bluuebunny/crossref_metadata_2025_split huggingface dataset:
TCR microclusters form spatially segregated domains and sequentially assemble in calcium-dependent kinetic steps
Authors: Yi Jason , Balagopalan Lakshmi , Nguyen Tiffany , McIntire Katherine M. , Samelson Lawrence E. 
Published: January 2019

AbstractEngagement of the T cell receptor (TCR) by stimulatory ligand results in the rapid formation of microclusters at sites of T cell activation. Whereas microclusters have been studied extensively using confocal microscopy, the spatial and kinetic relationships of their signaling components have not been well characterized due to limits in image resolution and acquisition speed. Here we show, using TIRF-SIM to examine the organization of microclusters at sub-diffraction resolution, the presence of two spatially distinct domains composed of ZAP70-bound TCR and LAT-associated signaling complex. Kinetic analysis of microcluster assembly reveal surprising delays between the stepwise recruitment of ZAP70 and signaling proteins to the TCR, as well as distinct patterns in their disassociation. These delays are regulated by intracellular calcium flux downstream of T cell activation. Our results reveal novel insights into the spatial and kinetic regulation of TCR microcluster formation and T cell activation.
Sex peptide receptor-regulated polyandry modulates the balance of pre- and post-copulatory sexual selection in Drosophila
Authors: Morimoto Juliano , McDonald Grant C. , Smith Emelia , Smith Damian T. , Perry Jennifer C. , Chapman Tracey , Pizzari Tommaso , Wigby Stuart 
Published: January 2019

AbstractPolyandry prolongs sexual selection on males by forcing ejaculates to compete for fertilisation. Recent theory predicts that increasing polyandry may weaken pre-copulatory sexual selection on males and increase the relative importance of post-copulatory sexual selection, but experimental tests of this prediction are lacking. Here, we manipulate the polyandry levels in groups of Drosophila melanogaster by deletion of the female sex peptide receptor. We show that groups in which the sex-peptide-receptor is absent in females (SPR-) have higher polyandry, and – as a result – weaker pre-copulatory sexual selection on male mating success, compared to controls. Post-copulatory selection on male paternity share is relatively more important in SPR- groups, where males gain additional paternity by mating repeatedly with the same females. These results provide experimental evidence that elevated polyandry weakens pre-copulatory sexual selection on males, shifts selection to post-copulatory events, and that the sex peptide pathway can play a key role in modulating this process in Drosophila.
ONECUT2 is a driver of neuroendocrine prostate cancer
Authors: Guo Haiyang , Ci Xinpei , Ahmed Musaddeque , Hua Junjie Tony , Soares Fraser , Lin Dong , Puca Loredana , Vosoughi Aram , Xue Hui , Li Estelle , Su Peiran , Chen Sujun , Nguyen Tran , Liang Yi , Zhang Yuzhe , Xu Xin , Xu Jing , Sheahan Anjali V. , Ba-Alawi Wail , Zhang Si , Mahamud Osman , Vellanki Ravi N. , Gleave Martin , Bristow Robert G. , Haibe-Kains Benjamin , Poirier John T. , Rudin Charles M. , Tsao Ming-Sound , Wouters Bradly G. , Fazli Ladan , Feng Felix Y. , Ellis Leigh , van der Kwast Theo , Berlin Alejandro , Koritzinsky Marianne , Boutros Paul C. , Zoubeidi Amina , Beltran Himisha , Wang Yuzhuo , He Housheng Hansen 
Published: January 2019

AbstractNeuroendocrine prostate cancer (NEPC), a lethal form of the disease, is characterized by loss of androgen receptor (AR) signaling during neuroendocrine transdifferentiation, which results in resistance to AR-targeted therapy. Clinically, genomically and epigenetically, NEPC resembles other types of poorly differentiated neuroendocrine tumors (NETs). Through pan-NET analyses, we identified ONECUT2 as a candidate master transcriptional regulator of poorly differentiated NETs. ONECUT2 ectopic expression in prostate adenocarcinoma synergizes with hypoxia to suppress androgen signaling and induce neuroendocrine plasticity. ONEUCT2 drives tumor aggressiveness in NEPC, partially through regulating hypoxia signaling and tumor hypoxia. Specifically, ONECUT2 activates SMAD3, which regulates hypoxia signaling through modulating HIF1α chromatin-binding, leading NEPC to exhibit higher degrees of hypoxia compared to prostate adenocarcinomas. Treatment with hypoxia-activated prodrug TH-302 potently reduces NEPC tumor growth. Collectively, these results highlight the synergy between ONECUT2 and hypoxia in driving NEPC, and emphasize the potential of hypoxia-directed therapy for NEPC patients.
Domain insertion permissibility-guided engineering of allostery in ion channels
Authors: Coyote-Maestas Willow , He Yungui , Myers Chad L. , Schmidt Daniel 
Published: January 2019

AbstractAllostery is a fundamental principle of protein regulation that remains hard to engineer, particularly in membrane proteins such as ion channels. Here we use human Inward Rectifier K+ Channel Kir2.1 to map site-specific permissibility to the insertion of domains with different biophysical properties. We find that permissibility is best explained by dynamic protein properties, such as conformational flexibility. Several regions in Kir2.1 that are equivalent to those regulated in homologs, such as G-protein-gated inward rectifier K+ channels (GIRK), have differential permissibility; that is, for these sites permissibility depends on the structural properties of the inserted domain. Our data and the well-established link between protein dynamics and allostery led us to propose that differential permissibility is a metric of latent allosteric capacity in Kir2.1. In support of this notion, inserting light-switchable domains into sites with predicted latent allosteric capacity renders Kir2.1 activity sensitive to light.
WDR76 is a RAS binding protein that functions as a tumor suppressor via RAS degradation
Authors: Jeong Woo-Jeong , Park Jong-Chan , Kim Woo-Shin , Ro Eun Ji , Jeon Soung Hoo , Lee Sang-Kyu , Park Young Nyun , Min Do Sik , Choi Kang-Yell 
Published: January 2019

AbstractStability regulation of RAS that can affect its activity, in addition to the oncogenic mutations, occurs in human cancer. However, the mechanisms for stability regulation of RAS involved in their activity and its roles in tumorigenesis are poorly explored. Here, we identify WD40-repeat protein 76 (WDR76) as one of the HRAS binding proteins using proteomic analyses of hepatocellular carcinomas (HCC) tissue. WDR76 plays a role as an E3 linker protein and mediates the polyubiquitination-dependent degradation of RAS. WDR76-mediated RAS destabilization results in the inhibition of proliferation, transformation, and invasion of liver cancer cells. WDR76−/− mice are more susceptible to diethylnitrosamine-induced liver carcinogenesis. Liver-specific WDR76 induction destabilizes Ras and markedly reduces tumorigenesis in HRasG12V mouse livers. The clinical relevance of RAS regulation by WDR76 is indicated by the inverse correlation of their expressions in HCC tissues. Our study demonstrates that WDR76 functions as a tumor suppressor via RAS degradation.
Retinal Microvascular Change in Hypertension as measured by Optical Coherence Tomography Angiography
Authors: Lee Woo Hyuk , Park Jae-Hyeong , Won Yeokyoung , Lee Min-Woo , Shin Yong-Il , Jo Young-Joon , Kim Jung-Yeul 
Published: January 2019

AbstractMany studies have reported the effect of hypertension on microcirculation of the retina. Advance of optical coherence tomography angiography (OCTA) allows us more detailed observations of microcirculation of the retina. Therefore, we compared OCTA parameters between chronic hypertension (disease duration of at least 10 yrs; Group A, 45 eyes), relieved hypertensive retinopathy (grade IV HTNR < 1 yr prior; Group B, 40 eyes), and normal controls [Group C (50 eyes) ≥ 50 yrs old and Group D (50 eyes) < 50 yrs old]. A 3 × 3 mm macular scan was performed in each group by OCTA. In vessel density of 3 mm full, group A and B were significantly decreased compared to normal control group (Group A vs. C; 19.4 mm−1vs. 20.1 mm−1, Group B vs. D; 19.8 mm−1vs. 21.8 mm−1, all p < 0.05). In foveal avascular zone, group A and B were significantly increased compared to normal control group (Group A vs. C; 0.35 mm2vs. 0.30 mm2, Group B vs. D; 0.36 mm2vs. 0.29 mm2, all p < 0.05). OCTA is useful for examining retinal microcirculatory changes in hypertension and we confirmed that hypertension affects the OCTA parameters. Considering the effect of hypertension on the change of microvasculature, care is required in the interpretation of OCTA parameters in various ophthalmic condition.
High intensity exercise inhibits carnitine palmitoyltransferase-I sensitivity to l-carnitine
Authors: Petrick Heather L. , Holloway Graham P. 
Published: January 2019

Abstract
The decline in fat oxidation at higher power outputs of exercise is a complex interaction between several mechanisms; however, the influence of mitochondrial bioenergetics in this process remains elusive. Therefore, using permeabilized muscle fibers from mouse skeletal muscle, we aimed to determine if acute exercise altered mitochondrial sensitivity to (1) adenosine diphosphate (ADP) and inorganic phosphate (Pi), or (2) carnitine palmitoyltransferase-I (CPT-I) independent (palmitoylcarnitine, PC) and dependent [palmitoyl-CoA (P-CoA), malonyl-CoA (M-CoA), and l-carnitine] substrates, in an intensity-dependent manner. As the apparent ADP Km increased to a similar extent following low (LI) and high (HI) intensity exercise compared with sedentary (SED) animals, and Pi sensitivity was unaltered by exercise, regulation of phosphate provision likely does not contribute to the well-established intensity-dependent shift in substrate utilization. Mitochondrial sensitivity to PC and P-CoA was not influenced by exercise, while M-CoA sensitivity was attenuated similarly following LI and HI. In contrast, CPT-I sensitivity to l-carnitine was only altered following HI, as HI exercise attenuated l-carnitine sensitivity by ∼40%. Moreover, modeling the in vivo concentrations of l-carnitine and P-CoA during exercise suggests that CPT-I flux is ∼25% lower following HI, attributed equally to reductions in l-carnitine content and l-carnitine sensitivity. Altogether, these data further implicate CPT-I flux as a key event influencing metabolic interactions during exercise, as a decline in l-carnitine sensitivity in addition to availability at higher power outputs could impair mitochondrial fatty acid oxidation.
Clinical Quality Improvement and Quality Improvement Research
Authors: Mormer Elaine , Stevans Joel 
Published: January 2019

Purpose
This article is intended to serve as a tutorial for speech-language pathology and audiology clinicians and researchers interested in pursuing quality improvement (QI) practice and research.

Method
Through a number of library database searches, author expertise, and first-hand experiences, we compiled this reference covering the history and landscape of clinical QI practice and QI research. We have included and explained definitions of QI activities and provided an overview of models and methods utilized in the implementation of QI programs. Drawing from scholarly literature on the QI process, we have included tools that should be useful for those clinicians and researchers pursuing QI projects. This article includes some examples of QI projects specific to speech-language pathology and audiology. One highlighted example examined a hospital process of identifying newly admitted patients at risk for communication breakdowns during patient–provider information exchange. Benefits and opportunities associated with QI activities are addressed, as well as barriers and facilitators.

Conclusion
QI practices and QI research are well within the scope of activities in which speech-language pathologists and audiologists should be engaged. QI is now recognized as a legitimate source of new knowledge and a direct route to improving outcomes and delivery of patient care across clinical settings.
Research–Practice Partnership: Application to Implementation of Multitiered System of Supports in Early Childhood Education
Authors: Goldstein Howard , McKenna Meaghan , Barker Robert M. , Brown Tracye H. 
Published: January 2019

Purpose
Research–practice partnerships (RPPs) offer a tool for identifying, generating, and implementing evidence-based strategies that improve practice, policies, and client outcomes. We offer a description of RPPs and elements that facilitate successful utilization. The origin of RPPs, various approaches, and anticipated barriers are discussed. We illustrate some of the challenges and rewards of establishing an RPP using an example of a project that sought to implement a multitiered system of supports among a variety of early childhood education classrooms in a large urban school district.

Method
A planning/leadership team established objectives and used surveys, focus groups, classroom observations, professional development records, and student outcome data to inform decision making.

Results
The district's progress in implementing multitiered system of supports in early childhood and ways in which implementation plans were modified as a result of data-based decision making are described. A number of unexpected obstacles interfered with original plans, requiring significant revisions in our theory of change and new strategies to overcome challenges.

Conclusion
This illustration helps elucidate critical elements of RPPs and highlights their applicability to researchers and practitioners in communication sciences and disorders.
A search for accreting young companions embedded in circumstellar disks
Authors: Cugno G. , Quanz S. P. , Hunziker S. , Stolker T. , Schmid H. M. , Avenhaus H. , Baudoz P. , Bohn A. J. , Bonnefoy M. , Buenzli E. , Chauvin G. , Cheetham A. , Desidera S. , Dominik C. , Feautrier P. , Feldt M. , Ginski C. , Girard J. H. , Gratton R. , Hagelberg J. , Hugot E. , Janson M. , Lagrange A.-M. , Langlois M. , Magnard Y. , Maire A.-L. , Menard F. , Meyer M. , Milli J. , Mordasini C. , Pinte C. , Pragt J. , Roelfsema R. , Rigal F. , Szulágyi J. , van Boekel R. , van der Plas G. , Vigan A. , Wahhaj Z. , Zurlo A. 
Published: January 2019

Context. In recent years, our understanding of giant planet formation progressed substantially. There have even been detections of a few young protoplanet candidates still embedded in the circumstellar disks of their host stars. The exact physics that describes the accretion of material from the circumstellar disk onto the suspected circumplanetary disk and eventually onto the young, forming planet is still an open question.
Aims. We seek to detect and quantify observables related to accretion processes occurring locally in circumstellar disks, which could be attributed to young forming planets. We focus on objects known to host protoplanet candidates and/or disk structures thought to be the result of interactions with planets.
Methods. We analyzed observations of six young stars (age 3.5–10 Myr) and their surrounding environments with the SPHERE/ZIMPOL instrument on the Very Large Telescope (VLT) in the Hα filter (656 nm) and a nearby continuum filter (644.9 nm). We applied several point spread function (PSF) subtraction techniques to reach the highest possible contrast near the primary star, specifically investigating regions where forming companions were claimed or have been suggested based on observed disk morphology.
Results. We redetect the known accreting M-star companion HD142527 B with the highest published signal to noise to date in both Hα and the continuum. We derive new astrometry (r=62.8−2.7+2.1 mas and PA=(98.7±1.8)°) and photometry (ΔN_Ha = 6.3−0.3+0.2 mag, ΔB_Ha = 6.7 ± 0.2 mag and ΔCnt_Ha = 7.3−0.2+0.3 mag) for the companion in agreement with previous studies, and estimate its mass accretion rate (Ṁ ≈ 1−2 × 10−10 M⊙yr−1). A faint point-like source around HD135344 B (SAO206462) is also investigated, but a second deeper observation is required to reveal its nature. No other companions are detected. In the framework of our assumptions we estimate detection limits at the locations of companion candidates around HD100546, HD169142, and MWC 758 and calculate that processes involving Hα fluxes larger than ~ 8 × 10−14–10−15 erg s−1 cm−2 (Ṁ > 10−10−10−12 M⊙yr−1) can be excluded. Furthermore, flux upper limits of ~10−14−10−15 erg s−1 cm−2 (Ṁ < 10−11–10−12 M⊙yr−1) are estimated within the gaps identified in the disks surrounding HD135344 B and TW Hya. The derived luminosity limits exclude Hα signatures at levels similar to those previously detected for the accreting planet candidate LkCa15 b.
Comet 67P/Churyumov-Gerasimenko rotation changes derived from sublimation-induced torques
Authors: Kramer T. , Läuter M. , Hviid S. , Jorda L. , Keller H. U. , Kührt E. 
Published: January 2019

Context.The change in rotation period and the orientation of the rotation axis of comet 67P/Churyumov-Gerasimenko (67P) can be deduced with high precision from images taken by the scientific imaging instruments on board the Rosetta mission. Non-gravitational forces are a natural explanation for these data.Aims.We describe observed changes in orientation of the rotation axis and the rotation period of 67P. We explain them based on a sublimation model with a best fit for the surface active fraction (model P). Torque effects of periodically changing gas emissions on the surface are considered.Methods.We solved the equation of state for the angular momentum in the inertial and the body-fixed frames and provide an analytic theory of the rotation changes in terms of Fourier coefficients, which are generally applicable to periodically forced rigid-body dynamics.Results.The torque-induced changes in rotation state constrain the physical properties of the surface, the sublimation rate, and the local active fraction of the surface.Conclusions.We determine a distribution of the local surface active fraction in agreement with the rotation properties, period, and orientation of 67P. The torque movement confirms that the sublimation increases faster than the insolation toward perihelion. The derived relatively uniform activity pattern is discussed in terms of related surface features.
Future scenarios of global plastic waste generation and disposal
Authors: Lebreton Laurent , Andrady Anthony 
Published: January 2019

AbstractThe accumulation of mismanaged plastic waste (MPW) in the environment is a global growing concern. Knowing with precision where litter is generated is important to target priority areas for the implementation of mitigation policies. In this study, using country-level data on waste management combined with high-resolution distributions and long-term projections of population and the gross domestic product (GDP), we present projections of global MPW generation at ~1 km resolution from now to 2060. We estimated between 60 and 99 million metric tonnes (Mt) of MPW were produced globally in 2015. In a business-as-usual scenario, this figure could triple to 155–265 Mt y−1 by 2060. The future MPW load will continue to be disproportionately high in African and Asian continents even in the future years. However, we show that this growth in plastic waste can be reduced if developing economies significantly invest in waste management infrastructures as their GDP grows in the future and if efforts are made internationally to reduce the fraction of plastic in municipal solid waste. Using our projections, we also demonstrate that the majority of MPW (91%) are transported via watersheds larger than 100 km2 suggesting that rivers are major pathways for plastic litter to the ocean.
High Rac1 activity is functionally translated into cytosolic structures with unique nanoscale cytoskeletal architecture
Authors: Marston Daniel J. , Anderson Karen L. , Swift Mark F. , Rougie Marie , Page Christopher , Hahn Klaus M. , Volkmann Niels , Hanein Dorit 
Published: January 2019

Significance
We have correlated signaling behaviors seen with biosensors (conformational changes of Rac1) with the nanoscale resolution of electron cryotomography. The workflow and approaches we describe bridge five orders of magnitude (tens of microns to nanometers) to identify, in the crowded environment within eukaryotic cells, distinct nanoarchitectures induced locally by Rac1 as it mediates cell motility, mechanosensing, and invasion. Our studies reveal a dynamic switching mechanism that generates a nanoscaffold system that can either propagate to highly complex actin filament architectures mandated by biological processes or completely dissipate. The workflow implemented here offers a powerful analytical tool not only for deciphering the function of Rho GTPase molecular switches but for the dynamics of many other macromolecular machines as well.
Clathrate hydrates in interstellar environment
Authors: Ghosh Jyotirmoy , Methikkalam Rabin Rajan J. , Bhuin Radha Gobinda , Ragupathy Gopi , Choudhary Nilesh , Kumar Rajnish , Pradeep Thalappil 
Published: January 2019

SignificanceFormation of clathrate hydrate (CH) requires high pressures and moderate temperatures, which enable their existence in marine sediments and the permafrost region of earth. The presence of CHs in interstellar medium (ISM) is still in question due to the extreme high vacuum and ultracold conditions present there. Here, we conclusively identified methane and carbon dioxide hydrates in conditions analogous to ISM. We found that molecular mobility and interactions play crucial roles in the formation of CHs, even though there is no external pressure to force cage formation. Various chemical processes on these hydrates in ISM may lead to relevant prebiotic molecules.
Accelerations – a new approach to quantify physical performance decline in male elite soccer?
Authors: Dalen Terje , Lorås Håvard , Hjelde Geir Håvard , Kjøsnes Terje Naess , Wisløff Ulrik 
Published: January 2019

AbstractThe aim of the current study was (1) to investigate whether the number of accelerations is a more precise estimate of performance decline in soccer compared to distances with high‐speed running (HSR) and (2) to compare changes in the number of accelerations and HSR distances across playing positions in order to examine whether the match profiles of the physical measures are consistent or demonstrate high interposition variability. The dataset includes domestic home games (N = 34) over three full seasons (2012–2014) for a team in the Norwegian Elite League. The change in the number of accelerations throughout the match demonstrates a more clear pattern compared to the distance covered by HSR. In numbers of accelerations, a systematic and linear decrease can be observed throughout the match, with 34% less accelerations from the first to the last 5‐minute period of the game (6.7 vs. 4.4 accelerations). This pattern of results captures the change in the number of accelerations across all positions. HSR distance had more variability during the match. All five positions investigated displayed a similar trend in accelerations and HSR profiles after the peak periods in each half. In contrast to the absolute number of accelerations, there were major positional differences in the mean HSR distance during the match. Our data suggest a more visible performance decline in the number of accelerations from the start to the end of the game, than the decline in the distance covered by HSR distance.