki S.A , Silva S.O.S , Santana-Clavijo N.F , Conselheiro J. A , Barone G.T , Menezes A.A.R , Pereira E.S , Brandão P.E 
Published: June 2020

AbtsractThe emergence and rapid dissemination worldwide of a novelCoronavirus(SARS-CoV-2) results in decrease of swabs availability for clinical samples collection, as well as, reagents for RT-qPCR diagnostic kits considered a confirmatory test for COVID-19 infection. This scenario, showed the requirement of improve de diagnostic capacity, so the aim of this study were to verify the possibility of reducing the reaction volume of RT-qPCR and to test cotton swabs as alternative for sample collection. RT-qPCR volumes and RNA sample concentration were optimized without affecting the sensitivity of assays, using both probe-based and intercalation dyes methods. Although rayon swabs showed better performance, cotton swabs could be used as alternative type for clinical sample collection. COVID-19 laboratory diagnosis is important to isolate and restrict the dissemination of virus, so seek for alternatives to decrease the coast of assays improve the control of disease.
Myristoylation alone is sufficient for PKA catalytic subunits to fractionally associate with the plasma membrane to regulate neuronal functions
Authors: Xiong Wei-Hong , Qin Maozhen , Zhong Haining 
Published: June 2020

AbstractMyristoylation is a post-translational modification that plays diverse functional roles in many protein species. The myristate moiety is considered insufficient for protein-membrane associations unless additional membrane-affinity motifs, such as a stretch of positively charged residues, are present. Here, we report that the electrically neutral N-terminal fragment of the protein kinase A catalytic subunit (PKA-C), in which myristoylation is the only functional motif, is sufficient for membrane association. This myristoylation can associate a fraction of PKA-C molecules or fluorescent proteins (FPs) to the plasma membrane in neuronal dendrites. The net neutral charge of PKA-C is evolutionally conserved, even though its membrane affinity can be readily tuned by changing charges near the myristoylation site. The observed membrane association, while moderate, is sufficient to concentrate PKA activity at the membrane by nearly 20-fold, and is required for PKA regulation of AMPA receptors at neuronal synapses. Our results indicate that myristoylation alone may be sufficient to drive functionally significant membrane association in the absence of assisting motifs. This provides a revised foundation for the understanding of how myristoylation regulates protein functions.
Abnormalities of the rib growth plate and the periphysis of previously healthy infants and toddlers dying suddenly and unexpectedly
Authors: Groff Elisa , Uday Suma , Zapata Vázquez Rita , Zainun Khairul , Cohen Marta C 
Published: June 2020

AbstractAimsHistological examination of the rib is of critical value in perinatal pathology and points to the health of the child preceding death. The rib is considered ideal because it is the most rapidly growing long bone in infants and demonstrates growth arrest at onset of the insult. We aimed to identify: 1: changes in the perichondrial ring in the rib of infants and children up to 16 months of age dying suddenly at our institution and 2: any association with presence of histological changes of vitamin D deficiency (VDD) /metabolic bone disease (MBD) in the growth plate.MethodsRetrospective review of the perichondrial rib histology and comparison with the presence or absence of histological features of VDD in the growth plate of 167 cases. The cases were anonymised and divided in six age/sex categories.ResultsPeriphyseal abnormalities were only seen in 38% of the cases; of whom 33% had established and 67% had mild changes. Only 14.5% of cases with established histological appearance of VDD at the growth plate had significant PR abnormality; of whom majority (83%) were ≤3 months of age and none ≥9 months old, reflecting a temporal relation with birth and beyond the perinatal period.ConclusionThe histological changes in the perichondrial ring are significantly associated with histological changes of VDD /MBD at the rib growth plate with an Odds Ratio of 3.04.
Evaluation on the diagnostic efficiency of different methods in detecting COVID-19
Authors: Yang Haitao , Lan Yuzhu , Yao Xiujuan , Lin Sheng , Xie Baosong 
Published: June 2020

AbstractObjectiveTo evaluate the diagnostic efficiency of different methods in detecting COVID-19 to provide preliminary evidence on choosing favourable method for COVID-19 detection.MethodsPubMed, Web of Science and Embase databases were searched for identifing eligible articles. All data were calculated utilizing Meta Disc 1.4, Revman 5.3.2 and Stata 12. The diagnostic efficiency was assessed via these indicators including summary sensitivity and specificity, positive likelihood ratio (PLR), negative LR (NLR), diagnostic odds ratio (DOR), summary receiver operating characteristic curve (sROC) and calculate the AUC.Results18 articles (3648 cases) were included. The results showed no significant threshold exist. EPlex: pooled sensitivity was 0.94; specificity was 1.0; PLR was 90.91; NLR was 0.07; DOR was 1409.49; AUC=0.9979, Q*=0.9840. Panther Fusion: pooled sensitivity was 0.99; specificity was 0.98; PLR was 42.46; NLR was 0.02; DOR was 2300.38; AUC=0.9970, Q*=0.9799. Simplexa: pooled sensitivity was 1.0; specificity was 0.97; PLR was 26.67; NLR was 0.01; DOR was 3100.93; AUC=0.9970, Q*=0.9800. Cobas®: pooled sensitivity was 0.99; specificity was 0.96; PLR was 37.82; NLR was 0.02; DOR was 3754.05; AUC=0.9973, Q*=0.9810. RT-LAMP: pooled sensitivity was 0.98; specificity was 0.99; PLR was 36.22; NLR was 0.04; DOR was 751.24; AUC=0.9905, Q*=0.9596. Xpert Xpress: pooled sensitivity was 0.99; specificity was 0.97; PLR was 27.44; NLR was 0.01; DOR was 3488.15; AUC=0.9977, Q*=0.9829.ConclusionsThese methods (ePlex, Panther Fusion, Simplexa, Cobas®, RT-LAMP and Xpert Xpress) bear higher sensitivity and specificity, and might be efficient methods complement to the gold standard.
COVID-19 Confirmed Cases and Fatalities in 883 U.S. Counties with a Population of 50,000 or More: Predictions Based on Social, Economic, Demographic Factors and Shutdown Days
Authors: Robertson Leon S. 
Published: June 2020

ABSTRACTThe spread of the COVID-19 virus is highly variable among U.S. counties. Seventeen factors known or thought to be related to spread of the COVID-19 virus were studied by Poisson regression analysis of confirmed cases and deaths in 883 U.S. counties with a population of 50,000 or more as of May 31, 2020. With little exception, each factor was predictive of incidence and mortality. The regression equation can be used to identify priority locations for preventive efforts and preparation for medical care caseloads when prevention is unsuccessful. Based on the correlation of cases and deaths to days since stay-at-home orders were issued, the orders reduced the cases about 48 percent and deaths about 50 percent. Focusing preventive efforts on the more vulnerable counties may be more effective and less economically damaging than statewide shutdowns.
Sex influences the effects of APOE genotype and Alzheimer’s diagnosis on neuropathology and memory
Authors: Duarte-Guterman Paula , Albert Arianne Y. , Barha Cindy K. , Galea Liisa A.M. 
Published: June 2020

AbstractAlzheimer’s disease (AD) is characterised by severe cognitive decline and pathological changes in the brain (brain atrophy, hyperphosphorylation of tau, and deposition of toxic amyloid-beta protein). Females have greater neuropathology (AD biomarkers and brain atrophy rates) and cognitive decline than males, however these effects can depend on diagnosis (amnestic mild cognitive impairment (aMCI) or AD) and APOE genotype (presence of ε4 alleles). Using the ADNI database (N=630 females, N=830 males), we analysed the effect of sex, APOE genotype (non-carriers or carriers of APOEε4 alleles), and diagnosis (cognitively normal (CN), early aMCI (EMCI), late aMCI (LMCI), probable AD) on cognition (memory and executive function), hippocampal volume, and AD biomarkers (CSF levels of amyloid beta, tau and ptau). Regardless of APOE genotype, memory scores were higher in CN, EMCI, and LMCI females compared to males but this sex difference was absent in probable AD, which may suggest a delay in the onset of cognitive decline or diagnosis and/or a faster trajectory of cognitive decline in females. We found that, regardless of diagnosis, CSF tau-pathology was disproportionately elevated in female carriers of APOEε4 alleles compared to males. In contrast, male carriers of APOEε4 alleles had reduced levels of CSF amyloid beta compared to females, irrespective of diagnosis. We also detected sex differences in hippocampal volume but the direction was dependent on the method of correction. Altogether results suggest that across diagnosis females show greater memory decline compared to males and APOE genotype affects AD neuropathology differently in males and females which may influence sex differences in incidence and progression of aMCI and AD.
Transgender fathering: children’s psychological and family outcomes
Authors: Condat Agnès , Mamou Grégor , Lagrange Chrystelle , Mendes Nicolas , Wielart Joy , Poirier Fanny , Medjkane François , Brunelle Julie , Drouineaud Véronique , Rosenblum Ouriel , Gründler Nouria , Ansermet François , Wolf Jean-Philippe , Falissard Bruno , Cohen David 
Published: June 2020

AbstractMedical advances in assisted reproductive technology have created new ways for transgender persons to become parents outside the context of adoption. The paucity of empirical data does not support the idea that trans-parenthood negatively impacts children’s development. However, the question has led to lively societal debates making the need for evidence-based studies urgent.We aimed to compare cognitive development, mental health, gender identity, quality of life and family dynamics using standardized instruments and experimental protocols in 32 children who were conceived by donor sperm insemination (DSI) in couples with a cisgender woman and a transgender man, the transition occurring before conception. We constituted two control groups matched for age, gender and family status.We found no significant difference between groups regarding cognitive development, mental health, and gender identity, meaning that neither the trans factor nor the use of DSI had any impact on these characteristics. The results of the descriptive analysis showed positive psycho-emotional development. Additionally, when we asked raters to differentiate the family drawings of the group of children of trans-fathers from those who were naturally conceived, no rater was able to differentiate the groups above chance levels, meaning that what children expressed through family drawing did not indicate cues related to trans-fatherhood. However, when we assessed mothers and fathers with the Five-Minute Speech Sample, we found that the emotions expressed by transgender fathers were higher than those of cisgender fathers who conceived by sex or by DSI.We conclude that the first empirical data regarding child development in the context of trans-parenthood are reassuring. We believe that this research will also improve transgender couple care and that of their children in a society where access to care remains difficult in this population. However, further research is needed with adolescents and young adults.
BATF3-dependent induction of IL-27 in B cells bridges the innate and adaptive stages of the antibody response
Authors: Yan Hui , Wang Rui , Wang Jingwei , Wu Shuai , Fernandez Maria , Rivera Carlos E. , Cervantes Christian , Moroney Justin B. , Li Xiao-Dong , Zhang Nu , Zan Hong , Meng Xiangzhi , Zhang Fushun , Zheng Siyuan , Chen Yidong , Yin Zhinan , Kedl Ross , Min Booki , Hunter Christopher A. , Xiang Yan , Casali Paolo , Xu Zhenming 
Published: June 2020

AbstractB cells are exposed to innate and T cell stimuli during the antibody response, although whether and how they functionally integrate such signals are unclear. Here we have identified IL-27 as the cytokine specifically produced by murine B cells upon sequential stimulation by TLR ligands and then CD154 and IL-21, the hallmark factors of T follicular helper cells, and during the T-dependent antibody response to a conjugated hapten or virus infection. B-cellIl27p28transcription is concomitant with increased locus accessibility and depends on newly induced BATF3 transcription factor. IL-27-producing B cells are inefficient in antibody secretion, but cooperate with IFNγ to promote proliferation, survival, class-switching and plasma cell differentiation of CD40-activated B cells, leading to optimal IgG2a and IgG1 responses. Overall, IL-27-producing B cells function as “helper” B cells that integrate the innate and adaptive stages of the antibody response.One-sentence summaryB cells integrate innate TLR and adaptive CD40 signals to induce BATF3 transcription factor for production of IL-27, which together with INFg optimizes antibody responses.
Linkage mapping and QTL analysis of flowering time using ddRAD sequencing with genotype error correction inBrassica napus
Authors: Scheben Armin , Severn-Ellis Anita , Patel Dhwani , Pradhan Aneeta , Rae Stephen , Batley Jacqueline , Edwards David 
Published: June 2020

AbstractBrassica napusis an important oilseed crop cultivated worldwide. During domestication and breeding ofB. napus, flowering time has been a target of selection because of its substantial impact on yield. Here we use double digest restriction-site associated DNA sequencing (ddRAD) to investigate the genetic basis of flowering inB. napus. An F2mapping population was derived from a cross between an early-flowering spring type and a late-flowering winter type. Flowering time in the mapping population differed by up to 25 days between individuals. High genotype error rates persisted after initial quality controls, as suggested by a genotype discordance of ∼12% between biological sequencing replicates. After genotype error correction, a linkage map spanning 3,605.70 cM and compromising 14,630 single nucleotide polymorphisms (SNPs) was constructed. A quantitative trail locus (QTL) on chromosome C2 was detected in the vicinity of flowering time genes includingFTandFLC. These findings demonstrate the effectiveness of the ddRAD approach to sample theB. napusgenome. Our results also suggest that ddRAD genotype error rates can be higher than expected in F2populations. Quality filtering and genotype correction and imputation can substantially reduce these error rates and allow effective linkage mapping and QTL analysis.
An exon DNA element modulates heterochromatin spreading in the master regulator for sexual commitment in malaria parasites
Authors: Cordon-Obras Carlos , Barcons-Simon Anna , Scheidig-Benatar Christine , Claës Aurelie , Sabatet Valentin , Loew Damarys , Scherf Artur 
Published: June 2020

ABSTRACTHeterochromatin is essential in all eukaryotes to maintain genome integrity, long-term gene repression and to help chromosome segregation during mitosis. However, heterochromatin regions must be restricted by boundary elements to avoid its spreading over actively transcribed loci. InPlasmodium falciparum, facultative heterochromatin is important to regulate parasite virulence, antigenic variation and transmission. However, the underlying molecular mechanisms regulating repressive regions remain unknown. To investigate this topic, we chose theap2-ggene, which forms a strictly delimited and independent heterochromatin island. Using electrophoretic motility shift assay (EMSA) we identified anap2-gexon element at the 3’ end binding nuclear protein complexes. Upon replacement of this region by agfpgene, we observed a shift in the heterochromatin boundary resulting in HP1 (Heterochromatin Protein 1) spreading over ∼2 additional kb downstream. We used this DNA element to purify candidate proteins followed by proteomic analysis. The identified complexes were found to be enriched in RNA-binding proteins, pointing to a potential role of RNA in the regulation of theap2-g3’ heterochromatin boundary. Our results provide insight into the unexplored topic of heterochromatin biology inP. falciparumand identify a DNA element within the master regulator of sexual commitment modulating heterochromatin spreading.
Virus-host protein-protein interactions between human papillomavirus 16 E6 A1 and D2/D3 sub-lineages: variances and similarities
Authors: Dayer Guillem , Masoom Mehran L. , Togtema Melissa , Zehbe Ingeborg 
Published: June 2020

AbstractHigh-risk strains of human papillomavirus are causative agents for cervical and other mucosal cancers with type 16 being the most frequent. Compared to the European Prototype (A1, denoted “EP”), the Asian-American (D2/D3, denoted “AA”) sub-lineage or “variant” is reported to have increased abilities to promote carcinogenesis. Few global interactome studies have looked at protein-protein interactions (PPIs) between host proteins and variants of the key transforming E6 protein. We applied a primary human foreskin keratinocyte model transduced with EP and AA variant E6 genes and co-immunoprecipitated expressed E6 proteins along with interacting cellular proteins to detect virus-host binding partners. We reasoned that, due to single nucleotide polymorphisms, AAE6 and EPE6 may have unique PPIs with host cellular proteins—conferring gain or loss of function—resulting in varied abilities to promote carcinogenesis. Using liquid chromatography-mass spectrometry and stringent interactor selection criteria based on the number of peptides, we identified 25 candidates: 6 unique to each of AAE6 and EPE6, along with 13 E6 targets common to both AAE6 and EPE6. We also applied a more inclusive process based on pathway selection and discovered 171 target proteins: 90 unique AAE6 and 61 unique EPE6 along with 20 common E6 targets between the two sub-lineages. Interpretations for both approaches were made using databases such as UniProt, BioGRID and Reactome. Detected E6 targets are implicated in important hallmarks of cancer: deregulating Notch and other signaling, energetics and hypoxia, DNA replication and repair, and immune response. Validation experiments, such as reverse co-immunoprecipitation and RNA interference, are required to substantiate these findings. Here, we provide an unprecedented resource for new research questions in HR HPV biology. The current data also underline our lab’s driving hypothesis that E6, being a “master regulator” in HPV-positive cancers, is an excellent candidate for anti-cancer treatment strategies.Author SummaryChronic infection with high-risk human papillomavirus (HPV) type 16 is the most prevalent cause of cervical and other mucosal cancers. The E6 oncoproteins of the European Prototype (EP) and the Asian-American (AA) HPV variants differentially promote carcinogenesis. We looked at protein-protein interactions between host proteins and two key HPV variant E6 proteins of these strains to reveal how high risk HPVs cause cancer, based on the proteins they bind to in infected cells. Our methodology combined molecular biology and data mining techniques using widely available databases. We confirmed and discovered novel virus-host associations that explained how HPV AA and EP variants differ in their carcinogenic capabilities, and confirmed the candidacy of the E6 protein as a viable target for HPV therapies.