bluuebunny/crossref_metadata_2025 huggingface dataset:
Stray field signatures of Néel textured skyrmions in Ir/Fe/Co/Pt multilayer films
Authors: Yagil A. , Almoalem A. , Soumyanarayanan Anjan , Tan Anthony K. C. , Raju M. , Panagopoulos C. , Auslaender O. M.
Published: May 2018

Skyrmions are nanoscale spin configurations with topological properties that hold great promise for spintronic devices. Here, we establish their Néel texture, helicity, and size in Ir/Fe/Co/Pt multilayer films by constructing a multipole expansion to model their stray field signatures and applying it to magnetic force microscopy images. Furthermore, the demonstrated sensitivity to inhomogeneity in skyrmion properties, coupled with a unique capability to estimate the pinning force governing dynamics, portend broad applicability in the burgeoning field of topological spin textures.
The effects of annealing temperature on the permittivity and electromagnetic attenuation performance of reduced graphene oxide
Authors: Wu Fan , Zeng Qiao , Xia Yilu , Sun Mengxiao , Xie Aming
Published: May 2018

Reduced graphene oxide (RGO) has been prepared through the thermal reduction method with different annealing temperatures to explore the effects of temperature on the permittivity and electromagnetic attenuation performance. The real and imaginary parts of permittivity increase along with the decrease in the oxygen functional group and the increase in the filler loading ratio. A composite only loaded with 1 wt. % of RGO can possess an effective electromagnetic absorption bandwidth of 7.60 GHz, when graphene oxide was reduced under 300 °C for 2 h. With the annealing temperature increased to 700 °C and the well reduced RGO loaded 7 wt. % in the composite, the electromagnetic interference shielding efficiency can get higher than 35 dB from 2 to 18 GHz. This study shows that controlling the oxygen functional groups on the RGO surface can also obtain an ideal electromagnetic attenuation performance without any other decorated nanomaterials.
Communication: Calculation of interatomic forces and optimization of molecular geometry with auxiliary-field quantum Monte Carlo
Authors: Motta Mario , Zhang Shiwei
Published: May 2018

We propose an algorithm for accurate, systematic, and scalable computation of interatomic forces within the auxiliary-field quantum Monte Carlo (AFQMC) method. The algorithm relies on the Hellmann-Feynman theorem and incorporates Pulay corrections in the presence of atomic orbital basis sets. We benchmark the method for small molecules by comparing the computed forces with the derivatives of the AFQMC potential energy surface and by direct comparison with other quantum chemistry methods. We then perform geometry optimizations using the steepest descent algorithm in larger molecules. With realistic basis sets, we obtain equilibrium geometries in agreement, within statistical error bars, with experimental values. The increase in computational cost for computing forces in this approach is only a small prefactor over that of calculating the total energy. This paves the way for a general and efficient approach for geometry optimization and molecular dynamics within AFQMC.
Acoustic phonon spectrum engineering in bulk crystals via incorporation of dopant atoms
Authors: Kargar Fariborz , Penilla Elias H. , Aytan Ece , Lewis Jacob S. , Garay Javier E. , Balandin Alexander A.
Published: May 2018

We report results of Brillouin—Mandelstam spectroscopy of transparent Al2O3 crystals with Nd dopants. The ionic radius and atomic mass of Nd atoms are distinctively different from those of the host Al atoms. Our results show that even a small concentration of Nd atoms incorporated into the Al2O3 samples produces a profound change in the acoustic phonon spectrum. The velocity of the transverse acoustic phonons decreases by ∼600 m/s at the Nd density of only ∼0.1%. Interestingly, the decrease in the phonon frequency and velocity with the doping concentration is non-monotonic. The obtained results, demonstrating that modification of the acoustic phonon spectrum can be achieved not only by traditional nanostructuring but also by low-concentration doping, have important implications for thermal management as well as thermoelectric and optoelectronic devices.
An integrative taxonomic approach reveals the first marine triclad (Platyhelminthes) trapped in a cave from a semiarid Neotropical environment
Authors: Souza Stella , Riutort Marta , Ferreira Rodrigo Lopes , Leal-Zanchet Ana
Published: May 2018

A new genus and species of the suborder Maricola, representing the first marine triclad living in freshwater within a cave, is described. These flatworms show specialised features, such as a lack of pigmentation and eyes, indicating their troglobitic condition. Until now, cave-dwelling triclads have only been found as representatives of the other two triclad lineages. The phylogenetic trees based on 18S rRNA and 28S rRNA genes showed their sequences to form a clade situated in a rather derived position within the Maricola. Combining maximum likelihood and Bayesian analyses along with morphological studies, we undertake the first integrative description of a marine triclad. The new genus is characterised by a secondary copulatory bursa and ovaries located behind the root of the pharynx. Nevertheless, its assignment to a family of Maricola was a difficult task especially due to the paucity of unique defining morphological features of their families. The new species is found in a semiarid environment that suffered marine transgressions and regressions during the Cretaceous, which may explain the presence of this originally marine species in a freshwater cave. The restricted distribution of the new species and recent environmental conditions detected at its type locality raise major concern for its conservation.
Australian pharmacists’ knowledge of the efficacy and safety of complementary medicines
Authors: Waddington Freya , Naunton Mark , Kyle Greg , O'Kane Gabrielle , Cooper Gabrielle , Thomas Jackson
Published: May 2018

Global usage and expenditure on complementary medicines is increasing. Over 50% of consumers purchase these products from pharmacies and expect pharmacists to provide them with appropriate information regarding efficacy and safety of these products. Internationally, pharmacists have identified their lack of detailed knowledge of the efficacy and safety of these products as a barrier to recommending these products. Currently, little is known about the actual knowledge Australian pharmacists have of these products. This research seeks to determine Australian pharmacists’ knowledge of the efficacy and safety of complementary medicines. An online survey was validated and distributed by three professional pharmacy bodies in Australia and online social media to survey Australian pharmacists’ knowledge of a selection of complementary medicines that are defined as having therapeutic benefits as per the Australian Therapeutic Guidelines. In total, 535 complete surveys were returned and included in the final analysis. Surveys were predominantly completed by community pharmacists. The mean knowledge score obtained was 62%. There were no statistically significantly different results from pharmacists with a nutritional qualification. Australian pharmacists appear to have a basic knowledge of complementary medicines with a defined clinical effect. Specialised and targeted education focussing on relevant and efficacious complementary medicines with strong clinical evidence base is required.
Corrigendum to: Distribution and relative abundance of forest duikers in Dassioko Sud Forest Reserve (coastal Côte d'Ivoire)
Authors: Yao K. A. , Bitty E. A. , Kassé K. B. , Kouakou Y. C. , Yaokokoré-Beibro K. H. , Bi S. Gonedelé , McGraw W. Scott
Published: May 2018

Context
Duikers play a vital role in maintaining forest ecosystems, as both seed dispersers and prey. In West Africa, duikers are also an important source of food and income; however, it is likely that some species are now being hunted at unsustainable levels. So as to contribute to duiker conservation, we used line-transect data and additional information on dung and track counts to estimate relative abundance and establish distribution patterns of forest duikers in Côte d'Ivoire's Dassioko Sud Forest Reserve (DSFR), a poorly known, remnant coastal rainforest. We also collected basic information on hunting pressure.

Methods
Forest duiker counts were made twice per month from July 2013 to March 2014 on six line transects of varying lengths (5.6–6.7km) and in different regions of the DSFR, representing different habitat types. The number of sightings per kilometre walked, defined as ‘encounter rate', was used to compute an index of relative abundance. We recorded all evidence of poachers and used these data to generate a poaching index (# poaching signs per kilometre) for different habitat types.

Key results
The DSFR has lost three of seven total forest duiker species and populations of the four remaining species are declining. Encounter rates were greatest for Philantomba maxwellii (0.46 indices km–1) and accounted for 68% of total encounters. Cephalophus niger, C. dorsalis and C. silvicultor were encountered at similar (0.07 indices km–1) but much lower rates. For all species, mean encounter rates were highest in degraded forest (0.38–0.73 indices km–1), followed by secondary (0.2–0.44 indices km–1) and primary (0.19–0.44 indices km–1) forest.

Conclusions
Of the four forest duiker species still present in the DSFR, the black, bay and yellow-backed duikers are the most affected by anthropogenic pressures. Duiker abundance in the DSFR varies with habitat type. This variation is apparently influenced by differences in forest structure, poaching pressure and proximity to villages.

Implications
The study provides baseline data for future managing of ungulate populations in the DSFR. We recommend that a biomonitoring study of duiker populations be initiated immediately to help determine population trends, investigate habitat preferences, and help curb illegal hunting activities in this important forest reserve.
High-temperature erosion behaviour of plasma-sprayed NiCrBSi–graphite coatings
Authors: Edward Anand E. , Natarajan S.
Published: May 2018

Plasma-sprayed NiCrBSi–graphite coatings have been subjected to solid particle erosion at elevated temperatures. The work reports the erosion resistance of NiCrBSi coatings with 4, 6 and 8 wt-% addition of graphite and optimum graphite content for erosion resistance. The coatings were analyzed using optical microscopy, XRD and scanning electron microscopy. Testing was carried out using air-jet erosion test rig, at an impact velocity of 70 m s−1 and at 45° and 90° angles with sand flow rate of 1 g min−1 at RT, 500°C and 650°C. Morphology of eroded surface shows crater, lip, groove formation and chipping as visible mechanism of material removal. Coating with 4wt% distribution of graphite exhibits higher erosion resistance as compared to the coating without graphite addition and improved microhardness. Microstructure images reveal that increase in graphite content above 4% results in the segregation of graphite and leading to soft islands in the coatings thereby decreasing the erosion resistance.
Ecosystem approach to fisheries in southern Lake Malawi: Status of the fisheries co-management
Authors: Njaya Friday
Published: May 2018

The decline of the valuable Chambo (Oreochromis species) in the southern part of Lake Malawi, where an Ecosystem Approach to Fisheries is being applied, is a major economic and ecological concern. Annual Chambo fish harvests have continued to show a downward trend especially for the past two decades thereby adversely affecting the livelihoods of many fishers, processors and traders along the value chain. As part of the institutional agenda within the ecosystem approach to fisheries, a key question remains on the status of the fisheries co-management, which was introduced in the area in the mid 1990s. This article applies a fishery performance indicator framework to assess the fisheries co-management in the study area as baseline information for the development of the ecosystem approach to fisheries. The assessment is based on an expert analysis by the author and a review of previous study reports on the fisheries co-management as a governance reform. Results show weak fisheries governance with the existence of several challenges and threats that continue to impact on the ecosystem status like continued use of illegal fishing practices, climate change and unlimited entry. To improve fisheries co-management, the fishing by-laws that were formulated in 2007 need to be approved by Mangochi district authorities within the on-going decentralization process.
Upper and lower body responses to repeated cyclical sprints
Authors: Halperin Israel , Collins Brandon W. , Monks Michael , Compton Chris T. , Yetman Joseph D. , Loucks‐Atkinson Angela , Basset Fabien , Button Duane C.
Published: May 2018

Purpose: To compare the physiological and perceptual responses of the upper and lower body to all‐out cyclical sprints with short or long rest periods between sprints.

Methods: Ten recreationally trained males completed four 10 × 10 s sprint protocols in a randomized order: upper body with 30 s and 180 s of rest between sprints, and lower body with 30 s and 180 s of rest between sprints. Additionally, maximum voluntary contractions (MVC) were measured at pre‐sprint and post‐sprints 5 and 10. Normalized (% of first sprint) peak power, MVC, heart rate (HR) and rating of perceived exertion (RPE) were compared between upper and lower body within the same recovery period, and absolute values (Watts, bpm, RPE scores) were compared within the same body part and between recovery periods.

Results: Trivial differences were identified in normalized peak power, HR and RPE values between the upper and lower body in both recovery conditions (<2%, d ≤ 0.1), but MVC forces were better maintained with the upper body (∼9.5%, d = 1.0) in both recovery conditions. Absolute peak power was lower (∼147 Watts, d = 1.3), and HR was higher (∼10 bpm, d = 0.73) in the 30 s compared to 180 s condition in both the upper and lower body whereas RPE scores were similar (<0.6 RPE units, d ≤ 0.1). Despite the reductions in peak power, MVC forces were better maintained in the 30 s condition in both upper (2.5 kg, d = 0.4) and lower (7.5 kg, d = 0.7) body.

Conclusions: Completing a commonly used repeated sprint protocol with the upper and lower body results in comparable normalized physiological and perceptual responses.
Centrosome amplification arises before neoplasia and increases upon p53 loss in tumorigenesis
Authors: Lopes Carla A.M. , Mesquita Marta , Cunha Ana Isabel , Cardoso Joana , Carapeta Sara , Laranjeira Cátia , Pinto António E. , Pereira-Leal José B. , Dias-Pereira António , Bettencourt-Dias Mónica , Chaves Paula
Published: May 2018

Centrosome abnormalities are a typical hallmark of human cancers. However, the origin and dynamics of such abnormalities in human cancer are not known. In this study, we examined centrosomes in Barrett’s esophagus tumorigenesis, a well-characterized multistep pathway of progression, from the premalignant condition to the metastatic disease. This human cancer model allows the study of sequential steps of progression within the same patient and has representative cell lines from all stages of disease. Remarkably, centrosome amplification was detected as early as the premalignant condition and was significantly expanded in dysplasia. It was then present throughout malignant transformation both in adenocarcinoma and metastasis. The early expansion of centrosome amplification correlated with and was dependent on loss of function of the tumor suppressor p53 both through loss of wild-type expression and hotspot mutations. Our work shows that centrosome amplification in human tumorigenesis can occur before transformation, being repressed by p53. These findings suggest centrosome amplification in humans can contribute to tumor initiation and progression.
Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses
Authors: Pardi Norbert , Hogan Michael J. , Naradikian Martin S. , Parkhouse Kaela , Cain Derek W. , Jones Letitia , Moody M. Anthony , Verkerke Hans P. , Myles Arpita , Willis Elinor , LaBranche Celia C. , Montefiori David C. , Lobby Jenna L. , Saunders Kevin O. , Liao Hua-Xin , Korber Bette T. , Sutherland Laura L. , Scearce Richard M. , Hraber Peter T. , Tombácz István , Muramatsu Hiromi , Ni Houping , Balikov Daniel A. , Li Charles , Mui Barbara L. , Tam Ying K. , Krammer Florian , Karikó Katalin , Polacino Patricia , Eisenlohr Laurence C. , Madden Thomas D. , Hope Michael J. , Lewis Mark G. , Lee Kelly K. , Hu Shiu-Lok , Hensley Scott E. , Cancro Michael P. , Haynes Barton F. , Weissman Drew
Published: May 2018

T follicular helper (Tfh) cells are required to develop germinal center (GC) responses and drive immunoglobulin class switch, affinity maturation, and long-term B cell memory. In this study, we characterize a recently developed vaccine platform, nucleoside-modified, purified mRNA encapsulated in lipid nanoparticles (mRNA-LNPs), that induces high levels of Tfh and GC B cells. Intradermal vaccination with nucleoside-modified mRNA-LNPs encoding various viral surface antigens elicited polyfunctional, antigen-specific, CD4+ T cell responses and potent neutralizing antibody responses in mice and nonhuman primates. Importantly, the strong antigen-specific Tfh cell response and high numbers of GC B cells and plasma cells were associated with long-lived and high-affinity neutralizing antibodies and durable protection. Comparative studies demonstrated that nucleoside-modified mRNA-LNP vaccines outperformed adjuvanted protein and inactivated virus vaccines and pathogen infection. The incorporation of noninflammatory, modified nucleosides in the mRNA is required for the production of large amounts of antigen and for robust immune responses.
The revival of the Gini importance?
Authors: Nembrini Stefano , König Inke R , Wright Marvin N
Published: May 2018

Motivation

Random forests are fast, flexible and represent a robust approach to analyze high dimensional data. A key advantage over alternative machine learning algorithms are variable importance measures, which can be used to identify relevant features or perform variable selection. Measures based on the impurity reduction of splits, such as the Gini importance, are popular because they are simple and fast to compute. However, they are biased in favor of variables with many possible split points and high minor allele frequency.

Results

We set up a fast approach to debias impurity-based variable importance measures for classification, regression and survival forests. We show that it creates a variable importance measure which is unbiased with regard to the number of categories and minor allele frequency and almost as fast as the standard impurity importance. As a result, it is now possible to compute reliable importance estimates without the extra computing cost of permutations. Further, we combine the importance measure with a fast testing procedure, producing p-values for variable importance with almost no computational overhead to the creation of the random forest. Applications to gene expression and genome-wide association data show that the proposed method is powerful and computationally efficient.

Availability and implementation

The procedure is included in the ranger package, available at https://cran.r-project.org/package=ranger and https://github.com/imbs-hl/ranger.

Supplementary information

Supplementary data are available at Bioinformatics online.
FlexiDot: highly customizable, ambiguity-aware dotplots for visual sequence analyses
Authors: Seibt Kathrin M , Schmidt Thomas , Heitkam Tony
Published: May 2018

FlexiDot is a cross-platform dotplot suite generating high quality self, pairwise and all-against-all visualizations. To improve dotplot suitability for comparison of consensus and error-prone sequences, FlexiDot harbors routines for strict and relaxed handling of ambiguities and substitutions. Our shading modules facilitate dotplot interpretation and motif identification by adding information on sequence annotations and sequence similarities. Combined with collage-like outputs, FlexiDot supports simultaneous visual screening of large sequence sets, enabling dotplot use for routine analyses.

Availability and implementation

FlexiDot is implemented in Python 2.7. Software and documentation are freely available at http://github.com/molbio-dresden/flexidot.

Supplementary information

Supplementary data are available at Bioinformatics online.
tp53-dependent and independent signaling underlies the pathogenesis and possible prevention of Acrofacial Dysostosis–Cincinnati type
Authors: Watt Kristin E N , Neben Cynthia L , Hall Shawn , Merrill Amy E , Trainor Paul A
Published: May 2018

Ribosome biogenesis is a global process required for growth and proliferation in all cells, but disruptions in this process surprisingly lead to tissue-specific phenotypic disorders termed ribosomopathies. Pathogenic variants in the RNA Polymerase (Pol) I subunit POLR1A cause Acrofacial Dysostosis–Cincinnati type, which is characterized by craniofacial and limb anomalies. In a zebrafish model of Acrofacial Dysostosis–Cincinnati type, we demonstrate that polr1a–/– mutants exhibit deficient 47S rRNA transcription, reduced monosomes and polysomes and, consequently, defects in protein translation. This results in Tp53-dependent neuroepithelial apoptosis, diminished neural crest cell proliferation and cranioskeletal anomalies. This indicates that POLR1A is critical for rRNA transcription, which is considered a rate limiting step in ribosome biogenesis, underpinning its requirement for neuroepithelial cell and neural crest cell proliferation and survival. To understand the contribution of the Tp53 pathway to the pathogenesis of Acrofacial Dysostosis–Cincinnati type, we genetically inhibited tp53 in polr1a–/– mutant embryos. Tp53 inhibition suppresses neuroepithelial apoptosis and partially ameliorates the polr1a mutant phenotype. However, complete rescue of cartilage development is not observed due to the failure to improve rDNA transcription and neural crest cell proliferation. Altogether, these data reveal specific functions for both Tp53-dependent and independent signaling downstream of polr1a in ribosome biogenesis during neural crest cell and craniofacial development, in the pathogenesis of Acrofacial Dysostosis–Cincinnati type. Furthermore, our work sets the stage for identifying Tp53-independent therapies to potentially prevent Acrofacial dysostosis–Cincinnati type and other similar ribosomopathies.
Consumer Spending and Property Taxes
Authors: Surico Paolo , Trezzi Riccardo
Published: May 2018

A sudden and temporary change to the Italian property tax system in 2011 generated significant variation in the amount of taxes paid across home-owners. Using new questions appositely added to the Survey on Household Income and Wealth, we exploit this cross-sectional variation to provide an unprecedented analysis of the consumption effects of a tax on housing wealth. A tax hike on the main dwelling leads to large expenditure cuts among mortgagors, who hold low liquid wealth despite owning sizable illiquid assets. In contrast, higher tax rates on other residential properties affect affluent households, thereby having a modest impact on their consumer spending. Our results provide novel and direct evidence in favor of recent theories that highlight the role of household debt in the transmission of economic policies.
Prison Staff and Prisoner Views on a Prison Smoking Ban: Evidence From the Tobacco in Prisons Study
Authors: Brown Ashley , Sweeting Helen , Logan Greig , Demou Evangelia , Hunt Kate
Published: May 2018

Introduction

In jurisdictions permitting prisoner smoking, rates are high (c75%), with smoking embedded in prison culture, leading to secondhand smoke exposures among staff and prisoners and challenges for smoking cessation. Momentum is building to ban smoking in prisons, but research on staff and prisoner views is lacking. We address this gap, providing evidence on staff and prisoner views throughout all Scottish prisons.

Methods

Data were collected prior to the announcement of a (November 2018) prison smoking ban throughout Scotland. Mixed methods were used: surveys of staff (online, N = 1271, ~27%) and prisoners (questionnaire, N = 2512, ~34%); 17 focus groups and two paired interviews with staff in 14 prisons.

Results

Staff were more positive than prisoners about bans and increased smoking restrictions, although prisoner views were more favorable should e-cigarettes be permitted. Nonsmokers were more positive than smokers. Whilst 74% staff and 22% prisoners agreed bans were a good idea, both groups acknowledged implementation and enforcement challenges. Staff views were influenced by beliefs about: acceptability of the policy in principle and whether/how bans could be achieved. Although some voiced doubts about smoke-free policies, staff likened a ban to other operational challenges. Staff raised concerns around needs for appropriate measures, resources and support, adequate lead-in time, and effective communication prior to a ban.

Conclusion

We recommend that regular and open opportunities for dialogue within and between different stakeholder groups are created when preparing for prison smoking bans and that specific measures to address staff and prisoner concerns are incorporated into plans to create and maintain smoke-free environments.

Implications

To our knowledge, this study is the first to research staff and prisoner views across a whole prison system prior to implementation of smoke-free policies. The results highlight potential challenges and suggest measures, which might help to maximize the success of bans. Our results are relevant for prison service managers responsible for the forthcoming introduction of a ban in Scottish prisons (November 2018) and for other prison systems and comparable institutions planning smoke-free initiatives. Given that prison smoking bans may be contentious, we recommend creating regular and open opportunities for dialogue between stakeholders when preparing for and maintaining smoke-free environments.
Continuity between koniocellular layers of dorsal lateral geniculate and inferior pulvinar nuclei in common marmosets
Authors: Huo Bing-Xing , Zeater Natalie , Lin Meng Kuan , Takahashi Yeonsook S. , Hanada Mitsutoshi , Nagashima Jaimi , Lee Brian C. , Hata Junichi , Grünert Ulrike , Miller Michael I. , Rosa Marcello G.P. , Okano Hideyuki , Martin Paul R. , Mitra Partha P.
Published: May 2018

In primates, the koniocellular (K) layers of the dorsal lateral geniculate nucleus (LGN) and the calbindin-rich subdivisions of the inferior pulvinar (IPul) nucleus are considered part of a thalamic matrix system which projects diffusely to superficial cortical layers. Activity in the matrix system is proposed to coordinate oscillatory activity in thalamocortical loops. Further, since both K cells and IPul are involved in visual processing pathways, especially in alternative pathways to visual cortex after V1 lesion in early life (“blindsight”), their functional similarities have been strongly implicated. Here we tested the hypothesis that calbindin-positive K cells and IPul cells constitute a continuous group of cells. By combining immunohistochemistry and a high-throughput neuronal tracing method, we found that both K cells and IPul form reciprocal connections with striate and extrastriate cortices; whereas principal laminae of LGN do not receive inputs from extrastriate cortex and only project sparsely to these areas. Retrograde labelled cells in lateral division of IPul merged seamlessly into the retrograde labelled cells in K layers. These results supported the continuity between LGN K layers and IPul, providing the anatomical basis for functional congruity of this part of dorsal thalamic matrix.
RNA polymerase II clustering through CTD phase separation
Authors: Boehning M. , Dugast-Darzacq C. , Rankovic M. , Hansen A. S. , Yu T. , Marie-Nelly H. , McSwiggen D.T. , Kokic G. , Dailey G. M. , Cramer P. , Darzacq X. , Zweckstetter M.
Published: May 2018

The carboxy-terminal domain (CTD) of RNA polymerase (Pol) II is an intrinsically disordered low-complexity region that is critical for pre-mRNA transcription and processing. The CTD consists of hepta-amino acid repeats varying in number from 52 in humans to 26 in yeast. Here we report that human and yeast CTDs undergo cooperative liquid phase separation at increasing protein concentration, with the shorter yeast CTD forming less stable droplets. In human cells, truncation of the CTD to the length of the yeast CTD decreases Pol II clustering and chromatin association whereas CTD extension has the opposite effect. CTD droplets can incorporate intact Pol II and are dissolved by CTD phosphorylation with the transcription initiation factor IIH kinase CDK7. Together with published data, our results suggest that Pol II forms clusters/hubs at active genes through interactions between CTDs and with activators, and that CTD phosphorylation liberates Pol II enzymes from hubs for promoter escape and transcription elongation.
Bayesian Multi-SNP Genetic Association Analysis: Control of FDR and Use of Summary Statistics
Authors: Lee Yeji , Luca Francesca , Pique-Regi Roger , Wen Xiaoquan
Published: May 2018

Multi-SNP genetic association analysis has become increasingly important in analyzing data from genome-wide association studies (GWASs) and molecular quantitative trait loci (QTL) mapping studies. In this paper, we propose novel computational approaches to address two outstanding issues in Bayesian multi-SNP genetic association analysis: namely, the control of false positive discoveries of identified association signals and the maximization of the efficiency of statistical inference by utilizing summary statistics. Quantifying the strength and uncertainty of genetic association signals has been a long-standing theme in statistical genetics. However, there is a lack of formal statistical procedures that can rigorously control type I errors in multi-SNP analysis. We propose an intuitive hierarchical representation of genetic association signals based on Bayesian posterior probabilities, which subsequently enables rigorous control of false discovery rate (FDR) and construction of Bayesian credible sets. From the perspective of statistical data reduction, we examine the computational approaches of multi-SNP analysis using z-statistics from single-SNP association testing and conclude that they likely yield conservative results comparing to using individual-level data. Built on this result, we propose a set of sufficient summary statistics that can lead to identical results as individual-level data without sacrificing power. Our novel computational approaches are implemented in the software package, DAP-G (https://github.com/xqwen/dap), which applies to both GWASs and genome-wide molecular QTL mapping studies. It is highly computationally efficient and approximately 20 times faster than the state-of-the-art implementation of Bayesian multi-SNP analysis software. We demonstrate the proposed computational approaches using carefully constructed simulation studies and illustrate a complete workflow for multi-SNP analysis of cis expression quantitative trait loci using the whole blood data from the GTEx project.
Ionizing radiation induces stem cell-like properties in a caspase-dependent manner in Drosophila
Authors: Verghese Shilpi , Su Tin Tin
Published: May 2018

Cancer treatments including ionizing radiation (IR) can induce cancer stem cell-like properties in non-stem cancer cells, an outcome that can interfere with therapeutic success. Yet, we understand little about what consequences of IR induces stem cell like properties and why some cancer cells show this response but not others. In previous studies, we identified a pool of epithelial cells in Drosophila larval wing discs that display IR-induced stem cell-like properties. These cells are resistant to killing by IR and, after radiation damage, change fate and translocate to regenerate parts of the disc that suffered more cell death. Here, we addressed how IR exposure results in the induction of stem cell-like behavior, and found a requirement for caspase activity. Unexpectedly, this requirement was mapped to the regenerative cells, suggesting a non-apoptotic role for caspases in the induction of stem cell-like behavior. We also performed a systematic probing of different regions of the wing disc by lineage tracing, in order to identify additional pools of cells with IR-induced regenerative properties. We identified two new populations of such cells. Unlike the original pool that helps regenerate the disc, the new pools of cells undergo abnormal regeneration to produce an ectopic, supernumerary wing disc. We also identified cells that lack the ability to display IR-induced regenerative behavior. Identification of different cell populations with different IR-induced regenerative potential will allow us to probe the molecular basis for these differences in the future.

AUTHOR SUMMARY

Ionizing Radiation (IR), alone or in combination with other therapies, is used to treat an estimated half of all cancer patients. Yet, we understand little about why some tumors cells respond to treatment while others grow back (regenerate). We identified specific pools of cells within a Drosophila organ that are capable of regeneration after damage by IR. We also identified what it is about IR damage that allows these cells to regenerate. These results help us understand how cells regenerate after IR damage and will aid in designing better therapies that involve radiation.
HIPPO signaling resolves embryonic cell fate conflicts during establishment of pluripotencyin vivo
Authors: Frum Tristan , Murphy Tayler , Ralston Amy
Published: May 2018

During mammalian development, the challenge for the embryo is to override intrinsic cellular plasticity to drive cells to distinct fates. Here, we unveil novel roles for the HIPPO signaling pathway segregates pluripotent and extraembryonic fates by controlling cell positioning as well as expression ofSox2,the first marker of pluripotency in the mouse early embryo. We show that maternal and zygotic YAP1 and WWTR1 repressSox2while promoting expression of the trophectoderm geneCdx2in parallel. Yet,Sox2is more sensitive thanCdx2toYap1/Wwtr1dosage, leading cells to a state of conflicted cell fate when YAP1/WWTR1 activity is moderate. Remarkably, HIPPO signaling activity resolves conflicted cell fate by repositioning cells to the interior of the embryo, independent of its role in regulatingSox2expression. Rather, HIPPO antagonizes apical localization of Par complex components PARD6B and aPKC. Thus, negative feedback between HIPPO and Par complex components ensure robust lineage segregation.
Robust Reference Powered Association Test of genome-wide association studies
Authors: Wang Yi , Li Yi , Hao Meng , Liu Xiaoyu , Zhang Menghan , Xiong Momiao , Wang Jiucun , Shugart Yin Yao , Jin Li
Published: May 2018

Genome-wide association studies (GWAS) have identified abundant genetic susceptibility loci, although they are far less from meeting the previous expectations due to low statistical power and false positive results. Effective statistical methods are required to further improve the analyses of massive GWAS data. Here we presented a new statistic (Robust Reference Powered Association Test,http://drwang.top/gwas.html) to use large public database as reference to reduce concern of potential population stratification. To evaluate the performance of this statistic for various situations, we simulated multiple sets of sample size and frequencies to compute statistical power. Furthermore, we applied our method to several real datasets (psoriasis genome-wide association datasets and schizophrenia genome-wide association dataset) to evaluate the performance. Careful analyses indicated that our newly developed statistic outperformed several previously developed GWAS applications. Importantly, this statistic is more robust than naive merging method in the presence of small control-reference differentiation, therefore likely to detect more association signals.
Frequency and synchrony of actomyosin oscillation during PCP-dependent convergent extension
Authors: Shindo Asako , Inoue Yasuhiro , Kinoshita Makoto , Wallingford John B.
Published: May 2018

Oscillatory actomyosin flows play a key role in single cell migration and in collective cell movements that shape invertebrates embryos, but the role of such oscillations in vertebrate morphogenesis remains poorly defined. Here, data from mathematical modeling andin vivo4D imaging of actomyosin in theXenopusgastrula suggest that oscillatory actomyosin contractions are a general feature of convergent extension by junction shrinking. We show that synchronous intracellular flows link two spatially distinct populations of actomyosin within individual cells, but that oscillations are asynchronousbetweenneighboring cells that share a shrinking cell-cell junction. We also show that the core PCP protein Prickle2 displays a parallel oscillatory behavior and is required for tuning the frequency of actomyosin contractions, indicating that PCP signaling controls not only the orientation of actomyosin contractions, but also their frequency. Together, these data provide new insights into the function and control of oscillatory actomyosin contractions in collective cell movement.
Anti-Microbial Resistance in Agents Causing Urinary Tract Infections
Authors: Rizvi Zuhair Ali , Jamal Ali Murad , Malik Ali Hassan , Ullah Naimat , Arshad Daneyal
Published: May 2018

BACKGROUND

Urinary Tract Infections are usually treated with empirical therapy by physicians based on previous knowledge of predictability of causative agents and their antimicrobial susceptibilities.

OBJECTIVE

The objective of this study was to determine the frequency of various pathogens causing urinary tract infections and their antimicrobial susceptibility in patients presenting in out-patient department of a tertiary care hospital.

MATERIALS AND METHODS

This descriptive cross sectional study was conducted in Out-Patient department of Urology of Benazir Bhutto Hospital during a period of 6 months from January 2017 to June 2017 after ethical approval from institutional research forum of Rawalpindi Medical University. 1000 patients (12 years old or above) that were clinically suspected for urinary tract infections were included in this study. Patients with co-morbidities like diabetes mellitus, renal pathologies, Immunodeficiency disorders, malignancies and congenital urogenital disorders were also excluded. Recipients of corticosteroid therapy or with a history of intake of broad spectrum antibiotics in previous 15 days were also excluded. Modified Kirby-Bauer disc diffusion method was used for determining the antimicrobial resistance against various antimicrobials.

RESULTS

A total of 530 (53%) isolates were found to be culture positive for E.coli(77.4%),Klebsiella (6.4%), Enterobacter (6.0%), Pseudomonas (3.8%), Staphylococcus saprophyticus (3.4%), Citrobacter (1.1%) and Morganella (0.4%).

Antimicrobial resistance against commonly used antimicrobials was alarmingly high

CONCLUSION

Surveillance of trends of antimicrobial susceptibility pattern is highly important.
Cellular Adaptive Response and Regulation of HIF after Low Dose Gamma-radiation Exposure
Authors: Gandhi Nitin Motilal
Published: May 2018

Purpose

Cellular damage due to low dose of γ-radiation (≤0.1 Gy) is generally extrapolated from observing the effects at higher doses. These estimations are not accurate. This has led to uncertainties while assessing the radiation risk factors at low doses. Although there are reports on the radiation induced adaptive response, the mechanism of action is not fully elucidated, leading to the uncertainties. One of the outcomes of low dose radiation exposure is believed to be adaptive response. The mechanism of adaptive response is not fully understood. Therefore, the study was undertaken to understand the role of hypoxia inducible factor (HIF) on radiation induced adaptive response.

Materials and methods

MCF-7 cells pre-exposed to low dose γ-radiation (0.1 Gy; Priming dose) were exposed to 2 Gy (challenging dose) 8 hrs after the priming dose and studied for the adaptive response. Cell death was measured by MTT assay, and apoptosis was measured by FACS analysis. DNA damage was measures by alkaline comet assay. HIF transcription activity was assayed using transiently transfected plasmid having HIF consensus sequence and luciferase as the reporter gene.

Results

Cells when exposed to 0.1 Gy priming dose 8 hrs prior to the higher dose (2 Gy; Challenging dose) results in lower amount of radiation induced damages compared to the cells exposed to 2 Gy alone. Cobalt chloride treatment in place of priming dose also results in the protection to cells when exposed to challenging dose. There was up-regulation of HIF activity when cells were exposed to priming dose, indicating the role of HIF in radiation induced response.

Conclusion

Results indicate the γ-radiation induced adaptive response. One of the mechanism proposed is up-regulation of HIF after low dose exposure, which protects the cells from damages when they are exposed to challenging dose of 2 Gy radiation dose.
PID1 alters antilipolytic action of insulin and increases lipolysis via Inhibited the activation of AKT/PKA Pathway
Authors: Yin Chunyan , Jin Yan , Liu Yuesheng , Wang Li , Xiao Yanfeng
Published: May 2018

Purpose

The aim was to investigate the mechanism for impaired control of lipolysis in obesity by investigating the effect of PID1 on insulin-induced activation of AKT/PKA/HSL pathway and lipolysis.

Methods

First, PID1 expression was detected in adipose tissue and blood insulin and glycerol levels were measured in high-fat diet-induced obese rats. Next, we examined the effect of different concentrations of insulin on lipolysis and AKT/PKA/HSL pathway in 3T3-L1cells. We also investigated the role of PID1 in regulating AKT/PKA/HSL cascade and lipolysis after insulin treatment and lipofectamine over-expression.

Results

PID1 expression is increased in adipose tissue from HFD rat and positive correlation with insulin levels and lipolysis. In 3T3-L1 adipocytes, we found that antilipolytic effect of insulin is mediated by AKT and AKT activated by insulin can results in phosphorylation of PKA and HSL and suppresses glycerol release. However, over-expression of PID1 counteracts insulin action as indicated by glycerol releaseand reduced level of Akt phosphorylation in accordance with a decrease in the activity of insulin-dependent PKA/HSLsignaling cascade.

Conclusions

All together, these data showed that activation of PID1 in adipose tissue increases lipolysis by altering the antilipolytic action of insulin. This suggests that PID1 may constitute a new strategy to ameliorate adipocyte lipolysis and hence to improve insulin sensitivity.
Human personality reflects spatio-temporal and time-frequency EEG structure
Authors: Runnova Anastasia E. , Maksimenko Vladimir A. , Zhuravlev Maksim O. , Protasov Pavel , Kulanin Roman , Khramova Marina V. , Pisarchik Alexander N. , Khramov Alexander E.
Published: May 2018

The brain controls all physiological processes in the organism and regulates its interaction with the external environment. The way the brain solves mental tasks is determined by individual human features, which are reflected in neuronal network dynamics, and therefore can be detected in neurophysiological data. Every human action is associated with a unique brain activity (motor-related, cognitive, etc.) represented by a specific oscillatory pattern in a multichannel electroencephalogram (EEG). The connection between neurophysiological processes and personal mental characteristics is manifested when using simple psycho-diagnostic tests (Schulte tables) in order to study the attention span. The analysis of spatio-temporal and time-frequency structures of the multichannel EEG using the Schulte tables allows us to divide subjects into three groups depending on their neural activity. The personality multi-factor profile of every participant can be individually described based on both the Sixteen Personality Factor Questionnaire (16PF) and a personal interview with an experienced psychologist. The correlation of the EEG-based personality classification with individual multi-factor profiles provides a possibility to identify human personality by analyzing electrical brain activity. The obtained results are of great interest for testing human personality and creating automatized intelligent programs that employ simple tests and EEG measurements for an objective estimation of human personality features.
Escherichia coliBcteriuria in pregnant women in Ghana: Antibiotic resistance pattern, Virulence Factors and Resistant genetic markers
Authors: Akua Forson Obeng , Bright Wilson , Nana-Adjei David , Quarchie Marjorie Ntiwaa , Obeng-Nkuramah Noah
Published: May 2018

The relevance ofEscherichia coliassociated bacteriuria infection in pregnant women is poorly understood, despite these strains sharing a similar virulence profile with other extra intestinal pathogenicE. coliproducing severe obstetric and neonatal infections. We characterized and determined the antimicrobial susceptibility, resistant genes and virulence profiles of 82E. coliisolates associated with asymptomatic bacteriuria in some pregnant in five very distinct hospitals in the Volta region from January, 2016 to April, 2016 using Kirby-Bauer disc diffusion and polymerase chain reaction.

High levels of antimicrobial resistance was observed to Ampicillin (79.3%), Tetracycline (70.7%) and Cotrimoxazole (59.8%), except for Cefuroxime (32.9%). Resistant genes analyses revealed 58.5% were positive forBlaTEMand 14.6% foraph(3)-Ia(aphA2). Virulence factors (VFs) was more widespread in pregnant women in the 2ndand 3rdtrimesters than 1sttrimester. VFs relating to adhesion (papC andiha), Protectins (traT), aerobactin acquisition (iutA) and iron acquisition systems (fyuA andirp2) were more prevalent in the resistantE. coliisolates. This study provides additional evidence for a link in bacteriuria and transmission of extra-intestinalE. coliin pregnant women to cause multi-resistant severe obstetric or neonatal infections. Considering the involvement of extra-intestinalE. coliin infections, our results may be helpful to develop strategies to prevent maternal and/ neonatal infections. In addition continuous surveillance is required to guide appropriate antibiotic usage in pregnant women.