bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.
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.
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

SignificanceOne 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

SignificanceCompetitive 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

Abstract
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

AbstractA 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.
Scrape off layer profiles interpreted with filament dynamics
Authors: Militello F. , Omotani J.T. 
Published: August 2016

Abstract
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

Abstract
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

Abstract
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.