bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep Sequencing Reveals Compartmentalized HIV-1 in the Semen of Men with and without STI-associated Urethritis
Authors: Council Olivia D. , Zhou Shuntai , McCann Chase D. , Hoffman Irving , Tegha Gerald , Kamwendo Deborah , Matoga Mitch , Kosakovsky Pond Sergei L. , Cohen Myron S. , Swanstrom Ronald 
Published: January 2020

AbstractConcurrent sexually transmitted infections (STI) can increase the probability of HIV-1 transmission primarily by increasing the viral load present in semen. In this study, we explored the relationship of HIV-1 in blood and seminal plasma in the presence and absence of urethritis and after treatment of the concurrent STI. Primer ID deep sequencing of the V1/V3 region of the HIV-1envgene was done for paired blood and semen samples from ART-naïve men living in Malawi with (n = 19) and without (n = 5) STI-associated urethritis; for a subset of samples full lengthenvgenes were generated for sequence analysis and to test entry phenotype. Cytokine concentrations in the blood and semen were also measured, and a reduction in the levels of pro-inflammatory cytokines was observed following STI treatment. We observed no difference in the prevalence of diverse compartmentalized semen-derived lineages in men with or without STI-associated urethritis, and these viral populations were largely stable during STI treatment. Clonal amplification of one or a few viral sequences accounted for nearly 50% of the viral population indicating a recent bottleneck followed by limited viral replication. We documented a case of superinfection where the new strain was restricted to the genital tract. We conclude that the male genital tract is a site where virus can be brought in from the blood, where localized sustained replication can occur, where a superinfecting strain can persist, and where specific genotypes can be amplified perhaps initially by cellular proliferation but further by limited viral replication.ImportanceHIV-1 is a sexually transmitted infection that co-exists with other STIs. Here we examine the impact of a concurrent STI resulting in urethritis on the HIV-1 population within the male genital tract. We found that viral populations remain largely stable even with treatment of the STI. These results show that viral populations within the male genital tract are defined by factors beyond transient inflammation associated with a concurrent STI.
Delivery mode impacts newborn gut colonization efficiency
Authors: Mitchell Caroline , Hogstrom Larson , Bryant Allison , Bergerat Agnes , Cher Avital , Pochan Shawna , Herman Penelope , Carrigan Maureen , Sharp Karen , Huttenhower Curtis , Lander Eric S. , Vlamakis Hera , Xavier Ramnik J. , Yassour Moran 
Published: January 2020

AbstractDelivery mode is the variable with the greatest influence on the infant gut microbiome composition in the first few months of life. Children born by Cesarean section (C-section) lack species from theBacteroidesgenus in their gut microbial community, and this difference can be detectable until 6-18 months of age. One hypothesis is that these differences stem from lack of exposure to the maternal vaginal microbiome, as children born by C-section do not pass through the birth canal; however,Bacteroidesspecies are not common members of the vaginal microbiome, thus this explanation seems inadequate. Here, we set out to re-evaluate this hypothesis by collecting rectal and vaginal samples before delivery from 73 mothers with paired stool from their infants in the first two weeks of life. We compared microbial profiles of infants born by planned, pre-labor C-section to those born by emergent, post-labor surgery (where the child was in the birth canal, but eventually delivered through an abdominal incision), and found no significant differences in the microbiome between these two groups. Both groups showed the characteristic signature lack ofBacteroidesspecies, despite their difference in exposure to the birth canal. Surprisingly, this signature was only evident in samples from week two of life, but not in the first week. Children born by C-section often had high abundance ofBacteroidesin their first few days of life, but these were not stable colonizers of the infant gut, as they were not detectable by week two. Finally, we used metagenomic sequencing to compare microbial strains in maternal vaginal and rectal samples and samples from their infants; we found evidence for mother-to-child transmission of rectal rather than vaginal strains. These results challenge birth canal exposure as the dominant factor in infant gut microbiome establishment and implicate colonization efficiency rather than exposure as a dictating factor of the newborn gut microbiome composition.
Creative destruction: a basic computational model of cortical layer formation
Authors: Bauer Roman , Clowry Gavin J , Kaiser Marcus 
Published: January 2020

AbstractOne of the most characteristic properties of many vertebrate neural systems is the layered organization of different cell types. This cytoarchitecture exists in the cortex, the retina, the hippocampus and many other parts of the central nervous system. The developmental mechanisms of neural layer formation have been subject to substantial experimental efforts. Here, we provide a general computational model for cortical layer formation in 3D physical space. We show that this multi-scale, agent-based model comprising two distinct stages of apoptosis, can account for the wide range of neuronal numbers encountered in different cortical areas and species. Our results demonstrate the phenotypic richness of a basic state diagram structure, and suggest a novel function for apoptosis. Moreover, slightly changed gene regulatory dynamics recapitulate characteristic properties observed in neurodevelopmental diseases. Overall, we propose a novel computational model using gene-type rules, exhibiting many characteristics of normal and pathological cortical development.
Potential inhibitors for 2019-nCoV coronavirus M protease from clinically approved medicines
Authors: Liu Xin , Wang Xiu-Jie 
Published: January 2020

AbstractStarting from December 2019, a novel coronavirus, named 2019-nCoV, was found to cause Severe Acute Respiratory (SARI) symptoms and rapid pandemic in China. With the hope to identify candidate drugs for 2019-nCoV, we adopted a computational approach to screen for available commercial medicines which may function as inhibitors for the Mproof 2019-nCoV. Up to 10 commercial medicines that may form hydrogen bounds to key residues within the binding pocket of 2019-nCoV Mprowere identified, which may have higher mutation tolerance than lopinavir/ritonavir and may also function as inhibitors for other coronaviruses with similar Mprobinding sites and pocket structures.
Landscape of transcript isoforms in single T cells infiltrating in non-small cell lung cancer
Authors: Li Jiesheng , Zhang Zemin , Ren Xianwen 
Published: January 2020

ABSTRACTSingle cell RNA-seq has enabled high-resolution characterization of molecular signatures of tumor-infiltrating lymphocytes. However, analyses at the transcript isoform level are rarely reported. As alternative splicing is critical to T cell differentiation and activation, here we proposed a computational method named as IDEA to comprehensively detect and annotate differentially used isoforms across cell subtypes. We applied IDEA on a scRNA-seq dataset of 12,346 T cells from non-small cell lung cancer. We found most genes tend to dominantly express one isoform in single T cells, enabling typing T cells according to the isotypes given a gene. Isotype analysis suggested that tumor-infiltrating T cells significantly preferred specific isotypes for 245 genes in CD8+ T cells and 456 genes in CD4+ T cells. Functional annotation suggests that the preferred isoforms involved in coding/non-coding switches, transcription start site changes, gains/losses of domains and subcellular translocation. Clonal analysis revealed that isoform switching occurred during T cell activation/differentiation. Our analysis provides precise characterization of the molecular events in tumor-infiltrating T cells and sheds new lights into the regulatory mechanisms of tumor-infiltrating T cells.
TrkB induced metastatic potential of cancer by suppression of BMP mediated tumor inhibitory activity
Authors: Kim Min Soo , Jin Wook 
Published: January 2020

AbstractOur previous observations also demonstrate that TrkB expression in breast cancer induces metastatic potential by both JAK2/STAT3 and PI3K/AKT activation and induced metastasis of breast cancer mediated suppression of RUNX3 and KEAP1 expression by TrkB. Also, TrkB induced metastatic potential of cancer and suppressed the growth inhibitory activity in response to BMP signaling by preventing BMRRI/BMPRII complex formation. The previous report BMP-2 and BMP4 trigger tumor inhibitory activity in colorectal cancer by upregulation of RUNX3 expression. Although TrkB may regulate tumor inhibitory activity by BMP-induced upregulation of RUNX3, it is not still fully understood how TrkB signaling adjusts to inhibit BMP signaling-mediated tumor suppression.Our findings provide important molecular insights into TrkB-mediated modulation of BMP signaling has remained unknown, and none of the studies still reported a correlation between TrkB and BMP signaling. Our current study surprisingly showed that unique role of TrkB in the regulation of BMP-induced tumor inhibitory activity and BMP-2-induced RUNX3 expression.
Obesity-driven changes in ECM composition promote local invasion and metastasis of breast tumors
Authors: Wishart Andrew , Peng Yifan , Conner Sydney , Guarin Justinne , Crews Rebecca , Fatherree Jackson , Greenberg Andrew S. , Oudin Madeleine J. 
Published: January 2020

AbstractThe extracellular matrix (ECM) is a major component of the tumor microenvironment that supports cellular growth, promotes local invasion from the primary tumor, and contributes to metastatic outgrowth in sites of colonization. Obesity is a systemic disease that causes chronic inflammation which can lead to ECM deposition and ultimately fibrosis in adipose tissues such as the mammary gland. Overweight breast cancer patients have increased metastasis to the lung and liver, exhibit resistance to chemotherapy and have worse outcomes. We found that ECM isolated from the mammary gland of both tumor-bearing and obese mice increased invasion of breast cancer cells and set out to investigate whether obesity-driven changes in ECM could identify novel drivers of invasion and metastasis in breast cancer. We performed proteomics of the mammary fat pads of both lean and obese mice and identified the entire landscape of obesity-driven ECM changes. In particular, we focused on Collagen VI, an ECM protein secreted by adipocytes in mammary tissues. Collagen VI is upregulated in the ECM of obese and tumor-bearing mice and is associated with poor outcome in human breast cancer. We found that Collagen VI drives adhesion, migration and invasion of several human breast cancer cell lines via crosstalk between the adhesion receptor NG2 and the receptor tyrosine kinase EGFR, and activation of MAPK signaling. Overall, these studies demonstrate that obesity can have profound effects on the ECM composition of tissues, which in turn can promote local invasion and metastasis.
Tracking evolutionary trends towards increasing complexity: a case study in Cyanobacteria
Authors: Moya Andrés , Oliver José L. , Verdú Miguel , Delaye Luis , Arnau Vicente , Bernaola-Galván Pedro , de la Fuente Rebeca , Díaz Wladimiro , Gómez-Martín Cristina , González Francisco M. , Latorre Amparo , Lebrón Ricardo , Román-Roldán Ramón 
Published: January 2020

AbstractProgressive evolution, the tendency towards increasing complexity, is a controversial issue in Biology, whose resolution requires a proper measurement of complexity. Genomes are the best entities to address this challenge, as they record the history and information gaining of organisms in their ongoing biotic and environmental interactions. Using six metrics of genome complexity, none of which is primarily associated to biological function, we measure genome complexity in 91 genomes from the phylum Cyanobacteria. Several phylogenetic analyses reveal the existence of progressive evolution towards higher genome complexity: 1) all the metrics detect strong phylogenetic signals; 2) ridge regressions detect positive trends towards higher complexity; and 3) classical proofs for progressive evolution (the minimum, the ancestor-descendent and the sub-clade tests), show that some of these positive trends are driven, being mainly due to natural selection. These findings support the existence of progressive genome evolution in this ancient and diverse group of organisms.
Reducing FASN expression sensitizes acute myeloid leukemia cells to differentiation therapy
Authors: Humbert Magali , Seiler Kristina , Mosimann Severin , Rentsch Vreni , McKenna Sharon L. , Tschan Mario P. 
Published: January 2020

AbstractFatty acid synthase (FASN) is the only human lipogenic enzyme available for de novo fatty acid synthesis and is often highly expressed in cancer cells. We found that FASN mRNA levels were significantly higher in acute myeloid leukemia (AML) patients than in healthy granulocytes or CD34+ hematopoietic progenitors. Accordingly, FASN levels decreased during all-trans retinoic acid (ATRA)-mediated granulocytic differentiation of acute promyelocytic leukemia (APL) cells, partially via autophagic degradation. Furthermore, our data suggests that inhibition of FASN expression levels using RNAi or (-)-epigallocatechin-3-gallate (EGCG), accelerates the differentiation of APL cell lines and significantly re-sensitized ATRA refractory non-APL AML cells. FASN reduction promoted translocation of transcription factor EB (TFEB) to the nucleus, paralleled by activation of CLEAR network genes and lysosomal biogenesis. Lysosomal biogenesis was activated, consistent with TFEB transcriptional activation of CLEAR network genes.Together, our data demonstrate that inhibition of FASN expression in combination with ATRA treatment facilitates granulocytic differentiation of APL cells and may extend differentiation therapy to non-APL AML cells.
Mechanism of DNA surface exploration and operator bypassing during target search
Authors: Marklund E. , van Oosten B. , Mao G. , Amselem E. , Kipper K. , Sabantsev A. , Emmerich A. , Globisch D. , Zheng X. , Lehmann L. C. , Berg O. , Johansson M. , Elf J. , Deindl S. 
Published: January 2020

SummaryMany proteins that bind specific DNA sequences search the genome by combining three dimensional (3D) diffusion in the cytoplasm with one dimensional (1D) sliding on non-specific DNA1–5. Here we combine resonance energy transfer and fluorescence correlation measurements to characterize how individuallacrepressor (LacI) molecules explore DNA during the 1D phase of target search. To track the rotation of sliding LacI molecules on the microsecond time scale during DNA surface search, we use real-time single-molecule confocal laser tracking combined with fluorescence correlation spectroscopy (SMCT-FCS). The fluorescence signal fluctuations are accurately described by rotation-coupled sliding, where LacI traverses ~40 base pairs (bp) per revolution. This distance substantially exceeds the 10.5-bp helical pitch of DNA, suggesting that the sliding protein frequently hops out of the DNA groove, which would result in frequent bypassing of target sequences. Indeed, we directly observe such bypassing by single-molecule fluorescence resonance energy transfer (smFRET). A combined analysis of the smFRET and SMCT-FCS data shows that LacI at most hops one to two grooves (10-20 bp) every 250 μs. Overall, our data suggest a speed-accuracy trade-off during sliding; the weak nature of non-specific protein-DNA interactions underlies operator bypassing but also facilitates rapid sliding. We anticipate that our SMCT-FCS method to monitor rotational diffusion on the microsecond time scale while tracking individual molecules with millisecond time resolution will be applicable to the real-time investigation of many other biological interactions and effectively extends the accessible time regime by two orders of magnitude.
WISP2/CCN5gene knockdown in vitro and in vivo exhibits proliferation promotion of breast cancer through targeting Skp2 and p27Kip1
Authors: Lv Yan , Zhang Chang , Li Xiao Jiang , Gao Shan , Zheng Xu , Han Yan Yan , Li Chong , Geng Qiang 
Published: January 2020

AbstractBackgroundEmerging evidence has demonstrated that WISP2/CCN5 is critically involved in tumorigenesis. However, the function of WISP2/CCN5 in breast cancer carcinogenesis is largely unclear.Methodswe aim to explore the effects and potential mechanisms of WISP2/CCN5 on proliferation of breast cancer cells and carcinogenesis of breast cancer xenograft. Lentivirus vector with WISP2/CCN5shRNA was transfected into MCF-7, and breast cancer cells and xenograft were conducted. Effect of WISP2/CCN5 on growth and carcinogenesis of breast cancer cells and xenografts was evaluated by MTT assay and tumor volume. The relationship between WISP2/CCN5, Skp2 and p27Kip1 was detected in vitro and in vivo by RT-PCR at mRNA level and Western blotting at protein level.ResultsThe result of MTT assay indicated that MCF-7 cell growth viability in WISP2/CCN5 gene knockdown group was significantly higher than negative vector group(P<0.05) or control group (P<0.05). It suggested that knockdown ofWISP2/CCN5gene by shRNA lentivirus plasmid promoted proliferation of MCF-7 cells. The growth curves of breast cancer xenograft showed that xenografts in WISP2/CCN5 knockdown group grew more quickly than negative vector group(P< 0.05) or control group (P< 0.05). Subsequently, the results of RT-PCR and Western blotting revealed thatWISP2/CCN5gene knockdown led to increased Skp2 and decreased p27Kip1 at mRNA and protein levels. WISP2/CCN5 exerts its inhibition on proliferation of MCF-7 cell line and suppressive functions on growth of breast carcinoma via regulation of Skp2 and p27Kip1at mRNA and protein levels. However,WISP2/CCN5gene knockdown resulted in loss of inhibition effect on MCF-7 and breast cancer.ConclusionsOur findings suggest that WISP2/CCN5 could be a useful therapeutic strategy for the treatment of breast cancer through targeting Skp2 and p27Kip1.
The histone variant macroH2A1.1 regulates RNA Polymerase II paused genes within defined chromatin interaction landscapes
Authors: Recoules Ludmila , Heurteau Alexandre , Raynal Flavien , Karasu Nezih , Moutahir Fatima , Bejjani Fabienne , Jariel-Encontre Isabelle , Cuvier Olivier , Sexton Thomas , Lavigne Anne-Claire , Bystricky Kerstin 
Published: January 2020

AbstractThe histone variant macroH2A1.1 (mH2A1.1) plays a role in cancer development and metastasis-related processes. To determine the underlying molecular mechanisms, we mapped genome-wide localization of endogenous mH2A1.1 in the human breast cancer cell MDA-MB 231. We demonstrate that mH2A1.1 specifically binds to active promoters and enhancers in addition to facultative heterochromatin. Selective knock-down of mH2A1.1 deregulates expression of hundreds of highly active genes. Depending on the chromatin landscape, mH2A1.1 acts through two distinct molecular mechanisms. The first is to limit excessive transcription in a predefined environment and relies on domain recruitment of mH2A1.1 at the promoter and gene body. The second mechanism is specific to RNA Pol II (Pol II) paused genes. It requires recruitment of mH2A1.1 restricted to the TSS of these genes. Moreover, we show that these processes occur in a predefined local 3D genome organization and are largely independent of enhancer-promoter looping. Among the genes activated by mH2A1.1, genes regulating mammary tumor cell migration are mostly dependent on Pol II release for their expression level, unlike other categories of mH2A1.1-regulated genes. We thus identified an intriguing new mode of transcriptional regulation by mH2A1.1 and propose that mH2A1.1 serves as a transcriptional modulator with a potential role in assisting the conversion of promoter-locked RNA polymerase II into a productive and elongated Pol II.
Seasonal and social factors associated with spacing in a wild territorial electric fish
Authors: Zubizarreta Lucía , Quintana Laura , Hernández Daniel , de Mello Franco Teixeira , Meerhoff Mariana , Honji Renato Massaaki , Moreira Renata Guimarães , Silva Ana C. 
Published: January 2020

AbstractThe expression of territorial behavior in wild species is especially suited to explore how animals integrate individual traits with dynamic environmental and social contexts. In this study, we focused on the seasonal variation of the determinants of territory size in the weakly electric fishGymnotus omarorum. This species is a seasonal breeder that displays year-long territorial aggression, in which female and male dyads exhibit indistinguishable non-breeding territorial agonistic behavior and the only significant predictor of contest outcome is body size. We carried out field surveys across seasons that included the identification of individual location, measurements of water physico-chemical variables, characterization of individual morphometric and physiological traits, and their correlation to spatial distribution. AlthoughGymnotus omarorumtolerates a wide range of dissolved oxygen concentration, territory size correlated with dissolved oxygen in both seasons. In the non-breeding season, we show that territory size is sexually monomorphic and explained only by body size. In the breeding season, while body size no longer correlated with territory size, evidence of sexual differences in territory size determinants emerged. First, the overall spatial arrangement adopted a sexual bias. Second, territory size depended on gonadal hormones in both sexes, which was expected for males, but not previously reported in females. Third, females’ territory size correlated with gonadal size and females showed relatively larger territories than males, probably to meet sexually dimorphic energetic requirements. This study provides evidence of seasonal changes in factors correlated with territory size and contributes to the understanding of the mechanisms underlying behavioral plasticity.
Telomere damage induces internal loops that generate telomeric circles
Authors: Mazzucco Giulia , Huda Armela , Galli Martina , Piccini Daniele , Giannattasio Michele , Pessina Fabio , Doksani Ylli 
Published: January 2020

AbstractExtrachromosomal telomeric circles are commonly invoked as important players in telomere maintenance, but their origin has remained elusive. Using electron microscopy analysis on purified telomeres we show that, apart from known structures, telomeric repeats accumulate internal loops (i-loops), that occur in proximity of nicks and single-stranded DNA gaps. I-loops are induced by single-stranded damage at normal telomeres and represent the majority of telomeric structures detected in ALT (Alternative Lengthening of Telomeres) tumor cells. Our data indicate that i-loops form as a consequence of the exposure of single-stranded DNA at telomeric repeats. Finally, we show that these damage-induced i-loops can be excised to generate extrachromosomal telomeric circles resulting in loss of telomeric repeats. Our results identify damage-induced i-loops as a new intermediate in telomere metabolism and reveal a simple mechanism that links telomere damage with the accumulation of extrachromosomal telomeric circles and telomere erosion.