bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncured PDMS Inhibits Myosin In Vitro Motility in a Microfluidic Flow Cell
Authors: Wang Yihua , Burghardt Thomas P. 
Published: September 2018

ABSTRACTThe myosin motor powers cardiac contraction and is frequently implicated in hereditary heart disease by its mutation. Principal motor function characteristics include myosin unitary step size, duty cycle, and force-velocity relationship for translating actin under load. These characteristics are sometimes measured in vitro with a motility assay detecting fluorescent labeled actin filament gliding velocity over a planar array of surface immobilized myosin. Assay miniaturization in a polydimethylsiloxane/glass (PDMS/glass) hybrid microfluidic flow channel is an essential component to a small sample volume assay applicable to costly protein samples however the PDMS substrate dramatically inhibits myosin motility. Myosin in vitro motility in a PDMS/glass hybrid microfluidic flow cell was tested under a variety of conditions to identify and mitigate the effect of PDMS on myosin. Substantial contamination by the monomeric species in polymerized PDMS flow cells is shown to be the cause of myosin motility inhibition. Normal myosin motility recovers by either extended cell aging (∼20 days) to allow more complete polymerization or by direct chemical extraction of the free monomers from the polymer substrate. PDMS flow cell aging is the low cost alternative compatible with the other PDMS and glass modifications needed for in vitro myosin motility assaying.
Mitotic replisome disassembly in vertebrates
Authors: Moreno Sara Priego , Jones Rebecca M. , Poovathumkadavil Divyasree , Gambus Agnieszka 
Published: September 2018

ABSTRACTRecent years have brought a breakthrough in our understanding of the process of eukaryotic DNA replication termination. We have shown that the process of replication machinery (replisome) disassembly at the termination of DNA replication forks in S-phase of the cell cycle is driven through polyubiquitylation of one of the replicative helicase subunits Mcm7. Our previous work in C.elegans embryos suggested also an existence of a back-up pathway of replisome disassembly in mitosis. Here we show, that in Xenopus laevis egg extract, any replisome retained on chromatin after S-phase is indeed removed from chromatin in mitosis. This mitotic disassembly pathway depends on formation of K6 and K63 ubiquitin chains on Mcm7 by TRAIP ubiquitin ligase and activity of p97/VCP protein segregase. The mitotic replisome pathway is therefore conserved through evolution in higher eukaryotes. However, unlike in lower eukaryotes it does not require SUMO modifications. This process can also remove any helicases from chromatin, including “active” stalled ones, indicating a much wider application of this pathway than just a “back-up” for terminated helicases.
Chromatin changes in Anopheles gambiae induced by a Plasmodium falciparum infection
Authors: Ruiz José L. , Yerbanga Rakiswendé S. , Lefèvre Thierry , Ouedraogo Jean B. , Corces Victor G. , Gómez-Díaz Elena 
Published: September 2018

ABSTRACTInfection by the human malaria parasite leads to important changes in mosquito phenotypic traits related to vector competence. However, we still lack a clear understanding of the underlying mechanisms and in particular, of the epigenetic basis for these changes. We have examined genome-wide distribution maps of H3K27ac, H3K9ac, H3K9me3 and H3K4me3 by ChIP-seq and the transcriptome by RNA-seq, of midguts from Anopheles gambiae mosquitoes infected with natural isolates of the human malaria parasite Plasmodium falciparum in Burkina Faso. We report 15,916 regions containing differential histone modification enrichment, of which 8,339 locate at promoters and/or intersect with genes. The functional annotation of these regions allowed us to identify infection responsive genes showing differential enrichment in various histone modifications, such as CLIP pro-teases, anti-microbial peptides encoding genes, and genes related to melanization responses and the complement system. Further, the motif analysis of regions differentially enriched in various histone modifications predicts binding sites that might be involved in the cis-regulation of these regions such as Deaf1, Pangolin and Dorsal transcription factors (TFs). Some of these TFs are known to regulate immunity gene expression in Drosophila and are involved in the Notch and JAK/STAT signaling pathways. The analysis of malaria infection-induced chromatin changes in mosquitoes is important not only to identify regulatory elements and genes underlying mosquito responses to a P. falciparum infection but also for possible applications to the genetic manipulation of mosquitoes and to other mosquito-borne systems.
Inferring Sequence-Structure Preferences of RNA-Binding Proteins with Convolutional Residual Networks
Authors: Koo Peter K. , Anand Praveen , Paul Steffan B. , Eddy Sean R. 
Published: September 2018

AbstractTo infer the sequence and RNA structure specificities of RNA-binding proteins (RBPs) from experiments that enrich for bound sequences, we introduce a convolutional residual network which we call ResidualBind. ResidualBind significantly outperforms previous methods on experimental data from many RBP families. We interrogate ResidualBind to identify what features it has learned from high-affinity sequences with saliency analysis along with 1st-order and 2nd-orderin silicomutagenesis. We show that in addition to sequence motifs, ResidualBind learns a model that includes the number of motifs, their spacing, and both positive and negative effects of RNA structure context. Strikingly, ResidualBind learns RNA structure context, including detailed base-pairing relationships, directly from sequence data, which we confirm on synthetic data. ResidualBind is a powerful, flexible, and interpretable model that can uncovercis-recognition preferences across a broad spectrum of RBPs.
A Genome-Wide Association Study Identifies SNP Markers for Virulence in Magnaporthe oryzae Isolates from Sub-Saharan Africa
Authors: Ganeshan Veena Devi , Opiyo Stephen O. , Mutiga Samuel K. , Rotich Felix , Thuranira David M. , Were Vincent M. , OuéDraogo Ibrahima , Zhou BO , Soanes Darren M. , Correll James C. , Wang Guo-Liang , Talbot Nicholas J. , Mitchell Thomas K. 
Published: September 2018

ABSTRACTThe fungal phytopathogen Magnaporthe oryzae causes blast disease in cereals such as rice and finger millet worldwide. In this study, we assessed genetic diversity of 160 isolates from nine sub-Saharan Africa (SSA) and other principal rice producing countries and conducted a genome-wide association study (GWAS) to identify the genomic regions associated with virulence of M. oryzae. GBS of isolates provided a large and high-quality 617K single nucleotide polymorphism (SNP) dataset. Disease ratings for each isolate was obtained by inoculating them onto differential lines and locally-adapted rice cultivars. Genome-wide association studies were conducted using the GBS dataset and sixteen disease rating datasets. Principal Component Analysis (PCA) was used an alternative to population structure analysis for studying population stratification from genotypic data. A significant association between disease phenotype and 528 SNPs was observed in six GWA analyses. Homology of sequences encompassing the significant SNPs was determined to predict gene identities and functions. Seventeen genes recurred in six GWA analyses, suggesting a strong association with virulence. Here, the putative genes/genomic regions associated with the significant SNPs are presented.
Visualizing Deep Mutational Scan Data
Authors: Sruthi C. K. , Balaram Hemalatha , Prakash Meher K. 
Published: September 2018

AbstractSite-directed and random mutagenesis are biochemical tools to obtain insights into the structure and function of proteins. Recent advances such as deep mutational scan have allowed a complete scan of all the amino acid positions in a protein with each of the 19 possible alternatives. Mapping out the phenotypic consequences of thousands of single point mutations in the same protein is now possible. Visualizing and analysing the rich data offers an opportunity to learn more about the effects of mutations, for a better understanding and engineering of proteins. This work focuses on such visualization analyses applied to the mutational data of TEM-1 β-lactamase. The data is examined in the light of the expected biochemical effects of single point mutations, with the goal of reinforcing or retraining the intuitions. Individual attributes of the amino acid mutations such as the solvent accessible area, charge type change, and distance from the catalytic center capture most of the relevant functional effects. Visualizing the data suggests how combinations of these attributes can be used for a better classification of the effects of mutations, when independently they do not offer a high predictability.
Olfactory object recognition based on fine-scale stimulus timing inDrosophila
Authors: Sehdev Aarti , Mohammed Yunusa G. , Triphan Tilman , Szyszka Paul 
Published: September 2018

SUMMARYOdorants of behaviorally relevant objects (e.g., food sources) intermingle with those from other sources. Therefore, to sniff out whether an odor source is good or bad – without actually visiting it – animals first need to segregate the odorants from different sources. To do so, animals could use temporal cues, since odorants from one source exhibit correlated fluctuations, while odorants from different sources are less correlated. However, it remains unclear whether animals can rely solely on temporal cues for odor source segregation. Here we show that 1) flies can use a few milliseconds differences in odorant arrival to segregate a target odorant from a binary mixture, 2) segregation does not improve when the target odorant arrives first, and 3) segregation works for odorants with innate, as well as learned valences. These properties of odor segregation parallel those of concurrent sound segregation and figure-ground segregation by onset asynchrony in humans.
IL-10 and ICOS differentially regulate T cell responses in the brain during chronicToxoplasma gondiiinfection
Authors: O’Brien Carleigh A. , Batista Samantha J. , Still Katherine M. , Harris Tajie H. 
Published: September 2018

AbstractControl of chronic CNS infection with the parasiteToxoplasma gondiirequires an ongoing T cell response in the brain. Immunosuppressive cytokines are also important for preventing lethal immunopathology during chronic infection. To explore the loss of suppressive cytokine exclusively during the chronic phase of infection we blocked IL-10 receptor (IL-10R). Blockade was associated with widespread changes in the inflammatory response, including increased antigen presenting cell (APC) activation, expansion of CD4+ T cells, and increased neutrophil recruitment to the brain, consistent with previous reports. We then sought to identify regulatory mechanisms contributing to IL-10 production, focusing on ICOS (inducible T cell costimulator), a molecule that promotes IL-10 production in many systems. Unexpectedly, ICOS-ligand (ICOSL) blockade led to a local expansion of effector T cells in the inflamed brain without affecting IL-10 production or APC activation. Instead, we found that ICOSL blockade led to changes in T cells associated with their proliferation and survival. Specifically, we observed increased expression of IL-2 associated signaling molecules, including CD25, STAT5 phosphorylation, Ki67, and Bcl-2 in T cells in the brain. Interestingly, increases in CD25 and Bcl-2 were not observed following IL-10R blockade. Also unlike IL-10R blockade, ICOSL blockade led to an expansion of both CD8+ and CD4+ T cells in the brain, with no expansion of peripheral T cell populations or neutrophil recruitment to the brain Overall, these results suggest that IL-10 and ICOS differentially regulate T cell responses in the brain during chronicT. gondiiinfection.
Active and repressed chromatin domains exhibit distinct nucleosome segregation during DNA replication
Authors: Escobar Thelma M. , Oksuz Ozgur , Descostes Nicolas , Bonasio Roberto , Reinberg Danny 
Published: September 2018

SummaryChromatin domains and their associated structures must be faithfully inherited through cellular division to maintain cellular identity. Yet, accessing the localized strategies preserving chromatin domain inheritance, specifically the transfer of parental, pre-existing nucleosomes with their associated post-translational modifications (PTMs) during DNA replication is challenging in living cells. We devised an inducible, proximity-dependent labeling system to irreversibly mark replication-dependent H3.1 and H3.2 histone-containing nucleosomes at single desired loci in mouse embryonic stem cells such that their fate after DNA replication could be followed. Strikingly, repressed chromatin domains are preserved through the local re-deposition of parental nucleosomes. In contrast, nucleosomes decorating active chromatin domains do not exhibit such preservation. Notably, altering cell fate leads to an adjustment in the positional inheritance of parental nucleosomes that reflects the corresponding changes in chromatin structure. These findings point to important mechanisms that contribute to parental nucleosome segregation to preserve cellular identity.
A fully automated spike sorting algorithm using t-distributed neighbor embedding and density based clustering
Authors: Nadian Mohammad Hossein , Karimimehr Saeed , Doostmohammadi Jafar , Ghazizadeh Ali , Lashgari Reza 
Published: September 2018

AbstractIn this study, a new spike sorting method was developed based on a combination of two methods, t-Distributed Stochastic Neighbor Embedding (t-SNE) and Density-Based Spatial Clustering of Applications with Noise (DBSCAN). Parameters of both methods were simultaneously optimized using a Genetic Algorithm (GA) using a simulated dataset containing 2 to 20 simultaneously recorded neurons. The performance of this method was evaluated using both the simulated dataset as well as real multichannel electrophysiological data. The results indicated that our fully automated algorithm using t-SNE-DBSCAN outperforms other state-of-the-art algorithms and human experts in spike sorting especially when there are a large number of simultaneously recorded units. Our algorithm also determines the noise waveforms and has an overall high sensitivity, precision and accuracy for correctly classifying waveforms belonging to each neuron (all >90%) without the need for manual corrections afterwards. Our method can be a crucial part of the analysis pipeline in particular when manual sorting of units is becoming prohibitive due to the sheer number of recorded neurons per session.
Theory on the looping mediated directional-dependent propulsion of transcription factors along DNA
Authors: Murugan R. 
Published: September 2018

ABSTRACTWe show that the looping mediated transcription activation by the combinatorial transcription factors (TFs) can be achieved via directional-dependent propulsion, tethered sliding and tethered binding-sliding-unbinding modes. In the propulsion mode, the first arrived TF at the cis-regulatory motifs (CRMs) further recruits other TFs via protein-protein interactions. Such TFs complex has two different types of DNA binding domains (DBDs) viz. DBD1 which forms tight site-specific complex with CRMs via hydrogen bonding network and the promoter specific DBD2s which form nonspecific interactions around CRMs. When the sum of these specific and cumulative nonspecific interactions is sufficient, then the flanking DNA of CRMs will be bent into a circle over the TFs complex. The number of TFs involved in the combinatorial regulation plays critical role here. When the site-specific interactions and the cumulative nonspecific interactions are strong enough to resist the dissociation, then the sliding of DBD2s well within the Onsager radius associated with the DBD2s-DNA interface towards the promoter is the only possible way to release the elastic stress of the bent DNA. The DBD2s form tight synaptosome complex upon finding the promoter via sliding. When the number of TFs is not enough to bend the DNA in to a circle, then tethered sliding or tethered binding-sliding-unbinding modes are the possibilities. In tethered sliding, the CRMs-TFs complex forms nonspecific contacts with DNA via dynamic loops and then slide along DNA towards promoter without dissociation. In tethered binding-sliding-unbinding, the CRMs-TFs performs several cycles of nonspecific binding-sliding-unbinding before finding the promoter. Elastic and entropic energy barriers associated with the looping of DNA shape up the distribution of distances between CRMs and promoters. The combinatorial regulation of TFs in eukaryotes has evolved to overcome the looping energy barrier.
Dengue fever is an emerging public health concern in the city of Multan, Pakistan: its seroprevalence and associated risk factors
Authors: Mukhtar Muhammad Uzair , Mukhtar Maria , Iqbal Naveed 
Published: September 2018

ABSTRACTThe prevalence of dengue IgG and IgM antibodies was investigated in 689 patients with suspected dengue. Of the 689 suspected cases, 373 (54.1%) were found to be positive for dengue antibodies, IgM being dominant. There was a significant relationship between incidence of dengue fever and season: all cases were reported during the rainy season, especially the post‐monsoon season (89.5%), with none during the dry season. More male (79.3%) than female individuals were positive cases and the incidence was highest in the 21–49 year age group (63%). This is the first seroprevalence study reported from Multan, Pakistan.
Effects of urbanisation and management practices on pollinators in tropical Africa
Authors: Guenat Solène , Kunin William E. , Dougill Andrew J. , Dallimer Martin 
Published: September 2018

Abstract

Urban expansion is an increasing threat to biodiversity, especially in tropical Africa where biodiversity hot spots are being encroached upon by fast‐growing cities. Threatened species include bees and other pollinators, which deliver important ecosystem services but are sensitive to land use changes.

We investigated the impact of urbanisation and vegetation management practices on pollinator abundance, bee diversity, and bee functional traits. We sampled 126 locations in a stratified random design across an urbanisation gradient in two medium‐sized cities in the West African Forests biodiversity hot spot, encompassing three management practices (farmed sites; amenity lands, i.e. green spaces managed for aesthetics; informal green spaces), and tested their effect with generalised linear models.

Urbanisation did not affect bee abundances or diversity but had a negative impact on both wasp and beetle abundances. There was also a management‐mediated impact of urbanisation on bee abundances, which decreased with urbanisation on farmed sites but not amenity land or informal green spaces. Management practices alone influenced bee abundances with farms harbouring fewer bees, and amenity lands fewer beetles.

Bee genera occurrence and dominance patterns were influenced by both urbanisation and management, with some otherwise common genera rare in urban areas.

Most functional traits were influenced by management, with fewer polylectic bees, cavity‐nesting bees and long‐tongued bees in farmed sites. Amenity lands hosted smaller bees and fewer savanna specialists. Some traits were influenced by urbanisation, with more long‐tongued bees and cavity‐nesting bees found in urban areas.

Synthesis and applications. Pollinator responses to urbanisation are complex. In our research, we demonstrate how bee, lepidopteran, and non‐fruit fly abundances have been maintained across an urbanisation gradient in tropical Africa, but not wasp and beetle abundances. Moreover, bee community composition and the distribution of traits shifted markedly. How green spaces were managed was also critical. We found that farmed sites hosted the lowest bee abundances and amenity lands the fewest beetles. Retaining informal green spaces and amenity lands in African cities, including protecting nesting sites for stingless bees, and limiting pesticide application would be important for conserving bees and the pollination service they provide to both crops and native vegetation.
Testing rangeland health theory in the Northern Great Plains
Authors: Reinhart Kurt O. , Rinella Matthew J. , Waterman Richard C. , Petersen Mark K. , Vermeire Lance T. 
Published: September 2018

Abstract

Correctly assessing whether rangeland ecosystem services are stable, improving, or degrading is of global importance. Soil aggregate stability (SAS) is widely used to infer rangeland health, partly because high SAS is thought to reduce run‐off by increasing infiltration. We studied the sensitivity of SAS to grazing and other disturbances, the effects of SAS on infiltration, and the utility of alternative indicators of infiltration in the Northern Great Plains.

To test grazing effects on SAS, we compared SAS between paired areas that were lightly to moderately grazed or excluded from grazing for 6 years. Additionally, we compared SAS between grazed and not‐grazed plots of a 2‐year controlled grazing experiment with moderate and severe grazing. We also applied herbicide, mowing, and fungicide treatments to test SAS responses to disturbances more generally, as well as effects of SAS and other factors on infiltration. To more generally test for a SAS–infiltration relationship, we performed a meta‐analysis of our data combined with other data from the region.

Grazing often reduced stability of small macroaggregates (0.25–1 mm) in the controlled grazing experiment but not the paired grazing area experiment. Grazing had no detectible effect on SAS of larger macroaggregates (1–2 mm). Herbicide tended to reduce SAS, and mowing sometimes increased SAS. Infiltration exhibited high plot‐to‐plot variation and was not significantly affected by treatments. Variation in infiltration was best explained by plant community composition variables and was not explained by either SAS or other soil properties. Our meta‐analysis revealed no general SAS–infiltration relationship.

Synthesis and applications. Our findings counter prevailing expectations that soil aggregate stability (SAS) is consistently sensitive to rangeland disturbance(s) and a leading indicator of soil water transport. Plant community composition properties were better predictors of infiltration. Our findings support the theory that excessive grazing increases the prevalence of a grazing tolerant species, which was associated with low levels of infiltration irrespective of SAS.