bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small-scale field testing of Alpha-cypermethrin water-dispersible granules in comparison with the recommended wettable powder formulation for indoor residual spraying against malaria vectors in Benin
Authors: Moiroux Nicolas , Djenontin Armel , Zogo Barnabas , Bouraima Aziz , Sidick Ibrahim , Pigeon Olivier , Pennetier Cédric 
Published: December 2017

AbstractBackgroudPyrethroids are the most common class of insecticide used worldwide for indoor residual spraying (IRS) against malaria vectors. Water-dispersible granules (WG) are a pyrethroid formulation to be applied after disintegration and dispersion in water with less risks of inhalation than using the usual wettable powder (WP) formulation. The objective of this small-scale field study was to evaluate efficacy and duration of insecticidal action of a new alpha-cypermethrin WG (250g a.i./Kg) against susceptible Anopheles gambiae in comparison with the WHO reference product (alpha-cypermethrin WP, 50g a.i./Kg) on the most common indoor surfaces in Benin.MethodsBoth formulations were applied at two target-dose concentrations in houses made of mud and cement in the Tokoli village in southern Benin. We measured the applied dose of insecticide by chemical analysis of filter paper samples collected from the sprayed inner walls. We recorded An. gambiae mortality and knock-down rates every 15 days during 6 months using standard WHO bioassays.ResultsThe alpha-cypermethrin WG formulation did not last as long as the WP formulation on both surfaces. The difference is higher with the 30mg/m2 concentration for which the WP formulation reached the 80% mortality threshold during 2 months on the mud-plastered walls (3 months on cement) whereas the WG formulation last only one month (2 months on cement).ConclusionsThe new WG formulation has a shorter efficacy than the WHO recommended WP formulation. In this trial, both the WG and WP formulations had low durations of efficacy that would need at least two rounds of spray to cover the entire transmission season.
Impact of antimicrobial treatment for acute otitis media on carriage dynamics of penicillin-susceptible and penicillin–non-susceptible Streptococcus pneumoniae: secondary analysis of a randomized, double-blind, placebo-controlled trial
Authors: Lewnard Joseph A. , Tähtinen Paula A. , Laine Miia K. , Lindholm Laura , Jalava Jari , Huovinen Pentti , Lipsitch Marc , Ruohola Aino 
Published: December 2017

ABSTRACTBackgroundConcerns that antimicrobial treatment may foster selection and transmission of resistant bacterial lineages have led to conflicting guidelines for clinical management of common non-severe infections. However, the impact of antimicrobial treatment on colonization dynamics is poorly understood. We used data from a previously-conducted trial of amoxicillin-clavulanate therapy for acute otitis media (AOM) to understand how antimicrobial treatment impacts the acquisition and clearance of Streptococcus pneumoniae lineages with varying susceptibility to penicillin.Methods and findingsWe measured impacts of antimicrobial treatment on nasopharyngeal carriage of penicillin-susceptible S. pneumoniae (PSSP) and penicillin–non-susceptible S. pneumoniae (PNSP) lineages at end-of-treatment and 15d, 30d, and 60d after treatment in a previously-conducted randomized, double-blind, placebo-controlled trial. Analyses were not specified in the original protocol. Among children 6-35 months of age with stringently-defined AOM, 162 were assigned amoxicillin-clavulanate, and 160 were assigned placebo. Children who did not show clinical improvement received open-label antimicrobial rescue treatment with amoxicillin-clavulanate irrespective of the randomized treatment assignment, to which both patients and physicians were blinded. The intention-to-treat populations of the intervention and placebo arms thus received care resembling immediate antimicrobial therapy and watchful waiting, respectively. Immediate amoxicillin-clavulanate reduced PSSP carriage prevalence by 88% (95%CI: 76-96%) at end-of-treatment and by 27% (–3-49%) after 60d, but did not measurably alter PNSP carriage prevalence throughout follow-up. By end-of-treatment, 7% of children who carried PSSP at enrollment remained colonized in the amoxicillin-clavulanate arm, compared to 61% of PSSP carriers who received placebo; differences in carriage prevalence persisted at least 60d after treatment among children who carried PSSP at enrollment. Among children not carrying pneumococci at enrollment, amoxicillin-clavulanate reduced PSSP acquisition by >80% over 15d. Among children who carried PNSP at enrollment, no differences in carriage prevalence of S. pneumoniae, PSSP, or PNSP were detected at follow-up visits.ConclusionsIn a setting with low PNSP prevalence, antimicrobial therapy for AOM conferred a selective impact on colonizing S. pneumoniae by accelerating clearance, and delaying acquisition, of penicillin-susceptible lineages. Absolute risk of carrying PNSP was unaffected by treatment (ClinicalTrials.gov: NCT00299455; Funding: NIH/NIGMS).
Milieu-Initiated Inversion of the Aqueous Polyproline II/Beta Propensity in the Alanine Tripeptide: Energetics Origin of the Onset of Amyloid Formation
Authors: Mirkin Noemi G. , Krimm Samuel 
Published: December 2017

ABSTRACTExtending our earlier analogous study of the alanine dipeptide (ADP), we have now analyzed the effect of the external environment on the polyproline II (P) and β relative energies, the P/β propensity, of the alanine tripeptide (ATP). Ab initio calculations of ATP(H2O)19 and ATP(H2O)19(HCl) exhibit the same propensity inversion as in ADP: in the pure-water case the PP conformation is favored while the addition of the HCl molecule results in the ββ conformation being of lower energy. A comparison, following an intermediate insertion and departure of an HCl molecule, shows that the energy of a hydrogen-bonded (H2O)19βATP::βATP(H2O)19 structure is lower than that of the sum of two separate PP systems, i.e., that the aggregated state of the peptide is favored. This arises from the basic physical response to their total environmental influences. Questions about quantitative results from molecular dynamics simulations, obviously needed to analyze longer chains and other side chains, are addressed via rigid-water calculations. The desirability of basing studies of amyloid formation on our proposed alternative milieufolding paradigm is discussed.
Tandem Duplicate Genes in Maize are Abundant and Date to Two Distinct Periods of Time
Authors: Kono Thomas J. Y. , Brohammer Alex B. , McGaugh Suzanne E. , Hirsch Candice N. 
Published: December 2017

ABSTRACTTandem duplicate genes are proximally duplicated and as such occur in the same genomic neighborhood. Using the maize B73 and PH207de novogenome assemblies, we identified thousands of tandem gene duplicates that account for ~10% of the genes. These tandem duplicates have a bimodal distribution of estimated ages corresponding to known periods of genomic instability. Tandem duplicates had a number of associated features that suggest origins in nonhomologous recombination based on smaller size distribution and higher rate of containing LTRs than non-tandem duplicates. Within relatively recent tandem duplicate genes, ~26% appear to be undergoing degeneration or divergence in function from the ancestral copy. Our results show that tandem duplicates are abundant in maize, arose in bursts throughout maize evolutionary history under multiple potential mechanisms, and may provide a substrate for novel phenotypic variation.
Transcriptional evaluation of the developmental accuracy, reproducibility and robustness of kidney organoids derived from human pluripotent stem cells
Authors: Phipson Belinda , Er Pei X , Hale Lorna , Yen David , Lawlor Kynan , Takasato Minoru , Sun Jane , Wolvetang Ernst , Oshlack Alicia , Little Melissa H 
Published: December 2017

AbstractWe have previously reported a protocol for the directed differentiation of human induced pluripotent stem cells to kidney organoids comprised of nephrons, proximal and distal epithelium, vasculature and surrounding interstitial elements. The utility of this protocol for applications such as disease modelling will rely implicitly on the developmental accuracy of the model, technical robustness of the protocol and transferability between iPSC lines. Here we report extensive transcriptional analyses of the sources of variation across the timecourse of differentiation from pluripotency to complete kidney organoid, focussing on repeated differentiations to day 18 organoid. Individual organoids generated within the same differentiation experiment show Spearman’s correlation coefficients of >0.99. The greatest source of variation was seen between experimental batch, with the enrichment for genes that also varied temporally between day 10 and day 25 organoids implicating nephron maturation as contributing to transcriptional variance between individual differentiation experiments. A morphological analysis revealed a transition from renal vesicle to capillary loop stage nephrons across the same time period. Distinct iPSC clones were also shown to display congruent transcriptional programs with inter-experimental and inter-clonal variation most strongly associated with nephron patterning. Even epithelial cells isolated from organoids showed transcriptional alignment with total organoids of the same day of differentiation. This data provides a framework for managing experimental variation, thereby increasing the utility of this approach for personalised medicine and functional genomics.
CosMIC: A Consistent Metric for Spike Inference from Calcium Imaging
Authors: Reynolds Stephanie , Abrahamsson Therese , Sjöström P. Jesper , Schultz Simon R. , Luigi Dragotti Pier 
Published: December 2017

AbstractIn recent years, the development of algorithms to detect neuronal spiking activity from two-photon calcium imaging data has received much attention. Meanwhile, few researchers have examined the metrics used to assess the similarity of detected spike trains with the ground truth. We highlight the limitations of the two most commonly used metrics, the spike train correlation and success rate, and propose an alternative, which we refer to as CosMIC. Rather than operating on the true and estimated spike trains directly, the proposed metric assesses the similarity of the pulse trains obtained from convolution of the spike trains with a smoothing pulse. The pulse width, which is derived from the statistics of the imaging data, reflects the temporal tolerance of the metric. The final metric score is the size of the commonalities of the pulse trains as a fraction of their average size. Viewed through the lens of set theory, CosMIC resembles a continuous Sørensen-Dice coefficient — an index commonly used to assess the similarity of discrete, presence/absence data. We demonstrate the ability of the proposed metric to discriminate the precision and recall of spike train estimates. Unlike the spike train correlation, which appears to reward overestimation, the proposed metric score is maximised when the correct number of spikes have been detected. Furthermore, we show that CosMIC is more sensitive to the temporal precision of estimates than the success rate.
Protein Interaction Screen on Peptide Matrix (PRISMA) reveals interaction footprints and the PTM-dependent interactome of intrinsically disordered C/EBPβ
Authors: Dittmar Gunnar , Perez Hernandez Daniel , Kowenz-Leutz Elisabeth , Kirchner Marieluise , Kahlert Günther , Wesolowski Radoslaw , Baum Katharina , Knoblich Maria , Muller Arnaud , Wolf Jana , Reimer Ulf , Leutz Achim 
Published: December 2017

SummaryCCAAT enhancer binding protein beta (C/EBPβ) is a pioneer transcription factor that specifies cell differentiation. C/EBPβ is intrinsically unstructured, a molecular feature common to many proteins involved in signal processing and epigenetics. The structure of C/EBPβ differs depending on alternative translation start site usage and multiple post-translational modifications (PTM). Mutation of distinct PTM sites in C/EBPβ alters designated protein interactions and cell differentiation, suggesting a C/EBPβ PTM indexing code determines epigenetic outcomes. Herein, we systematically explored the interactome of C/EBPβ using an array of spot-synthesised C/EBPβ-derived linear tiling peptides with and without PTM, combined with mass spectrometric proteomic analysis of protein interactions. We identified interaction footprints of ~1300 proteins in nuclear cell extracts, many with chromatin modifying, remodelling and RNA processing functions. The results suggest C/EBPβ acts as a multi-tasking molecular switchboard, integrating signal-dependent modifications and structural plasticity to orchestrate interactions with numerous protein complexes directing cell fate and function.HighlightsPeptide array based interaction proteomics map SLiM and PTM dependent C/EBPβ interactomeNovel links between C/EBPβ, RNA processing, transcription elongation, MLL, NuRD were revealedC/EBPβ structure organizes modular hub function for gene regulatory machineryPRISMA is suitable to resolve protein interactions and networks based on intrinsically disordered proteins
Hybrid correction of highly noisy Oxford Nanopore long reads using a variable-order de Bruijn graph
Authors: Morisse Pierre , Lecroq Thierry , Lefebvre Arnaud 
Published: December 2017

AbstractMotivationThe recent rise of long read sequencing technologies such as Pacific Biosciences and Oxford Nanopore allows to solve assembly problems for larger and more complex genomes than what allowed short reads technologies. However, these long reads are very noisy, reaching an error rate of around 10 to 15% for Pacific Biosciences, and up to 30% for Oxford Nanopore. The error correction problem has been tackled by either self-correcting the long reads, or using complementary short reads in a hybrid approach, but most methods only focus on Pacific Biosciences data, and do not apply to Oxford Nanopore reads. Moreover, even though recent chemistries from Oxford Nanopore promise to lower the error rate below 15%, it is still higher in practice, and correcting such noisy long reads remains an issue.ResultsWe present HG-CoLoR, a hybrid error correction method that focuses on a seed-and-extend approach based on the alignment of the short reads to the long reads, followed by the traversal of a variable-order de Bruijn graph, built from the short reads. Our experiments show that HG-CoLoR manages to efficiently correct Oxford Nanopore long reads that display an error rate as high as 44%. When compared to other state-of-the-art long read error correction methods able to deal with Oxford Nanopore data, our experiments also show that HG-CoLoR provides the best trade-off between runtime and quality of the results, and is the only method able to efficiently scale to eukaryotic genomes.Availability and implementationHG-CoLoR is implemented is C++, supported on Linux platforms and freely available athttps://github.com/morispi/HG-CoLoRContact:pierre.morisse2@univ-rouen.frSupplementary informationSupplementary data are available atBioinformaticsonline.
Increased susceptibility to intracellular bacteria and necrotic inflammation driven by a dysregulated macrophage response to TNF
Authors: Bhattacharya Bidisha , Chattrerjee Sujoy , Berland Robert , Pichugin Alexander , Gao Yuanwei , Connor John , Ivanov Alexander , Yan Bo-Shiun , Kobzik Lester , Kramnik Igor 
Published: December 2017

AbstractHost susceptibility to tuberculosis and several other intracellular bacteria is controlled by a mouse genetic locus, sst1. Necrotic inflammatory lesions, similar to human TB granulomas, are a hallmark of the sst1 susceptible phenotype. Our previous work established that increased disease severity in sst1 susceptible mice reflects dysfunctional macrophage effector or tolerance mechanisms, but the molecular mechanisms have been unclear.We demonstrate that sst1-deficient macrophages develop aberrant, biphasic responses to TNF, characterized by super-induction of stress and type I interferon pathways after prolonged TNF stimulation. This late stage response was initiated by oxidative stress and Myc. It was driven via a JNK - IFNβ - PKR feed-forward circuit locking the susceptible macrophages in a state of escalating stress. Consequently, prolonged TNF stimulation of the susceptible macrophages reduced their resilience to subsequent infection with intracellular bacteria.The data support a generalizable paradigm in host - pathogen interactions, where susceptibility emerges gradually within inflammatory tissue due to imbalanced macrophage responses to growth, differentiation, activation and stress stimuli prior to encountering pathogens. This explains how successful pathogens may locally bypass mechanisms of resistance in otherwise immunocompetent hosts and suggests novel therapeutic strategies.
Multiplexed imaging of high density libraries of RNAs with MERFISH and expansion microscopy
Authors: Wang Guiping , Moffitt Jeffrey R. , Zhuang Xiaowei 
Published: December 2017

AbstractAs an image-based single-cell transcriptomics approach, multiplexed error-robust fluorescence in situ hybridization (MERFISH) allows hundreds to thousands of RNA species to be identified, counted and localized in individual cells while preserving the native spatial context of RNAs. In MERFISH, RNAs are identified via a combinatorial labeling approach that encodes RNA species with error-robust barcodes followed by sequential rounds of single-molecule FISH (smFISH) to read out these barcodes. The accuracy of RNA identification relies on spatially separated signals from individual RNA molecules, which limits the density of RNAs that can be measured and makes the multiplexed imaging of a large number of high-abundance RNAs challenging. Here we report an approach that combines MERFISH and expansion microscopy to substantially increase the total density of RNAs that can be measured. Using this approach, we demonstrate accurate identification and counting of RNAs, with a near 100% detection efficiency, in a ~130-RNA library composed of many high-abundance RNAs, the total density of which is more than 10 fold higher than previously reported. In parallel, we demonstrate the combination of MERFISH with immunofluorescence. These advances increase the versatility of MERFISH and will facilitate its application of a wide range of biological problems.
Wolbachia Infection Associated with Increased Recombination in Drosophila
Authors: Singh Nadia D. 
Published: December 2017

AbstractWolbachia is maternally-transmitted endosymbiotic bacteria that infects a large diversity of arthropod and nematode hosts. Some strains of Wolbachia are parasitic, manipulating host reproduction to benefit themselves, while other strains of Wolbachia exhibit obligate or facultative mutualisms with their host. The effects of Wolbachia on its host are many, though primarily relate to host immune and reproductive function. Here we test the hypothesis that Wolbachia infection alters the frequency of homologous recombination during meiosis. We useD. melanogasteras a model system, and survey recombination in eight Wolbachia-infected and Wolbachia-uninfected strains, controlling for genotype. We measure recombination in two intervals of the genome. Our results indicate that Wolbachia infection is associated with increased recombination in one genomic interval and not the other. The effect of Wolbachia infection on recombination is thus heterogenous across the genome. Our data also indicate a reproductive benefit of Wolbachia infection; infected females show higher fecundity than their uninfected genotypic controls. Given the prevalence of Wolbachia infection in natural populations, our findings suggest that Wolbachia infection is likely to contribute to recombination rate and fecundity variation among individuals in nature.
Cervical spine traumatic epidural haematomas: Incidence and characteristics
Authors: Brichko Lisa , Giddey Birinder , Tee Jin , Niggemeyer Louise , Fitzgerald Mark 
Published: December 2017

AbstractObjectiveCervical spine traumatic epidural haematomas (CSTEH) can cause potentially devastating neurological deficits if not promptly identified. Study aims were to determine the incidence, characteristics and outcomes for patients with CSTEH.MethodsA retrospective study was performed at a tertiary hospital with an adult Level 1 Trauma Centre on all consecutive patients diagnosed with CSTEH over a 4 year period. Medical record review was undertaken for all patients with the diagnoses of CSTEH to identify patient characteristics including age, mechanism of injury and co‐morbid conditions. Additional data was extracted regarding radiology interpretation, surgical interventions, thromboembolic chemoprophylaxis use, discharge disposition and neurological outcomes.ResultsA total of 27 888 patients were admitted with traumatic injuries between 1 July 2010 and 30 June 2014, of which 1916 patients sustained cervical spine injuries. The incidence of CSTEH was 0.6% among all trauma patients and 9.1% among patients with any cervical spine injury. Of those with CSTEH, 89 patients (50.9%) had neurological deficits consistent with the anatomical location of the epidural haematoma. Magnetic resonance imaging diagnosed CSTEH in 132 patients (75.4%), of whom 23 patients (13.1%) had normal computed tomography cervical spine imaging. Among the patients diagnosed with CSTEH, 13 (7.4%) died and 78 (44.6%) required cervical spine surgical decompressions.ConclusionThis study shows a high incidence of CSTEH among trauma patients. CSTEH is associated with significant morbidity and mortality. High clinical vigilance is required to allow the request and acquisition of urgent magnetic resonance imaging to diagnose CSTEH as the entity is often not evident on initial cervical spine computed tomography investigations.
Mechanism of Antibacterial Activities of a Rice Hull Smoke Extract (RHSE) Against Multidrug‐Resistant Salmonella Typhimurium In Vitro and in Mice
Authors: Kim Sung Phil , Lee Sang Jong , Nam Seok Hyun , Friedman Mendel 
Published: December 2017

AbstractThe present study tested antibacterial activity of a rice hull smoke extract (RHSE) against a multidrug‐resistant strain of Salmonella Typhimurium and examined its mode of suppressive action in vitro and in mice. In vitro studies showed that the minimum inhibitory concentration (MIC) value of RHSE was 1.29% (v/v). The inactivation was confirmed by complete loss of cell viability in the range of 104 to 107 colony forming units of the resistant Salmonella Typhimurium strain. Agarose and sodium dodecyl sulfate–polyacrylamide gel electrophoreses were used to evaluate the integrities of bacterial genomic DNA and total cellular protein profiles. The antibacterial action of RHSE results from a leakage of intracellular macromolecules following rupture of bacterial cells. Scanning electron microscopy of the cells shows that RHSE also induced deleterious morphological changes in the bacterial cell membrane of the pathogens. In vivo antibacterial activity of RHSE at a 1 × MIC concentration was examined in a bacterial gastroenteritis model using Balb/c mice orally infected with the Salmonella Typhimurium. The results show greatly decreased excretion of the bacteria into the feces and suppressed translocation of the bacteria to internal organs (cecum, mesenteric lymph node, spleen, and liver) compared with the infected mice not subjected to the RHSE treatment. Collectively, the present findings indicate that the mechanism of the antibacterial activities both in vitro and in the gastroenteritis environment of the animal model is the result of the direct disruption of cell structure, leading to cell death. RHSE has the potential to serve as a multifunctional food additive that might protect consumers against infections by antibiotic‐resistant microorganisms.Practical ApplicationThe rice hull derived liquid smoke has the potential to complement widely used wood‐derived smoke as an antimicrobial flavor and health‐promoting formulation for application in foods and feeds.