bluuebunny/crossref_metadata_2025 huggingface dataset:
Probabilistic analysis for identifying the driving force of protein folding
Authors: Tokunaga Yoshihiko , Yamamori Yu , Matubayasi Nobuyuki
Published: March 2018

Toward identifying the driving force of protein folding, energetics was analyzed in water for Trp-cage (20 residues), protein G (56 residues), and ubiquitin (76 residues) at their native (folded) and heat-denatured (unfolded) states. All-atom molecular dynamics simulation was conducted, and the hydration effect was quantified by the solvation free energy. The free-energy calculation was done by employing the solution theory in the energy representation, and it was seen that the sum of the protein intramolecular (structural) energy and the solvation free energy is more favorable for a folded structure than for an unfolded one generated by heat. Probabilistic arguments were then developed to determine which of the electrostatic, van der Waals, and excluded-volume components of the interactions in the protein-water system governs the relative stabilities between the folded and unfolded structures. It was found that the electrostatic interaction does not correspond to the preference order of the two structures. The van der Waals and excluded-volume components were shown, on the other hand, to provide the right order of preference at probabilities of almost unity, and it is argued that a useful modeling of protein folding is possible on the basis of the excluded-volume effect.
A tesselation-based model for intensity estimation and laser plasma interactions calculations in three dimensions
Authors: Colaïtis A. , Chapman T. , Strozzi D. , Divol L. , Michel P.
Published: March 2018

A three-dimensional laser propagation model for computation of laser-plasma interactions is presented. It is focused on indirect drive geometries in inertial confinement fusion and formulated for use at large temporal and spatial scales. A modified tesselation-based estimator and a relaxation scheme are used to estimate the intensity distribution in plasma from geometrical optics rays. Comparisons with reference solutions show that this approach is well-suited to reproduce realistic 3D intensity field distributions of beams smoothed by phase plates. It is shown that the method requires a reduced number of rays compared to traditional rigid-scale intensity estimation. Using this field estimator, we have implemented laser refraction, inverse-bremsstrahlung absorption, and steady-state crossed-beam energy transfer with a linear kinetic model in the numerical code Vampire. Probe beam amplification and laser spot shapes are compared with experimental results and pf3d paraxial simulations. These results are promising for the efficient and accurate computation of laser intensity distributions in holhraums, which is of importance for determining the capsule implosion shape and risks of laser-plasma instabilities such as hot electron generation and backscatter in multi-beam configurations.
Design of pressure-sensing diaphragm for MEMS capacitance diaphragm gauge considering size effect
Authors: Li Gang , Li Detian , Cheng Yongjun , Sun Wenjun , Han Xiaodong , Wang Chengxiang
Published: March 2018

MEMS capacitance diaphragm gauge with a full range of (1∼1000) Pa is considered for its wide application prospect. The design of pressure-sensing diaphragm is the key to achieve balanced performance for this kind of gauges. The optimization process of the pressure-sensing diaphragm with island design of a capacitance diaphragm gauge based on MEMS technique has been reported in this work. For micro-components in micro scale range, mechanical properties are very different from that in the macro scale range, so the size effect should not be ignored. The modified strain gradient elasticity theory considering size effect has been applied to determine the bending rigidity of the pressure-sensing diaphragm, which is then used in the numerical model to calculate the deflection-pressure relation of the diaphragm. According to the deflection curves, capacitance variation can be determined by integrating over the radius of the diaphragm. At last, the design of the diaphragm has been optimized based on three parameters: sensitivity, linearity and ground capacitance. With this design, a full range of (1∼1000) Pa can be achieved, meanwhile, balanced sensitivity, resolution and linearity can be kept.
Design and development of a novel strain gauge automatic pasting device for mini split Hopkinson pressure bar
Authors: Huang Wenkai , Huan Shi , He Junfeng , Jiang Jichang
Published: March 2018

In a split Hopkinson pressure bar (SHPB) experiment, the pasting quality of strain gauges will directly affect the accuracy of the measurement results. The traditional method of pasting the strain gauges is done manually by the experimenter. In the process of pasting, it is easy to shift or twist the strain gauge, and the experimental results are greatly affected by human factors. In this paper, a novel type automatic pasting device for strain gauges is designed and developed, which can be used to accurately and rapidly paste the strain gauges. The paste quality is reliable, and it can guarantee the consistency of SHPB experimental measurement. We found that a clamping force of 74 N achieved a success rate of 97%, whilst ensuring good adhesion.
Automated translating beam profiler for in situ laser beam spot-size and focal position measurements
Authors: Keaveney James
Published: March 2018

We present a simple and convenient, high-resolution solution for automated laser-beam profiling with axial translation. The device is based on a Raspberry Pi computer, Pi Noir CMOS camera, stepper motor, and commercial translation stage. We also provide software to run the device. The CMOS sensor is sensitive over a large wavelength range between 300 and 1100 nm and can be translated over 25 mm along the beam axis. The sensor head can be reversed without changing its axial position, allowing for a quantitative estimate of beam overlap with counter-propagating laser beams. Although not limited to this application, the intended use for this device is the automated measurement of the focal position and spot-size of a Gaussian laser beam. We present example data of one such measurement to illustrate device performance.
Lower-hybrid oscillations in a cold magnetized electron-positron-ion plasma
Authors: Verma Prabal Singh
Published: March 2018

In this paper, we obtain the dispersion relation for the lower-hybrid oscillations/waves in a cold magnetized electron-positron-ion (e-p-i) plasma. It is found that the frequency of the lower-hybrid oscillations in an e-p-i plasma is approximate 1/3 times the frequency of lower-hybrid oscillations in an electron-ion (e-i) plasma, provided the plasma density is high, and the equilibrium densities of the positron and the ion are balanced. The present work may have some relevance for laboratory/astrophysical e-p-i plasmas.
Facile Synthesis of Pentamethylcyclopentadienyl Ruthenium Half-Sandwich Complexes by Naphthalene Displacement
Authors: Stone Jeremy , Jago David , Sobolev Alexandre , Spackman Mark , Koutsantonis George
Published: March 2018

Ruthenium half-sandwich complexes are central in a wide range of diverse applications in the field of organometallic chemistry. As such, exploration of their preparation and reactivity is crucial for development of their chemistry. Herein, we present alternative synthetic methods for the preparation of Cp*Ru(dppm)Cl, Cp*Ru(dppe)Cl, Cp*Ru(dppf)Cl, [Cp*Ru(COD)(MeCN)]BF4, and [Cp*Ru(bpy)(MeCN)]BF4 (dppm = 1,2-bis(diphenylphosphino)methane; dppe = 1,2-bis(diphenylphosphino) ethane; dppf = 1,2-bis(diphenylphosphino)ferrocene; COD = 1,5-cyclooctadiene; bpy= 2,2′-bipyridine), starting from the easily accessible [Cp*Ru(η6-C10H8)]BF4. The single-crystal X-ray structure determinations for [Cp*Ru(COD)(MeCN)]BF4, and [Cp*Ru(bpy)(MeCN)]BF4 are also presented.
Identification of two hatch date-dependent cohorts and variation in early growth rate of mud carp (Cirrhinus molitorella) in the Pearl River Delta, China
Authors: Huang Yanfei , Li Xinhui , Zhu Shuli , Wu Zhi
Published: March 2018

Cirrhinus molitorella is one of the most important commercial fish species in the Pearl River, but there are few published studies on the early growth of this species. In the present study, seasonal recruitment patterns, temporal variations in early growth rates and environmental variables were analysed. In all, 1512 individuals were collected during monthly sampling from July 2015 to January 2016, ranging from 30.8- to 84.9-mm standard length (SL). A subsample of 276 juveniles was aged from 68 to 193 days, with hatch dates between 2 February and 19 September, by determining daily increments in otoliths. Monthly abundance data and SL frequency distributions showed that there were two major temporal cohorts of juvenile recruitment, which hatched primarily in April and July. Average growth rate, estimated by the linear relationship between age and SL, was greater for the April cohort (0.49mmday–1) than the July cohort (0.37mmday–1). Mean increment widths from the 23rd increment onwards were significantly greater for the April than July cohort (P<0.05). The slower growth observed in the July cohort was probably due to poorer food availability caused by high river discharge volumes. These results are important for predicting recruitment dynamics and managing the C. molitorella fishery.
Ichthyofaunal assemblages in shallow littoral habitats of permanently open estuaries and intermittently closed and open lakes or lagoons in Otago, New Zealand
Authors: Taddese Fasil , Schallenberg Marc , Mikheev Pavel , Jarvis Matt G. , Closs Gerard P.
Published: March 2018

Fish assemblages of New Zealand estuaries are poorly studied, and knowledge of the effects of estuary–ocean connections on the ichthyofaunal composition of estuaries remains limited. Understanding the status of fish composition of estuaries is crucial for planning for sustainable management of aquatic ecosystems. In the present study we sampled fish using a seine net from lower reaches of six permanently open estuaries and six intermittently closed and open lakes or lagoons (ICOLLs) along the Otago coastline during winter 2016 and summer 2017. Marked differences in ichthyofaunal composition were observed in the shallow littoral habitats of permanently open estuaries and ICOLLs. Fish assemblages reflected estuary–ocean connection status of estuaries during both seasons. ICOLLs showed greater fish abundance than permanently open systems. Fish abundance was higher in summer than in winter in both estuary types. Fish species with marine–estuarine opportunist and estuarine–migrant life histories dominated permanently open estuaries. Conversely, species with a diadromous life history but known to form landlocked populations were abundant in ICOLLs. Salinity and temperature were correlated with fish abundance in both estuary types.
Current perspectives of CASA applications in diverse mammalian spermatozoa
Authors: van der Horst Gerhard , Maree Liana , du Plessis Stefan S.
Published: March 2018

Since the advent of computer-aided sperm analysis (CASA) some four decades ago, advances in computer technology and software algorithms have helped establish it as a research and diagnostic instrument for the analysis of spermatozoa. Despite mammalian spermatozoa being the most diverse cell type known, CASA is a great tool that has the capacity to provide rapid, reliable and objective quantitative assessment of sperm quality. This paper provides contemporary research findings illustrating the scientific and commercial applications of CASA and its ability to evaluate diverse mammalian spermatozoa (human, primates, rodents, domestic mammals, wildlife species) at both structural and functional levels. The potential of CASA to quantitatively measure essential aspects related to sperm subpopulations, hyperactivation, morphology and morphometry is also demonstrated. Furthermore, applications of CASA are provided for improved mammalian sperm quality assessment, evaluation of sperm functionality and the effect of different chemical substances or pathologies on sperm fertilising ability. It is clear that CASA has evolved significantly and is currently superior to many manual techniques in the research and clinical setting.
Assessment of sugarcane varieties for their stability and yield potential in Fiji
Authors: Naidu P. N. , Khan M. G. M. , Jokhan A. D.
Published: March 2018

The Sugar Research Institute of Fiji breeds and produces new varieties of sugarcane for the Fiji sugar industry for commercial production. The development of sugar cane varieties that show superior performance in different environments is a major challenge for breeders due to the response of genotypes across environments. This study was to evaluate the relative performance the genotypes during breeding program and identify promising ones that could be released for cultivation. Thus, an investigation was carried out to determine the magnitude of Genotype Environment interactions and the stability analysis of the genotypes cultivated in Fiji. Seventeen genotypes including three commercial varieties were evaluated in five locations using a randomized block design with three replications. The pooled analysis of variance carried out for the effect of environments, genotypes, and their interactions. The stability analysis was also performed using the Eberhart & Russell’s (1966) model. Further, a cluster analysis was proposed for identifying the similar and stable genotypes. The results showed that there were highly significant (p
What do predator diets tell us about mammal declines in Kakadu National Park?
Authors: Stokeld Danielle , Fisher Alaric , Gentles Tim , Hill Brydie , Triggs Barbara , Woinarski John C. Z. , Gillespie Graeme R.
Published: March 2018

Context
Small- and medium-sized native mammals have suffered severe declines in much of northern Australia, including within protected areas such as Kakadu National Park. Several factors have been implicated in these declines but predation, particularly by feral cats (Felis catus), has been identified as potentially the most direct cause of decline for many species.

Aims
We evaluated how prey frequency changed in cat and dingo scats in Kakadu from the early 1980s to 2013–15, with this period spanning a severe decline in the small- and medium-sized mammal fauna.

Methods
Chi-square test of independence and Fisher’s exact test were used to compare prey frequencies between dingoes and cats, and among years to assess significance of temporal change.

Key results
Small-sized native mammals were the prey item occurring at the highest frequency in scats for both dingoes and cats in the 1980s. Prey content in dingo and cat scats differed in the 2010s with macropods predominating in the scats of dingoes, and medium-sized native mammals predominating in cat scats. The frequency of occurrence of small-sized native mammals declined in both dingo and cat scats between the 1980s and 2010 sampling periods, while the frequency of occurrence of medium-sized native mammals remained constant in dingo scats and increased in cat scats.

Conclusions
Small mammals were a major component of the diets of both dingoes and cats in Kakadu in the 1980s, when small mammals were much more abundant. Despite marked reduction from the 1980s to the 2010s in the capture rates of both small- and medium-sized native mammals, some species continue to persist in the diets of cats and dingoes at disproportionally high frequencies. Both predators continue to exert predatory pressure on mammal populations that have already experienced substantial declines.

Implications
Although predation by feral cats is a major threat to small- and medium-sized native mammals, dingoes may also play an important role in limiting their recovery. Disturbance from fire and grazing by introduced herbivores has been shown to augment predatory impacts of feral cats on native mammals. Predation more generally, not just by feral cats, may be exacerbated by these disturbance processes. Management programs that solely focus on mitigating the impact of feral cats to benefit threatened species may be inadequate in landscapes with other significant disturbance regimes and populations of predators.
Effects of gap-based silviculture on thermal biology of a terrestrial reptile
Authors: Agha Mickey , Todd Brian D. , Augustine Ben , Lhotka John M. , Fleckenstein Leo J. , Lewis Mariah , Patterson Clint , Stringer Jeffrey W. , Price Steven J.
Published: March 2018

Context
Terrestrial reptiles require varied thermal environments to promote optimal physiological performance, growth, reproduction, and survival.

Aims
Our study was designed to determine whether gap-based silvicultural practices offer suitable thermal environments for eastern box turtles (Terrapene carolina) by examining environmental temperature variation and body temperature of eastern box turtles in, and adjacent to, canopy gaps.

Methods
We recorded box turtle body temperature from 20 radio-tracked turtles and environmental temperatures (canopy gaps and undisturbed habitat) using temperature loggers from June to September 2014 in a managed forest after canopy gaps (0.28–1.13 ha gap–1) were created via gap-based silviculture.

Key results
Over the four-month study period, gap temperatures were generally higher than adjacent undisturbed microhabitats. Box turtle body temperatures were closely correlated with environmental temperatures in undisturbed habitat in June and July. Turtle body temperatures were, however, closely correlated with environmental temperatures in canopy gaps in August and September. In addition, box turtles in our study had activity areas that overlapped canopy gaps from 0 to 65%, depending on the individual. As percentage overlap of canopy gaps increased, turtle body temperatures were increasingly correlated with canopy gap temperatures. Furthermore, as percentage overlap of canopy gaps increased, daily mean body temperature records consistently stayed within the preferred box turtle body temperature range (20.2–26.2°C).

Conclusions
Our study suggests that gap-based silviculture can create thermally compatible environments for box turtles depending on the time of day and year, and that box turtles use these microhabitats to thermoregulate.

Implications
The application of relatively small-scale silvicultural practices (≤1 ha gap–1) that provide heterogeneity in forest structure, composition, and function may be a useful alternative to clearcutting and other intensive harvesting methods that are associated with declines in terrestrial reptile populations.
Rodenticide application strategies for intertidal rat habitats
Authors: Siers Shane R. , Berentsen Are R. , McAuliffe Thomas W. , Foster Dean K. , Rex Kristen
Published: March 2018

Context
Successful eradications of invasive rats from islands are paying tremendous conservation dividends, but failed eradications are economically and environmentally costly. For an eradication using rodenticides, every rat in every habitat must have sufficient exposure to toxic bait to receive a lethal dose. A post-operational review of a failed rat eradication on Wake Atoll, central Pacific Ocean, suggested that inadequate treatment of an intertidal habitat within the lagoon might have caused or contributed to the failure to kill all Polynesian rats (Rattus exulans), which have since recovered in number. This habitat could not be treated by aerial broadcast due to concerns about loss of bait to tidal action and perceived contamination of the marine environment.

Aims
In preparation for a second attempt, we developed two alternative bait application strategies to distribute enough bait for a long enough period of time to successfully target rats, while minimising bait entering the ocean.

Methods
We used camera traps and experimental bait provisioning methods to document rat foraging in the target habitat and uptake of bait. We developed two baiting strategy alternatives, and employed one of these strategies in a placebo bait application to demonstrate bait uptake by rats foraging within this tidally inundated habitat.

Key results
Our results show active foraging by rats in the target habitat. Provisioning of placebo bait by various means preventing bait spillage into the marine environment was followed by heavy feeding by rats and minimal bait interference by crabs.

Conclusions
We consider it likely that such a bait application strategy will be considered as an alternative during a future eradication attempt on Wake Atoll.

Implications
The techniques we explore here will be useful for rodent suppression in other wetland areas requiring rodent control while protecting sensitive aquatic resources.
Identifying psychological responses of stigmatized groups to referendums
Authors: Flores Andrew R. , Hatzenbuehler Mark L. , Gates Gary J.
Published: March 2018

Significance

Voter initiatives and referendums concerning the rights of marginalized groups are utilized in 27 states, but research on the psychosocial consequences of these initiatives is underdeveloped. This research combines official records of televised advertisements from same-sex marriage campaigns with psychological outcomes among a probabilistic sample of lesbian, gay, bisexual, and transgender (LGBT) people. A novel design assesses advertisement effects on LGBT people unlikely affected by these campaigns in other ways, providing unbiased estimates. Greater ad exposure was associated with more stress among LGBT respondents; negative ads evoked sadness, whereas positive ads evoked enjoyment and happiness. No associations were observed among non-LGBT respondents. Voter referendums thus represent a source of minority stress and resilience for marginalized groups.
The opportunity cost of animal based diets exceeds all food losses
Authors: Shepon Alon , Eshel Gidon , Noor Elad , Milo Ron
Published: March 2018

Significance

With a third of all food production lost via leaky supply chains or spoilage, food loss is a key contributor to global food insecurity. Demand for resource-intensive animal-based food further limits food availability. In this paper, we show that plant-based replacements for each of the major animal categories in the United States (beef, pork, dairy, poultry, and eggs) can produce twofold to 20-fold more nutritionally similar food per unit cropland. Replacing all animal-based items with plant-based replacement diets can add enough food to feed 350 million additional people, more than the expected benefits of eliminating all supply chain food loss.
Loss of TDP43 inhibits progression of triple-negative breast cancer in coordination with SRSF3
Authors: Ke Hao , Zhao Limin , Zhang Honglei , Feng Xu , Xu Haibo , Hao Junjun , Wang Shaowei , Yang Qin , Zou Li , Su Xiaosan , Wang Liqiong , Wu Chunlian , Wang Yang , Nie Jianyun , Jiao Baowei
Published: March 2018

Significance

Triple-negative breast cancer (TNBC) is responsible for significant mortality among breast cancer subtypes, with its treatment largely unsuccessful due to ineffective targeted therapies. Our bioinformatics analysis demonstrates a unique alternative splicing pattern in TNBC compared with those of other breast cancers. In analyzing the underlying mechanism of the distinct alternative splicing profile,
TDP43
, a critical gene previously implicated in neurodegenerative disease, is found to promote TNBC progression. Mechanistically,
TDP43
regulates extensive alternative splicing events, including downstream gene
PAR3
, by forming a complex with SRSF3 to regulate alternative splicing events coordinately. Splicing factors TDP43 and SRSF3, which are likely responsible for the unique alternative splicing, could serve as potential targets for TNBC therapy.
Kv4.2 autism and epilepsy mutation enhances inactivation of closed channels but impairs access to inactivated state after opening
Authors: Lin Meng-chin A. , Cannon Stephen C. , Papazian Diane M.
Published: March 2018

Significance

Neuronal somatodendritic A-type potassium channels inactivate without opening in response to subthreshold depolarizations. Closed-state inactivation dynamically modulates excitability and regulates changes in synaptic strength. A mutation, V404M, in the Kv4.2 channel subunit is associated with infant-onset epilepsy and autism. Surprisingly, V404M enhances inactivation of channels that have not opened but dramatically impairs inactivation after opening. We show that increased side-chain volume is largely responsible for these seemingly paradoxical effects. Our results support the conclusion that open channels must close before inactivating and in contrast to previous proposals, suggest that voltage sensor and pore domains of the channel do not dissociate during inactivation. We propose that disruption of closed-state inactivation underlies epilepsy and autism in affected individuals.
PUMA amplifies necroptosis signaling by activating cytosolic DNA sensors
Authors: Chen Dongshi , Tong Jingshan , Yang Liheng , Wei Liang , Stolz Donna B. , Yu Jian , Zhang Jianke , Zhang Lin
Published: March 2018

Significance

Necroptosis is a regulated form of necrotic cell death that is important in physiology and human diseases. However, the signaling process leading to eventual cell death in necroptosis remains unclear. We show that
PUMA
, a proapoptotic BH3-only Bcl-2 family member, is induced and plays a role in necroptotic death. PUMA induction enhances necroptotic signaling by promoting the release of mitochondrial DNA and activation of cytosolic DNA sensors. We provide genetic evidence for the functional role of PUMA in necroptosis-mediated developmental defects in mice. Our results demonstrate a previously unknown function of Bcl-2 family proteins and reveal a signal amplification mechanism mediated by PUMA and cytosolic DNA sensors that is involved in TNF-driven necroptosis in vitro and in vivo.
Global increase and geographic convergence in antibiotic consumption between 2000 and 2015
Authors: Klein Eili Y. , Van Boeckel Thomas P. , Martinez Elena M. , Pant Suraj , Gandra Sumanth , Levin Simon A. , Goossens Herman , Laxminarayan Ramanan
Published: March 2018

Significance

Antibiotic resistance, driven by antibiotic consumption, is a growing global health threat. Our report on antibiotic use in 76 countries over 16 years provides an up-to-date comprehensive assessment of global trends in antibiotic consumption. We find that the antibiotic consumption rate in low- and middle-income countries (LMICs) has been converging to (and in some countries surpassing) levels typically observed in high-income countries. However, inequities in drug access persist, as many LMICs continue to be burdened with high rates of infectious disease-related mortality and low rates of antibiotic consumption. Our findings emphasize the need for global surveillance of antibiotic consumption to support policies to reduce antibiotic consumption and resistance while providing access to these lifesaving drugs.
South American monsoon response to iceberg discharge in the North Atlantic
Authors: Stríkis Nicolás M. , Cruz Francisco W. , Barreto Eline A. S. , Naughton Filipa , Vuille Mathias , Cheng Hai , Voelker Antje H. L. , Zhang Haiwei , Karmann Ivo , Edwards R. Lawrence , Auler Augusto S. , Santos Roberto Ventura , Sales Hamilton Reis
Published: March 2018

Significance

Here, we present a precisely dated speleothem record of South American monsoon precipitation covering the period encompassed by the last six Heinrich Stadials. Our monsoon record allows us to determine the timing of regional hydroclimatic expression of Heinrich Stadials over tropical lowland South America. By comparing our record with sea-surface temperature reconstructions from the subtropical North Atlantic, our results provide evidence connecting South American monsoon precipitation and methane release with the events of iceberg discharge depicted by the deposits of ice-rafted detritus. These results are relevant to climate modelers and paleoclimatologists interested in abrupt climate change, tropical–extratropical climate teleconnections, and paleo-reconstructions of the monsoon and the tropical hydrologic cycle.
Amide-forming chemical ligation via
O
-acyl hydroxamic acids
Authors: Dunkelmann Daniel L. , Hirata Yuki , Totaro Kyle A. , Cohen Daniel T. , Zhang Chi , Gates Zachary P. , Pentelute Bradley L.
Published: March 2018

Significance

Methods for the chemoselective formation of peptide bonds in water generally leverage the exceptional reactivity of thiol nucleophiles. Here, we demonstrate that hydroxamic acids—incorporated into the side chain of asparagine or aspartic acid—can be leveraged analogously.
N
-terminal hydroxy-asparagine-peptides react with peptide-
α
thioesters to form “
O
-acyl hydroxamic acid isopeptides," which rearrange to peptide bonds via a facile
O
,
N
-acyl shift. The hydroxy-asparagine residue can be converted to either aspartic acid or asparagine, to furnish amide-linked ligation products comprising entirely canonical residues. Taken together, these observations form the basis of a strategy for peptide ligation that circumvents the requirement for Xaa-Cys ligation “sites.”
MDMX acidic domain inhibits p53 DNA binding in vivo and regulates tumorigenesis
Authors: Huang Qingling , Chen Lihong , Yang Leixiang , Xie Xiaoling , Gan Lin , Cleveland John L. , Chen Jiandong
Published: March 2018

Significance

MDMX is an important regulator of p53 during embryonic development and malignant transformation. Using a combination of mouse knockin model, cell culture, and biochemical analysis, we demonstrate that the MDMX acidic domain interacts with the p53 DNA-binding domain and inhibits p53 DNA binding in the test tube and in tissues. This interaction is important for regulating p53 transcriptional activity and tumor suppressor function under physiological conditions. Furthermore, the results suggest that the MDMX acidic domain has p53-independent function that inhibits the progression of Myc-mediated lymphomas. The study provides physiological evidence on the mechanism of p53 regulation by MDMX, and identifies the structural basis for novel MDMX activities that warrants future investigation.
Lévy flight movements prevent extinctions and maximize population abundances in fragile Lotka–Volterra systems
Authors: Dannemann Teodoro , Boyer Denis , Miramontes Octavio
Published: March 2018

Significance

The ubiquity of scale-free mobility in nature, as observed in systems ranging from microorganisms to fishing boats, has stimulated a number of foraging theories and individual-based random search models. Here, we unveil an essential yet unexplored property of multiple-scale motion, which relates to the stability of entire populations. We use Lotka–Volterra models to predict that foragers diffusing normally tend to go extinct in fragile fragmented ecosystems, whereas their populations become resilient to degraded conditions and have maximized abundances when individuals perform scale-free Lévy flights. Our analytical and simulated results shift the scope of multiple-scale foraging from the individual level to the scales of collective phenomena that are of primary interest in conservation biology.
New tRNA contacts facilitate ligand binding in a
Mycobacterium smegmatis
T box riboswitch
Authors: Sherwood Anna V. , Frandsen Jane K. , Grundy Frank J. , Henkin Tina M.
Published: March 2018

Significance

T box riboswitches regulate the expression of amino acid-related genes using a specific uncharged tRNA as their ligand. Previous work demonstrated that the conserved Stem II S-turn motif and Stem IIA/B pseudoknot element of the riboswitch are important for tRNA-dependent regulation; however, their function remained unknown. We identified contacts between these RNA elements and the tRNA ligand, providing evidence that they directly interact with tRNA. This represents an example of tRNA recognition by an S-turn motif or pseudoknot element, contributing to the understanding of alternative roles for tRNA and other RNA–RNA interactions. Furthermore, the novelty of these contacts makes them optimal targets for the ongoing development of antibiotics that target T box riboswitches.
A zipped-helix cap potentiates HAMP domain control of chemoreceptor signaling
Authors: Flack Caralyn E. , Parkinson John S.
Published: March 2018

Significance

The ability to sense and respond adaptively to environmental changes is central to all forms of life. The bacterial chemotaxis system offers an ideal model system for the study of transmembrane and intracellular signaling mechanisms at the molecular level. Our studies of the
Escherichia coli
serine chemoreceptor have identified an evolutionarily conserved structural motif that is essential for control of receptor signal output by HAMP (histidine kinases, adenylate cyclases, methyl-accepting proteins, and phosphatases) domains, the versatile input–output devices that operate in a variety of bacterial signaling proteins.
Structural basis for the ethanol action on G-protein–activated inwardly rectifying potassium channel 1 revealed by NMR spectroscopy
Authors: Toyama Yuki , Kano Hanaho , Mase Yoko , Yokogawa Mariko , Osawa Masanori , Shimada Ichio
Published: March 2018

Significance

Ethanol exerts various functions by acting on ion channels in neural systems. Despite its biological importance, molecular mechanisms underlying the ethanol action remained unknown, due to the weak binding affinity and the dynamic nature of the interaction. Here, by using solution NMR techniques, we investigated the molecular interaction of ethanol with G-protein–activated inwardly rectifying potassium channel (GIRK), which is a physiologically relevant target of ethanol, and revealed that ethanol activates GIRK by shifting the conformational equilibrium of GIRK to stabilize the open conformation of the cytoplasmic ion gate. These findings provide structural insights into mechanisms of the ethanol action for various types of ethanol-sensitive signaling molecules and would facilitate the developments of pharmaceutical compounds targeting ion channels.
Light-induced dilation in nanosheets of charge-transfer complexes
Authors: Zhang Zhuolei , Remsing Richard C. , Chakraborty Himanshu , Gao Wenxiu , Yuan Guoliang , Klein Michael L. , Ren Shenqiang
Published: March 2018

Significance

Photostrictive compounds are promising device materials because of their fundamental photophysical properties and light-induced strain applications. Although molecular charge-transfer crystals exhibiting light–matter interactions have been successfully deployed in optoelectronics, an air-stable molecular material that couples photons and electrons, achieving photostriction through the coupling of light and mechanical degrees of freedom, has not yet been discovered. Herein, we report a substantial light-induced dilation in a molecular material at room temperature, which is accompanied by simultaneous photocurrent generation. This finding opens avenues for coupling optical, electronic, and mechanical functionalities for possible use in remote wireless photoswitchable devices.
Anti–CTLA-4 therapy requires an Fc domain for efficacy
Authors: Ingram Jessica R. , Blomberg Olga S. , Rashidian Mohammad , Ali Lestat , Garforth Scott , Fedorov Elena , Fedorov Alexander A. , Bonanno Jeffrey B. , Le Gall Camille , Crowley Stephanie , Espinosa Camilo , Biary Tamara , Keliher Edmund J. , Weissleder Ralph , Almo Steven C. , Dougan Stephanie K. , Ploegh Hidde L. , Dougan Michael
Published: March 2018

Significance

Ipilimumab, an antibody that recognizes cytotoxic T lymphocyte antigen (CTLA)-4, was the first approved “checkpoint”-blocking anticancer therapy. In mice, the response to antibodies against CTLA-4 depends entirely on expression of the Fcγ receptor. We developed H11, an alpaca heavy chain-only antibody fragment against CTLA-4 that lacks an Fc portion and inhibits interactions between CTLA-4 and its ligand. By using H11 to visualize CTLA-4 expression in the whole animal, we found that accessible CTLA-4 is largely confined to the tumor; however, H11 treatment has minimal effects on antitumor responses. Installing the murine IgG2a constant region on H11 greatly enhances antitumor response. We were thus able to dissociate CTLA-4 blockade from CTLA-4–dependent receptor engagement as an explanation for the antitumor effect.
Inhibition of Enhancer of zeste homolog 2 (EZH2) induces natural killer cell-mediated eradication of hepatocellular carcinoma cells
Authors: Bugide Suresh , Green Michael R. , Wajapeyee Narendra
Published: March 2018

Significance

Natural killer (NK) cells play an important role as a first line of immunological defense against tumor initiation. However, cancer cell intrinsic factors that regulate NK cell activity against cancer cells are not fully known. We performed a chemical genetics screen using small-molecule inhibitors of epigenetic factors and identified Enhancer of zeste homolog 2 (EZH2) as a key regulator of NK cell-mediated eradication of hepatocellular carcinoma cells. These results uncover a role of EZH2 in the regulation of NK cells as a mechanism to promote oncogenesis. EZH2 inhibitors are in clinical trials for treatment of EZH2 mutant lymphomas and solid tumors with INI1 deficiency. Our findings may guide uses of EZH2 inhibitors for cancer treatment and encourage their preclinical testing in immunocompetent hosts.
Everolimus rescues multiple cellular defects in laminopathy-patient fibroblasts
Authors: DuBose Amanda J. , Lichtenstein Stephen T. , Petrash Noreen M. , Erdos Michael R. , Gordon Leslie B. , Collins Francis S.
Published: March 2018

Significance

The lamin proteins are an important component of the nuclear scaffold. Abnormal lamins can cause a variety of disorders called laminopathies, one of which is the premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS). Cells from HGPS patients show improvement when treated with rapamycin and everolimus. These drugs stimulate the cellular system that disposes of abnormal proteins. Several other laminopathies also produce abnormal lamin proteins, so we hypothesized that everolimus would also be beneficial. We treated cells from six different laminopathy patients with everolimus and saw improved nuclear shape in most cells. Treatment also increased the cells’ ability to multiply and delayed senescence. These results suggest that everolimus might have clinical benefit for multiple laminopathy syndromes.
Monteverdi, the 1610 Vespers and the Beginnings of the Modern Musical Work
Authors: Butt John
Published: March 2018

The elevated status of Monteverdi's 1610 Vespers over the last century provides the starting point for an enquiry into which factors render it so durable. In going against the grain of recent attempts to discern the possible liturgical context for its original performance, this study claims that the collection as a whole (components of which undoubtedly had liturgical origins) can only be exemplary. Moreover, Monteverdi, in his intense engagement with the impersonation of liturgical chanting, has effectively rendered it the analogue of an actual service. Several features suggest that he is capturing something of the listening experience of a liturgy, complete with its distortions and memories. As a collection that is ‘about’ Vespers and which doubles the experience one might be having, this has something in common with the ‘musical work’ as defined by later classical practice, and its very religiosity resonates with the secularized ideology of musical autonomy.
Mastery and Masquerade in the Transatlantic Blues Revival
Authors: Cole Ross
Published: March 2018

Focusing on two influential broadcasts staged for British television in 1963–4, this article traces transatlantic attitudes towards blues music in order to explore the constitutive relationship between race, spectatorship and performativity. During these programmes, I claim, a form of mythic history is translated into racial nature. Ultimately, I argue that blues revivalism coerced African American musicians into assuming the mask of blackface minstrelsy – an active personification of difference driven by a lucrative fantasy on the terms of white demand. I ask why this imagery found such zealous adherents among post-war youth, situating their gaze within a longer tradition of colonialist display. Subaltern musicians caught within this regime were nonetheless able to ‘speak’ via sung performances that signified on the coordinates of their own marginalization. The challenge for musicology is thus to heed the relational syncretism arising from intercultural contact while acknowledging the lived experience of African American artists unable fully to evade the preordained mask of alterity.
New Music for New South Africans: The New Music Indabas in South Africa, 2000–02
Authors: Stolp Mareli
Published: March 2018

This article explores the content, scope and impact of an annual contemporary music festival in South Africa, the first of which was presented in 2000 by New Music South Africa (NMSA), the South African chapter of the International Society for Contemporary Music (ISCM). It explores the New Music Indabas of 2000–02 against the background of the political and cultural transformations that characterized South Africa, especially in the aftermath of the end of apartheid. Research into the archive of NMSA provided an entry point into understanding South African cultural, social and political life in the early years of the country's democracy. The ‘separate development’ rhetoric of the totalitarian apartheid regime, in power from 1948 to 1994, prevented cultural exchange and connection between musics and musicians in South Africa for decades; this article explores the ways in which the New Music Indabas attempted to right these historical imbalances, and to forge new directions for South African art-music production and practice.
Interest in Prescribing Buprenorphine among Resident and Attending Physicians at An Urban Teaching Clinic
Authors: James Jocelyn R. , Gordon Leah M. , Klein Jared W. , Merrill Joseph O. , Tsui Judith I.
Published: March 2018

Background: Opioid use disorders are a major medical and public health concern. Buprenorphine is approved for the treatment of opioid use disorders; however, a shortage of physicians prescribing buprenorphine is a significant barrier to treatment access. The aims of this study were to evaluate opinions of internal medicine attending and resident physicians about buprenorphine and assess interest in becoming waivered to prescribe. Methods: Internal medicine resident and attending physicians at a primary care clinic in a large academic hospital were invited to complete surveys. The study sample was composed of physicians who were not waivered to prescribe buprenorphine. Survey data included demographic information, level of training, buprenorphine waiver status, interest in becoming waivered to prescribe buprenorphine, and beliefs about buprenorphine for treatment of opioid use disorders. High interest in becoming waivered was defined as a Likert response >3 (1 = No interest, 5 = Very interested). Results: Of the 44 physician respondents, 39 were not waivered to prescribe buprenorphine and constituted the sample; of those, 27 were residents and 12 were attending physicians. Twenty-six of the 39 nonwaivered respondents (66.7%) had high interest in becoming waivered. Those with high interest in becoming waivered were significantly more likely to be younger ( P = .007) and to strongly believe in buprenorphine effectiveness ( P = .023). Discussion: Most physicians in this academic training program showed high interest in prescribing buprenorphine, and belief in buprenorphine effectiveness was associated with high interest in becoming waivered.
Investigation of procoagulant activity in extracellular vesicles isolated by differential ultracentrifugation
Authors: Nielsen Thøger , Kristensen Anne Flou , Pedersen Shona , Christiansen Gunna , Kristensen Søren Risom
Published: March 2018

Tissue factor (TF) is the main initiator of coagulation and procoagulant phospholipids (PPL) are key components in promoting coagulation activity in blood. Both TF and PPL may be presented on the surface of extracellular vesicles (EVs), thus contributing to their procoagulant activity. These EVs may constitute a substantial part of pathological hypercoagulability that is responsible for triggering a higher risk of thrombosis in certain patients. The aim of this study was to describe a model system for the isolation of EVs required for investigating their effect on coagulation. Differential ultracentrifugation (DUC) with and without a single washing step was used to isolate and evaluate the procoagulant capacity of EVs from healthy volunteers through analysis of thrombin generation and PPL activity. Ultracentrifugation at 20,000 × g and 100,000 × g resulted in pellets containing larger vesicles and smaller vesicles, respectively. Isolation yield of particle concentration was assessed by nanoparticle tracking analysis. Immunoelectron microscopy and western blotting revealed vesicles positive for the commonly used EV‐marker CD9. Plasma proteins and lipoproteins were co‐isolated with the EVs; however, application of a washing step clearly diminished the amount of contaminants. The isolated EVs were capable of enhancing thrombin generation, mainly due to PPL predominantly present in pellets from 20,000 × g centrifugation, and correlated with the activity measured by a PPL activity assay. Thus, DUC was proficient for the isolation of EVs with minimal contamination from plasma proteins and lipoproteins, and the setup can be used to study EV‐associated procoagulant activity. This may be useful in determining the procoagulant activity of EVs in patients at potentially increased risk of developing thrombosis, e.g. cancer patients.

Abbreviations: TF: Tissue factor; PL: Phospholipids; EVs: Extracellular vesicles; FXa: Activated coagulation factor X; TGA: Thrombin generation assay; PPL: Procoagulant phospholipids; DUC: Differential ultracentrifugation; NTA: Nanoparticle tracking analysis; TEM: Transmission electron microscopy; SPP: Standard pool plasma; CTI: Corn trypsin inhibitor; 20K: 20,000 × g; 100K: 100,000 × g; FVIII: Coagulation factor VIII
Engagements, grammars, and the public: From the liberal grammar to individual interests
Authors: Eranti Veikko
Published: March 2018

This article explores the role of individual interests within the pragmatic sociology of engagements, developed by Laurent Thévenot. He developed the idea of multiple regimes of engaging with the world – cognitive models of information-processing and what kind of good is engaged in different situations. In this article I argue that the way the sociology of engagements is currently formulated does not sufficiently allow for analysing public participation and disputes in situations where individual interests play a crucial role in public debates. The article presents a slight reformulation of what Thévenot calls the grammar of individuals in a liberal public, based on (a) an understanding of how individual interests relate to the common good and general will, (b) the constitution of legitimate actors within polities, and (c) the separation between the levels of generality and publicity. This reformulation might be called the grammar of individual interests, clarifying and simplifying earlier terminology.
Structural mechanisms of CFTR function and dysfunction
Authors: Hwang Tzyh-Chang , Yeh Jiunn-Tyng , Zhang Jingyao , Yu Ying-Chun , Yeh Han-I , Destefano Samantha
Published: March 2018

Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) chloride channel plays a critical role in regulating transepithelial movement of water and electrolyte in exocrine tissues. Malfunction of the channel because of mutations of the cftr gene results in CF, the most prevalent lethal genetic disease among Caucasians. Recently, the publication of atomic structures of CFTR in two distinct conformations provides, for the first time, a clear overview of the protein. However, given the highly dynamic nature of the interactions among CFTR’s various domains, better understanding of the functional significance of these structures requires an integration of these new structural insights with previously established biochemical/biophysical studies, which is the goal of this review.