bluuebunny/crossref_metadata_2025 huggingface dataset:
Balancing animal, pasture and environmental outcomes in grazing management experiments
Authors: Michalk D. L. , Badgery W. B. , Kemp D. R.
Published: June 2017

About 60% of the gross value of Australia’s agriculture (AU$49 billion) is produced from the 85 million ha of temperate grasslands of southern Australia. A large part of this production comes from grazing livestock in the high-rainfall zone (HRZ) where 40% of the area has been retained as native and naturalised pastures, located in variable landscapes. These native pastures have seen a decline in productivity and increasing environmental problems, such as erosion, due to a loss of productive perennial species over recent decades. Grazing management systems have been advocated to not only balance the quality and quantity of forage with the nutritional demands of grazing animals, but also to manage the degradation caused by grazing. There has been an evolution of grazing management research through national projects from Temperate Pasture Sustainability Key Program to Sustainable Grazing Systems and then EverGraze, which has shifted from a focus on small plots and fixed stocking rates, to large-plot and farmlet experiments that include landscape variability and flexible grazing systems that more closely resemble commercial practice. These experiments generate reliable plant and animal response data that can be used to validate system models needed to assess the spatial and temporal challenges of grassland management. The present paper introduces the research conducted at the Orange proof site as part of the national EverGraze program. The research investigated the interactions between landscape variability and grazing method (1-, 4- and 20-paddock grazing management treatments) with flexible stocking rates. The following three key questions were addressed: (1) does increasing the number of paddocks and implementing rotational grazing result in a higher stocking rate, higher per hectare production and better economic outcomes; (2) which is the most appropriate combination of grazing method and stocking rate to achieve a higher and more stable perennial component to improve production and environmental benefits in different parts of the landscape; and (3) can landscape variability be identified, mapped and effectively managed on HRZ native grassland properties? This special edition of Animal Production Science answers these questions and provides recommendations for managing HRZ native pastures.
Integrated care among healthcare providers in shared maternity care: what is the role of paper and electronic health records?
Authors: Hawley Glenda , Hepworth Julie , Jackson Claire , Wilkinson Shelley A.
Published: June 2017

This study examines a paper hand-held record and a shared electronic health record in an Australian tertiary hospital healthcare maternity setting and the role that both types of records play in facilitating integrated care among healthcare providers. A qualitative research design was used where five focus groups were conducted in two phases with 69 hospital healthcare providers. In total, 32 interviews were also carried out with general practitioners. Transcripts were analysed using qualitative content analysis. Three key themes were identified: (1) selective use of records; (2) records as communication of care; and (3) negativity about the use of records. This study demonstrates that healthcare providers do not effectively share information using either a paper hand-held record or a shared electronic health record. Considering a national commitment to e-health innovation, a multi-professional input, organisational support and continuing education are identified as crucial to realising the potential of a maternity shared electronic health record to facilitate integrated care.
Regulation of spinogenesis in mature Purkinje cells via mGluR/PKC-mediated phosphorylation of CaMKIIβ
Authors: Sugawara Takeyuki , Hisatsune Chihiro , Miyamoto Hiroyuki , Ogawa Naoko , Mikoshiba Katsuhiko
Published: June 2017

Significance

The cerebellar cortex, and its sole output, Purkinje cells, is essential for motor coordination and learning. Dendritic spines of Purkinje cells are the primary sites of cerebellar synaptic plasticity. Therefore, maintenance of spine structure of mature Purkinje cells is a critical aspect of cerebellar functions, but the underlying mechanisms remain unclear. Here we described an activity-dependent regulatory mechanism of spines in Purkinje cells. We found that F-actin cross-linking activity of Ca
2+
/calmodulin-dependent protein kinase II β isoform is controlled by protein kinase C-mediated phosphorylation, which is triggered by group I metabotropic glutamate receptor signaling. Defective function of the phosphorylation leads to excess spine development in mature Purkinje cells. Our findings revealed a mechanism for proper maintenance of cerebellar Purkinje cell spines.
Impact of nutrition on social decision making
Authors: Strang Sabrina , Hoeber Christina , Uhl Olaf , Koletzko Berthold , Münte Thomas F. , Lehnert Hendrik , Dolan Raymond J. , Schmid Sebastian M. , Park Soyoung Q.
Published: June 2017

Significance

Food intake is essential for survival in all species for meeting energetic demands. However, food intake also modulates various biochemical processes underlying cognition. Across two studies, we showed that different macronutrient compositions in standard European meals affect plasma neurotransmitter precursor levels, and these in turn influence social decision making. Our results provide evidence that variations in the macronutrient content of a normal European meal exert a significant impact on high-level human cognition. This study opens perspectives on nutrition-driven cognition modulation. The results have implications for education, economics, and public policy by emphasizing the importance of a balanced diet on fundamental expressions of cognition.
Pharmacology of the Na
v
1.1 domain IV voltage sensor reveals coupling between inactivation gating processes
Authors: Osteen Jeremiah D. , Sampson Kevin , Iyer Vivek , Julius David , Bosmans Frank
Published: June 2017

Significance

Na
v
1.1 is a potential therapeutic target for brain disorders, such as epilepsy, Alzheimer's disease, and autism. Moreover, this voltage-gated sodium (Na
v
) channel subtype contributes to mechanical pain by regulating excitability in a specific subset of sensory neurons within the peripheral nervous system. The results of our study shed light on the molecular mechanisms underlying Na
v
1.1 inactivation and suggest pharmacologic approaches to address relevant disease-related phenotypes.
Microsymbiont discrimination mediated by a host-secreted peptide in
Medicago truncatula
Authors: Yang Shengming , Wang Qi , Fedorova Elena , Liu Jinge , Qin Qiulin , Zheng Qiaolin , Price Paul A. , Pan Huairong , Wang Dong , Griffitts Joel S. , Bisseling Ton , Zhu Hongyan
Published: June 2017

Significance

The legume–rhizobial symbiosis culminates in the formation of nitrogen-fixing root nodules. This symbiotic relationship plays a critical role in sustainable agriculture because it reduces the need for nitrogen fertilizers. However, nitrogen fixation efficiency varies tremendously between different plant–bacteria combinations, and the molecular mechanisms that regulate this specificity are not well understood. We report that this specificity is regulated by nodule-specific cysteine-rich (NCR) peptides in
Medicago truncatula
, a model legume closely related to alfalfa (
Medicago sativa
). Our finding provides insights into cross-kingdom signaling in host–bacterial symbioses and makes NCRs attractive agents for engineering legume–rhizobia pairs to optimize nitrogen fixation performance.
Weak protein–protein interactions in live cells are quantified by cell-volume modulation
Authors: Sukenik Shahar , Ren Pin , Gruebele Martin
Published: June 2017

Significance

Weak, transient protein complexes are emerging as vital to cell function and regulation, with roles ranging from stabilization of a protein structure to driving cytoplasmic phase separations. Because of their fleeting nature and sensitivity, such complexes are notoriously hard to characterize. We develop and validate a method to quantify such “quinary interactions” inside the cell itself, and apply it to the putative interaction of the glycolytic enzymes GAPDH and PGK. Our method can characterize weak protein–protein interactions in live cells, with future application to other biomolecular species, such as RNAs.
Selective replication of oncolytic virus M1 results in a bystander killing effect that is potentiated by Smac mimetics
Authors: Cai Jing , Lin Yuan , Zhang Haipeng , Liang Jiankai , Tan Yaqian , Cavenee Webster K. , Yan Guangmei
Published: June 2017

Significance

Although oncolytic therapy is showing great potential in clinical trials, not all patients benefit from it. Combining oncolytic viruses with anticancer chemicals could provide a better chance to increase the response rate. Here, we report that the combination of an alphavirus (M1) that we identified previously and second mitochondria-derived activator of caspases (Smac) mimetic compounds (SMCs) shows substantial oncolytic effect in vitro, in vivo, and ex vivo (samples from patients’ tumor tissues). The combined effect is mediated by a bystander killing effect and increased replication of M1. Our work provides an example for potentiating the response rate in refractory samples by synergizing oncolytic virus with other anticancer chemicals. We predict that this treatment strategy will be a promising tool to combat cancer in the future.
How temporal patterns in rainfall determine the geomorphology and carbon fluxes of tropical peatlands
Authors: Cobb Alexander R. , Hoyt Alison M. , Gandois Laure , Eri Jangarun , Dommain René , Abu Salim Kamariah , Kai Fuu Ming , Haji Su’ut Nur Salihah , Harvey Charles F.
Published: June 2017

Significance

A dataset from one of the last protected tropical peat swamps in Southeast Asia reveals how fluctuations in rainfall on yearly and shorter timescales affect the growth and subsidence of tropical peatlands over thousands of years. The pattern of rainfall and the permeability of the peat together determine a particular curvature of the peat surface that defines the amount of naturally sequestered carbon stored in the peatland over time. This principle can be used to calculate the long-term carbon dioxide emissions driven by changes in climate and tropical peatland drainage. The results suggest that greater seasonality projected by climate models could lead to carbon dioxide emissions, instead of sequestration, from otherwise undisturbed peat swamps.
Functional proteogenomics reveals biomarkers and therapeutic targets in lymphomas
Authors: Rolland Delphine C. M. , Basrur Venkatesha , Jeon Yoon-Kyung , McNeil-Schwalm Carla , Fermin Damian , Conlon Kevin P. , Zhou Yeqiao , Ng Samuel Y. , Tsou Chih-Chiang , Brown Noah A. , Thomas Dafydd G. , Bailey Nathanael G. , Omenn Gilbert S. , Nesvizhskii Alexey I. , Root David E. , Weinstock David M. , Faryabi Robert B. , Lim Megan S. , Elenitoba-Johnson Kojo S. J.
Published: June 2017

Significance

An important goal in precision oncology is the identification of biomarkers and therapeutic targets. We identified and annotated a compendium of N-glycoproteins from diverse human lymphoid neoplasia, an attractive class of proteins with potential to serve as cancer biomarkers and therapeutic targets. In anaplastic lymphoma kinase-positive (ALK
+
) anaplastic large cell lymphoma (ALCL), integration of N-glycoproteomics and transcriptome sequencing revealed an underappreciated and targetable ALK-regulated cytokine/receptor signaling network highlighting the utility of functional proteogenomics for discovery of cancer biomarkers and therapeutic targets.
Subsurface oxide plays a critical role in CO
2
activation by Cu(111) surfaces to form chemisorbed CO
2
, the first step in reduction of CO
2
Authors: Favaro Marco , Xiao Hai , Cheng Tao , Goddard William A. , Yano Junko , Crumlin Ethan J.
Published: June 2017

Significance

Combining ambient pressure X-ray photoelectron spectroscopy experiments and quantum mechanical density functional theory calculations, this work reveals the essential first step for activating CO
2
on a Cu surface, in particular, highlighting the importance of copper suboxide and the critical role of water. These findings provide the quintessential information needed to guide the future design of improved catalysts.
Vector development and vitellogenin determine the transovarial transmission of begomoviruses
Authors: Wei Jing , He Ya-Zhou , Guo Qi , Guo Tao , Liu Yin-Quan , Zhou Xue-Ping , Liu Shu-Sheng , Wang Xiao-Wei
Published: June 2017

Significance

The majority of plant viruses are transmitted by insect vectors. Transovarial transmission of virus from female vectors to offspring can be very important in maintaining a source of infection and therefore has great epidemiological relevance. Identification of vector and virus components involved in transovarial transmission can lead to new strategies to combat virus spread. Here, we found that the specific interaction between viral coat protein and vector vitellogenin determines transovarial transmissibility of begomoviruses, which have caused great damage to agricultural production and are generally believed not to be transovarially transmitted by insect vectors. Our study gives valuable clues for designing strategies to block begomovirus transmission and provides insights into the evolution and global spread of begomoviruses.
Crystal structures and atomic model of NADPH oxidase
Authors: Magnani Francesca , Nenci Simone , Millana Fananas Elisa , Ceccon Marta , Romero Elvira , Fraaije Marco W. , Mattevi Andrea
Published: June 2017

Significance

Reactive oxygen species (ROS) are far from being only an inevitable byproduct of respiration. They are instead actively generated by NADPH oxidases (NOXs), a family of highly regulated enzymes that underpin complex functions in the control of cell proliferation and antibacterial defense. By investigating the individual catalytic domains, we elucidate the core of the NOX 3D structure. An array of cofactors is spatially organized to transfer reducing electrons from the intracellular milieu to the ROS-generating site, exposed to the outer side of the cell membrane. This redox chain is finely tuned by structural elements that cooperate to control NADPH binding, thereby preventing noxious spills of ROS. Our findings indicate avenues for the pharmacological manipulation of NOX activity.
Dynamics of avian haemosporidian assemblages through millennial time scales inferred from insular biotas of the West Indies
Authors: Soares Leticia , Latta Steven C. , Ricklefs Robert E.
Published: June 2017

Significance

To study long-term changes in ecological assemblages in the absence of a fossil record, we take advantage of the joining and separation of islands on shallow banks in the West Indies archipelago caused by glacial-cycle sea-level changes. We compare pairs of assemblages of avian malaria parasites on islands that were connected during periods of low sea levels and subsequently isolated about 2.5 ka with assemblages on islands that were never connected, as well as assemblages sampled over local scales of time and space on a single island. This approach reveals millennial-scale change in the prevalence of parasite lineages followed by lineage replacement over longer periods, providing unique access to long-term change.
Gel-forming mucins form distinct morphologic structures in airways
Authors: Ostedgaard Lynda S. , Moninger Thomas O. , McMenimen James D. , Sawin Nicholas M. , Parker Connor P. , Thornell Ian M. , Powers Linda S. , Gansemer Nicholas D. , Bouzek Drake C. , Cook Daniel P. , Meyerholz David K. , Abou Alaiwa Mahmoud H. , Stoltz David A. , Welsh Michael J.
Published: June 2017

Significance

Mucus propelled by cilia is key for removing particulates from lungs by mucociliary transport. The major structural components of airway mucus are two gel-forming mucins, MUC5B and MUC5AC. These mucins exhibit distinct morphologic structures. MUC5B is secreted by submucosal glands in the form of strands. MUC5AC is secreted by goblet cells as threads and thin sheets. After emerging onto the airway surface, the two mucins associate to form MUC5B strands partially covered with MUC5AC. These distinct morphologic structures likely enable efficient mucociliary transport. In cystic fibrosis, strands become entangled, MUC5B often fills submucosal gland ducts, and MUC5AC sheets are larger, are more abundant, and overlie strands. Disrupted anion secretion in cystic fibrosis alters mucin morphology, which will impair mucociliary transport.
Mouse model of hematogenous implant-related
Staphylococcus aureus
biofilm infection reveals therapeutic targets
Authors: Wang Yu , Cheng Lily I. , Helfer David R. , Ashbaugh Alyssa G. , Miller Robert J. , Tzomides Alexander J. , Thompson John M. , Ortines Roger V. , Tsai Andrew S. , Liu Haiyun , Dillen Carly A. , Archer Nathan K. , Cohen Taylor S. , Tkaczyk Christine , Stover C. Kendall , Sellman Bret R. , Miller Lloyd S.
Published: June 2017

Significance

Hematogenous implant-related infections are an important clinical problem because bacteria spread from the bloodstream to a previously well-functioning implant and result in infectious complications and failure of a medical device or prosthesis. To study these infections, we developed a preclinical animal model of a
Staphylococcus aureus
hematogenous implant infection with the capability to monitor noninvasively and longitudinally the dissemination of the bacteria from the blood to a surgically placed orthopedic implant. Using this model, α-toxin and clumping factor A were identified as key factors that contributed to the pathogenesis of these infections by promoting biofilm formation. Finally, neutralizing antibodies against these factors provided a targeted, nonantibiotic alternative approach to help prevent these difficult-to-treat and costly infections.
Age of Jupiter inferred from the distinct genetics and formation times of meteorites
Authors: Kruijer Thomas S. , Burkhardt Christoph , Budde Gerrit , Kleine Thorsten
Published: June 2017

Significance

Jupiter is the most massive planet of the Solar System and its presence had an immense effect on the dynamics of the solar accretion disk. Knowing the age of Jupiter, therefore, is key for understanding how the Solar System evolved toward its present-day architecture. However, although models predict that Jupiter formed relatively early, until now, its formation has never been dated. Here we show through isotope analyses of meteorites that Jupiter’s solid core formed within only ∼1 My after the start of Solar System history, making it the oldest planet. Through its rapid formation, Jupiter acted as an effective barrier against inward transport of material across the disk, potentially explaining why our Solar System lacks any super-Earths.
Numbers of presynaptic Ca
2+
channel clusters match those of functionally defined vesicular docking sites in single central synapses
Authors: Miki Takafumi , Kaufmann Walter A. , Malagon Gerardo , Gomez Laura , Tabuchi Katsuhiko , Watanabe Masahiko , Shigemoto Ryuichi , Marty Alain
Published: June 2017

Significance

Release–docking sites have been considered from a morphological point of view as the sites where synaptic vesicles dock and fuse with the active-zone membrane. Functionally, docking sites limit the maximum number of vesicles released per action potential, determining synaptic strength. Until now it has not been possible to establish a clear link between morphological and functional aspects of docking sites in mammalian brain synapses. Recent data suggest that calcium channels form several clusters in the active zone. Here, we show that the number of the clusters matches that of functional docking sites and both parameters change in parallel with age and synaptic size. Based on these results we propose a one-to-one correspondence between docking sites and calcium channel clusters.
Efficient, ultra-high-affinity chromatography in a one-step purification of complex proteins
Authors: Vassylyeva Marina N. , Klyuyev Sergiy , Vassylyev Alexey D. , Wesson Hunter , Zhang Zhuo , Renfrow Matthew B. , Wang Hengbin , Higgins N. Patrick , Chow Louise T. , Vassylyev Dmitry G.
Published: June 2017

Significance

Protein purification is a primary step and the basis for numerous biochemical and biomedical studies. It is particularly crucial for high-resolution structural analysis and industrial protein production, where it has to meet the high-yield, high-purity, and high-activity (HHH) requirement. However, the HHH purification of many proteins or protein complexes remains a difficult, target-dependent, and multistep process. The ultra-high-affinity (CL7/Im7) purification system described in this work allows for one-step HHH purification of a wide range of traditionally challenging biological molecules, including eukaryotic, membrane, toxic, and DNA/RNA-binding proteins and complexes. It might emerge as an efficient, universal tool for high-throughput isolation of many significant biological systems to advance modern biological studies as well as manufacturing of therapeutic proteins.
Human genome-wide repair map of DNA damage caused by the cigarette smoke carcinogen benzo[a]pyrene
Authors: Li Wentao , Hu Jinchuan , Adebali Ogun , Adar Sheera , Yang Yanyan , Chiou Yi-Ying , Sancar Aziz
Published: June 2017

Significance

Benzo[a]pyrene (BaP) is a widespread potent carcinogen found in food, coal tar, cigarette smoke, and industrial smoke. Cigarette smoking is the leading cause of lung cancer, and the mutagenesis in smoking-associated lung cancer is determined by multiple factors, including nucleotide excision repair. We have developed a general method for genome-wide mapping of nucleotide excision repair at single-nucleotide resolution and applied it to generate repair maps of UV- and BaP-induced DNA damage in human. Results show a novel sequence specificity of BaP diol epoxide-deoxyguanosine repair. This general method can be used to study repair of all types of DNA damages that undergo nucleotide excision repair.
Intraoperative assessment of tumor margins during glioma resection by desorption electrospray ionization-mass spectrometry
Authors: Pirro Valentina , Alfaro Clint M. , Jarmusch Alan K. , Hattab Eyas M. , Cohen-Gadol Aaron A. , Cooks R. Graham
Published: June 2017

Significance

Gliomas infiltrate into surrounding healthy brain tissue. Microsurgical resection aims for maximal tumor resection while minimizing morbidity. Surgical margins are defined based on the surgeon’s experience, visual observation, and neuronavigation. Surgical margin assessment is rarely undertaken intraoperatively due to time constraints and unreliability of such evaluation. Routine, pathologic intraoperative examination provides no molecular information. Molecular measurements using mass spectrometry can be made rapidly on tissue during surgery to identify tissue types, estimate tumor infiltration, and recognize the presence of prognostic mutations by monitoring oncometabolites and phospholipids. This intraoperative study demonstrates the power of mass spectrometry in assessing diagnostic and prognostic information on discrete surgeon-defined points along the resection margins to improve tumor resection, even in regions without MRI contrast enhancement.
The superplasticity and microstructure evolution of coarse-grained Ti40 alloy
Authors: Zhang Xuemin , Zeng Weidong , Li Yue , Jiao Benqi , Yuan Zhanwei , Chen Yongnan , Sun Zhiping
Published: June 2017

The superplastic deformation characteristics of coarse-grained Ti40 alloy have been studied in the temperature and strain rate range of 760–880°C and 5 × 10−4 to 1 × 10−2 s−1, respectively. The alloy exhibited good superplasticity in all test conditions except at 760°C and strain rate higher than 5 × 10−3 s−1, with the maximum elongation of 436% at 840°C, 1 × 10−3 s−1. The activation energy value was found to be close to the self-diffusion activation energy of Ti40 alloy, suggesting that the rate controlling mechanism was lattice diffusion. The coarse grain was elongated and refined which can be attributed to the occurrence of dynamic recovery and continuous dynamic recrystallisation. These processes were promoted by the subgrain formation and evolution, resulting in the good superplasticity of Ti40 alloy with coarse grains.
Effects of initial undercooling on microstructure formation and recrystallisation of undercooled melts
Authors: Xu Xiao Long , Hou Hua , Liu Feng
Published: June 2017

The critical undercoolings for the two grain refinement events and the onset of recrystallisation event are determined by detailed analysis of the microstructure evolution of bulk undercooled Ni–20 at.-%Cu alloy melts. The first grain refinement event occurred in the low undercooling range was explained by dendrite remelting. The second grain refinement event occurred in the high undercooling range was due to the combined effects of dendrite remelting stress-induced dendrite breakup during recalescence and recrystallisation during the near-equilibrium solidification stage after recalescence. The micro-stress induced by the solidification contraction during recalescence in the so called ‘first mushy zone’ would lead to distortion and breakup of primary dendrites. The stress-induced broken-up dendrites have sufficient driving force for recrystallisation.
WSF-P-1, a novel AMPK activator, promotes adiponectin multimerization in 3T3-L1 adipocytes
Authors: Wang Yao , Zhang Yudian , Wang Yunyun , Peng Han , Rui Jian , Zhang Zhijie , Wang Shifa , Li Zhen
Published: June 2017

Adiponectin, an adipokine with insulin-sensitizing effect, is secreted from adipocytes into circulation as high, medium, and low molecular weight forms (HMW, MMW, and LMW). The HMW adiponectin oligomers possess the most potent insulin-sensitizing activity. WSF-P-1(N-methyl-1,2,3,4,5,6-hexahydro-1,1,5,5-tetramethyl-7H-2,4α-methanonaphthalen-7-amine) is derived from natural sesquiterpene longifolene by chemical modifications. We found that WSF-P-1 activates AMPK in both 3T3-L1 adipocytes and 293T cells in this study. Activation of AMPK by WSF-P-1 promotes the assembly of HMW adiponectin and increases the HMW/total ratio of adiponectin in 3T3-L1 adipocytes. We demonstrated that the Ca2+-dependent CaMKK signaling pathway is involved in WSF-P-1-induced AMPK activation and adiponectin multimerization. WSF-P-1 also activates GLUT1-mediated glucose uptake in 3T3-L1 adipocytes, making it a potential drug candidate for the treatment of type 2 diabetes, obesity, and other obesity-related metabolic diseases.
Metoprolol Increases Uric Acid and Risk of Gout in African Americans With Chronic Kidney Disease Attributed to Hypertension
Authors: Juraschek Stephen P , Appel Lawrence J , Miller Edgar R
Published: June 2017

BACKGROUND

There is little evidence guiding selection of nondiuretic, antihypertensive agents with a goal of lowering uric acid (SUA) and minimizing gout risk.

METHODS

In the African American Study of Kidney Disease and Hypertension (AASK) trial, African Americans with chronic kidney disease were randomly assigned to metoprolol (a beta-blocker), ramipril (an angiotensin-converting enzyme inhibitors [ACEi]), or amlodipine (a dihydropyridine calcium-channel blocker). SUA was measured at baseline and 12 months. Gout-related hospitalizations were based on ICD9 codes. Gout-related medication use (GRMs) was based on active prescriptions of allopurinol, colchicine, or probenecid during the baseline visit of the AASK cohort phase. We examined the effect of drug assignment on 12-month SUA (linear regression), gout-related hospitalization (Cox regression), and GRM (logistic regression).

RESULTS

Of the 630 participants, 40% were female with a mean age of 55 years (SD, 10), mean SUA of 8.2 mg/dl (2.0), and mean serum creatinine of 1.8 mg/dl (0.6). After 12 months, metoprolol increased SUA by 0.3 mg/dl, while ramipril or amlodipine had no effect on SUA. Compared to ramipril, metoprolol significantly increased 12-month SUA (0.40; 0.10, 0.70 mg/dl; P = 0.009), nonsignificantly increased risk of gout-related hospitalization (hazard ratio: 3.87; 0.82, 18.26; P = 0.09), and significantly increased the odds of GRM (odds ratio: 1.62; 1.03, 2.54; P = 0.04). While metoprolol was associated with a higher 12-month SUA compared with amlodipine (0.57; 0.18, 0.95; P = 0.004), there was no difference in gout-related hospitalizations or GRM.

CONCLUSIONS

Metoprolol increased SUA and GRM in African American adults. Health professionals treating patients with kidney disease at risk for gout should avoid metoprolol and possibly consider an ACEi.

CLINICAL TRIALS REGISTRATION

Trial Number NCT00582777.
StereoGene: rapid estimation of genome-wide correlation of continuous or interval feature data
Authors: Stavrovskaya Elena D , Niranjan Tejasvi , Fertig Elana J , Wheelan Sarah J , Favorov Alexander V , Mironov Andrey A
Published: June 2017

Motivation

Genomics features with similar genome-wide distributions are generally hypothesized to be functionally related, for example, colocalization of histones and transcription start sites indicate chromatin regulation of transcription factor activity. Therefore, statistical algorithms to perform spatial, genome-wide correlation among genomic features are required.

Results

Here, we propose a method, StereoGene, that rapidly estimates genome-wide correlation among pairs of genomic features. These features may represent high-throughput data mapped to reference genome or sets of genomic annotations in that reference genome. StereoGene enables correlation of continuous data directly, avoiding the data binarization and subsequent data loss. Correlations are computed among neighboring genomic positions using kernel correlation. Representing the correlation as a function of the genome position, StereoGene outputs the local correlation track as part of the analysis. StereoGene also accounts for confounders such as input DNA by partial correlation. We apply our method to numerous comparisons of ChIP-Seq datasets from the Human Epigenome Atlas and FANTOM CAGE to demonstrate its wide applicability. We observe the changes in the correlation between epigenomic features across developmental trajectories of several tissue types consistent with known biology and find a novel spatial correlation of CAGE clusters with donor splice sites and with poly(A) sites. These analyses provide examples for the broad applicability of StereoGene for regulatory genomics.

Availability and implementation

The StereoGene C ++ source code, program documentation, Galaxy integration scripts and examples are available from the project homepage http://stereogene.bioinf.fbb.msu.ru/

Supplementary information

Supplementary data are available at Bioinformatics online.
PhylOligo: a package to identify contaminant or untargeted organism sequences in genome assemblies
Authors: Mallet Ludovic , Bitard-Feildel Tristan , Cerutti Franck , Chiapello Hélène
Published: June 2017

Motivation

Genome sequencing projects sometimes uncover more organisms than expected, especially for complex and/or non-model organisms. It is therefore useful to develop software to identify mix of organisms from genome sequence assemblies.

Results

Here we present PhylOligo, a new package including tools to explore, identify and extract organism-specific sequences in a genome assembly using the analysis of their DNA compositional characteristics.

Availability and implementation

The tools are written in Python3 and R under the GPLv3 Licence and can be found at https://github.com/itsmeludo/Phyloligo/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Generating prosperity, creating crisis: impacts of resource development on diverse groups in northern communities
Authors: Stienstra Deborah , Manning Susan M , Levac Leah , Baikie Gail
Published: June 2017

Northern Canada illustrates the contradictory dynamics in resource development – at once generating prosperity and inclusion within some communities and for some people, and creating or perpetuating crisis in some communities and exclusion for some people. Existing literature related to resource extraction and development focuses on the impacts on the environment and government regulatory mechanisms. Few authors or policy makers pay attention to how multiple and diverse groups within communities are affected by resource development. Building from research in a community-university research alliance, the authors argue that these competing dynamics are initiated and sustained through resource development projects and have disproportionate effects on historically marginalized groups within northern communities. This article presents the results of a comprehensive scoping review of the literature related to the social and economic impacts of resource extraction in Northern Canada. Some of the impacts of resource extraction clearly generate prosperity, while others can move communities towards crises and some do both. Using intersectionality, we argue that policy makers, especially those responsible for community development and regulating resource development projects, require a multilayered analysis to understand and redress the unequal effects of resource development on northern communities.
Loneliness, Social Integration, and Incident Dementia Over 6 Years: Prospective Findings From the English Longitudinal Study of Ageing
Authors: Rafnsson Snorri Bjorn , Orrell Martin , d’Orsi Eleonora , Hogervorst Eef , Steptoe Andrew
Published: June 2017

Objectives

Social relationships are important for the maintenance of cognitive function at older ages, with both objective features of social networks and perceived social connections (loneliness) being relevant. There is limited evidence about how different aspects of social experience predict diagnosed dementia.

Methods

The sample comprised 6,677 dementia-free individuals at baseline (2004) from the English Longitudinal Study of Ageing. Baseline information on loneliness, number of close relationships, marital status, and social isolation (contact with family and friends and participation in organizations) was analyzed in relation to incident dementia over an average 6.25 years using Cox regression, controlling for potential confounding factors.

Results

Two hundred twenty participants developed dementia during follow-up. In multivariable analyses, dementia risk was positively related to greater loneliness (hazard ratio 1.40, 95% confidence interval 1.09–1.80, p = .008), and inversely associated with number of close relationships (p < .001) and being married (p = .018). Sensitivity analyses testing for reverse causality and different criteria for diagnosing dementia confirmed the robustness of these findings. There was no association with social isolation.

Discussion

Dementia risk is associated with loneliness and having fewer close relationships in later life. The underlying mechanisms remain to be elucidated, but efforts to enhance older peoples’ relationship quality may be relevant to dementia risk.
Hepatitis E Virus–Associated Meningoencephalitis in a Lung Transplant Recipient Diagnosed by Clinical Metagenomic Sequencing
Authors: Murkey Jamie A. , Chew Kara W. , Carlson Margrit , Shannon Chelsea L. , Sirohi Deepika , Sample Hannah A. , Wilson Michael R. , Vespa Paul , Humphries Romney M. , Miller Steve , Klausner Jeffrey D. , Chiu Charles Y.
Published: June 2017

Hepatitis E virus (HEV) infection uncommonly causes chronic hepatitis and neurologic disease. We describe a case of genotype 3a HEV meningoencephalitis diagnosed by metagenomic next-generation sequencing, illustrating the power of an unbiased molecular approach to microbial testing and the first reported case of HEV infection presumably acquired through lung transplantation.
The Potyvirus Particle Recruits the Plant Translation Initiation Factor eIF4E by Means of the VPg covalently Linked to the Viral RNA
Authors: Tavert-Roudet Geneviève , Anne Agnès , Barra Amandine , Chovin Arnaud , Demaille Christophe , Michon Thierry
Published: June 2017

The viral protein genome-linked (VPg) of potyviruses is a protein covalently linked to the 5′ end of viral RNA. It interacts with eIF4E, a component of the cellular translation initiation complex. It has been suggested that the 5′ RNA-linked VPg could mimic the cellular mRNA cap, promoting synthesis of viral proteins. Here, we report evidence for recruitment of the plant eIF4E by Lettuce mosaic virus (LMV, potyvirus) particles via the 5′ RNA-linked VPg. Analysis of the viral population was performed by enzyme-linked immunosorbent assay–based tests, either with crude extracts of LMV-infected tissues or purified viral particles. In both cases, LMV-VPg and LMV-eIF4E subpopulations could be detected. After reaching a maximum within the first 2 weeks postinoculation, these populations decreased and very few labeled particles were found later than 3 weeks postinoculation. The central domain of VPg (CD-VPg) was found to be exposed at the surface of the particles. Using a purified recombinant lettuce eIF4E and CD-VPg–specific antibodies, we demonstrate that the plant factor binds to the VPg via its central domain. Moreover, the plant eIF4E factor could be imaged at one end of the particles purified from LMV plant extracts, by immunoredox atomic force microscopy coupled to scanning electrochemical microscopy. We discuss the biological significance of these results.
Signaling Mechanisms Underlying Resistance Responses: What Have We Learned, and How Is It Being Applied?
Authors: Kachroo Aardra , Vincelli Paul , Kachroo Pradeep
Published: June 2017

Plants have evolved highly specific mechanisms to resist pathogens including preformed barriers and the induction of elaborate signaling pathways. Induced signaling requires recognition of the pathogen either via conserved pathogen-derived factors or specific pathogen-encoded proteins called effectors. Recognition of these factors by host encoded receptor proteins can result in the elicitation of different tiers of resistance at the site of pathogen infection. In addition, plants induce a type of systemic immunity which is effective at the whole plant level and protects against a broad spectrum of pathogens. Advances in our understanding of pathogen-recognition mechanisms, identification of the underlying molecular components, and their significant conservation across diverse plant species has enabled the development of novel strategies to combat plant diseases. This review discusses key advances in plant defense signaling that have been adapted or have the potential to be adapted for plant protection against microbial diseases.
Evaluation of a Clinical Protocol to Assess and Diagnose Neuropathic Pain During Acute Hospital Admission
Authors: Bélanger Lise M.A. , Umedaly Hamed S. , Noonan Vanessa K. , Park So Eyun , Prince Jennifer , Thorogood Nancy P. , Shen Tian , Townson Andrea F. , Street John T. , Dvorak Marcel F. , Negraeff Michael
Published: June 2017

Objectives:

A clinical protocol was developed for clinicians to routinely assess and initiate treatment for patients with neuropathic pain (NP) in an acute care setting. The objectives of this study were to: (1) determine the incidence and onset of NP in patients with traumatic spinal cord injury during acute care and (2) describe how the implementation of a clinical protocol impacts the assessment and diagnosis of NP.

Materials and Methods:

The study was a cohort analysis with a pre-post-test utilizing a historical control. Data were retrospectively collected from a patient registry and charts. Participants were randomly selected in cohort 1 (control) and cohort 2 (NP clinical protocol).

Results:

The incidence of NP was 56% without significant difference between the cohorts (P=0.3). Onset of NP was 8 days (SD=14) across the study and >85% of the participants with NP were diagnosed within 2 weeks. Participants with incomplete injuries had a significant earlier onset than participants with complete injuries (6.2±12.8, 10.9±15.8 d; P=0.003). The mean number of days from hospital admission to initial assessment decreased with use of the NP clinical protocol (3.7±5.7 d; P=0.02).

Discussion:

This study demonstrates a high incidence and early onset of NP in traumatic spinal cord injury during acute hospital care, with an earlier emergence in participants with incomplete injury. The NP clinical protocol ensured continuous assessment and documentation of NP while decreasing the time to an initial screen, but did not impact diagnosis.
OTA/AO Classification Is Highly Predictive of Acute Compartment Syndrome After Tibia Fracture: A Cohort of 2885 Fractures
Authors: Beebe Michael J. , Auston Darryl A. , Quade Jonathan H. , Serrano-Riera Rafael , Shah Anjan R. , Watson David T. , Sanders Roy W. , Mir Hassan R.
Published: June 2017

Objective:

To determine the correlation between the OTA/AO classification of tibia fractures and the development of acute compartment syndrome (ACS).

Design:

Retrospective review of prospectively collected database.

Setting:

Single Level 1 academic trauma center.

Patients:

All patients with a tibia fracture from 2006 to 2016 were reviewed for this study. Three thousand six hundred six fractures were initially identified. Skeletally mature patients with plate or intramedullary fixation managed from initial injury through definitive fixation at our institution were included, leaving 2885 fractures in 2778 patients.

Methods:

After database and chart review, univariate analyses were conducted using independent t tests for continuous data and χ2 tests of independence for categorical data. A simultaneous multivariate binary logistic regression was developed to identify variables significantly associated with ACS.

Results:

ACS occurred in 136 limbs (4.7%). The average age was 36.2 years versus 43.3 years in those without (P < 0.001). Men were 1.7 times more likely to progress to ACS than women (P = 0.012). Patients who underwent external fixation were 1.9 times more likely to develop ACS (P = 0.003). OTA/AO 43 injuries were at least 4.0 times less likely to foster ACS versus OTA/AO 41 or 42 injuries (P < 0.007). OTA/AO 41-C injuries were 5.5 times more likely to advance to ACS compared with OTA/AO 41-A (P = 0.03). There was a significantly higher rate of ACS in OTA/AO 42-B (P = 0.005) and OTA/AO 42-C (P = 0.002) fractures when compared with OTA/AO 42-A fractures. In the distal segment, fracture type did not predict the risk of ACS (P > 0.15). Group 1 fractures had a lower rate of ACS compared with group 2 (P = 0.03) and group 3 (P = 0.003) fractures in the middle segment only. Bilateral tibia fractures had a 2.7 times lower rate of ACS (P = 0.04). Open injury, multiple segment injury, fixation type, and concurrent pelvic or femoral fractures did not predict ACS.

Conclusions:

In this large cohort of tibia fractures, we found that the age, sex, and OTA/AO classification were highly predictive for the development of ACS.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Arthroscopic Reconstruction of the Anterior Inferior Tibiofibular Ligament for Chronic Disruption of the Distal Tibiofibular Syndesmosis: Technical Note
Authors: Yoo Jae-Sung , Yang Eun-Ah
Published: June 2017

The distal tibiofibular syndesmosis provides stability to the ankle mortise, and it is composed of the anterior inferior tibiofibular, posterior inferior tibiofibular, interosseous, and inferior transverse tibiofibular ligaments and the interosseous membrane. During external rotation of the foot the fibula is translated posteriorly and rotated externally, which results in a high tension of the anterior inferior tibiofibular ligament. This may attribute to the isolated rupture of the anterior inferior tibiofibular ligament. Rupture of the anterior inferior tibiofibular ligament, in its turn, causes instability of the ankle mortise. Reconstructive options for chronic syndesmosis disruption include arthroscopic debridement and screw fixation, arthrodesis of the syndesmosis, advancement of the anterior tibiofibular ligament, reconstruction of the interosseous and anterior inferior tibiofibular ligament. We describe an arthroscopic technique of anatomic reconstruction of the anterior inferior tibiofibular ligaments with tibialis allograft and biodegradable syndesmotic screw fixation.
Wrist Arthrodesis With Femoral Head Structural Allograft After Failed Total Wrist Arthroplasty
Authors: Grandizio Louis C. , Maschke Steven
Published: June 2017

The failed total wrist arthroplasty represents a challenging reconstructive problem for the upper extremity surgeon. Bone loss, poor bone quality, and soft tissue defects all present technical challenges when considering revision procedures. Our purpose is to describe a technique for wrist arthrodesis after failed total wrist arthroplasty utilizing fresh-frozen femoral head allograft and dorsal plate fixation. We describe a simple method of allograft preparation for this procedure, as graft preparation and implantation can be time consuming and technically challenging.
Superior Capsule Reconstruction for Irreparable Rotator Cuff Tears: A Novel Technique Using Mulberry Knots
Authors: Stone Michael A. , Namdari Surena , Omid Reza
Published: June 2017

Irreparable rotator cuff tears are a challenging treatment dilemma for the orthopedic surgeon. Superior capsule reconstruction (SCR) using acellular dermal allograft has grown in popularity, and a number of techniques have recently been described, including mini-open and all-arthroscopic. Although there are no current long-term studies evaluating outcomes using acellular dermal graft, biomechanical studies indicate that clinical application could result in reliable restoration of function. There is currently no standardized technique for graft passage for SCR. The technique described in this article presents a novel technique for the passage of the acellular dermal graft using Mulberry knots for SCR.
Surgery for patients with newly diagnosed advanced ovarian cancer: which patient, when and extent?
Authors: Eggink Florine A. , Koopmans Corine M. , Nijman Hans W.
Published: June 2017

Purpose of review

Cytoreduction to no residual disease is the mainstay of primary treatment for advanced epithelial ovarian cancer (AdvEOC). This review addresses recent insights on optimal patient selection, timing, and extent of surgery, intended to optimize cytoreduction in patients with AdvEOC.

Recent findings

Clinical guidelines recommend primary cytoreductive surgery (PCS) for AdvEOC patients with a high likelihood of achieving complete cytoreduction with acceptable morbidity. In line with this, preoperative prediction markers such as cancer antigen-125, histologic and genomic factors, innovative imaging modalities, and the performance of a diagnostic laparoscopy have been suggested to improve clinical decision-making with regard to optimal timing of cytoreductive surgery. To determine whether these strategies should be incorporated into clinical practice validation in randomized clinical trials is essential.

The past decade has seen a paradigm shift in the number of AvdEOC patients that are being treated with upfront neoadjuvant chemotherapy instead of PCS. However, although neoadjuvant chemotherapy may reduce morbidity at the time of interval cytoreductive surgery, no favorable impact on survival has been demonstrated and it may induce resistance to chemotherapy. Therefore, optimizing patient selection for PCS is crucial. Furthermore, surgical innovations in patients diagnosed with AvdEOC should focus on improving survival outcomes.