bluuebunny/crossref_metadata_2025_split huggingface dataset:
PuMA: a papillomavirus genome annotation tool
Authors: Pace J. , Youens-Clark K. , Freeman C. , Hurwitz B. , Van Doorslaer K. 
Published: August 2019

ABSTRACTHigh-throughput sequencing technologies provide unprecedented power to identify novel viruses from a wide variety of (environmental) samples. The field of ‘viral metagenomics’ has dramatically expanded our understanding of viral diversity. Viral metagenomic approaches imply that many novel viruses will not be described by researchers who are experts on the genomic organization of that virus. There is a need to develop analytical approaches to reconstruct, annotate, and classify viral genomes. We have developed the papillomavirus annotation tool (PuMA) to provide researchers with a convenient and reproducible method to annotate novel papillomaviruses. PuMA provides an accessible method for automated papillomavirus genome annotation. PuMA currently has a 98% accuracy when benchmarked against the 481 reference genomes in the papillomavirus episteme (PaVE). Finally, PuMA was used to annotate 168 newly isolated papillomaviruses, and successfully annotated 1424 viral features. To demonstrate its general applicability, we developed a version of PuMA that can annotate polyomaviruses.PuMA is available on GitHub (https://github.com/KVD-lab/puma) and through the iMicrobe online environment (https://www.imicrobe.us/#/apps/puma)
DNA unwinding mechanism of a eukaryotic replicative CMG helicase
Authors: Yuan Zuanning , Georgescu Roxana , Bai Lin , Zhang Dan , Li Huilin , O’Donnell Mike 
Published: August 2019

ABSTRACTHigh-resolution structures have not been reported for replicative helicases at a replication fork at atomic resolution, a prerequisite to understand the unwinding mechanism. The eukaryotic replicative CMG helicase contains a Mcm2-7 motor ring, with the N-tier ring in front and the C-tier motor ring behind. The N-tier ring is structurally divided into a zinc finger (ZF) sub-ring followed by the OB fold ring. Here we report the cryo-EM structure of CMG on forked DNA at 3.9 Å, revealing that parental DNA enters the ZF sub-ring and strand separation occurs at the bottom of the ZF sub-ring, where the lagging strand is blocked and diverted sideways by OB hairpin-loops of Mcm3, Mcm4, Mcm6, and Mcm7. Thus, instead of employing a separation pin, unwinding is achieved via a “dam-and-diversion tunnel” for steric exclusion unwinding. The C-tier motor ring contains spirally configured PS1 and H2I loops of Mcms 2, 3, 5, 6 that translocate on the spirally-configured leading strand, and thereby pull the preceding DNA segment through the diversion tunnel for strand separation.
A Maxent modelling with a geospatial approach for the Habitat suitability of Flamingos in an Evanescing Ramsar site (Sambhar Lake, India) over the changing climatic scenarios
Authors: Kshitij Divyansh Laxmikant Sharma , Raj Alok 
Published: August 2019

AbstractWetlands play a crucial role in the biosphere and provide numerous services. They performed multiple functions such as groundwater recharge, water purification, conservation of biological resources, act as a carbon sink and habitat of amphibians and birds. A Ramsar site-the Sambhar Lake is one of the largest inland saline wetland present in the arid region of Rajasthan, India has unique habitat suitability for the winter avifauna migrants like flamingoes and falcons. The occurrence of suitable climatic conditions and food availability like brine shrimps (Artemia salina) attracts flocks of migratory birds. From the last three decades, Sambhar Lake has been continuously facing degradation due to anthropogenic activities, which disturb Lake’s natural ecology and existence. These cause disturbances in habitat suitability of migratory birds in the Sambhar Lake, which leads to a reduction of population density of migratory birds. Therefore, this study aimed to assess the degradation and vulnerability of Sambhar Lake and the habitat suitability of migratory birds using Maxent Habitat Suitability model. This model provides a platform to integrate the bird’s occurrence data with the bioclimatic variables using remote sensing and Geographical Information System, and provides bird’s habitat suitability as well as predicts future bird’s occurrence scenarios. Landsat-5 and Sentinel-2 imagery for the year 1996 and 2019 respectively were used in this study. Four indicators such as LULC NDWI, MSI and SABI depicts the environmental condition of the Sambhar Lake. Output form Maxent model reveals that the Sambhar lake area with increasing anthropogenic activities has become unsuitable for flamingos. A remarkable loss of breeding sites of animal, particularly avian fauna (flamingos) is seen in the recent years due to different types of threats posed on the Ramsar site. Increase in Salt crust and Vegetation area from 36.8055 to 123.837 Sq. Km. and 26.5347 to 36.857 Sq. Km. respectively have taken place. While a decrease in saline water area from 88.8309 to 19.3256 Sq. Km has been observed, within the vicinity of Sambhar Lake as clearly shown through LULC map. The future prediction of the distribution of species in the region for the year 2050 shows that the most suitable regions will be near to Jhapok and nearby waters of Salt Lake City as the drains from the city opens in the lake where the flamingoes get Algae in the form of food. Active steps are needed for the lake conservation to reduce the risks of migratory bird’s population.
Catecholaminergic axons in the neocortex of adult mice regrow following brain injury
Authors: Dougherty Sarah E. , Kajstura Tymoteusz J. , Jin Yunju , Chan-Cortés Michelle H. , Kota Akhil , Linden David J. 
Published: August 2019

AbstractSerotonin axons in the adult rodent brain can regrow and recover their function following several forms of injury including controlled cortical impact (CCI), a neocortical stab wound, or systemic amphetamine toxicity. To assess whether this capacity for regrowth is unique to serotonergic fibers, we used CCI and stab injury models to assess whether fibers from other neuromodulatory systems can also regrow following injury. Using tyrosine-hydoxylase (TH) immunohistochemistry we measured the density of catecholaminergic axons before and at various time points after injury. One week after CCI injury we observed a pronounced loss, across cortical layers, of TH+ axons posterior to the site of injury. One month after CCI injury the same was true of TH+ axons both anterior and posterior to the site of injury. This loss was followed by significant recovery of TH+ fiber density across cortical layers, both anterior and posterior to the site of injury, measured three months after injury. TH+ axon loss and recovery over weeks to months was also observed throughout cortical layers using the stab injury model. Double label immunohistochemistry revealed that nearly all TH+ axons in neocortical layer 1/2 are also dopamine-beta-hyroxylase+ (DBH+; presumed norepinephrine), while TH+ axons in layer 5 are a mixture of DBH+ and dopamine transporter+ types. This suggests that noradrenergic axons can regrow following CCI or stab injury in the adult mouse neocortex and leaves open the question of whether dopaminergic axons can do the same.HighlightsWe measured catecholaminergic axon density using tyrosine hydroxylase immunohistochemistry following two forms of brain injury.Both controlled cortical impact and cortical stab injuries caused extensive damage to catecholaminergic axons in the neocortex of adult mice.Following both types of injury, axon density slowly returned to control values over many weeks, including, in the case of stab injury, regrowth across the stab rift.Together with previous results showing serotonin axon regrowth, these findings suggest that monaminergic axons have an unusual capacity for regrowth following injury in the adult mammalian brain
Targeting MEK5 impairs non-homologous end-joining repair and sensitizes prostate cancer to DNA damaging agents
Authors: Broustas Constantinos G. , Duval Axel J. , Chaudhary Kunal R. , Friedman Richard A. , Virk Renu K. , Lieberman Howard B. 
Published: August 2019

AbstractRadiotherapy is commonly used to treat a variety of solid human tumors, including localized prostate cancer. However, treatment failure often ensues due to tumor intrinsic or acquired radioresistance. Here we find that the MEK5/ERK5 signaling pathway is associated with resistance to genotoxic stress in aggressive prostate cancer cells. MEK5 knockdown by RNA interference sensitizes prostate cancer cells to ionizing radiation (IR) and etoposide treatment, as assessed by clonogenic survival and short-term proliferation assays. Mechanistically, MEK5 downregulation impairs phosphorylation of the catalytic subunit of DNA-PK at serine 2056 in response to IR or etoposide treatment. Although MEK5 knockdown does not influence the initial appearance of radiation- and etoposide-induced γH2AX and 53BP1 foci, it markedly delays their resolution, indicating a DNA repair defect. A cell-based assay shows that non-homologous end joining (NHEJ) is compromised in cells with ablated MEK5 protein expression. Finally, MEK5 silencing combined with focal irradiation causes strong inhibition of tumor growth in mouse xenografts, compared with MEK5 depletion or radiation alone. These findings reveal a convergence between MEK5 signaling and DNA repair by NHEJ in conferring resistance to genotoxic stress in advanced prostate cancer and suggest targeting MEK5 as an effective therapeutic intervention in the management of this disease.
Simulations of proposed mechanisms of FtsZ-driven cell constriction
Authors: Nguyen Lam T. , Oikonomou Catherine M. , Jensen Grant J. 
Published: August 2019

ABSTRACTTo divide, bacteria must constrict their membranes against significant force from turgor pressure. A tubulin homo-log, FtsZ, is thought to drive constriction, but how FtsZ filaments might generate constrictive force in the absence of motor proteins is not well understood. There are two predominant models in the field. In one, filaments overlap to form complete rings around the circumference of the cell; as filaments slide against each other to maximize lateral contact, the rings constrict. In the other, filaments exert force on the membrane by a GTP-hydrolysis-induced switch in conformation from straight to bent. Here we developed software, ZCONSTRICT, for quantitative 3D simulations of Gram-negative bacterial cell division to test these two models and identify critical conditions required for them to work. We find that the avidity of lateral interactions quickly halts the sliding of filaments, so a mechanism such as depolymerization or treadmilling is required to sustain constriction by filament sliding. For filament bending, we find that a mechanism such as the presence of a rigid linker is required to constrain bending within the division plane and maintain the distance observed in vivo between the filaments and the membrane. We also explored the recent observation of constriction associated with a single FtsZ filament and found that it can be explained by the filament bending model if there is a rigid connection between the filament and the cell wall. Together, our work sheds light on the physical principles underlying bacterial cell division and informs future experiments to elucidate the mechanism of FtsZ.
Therapeutically exploring persister metabolism in bacteria
Authors: Mohiuddin Sayed G. , Hoang Thuy , Saba Adesola , Karki Prashant , Orman Mehmet A. 
Published: August 2019

ABSTRACTBacterial persisters are rare phenotypic variants that are temporarily tolerant to high concentrations of antibiotics. We have previously discovered that persisters are mostly derived from stationary-phase cells with high redox activities that are maintained by endogenous protein and RNA degradation. This intracellular degradation resulted in self-inflicted damage that transiently repressed the cellular functions targeted by antibiotics. Leveraging this knowledge, we developed an assay integrating a degradable fluorescent protein system and a small library, containing FDA-approved drugs and antibiotics, to detect chemicals that target persister metabolism. We identified several metabolic inhibitors, including anti-psychotic drugs, that can reduce Escherichia coli persistence. These chemical inhibitors also reduce Pseudomonas aeruginosa persistence, potentially verifying the existence of similar mechanisms in a medically relevant organism.
Effects of Topical Antimicrobial Formulations on Pseudomonas aeruginosa Biofilm in an In vivo Porcine Burn Wound Model
Authors: Davis S.C. , Solis M. , Gil J. , Valdes J. , Higa A. , Metzger S. A. , Kalan L. 
Published: August 2019

AbstractSilver has been incorporated into a variety of wound dressings and topical agents to prevent and combat wound infections. Pseudomonas aeruginosa is a common cause of burn wound infections and well-known biofilm producer. The objective of this study was to evaluate the effects of a panel of wound dressings containing different silver formulations on P. aeruginosa biofilms using an in vivo porcine burn wound model. Second-degree burns were created on the skin of specific pathogen-free pigs (n = 3) and inoculated with 2.14 × 105 cfu P. aeruginosa per wound. Biofilms were allowed to develop for 24 h, and then each wound was treated with one of 6 treatments: silver oxynitrate dressing (OXY), silver oxynitrate powder (POWD), nanocrystalline silver dressing (NANO), silver chloride dressing (AGCL), silver sulfadiazine (SSD), or a negative control polyurethane film with no silver-based formulation (NEG). Wounds were cultured at D3 post-infection (n = 3 per pig per treatment) and at D6 post-infection (n = 3 per pig per treatment) for quantification of bacteria. On D6, biopsies (n = 3 per treatment) were taken from POWD, SSD, and NEG wounds and wound healing progress was evaluated histologically. At the time of treatment initiation, 24 h post-infection, 8.71 log cfu P. aeruginosa were present in burn wounds. On D3 and D6, all treatments significantly reduced bacterial counts in wounds as compared to NEG, but POWD caused an approximately 7-log reduction in bacterial counts on both days and was the only treatment to reduce the bacterial counts to below the threshold for detecting bacteria. The OXY, NANO, and SSD treatments had similar reductions in bacterial recovery on D3 and D6 of approximately 2.5-4 log. The histological healing metrics of reepithelialization percentage, epithelial thickness, white cell infiltration, angiogenesis, and granulation tissue formation were similar among wounds from POWD, SSD, and NEG groups at 6 days post-infection. Silver oxynitrate powder reduced P. aeruginosa growth in burn wounds more effectively than other silver-based dressings but did not impact wound healing.
Geomagnetic field absence reduces adult body weight of a migratory insect by disrupting feeding behavior and appetite regulation
Authors: Wan Guijun , Jiang Shoulin , Zhang Ming , Zhao Jingyu , Zhang Yingchao , Pan Weidong , Sword Gregory A. , Chen Fajun 
Published: August 2019

AbstractThe geomagnetic field (GMF) is well documented for its essential role as a cue used in animal orientation or navigation. Recent evidence indicates that the absence of GMF can trigger stress-like responses such as reduced body weight, as we have previously shown in newly emerged adults of the brown planthopper,Nilaparvata lugens. To test the hypothesis that reduced feeding in the absence of the GMF leads to a decrease ofN. lugensbody weight, we compared magnetic responses in feeding behavior, glucose levels, and expression of magnetoreception- and appetite-related genes in brown planthopper nymphs exposed to either a near-zero magnetic field (NZMF, i.e., GMF absence) or typical GMF conditions. In addition to observing the expected responses in the expression of the potential magnetosensorcryptochromes, the food intake of 5thinstar nymphs was significantly reduced in insects reared in the absence of GMF. Insects that exhibited reduced feeding reared in the absence of the GMF also had higher glucose levels which is associated with food aversion. Expression patterns of appetite-related neuropeptide genes were also altered in the absence of GMF in a manner consistent with diminishing appetite. These findings support the hypothesis that strong changes in GMF intensity can affect insect feeding behavior and underlying regulatory processes. Our results provide further evidence that magnetoreception and regulatory responses to GMF changes can affect a wide variety of biological processes.
Megacities as drivers of national outbreaks: the role of holiday travel in the spread of infectious diseases
Authors: Mahmud Ayesha S. , Kabir Md. Iqbal , Engø-Monsen Kenth , Tahmina Sania , Riaz Baizid Khoorshid , Hossain Md. Akram , Khanom Fahmida , Rahman Md. Mujibor , Rahman Md. Khalilur , Sharmin Mehruba , Hossain Dewan Mashrur , Yasmin Shakila , Ahmed Md. Mokhtar , Lusha Mirza Afreen Fatima , Buckee Caroline O. 
Published: August 2019

AbstractHuman mobility connects populations and can lead to large fluctuations in population density, both of which are important drivers of epidemics. Measuring population mobility during infectious disease outbreaks is challenging, but is a particularly important goal in the context of rapidly growing and highly connected urban centers in low and middle income countries, which can act to amplify and spread local epidemics nationally and internationally. Here, we combine estimates of population movement from mobile phone data for over 4 million subscribers in the megacity of Dhaka, Bangladesh, one of the most densely populated cities globally. We combine mobility data with epidemiological data from a household survey, to understand the role of population mobility on the spatial spread of the mosquito-borne virus chikungunya within and outside Dhaka city during a large outbreak in 2017. The peak of the 2017 chikungunya outbreak in Dhaka coincided with the annual Eid holidays, during which large numbers of people traveled from Dhaka to their native region in other parts of the country. We show that regular population fluxes around Dhaka city played a significant role in determining disease risk, and that travel during Eid was crucial to the spread of the infection to the rest of the country. Our results highlight the impact of large-scale population movements, for example during holidays, on the spread of infectious diseases. These dynamics are difficult to capture using traditional approaches, and we compare our results to a standard diffusion model, to highlight the value of real-time data from mobile phones for outbreak analysis, forecasting, and surveillance.
TGFβ regulation of perilacunar/canalicular remodeling is sexually dimorphic
Authors: Dole Neha S. , Yee Cristal S. , Mazur Courtney M. , Acevedo Claire , Alliston Tamara 
Published: August 2019

1.AbstractBone fragility is the product of defects in bone mass and bone quality, both of which show sex-specific differences. Despite this, the cellular and molecular mechanisms underpinning the sexually dimorphic control of bone quality remain unclear, limiting our ability to effectively prevent fractures, especially in postmenopausal osteoporosis. Recently, using male mice, we found that systemic or osteocyte-intrinsic inhibition of TGFβ signaling, achieved using the 9.6-kb DMP1 promoter-driven Cre recombinase (TβRIIocy−/−mice), suppresses osteocyte perilacunar/canalicular remodeling (PLR) and compromises bone quality. Since systemic TGFβ inhibition more robustly increases bone mass in female than male mice, we postulated that sex-specific differences in bone quality could likewise result, in part, from dimorphic regulation of PLR by TGFβ. Moreover, since lactation induces PLR, we examined the effect of TGFβ inhibition on the female skeleton during lactation. In contrast to males, female mice that possess an osteocyte-intrinsic defect in TGFβ signaling were protected from TGFβ-dependent defects in PLR and bone quality. The expression of requisite PLR enzymes, the lacuno-canalicular network, and the flexural strength of female TβRIIocy−/−bone was intact. With lactation, however, bone loss, and induction in PLR and osteocytic parathyroid hormone type I receptor (PTHR1) expression, were suppressed in TβRIIocy−/−bone, relative to wild-type. Indeed, differential control of PTHR1 expression, by TGFβ and other factors, may contribute to dimorphism in PLR regulation in male and female TβRIIocy−/−mice. These findings provide key insights into the sex-based differences in osteocyte PLR that underlie bone quality and highlight TGFβ signaling as a crucial regulator of lactation-induced PLR.
Screening and identification of MicroRNAs expressed in perirenal adipose tissue during rabbit growth
Authors: Wang Guoze , Guo Guo , Tian Xueting , Hu Shenqiang , Du Kun , Mao Jingxin , Jia Xianbo , Chen Shiyi , Wang Jie , Lai Songjia 
Published: August 2019

AbstractMiRNAs regulate adipose tissue development, which are closely related to subcutaneous and intramuscular fat deposition and adipocyte differentiation. As an important economic and agricultural animal, rabbits have low adipose tissue deposition and are an ideal model to study adipose regulation. However, the miRNAs related to fat deposition during the growth and development of rabbits are poorly defined. In this study, miRNA-sequencing and bioinformatics analyses were used to profile the miRNAs in rabbit perirenal adipose tissue at 35, 85 and 120 days post-birth. Differentially expressed (DE) miRNAs between different stages were identified by DEseq in R. Target genes of DE miRNAs were predicted by TargetScan and miRanda. To explore the functions of identified miRNAs, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Approximately 1.6 GB of data was obtained by miRNA-seq. A total of 987 miRNAs (780 known and 207 newly predicted) and 174 DE miRNAs were identified. The miRNAs ranged from 18nt to 26nt. GO enrichment and KEGG pathway analyses revealed that the target genes of the DE miRNAs were mainly involved in zinc ion binding, regulation of cell growth, MAPK signaling pathway, and other adipose hypertrophy-related pathways. Six DE miRNAs were randomly selected and their expression profiles were validated by q-PCR. In summary, we provide the first report of the miRNA profiles of rabbit adipose tissue during different growth stages. Our data provide a theoretical reference for subsequent studies on rabbit genetics, breeding and the regulatory mechanisms of adipose development.
The structural basis of Indisulam-mediated recruitment of RBM39 to the DCAF15-DDB1-DDA1 E3 ligase complex
Authors: Bussiere Dirksen E. , Xie Lili , Srinivas Honnappa , Shu Wei , Burke Ashley , Be Celine , Zhao Junping , Godbole Adarsh , King Dan , Karki Rajeshri G. , Hornak Viktor , Xu Fangmin , Cobb Jennifer , Carte Nathalie , Frank Andreas O. , Frommlet Alexandra , Graff Patrick , Knapp Mark , Fazal Aleem , Okram Barun , Jiang Songchun , Michellys Pierre-Yves , Beckwith Rohan , Voshol Hans , Wiesmann Christian , Solomon Jonathan , Paulk Joshiawa 
Published: August 2019

AbstractThe anti-cancer agent Indisulam inhibits cell proliferation by causing degradation of RBM39, an essential mRNA splicing factor. Indisulam promotes an interaction between RBM39 and the DCAF15 E3 ligase substrate receptor leading to RBM39 ubiquitination and proteasome-mediated degradation. To delineate the precise mechanism by which Indisulam mediates DCAF15-RBM39 interaction, we solved the DCAF15-DDB1-DDA1-Indisulam-RBM39(RRM2) complex structure to 2.3 Å. DCAF15 has a novel topology which embraces the RBM39(RRM2) domain largely via nonpolar interactions, and Indisulam binds between DCAF15 and RBM39(RRM2) and coordinates additional interactions between the two proteins. Studies with RBM39 point mutants and Indisulam analogs validated the structural model and defined the RBM39 alpha-helical degron motif. The degron is found only in RBM23 and RBM39 and only these proteins were detectably downregulated in Indisulam-treated HCT116 cells. This work further explains how Indisulam induces RBM39 degradation and defines the challenge of harnessing DCAF15 to degrade novel targets.