bluuebunny/crossref_metadata_2025 huggingface dataset:
Bird assemblage vulnerability depends on the diversity and biogeographic histories of islands
Authors: Weeks Brian C. , Gregory Nichar , Naeem Shahid
Published: August 2016

Significance

Biodiversity is broadly thought to be positively associated with a wide array of ecosystem functions and properties. Because these properties may reduce extinction risk, for example, by making functioning more stable and ecosystems less prone to invasion, biodiverse islands have the potential to accumulate species over evolutionary time that are more vulnerable to extinction. We find that bird diversity is positively related to the collective vulnerability of species in a set of assemblages. This relationship is highly contingent on biogeographic history, a factor often overlooked in biodiversity and ecosystem-functioning studies. Our findings expose a paradox: biodiverse systems, as more robust systems, may experience greater biodiversity loss over ecological time because they accumulate more vulnerable species over evolutionary time.
Emergence of ion channel modal gating from independent subunit kinetics
Authors: Bicknell Brendan A. , Goodhill Geoffrey J.
Published: August 2016

Significance

Many key features of the behavior of cells are controlled by ion channels—pores in cell membranes that are sometimes open and sometimes closed. It is therefore critically important to understand what controls these opening and closing events. This is challenging because ion channels exhibit stochastic dynamics over several timescales, from the rapid kinetics of a single opening to the slow switching between distinct levels of activity known as modal gating. By mathematically modeling the basic biophysical events that control ion channel opening, we introduce a new principle for understanding the origin of modal gating. Although we focus on the inositol 1,4,5-trisphosphate receptor channel, the framework can be applied more generally to other ion channels.
Bioelectric impact of pathological angiogenesis on vascular function
Authors: Puro Donald G. , Kohmoto Ryohsuke , Fujita Yasushi , Gardner Thomas W. , Padovani-Claudio Dolly A.
Published: August 2016

Significance

Angiogenesis is essential for the health of all vertebrates, but the outgrowth of new blood vessels also plays a role in disease by facilitating tumorigenesis, boosting inflammation, and causing blindness. Despite intensive investigation, pathological angiogenesis remains a formidable clinical challenge. Here we adopted an experimental strategy focusing on the bioelectric impact of neovascularization. Surprisingly, although the transmembrane voltage of vascular cells is known to regulate blood flow, no previous electrophysiological analysis of pathological angiogenesis has been reported. Using animal models and human specimens of retinal neovascularization, we discovered that neovascular complexes generate an extremely high voltage, whose transmission into the retinovascular network exerts a function-altering impact. Uncovering bioelectric mechanisms in the pathogenesis of neovascularization is likely to reveal new therapeutic targets.
Autophagy and ubiquitin–proteasome system contribute to sperm mitophagy after mammalian fertilization
Authors: Song Won-Hee , Yi Young-Joo , Sutovsky Miriam , Meyers Stuart , Sutovsky Peter
Published: August 2016

Significance

Maternal inheritance of mitochondria and mitochondrial genes is a major developmental paradigm in mammals. Propagation of paternal, sperm-contributed mitochondrial genes, resulting in heteroplasmy, is seldom observed in mammals, due to postfertilization targeting and degradation of sperm mitochondria, referred to as “sperm mitophagy.” Our and others’ recent results suggest that postfertilization sperm mitophagy is mediated by the ubiquitin–proteasome system, the major protein-turnover pathway that degrades proteins and the autophagic pathway. Here we demonstrate that the co-inhibition of the ubiquitin-binding autophagy receptors, sequestosome 1 (SQSTM1) and gamma-aminobutyric acid receptor-associated protein (GABARAP), and the ubiquitinated protein dislocase valosin-containing protein (VCP)-dependent pathways delayed postfertilization sperm mitophagy. Our findings provide the mechanisms guiding sperm mitochondrion recognition and disposal during preimplantation embryo development, which prevents a potentially detrimental effect of heteroplasmy.
Changes in active site histidine hydrogen bonding trigger cryptochrome activation
Authors: Ganguly Abir , Manahan Craig C. , Top Deniz , Yee Estella F. , Lin Changfan , Young Michael W. , Thiel Walter , Crane Brian R.
Published: August 2016

Significance

There are few detailed mechanistic models that describe how light-sensing proteins convert photochemistry into conformational signals. Combined computational and experimental investigations reveal how photoreduction of the
Drosophila
cryptochrome (dCRY) flavin induces protonation of a neighboring conserved His residue. Altered His hydrogen bonding then leads to conformational change in a key regulatory element of the protein. These data provide further evidence for involvement of a flavin anionic semiquinone in the dCRY signaling state and allow for the design of variants that can be used to separate dCRY biological functions or as tools for optogenetics.
Biophysical insight into mechanisms of sonoporation
Authors: Helfield Brandon , Chen Xucai , Watkins Simon C. , Villanueva Flordeliza S.
Published: August 2016

Significance

Gas-filled microbubbles physically oscillate in an ultrasound field and have been shown to potentiate the delivery of therapeutic payloads. The biophysical mechanisms by which vibrating microbubbles stimulate macromolecule uptake across the cell membrane, however, remain unknown. With a coupled microscopy system capable of bright-field imaging up to 25 million frames per second, we show correlations between microsecond-scale bubble oscillations and second-to-minute–scale macromolecule diffusion, uniquely highlighting that microbubble-induced shear stress is a threshold indicator for membrane pore generation. Further insight into membrane reorganization using real-time confocal microscopy demonstrates that ultrasound-triggered microbubbles create resealing pores through both layers of cellular membrane, and gaps between confluent cells. This work presents mechanistic, biophysical insight into sonoporation as a tool for local delivery of therapeutic macromolecules.
Structures of the activator of
K. pneumonia
biofilm formation, MrkH, indicates PilZ domains involved in c-di-GMP and DNA binding
Authors: Schumacher Maria A. , Zeng Wenjie
Published: August 2016

Significance

Klebsiella pneumonia
is an important cause of refractory nosocomial infections, the pathogenicity of which is largely a result of the bacteria’s ability to form biofilms on biomedical devices. A 3′,5′-cyclic diguanylic acid (c-di-GMP)–activated transcription activator, MrkH, drives biofilm formation. Here we describe structures of MrkH in its apo- and c-di-GMP–bound states. MrkH consists of two domains, both of which have PilZ-like folds. PilZ domains are known signaling modules, but, to our knowledge, MrkH is the first PilZ-containing protein to function in DNA binding. MrkH shows no homology to any human protein. Hence, our combined data, which uncovered the mechanism of c-di-GMP activation of MrkH, set the stage for the rational development of novel antimicrobial agents that target biofilm formation by
K. pneumonia
.
Precision glycocalyx editing as a strategy for cancer immunotherapy
Authors: Xiao Han , Woods Elliot C. , Vukojicic Petar , Bertozzi Carolyn R.
Published: August 2016

Significance

Successful tumors are able to evade the immune system, which is otherwise capable of killing transformed cells. Therapies that prevent this evasion have become revolutionary treatments for incurable cancers. One mechanism of evasion is the presentation of sugars, called sialic acids, within the cell surface’s sugar coating, or glycocalyx. Here, we designed biotherapeutic molecules, termed “antibody–enzyme conjugates,” that selectively remove sialic acids from tumor cells. The antibody directs the enzyme to the cancer cells, the enzyme cleaves the sugars, and then the antibody directs immune cells to kill the desialylated cancer cells. The conjugate increased tumor cell killing compared with the antibody alone. Editing the cancer cell glycocalyx with an antibody–enzyme conjugate represents a promising approach to cancer immune therapy.
Structural characterization of acyl-CoA oxidases reveals a direct link between pheromone biosynthesis and metabolic state in
Caenorhabditis elegans
Authors: Zhang Xinxing , Li Kunhua , Jones Rachel A. , Bruner Steven D. , Butcher Rebecca A.
Published: August 2016

Significance

In nematodes, acyl-CoA oxidases function not only in primary metabolism, where they participate in the breakdown of long-chain fatty acids, but also in secondary metabolism, where they participate in the biosynthesis of the ascarosides, a family of pheromones that regulate development and behavior. Here, we provide a molecular basis for the diverse substrate specificities of the acyl-CoA oxidases. Unlike their homologs in other organisms, the acyl-CoA oxidases of nematodes bind ATP at the dimer interface, leading to a conformational change that promotes FAD cofactor binding and enzyme activity. Our results suggest a mechanism by which the biosynthesis of most ascarosides is increased under conditions that promote higher cellular ATP concentrations in the worm.
Reassessment of long-term depression in cerebellar Purkinje cells in mice carrying mutated GluA2 C terminus
Authors: Yamaguchi Kazuhiko , Itohara Shigeyoshi , Ito Masao
Published: August 2016

Significance

Long-term depression (LTD), a unique type of synaptic plasticity exhibited by cerebellar Purkinje cells, has been postulated to play a key role in motor learning. This LTD hypothesis of motor learning has been supported by observations of the coincidence of inactivation of LTD by genetic or pharmacological manipulation with the impairment of motor learning. A controversy, however, has recently arisen because of the observation that in certain mutant mice, this coincidence did not occur; motor learning normally proceeded even when LTD was not induced. We reexamined these mutant mice and found that LTD was inducible even in these mutant mice when stimulation conditions were adequately modified. The present observations support the LTD hypothesis of motor learning.
Paradoxical signaling regulates structural plasticity in dendritic spines
Authors: Rangamani Padmini , Levy Michael G. , Khan Shahid , Oster George
Published: August 2016

Significance

The basis for learning and memory formation is in tiny

(

1
−
2

μm) membranous protrusions along short branched extensions (dendrites) of nerve cells (neurons) called dendritic spines. Recently, common themes have begun to emerge in identifying the cellular basis of many conditions associated with learning and memory, mainly through the observation of dynamic changes to the dendritic spine. The ability of the dendritic spine to grow, shrink, and change shape has long been associated with synaptic plasticity, learning, and memory. We develop a mathematical model that couples the biochemical signaling machinery and the actin remodeling events to provide insight into the dynamics of the dendritic spine.
2-Sulfonylpyrimidines: Mild alkylating agents with anticancer activity toward p53-compromised cells
Authors: Bauer Matthias R. , Joerger Andreas C. , Fersht Alan R.
Published: August 2016

Significance

Cancers with mutant p53 often show increased metastasis, genomic instability, and higher chemoresistance. The development of drugs targeting tumors with mutant p53 background is a current strategy for anticancer therapy. We found that certain activated electrophilic 2-sulfonylpyrimidines are a new class of thiol-reactive anticancer agents. These agents are especially effective in killing cancer cells with mutant or inactivated p53 or impaired reactive oxygen species detoxification and have relatively low cytotoxicity toward normal cells; they are mild electrophiles, some of which will, for example, stabilize mutant p53 by selective targeting of its thiol groups and have little general alkylating reactivity.
Semantic representations in the temporal pole predict false memories
Authors: Chadwick Martin J. , Anjum Raeesa S. , Kumaran Dharshan , Schacter Daniel L. , Spiers Hugo J. , Hassabis Demis
Published: August 2016

Significance

False memories can arise in daily life through a mixture of factors, including misinformation and prior conceptual knowledge. This can have serious consequences in settings, such as legal eyewitness testimony, which depend on the accuracy of memory. We investigated the brain basis of false memory with fMRI, and found that patterns of activity in the temporal pole region of the brain can predict false memories. Furthermore, we show that each individual has unique patterns of brain activation that can predict their own idiosyncratic set of false-memory errors. Together, these results suggest that the temporal pole may be responsible for the conceptual component of illusory memories.
Regulatory network analysis reveals novel regulators of seed desiccation tolerance in
Arabidopsis thaliana
Authors: González-Morales Sandra Isabel , Chávez-Montes Ricardo A. , Hayano-Kanashiro Corina , Alejo-Jacuinde Gerardo , Rico-Cambron Thelma Y. , de Folter Stefan , Herrera-Estrella Luis
Published: August 2016

Significance

Seed desiccation tolerance (DT) is one of the most fascinating processes of higher plants, and has played a fundamental role in the evolution of land plants. DT allows plant seeds to remain viable in the dry state for years and even centuries. What the key transcription factors (TFs) are that activate the mechanisms that allow plant seeds to maintain cellular and DNA integrity for centuries remains largely unknown. In this paper, we report the identification of the TFs that act as major nodes of the transcriptional networks that regulate the acquisition of seed DT. We also report the functional validation of several of the major regulators of seed DT in plants.
Light-driven carbon dioxide reduction to methane by nitrogenase in a photosynthetic bacterium
Authors: Fixen Kathryn R. , Zheng Yanning , Harris Derek F. , Shaw Sudipta , Yang Zhi-Yong , Dean Dennis R. , Seefeldt Lance C. , Harwood Caroline S.
Published: August 2016

Significance

One of the most important life-sustaining metabolisms that results from a net reduction reaction is the conversion of nitrogen gas to ammonia by nitrogenase in a process known as nitrogen fixation. A nitrogenase variant has been described that converts carbon dioxide to methane in vitro. Here, we expressed this variant in an engineered strain of the photosynthetic bacteriumRhodopseudomonas palustrisand showed biological light-driven methane production. Its ability to reduce carbon dioxide at ambient temperature and pressure with a single enzyme and energy provided by light makes the methane-producing strain ofR. palustrisan excellent starting point to understand how a biological system can marshal resources to produce an energy-rich hydrocarbon in one enzymatic step.
How chimpanzees cooperate in a competitive world
Authors: Suchak Malini , Eppley Timothy M. , Campbell Matthew W. , Feldman Rebecca A. , Quarles Luke F. , de Waal Frans B. M.
Published: August 2016

Significance

Competitive tendencies may make it hard for members of a group to cooperate with each other. Humans use many different “enforcement” strategies to keep competition in check and favor cooperation. To test whether one of our closest relatives uses similar strategies, we gave a group of chimpanzees a cooperative problem that required joint action by two or three individuals. The open-group set-up allowed the chimpanzees a choice between cooperation and competitive behavior like freeloading. The chimpanzees used a combination of partner choice and punishment of competitive individuals to reduce competition. In the end, cooperation won. Our results suggest that the roots of human cooperation are shared with other primates.
Overexpression screens identify conserved dosage chromosome instability genes in yeast and human cancer
Authors: Duffy Supipi , Fam Hok Khim , Wang Yi Kan , Styles Erin B. , Kim Jung-Hyun , Ang J. Sidney , Singh Tejomayee , Larionov Vladimir , Shah Sohrab P. , Andrews Brenda , Boerkoel Cornelius F. , Hieter Philip
Published: August 2016

Significance

Chromosome instability (CIN) is well established as an enabling characteristic of cancer that contributes to cancer initiation and progression. Here, we identify 245 genes whose individual overexpression causes CIN in yeast, and we show that the overexpression of several of these dosage CIN (dCIN) genes also causes CIN in human cells. We demonstrate that genetic screens in yeast can be used to determine candidate target genes for specific killing of cancer cells overexpressing dCIN genes. Rhabdomyosarcoma cells with elevated levels of Tdp1 are one example where the histone deacetylase inhibitors valproic acid and trichostatin A can be used to specifically kill these cells. We have generated a list of dCIN candidate genes that can facilitate selective targeting of tumor cells.
Clues to the mechanism of cholesterol transfer from the structure of NPC1 middle lumenal domain bound to NPC2
Authors: Li Xiaochun , Saha Piyali , Li Jian , Blobel Günter , Pfeffer Suzanne R.
Published: August 2016

Significance

Niemann–Pick C1 (NPC1) and Niemann–Pick C2 (NPC2) cooperate in the export of LDL-derived cholesterol from lysosomes; mutations in these proteins lead to Niemann–Pick type C disease. We present here the crystal structure of an NPC1–NPC2 complex and show that the amino acid residues that are important for this interaction in vitro are also important for cholesterol export from lysosomes of cultured cells. These data provide key information related to the mechanism by which these proteins catalyze cholesterol transport and form the basis for a molecular model for how cholesterol is transferred from NPC2 onto NPC1 protein.
Do Higher Size and Reduced Bag Limits Improve Northern Pike Size Structure in Wisconsin Lakes?
Authors: Oele Daniel L. , Rypel Andrew L. , Lyons John , Cunningham Paul , Simonson Tim
Published: August 2016

Minimum length limits (MLLs) combined with reduced bag limits are frequently used by fisheries managers to improve size-structure in Northern Pike Esox lucius populations. We evaluated the effectiveness of a relatively moderate 660-mm MLL and a two-fish-daily bag limit (hereafter, “moderate limit”) and a relatively conservative 813 mm MLL and one-fish-daily bag limit (hereafter, “conservative limit”) on size structure of Northern Pike in Wisconsin lakes. We used a before–after-control–impact design on a series of treatment and reference lakes to test the efficacy of each regulation. Across seven moderate-limit lake pairs, mean and mean maximum total length (i.e., mean of the 10 longest fish) in treatment lakes did not differ relative to reference lakes, where there was no MLL and a five-fish-daily bag limit (relatively liberal; hereafter, “liberal limit”). Across five conservative treatment lakes, there was a significant reduction in mean size relative to references, but mean maximum size increased significantly by an average of 104 mm. A linear mixed-effect regression of 990 Northern Pike populations similarly suggested that higher size and reduced bag limits were related to improved size structure. Northern Pike populations in the moderate-limit lakes and conservative-limit lakes increased by an average of 35 mm and 45 mm, respectively, compared with the liberal-limits lakes. Size structure was significantly and positively related to increased angler effort and reduced Northern Pike densities and was negatively related to longitude and mean Secchi depth, revealing the importance of lake characteristics in mediating regulation efficacy. Proportional size structure differed significantly between the southern and northern management zones of Wisconsin for the 20 years before and after implementation of regional regulations (moderate limit in south versus conservative limit in north). Analysis of long-term creel data revealed that catch rates of Northern Pike have been increasing over time, and anglers have focused on fewer, larger fish. We conclude that higher MLLs and reduced bag limits are effective at improving availability of large Northern Pike in Wisconsin lakes but are best utilized in certain lake and population types.

Received September 4, 2015; accepted April 11, 2016 Published online August 23, 2016
Time‐restricted feeding in young men performing resistance training: A randomized controlled trial†
Authors: Tinsley Grant M. , Forsse Jeffrey S. , Butler Natalie K. , Paoli Antonio , Bane Annie A. , La Bounty Paul M. , Morgan Grant B. , Grandjean Peter W.
Published: August 2016

A randomized controlled trial was conducted to examine eight weeks of resistance training (RT) with and without time‐restricted feeding (TRF) in order to assess nutrient intake and changes in body composition and muscular strength in young recreationally active males. The TRF programme consisted of consuming all calories within a four‐hour period of time for four days per week, but included no limitations on quantities or types of foods consumed. The RT programme was performed three days per week and consisted of alternating upper and lower body workouts. For each exercise, four sets leading to muscular failure between 8 and 12 repetitions were employed. Research visits were conducted at baseline, four, and eight weeks after study commencement. Measurements of total body composition by dual‐energy X‐ray absorptiometry and muscle cross‐sectional area by ultrasound were obtained. Upper and lower body strength and endurance were assessed, and four‐day dietary records were collected. TRF reduced energy intake by ∼650 kcal per day of TRF, but did not affect total body composition within the duration of the study. Cross‐sectional area of the biceps brachii and rectus femoris increased in both groups. Effect size data indicate a gain in lean soft tissue in the group that performed RT without TRF (+2.3 kg, d = 0.25). Upper and lower body strength and lower body muscular endurance increased in both groups, but effect sizes demonstrate greater improvements in the TRF group. Overall, TRF reduced energy intake and did not adversely affect lean mass retention or muscular improvements with short‐term RT in young males.
The Effect of Question Order on Evaluations of Test Performance: Can the Bias Dissolve?
Authors: Bard Gabriele , Weinstein Yana
Published: August 2016

Question difficulty order has been shown to affect students’ global postdictions of test performance. We attempted to eliminate the bias by letting participants experience the question order manipulation multiple times. In all three experiments, participants answered general knowledge questions and self-evaluated their performance. In Experiment 1, participants studied questions and answers in easy–hard or hard–easy question order prior to taking a test in the same order. In Experiment 2, participants took the same test twice in the opposite question order (easy–hard then hard–easy, or hard–easy then easy–hard). In Experiment 3, participants took two different tests in the opposite question order (easy–hard then hard–easy, or hard–easy then easy–hard). In all three experiments, we were unable to eliminate the bias, which suggests that repeated exposure is insufficient to overcome a strong initial anchor.
Communicative Functions of Directional Verbal Probabilities: Speaker's Choice, Listener's Inference, and Reference Points
Authors: Honda Hidehito , Yamagishi Kimihiko
Published: August 2016

Verbal probabilities have directional communicative functions, and most can be categorized as positive (e.g., “it is likely”) or negative (e.g., “it is doubtful”). We examined the communicative functions of verbal probabilities based on the reference point hypothesis According to this hypothesis, listeners are sensitive to and can infer a speaker's reference points based on the speaker's selected directionality. In four experiments (two of which examined speakers’ choice of directionality and two of which examined listeners’ inferences about a speaker's reference point), we found that listeners could make inferences about speakers’ reference points based on the stated directionality of verbal probability. Thus, the directionality of verbal probabilities serves the communicative function of conveying information about a speaker's reference point.
Scrape off layer profiles interpreted with filament dynamics
Authors: Militello F. , Omotani J.T.
Published: August 2016

A theoretical framework is developed to link the density profiles in the scrape off layer (SOL) with the fluctuations (filaments) that generate them. The framework is based on the dynamics of independent filaments and their statistical behaviour and can be used to rigorously understand the mechanisms that lead to flattening and broadening of the SOL profiles as well as the radial increase of the relative fluctuation amplitude.
Simulation of EAST vertical displacement events by tokamak simulation code
Authors: Qiu Qinglai , Xiao Bingjia , Guo Yong , Liu Lei , Xing Zhe , Humphreys D.A.
Published: August 2016

Vertical instability is a potentially serious hazard for elongated plasma. In this paper, the tokamak simulation code (TSC) is used to simulate vertical displacement events (VDE) on the experimental advanced superconducting tokamak (EAST). Key parameters from simulations, including plasma current, plasma shape and position, flux contours and magnetic measurements match experimental data well. The growth rates simulated by TSC are in good agreement with TokSys results. In addition to modeling the free drift, an EAST fast vertical control model enables TSC to simulate the course of VDE recovery. The trajectories of the plasma current center and control currents on internal coils (IC) fit experimental data well.
Model development of plasma implanted hydrogenic diffusion and trapping in ion beam damaged tungsten
Authors: Barton J.L. , Wang Y.Q. , Doerner R.P. , Tynan G.R.
Published: August 2016

A Cu ion beam is used to induce controlled levels of damage (10−3, 10−2, and 10−1 dpa) in room temperature W samples. A single 5 MeV beam energy yielding a peaked damage profile 0.8 μm into the material, or three beam energies (0.5, 2, and 5 MeV) producing a relatively uniform damage profile from the near surface up to 0.8 μm were used. The W samples were then exposed to a D plasma ion fluence of 1024 ions m−2 at 380 K, and the resulting D retention was measured using the D(3He,p)4He reaction analysis (NRA) and thermal desorption spectroscopy (TDS). We observe that within experimental error there is no significant difference in retention whether the damage profile is peaked or uniform. The increase in retention is observed to increase proportional to

d
p
a

0.66

estimated from the dpa peak calculated from the SRIM program. A simplified retention model is proposed that provides concentration profiles that can be directly compared to NRA data and total retention measurements. Taking the trapping energies due to three defect types calculated from density functional theory (DFT), the only free-parameters are three defect densities of in-grain monovacancies, dislocations, and grain boundary vacancies, and we assume these defects to be the dominant trapping locations. The model can fit D retention data in a pristine W sample within the experimental error of the measurements, and in subsequent modeling these intrinsic defect densities are then fixed. We model the retention profile after ion damage by adding the SRIM predicted vacancy profile to the intrinsic monovacancy defect density. Since the increase in retention, and therefore the increase in vacancy production, does not increase linearly with dpa, a correction factor is multiplied to the predicted vacancy profile to fit the data. A new diffusion coefficient is calculated with the model that is a function of the concentration of trapped atoms. This calculation may resolve discrepancies of various diffusivity measurements and models in the literature.
Integrating genomic information with protein sequence and 3D atomic level structure at the RCSB protein data bank
Authors: Prlić Andreas , Kalro Tara , Bhattacharya Roshni , Christie Cole , Burley Stephen K. , Rose Peter W.
Published: August 2016

Summary: The Protein Data Bank (PDB) now contains more than 120,000 three-dimensional (3D) structures of biological macromolecules. To allow an interpretation of how PDB data relates to other publicly available annotations, we developed a novel data integration platform that maps 3D structural information across various datasets. This integration bridges from the human genome across protein sequence to 3D structure space. We developed novel software solutions for data management and visualization, while incorporating new libraries for web-based visualization using SVG graphics.

Availability and Implementation: The new views are available from http://www.rcsb.org and software is available from https://github.com/rcsb/.

Contact:  andreas.prlic@rcsb.org

Supplementary information:  Supplementary data are available at Bioinformatics online.
Predicting the errors of predicted local backbone angles and non-local solvent- accessibilities of proteins by deep neural networks
Authors: Gao Jianzhao , Yang Yuedong , Zhou Yaoqi
Published: August 2016

Motivation: Backbone structures and solvent accessible surface area of proteins are benefited from continuous real value prediction because it removes the arbitrariness of defining boundary between different secondary-structure and solvent-accessibility states. However, lacking the confidence score for predicted values has limited their applications. Here we investigated whether or not we can make a reasonable prediction of absolute errors for predicted backbone torsion angles, Cα-atom-based angles and torsion angles, solvent accessibility, contact numbers and half-sphere exposures by employing deep neural networks.

Results: We found that angle-based errors can be predicted most accurately with Spearman correlation coefficient (SPC) between predicted and actual errors at about 0.6. This is followed by solvent accessibility (SPC∼0.5). The errors on contact-based structural properties are most difficult to predict (SPC between 0.2 and 0.3). We showed that predicted errors are significantly better error indicators than the average errors based on secondary-structure and amino-acid residue types. We further demonstrated the usefulness of predicted errors in model quality assessment. These error or confidence indictors are expected to be useful for prediction, assessment, and refinement of protein structures.

Availability and Implementation: The method is available at http://sparks-lab.org as a part of SPIDER2 package.

Contact:  yuedong.yang@griffith.edu.au or yaoqi.zhou@griffith.edu.au

Supplementary information:  Supplementary data are available at Bioinformatics online.
Temperature-Dependent Wsm1 and Wsm2 Gene-Specific Blockage of Viral Long-Distance Transport Provides Resistance to Wheat streak mosaic virus and Triticum mosaic virus in Wheat
Authors: Tatineni Satyanarayana , Wosula Everlyne N. , Bartels Melissa , Hein Gary L. , Graybosch Robert A.
Published: August 2016

Wheat streak mosaic virus (WSMV) and Triticum mosaic virus (TriMV) are economically important viral pathogens of wheat. Wheat cvs. Mace, carrying the Wsm1 gene, is resistant to WSMV and TriMV, and Snowmass, with Wsm2, is resistant to WSMV. Viral resistance in both cultivars is temperature sensitive and is effective at 18°C or below but not at higher temperatures. The underlying mechanisms of viral resistance of Wsm1 and Wsm2, nonallelic single dominant genes, are not known. In this study, we found that fluorescent protein–tagged WSMV and TriMV elicited foci that were approximately similar in number and size at 18 and 24°C, on inoculated leaves of resistant and susceptible wheat cultivars. These data suggest that resistant wheat cultivars at 18°C facilitated efficient cell-to-cell movement. Additionally, WSMV and TriMV efficiently replicated in inoculated leaves of resistant wheat cultivars at 18°C but failed to establish systemic infection, suggesting that Wsm1- and Wsm2-mediated resistance debilitated viral long-distance transport. Furthermore, we found that neither virus was able to enter the leaf sheaths of inoculated leaves or crowns of resistant wheat cultivars at 18°C but both were able to do so at 24°C. Thus, wheat cvs. Mace and Snowmass provide resistance at the long-distance movement stage by specifically blocking virus entry into the vasculature. Taken together, these data suggest that both Wsm1 and Wsm2 genes similarly confer virus resistance by temperature-dependent impairment of viral long-distance movement.
Efficient Diagnosis of Ratoon Stunting Disease of Sugarcane by Quantitative PCR on Pooled Leaf Sheath Biopsies
Authors: Young Anthony J. , Kawamata Asuka , Ensbey Mark A. , Lambley Eleanore , Nock Catherine J.
Published: August 2016

Ratoon stunting disease (RSD), caused by the bacterium Leifsonia xyli subsp. xyli, is arguably one of the most devastating diseases of sugarcane. Four diagnostic techniques were compared for 100 fields of sugarcane (Saccharum interspecific hybrids) of unknown infection status. These were quantitative polymerase chain reaction on pooled leaf sheath biopsies (LSB-qPCR), conventional PCR on the same templates (LSB-PCR), evaporative-binding enzyme immunoassay (EB-EIA) coupled with phase contrast microscopy (PCM) on expressed xylem sap from the same fields, and conventional PCR on the same xylem sap samples. LSB-qPCR and LSB-PCR detected the causal agent in 27 and 18 fields, respectively, whereas, from samples of expressed xylem sap from the same fields, conventional PCR identified 12 infections and EB-EIA/PCM detected L. xyli subsp. xyli in 3 fields. The sensitivities of qPCR and PCR were approximately 103 and 104 CFU ml−1, respectively, determined from plate counts of a dilution series. Tests were conducted on a further 139 LSB samples from across the Australian industry, with qPCR and PCR diagnosing RSD in 31 and 25 fields, respectively. Using qPCR and PCR on LSB samples, RSD was diagnosed in a range of cultivars throughout the year, and qPCR and PCR could detect L. xyli subsp. xyli in sugarcane ranging from 3 months to greater than 1 year old.
Strain-Specific Resistance to Potato virus Y (PVY) in Potato and Its Effect on the Relative Abundance of PVY Strains in Commercial Potato Fields
Authors: Funke Cassandra N. , Nikolaeva Olga V. , Green Kelsie J. , Tran Lisa T. , Chikh-Ali Mohamad , Quintero-Ferrer Arturo , Cating Robert A. , Frost Kenneth E. , Hamm Philip B. , Olsen Nora , Pavek Mark J. , Gray Stewart M. , Crosslin James M. , Karasev Alexander V.
Published: August 2016

Potato virus Y (PVY) is a serious threat to potato production due to effects on tuber yield and quality, in particular, due to induction of potato tuber necrotic ringspot disease (PTNRD), typically associated with recombinant strains of PVY. These recombinant strains have been spreading in the United States for the past several years, although the reasons for this continuing spread remained unclear. To document and assess this spread between 2011 and 2015, strain composition of PVY isolates circulating in the Columbia Basin potato production area was determined from hundreds of seed lots of various cultivars. The proportion of nonrecombinant PVYO isolates circulating in Columbia Basin potato dropped ninefold during this period, from 63% of all PVY-positive plants in 2011 to less than 7% in 2015. This drop in PVYO was concomitant with the rise of the recombinant PVYN-Wi strain incidence, from less than 27% of all PVY-positive plants in 2011 to 53% in 2015. The proportion of the PVYNTN recombinant strain, associated with PTNRD symptoms in susceptible cultivars, increased from 7% in 2011 to approximately 24% in 2015. To further address the shift in strain abundance, screenhouse experiments were conducted and revealed that three of the four most popular potato cultivars grown in the Columbia Basin exhibited strain-specific resistance against PVYO. Reduced levels of systemic movement of PVYO in such cultivars would favor spread of recombinant strains in the field. The negative selection against the nonrecombinant PVYO strain is likely caused by the presence of the Nytbr gene identified in potato cultivars in laboratory experiments. Presence of strain-specific resistance genes in potato cultivars may represent the driving force changing PVY strain composition to predominantly recombinant strains in potato production areas.
Response to “On Seed Transmissibility of Soybean vein necrosis-associated virus in Symptomless Soybean Seedlings”
Authors: Smith D. L.
Published: August 2016

A response to M. R. Hajimorad's letter regarding a recent PLoS One paper, in which Groves et al (2016) claims that Soybean vein necrosis-associated virus (SVNaV) was seed transmissible in symptomless seedlings derived from a seed lot of a field-grown soybean variety with symptoms indicative of virus infection.

Accepted for publication 28 July 2016.
100 Most Influential Publications in Scoliosis Surgery
Authors: Zhou James Jun , Koltz Michael T. , Agarwal Nitin , Tempel Zachary J. , Kanter Adam S. , Okonkwo David O. , Hamilton D. Kojo
Published: August 2016

Study Design.

Bibliometric analysis.

Objective.

To apply the established technique of citation analysis to identify the 100 most influential articles in scoliosis surgery research published between 1900 and 2015.

Summary of Background Data.

Previous studies have applied the technique of citation analysis to other areas of study. This is the first article to apply this technique to the field of scoliosis surgery.

Methods.

A two-step search of the Thomson Reuters Web of Science was conducted to identify all articles relevant to the field of scoliosis surgery. The top 100 articles with the most citations were identified based on analysis of titles and abstracts. Further statistical analysis was conducted to determine whether measures of author reputation and overall publication influence affected the rate at which publications were recognized and incorporated by other researchers in the field.

Results.

Total citations for the final 100 publications included in the list ranged from 82 to 509. The period for publication ranged from 1954 to 2010. Most studies were published in the journal Spine (n = 63). The most frequently published topics of study were surgical techniques (n = 35) and outcomes (n = 35). Measures of author reputation (number of total studies in the top 100, number of first-author studies in the top 100) were found to have no effect on the rate at which studies were adopted by other researchers (number of years until first citation, and number of years until maximum citations). The number of citations/year a publication received was found to be negatively correlated with the rate at which it was adopted by other researchers, indicating that more influential manuscripts attained more rapid recognition by the scientific community at large.

Conclusion.

In assembling this publication, we have strived to identify and recognize the 100 most influential articles in scoliosis surgery research from 1900 to 2015.

Level of Evidence: N/A
Validity and Reliability of a New Measure of Nursing Experience With Unintended Consequences of Electronic Health Records
Authors: Gephart Sheila M. , Bristol Alycia A. , Dye Judy L. , Finley Brooke A. , Carrington Jane M.
Published: August 2016

Unintended consequences of electronic health records represent undesired effects on individuals or systems, which may contradict initial goals and impact patient care. The purpose of this study was to determine the extent to which a new quantitative measure called the Carrington-Gephart Unintended Consequences of Electronic Health Record Questionnaire (CG-UCE-Q) was valid and reliable. Then, it was used to describe acute care nurses’ experience with unintended consequences of electronic health records and relate them to the professional practice environment. Acceptable content validity was achieved for two rounds of surveys with nursing informatics experts (n = 5). Then, acute care nurses (n = 144) were recruited locally and nationally to complete the survey and describe the frequency with which they encounter unintended consequences in daily work. Principal component analysis with oblique rotation was applied to evaluate construct validity. Correlational analysis with measures of the professional practice environment and workarounds was used to evaluate convergent validity. Test-retest reliability was measured in the local sample (N = 68). Explanation for 63% of the variance across six subscales (patient safety, system design, workload issues, workarounds, technology barriers, and sociotechnical impact) supported construct validity. Relationships were significant between subscales for electronic health record-related threats to patient safety and low autonomy/leadership (P < .01), poor communication about patients (P < .01), and low control over practice (P < .01). The most frequent sources of unintended consequences were increased workload, interruptions that shifted tasks from the computer, altered workflow, and the need to duplicate data entry. Convergent validity of the CG-UCE-Q was moderately supported with both the context and processes of workarounds with strong relationships identified for when nurses perceived a block and altered process to work around it to subscales in the CG-UCE-Q for electronic health record system design (P < .01) and technological barriers (P < .01).
Bilateral Vestibulopathy Aggravates Balance and Gait Disturbances in Sensory Ataxic Neuropathy, Dysarthria, and Ophthalmoparesis: A Case Report
Authors: van Leeuwen Roeland B. , Smits Bart W. , Rodenburg Richard J. , van Engelen Baziel G.
Published: August 2016

In patients with a triad of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO), the presenting features are mainly ataxia or ptosis. SANDO patients often have impaired balance and gait, which is not surprising considering the combination of sensory ataxic neuropathy, and additional symptoms like cerebellar ataxia and limb girdle weakness. We describe a SANDO patient who noticed an increasingly impaired balance and gait, without any dizziness. Neurological investigation revealed an external ophthalmeplegia and a cerebellar ataxia; the head impulse test was not reliable because of eye movement disorders. The caloric reflex tests showed lack of responses on both sides, compatible with severe bilateral vestibulopathy. Making the diagnosis of bilateral vestibulopathy in SANDO patients may have implications for the management of the patient, because specific vestibular rehabilitation can improve gaze and postural stability.
Ulnar Neuropathy at the Elbow in Chronic Alcohol-Dependent Subjects
Authors: Zambelis T. , Kanelli S. , Tzavellas E. , Paparrigopoulos T. , Karandreas N.
Published: August 2016

Objectives:

To evaluate the occurrence of Ulnar neuropathy at the elbow (UNE) among alcohol dependent subjects.

Method:

The study sample comprised 99 consecutive alcohol dependent subjects treated for detoxification voluntarily in the specialized unit of the Athens University Psychiatric Clinic in an inpatient basis.

Results:

UNE was found in 51 subjects (51.5%): in 40.4% on the right side, in 44.6% on the left and in 20.1% on both. Polyneuropathy was diagnosed in 41.4% of the total sample. Statistical analysis showed UNE significantly associated with age of the subjects, age at alcohol dependence onset and duration of alcohol dependence. Was more frequent in men and the probability of UNE was lower in obese subjects.

Conclusions:

UNE is frequent among alcohol dependent subjects and they must be instructed to avoid abnormal postures and to protect their elbow while working with the elbows flexed and resting on a hard object.
Comparative Long-Term Evaluation of Patients With Juvenile Inflammatory Myopathies
Authors: Elahi Hafiz A. , Bertorini Tulio E. , Igarashi Masanori , Mays William H. , Whitaker John N.
Published: August 2016

Objectives:

We conducted a retrospective study analyzing the clinical features, laboratory findings, demographics, and long-term prognoses of patients with juvenile inflammatory myopathies to determine possible predictors indicating the use of aggressive immunotherapy and the response to and complications of treatment.

Methods:

The medical records of 41 patients with juvenile inflammatory myopathies seen at University of Tennessee–affiliated hospitals in Memphis from 1969 to 2008 were evaluated. Patients' clinical characteristics, laboratory studies, muscle biopsies, and electromyography were reviewed. All patients were treated with prednisone initially; additionally, 14 patients received varying combinations of other immunosuppressant therapies.

Results:

Seventy-three percent of the patients experienced remission. Patients in the group that did not go into remission had specific characteristics at onset: they were comparatively older and had more severe rashes, contractures, arthritis, and systemic involvement. Also, patients with positive autoantibodies (antinuclear antibody, rheumatoid arthritis factor) had better outcomes.

Conclusions:

Juvenile inflammatory myopathies have relatively good prognoses. Initial presentation at advanced age or with severe rash, systemic vasculopathies, anemia, or arthritis portends refractory disease; in these patients, second- and third-line therapies improve outcome.
A Review of Azathioprine-Associated Hepatotoxicity and Myelosuppression in Myasthenia Gravis
Authors: Jack Kristin L. , Koopman Wilma J. , Hulley Denise , Nicolle Michael W.
Published: August 2016

Objectives:

Myasthenia gravis (MG) is an autoimmune disorder in which antibodies interfere with neuromuscular transmission. Azathioprine (AZA) is an immunosuppressant frequently used for treatment of various autoimmune conditions, including MG. The literature suggests that the rates of AZA-associated hepatotoxicity and myelosuppression in MG are highly variable. Published studies have not formally analyzed their pattern, severity, timing, and/or recovery. We assessed the prevalence, pattern and timing of AZA associated toxicity in a large group of MG patients.

Methods:

We identified 113 patients with MG with AZA-associated toxicity among 571 managed with this immunosuppressant. The timing of when toxicities occurred as well as pattern of laboratory abnormalities was assessed.

Results:

The overall prevalence of hepatotoxicity and myelosuppression was 15.2% and 9.1%, respectively. The most common pattern of hepatotoxicity seen was gamma-glutamyl transpeptidase (GGT) enzyme elevation in 67.8% of patients. Of note, 21.2% of patients with myelosuppression had normocytic anemia, 17.3% had pancytopenia, and another 17.3% developed macrocytic anemia.

Conclusions:

AZA-associated hepatotoxicity and myelosuppression in MG are not uncommon and may be underrecognized depending on the timing, frequency, and specific tests ordered for blood work monitoring.