bluuebunny/crossref_metadata_2025 huggingface dataset:
Misrepresentation and distortion of research in biomedical literature
Authors: Boutron Isabelle , Ravaud Philippe
Published: March 2018

Publication in peer-reviewed journals is an essential step in the scientific process. However, publication is not simply the reporting of facts arising from a straightforward analysis thereof. Authors have broad latitude when writing their reports and may be tempted to consciously or unconsciously “spin” their study findings. Spin has been defined as a specific intentional or unintentional reporting that fails to faithfully reflect the nature and range of findings and that could affect the impression the results produce in readers. This article, based on a literature review, reports the various practices of spin from misreporting by “beautification” of methods to misreporting by misinterpreting the results. It provides data on the prevalence of some forms of spin in specific fields and the possible effects of some types of spin on readers’ interpretation and research dissemination. We also discuss why researchers would spin their reports and possible ways to avoid it.
Correlation analysis framework for localization-based superresolution microscopy
Authors: Schnitzbauer Joerg , Wang Yina , Zhao Shijie , Bakalar Matthew , Nuwal Tulip , Chen Baohui , Huang Bo
Published: March 2018

Significance

Correlation analysis is one of the most widely used image-processing methods. In the quantitative analysis of localization-based superresolution images, there still lacks a generalized coordinate-based correlation analysis framework to take full advantage of the superresolution information. We propose a coordinate-based correlation analysis framework for localization-based superresolution microscopy. We mathematically prove that point-point distance distribution is equivalent to pixel-based correlation function. This framework can be easily extended to model the effect of localization uncertainty, to the time domain and other distance definitions. We demonstrated the versatility and advantages of our framework in three applications of superresolution microscopy: model-free image alignment and averaging for structural analysis, spatiotemporal correlation analysis for mapping molecule diffusion, and quantifying spatial relationships between complex structures.
Cross-resistance to dicamba, 2,4-D, and fluroxypyr in
Kochia scoparia
is endowed by a mutation in an
AUX/IAA
gene
Authors: LeClere Sherry , Wu Chenxi , Westra Philip , Sammons R. Douglas
Published: March 2018

Significance

Because auxin herbicides selectively control broadleaf weeds, their use is extremely valuable in crops, such as wheat and corn. Although auxin-resistant weeds have appeared rarely over the past 60 years of herbicide use, they pose a major challenge in these cropping systems. Several groups have investigated the mechanisms of resistance for several of these weed species; this paper reports the identification of the underlying genetic mechanism of auxin resistance in a field-derived weed species. This mutation sits within a highly conserved region previously identified in
Arabidopsis
studies as vital for auxin signaling and points to the importance of studies in model systems to predict resistance mechanisms.
Reconstructing a metazoan genetic pathway with transcriptome-wide epistasis measurements
Authors: Angeles-Albores David , Puckett Robinson Carmie , Williams Brian A. , Wold Barbara J. , Sternberg Paul W.
Published: March 2018

Significance

Transcriptome profiling quantitatively measures gene expression genome-wide. There is widespread interest in using transcriptomic profiles as phenotypes for epistasis analysis. Though epistasis measurements can be performed using individual transcripts, this results in many scores that must be interpreted independently. We developed a statistic that summarizes these measurements, simplifying analysis. Moreover, epistasis analysis has previously only been performed on cDNA extracted from single cells. We show that whole-organism RNA-sequencing (RNA-seq) can be used to characterize interactions between genes. With the advent of genome engineering, mutants can be created easily in many organisms. Thus, phenotyping is now the rate-limiting step toward reconstructing interaction networks. Our work potentially represents a solution to this problem because RNA-seq is sensitive to a variety of genetic perturbations.
Transitions from a Kondo-like diamagnetic insulator into a modulated ferromagnetic metal in FeGa
3−y
Ge
y
Authors: Zhang Yao , Chen Jie-Sheng , Ma Jie , Ni Jiamin , Imai Masaki , Michioka Chishiro , Hadano Yuta , Avila Marcos A. , Takabatake Toshiro , Li Shiyan , Yoshimura Kazuyoshi
Published: March 2018

Significance

A unifying mechanism for the origin of ferromagnetism which takes into account both well-known and polar extreme theories, namely, the localized- and itinerant-electron regimes, remains a longstanding mystery. Here, we study a particularly interesting system of FeGa

3−
y

Ge

y

, within which the magnetic orderings can be adjusted by the Ge-electron filling control, turning from itinerancy to adequate localized through a ferromagnetic quantum critical transition with increasing

y

. By involving the effects of the spin fluctuations in general, the theoretical estimations of the magnetic properties at the intermediate state of magnetic orderings formulated in terms of the correlation between itinerancy electrons and the spin fluctuations are in quantitative agreements with experimental observations. Our analysis shows a potential universality to all itinerant ferromagnets.
Sign of selection on mutation rate modifiers depends on population size
Authors: Raynes Yevgeniy , Wylie C. Scott , Sniegowski Paul D. , Weinreich Daniel M.
Published: March 2018

Significance

It has been known since the early days of population genetics that population size plays a critical role in natural selection. In small populations, selection on alleles that intrinsically affect fitness can be overwhelmed by genetic drift, rendering both beneficial and deleterious alleles selectively neutral. In contrast, alleles that increase the genomic mutation rate (mutators) experience indirect selection, which acts not on their fitness effects but on their genomic associations with fitness-affecting alleles. Here, we show that the sign of indirect selection on mutators can change depending on population size. This phenomenon of sign inversion in selective effect reflects a qualitatively distinct role of population size in evolution and may be broadly important in other instances of indirect selection.
UBD
modifies
APOL1
-induced kidney disease risk
Authors: Zhang Jia-Yue , Wang Minxian , Tian Lei , Genovese Giulio , Yan Paul , Wilson James G. , Thadhani Ravi , Mottl Amy K. , Appel Gerald B. , Bick Alexander G. , Sampson Matthew G. , Alper Seth L. , Friedman David J. , Pollak Martin R.
Published: March 2018

Significance

Two common variants in the
APOL1
gene explain most of the high rate of kidney disease in people of recent African ancestry. However, not all
APOL1
high-risk individuals develop kidney disease. Here we identified the
UBD
locus as a genetic modifier of
APOL1
kidney disease using admixture mapping. Focal segmental glomerulosclerosis patients have significantly increased African ancestry at the
UBD
locus, which associates with lower
UBD
gene expression. Using a cell-based system, we show that UBD and APOL1 interact functionally and that higher levels of
UBD
expression mitigate
APOL1
-mediated cell death. These findings are important for understanding the genetic and functional modifiers of the human
APOL1
-associated phenotype and the biological pathways relevant to
APOL1
-associated cell damage.
Bilobal architecture is a requirement for calmodulin signaling to Ca
V
1.3 channels
Authors: Banerjee Rahul , Yoder Jesse B. , Yue David T. , Amzel L. Mario , Tomaselli Gordon F. , Gabelli Sandra B. , Ben-Johny Manu
Published: March 2018

Significance

Calmodulin (CaM) regulation of voltage-gated calcium (Ca
V
) channels constitutes a prototypic biological feedback mechanism that contributes prominently toward Ca
2+
homeostasis in neurons and cardiac myocytes. Here, by partitioning CaM molecularly into its two elemental domains or lobes, we uncover a distinctive nonlinearity in CaM signaling to Ca
V
channels. Ca
V
channels detect the coincident binding of two CaM lobes to up-regulate channel activity. This mechanism elaborates a molecular logic operation that enables channels to detect combinations of spatiotemporal Ca
2+
signals and perform higher-order computations on Ca
2+
signals. These findings uncover the unified mechanistic basis for Ca
V
channel feedback and, in so doing, shed light on the versatility of CaM in decoding cellular Ca
2+
signals.
History meets palaeoscience: Consilience and collaboration in studying past societal responses to environmental change
Authors: Haldon John , Mordechai Lee , Newfield Timothy P. , Chase Arlen F. , Izdebski Adam , Guzowski Piotr , Labuhn Inga , Roberts Neil
Published: March 2018

History and archaeology have a well-established engagement with issues of premodern societal development and the interaction between physical and cultural environments; together, they offer a holistic view that can generate insights into the nature of cultural resilience and adaptation, as well as responses to catastrophe. Grasping the challenges that climate change presents and evolving appropriate policies that promote and support mitigation and adaptation requires not only an understanding of the science and the contemporary politics, but also an understanding of the history of the societies affected and in particular of their cultural logic. But whereas archaeologists have developed productive links with the paleosciences, historians have, on the whole, remained muted voices in the debate until recently. Here, we suggest several ways in which a consilience between the historical sciences and the natural sciences, including attention to even distant historical pasts, can deepen contemporary understanding of environmental change and its effects on human societies.
Universal linear and nonlinear electrodynamics of a Dirac fluid
Authors: Sun Zhiyuan , Basov Dmitry N. , Fogler Michael M.
Published: March 2018

Significance

Electrons in pristine solids behave as a hydrodynamic fluid in a certain range of temperatures and frequencies. We show that the response of such a fluid to an electromagnetic field is different from what is predicted by the usual kinetic theory. Certain aspects of this response are universal, for example, a direct relation between the linear and second-order nonlinear optical conductivities. Discovery of this relation enriches our understanding of the light–matter interaction in diverse electron systems and new materials such as graphene.
Programmable RNA recognition using a CRISPR-associated Argonaute
Authors: Lapinaite Audrone , Doudna Jennifer A. , Cate Jamie H. D.
Published: March 2018

Significance

Argonaute proteins are present in bacteria, archaea, and eukaryotes. They play an important role in a wide range of biological processes, from transcriptional and translational gene expression regulation to defense against viruses and silencing of mobile genetic elements. Here we present mechanistic insights into the interactions of the clustered regularly interspaced short palindromic repeats (CRISPR)-associated
Marinitoga piezophila
Argonaute (MpAgo) with its guide RNA (gRNA) and RNA substrates. By modifying the 5′-nucleotide of the gRNA, we demonstrate that MpAgo–gRNA complexes (RNPs) are easily programmable, have high affinity to fully complementary RNA substrates, and can discriminate by more than 300-fold between substrates that differ by only a single nucleotide. These MpAgo RNPs should be useful for probing endogenous RNAs in living cells.
Lateral cerebellum is preferentially sensitive to high sonic hedgehog signaling and medulloblastoma formation
Authors: Tan I-Li , Wojcinski Alexandre , Rallapalli Harikrishna , Lao Zhimin , Sanghrajka Reeti M. , Stephen Daniel , Volkova Eugenia , Korshunov Andrey , Remke Marc , Taylor Michael D. , Turnbull Daniel H. , Joyner Alexandra L.
Published: March 2018

Significance

Cerebellar tumor medulloblastoma (MB) is no longer considered a single disease as it has been separated into four subgroups with further subdivisions based on genomic and clinical data. Mechanistic understandings of the stratification within subgroups should allow for better-targeted treatments. We redefined the main cell of origin by showing that granule cell precursors (GCPs) are heterogeneous with molecularly distinct populations based on their location. As a consequence, GCPs respond differentially to two driver mutations, and a subset of GCPs is more susceptible to Sonic hedgehog (SHH) pathway elevation and forms tumors more readily. These results provide insights into the preferential location of human SHH-MBs in the lateral cerebellum and the cellular and genetic factors influencing SHH-MB progression.
Simple mechanosense and response of cilia motion reveal the intrinsic habits of ciliates
Authors: Ohmura Takuya , Nishigami Yukinori , Taniguchi Atsushi , Nonaka Shigenori , Manabe Junichi , Ishikawa Takuji , Ichikawa Masatoshi
Published: March 2018

Significance

Single-celled microorganisms are important in ecosystems, and their behaviors impact the Earth’s environments. To survive in harsh environments, these organisms frequently act as though exercising discretion. How do they achieve such intelligent behaviors? In this work, we focused on the accumulation of ciliates on solid/fluid interfaces, where they can obtain sufficient nutrients and a stable environment. This phenomenon is not described in the standard hydrodynamics of microswimmers. Our experiment and simulation revealed that simple principles, the anisotropic shape of the cell and the mechanosensing nature of cilia, induce the accumulation of ciliates on solid/fluid interfaces. The contribution of our work is that a simple response of the cellular apparatus and fluid dynamics explain the apparently clever behavior of ciliates.
Blindfold learning of an accurate neural metric
Authors: Gardella Christophe , Marre Olivier , Mora Thierry
Published: March 2018

Significance

To understand how neural signals code sensory stimuli, most approaches require knowing both the true stimulus and the neural response. The brain, however, only has access to the neural signals put out by sensory organs. How can it learn to relate neural responses to sensory stimuli, especially for responses to which it has never been exposed? Here we show how to solve this problem by building a metric on neural responses such that responses to the same stimulus are close. Although the metric is built with no access to the stimulus, it outperforms all existing metrics in fine discrimination tasks, suggesting a way the brain could make sense of its sensory output.
Requirement for intron structures in activating the
Cd8a
locus
Authors: Wada Hisashi , Yasmin Nighat , Kakugawa Kiyokazu , Ohno-Oishi Michiko , Nieke Sebastian , Miyamoto Chizuko , Muroi Sawako , Taniuchi Ichiro
Published: March 2018

Significance

Understanding the mechanisms controlling reactivation of the
Cd8a
gene is important to elucidate molecular mechanisms of lineage commitment toward CD8
+
cytotoxic T cells. By analyzing the expression of hCD2 reporter from manipulated
Cd8a
alleles with distinct polyadenylation signal positions or intron structures defective in RNA splicing, we found that intron structures are essential for hCD2 expression in CD8
+
T cells. This occurred at least in part through the induction of DNA demethylation at intronic regions. In contrast,
Cd8a
gene was transcribed in CD8
+
T cells from a mutant
Cd8a
locus lacking intron structures, albeit at a lower level. Our observations highlight the possible involvement of intron structures in the regulation of
Cd8a
gene during T cell development.
Immune-modulating enzyme indoleamine 2,3-dioxygenase is effectively inhibited by targeting its apo-form
Authors: Nelp Micah T. , Kates Patrick A. , Hunt John T. , Newitt John A. , Balog Aaron , Maley Derrick , Zhu Xiao , Abell Lynn , Allentoff Alban , Borzilleri Robert , Lewis Hal A. , Lin Zeyu , Seitz Steven P. , Yan Chunhong , Groves John T.
Published: March 2018

Significance

Indoleamine 2,3-dioxygenase (IDO1) is a heme protein that catalyzes the dioxygenation of tryptophan. Cells expressing this activity are able to profoundly alter their surrounding environment to suppress the immune response. Cancer cells exploit this pathway to avoid immune-mediated destruction. Through a range of kinetic, structural, and cellular assays, we show that two classes of highly selective inhibitors of IDO1 act by competing with heme binding to apo-IDO1. This shows that IDO1 is dynamically bound to its heme cofactor in what is likely a critical step in the regulation of this enzyme. These results have elucidated a previously undiscovered role for the ubiquitous heme cofactor in immune regulation, and it suggests that other heme proteins in biology may be similarly regulated.
Extrachromosomal circular DNA-based amplification and transmission of herbicide resistance in crop weed
Amaranthus palmeri
Authors: Koo Dal-Hoe , Molin William T. , Saski Christopher A. , Jiang Jiming , Putta Karthik , Jugulam Mithila , Friebe Bernd , Gill Bikram S.
Published: March 2018

Significance

Glyphosate is a nonselective herbicide used around the globe for weed control in glyphosate-resistant (GR) and noncrop situations. The extensive and exclusive use of glyphosate has led to the evolution of herbicide resistance in many crop weeds. The molecular target of glyphosate, the 5-enolpyruvlyshikimate-3-phosphate synthase (
EPSPS
) gene, confers resistance upon amplification and was first documented in GR
Amaranthus palmeri
. We now report that amplified
EPSPS
copies in GR
A. palmeri
are present in the form of extrachromosomal circular DNA molecules (eccDNAs) with various conformations. We discovered that eccDNAs are transmitted to the next generation by tethering to mitotic and meiotic chromosomes. These results represent a report of extrachromosomal structures that drive rapid adaptive evolution in higher organisms.
Phosphorylation-induced unfolding regulates p19
INK4d
during the human cell cycle
Authors: Kumar Amit , Gopalswamy Mohanraj , Wolf Annika , Brockwell David J. , Hatzfeld Mechthild , Balbach Jochen
Published: March 2018

Significance

Cell cycle progression is tightly controlled in healthy organisms and often perturbed in human diseases, including, most prominently, many forms of cancers. Cyclin-dependent protein kinases and their inhibitors, such as p19
INK4d
, regulate the different stages of the cell cycle. Here, we demonstrate how sequential phosphorylation of p19
INK4d
at two sites first destabilizes and then unfolds the N-terminal half of the protein, which dissociates its cyclin-dependent protein kinase-inhibitory complex and primes p19
INK4d
for cellular degradation. Our results define a structural mechanism by which phosphorylation-induced protein unfolding controls a key step in cell cycle progression.
Measuring discursive influence across scholarship
Authors: Gerow Aaron , Hu Yuening , Boyd-Graber Jordan , Blei David M. , Evans James A.
Published: March 2018

Significance

Scientific and scholarly influence is multifaceted, shifts over time, and varies across disciplines. We present a dynamic topic model to credit documents with influence that shapes future discourse based on their content and contextual features. We trace discursive innovation in scholarship and identify the influence of particular articles along with their authors, affiliations, and journals. In collections of science, social science, and humanities research spanning over a century, our measure helps predict citations and reveals signals that recognize authors who make diverse contributions and whose contributions take longer to be appreciated, allowing us to compensate for bias in citation behavior.
Population genomic analysis of elongated skulls reveals extensive female-biased immigration in Early Medieval Bavaria
Authors: Veeramah Krishna R. , Rott Andreas , Groß Melanie , van Dorp Lucy , López Saioa , Kirsanow Karola , Sell Christian , Blöcher Jens , Wegmann Daniel , Link Vivian , Hofmanová Zuzana , Peters Joris , Trautmann Bernd , Gairhos Anja , Haberstroh Jochen , Päffgen Bernd , Hellenthal Garrett , Haas-Gebhard Brigitte , Harbeck Michaela , Burger Joachim
Published: March 2018

Significance

Many modern European states trace their roots back to a period known as the Migration Period that spans from Late Antiquity to the early Middle Ages. We have conducted the first population-level analysis of people from this era, generating genomic data from 41 graves from archaeological sites in present-day Bavaria in southern Germany mostly dating to around 500 AD. While they are predominantly of northern/central European ancestry, we also find significant evidence for a nonlocal genetic provenance that is highly enriched among resident Early Medieval women, demonstrating artificial skull deformation. We infer that the most likely origin of the majority of these women was southeastern Europe, resolving a debate that has lasted for more than half a century.
Design and validation of the revised Regional Identity Scale (RIS-2) / Diseño y validación de la Escala de Identidad Regional revisada (RIS-2)
Authors: Asún Rodrigo , Zúñiga Claudia , Morales José-Francisco
Published: March 2018

With the objective of theoretically and psychometrically updating the Regional Identity Scale (RIS) proposed by Zúñiga and Asún in 2004 and expanding the population for which it shows evidence of validity, a revision and revalidation of this instrument was performed via two studies. The first study included 1,113 university students from four regions of Chile, and the second included 1,200 adults from the same regions. Both samples were obtained via a random design through multistage conglomerates. The results enable us to propose a new version of the original scale (RIS-2) with suitable reliability indexes, solid evidence of both convergent validity and internal structure validity, and items with satisfactory psychometric quality. Furthermore, we verify the presence of a multifactor structure with three highly correlated dimensions. We conclude that the RIS-2 is a reliable, valid and conceptually broader instrument than the preceding version, so it is a useful tool to measure the intensity of regional identity in both university students and the adult population.
Housing versus Treatment First for Supportive Housing Participants with Substance use Disorders: A Comparison of Housing and Public Service use Outcomes
Authors: Hall Gerod , Walters Sarah , Gould Hannah , Lim Sungwoo
Published: March 2018

Background

Homeless persons with substance use disorders (SUD) have high disease risk, poor access to health care, and are frequent users of Medicaid and other social services. Low-demand supportive housing with no prerequisites for treatment or sobriety has been shown to improve housing stability and decrease public service use for chronically homeless persons with serious mental illness (SMI) and chronic medical conditions. The impact of low-demand housing on individuals with SUD but without co-occurring SMI has been little studied. This evaluation compares housing retention and use of crisis public services (jail, emergency department visits, hospitalization, and substance detoxification) between individuals treated and untreated for SUD before move-in to a low-demand supportive housing program in New York City.

Methods

The authors used matched administrative records for individuals with SUD but no SMI placed in supportive housing during 2007–2012. Participants received SUD treatment ( n = 1425; treated participants) or were not treated ( n = 512; active users) at housing application. Propensity score–weighted regression analyses were used to best estimate the effect of SUD treatment on incarceration, public service utilization, and housing retention.

Results

Persons not treated for SUD had a significantly longer tenure in supportive housing than treated participants. However, not treated tenants were more likely to be incarcerated. Opioid agonist therapy and older age decreased the risk of housing discharge, whereas detoxification and inpatient SUD treatment increased the risk of discharge.

Conclusions

Persons with SUD can achieve residential stability in supportive housing that does not require SUD treatment before admission.
The salience of silence: the silence of salience
Authors: Waistell Jeff
Published: March 2018

This is a unique study of an almost silent and still film of the organization of silence. The film “Into Great Silence” (IGS) shows how Carthusian monks organize silence, punctuating and structuring it with recurring rituals and routines. Carthusian silence is discourse: it is their way of communicating, interacting, and sustaining their organization. The salience of Carthusian silence is that it is where they can discern divine presence. By studying IGS, the researcher overcame the challenges of access to the monastery, of studying silence, and of appraising the implicit salience of Carthusian silence. The film invites viewers to silent introspection through sound art, visual poetry, and a silent metaphorical discourse that relies on symbols. IGS utilizes reverse visual metaphor, with metaphorical images that move the audience from images to abstract territories. The researcher also reflects on his own personal experience during his stays at a Carthusian Charterhouse, when he was a novitiate candidate in the sole English Carthusian Monastery (St. Hugh’s Charterhouse, Parkminster, near Horsham in West Sussex, England). Although he did not pursue this vocation, his two periods in the monastery left him with an indelible impression of a religious order that has not changed for nearly a millennium, and which imparted a deep awareness and appreciation of silence, solitude, and stillness. The paper draws out lessons for research and organizations.
Understanding Hypothetical Bias: An Enhanced Meta‐Analysis
Authors: Penn Jerrod M , Hu Wuyang
Published: March 2018

The presence of hypothetical bias (HB) associated with stated preference methods has garnered frequent attention in the broad literature trying to describe and understand human behavior, often seen in environmental valuation, marketing studies, transportation choices, medical research, and others. This study presents an updated meta‐analysis to explore the source of HB and methods to mitigate it. While previous meta‐analysis on this topic often involves a few dozen articles, this analysis includes 131 studies after reviewing over 500 published and unpublished articles. This enables the inclusion of several important factors that have not been investigated before. These include relatively recent willingness to pay elicitation methods such as choice experiments and the Turnbull lower bound estimator. Newly emerged HB reduction techniques such as consequentiality and certainty follow‐up treatments are also included. For explanatory variables that have been examined in previous studies, this analysis does not always report consistent findings. In particular, holding everything constant and contrary to commonly‐held beliefs, the method of auction does not offer much reduction to HB compared to more conventional methods such as a referendum vote. However, choice experiment, cheap talk, consequentiality and certainty follow‐up all significantly contributed to explaining and mitigating the magnitude of HB. These results help practitioners to understand HB's presence and choose appropriate methods for amelioration. The framework established through this study also enables future analyses targeted at understanding variations built upon one or multiple HB mitigation techniques.
The Fukushima Daiichi Nuclear Power Plant accident and school bullying of affected children and adolescents: the need for continuous radiation education
Authors: Sawano Toyoaki , Nishikawa Yoshitaka , Ozaki Akihiko , Leppold Claire , Tsubokura Masaharu
Published: March 2018

The health threats of radiation-release incidents are diverse and long term. In addition to direct radiation effects, it is imperative to manage the indirect effects of radiation such as stigma, prejudice and broader mental health impacts. Six years after the Fukushima Daiichi Nuclear Power Plant accident of March 2011, bullying caused by stigma and prejudice toward evacuees, including children, has become a social problem in Japan. This phenomenon may be associated with the fact that knowledge about radiation has still not reached the general public, and to a potential lack of motivation among Japanese citizens to learn about radiation and bullying. Continuous and sustained education regarding radiation is warranted in order to enhance the general knowledge level about the effects of radiation in Japan after the Fukushima Daiichi Nuclear Power Plant accident, and this education will become an important reference for education after future nuclear disasters.
Suzaku observations of low surface brightness cluster Abell 1631
Authors: Babazaki Yasunori , Mitsuishi Ikuyuki , Ota Naomi , Sasaki Shin , Böhringer Hans , Chon Gayoung , Pratt Gabriel W , Matsumoto Hironori
Published: March 2018

We present analysis results for a nearby galaxy cluster Abell 1631 at z = 0.046 using the X-ray observatory Suzaku. This cluster is categorized as a low X-ray surface brightness cluster. To study the dynamical state of the cluster, we conduct four-pointed Suzaku observations and investigate physical properties of the Mpc-scale hot gas associated with the A 1631 cluster for the first time. Unlike relaxed clusters, the X-ray image shows no strong peak at the center and an irregular morphology. We perform spectral analysis and investigate the radial profiles of the gas temperature, density, and entropy out to approximately 1.5 Mpc in the east, north, west, and south directions by combining with the XMM-Newton data archive. The measured gas density in the central region is relatively low (a few ×10−4 cm−3) at the given temperature (∼2.9 keV) compared with X-ray-selected clusters. The entropy profile and value within the central region (r < 0.1 r200) are found to be flatter and higher (≳400 keV cm2). The observed bolometric luminosity is approximately three times lower than that expected from the luminosity–temperature relation in previous studies of relaxed clusters. These features are also observed in another low surface brightness cluster, Abell 76. The spatial distributions of galaxies and the hot gas appear to be different. The X-ray luminosity is relatively lower than that expected from the velocity dispersion. A post-merger scenario may explain the observed results.
Environmental science and policy: A meta-synthesis of case studies on boundary organizations and spanning processes
Authors: Jensen-Ryan Danielle K , German Laura A
Published: March 2018

We conducted a meta-synthesis of published qualitative articles to better understand how features and strategies of boundary organizations and spanning processes influence whether environmental science was utilized in politically oriented outcomes. Meta-synthesis is a peer-reviewed research technique which is becoming more prolific as disciplines compare qualitative research studies and generalize qualitative knowledge. In this work, thirty-nine published case studies were analysed through a systematic grounded theory approach and thirty-nine structured interviews were performed with authors to validate the results. Overall, forty-seven boundary spanning variables were evaluated using disaggregated statistics to determine correlation with policy outcomes. Our results develop the possibility that successful boundary spanning linkages may be less about utilizing formal boundary organizations and more about fostering the process through which science and policy are intermingled.
Mitochondrial Fusion Suppresses Pancreatic Cancer Growth via Reduced Oxidative Metabolism
Authors: Yu Meifang , Huang Yanqing , Deorukhkar Amit , Fujimoto Tara N. , Govindaraju Suman , Molkentine Jessica M. , Lin Daniel , Kang Ya’an , Koay Eugene J. , Fleming Jason B. , Gupta Sonal , Maitra Anirban , Taniguchi Cullen M.
Published: March 2018

Pancreatic cancer is a highly lethal disease whose aggressive biology that is driven by mitochondrial oxidative metabolism. Mitochondria normally form a network of fused organelles, but we find that patient-derived and genetically engineered murine pancreatic cancer cells exhibit highly fragmented mitochondria with robust oxygen consumption rates (OCR). When mitochondrial fusion was activated by the genetic or pharmacological inhibition Drp1, the morphology and metabolism of human and murine pancreatic cancer cells more closely resembled that of normal pancreatic epithelial cells. This reduced metabolism was correlated with slower tumor growth, fewer metastases, and enhanced survival in a syngeneic orthotopic model. Similarly, directly activating mitochondrial fusion by overexpression of Mfn2 also reduced tumor growth and metastases. Mitochondrial fusion in pancreatic cancer cells was associated with reduced mitochondrial mass and Complex I expression and function. Thus, these data suggest that enhancing mitochondrial fusion through Drp1 inhibition or enhanced Mfn2 expression or function has strong tumor suppressive activity against pancreatic cancer and may thus represent a highly novel and efficacious therapeutic target.
3D micro-environment regulates NF–κβ dependent adhesion to induce monocyte differentiation
Authors: Bhattacharya Anindita , Agarwal Mahesh , Mukherjee Rachita , Sen Prosenjit , Sinha Deepak Kumar
Published: March 2018

Differentiation of monocytes entails their relocation from blood to the tissue, hence accompanied by an altered physicochemical micro-environment. While the mechanism by which the biochemical make-up of the micro-environment induces differentiation is known, the fluid-like to gel-like transition in the physical micro-environment is not well understood. Monocytes maintain non-adherent state to prevent differentiation. We establish that irrespective of the chemical makeup, a 3D gel-like micro-environment induces a positive-feedback loop of adhesion-MAPK-NF-κβ activation to facilitate differentiation. In 2D fluid-like micro-environment, adhesion alone is capable of inducing differentiation via the same positive-feedback signalling. Chemical inducer treatment in fluid-like micro-environment, increases the propensity of monocyte adhesion via a brief pulse of p-MAPK. The adhesion subsequently elicit differentiation, establishing that adhesion is both necessary and sufficient to induce differentiation in 2D/3D micro-environment. Our findings challenge the notion that adhesion is a result of monocyte differentiation. Rather it’s the adhesion which triggers the differentiation of monocytes. MAPK, and NF-κβ being key molecules of multiple signaling pathways, we hypothesize that biochemically inert 3D gel-like micro-environment would also influence other cellular functions.

Summary statement

This article brings out a new insight into the novel mechanisms of monocyte differentiation solely driven by physical micro-environment and adhesion.
The BRCA1-BARD1 complex associates with the synaptonemal complex and pro-crossover factors and influences RAD-51 dynamics duringCaenorhabditis elegansmeiosis
Authors: Janisiw Eva , Dello Stritto Maria Rosaria , Jantsch Verena , Silva Nicola
Published: March 2018

During meiosis, the maternal and paternal homologous chromosomes must align along their entire length and recombine to achieve faithful segregation in the gametes. Meiotic recombination is accomplished through the formation of DNA double-strand breaks, a subset of which can mature into crossovers to link the parental homologous chromosomes and promote their segregation. Breast and ovarian cancer susceptibility protein BRCA1 and its heterodimeric partner BARD1 play a pivotal role in DNA repair in mitotic cells; however, their functions in gametogenesis are less well understood. Here we show that localization of BRC-1 and BRD-1 (Caenorhabditis elegansorthologues of BRCA1 and BARD1) is dynamic during meiotic prophase I; they ultimately becoming concentrated at regions surrounding the presumptive crossover sites, co-localizing with the pro-crossover factors COSA-1, MSH-5 and ZHP-3. The synaptonemal complex is essential for BRC-1 loading onto chromosomes but recombination is not. BRC-1 forms an in vivo complex with the synaptonemal complex component SYP-3 and the crossover-promoting factor MSH-5. Furthermore, BRC-1 is essential for efficient stage-specific recruitment of the RAD-51 recombinase to DNA damage sites when synapsis is impaired and upon induction of exogenous DNA double-strand breaks. Taken together, our data provide new insights into the localization and meiotic function of the BRC-1–BRD-1 complex and highlight their essential role in DNA double-strand break repair during gametogenesis.

Author summary

Sexually reproducing species rely on meiosis to transmit their genetic information across generations. Parental chromosomes (homologues) undergo many distinctive processes in their complex journey from attachment to segregation. The physiological induction of DNA double strand breaks is crucial for promoting correct chromosome segregation: they are needed to activate the DNA repair machinery responsible for creating physical connections, or crossovers (COs), between the homologues. In turn, crossovers promote the accurate segregation of the chromosomes in daughter cells. The BRCA1–BARD1 complex has a pivotal role during DNA repair in somatic cells and is exclusively located on unaligned chromosomal regions during mammalian meiosis. We show that inCaenorhabditis elegans, BRCA1 and BARD1 localize to chromosomes at all stages of meiotic prophase I and are enriched at presumptive crossover sites. We found that BRCA1 promotes DNA loading of the repair factor RAD-51 in specific mutant backgrounds and upon exogenous damage induction. Our data provide evidence for a direct physical association between BRCA1 and pro-crossover factors (including the synaptonemal complex) and identify an important role for BRCA1 in stimulating meiotic DNA repair. Further studies are necessary to identify the substrates acted upon by BRCA1–BARD1 complex to maintain genome stability in the gametes.
Molecular Dynamics Simulation of the E.coli FtsZ
Authors: Muthukumar Vidyalakshmi C
Published: March 2018

Previous molecular dynamics studies of the FtsZ protein revealed that the protein has high intrinsic flexibility which the crystal structures were unable to reveal. The initial configuration in these studies was based on the available crystal structure data and therefore, the effect of the C-terminal Intrinsically Disordered Region (IDR) of FtsZ could not be observed in these previous studies. Recent investigations have revealed that the C-terminal IDR is crucial for FtsZ assembly in vitro and Z ring formation in vivo. Therefore, in this study, we simulate FtsZ with the IDR.

Simulations of the FtsZ monomer in different nucleotide bound forms (without nucleotide, GTP, GDP) were performed. In the conformations of FtsZ monomer with GTP, GTP binds variably with the protein. Such variable interaction with the monomer has not been observed in any previous simulation studies of FtsZ and not observed in crystal structures. The central helix bends towards the C-terminal domain in the GTP bound form, thus making way for polymerization. Nucleotide dependent small shift/rotation of the C-terminal domain was observed in average structures.
Molecular Dynamics simulation of the E.coli FtsZ dimer
Authors: Muthukumar Vidyalakshmi C
Published: March 2018

FtsZ dimer was studied to gain insights into FtsZ protofilament formation. In a previous simulation study of the M.janaschii dimer it was found that the monomer-monomer contacts in the GDP bound dimer is lower which results in the high curvature of the GDP bound protofilaments. In this study, we have simulated the E.coli FtsZ dimer. The initial structure was obtained from our previous study in which we had simulated the E.coli FtsZ monomer with its C-terminal IDR (Intrinsically Disordered region) built by homology modelling. The M.janaschii FtsZ dimer subunit contacts were used in the initial configuration. Simulations of the dimer were performed with GTP, GDP and ATP. We observed that the C-terminal domain rotates considerably during dimerization. We also observed the different dynamics of the GTP, GDP and ATP bound dimers due to which assembly into straight protofilaments is favoured only in the presence of GTP.
Assembly of a Parts List of the Human Mitotic Cell Cycle Machinery
Authors: Giotti Bruno , Chen Sz-Hau , Barnett Mark W. , Regan Tim , Ly Tony , Wiemann Stefan , Hume David A. , Freeman Tom C.
Published: March 2018

The set of proteins required for mitotic division remains poorly characterised. Here, an extensive series of correlation analyses of human and mouse transcriptomics data was performed to identify genes strongly and reproducibly associated with cells undergoing S/G2-M phases of the cell cycle. In so doing, a list of 701 cell cycle-associated genes was defined and shown that whilst many are only expressed during these phases, the expression of others is also driven by alternative promoters. Of this list, 496 genes have known cell cycle functions, whereas 205 were assigned as putative cell cycle genes, 53 of which are functionally uncharacterised. Among these, 27 were screened for subcellular localisation revealing many to be nuclear localised and at least four to be novel centrosomal proteins. Furthermore, 10 others inhibited cell proliferation upon siRNA knockdown. This study presents the first comprehensive list of human cell cycle proteins, identifying many new candidate proteins.
Disabling Gβγ SNARE interaction in transgenic mice disrupts GPCR-mediated presynaptic inhibition leading to physiological and behavioral phenotypes
Authors: Zurawski Zack , Thompson Gray Analisa D. , Brady Lillian J. , Page Brian , Church Emily , Harris Nicholas A. , Dohn Michael R. , Yim Yun Young , Hyde Karren , Mortlock Douglas P. , Winder Danny G. , Alford Simon , Jones Carrie K. , Hamm Heidi E.
Published: March 2018

Gi/o-coupled G-protein coupled receptors modulate neurotransmission presynaptically through inhibition of exocytosis. Release of Gβγ subunits decreases the activity of voltage-gated calcium channels (VGCC), decreasing excitability. A less understood Gβγ–mediated mechanism downstream of calcium entry is the binding of Gβγ to SNARE complexes. Here, we create a mouse partially deficient in this interaction. SNAP25Δ3 homozygote animals are developmentally normalbut impaired gait and supraspinal nociception. They also have elevated stress-induced hyperthermia and impaired inhibitory postsynaptic responses to α2A-AR, but normal inhibitory postsynaptic responses to Gi/o-coupled GABABreceptor activation. SNAP25Δ3 homozygotes have deficits in inhibition of hippocampal postsynaptic responses to 5 HT1bagonists that affect hippocampal learning. These data suggest that Gi/o-coupled GPCR inhibition of exocytosis through the Gβγ-SNARE interaction is a crucial component of numerous physiological and behavioral processes.
Investigation on oxidation behaviors of Ti-Si-N coating at high temperature
Authors: Wan Q. , Chen Y.M. , Liu H.D. , Yang B.
Published: March 2018

Purpose

Ti-Si-N coating with nanocomposite structure is a promising protective coating for cutting tools which will be subject to high temperature oxidation during service. This study aims to investigate the thermal stability of Ti-Si-N coatings and lays the foundation for its application in high speed dry cutting.

Design/methodology/approach

Nanocomposite Ti-Si-N coating was deposited on stainless substrate and silicon wafer (100) by Ti90Si10 alloy target by using cathodic arc ion plating. The microstructure of Ti-Si-N coating had been detected by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS).

Findings

The results suggested that the coating was TiN nanocrystals with a diameter of 6.3 nm surrounded by amorphous Si3N4. The oxidation test was conducted under 550, 650, 750, 800, 850, 900 and 950°C for 2 h. The structure evolution was observed by Scanning electron microscope (SEM), energy dispersive spectrum (EDS), XRD and XPS. The results indicated that rutile has been formed at 650°C, while Si3N4 began to oxidized at 800°C. The grain size of TiN increased from 6.3 to 13 nm as the samples oxidized from 550 to 800. Micro-crack also formed in samples oxidized over 900°C.

Originality/value

Ti-Si-N coating, in this study, was deposited by cathodic arc ion plating using alloy target at high-bias voltage. The oxidation temperature ranged from 500 to 950°C with TiN coating as reference.
Assessing the risk profile of dairy farms: application of the Income Stabilisation Tool in Italy
Authors: Trestini Samuele , Szathvary Serena , Pomarici Eugenio , Boatto Vasco
Published: March 2018

Purpose

This paper bridges the gap between theory and practice in the application of the Income Stabilisation Tool (IST). With an application to the dairy sector, the purpose of this paper is to propose methodology for the quantification of reference income when farm structural change occurs and estimate the role of farm attributes on the probability of income loss, offering an ex ante evaluation of farm resilience to risk.

Design/methodology/approach

Based on a balanced Farm Accountancy Network farm-level panel ranging from 2008 to 2014, three hypotheses of reference income calculation are tested to assess whether farms structural changes over the years significantly affect the level of IST indemnification. The role of farm characteristics on the probability of an income reduction is then evaluated by estimating a multinomial logit model.

Findings

Results show that farms’ structural changes significantly affect IST indemnities and need to be considered in calculating the reference income. The estimated model suggests that farm characteristics significantly affect the probability of a severe income drop and hence risk resilience. Extensive livestock systems seem to reduce the probability of an income drop, while farms in upland areas managed by young farmers seem to experience increased risk exposure.

Originality/value

The research provides one of the first attempts to define risk profile of dairy farms by modelling the probability of an income reduction on observable attributes. Indeed, among different sectors, dairy farms emerge as the main candidates for the application of the IST.
Exploratory innovation, exploitative innovation and employee creativity
Authors: Hong Jin , Hou Bojun , Zhu Kejia , Marinova Dora
Published: March 2018

Purpose

The purpose of this study is to investigate the relationships between exploratory/exploitative innovation and employee creativity in the Chinese context and how these two relationships can be moderated by an important cultural dimension – collectivism.

Design/methodology/approach

A theoretical framework was developed to explore the relationships between exploratory/exploitative innovation, employee creativity and collectivism. Data were collected by sending out surveys to managers and employees in various industries in mainland China. Hypotheses were tested using hierarchical regressions.

Findings

The results show that both exploratory innovation and exploitative innovation are positively related to employee creativity. Furthermore, collectivism negatively moderates the effects of both types of innovation on employee creativity, despite its positive main effect.

Originality/value

This study explores the relationship between organizational innovation and individual employee creativity in the Chinese context. This paper empirically analyzes the moderating effect of collectivism in the relationship between organizational innovation and employee creativity. It also indicates the factors inherent in Chinese culture that influence innovation and gives explanations from education, subordinate relation, etc.