bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-582-5p/miR-590-5p targeted CREB1/CREB5–NF-κB signaling and caused opioid-induced immunosuppression in human monocytes
Authors: Long X , Li Y , Qiu S , Liu J , He L , Peng Y 
Published: March 2016

AbstractChronic opioid abusers are more susceptible to bacterial and viral infections, but the molecular mechanism underlying opioid-induced immunosuppression is unknown. MicroRNAs (miRNAs) are emerging as key players in the control of biological processes, and may participate in immune regulation. In this study, we investigated the molecular mechanisms in opioid-induced and miRNA-mediated immunosuppression, in the context of miRNA dysregulation in opioid abusers. Blood samples of heroin abusers were collected and analyzed using miRNA microarray analysis and quantitative PCR validation. The purified primary human monocytes were cultured in vitro to explore the underlying mechanism. We found that morphine and its derivative heroin significantly decreased the expression levels of miR-582-5p and miR-590-5p in monocytes. cAMP response element-binding protein 1 (CREB1) and CREB5 were detected as direct target genes of miR-582-5p and miR-590-5p, respectively, by using dual-luciferase assay and western bolt. Functional studies showed that knockdown of CREB1/CREB5 increased tumor necrosis factor alpha (TNF-α) level and enhanced expression of phospho–NF-κB p65 and NF-κB p65. Our results demonstrated that miR-582-5p and miR-590-5p play important roles in opioid-induced immunosuppression in monocytes by targeting CREB1/CREB5–NF-κB signaling pathway.
LSD1 modulates stress-evoked transcription of immediate early genes and emotional behavior
Authors: Rusconi Francesco , Grillo Barbara , Ponzoni Luisa , Bassani Silvia , Toffolo Emanuela , Paganini Leda , Mallei Alessandra , Braida Daniela , Passafaro Maria , Popoli Maurizio , Sala Mariaelvina , Battaglioli Elena 
Published: March 2016

Significance
In mammals, different forms of stress, including psychosocial stress, can affect several aspects of health, fostering mood and anxiety disorders in humans. However, a lack of knowledge about the mechanisms underlying the brain physiology of the stress response hinders the development of new therapeutic strategies. We describe the role of the epigenetic enzyme Lysine-Specific Demethylase 1 (LSD1) in the transduction pathway that translates social stress into an altered transcriptional physiology of plasticity genes in hippocampus. In particular, we show that in the brain LSD1 is finely tuned by a mammal-restricted splicing-based mechanism, and its demethylase activity consistently affects anxiety-like behavior in mice. This work addresses a fundamental mechanism, explaining a brain-related phenotype as a result of genome–environment interactions mediated by the epigenome.
Optogenetic skeletal muscle-powered adaptive biological machines
Authors: Raman Ritu , Cvetkovic Caroline , Uzel Sebastien G. M. , Platt Randall J. , Sengupta Parijat , Kamm Roger D. , Bashir Rashid 
Published: March 2016

Significance
Understanding the design rules that govern the structure and function of natural biological systems gives us the ability to forward engineer machines integrated with and powered by biological components. Such machines, or “bio-bots,” can sense, process, and respond to dynamic environmental signals in real time, enabling a variety of applications. Here we present a modular optogenetic muscle actuator used to power actuation and locomotion of 3D printed flexible skeletons. Observing and controlling the functional response of such muscle-powered machines helps replicate the complex adaptive functionality we observe in natural biological systems. This demonstration thus sets the stage for building the next generation of bio-integrated machines and systems targeted at a diverse array of functional tasks.
Galápagos hydroclimate of the Common Era from paired microalgal and mangrove biomarker
2
H/
1
H values
Authors: Nelson Daniel B. , Sachs Julian P. 
Published: March 2016

Significance
The equatorial Pacific is centrally important in Earth’s climate system. Changes there cause disruptions to global economies and food and water security. Yet, projected tropical precipitation changes in response to higher greenhouse gas concentrations remain uncertain, due in part to a scarcity of paleoclimate records to validate models. We therefore applied a new method in Galápagos lakes for reconstructing rainfall and salinity using sedimentary lipids from microalgae and mangrove trees. Our data revise the understanding of changes over the Common Era to provide a spatially and temporally coherent view of tropical Pacific rainfall. We separate convergence zone from El Niño-driven changes and observe substantial fluctuations even in the absence of perturbations as large as current anthropogenic forcing.
Force-producing ADP state of myosin bound to actin
Authors: Wulf Sarah F. , Ropars Virginie , Fujita-Becker Setsuko , Oster Marco , Hofhaus Goetz , Trabuco Leonardo G. , Pylypenko Olena , Sweeney H. Lee , Houdusse Anne M. , Schröder Rasmus R. 
Published: March 2016

Significance
The force-generating state of myosin bound to actin is a key state in the chemomechanical cycle of this motor, but the structural details of the force-generating state are unknown. CryoEM structures of myosin V bound to actin with and without nucleotide reveal a previously unidentified conformation of elements associated with nucleotide binding and, most importantly, of the β-sheet that controls the position of nucleotide-binding elements. These specific structural features explain how myosin can bind strongly to both actin and MgADP, allowing force to be developed. Thus, this structure provides fundamental insights into how myosin works. It also provides insights into how strain may prevent release of MgADP, which is a critical property for the cellular roles of many myosins, including myosin V.
High-seas fish wars generate marine reserves
Authors: Herrera Guillermo E. , Moeller Holly V. , Neubert Michael G. 
Published: March 2016

Significance
Marine reserves—areas where fishing is prohibited—have been implemented to conserve fish stocks and their habitats. They have been established in near-shore fisheries, where a single state (or “sole owner”) regulates the distribution of fishing effort. Modeling has shown that, under some conditions, the sole owner may also use closed areas to maximize sustainable profit. Here, we show that reserves may also play a role in fisheries management on the high seas, where a limited number of states compete in a noncooperative fishing game. Our theoretical analysis complements recent empirical studies of high-seas protected areas and is relevant in other management contexts characterized by a limited number of harvesters.
Diverse high-torque bacterial flagellar motors assemble wider stator rings using a conserved protein scaffold
Authors: Beeby Morgan , Ribardo Deborah A. , Brennan Caitlin A. , Ruby Edward G. , Jensen Grant J. , Hendrixson David R. 
Published: March 2016

Significance
Many bacteria swim using helical propellers, flagella. Intriguingly, different bacteria show different swimming abilities, strikingly illustrated by the abilities of some to bore through viscous fluids (e.g., gastrointestinal mucus) in which others are completely immobilized. We used 3D electron microscopy to show that differences can be explained by the structures of the torque-generating motors: two diverse high-torque motors position additional torque-generating complexes at wider radii from the axial driveshaft than in the model enteric bacteria; this positioning is consistent with the exertion of greater leverage to rotate the flagellum and thus greater torque generation. Intriguingly, these torque-generating complexes are scaffolded at wider radii by a conserved but divergent family of structures, suggesting an ancient origin of reconfiguring torque output.
Phasic, suprathreshold excitation and sustained inhibition underlie neuronal selectivity for short-duration sounds
Authors: Alluri Rishi K. , Rose Gary J. , Hanson Jessica L. , Leary Christopher J. , Vasquez-Opazo Gustavo A. , Graham Jalina A. , Wilkerson Jeremy 
Published: March 2016

Significance
Understanding how excitatory and inhibitory inputs are integrated to achieve sensory selectivity is an important, but elusive, goal in neuroscience. Whole-cell recordings in vivo have revealed excitation and inhibition, but the computational mechanisms are generally unclear. In the inferior colliculus, neurons exist that respond selectively to short-duration sounds; the mechanistic basis of this selectivity has long been debated. We combined whole-cell recordings, in vivo, with conductance extraction algorithms and focal pharmacological manipulations to show that duration selectivity results from an anticoincidence of suprathreshold excitation and inhibition. These results challenge the widely held view that postinhibitory rebound depolarization must coincide with subthreshold excitation to generate duration selectivity.
Stability of the human polymerase δ holoenzyme and its implications in lagging strand DNA synthesis
Authors: Hedglin Mark , Pandey Binod , Benkovic Stephen J. 
Published: March 2016

Significance
The results from the reported studies indicate that the human lagging strand polymerase, pol δ, maintains a loose association with the sliding clamp, proliferating cell nuclear antigen (PCNA), while replicating and rapidly dissociates on stalling, leaving PCNA behind on the DNA. This behavior has profound implications on lagging strand synthesis as it limits the extent of processive DNA synthesis on undamaged DNA and promotes the rapid dissociation of pol δ on stalling at a replication-blocking lesion. This challenges the accepted models for polymerase recycling and exchange on the lagging strand and instead suggests passive mechanisms for the human system. These studies provide valuable insight for future experiments in the fields DNA replication, DNA repair, and DNA damage tolerance.
Spironolactone blocks Epstein–Barr virus production by inhibiting EBV SM protein function
Authors: Verma Dinesh , Thompson Jacob , Swaminathan Sankar 
Published: March 2016

Significance
Epstein–Barr virus is a human herpesvirus associated with several types of malignancy. We show that spironolactone, a drug used to block mineralocorticoid activity, also has anti-EBV activity and that it acts by inhibiting the function of an essential EBV protein SM, which preferentially increases expression of specific EBV genes. We also show that the mineralocorticoid blocking activity is not the basis for spironolactone’s antiviral activity. Because the SM protein acts at steps of the viral life cycle distinct from those targeted by currently available therapies, this study paves the way for development of novel anti-EBV drugs to address emerging problems of drug resistance and toxicity.
A RhoA and Rnd3 cycle regulates actin reassembly during membrane blebbing
Authors: Aoki Kana , Maeda Fumiyo , Nagasako Tomoya , Mochizuki Yuki , Uchida Seiichi , Ikenouchi Junichi 
Published: March 2016

Significance
The plasma membrane and the underlying actin cortex show dynamic interactions. When the plasma membrane detaches from the actin cortex, the plasma membrane protrudes. The protruded membrane is called a membrane bleb and is often observed during cell migration or cytokinesis. In the present study, we determined the molecular mechanisms involved in the reassembly of the actin cortex in membrane blebs using live-cell imaging.
Gene deficiency and pharmacological inhibition of soluble epoxide hydrolase confers resilience to repeated social defeat stress
Authors: Ren Qian , Ma Min , Ishima Tamaki , Morisseau Christophe , Yang Jun , Wagner Karen M. , Zhang Ji-chun , Yang Chun , Yao Wei , Dong Chao , Han Mei , Hammock Bruce D. , Hashimoto Kenji 
Published: March 2016

Significance
Depression is the most common and debilitating psychiatric disorder in the world. However, the precise mechanisms underlying depression remain largely unknown. Recent evidence suggests that soluble epoxide hydrolase (sEH) plays a key role in inflammation, which is involved in depression. The sEH inhibitor, TPPU, showed antidepressant effects in animal models of depression. Expression of sEH protein was increased in the brain of chronically stressed (susceptible) mice and depressed patients. Prophylactic sEH inhibition or sEH-KO resulted in resilience to repeated social defeat stress, associated with increased BDNF-TrkB signaling in prefrontal cortex and hippocampus of KO mice. This study shows that sEH plays a key role in the pathophysiology of depression, and that its inhibitors could be potential therapeutic drugs for depression.
BRCA2 regulates DMC1-mediated recombination through the BRC repeats
Authors: Martinez Juan S. , von Nicolai Catharina , Kim Taeho , Ehlén Åsa , Mazin Alexander V. , Kowalczykowski Stephen C. , Carreira Aura 
Published: March 2016

Significance
The function of BRCA2 (breast cancer susceptibility protein 2) in mitotic homologous recombination is well established; this role for BRCA2 includes promotion of RAD51 recombination function by regulating its assembly on DNA. However, loss of BRCA2 also leads to aberrant meiosis. Even though interaction of BRCA2 and the meiotic counterpart of RAD51, DMC1 (DNA meiotic recombinase 1), was reported, the specific role of BRCA2 in meiotic recombination is unknown. We demonstrate that the BRC repeats interact with DMC1 to stimulate both association with ssDNA and homologous DNA pairing. Furthermore, we demonstrate strong stimulation by BRCA2 of DNA strand exchange promoted by DMC1, even using ssDNA complexed with RPA (replication protein-A). These findings define BRCA2 as a mediator of meiotic recombination.
Four-dimensional maps of the human somatosensory system
Authors: Avanzini Pietro , Abdollahi Rouhollah O. , Sartori Ivana , Caruana Fausto , Pelliccia Veronica , Casaceli Giuseppe , Mai Roberto , Lo Russo Giorgio , Rizzolatti Giacomo , Orban Guy A. 
Published: March 2016

Significance
Here, we show how anatomical and functional data recorded from patients undergoing stereo-EEG can be combined to generate highly resolved four-dimensional maps of human cortical processing. We used this technique, which provides spatial maps of the active cortical nodes at a millisecond scale, to depict the somatosensory processing following electrical stimulation of the median nerve in nearly 100 patients. The results showed that human somatosensory system encompasses a widespread cortical network including a phasic component, centered on primary somatosensory cortex and neighboring motor, premotor, and inferior parietal regions, as well as a tonic component, centered on the opercular and insular areas, lasting more than 200 ms.
First international comparison of primary absorbed dose to water standards in the medium-energy X-ray range
Authors: Büermann Ludwig , Guerra Antonio Stefano , Pimpinella Maria , Pinto Massimo , Pooter Jacco de , Prez Leon de , Jansen Bartel , Denoziere Marc , Rapp Benjamin 
Published: March 2016

This report presents the results of the first international comparison of primary measurement standards of absorbed dose to water for the medium-energy X-ray range. Three of the participants (VSL, PTB, LNE-LNHB) used their existing water calorimeter based standards and one participant (ENEA) recently developed a new standard based on a water-graphite calorimeter. The participants calibrated three transfer chambers of the same type in terms of absorbed dose to water (N

Dw) and in addition in terms of air kerma (NK
) using the CCRI radiation qualities in the range 100 kV to 250 kV. The additional NK values were intended to be used for a physical analysis of the ratios N

Dw/NK
.
All participants had previously participated in the BIPM.RI(I)-K3 key comparison of air kerma standards. Ratios of pairs of NMI's NK
results of the current comparison were found to be consistent with the corresponding key comparison results within the expanded uncertainties of 0.6 % - 1 %. The N

Dw results were analysed in terms of the degrees of equivalence with the comparison reference values which were calculated for each beam quality as the weighted means of all results. The participant's results were consistent with the reference value within the expanded uncertainties. However, these expanded uncertainties varied significantly and ranged between about 1-1.8 % for the water calorimeter based standards and were estimated at 3.7 % for the water-graphite calorimeter.
It was shown previously that the ratios N

Dw/NK
for the type of ionization chamber used as transfer chamber in this comparison were very close (within less than 1 %) to the calculated values of (μ̄en/ρ)w,a
d, the mean values of the water-to-air ratio of the mass-energy-absorption coefficients at the depth d in water. Some of the participant's results deviated significantly from the expected behavior.

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.
The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Excess strain in the Echigo Plain sedimentary basin, NE Japan: evidence from coseismic deformation of the 2011 Tohoku-oki earthquake
Authors: Nishimura T. , Suito H. , Kobayashi T. , Dong Q. , Shibayama T. 
Published: March 2016

AbstractCoseismic deformation depends on both the source fault and on the elastic properties of the crust. Large coseismic deformation associated with the 2011 Mw 9.0 Tohoku-oki earthquake enabled us to investigate strain anomalies from crustal inhomogeneity. Concentrated contractional strain was observed in the Echigo Plain (Niigata-Kobe Tectonic Zone) before the Tohoku-oki earthquake, whereas continuous and campaign global navigation satellite system measurements show a widespread distribution of coseismic extensional strain in and around the plain. A 1-D displacement profile shows high strain (7.2 ± 0.7 microstrain) in a 17 km long section across the Echigo Plain and low strain (3.3 ± 0.4 microstrain) along a 15 km long section east of the plain, despite the latter being closer to the megathrust fault source. We performed numerical modelling of coseismic deformation using a heterogeneous subsurface structure and successfully reproduced excess extension in the plain, which is filled by low-rigidity sediments. This study demonstrates the importance of considering heterogeneous crust in deformation modelling.
Automatic detection of social rhythms in bipolar disorder
Authors: Abdullah Saeed , Matthews Mark , Frank Ellen , Doherty Gavin , Gay Geri , Choudhury Tanzeem 
Published: March 2016

Objective To evaluate the feasibility of automatically assessing the Social Rhythm Metric (SRM), a clinically-validated marker of stability and rhythmicity for individuals with bipolar disorder (BD), using passively-sensed data from smartphones.
Methods Seven patients with BD used smartphones for 4 weeks passively collecting sensor data including accelerometer, microphone, location, and communication information to infer behavioral and contextual patterns. Participants also completed SRM entries using a smartphone app.
Results We found that automated sensing can be used to infer the SRM score. Using location, distance traveled, conversation frequency, and non-stationary duration as inputs, our generalized model achieves root-mean-square-error of 1.40, a reasonable performance given the range of SRM score (0–7). Personalized models further improve performance with mean root-mean-square-error of 0.92 across users. Classifiers using sensor streams can predict stable (SRM score ≥3.5) and unstable (SRM score &lt;3.5) states with high accuracy (precision: 0.85 and recall: 0.86).
Conclusions Automatic smartphone sensing is a feasible approach for inferring rhythmicity, a key marker of wellbeing for individuals with BD.
Precision medicine: opportunities, possibilities, and challenges for patients and providers
Authors: Adams Samantha A , Petersen Carolyn 
Published: March 2016

AbstractPrecision medicine approaches disease treatment and prevention by taking patients’ individual variability in genes, environment, and lifestyle into account. Although the ideas underlying precision medicine are not new, opportunities for its more widespread use in practice have been enhanced by the development of large-scale databases, new methods for categorizing and representing patients, and computational tools for analyzing large datasets. New research methods may create uncertainty for both healthcare professionals and patients. In such situations, frameworks that address ethical, legal, and social challenges can be instrumental for facilitating trust between patients and providers, but must protect patients while not stifling progress or overburdening healthcare professionals. In this perspective, we outline several ethical, legal, and social issues related to the Precision Medicine Initiative’s proposed changes to current institutions, values, and frameworks. This piece is not an exhaustive overview, but is intended to highlight areas meriting further study and action, so that precision medicine’s goal of facilitating systematic learning and research at the point of care does not overshadow healthcare’s goal of providing care to patients.
General relativistic considerations of the field shedding model of fast radio bursts
Authors: Punsly Brian , Bini Donato 
Published: March 2016

Abstract
Popular models of fast radio bursts (FRBs) involve the gravitational collapse of neutron star progenitors to black holes. It has been proposed that the shedding of the strong neutron star magnetic field (B) during the collapse is the power source for the radio emission. Previously, these models have utilized the simplicity of the Schwarzschild metric which has the restriction that the magnetic flux is magnetic ‘hair’ that must be shed before final collapse. But neutron stars have angular momentum and charge and a fully relativistic Kerr–Newman solution exists in which B has its source inside of the event horizon. In this Letter, we consider the magnetic flux to be shed as a consequence of the electric discharge of a metastable collapsed state of a Kerr–Newman black hole. It has also been argued that the shedding model will not operate due to pair creation. By considering the pulsar death line, we find that for a neutron star with B = 1011–1013 G and a long rotation period, &gt;1s this is not a concern. We also discuss the observational evidence supporting the plausibility of magnetic flux shedding models of FRBs that are spawned from rapidly rotating progenitors.