bluuebunny/crossref_metadata_2025_split huggingface dataset:
A dispensable role of mitochondrial fission protein 1 (Fis1) in the erythrocytic development ofPlasmodium falciparum
Authors: Maruthi Mulaka , Ling Liqin , zhou Jing , Ke Hangjun 
Published: June 2020

AbstractMalaria remains a huge global health burden and control of this disease has run into a severe bottleneck. To defeat malaria and reach the goal of eradication, a deep understanding of parasite biology is urgently needed. The mitochondrion of the malaria parasite is essential throughout the parasite’s lifecycle and has been validated as a clinical drug target. In the asexual development ofPlasmodium spp., the single mitochondrion grows from a small tubular structure to a complex branched network. At the end of schizogony when 8-32 merozoites are produced, the branched mitochondrion is precisely divided, distributing one mitochondrion to each forming daughter merozoite. In mosquito and liver stages, the giant mitochondrial network is split into thousands of pieces then daughter mitochondria are segregated into individual progeny. Despite the significance of mitochondrial fission inPlasmodium, the underlying mechanism is largely unknown. Studies of mitochondrial fission in model eukaryotes have revealed that several mitochondrial fission adaptor proteins are involved in recruiting dynamin GTPases to physically split mitochondrial membranes. Apicomplexan parasites, however, share no identifiable homologs of mitochondrial fission adaptor proteins of yeast or human, except for Fis1. Here, we investigated the localization and essentiality of the Fis1 homolog inPlasmodium falciparum, PfFis1 (PF3D7_1325600), during the asexual lifecycle. We found that PfFis1 requires an intact C-terminus for mitochondrial localization but is not essential for parasite development or mitochondrial fission. The dispensable role of PfFis1 indicatesPlasmodiumcontains additional fission adaptor proteins on the mitochondrial outer membrane that could be essential for mitochondrial fission.ImportanceMalaria is responsible for over 230 million clinical cases and ∼ half a million deaths each year. The single mitochondrion of the malaria parasite functions as a metabolic hub throughout the parasite’s developmental cycle as well as a source of ATP in certain stages. To pass on its essential functions, the parasite’s mitochondrion needs to be properly divided and segregated into all progeny during cell division via a process named mitochondrial fission. Due to the divergent nature ofPlasmodium spp., molecular players involved in mitochondrial fission and their mechanisms of action remain largely unknown. We found that Fis1, the only identifiable mitochondrial fission adaptor protein evolutionarily conserved in the phylum of Apicomplexa, however, is not essential forPlasmodium falciparum. Our data suggest that malaria parasites use redundant fission adaptor proteins on the mitochondrial outer membrane to mediate the fission process.
Whole-Genome Sequence Typing shows extensive diversity ofListeria monocytogenesin the outdoor environment and poultry processing plants
Authors: Louha Swarnali , Meinersmann Richard J. , Abdo Zaid , Berrang Mark E. , Glenn Travis C. 
Published: June 2020

ABSTRACTA reliable and standardized classification ofListeria monocytogenes(Lm) is important for accurate strain identification during outbreak investigations. Current whole-genome sequencing (WGS) based approaches for strain characterization either lack standardization, rendering them less suitable for data exchange, or are not freely available. Thus, we developed a portable and open-source tool Haplo-ST to improve standardization and provide maximum discriminatory potential to WGS data tied to an MLST (multi locus sequence typing) framework. Haplo-ST performs whole-genome MLST (wgMLST) forLmwhile allowing for data exchangeability worldwide. This tool takes in (i) raw WGS reads as input, (ii) cleans the raw data according to user specified parameters, (iii) assembles genes across loci by mapping to genes from reference strains, (iv) assigns allelic profiles to assembled genes and provides a wgMLST subtyping for each isolate. Data exchangeability relies on the tool assigning allelic profiles based on a centralized nomenclature defined by the widely-used BIGSdb-Lmdatabase. Tests on Haplo-ST’s performance with simulated reads fromLmreference strains yielded a high sensitivity of 97.5%, and coverage depths of ≥ 20× was found to be sufficient for wgMLST profiling. We used Haplo-ST to characterize and differentiate between two groups ofLmisolates, derived from the natural environment and poultry processing plants. Phylogenetic reconstruction showed sharp delineation of lineages within each group and no lineage-specificity was observed with isolate phenotypes (transient vs. persistent) or origins. Genetic differentiation analyses between isolate groups identified 21 significantly differentiated loci, potentially enriched for adaptation and persistence ofLmwithin poultry processing plants.IMPORTANCEWe have developed an open-source tool that provides allele-based subtyping ofLmisolates at the whole genome level. Along with allelic profiles, this tool also generates allele sequences, and identifies paralogs, which is useful for phylogenetic tree reconstruction and deciphering relationships between closely related isolates. More broadly, Haplo-ST is flexible and can be adapted to characterize the genome of any haploid organism simply by installing an organism-specific gene database. Haplo-ST also allows for scalable subtyping of isolates; fewer reference genes can be used for low resolution typing, whereas higher resolution can be achieved by increasing the number of genes used in the analysis. Our tool enabled clustering ofLmisolates into lineages and detection of potential loci for adaptation and persistence in food processing environments. Findings from these analyses highlights the effectiveness of Haplo-ST in subtyping and evaluating relationships among isolates for routine surveillance, outbreak investigations and source tracking.
Disruption of the MreB elongasome is overcome by mutations in the TCA cycle
Authors: Barton Brody , Grinnell Addison , Morgenstein Randy M. 
Published: June 2020

AbstractThe bacterial actin homolog, MreB, is highly conserved among rod-shaped bacteria and essential for growth under normal growth conditions. MreB directs the localization of cell wall synthesis and loss of MreB results in round cells and death. Using the MreB depolymerizing drug, A22, we show that changes to central metabolism through deletion of malate dehydrogenase from the TCA cycle results in cells with an increased tolerance to A22. We hypothesize that deletion of malate dehydrogenase leads to the upregulation of gluconeogenesis resulting in an increase in cell wall precursors. Consistent with this idea, metabolite analysis revealed thatmdhdeletion cells possess elevated levels of several glycolysis/gluconeogenesis compounds and the cell wall precursor, UDP-NAG. In agreement with these results, the increased A22 resistance phenotype can be recapitulated through the addition of glucose to the media. Finally, we show that this increase in antibiotic tolerance is not specific to A22 but also applies to the cell wall-targeting antibiotic, mecillinam.
Integrative omics data analysis uncovers biomarker genes and potential candidate drugs for G3 medulloblastoma
Authors: Guo Loreina , Cornick Kendall , Xu Vincent , Hao Tianyao , Ilagan Ma. Xenia G. , Buchser William , Rubin Joshua B. , Li Fuhai 
Published: June 2020

AbstractMedulloblastoma (MB) is the most common malignant brain tumor in infants and children. Four molecular subtypes of MB are recognized: WNT, SHH, Group 3 (G3), and Group 4 (G4). Compared with WNT and SHH subtypes, G3 MBs exhibit significantly worse outcomes and higher metastatic rates, and there is no effective treatment yet. Moreover, G3 and G4 MBs are much more common in boys than girls, i.e., sex bias, which also plays important roles in cancer prognosis and drug response. However, the molecular mechanism of G3 remains unclear, and there are no well-identified biomarker genes associated with these phenotypes, i.e., worse survival rate, higher metastasis rate, and sex bias. In this exploratory study, we aim to identify potential biomarkers associated with the three phenotypes using integrative analysis of gene expression, methylation and copy number variation datasets. In the results, we identified a set of biomarker genes and linked them into a network signature. The network signature showed better performance in the separation of G3 MB patients into subtypes with a significant difference in terms of the three phenotypes. To identify potentially effective drugs for G3 MBs, a set of drugs with diverse targets were prioritized, which can potentially inhibit the network signature. These drugs or combinations thereof might be effective for G3 treatment.
Live-cell single-molecule tracking highlights requirements for stable Smc5/6 chromatin associationin vivo
Authors: Etheridge Thomas J. , Villahermosa Desiree , Campillo-Funollet Eduard , Herbert Alex , Irmisch Anja , Watson Adam T. , Dang Hung Q. , Osborne Mark A. , Oliver Antony W. , Carr Antony M. , Murray Johanne M. 
Published: June 2020

AbstractThe essential Smc5/6 complex is required in response to replication stress and is best known for ensuring the fidelity of homologous recombination. Using single-molecule tracking in live fission yeast to investigate Smc5/6 chromatin association, we show that Smc5/6 is chromatin associated in unchallenged cells and this depends on the non-SMC protein Nse6. We define a minimum of two Nse6-dependent sub-pathways, one of which requires the BRCT-domain protein Brc1. Using defined mutants in genes encoding the core Smc5/6 complex subunits we show that the Nse3 double-stranded DNA binding activity and the arginine fingers of the two Smc5/6 ATPase binding sites are critical for chromatin association. Interestingly, disrupting the ssDNA binding activity at the hinge region does not prevent chromatin association but leads to elevated levels of gross chromosomal rearrangements during replication restart. This is consistent with a downstream function for ssDNA binding in regulating homologous recombination.
Fine-mapping, trans-ancestral and genomic analyses identify causal variants, cells, genes and drug targets for type 1 diabetes
Authors: Robertson C.C. , Inshaw J.R.J. , Onengut-Gumuscu S. , Chen W.M. , Flores Santa Cruz D. , Yang H. , Cutler A.J. , Crouch D.J.M. , Farber E. , Bridges S.L. , Edberg J.C. , Kimberly R.P. , Buckner J.H. , Deloukas P. , Divers J. , Dabelea D. , Lawrence J.M. , Marcovina S. , Shah A.S. , Greenbaum C.J. , Atkinson M.A. , Gregersen P.K. , Oksenberg J.R. , Pociot F. , Rewers M.J. , Steck A.K. , Dunger D.B. ,   Type 1 Diabetes Genetics Consortium, Wicker L.S. , Concannon P. , Todd J.A. , Rich S.S. 
Published: June 2020

AbstractWe report the largest and most ancestrally diverse genetic study of type 1 diabetes (T1D) to date (61,427 participants), yielding 152 regions associated to false discovery rate < 0.01, including 36 regions associated to genome-wide significance for the first time. Credible sets of disease-associated variants are specifically enriched in immune cell accessible chromatin, particularly in CD4+effector T cells. Colocalization with chromatin accessibility quantitative trait loci (QTL) in CD4+T cells identified five regions where differences in T1D risk and chromatin accessibility are potentially driven by the same causal variant. Allele-specific chromatin accessibility further refined the set of putative causal variants with functional relevance in CD4+T cells and integration of whole blood expression QTLs identified candidate T1D genes, providing high-yield targets for mechanistic follow-up. We highlight rs72938038 inBACH2as a candidate causal T1D variant, where the T1D risk allele leads to decreased enhancer accessibility andBACH2expression in T cells. Finally, we prioritise potential drug targets by integrating genetic evidence, functional genomic maps, and immune protein-protein interactions, identifying 12 genes implicated in T1D that have been targeted in clinical trials for autoimmune diseases. These findings provide an expanded genomic landscape for T1D, including proposed genetic regulatory mechanisms of T1D-associated variants and genetic support for therapeutic targets for immune intervention.
FastPG: Fast clustering of millions of single cells
Authors: Bodenheimer Tom , Halappanavar Mahantesh , Jefferys Stuart , Gibson Ryan , Liu Siyao , Mucha Peter J. , Stanley Natalie , Parker Joel S. , Selitsky Sara R. 
Published: June 2020

AbstractCurrent single-cell experiments can produce datasets with millions of cells. Unsupervised clustering can be used to identify cell populations in single-cell analysis but often leads to interminable computation time at this scale. This problem has previously been mitigated by subsampling cells, which greatly reduces accuracy. We built on the graph-based algorithm PhenoGraph and developed FastPG which has the same cell assignment accuracy but is on average 27x faster in our tests. FastPG also has higher cell assignment accuracy than two other fast clustering methods, FlowSOM and PARC.AvailabilityFastPG is available here:https://github.com/sararselitsky/FastPG
Phylogenetic pattern of SARS-CoV-2 from COVID-19 patients from Bosnia and Herzegovina: lessons learned to optimize future molecular and epidemiological approaches
Authors: Goletic Teufik , Konjhodzic Rijad , Fejzic Nihad , Goletic Sejla , Eterovic Toni , Softic Adis , Kustura Aida , Salihefendic Lana , Ostojic Maja , Travar Maja , Mrdjen Visnja , Tihic Nijaz , Jazic Sead , Musa Sanjin , Marjanovic Damir , Hukic Mirsada 
Published: June 2020

AbstractWhole Genome Sequence of four samples from COVID-19 outbreaks was done in two laboratories in Bosnia and Herzegovina (Veterinary Faculty Sarajevo and Alea Genetic Center). All four BiH sequences cluster mainly with European ones (Italy, Austria, France, Sweden, Cyprus, England). The constructed phylogenetic tree indicates probable multiple independent introduction events. The success of future containment measures concernig new introductions will be highly challenging for country due to the significant proportion of BH population living abroad.
Postponing production exponentially enhances the molecular memory of a stochastic switch
Authors: Bokes Pavol 
Published: June 2020

AbstractDelayed production can substantially alter the qualitative behaviour of feedback systems. Motivated by stochastic mechanisms in gene expression, we consider a protein molecule which is produced in randomly timed bursts, requires an exponentially distributed time to activate, and then partakes in positive regulation of its burst frequency. Asymptotically analysing the underlying master equation in the large-delay regime, we provide tractable approximations to time-dependent probability distributions of molecular copy numbers. Importantly, the presented analysis demonstrates that positive feedback systems with large production delays can constitute a stable toggle switch even if they operate with low copy numbers of active molecules.
Human Prostate Cancer-Associated Macrophage Subtypes with Prognostic Potential Revealed by Single-cell Transcriptomics
Authors: Siefert Joseph C , Cioni Bianca , Muraro Mauro J , Alshalalfa Mohammed , Vivié Judith , van der Poel Henk , Feng Felix Y , Wessels Lodewyk , Zwart Wilbert , Bergman Andries M 
Published: June 2020

ABSTRACTMacrophages in the tumor microenvironment are causally linked with prostate cancer development and progression, yet little is known about their composition in neoplastic human tissue. By performing single cell transcriptomic analysis of human prostate cancer resident macrophages, three distinct populations were identified in the diseased prostate. Unexpectedly, macrophages isolated from the tumor-adjacent site of the prostatectomy specimen were identical to those from the tumorous site. Markers associated with canonical M1 and M2 macrophage phenotypes were identifiable, however these were not the main factors defining unique subtypes. The genes selectively associated with each macrophage cluster were used to develop a gene signature which was highly associated with both recurrence-free and metastasis-free survival. These results highlight the relevance of tissue-specific macrophage subtypes in the tumour microenvironment for prostate cancer progression and demonstrates the utility of profiling single-cell transcriptomics in human tumor samples as a strategy to design gene classifiers for patient prognostication.
Colors everywhere: enhanced chromatic processing across the first visual synapse in the zebrafish central brain
Authors: Guggiana Nilo Drago A. , Riegler Clemens , Hübener Mark , Engert Florian 
Published: June 2020

SummaryLarval zebrafish (Danio rerio) are an ideal organism to study color vision, as their eye possesses four types of cone photoreceptors, covering most of the visible range and into the UV [1,2]. Additionally, their entire eye and nervous system are accessible to imaging, given they are naturally transparent [3–5]. Relying on this advantage, recent research has found that, through a set of color specific horizontal, bipolar and retinal ganglion cells (RGCs) [6–8], the eye then relays tetrachromatic information to several retino-recipient areas (RAs) [9,10]. The main RA is the optic tectum, receiving 97% of the RGC axons via the neuropil mass termed Arborization Field 10 (AF10) [11,12]. In this work, we aim to understand the processing of color signals at the interface between RGCs and their targets in the brain. We used 2-photon calcium imaging to separately measure the responses of RGCs and neurons in the dorsal brain to stimulation with four different colors in awake animals. We find that color information is widespread throughout the larval brain, with a large variety of color responses among RGCs, and an even greater diversity in their targets. Specific combinations of response types are localized to specific nuclei, but we observe no single color processing structure. In the main interface in this pathway, the connection between Arborization Field 10 and the tectum, we observe key elements of color processing such as enhanced signal decorrelation and improved decoding [13,14]. Finally, when presenting a richer set of stimuli, we identify parallel processing of color, motion and luminance information in the same cells/terminals, evidence of a rich color vision machinery in this small vertebrate brain.
DNA damage inhibits root growth by enhancing cytokinin biosynthesis inArabidopsis thaliana
Authors: Takahashi Naoki , Inagaki Soichi , Nishimura Kohei , Sakakibara Hitoshi , Antoniadi Ioanna , Karady Michal , Ljung Karin , Umeda Masaaki 
Published: June 2020

AbstractPlant root growth is influenced by external factors to adapt to changing environmental conditions. However, the mechanisms by which environmental stresses affect root growth remain elusive. Here we found that DNA double-strand breaks (DSBs) induce the expression of genes for the synthesis of cytokinin hormones and enhance the accumulation of cytokinins in theArabidopsisroot tip. This is a programmed response to DSBs through the DNA damage signaling pathway. Our data showed that activation of cytokinin signalling suppresses the expression ofPIN-FORMEDgenes that encode efflux carriers of another plant hormone, auxin, thereby disturbing downward auxin flow and causing cell cycle retardation in the G2 phase. Elevated cytokinin signalling also promotes an early transition from cell division to endoreplication, resulting in a reduction of the root meristem size. We propose that in response to DNA stress, plants inhibit root growth by orchestrating hormone biosynthesis and signalling.
Using cost-effective surveys from platforms of opportunity to assess cetacean occurrence patterns for marine park management in the heart of the Coral Triangle
Authors: Sahri Achmad , Mustika Putu Liza Kusuma , Purwanto  , Murk Albertinka J. , Scheidat Meike 
Published: June 2020

ABSTRACTThe Wakatobi National Park (WNP) at the heart of Coral Triangle is an important area for cetaceans in Indonesia. Currently there is insufficient information on spatio-temporal occurrence patterns of cetaceans to inform effective conservation strategies. This study used platforms of opportunity from May 2004 to May 2012 as a cost-effective way to address this knowledge gap. A database was created of cetacean sightings per surveyed days at sea, allowing for an analysis of species diversity and habitat use around the islands. A total of 11 cetacean species were identified. Spinner and bottlenose dolphins were sighted most often, followed by melon-headed and sperm whales. Spinner dolphin showed a wide distribution in the area, whilst bottlenose dolphin and melon-headed whale occupied the waters between the main islands and south atolls. Sperm whales occurred mostly in waters to the north of the main islands and as melon-headed whales were mostly found in deep waters. Most cetacean sightings occurred in the zones designated for human use, indicating where potential conflicts might occur. No sightings were found in the Park core zone, indicating a mismatch between WNP design and the ecological needs of the cetaceans. A sub-sample of the data from dedicated fishing monitoring trips was used to derive a sighting frequency. Occurrence of both small and large cetaceans was highest during inter-monsoonal seasons, possibly related to an increase of prey availability due to seasonal upwelling and increase in survey activity. Inter-annual occurrence of cetaceans was variable, with no large cetaceans being sighted in 2010-2012, likely due to reduced survey efforts. In areas with limited resources for designated surveys, the use of platforms of opportunity can be a cost-effective tool to provide valuable data on cetacean occurrence. It helps identify potentially important areas as well as highlight where to direct designated research efforts. We discuss the implications of our findings for the conservation management of these cetaceans and give suggestions for improved marine park management.