bluuebunny/crossref_metadata_2025 huggingface dataset:
Peptide‐poly(tert‐butyl methacrylate) conjugate into composite micelles in organic solvents versus peptide‐poly(methacrylic acid) conjugate into spherical and worm‐like micelles in water: Synthesis and self‐assembly
Authors: Saha Anupam , Jana Somdeb , Mandal Tarun K.
Published: June 2016

Peptide–polymer conjugates are versatile class of biomaterials composed of a peptide block covalently linked with a synthetic polymer block. This report demonstrates the synthesis of peptide‐poly(tert‐butyl methacrylate) (Peptide‐PtBMA) conjugates of varying molecular weights via a “grafting from” atom transfer radical polymerization (ATRP) technique using as‐synthesized peptide‐based initiator in toluene. Peptide‐PtBMA conjugate is soluble in many organic solvents and undergoes self‐assembly into micro/nanospheres in DMF/THF as observed from both FESEM and DLS results. The conjugate micro/nanospheres are nothing but the composite micelles formed by the secondary aggregation of primary micelles generated initially in these organic solvents. The hydrolysis of tert‐butyl groups of Peptide‐PtBMA conjugate leads to the formation of peptide‐poly(methacrylic acid) (Peptide‐PMA) conjugate. The circular dichroism (CD) analysis exhibits the presence of β‐sheet conformation of peptide moiety in synthesized conjugates. The formed Peptide‐PMA conjugate is soluble in water and owing to its amphiphilic character, the conjugate molecules self‐assemble into spherical micelles as well as worm‐like micelles upon increasing the concentration of conjugate in water. However, the sodium salt of Peptide‐PMA conjugates (Peptide‐PMAS) self‐assembles into only spherical swollen micelles in water at higher (pH ∼10). The critical aggregation concentrations (CACs) of both Peptide‐PMA and Peptide‐PMAS micelles are measured by fluorescence spectroscopy. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 3019–3031
Cancer beliefs and patient activation in a diverse, multilingual primary care sample
Authors: Hay Jennifer L. , Zabor Emily C. , Kumar Julie , Brennessel Debra , Kemeny Margaret M. , Lubetkin Erica I.
Published: June 2016

Objectives

Greater patient activation, defined as having the knowledge, skills, and confidence to manage one's health, is associated with cancer control behaviors. Cancer risk beliefs may be associated with patient activation, and delineating this relationship could inform cancer control interventions across diverse patient subgroups. This study examines associations between cancer risk beliefs, language preference, and patient activation within a multilingual urban primary care setting.

Design

Patients 18 years and older within a New York City public hospital serving a large proportion of non–native‐born Americans were surveyed regarding their cancer risk beliefs and patient activation in Haitian Creole, Spanish, or English based on language preference during a health care visit.

Results

The sample (N = 460) included 150 Haitian Creole speakers, 159 Spanish speakers, and 151 English speakers and was primarily non‐White (92%). Most participants (84%) had not been born in the United States. Cancer risk beliefs differed across language preference. Beliefs that cancer could be avoided by minimizing thoughts about cancer risk were significantly higher in Haitian Creole speakers than in others; reported negative emotion when thinking about cancer risk was higher in Spanish and English than in Haitian Creole speakers. These cancer risk beliefs were positively related to patient activation, even when controlling for language preference.

Conclusion

Cancer risk beliefs differ across language preference and are related to patient activation, making them potentially important in cancer control. Consideration of language represents important demographic stratification for understanding the frequency and relevance of different beliefs about cancer and patient activation.
Potential DNA binding and nuclease functions of ComEC domains characterized in silico
Authors: Baker James A. , Simkovic Felix , Taylor Helen M.C. , Rigden Daniel J.
Published: June 2016

Bacterial competence, which can be natural or induced, allows the uptake of exogenous double stranded DNA (dsDNA) into a competent bacterium. This process is known as transformation. A multiprotein assembly binds and processes the dsDNA to import one strand and degrade another yet the underlying molecular mechanisms are relatively poorly understood. Here distant relationships of domains in Competence protein EC (ComEC) of Bacillus subtilis (Uniprot: P39695) were characterized. DNA‐protein interactions were investigated in silico by analyzing models for structural conservation, surface electrostatics and structure‐based DNA binding propensity; and by data‐driven macromolecular docking of DNA to models. Our findings suggest that the DUF4131 domain contains a cryptic DNA‐binding OB fold domain and that the β‐lactamase‐like domain is the hitherto cryptic competence nuclease. Proteins 2016; 84:1431–1442. © 2016 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.
The part of a long beta hairpin from the scrapie form of the human prion protein is reconstructed in the synthetic CC36 protein
Authors: Khrustalev Vladislav Victorovich , Khrustaleva Tatyana Aleksandrovna , Szpotkowski Kamil , Poboinev Victor Vitoldovich , Kakhanouskaya Katsiaryna Yurieuna
Published: June 2016

Mechanisms of beta sheet formation by the human prion protein are not clear yet. In this work, we clarified the role of the region containing C‐half of the second helix and N‐half of the third helix of that protein in the process of alpha helix to beta sheet transition. Solid phase automatic synthesis of the original peptide (CC36: Cys179–Cys214) failed because of the beta hairpin formation in the region 206‐MERVVEQMC‐214 with a high beta strand potential. Using Met206Arg and Val210Arg substitutions, we increased the probability of alpha helix formation by that sequence. After that modification, the complete CC36 peptide with disulfide bond has been synthesized. Modified peptide has been studied by circular dichroism (CD) and fluorescence spectrography. According to the CD spectra analysis, the CC36 peptide contains 37% of residues in beta sheet and just 15% in helix. Thermal analysis under the control of CD shows that the secondary structure content of the peptide is stable from 5°C to 80°C. Dissociation of oligomers of the CC36 peptide finishes at 37°C according to the fluorescence analysis. The CC36 peptide is able to bind Mn2+ cations, which causes small temperature‐associated structural shifts at concentrations of 2 – 10·10−6 M. Predicted beta hairpin of the CC36 peptide (two beta strands are: 184‐IKQHTVT‐190 and 197‐TETDVKM‐205) should be the part of a longer beta hairpin from the scrapie form of the prion protein (PrPSc). Analogs of the CC36 peptide may be considered as antigens for the future development of a vaccine against PrPSc. Proteins 2016; 84:1462–1479. © 2016 Wiley Periodicals, Inc.
Accelerated molecular dynamics simulations of the octopamine receptor using GPUs: discovery of an alternate agonist‐binding position
Authors: Kastner Kevin W. , Izaguirre Jesús A.
Published: June 2016

Octopamine receptors (OARs) perform key biological functions in invertebrates, making this class of G‐protein coupled receptors (GPCRs) worth considering for insecticide development. However, no crystal structures and very little research exists for OARs. Furthermore, GPCRs are large proteins, are suspended in a lipid bilayer, and are activated on the millisecond timescale, all of which make conventional molecular dynamics (MD) simulations infeasible, even if run on large supercomputers. However, accelerated Molecular Dynamics (aMD) simulations can reduce this timescale to even hundreds of nanoseconds, while running the simulations on graphics processing units (GPUs) would enable even small clusters of GPUs to have processing power equivalent to hundreds of CPUs. Our results show that aMD simulations run on GPUs can successfully obtain the active and inactive state conformations of a GPCR on this reduced timescale. Furthermore, we discovered a potential alternate active‐state agonist‐binding position in the octopamine receptor which has yet to be observed and may be a novel GPCR agonist‐binding position. These results demonstrate that a complex biological system with an activation process on the millisecond timescale can be successfully simulated on the nanosecond timescale using a simple computing system consisting of a small number of GPUs. Proteins 2016; 84:1480–1489. © 2016 Wiley Periodicals, Inc.
Cardiovascular Safety Assessment in Early‐Phase Clinical Studies: A Meta‐Analytical Comparison of Exposure‐Response Models
Authors: Conrado DJ , Chen D , Denney WS
Published: June 2016

Exposure‐response analysis of QT interval in clinical studies has been proposed as a thorough QT study alternative. Many exposure‐response model structures have been proposed for cardiovascular (CV) safety markers, but few studies have compared models across multiple drugs. To recommend preferred drug‐effect exposure‐response models on vital signs and electrocardiogram (ECG) intervals, an individual‐level model‐based meta‐analysis (39 studies and 1,291 subjects) compared 90 model structures. Models were selected to describe the data and cross‐validate studies on the same drug. The most commonly selected baseline model was an unstructured model (estimation of a value at each study nominal time) for all measures but blood pressure. The unstructured model estimated a better cross‐validated drug‐effect when considering all markers. A linear model was the most commonly selected to characterize drug‐effect on all markers. We propose these models as a starting point assisting with CV safety exposure‐response assessment in nondedicated small studies with healthy subjects.
Government spending and the distribution of economic growth
Authors: Mayer Susan E. , Lopoo Leonard M. , Groves Lincoln H.
Published: June 2016

In the United States, total government spending, and especially government social spending, has increased greatly over the last 50 years. What effect this has had on economic growth is a subject of intense debate among politicians, policymakers, and economists. However, there has been less attention paid to the distributional effects of government spending even though economic inequality has grown greatly over the last generation and much social spending is at least indirectly intended to reduce inequality. The effects of government social spending in the United States on growth in family income at deciles of the income distribution were estimated. The results suggested that social spending but not non‐social spending was likely to increase growth in family income per capita measured over 10‐year intervals. The largest effects of social spending were for deciles below the median income. At no point in the distribution does social spending have a negative effect.
Windswept hip deformity in children with cerebral palsy: A population-based prospective follow-up
Authors: Hägglund Gunnar , Lauge-Pedersen Henrik , Persson Bunke Måns , Rodby-Bousquet Elisabet
Published: June 2016

Purpose

To analyze the development of windswept hip deformity (WS) in a total population of children with cerebral palsy (CP) up to 20 years of age, the association between WS and hip dislocation, and femoral varus osteotomy and scoliosis, and the impact of a hip surveillance program on the subsequent incidence of WS.

Methods

This is a prospective study on children with CP in southern Sweden included in the Swedish follow-up programme and registry for CP (CPUP). All children born between 1990 and 1995 with CP were included; those born between 1990 and 1991 did not partake in the hip surveillance program until they were older (3–5 years of age) and served as a historic control group. Children born between 1992 and 1995 were included in the hip surveillance program from about 2 years of age and constituted the study group.

Results

In the control group, 12 of 68 children (18 %) developed WS. In the study group of 139 children, 13 (9 %) developed WS (p = 0.071). Of all 25 children with WS, 21 also developed scoliosis and 5 developed a hip dislocation. The number of children with WS starting in the lower extremities was significantly lower in the study group ( p = 0.028). No difference between the two groups was seen regarding WS that started in combination with scoliosis.

Conclusion

With early inclusion in a hip surveillance program and early treatment of contractures, it appears possible to reduce the frequency of WS starting in the lower extremities.
Distribution systems in omni-channel retailing
Authors: Hübner Alexander , Holzapfel Andreas , Kuhn Heinrich
Published: June 2016

The growing importance of online sales means that traditional bricks-and-mortar retailers need to create new distribution systems to serve customers through multiple channels. Building an effective and efficient omni-channel (OC) distribution system, however, leads to multiple challenges. The questions arise for example, from where online orders should be fulfilled, how delivery and return processes can be organized, and which context-specific OC distribution systems exist. Answering these questions retail research and practice require an overall view of the distribution concepts for direct-to-customer and store deliveries in OC retailing, including the associated return processes. This overall picture is still missing in the literature. We conducted an exploratory study to close this observable gap in the literature. This exploratory study is based on semi-structured interviews with major OC retailers in German-speaking countries and was complemented by market data research and discussions with further experts in the field of OC retailing. Based on the results of the study, the forward distribution system in OC retailing is characterized by the sources (supplier DCs, retailer DCs, stores) and destinations (home, store) which describe the options for store delivery, home delivery, and store pickup. Return processes are likewise characterized by the sources (store, home) and destinations (store, DC, return center). This framework forms the foundation for analyzing contextual criteria, identifying when the different conceptual designs are applied, determining industry-specific characteristics, and illustrating ways to further advance OC retailing. The present paper, therefore, contributes to the literature in three main areas: (1) it identifies and systematizes the forward and backward concepts in OC retailing, (2) it reveals application and development areas for achieving excellence in OC fulfillment and logistics, and (3) shows the need for developing sector- and context-specific OC distribution systems.
Brief report: Longitudinal associations between sedentary behaviours and depressive symptoms in adolescent girls
Authors: Raudsepp Lennart
Published: June 2016

The purpose of this study was to examine longitudinal associations between sedentary behaviours (SB) and depressive symptoms in adolescent girls. Participants (n = 341) completed the self‐report ecological momentary assessments diary for the measurement of sedentary behaviours and completed the Center for Epidemiological Studies Depression scale (CES‐D) at three time points during a 4‐year period. The association between SB and depressive symptoms over time was examined with latent growth models. Both depressive symptoms and SB increased over time. Baseline levels of depressive symptoms were predictive of change in SB, but initial levels of SB did not predict changes in depressive symptoms. These prospective associations remained controlling for age, home electronic equipment and socioeconomic status.
Sexual intercourse among adolescent daughters of mothers with depressive symptoms from minority families
Authors: Sang Jina , Cederbaum Julie A. , Hurlburt Michael S.
Published: June 2016

This study investigated the association between maternal depressive symptoms and adolescent engagement in sexual intercourse in a non‐clinical sample of mothers and their adolescent daughters from minority families. The current study explores ways in which maternal depression, family factors, and adolescent sex interact. Data were from a cross‐sectional study of 176 mother–daughter dyads, including a subset of mothers with HIV. Logistic regression analyses revealed that among mothers who were not current marijuana users, more maternal depressive symptoms was associated with daughters' engagement in sexual intercourse. Neither parent‐child conflict nor parental involvement significantly mediated the relationship between maternal depressive symptoms and adolescent sex. This study provides the first empirical evidence that non‐clinical depressive symptoms in mothers are associated with adolescent engagement in sexual intercourse.
Extracellular space diffusion analysis in the infant and adult rat striatum using magnetic resonance imaging
Authors: Yang Shuangfeng , Wang Yan , Li Kai , Tang Xiaolu , Zhang Kuo , Shi Chunyan , Han Hongbin , Peng Yun
Published: June 2016

The extracellular space (ECS) in the brain provides an extrasynaptic transfer channel among neurons, axons and glial cells. It is particularly important in the early stage after birth, when angiogenesis is not yet complete and the ECS may provide the main pathway for metabolite transport. However, the characteristics of extracellular transport remain unclear. In this study, a novel magnetic resonance imaging (MRI) method was used to perform real‐time visualization and quantification of diffusion in the brain ECS of infant (postnatal day 10 (P10)) and adult rats. Using a modified diffusion equation and the linear relationship between the signal intensity and the gadolinium‐diethylenetriaminepentaacetic acid (Gd‐DTPA) concentration, diffusion parameters were obtained; these parameters include the effective diffusion coefficient (D*), clearance rate (k'), tortuosity (λ) and the volume fraction of distribution (Vd%). There were significant differences in the diffusion parameters between P10 and adult rats. This finding provides a reference for future treatment of brain diseases using drugs administered via interstitial pathways.
Health education and clinical care of immigrant women with female genital mutilation/cutting who request postpartum reinfibulation
Authors: Abdulcadir Jasmine , McLaren Sophie , Boulvain Michel , Irion Olivier
Published: June 2016

Objective

To evaluate the percentage of women with female genital mutilation/cutting who request postpartum reinfibulation, and to assess outcomes after specific care and counseling.

Methods

A retrospective review was undertaken of consecutive medical files of immigrant women with FGM/C who attended a center in Geneva, Switzerland, between April 1, 2010, and January 8, 2014. The number of postpartum reinfibulation requests and outcomes were assessed. If a patient requests postpartum reinfibulation despite receiving detailed information and counseling, a longer follow‐up is arranged for further counseling.

Results

Among 196 women with FGM/C, 8 (4.1%) requested postpartum reinfibulation. All eight were of East African origin, had FGM/C type III, and received a longer and more targeted follow‐up than did those who did not request reinfibulation. After at least 1 year of follow‐up, none of the eight was willing to undergo reinfibulation. One woman who attended the clinic only once during her first pregnancy consulted the emergency ward of the study center 3 years later because of postcoital bleeding following infibulation performed in her home country a few months after her second delivery in Switzerland.

Conclusion

Specific care and counseling for women with FGM/C type III can improve the acceptability of defibulation without reinfibulation.
Long‐term functional outcomes following mesh‐augmented posterior vaginal prolapse repair
Authors: Weintraub Adi Y. , Friedman Talia , Baumfeld Yael , Neymeyer Joerg , Neuman Menahem , Krissi Haim
Published: June 2016

Objective

To assess long‐term patient‐centered functional outcomes following posterior vaginal wall repair using mesh implants.

Method

The present prospective telephone interview study enrolled a cohort of women who had undergone posterior vaginal wall repair with mesh between January 1, 2006 and February 28, 2009, at a single center in Israel. Patients were asked to report long‐term outcomes, and demographic, clinical, intraoperative, and postoperative follow‐up data were retrieved from patients’ medical files. Multivariable logistic regression models were used to asses associations between baseline characteristics and long‐term outcomes.

Results

In total, 102 patients were contacted, with 80 (78.4%) at 61–83 months after surgery agreeing to participate. A recurrence of prolapse symptoms was reported by 14 patients (18%) (12 required a corrective procedure), mesh had been removed from two patients owing to erosion/extrusion, and two others had undergone removal of granulation tissue. Long‐term, bothersome symptoms were reported by 13 (16%) patients. Parity and previous hysterectomy were associated with lower odds of long‐term adverse outcomes, and the location of the apical (C/D) pelvic organ prolapse quantification point and a change in its position following surgery were associated with increased odds of adverse outcomes.

Conclusion

The long‐term adverse‐outcome rate was low for patients who underwent posterior vaginal mesh augmentation. These results highlight the importance of apical support for good long‐term functional outcomes.
Choice under incomplete information on incumbents: Why consumers with stronger preferences are more likely to abandon their prior choices
Authors: Irmak Caglar , Kramer Thomas , Sen Sankar
Published: June 2016

Consumers often encounter information about new brands that is not available for their preliminary or prior choices. For example, continued browsing might expose consumers to information that is unknown for an option they already placed in their shopping cart. How might preference strength affect their reactions to such missing information on their prior choices? Much research suggests that consumers with strong prior preferences are likely to employ motivated reasoning to bolster and retain the preliminary choice. However, we document a heretofore unexamined condition under which those with relatively stronger prior preferences for an incumbent are more likely to abandon it than those with weaker prior preferences. We argue that this occurs because those with relatively stronger (vs. weaker) prior preferences experience more cognitive dissonance when information on new attributes is missing on just the incumbent but not on its competitors.
Role of 2D Strain in the Early Identification of Cardiac Dysfunction and in the Risk Stratification of Arteriogenic Erectile Dysfunction Patients
Authors: Zehir Regayip , Karabay Can Yucel , Kocabay Gonenc , Erdem Mehmet Remzi , Balaban Muhsin , Kirma Cevat
Published: June 2016

Background

Vasculogenic erectile dysfunction is a harbinger of vascular disease. Comprehensive cardiac workup is accepted to be beneficial in men with this condition, especially those with otherwise unrecognized cardiovascular disease. We aimed to evaluate the role of two-dimensional speckle-tracking echocardiography (2D-STE) for noninvasive evaluation in patients with documented arteriogenic erectile dysfunction.

Methods

64 consecutive men with Doppler proven erectile dysfunction of more than 3 months of duration were recruited. Patients divided into 2 groups according to mean peak systolic velocity (PSV). Patients with PSV <20 cm/sn constituted Group 1 and patients with PSV ≥20 cm/sn constituted Group 2. All underwent echocardiography and were compared. According to the 2D-STE analysis for the left atrium (LA); strain during ventricular systole (LARes), during late diastole (LA-Pump), strain rate during ventricular contraction (LA-SRs), during passive ventricular filling (LA-SRe), during active atrial contraction (LASRa) values and for LV; global longitudinal strain (GLS), strain rate in systole (GSRs), strain rate in early diastole (GSRe), and strain rate in late diastole (GSRa) values were obtained.

Results

Beside diastolic parameters, LA-Res and LA-Pump were found to be significantly different between groups. GLS and GSR values were lower in Group 1. Moreover, correlation analysis revealed a significant correlation of GLS values with PSV (r = −0.4, P = .001).

Conclusion

Myocardial deformation parameters by 2D-STE are valuable for detection of subclinical cardiovascular dysfunction in men with arteriogenic erectile dysfunction. This noninvasive method may be used as an emerging prognostic marker for risk stratification.
Theoretical and numerical research of wire array Z-pinch and dynamic hohlraum at IAPCM
Authors: Ding Ning , Zhang Yang , Xiao Delong , Wu Jiming , Dai Zihuan , Yin Li , Gao Zhiming , Sun Shunkai , Xue Chuang , Ning Cheng , Shu Xiaojian , Wang Jianguo
Published: June 2016

Dense Z-pinch plasmas are powerful and energy-efficient laboratory sources of X-rays, and show the possibility to drive inertial confinement fusion (ICF). Recent advances in wire-array Z-pinch and Z-pinch dynamic hohlraum (ZPDH) researches at the Institute of Applied Physics and Computational Mathematics are presented in this paper. Models are setup to study different physical processes. A full circuit model (FCM) was used to study the coupling between Z-pinch implosion and generator discharge. A mass injection model with azimuthal modulation was setup to simulate the wire-array plasma initiation, and the two-dimensional MHD code MARED was developed to investigate the Z-pinch implosion, MRT instability, stagnation and radiation. Implosions of nested and quasi-spherical wire arrays were also investigated theoretically and numerically. Key processes of ZPDH, such as the array–foam interaction, formation of the hohlraum radiation, as well as the following capsule ablation and implosion, were analyzed with different radiation magneto-hydrodynamics (RMHD) codes. An integrated 2D RMHD simulation of dynamic hohlraum driven capsule implosion provides us the physical insights of wire-array plasma acceleration, shock generation and propagation, hohlraum formation, radiation ablation, and fuel compression.
Geoscientists Visit Their Legislators on Capitol Hill
Authors: Borgfeldt Taylor
Published: June 2016

The American Geophysical Union's Congressional Visits Day acquaints members of Congress with the breadth of geophysical research being carried out in their districts and across the nation.
Focusing the Human Lens on Glacial Outburst Floods
Authors: Wendel JoAnna
Published: June 2016

To better prepare mountain communities for possible floods, experts say that it is important to understand the communities themselves.
The Ca2+/Mn2+-transporting SPCA2 pump is regulated by oxygen and cell density in colon cancer cells
Authors: Jenkins James , Papkovsky Dmitri B. , Dmitriev Ruslan I.
Published: June 2016

The mammalian SPCA1 and SPCA2 ATPases localize in membranes of the secretory pathway and transport ions of Ca2+ and Mn2+. The role of tissue-specific SPCA2 isoform, highly expressed in lungs, mammary gland and gastrointestinal tract, is poorly understood. To elucidate the function of SPCA2, we studied human colon cancer HCT116 cells, grown under ambient and decreased O2 levels. We found that in contrast with other Ca2+-ATPase isoforms the expression of SPCA2 was up-regulated under hypoxia (3% O2), in both adherent (2D) and spheroid (3D) cultures. In spheroids, experiencing lowest O2 levels (30–50 μM, measured by phosphorescence lifetime imaging microscopy), we observed lower staining with reactive oxygen species (ROS)-specific fluorescent probe, which correlated with increased SPCA2. However, SPCA2 expression was up-regulated in cells exposed to reactive oxygen and nitrogen species donors, and when grown at higher density. We noticed that the culture exposed to hypoxia showed overall increase in S phase-positive cells and hypothesized that SPCA2 up-regulation under hypoxia can be linked to Mn2+-dependent cell cycle arrest. Consequently, we found that SPCA2-transfected cells display a higher number of cells entering S phase. Altogether, our results point at the important role of SPCA2 in regulation of cell cycle in cancer cells.
Directly measuring single-molecule heterogeneity using force spectroscopy
Authors: Hinczewski Michael , Hyeon Changbong , Thirumalai D.
Published: June 2016

Significance

The relationship between structure and function is the heart of modern cell biology. Technological innovations in manipulating single molecules of proteins, DNA/RNA, and their complexes, are beginning to reveal the surprising intricacies of this relationship. In certain cases, the same molecule randomly switches between various long-lived structures, each with different functional properties. We present a theory to extract the extent and dynamics of these structural fluctuations from single-molecule experimental data. We find large heterogeneity in DNA and RNA complexes, supporting the notion that energy landscapes involving nucleic acids are rugged. Our work shows that functional heterogeneity is far more common than previously thought and suggests experimental approaches for estimating the timescales of these fluctuations with unprecedented accuracy.
FtsK translocation permits discrimination between an endogenous and an imported Xer/
dif
recombination complex
Authors: Fournes Florian , Crozat Estelles , Pages Carine , Tardin Catherine , Salomé Laurence , Cornet François , Rousseau Philippe
Published: June 2016

Significance

This study focuses on a molecular machine (Xer/
dif
/FtsK) involved in circular chromosome processing during the bacterial cell cycle. Xer site-specific recombinases are well known to act at the chromosomal
dif
(dimer resolution) sites for chromosome dimer resolution (CDR). The Xer/
dif
recombination machine is, however, highly versatile and is also implicated in integration and excision of mobile genetic elements (MGE). Whereas CDR depends on the FtsK DNA translocase, MGE mobility somehow escapes this control. Focusing on the case of the gonococcal genetic island found in pathogenic
Neisseria
species, we reveal how FtsK distinguishes a Xer/
dif
complex involved in vertical genetic transfer (CDR) from one involved in horizontal gene transfer (MGE mobility).
Tumor-associated fibroblasts predominantly come from local and not circulating precursors
Authors: Arina Ainhoa , Idel Christian , Hyjek Elizabeth M. , Alegre Maria-Luisa , Wang Ying , Bindokas Vytautas P. , Weichselbaum Ralph R. , Schreiber Hans
Published: June 2016

Significance

Fibroblasts constitute an important element of tumors and have received considerable attention in recent years due to their tumor-promoting and immunosuppressive properties. As a consequence, tumor-associated fibroblasts (TAFs) are considered an attractive target for cancer therapies. However, their origin remains controversial, with some evidence pointing at a local origin, whereas many publications suggest a significant contribution of progenitors from bone marrow. We found that TAFs derive almost exclusively from local sources. Therefore, therapeutic strategies to target fibroblasts must exploit local recruitment and the unique transcriptional and response patterns of fibroblasts from different sites.
Relating conformation to function in integrin α
5
β
1
Authors: Su Yang , Xia Wei , Li Jing , Walz Thomas , Humphries Martin J. , Vestweber Dietmar , Cabañas Carlos , Lu Chafen , Springer Timothy A.
Published: June 2016

Significance

β
1
integrins form the largest and most diverse integrin subfamily, with 12 distinct αβ heterodimers. Together, the seven other integrin β-subunits form an equal number of 12 heterodimers. Despite speculation that different integrin subfamilies may differ in activation mechanism or conformation, we show that α
5
β
1
, similar to β
2
and β
3
integrins, can adopt the bent-closed, extended-closed, and extended-open overall global conformational states. We characterize nine function-perturbing antibodies for the subunit and domain they bind and the conformation they stabilize. Only the extended-open α
5
β
1
conformation mediates adhesion to fibronectin. Our results enable many cell biological studies on the 12 β
1
integrins to be interpreted in terms of the integrin conformational states on cell surfaces that are stabilized.
Electron collisions with atoms, ions, molecules, and surfaces: Fundamental science empowering advances in technology
Authors: Bartschat Klaus , Kushner Mark J.
Published: June 2016

Electron collisions with atoms, ions, molecules, and surfaces are critically important to the understanding and modeling of low-temperature plasmas (LTPs), and so in the development of technologies based on LTPs. Recent progress in obtaining experimental benchmark data and the development of highly sophisticated computational methods is highlighted. With the cesium-based diode-pumped alkali laser and remote plasma etching of Si
3
N
4
as examples, we demonstrate how accurate and comprehensive datasets for electron collisions enable complex modeling of plasma-using technologies that empower our high-technology–based society.
Caenorhabditis elegans
responses to bacteria from its natural habitats
Authors: Samuel Buck S. , Rowedder Holli , Braendle Christian , Félix Marie-Anne , Ruvkun Gary
Published: June 2016

Significance

Caenorhabditis
elegans
is a major model organism, both from the pathogenesis dimension and also for metabolism, aging, and developmental biology perspectives. And yet, its natural ecology, most especially, its natural microbiome, is almost untouched. Here we establish the natural microbial community of
C. elegans
. Using extensive culture collections, we categorize its spectrum of responses (from antagonistic to beneficial) to a wide breadth of wild bacteria with nearly 80% of isolates supporting robust growth. In the wild, specific microbes correlate with the population state of the animals, which is supported by reconstruction experiments in the lab. Thus, a simplified natural community related to that found in the wild can now be studied in the laboratory for its impact on
C. elegans
physiology.
Quality Standards, Industry Structure, and Welfare in a Global Economy
Authors: Gaigné Carl , Larue Bruno
Published: June 2016

We study the impact that mimimum quality standards have on industry structure, trade, and welfare when firms can develop their own private standard with a higher quality than the public standard. We introduce vertical differentiation in a firm‐based trade model in which firms differ in terms of their productivity and non‐cooperatively select the quality and price of their product. A higher public standard increases prices set by constrained and unconstrained firms, but the effect on firms' output is generally ambiguous for both types of firms. The most productive firms raise their private standard and enjoy higher profits at the expense of less productive firms. A public standard can increase welfare, especially when there is a high concentration of low productivity domestic firms because of a better allocation of resources.
An assessment of post-release mortality for a commonly discarded deep-sea isopod (Bathynomus giganteus) using reflex impairment
Authors: Talwar Brendan , Brooks Edward J. , Dean Grubbs R.
Published: June 2016

Estimates of post-release mortality (PRM) rates for discarded bycatch are largely unknown across marine fisheries and represent a substantial source of uncertainty when estimating total fishery mortality. One way to predict PRM is through the use of reflex action mortality predictors (RAMP), whereby the presence or absence of target reflexes and known post-release fate are used to create a delayed mortality model. We employed reflex impairment assessments in concert with post-capture caging and video monitoring to predict 5-d PRM rates for the deep-sea giant isopod Bathynomus giganteus, a common bycatch species in numerous deepwater fisheries worldwide, and also considered the factors contributing to mortality. Mortality rates 5 d post-capture ranged from 50 to 100% and both RAMP scores and time at the surface were significant predictors of mortality, although our conclusions regarding the effect of surface time are limited. In-cage video documented little movement within the 24-h monitoring period following capture, and it appeared that surviving individuals often fed within the holding period after cage deployment. Our results suggest that PRM in B. giganteus is common and that this unaccounted source of mortality should be quantified for other deep-sea crustaceans captured as bycatch.
Association of nadir oxygen delivery on cardiopulmonary bypass with serum glial fibrillary acid protein levels in paediatric heart surgery patients
Authors: Magruder J. Trent , Hibino Narutoshi , Collica Sarah , Zhang Huaitao , Harness H. Lynn , Heitmiller Eugenie S. , Jacobs Marshall L. , Cameron Duke E. , Vricella Luca A. , Everett Allen D.
Published: June 2016

OBJECTIVES

Protecting the brain during cardiac surgery is a major challenge. We evaluated associations between nadir oxygen delivery (DO2) during paediatric cardiac surgery and a biomarker of brain injury, glial fibrillary acidic protein (GFAP).

METHODS

Blood samples were obtained during a prospective, single-centre observational study of children undergoing congenital heart surgery with cardiopulmonary bypass (CPB) (2010–2011). Remnant blood samples, collected serially prior to cannulation for bypass and until incision closure, were analysed for GFAP levels. Perfusion records were reviewed to calculate nadir DO2. Linear regression analysis was used to assess the association between nadir DO2 and GFAP levels.

RESULTS

A total of 116 consecutive children were included, with the median age of 0.75 years (interquartile range: 0.42–8.00) and the median weight of 8.3 kg (5.8–20.0). Single-ventricle anatomy was present in 19 patients (16.4%). Deep hypothermic circulatory arrest (DHCA) was used in 14 patients (12.1%). On univariable analysis, nadir DO2 was significantly associated with GFAP values measured during rewarming on CPB (P = 0.005) and after CPB decannulation (P = 0.02). On multivariable analysis controlling for CPB time, DHCA and procedure risk category, a significant negative relationship remained between nadir DO2 and post-CPB GFAP (P = 0.03).

CONCLUSIONS

Lower nadir DO2 is associated with increased GFAP levels, suggesting that diminished DO2 during paediatric heart surgery may be contributing to neurological injury. The DO2–GFAP relationship may provide a useful measure for the implementation of neuroprotective strategies in paediatric heart surgery, including goal-directed perfusion.
Discovery of hard phase lags in the pulsed emission of GRO J1744−28
Authors: D'Aì A. , Burderi L. , Di Salvo T. , Iaria R. , Pintore F. , Riggio A. , Sanna A.
Published: June 2016

We report on the discovery and energy dependence of hard phase lags in the 2.14 Hz pulsed profiles of GRO J1744−28. We used data from XMM–Newton and NuSTAR. We were able to well constrain the lag spectrum with respect to the softest (0.3–2.3 keV) band: the delay shows increasing lag values reaching a maximum delay of ∼12 ms, between 6 and 6.4 keV. After this maximum, the value of the hard lag drops to ∼7 ms, followed by a recovery to a plateau at ∼9 ms for energies above 8 keV. NuSTAR data confirm this trend up to 30 keV, but the measurements are statistically poorer, and therefore, less constraining. The lag-energy pattern up to the discontinuity is well described by a logarithmic function. Assuming this is due to a Compton reverberation mechanism, we derive a size for the Compton cloud Rcc ∼ 120 Rg, consistent with previous estimates on the magnetospheric radius. In this scenario, the sharp discontinuity at ∼6.5 keV appears difficult to interpret and suggests the possible influence of the reflected component in this energy range. We therefore propose the possible coexistence of both Compton and disc reverberation to explain the scale of the lags and its energy dependence.
A close look at secular evolution: boxy/peanut bulges reduce gas inflow to the central kiloparsec
Authors: Fragkoudi F. , Athanassoula E. , Bosma A.
Published: June 2016

In this Letter we investigate the effect of boxy/peanut (b/p) bulges on bar-induced gas inflow to the central kiloparsec, which plays a crucial role on the evolution of disc galaxies. We carry out hydrodynamic gas response simulations in realistic barred galaxy potentials, including or not the geometry of a b/p bulge, to investigate the amount of gas inflow induced in the different models. We find that b/p bulges can reduce the gas inflow rate to the central kiloparsec by more than an order of magnitude, which leads to a reduction in the amount of gas available in the central regions. We also investigate the effect of the dark matter halo concentration on these results, and find that for maximal discs, the effect of b/p bulges on gas inflow remains significant. The reduced amount of gas reaching the central regions due to the presence of b/p bulges could have significant repercussions on the formation of discy- (pseudo-) bulges, on the amount of nuclear star formation and feedback, on the fuel reservoir for AGN activity, and on the overall secular evolution of the galaxy.
Biochemical and genetic analysis of the role of the viral polymerase in enterovirus recombination
Authors: Woodman Andrew , Arnold Jamie J. , Cameron Craig E. , Evans David J.
Published: June 2016

Genetic recombination in single-strand, positive-sense RNA viruses is a poorly understand mechanism responsible for generating extensive genetic change and novel phenotypes. By moving a critical cis-acting replication element (CRE) from the polyprotein coding region to the 3′ non-coding region we have further developed a cell-based assay (the 3′CRE-REP assay) to yield recombinants throughout the non-structural coding region of poliovirus from dually transfected cells. We have additionally developed a defined biochemical assay in which the only protein present is the poliovirus RNA dependent RNA polymerase (RdRp), which recapitulates the strand transfer events of the recombination process. We have used both assays to investigate the role of the polymerase fidelity and nucleotide turnover rates in recombination. Our results, of both poliovirus intertypic and intratypic recombination in the CRE-REP assay and using a range of polymerase variants in the biochemical assay, demonstrate that RdRp fidelity is a fundamental determinant of recombination frequency. High fidelity polymerases exhibit reduced recombination and low fidelity polymerases exhibit increased recombination in both assays. These studies provide the basis for the analysis of poliovirus recombination throughout the non-structural region of the virus genome and provide a defined biochemical assay to further dissect this important evolutionary process.
Anatomic Fat Depots and Coronary Plaque Among Human Immunodeficiency Virus-Infected and Uninfected Men in the Multicenter AIDS Cohort Study
Authors: Palella Frank J. , McKibben Rebeccah , Post Wendy S. , Li Xiuhong , Budoff Matthew , Kingsley Lawrence , Witt Mallory D. , Jacobson Lisa P. , Brown Todd T.
Published: June 2016

Methods.  In a cross-sectional substudy of the Multicenter AIDS Cohort Study, noncontrast cardiac computed tomography (CT) scanning for coronary artery calcium (CAC) scoring was performed on all men, and, for men with normal renal function, coronary CT angiography (CTA) was performed. Associations between fat depots (visceral adipose tissue [VAT], abdominal subcutaneous adipose tissue [aSAT], and thigh subcutaneous adipose tissue [tSAT]) with coronary plaque presence and extent were assessed with logistic and linear regression adjusted for age, race, cardiovascular disease (CVD) risk factors, body mass index (BMI), and human immunodeficiency virus (HIV) parameters.

Results.  Among HIV-infected men (n = 597) but not HIV-uninfected men (n = 343), having greater VAT was positively associated with noncalcified plaque presence (odds ratio [OR] = 1.04, P < .05), with a significant interaction (P < .05) by HIV serostatus. Human immunodeficiency virus-infected men had lower median aSAT and tSAT and greater median VAT among men with BMI <25 and 25–29.9 kg/m2. Among HIV-infected men, VAT was positively associated with presence of coronary plaque on CTA after adjustment for CVD risk factors (OR = 1.04, P < .05), but not after additional adjustment for BMI. There was an inverse association between aSAT and extent of total plaque among HIV-infected men, but not among HIV-uninfected men. Lower tSAT was associated with greater CAC and total plaque score extent regardless of HIV serostatus.

Conclusions.  The presence of greater amounts of VAT and lower SAT may contribute to increased risk for coronary artery disease among HIV-infected persons.
Unanticipated Effects of New Drug Availability on Antiretroviral Durability: Implications for Comparative Effectiveness Research
Authors: Eaton Ellen F. , Tamhane Ashutosh R. , Burkholder Greer A. , Willig James H. , Saag Michael S. , Mugavero Michael J.
Published: June 2016

Background.  Durability of antiretroviral (ARV) therapy is associated with improved human immunodeficiency virus (HIV) outcomes. Data on ARV regimen durability in recent years and clinical settings are lacking.

Methods.  This retrospective follow-up study included treatment-naive HIV-infected patients initiating ARV therapy between January 2007 and December 2012 in a university-affiliated HIV clinic in the Southeastern United States. Outcome of interest was durability (time to discontinuation) of the initial regimen. Durability was evaluated using Kaplan-Meier survival analyses. Cox proportional hazard analyses was used to evaluate the association among durability and sociodemographic, clinical, and regimen-level factors.

Results.  Overall, 546 patients were analyzed. Median durability of all regimens was 39.5 months (95% confidence interval, 34.1–44.4). Commonly prescribed regimens were emtricitabine and tenofovir with efavirenz (51%; median duration = 40.1 months) and with raltegravir (14%; 47.8 months). Overall, 67% of patients had an undetectable viral load at the time of regimen cessation. Discontinuation was less likely with an integrase strand transfer inhibitor (adjusted hazards ratio [aHR] = 0.35, P = .001) or protease inhibitor-based regimen (aHR = 0.45, P = .006) and more likely with a higher pill burden (aHR = 2.25, P = .003) and a later treatment era (aHR = 1.64, P < .001).

Conclusions.  Initial ARV regimen longevity declined in recent years contemporaneous with the availability of several new ARV drugs and combinations. Reduced durability mostly results from a preference for newly approved regimens rather than indicating failing therapy, as indicated by viral suppression observed in a majority of patients (67%) prior to regimen cessation. Durability is influenced by extrinsic factors including new drug availability and provider preference. Medication durability must be interpreted carefully in the context of a dynamic treatment landscape.