bluuebunny/crossref_metadata_2025 huggingface dataset:
Abdominal obesity in adolescents: Development of age‐specific waist circumference cut‐offs linked to adult IDF criteria
Authors: Bravo Jorge , Raimundo Armando M. , Santos Diana A. , Timón Rafael , Sardinha Luís B.
Published: July 2017

Objectives

The purpose of this study was to develop age‐ and sex‐specific waist circumference (WC) cut‐off points, linked to older adolescent and adult criteria for abdominal obesity, to be applied to children in the clinical setting.

Methods

A total of 16,788 adolescents aged 10 to 16 years were assessed for WC. Smoothed age and sex‐specific WC curves were obtained using Cole's LMS method.

Results

Percentiles that corresponded to the International Diabetes Federation (IDF) recommendations used for older adolescents and adults (16+ years old) were the 97th percentile for boys and the 87th percentile for girls. Using these cutoffs, a total of 368 boys and 1138 girls were categorized as abdominally obese, in contrast to 1654 boys and 987 girls that were identified using the current IDF pediatric criteria (90th percentile).

Conclusions

We provide age‐ and sex‐specific cut‐off points that can be used to identify abdominal obesity in adolescents. The present findings provide a tool that can be used in the clinical setting for the early detection and prevention of adult obesity. Population‐specific cutoffs may be required for pediatric ages to diagnose children at risk.
Sexual and Regional Differences in Myosin Heavy Chain Expression in the Rat External Urethral Sphincter
Authors: Tsumori Toshiko , Tsumiyama Wakako
Published: July 2017

The external urethral sphincter is a unique striated muscle surrounding the urethra that plays a crucial role in urinary continence, and a comprehensive understanding of its morphology is needed to determine the pathophysiology underlying urinary incontinence and find suitable therapies. Differences between the sexes and among species regarding the fiber types present remain controversial. This study used triple immunofluorescence labeling to visualize one slow (Type 1) and two fast (Types 2A and 2B) myosin isoforms in rat external urethral sphincters from both sexes. Type 2A fibers predominated throughout the sphincter and Type 2B fibers were restricted to the proximal one‐third of the external urethral sphincter in the female rats. Type 1 fibers were present adluminally and were concentrated in the proximal and distal segments of the sphincter. While most of the male external urethral sphincter comprised Type 2B fibers, Type 2A fibers intermingled among these fibers in the proximal one‐third of the sphincter, and a few Type 1 fibers were present that were restricted to the adluminal region of the proximal segment. The fiber‐type compositions and their areal densities changed in both sexes after gonadectomy. The areal density of the Type 1 fibers increased significantly in the ovariectomized females, especially in the distal segment. In the orchidectomized males, the areal densities of the Types 1 and 2A fibers increased significantly, but that of the Type 2B fibers decreased. These results indicate that myosin heavy chain expression in the rat external urethral sphincter is sexually dimorphic and shows regional differences. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:2058–2069, 2017. © 2017 Wiley Periodicals, Inc.
A Nanosized Gly‐Decorated Praseodymium‐Stabilized Selenotungstate Cluster: Synthesis, Structure, and Oxidation Catalysis
Authors: Yang Ling , Li Li , Guo Jipeng , Liu Qisen , Ma Pengtao , Niu Jingyang , Wang Jingping
Published: July 2017

A flexible one‐pot strategy with pyramidal SeIV heteroatoms was employed for the assembly of the praseodymium‐containing gly‐decorated polyoxotungstate [{Pr3(H2O)10[Se2W22O76(gly)2]}2(Se2W7O30H2)]18− (1 a), which is constructed from one {Se2W7O30H2} unit and two identical {Pr3(H2O)10[Se2W22O76(gly)2]} units. Furthermore, the catalytic performance of Cs2Na4H12[{Pr3(H2O)10[Se2W22O76(gly)2]}2(Se2W7O30H2)]⋅25 H2O (1) for alkene epoxidation with hydrogen peroxide was investigated under mild reaction conditions, and the experimental results suggested that compound 1 exhibits good catalytic performance for the epoxidation of cyclooctene.
Integrated gut/liver microphysiological systems elucidates inflammatory inter‐tissue crosstalk
Authors: Chen Wen L.K. , Edington Collin , Suter Emily , Yu Jiajie , Velazquez Jeremy J. , Velazquez Jason G. , Shockley Michael , Large Emma M. , Venkataramanan Raman , Hughes David J. , Stokes Cynthia L. , Trumper David L. , Carrier Rebecca L. , Cirit Murat , Griffith Linda G. , Lauffenburger Douglas A.
Published: July 2017

A capability for analyzing complex cellular communication among tissues is important in drug discovery and development, and in vitro technologies for doing so are required for human applications. A prominent instance is communication between the gut and the liver, whereby perturbations of one tissue can influence behavior of the other. Here, we present a study on human gut‐liver tissue interactions under normal and inflammatory contexts, via an integrative multi‐organ platform comprising human liver (hepatocytes and Kupffer cells), and intestinal (enterocytes, goblet cells, and dendritic cells) models. Our results demonstrated long‐term (>2 weeks) maintenance of intestinal (e.g., barrier integrity) and hepatic (e.g., albumin) functions in baseline interaction. Gene expression data comparing liver in interaction with gut, versus isolation, revealed modulation of bile acid metabolism. Intestinal FGF19 secretion and associated inhibition of hepatic CYP7A1 expression provided evidence of physiologically relevant gut‐liver crosstalk. Moreover, significant non‐linear modulation of cytokine responses was observed under inflammatory gut‐liver interaction; for example, production of CXCR3 ligands (CXCL9,10,11) was synergistically enhanced. RNA‐seq analysis revealed significant upregulation of IFNα/β/γ signaling during inflammatory gut‐liver crosstalk, with these pathways implicated in the synergistic CXCR3 chemokine production. Exacerbated inflammatory response in gut‐liver interaction also negatively affected tissue‐specific functions (e.g., liver metabolism). These findings illustrate how an integrated multi‐tissue platform can generate insights useful for understanding complex pathophysiological processes such as inflammatory organ crosstalk. Biotechnol. Bioeng. 2017;114: 2648–2659. © 2017 Wiley Periodicals, Inc.
Prussian Blue‐Derived Synthesis of Hollow Porous Iron Pyrite Nanoparticles as Platinum‐Free Counter Electrodes for Highly Efficient Dye‐Sensitized Solar Cells
Authors: Chen Jeffrey E. , Fan Miao‐Syuan , Chen Yen‐Lin , Deng Yu‐Heng , Kim Jung Ho , Alamri Hatem R. , Alothman Zeid A. , Yamauchi Yusuke , Ho Kuo‐Chuan , Wu Kevin C.‐W.
Published: July 2017

Iron pyrite has long been an attractive material for environmental and energy applications, but is hampered by a lack of control over morphology and purity. Hollow porous iron pyrite nanoparticles were synthesized by a direct sulfurization of iron oxide derived from Prussian blue. The high efficiencies of these hollow porous iron pyrite nanoparticles as effective dye‐sensitized solar cell counter electrodes were demonstrated, with an efficiency of 7.31 %.
Production of chemicals from microalgae lipids – status and perspectives
Authors: Hess Sandra K. , Lepetit Bernard , Kroth Peter G. , Mecking Stefan
Published: July 2017

The engineering of algae strains, cultivation, and further processing steps in microalgae production are considered in view of the utilization of microalgae lipids for chemicals. Insights from biofuel production trials on the one hand and existing processes for very high‐value pharmaceuticals on the other hand are instructive to this end. A recent example of the production of a surfactant from chemical intermediates gained from algae oil and further opportunities are discussed.

Microalgae oil lipids are discussed as an alternative source for chemicals. The tuning of lipid production in microalgae via genetic engineering and cultivation optimization for this purpose is reviewed. We further illuminate the bottlenecks of upscaling and the state of the art in industrial algae production by means of three concrete case studies. We give insights into the catalytic functionalization to high‐value products.
Recognition memory: Cellular evidence of a massive contribution of the LEC to familiarity and a lack of involvement of the hippocampal subfields CA1 and CA3
Authors: Atucha Erika , Karew Artem , Kitsukawa Takashi , Sauvage Magdalena M.
Published: July 2017

A highly debated issue in memory research is whether familiarity is supported by the parahippocampal region, especially the lateral (LEC) and the perirhinal (PER) cortices, or whether it is supported by the same brain structure as recollection: the hippocampus. One reason for this is that conflicting results have emerged regarding the contribution of the hippocampus to familiarity. This might stem from the lack of dissociation between hippocampal subfields CA1 and CA3 as these areas are involved to a different extent in processes which are pertinent to familiarity. Another reason is that empirical evidence for a contribution of the LEC is still missing. Furthermore, it is unclear whether the superficial and the deep layers of the LEC would equally contribute to this process as these layers are differentially recruited during memory retrieval which partly relies on familiarity. To identify the specific contribution of the LEC, CA1, and CA3, we imaged with cellular resolution activity in the brain of rats performing a version of a standard human memory task adapted to rats that yields judgments based on familiarity. Using this translational approach, we report that in striking contrast to CA1 and CA3, the LEC is recruited for familiarity‐judgments and that its contribution is comparable to that of the PER. These results show for the first time that the LEC, specifically its deep layers, contributes to familiarity and constitute the first cellular evidence that the hippocampus does not, thus establishing that familiarity does not share the same neural substrate as recollection.
Hippocampal gamma‐slow oscillation coupling in macaques during sedation and sleep
Authors: Richardson Andrew G. , Liu Xilin , Weigand Pauline K. , Hudgins Eric D. , Stein Joel M. , Das Sandhitsu R. , Proekt Alexander , Kelz Max B. , Zhang Milin , Van der Spiegel Jan , Lucas Timothy H.
Published: July 2017

Behavioral and neurophysiological evidence suggests that the slow (≤1 Hz) oscillation (SO) during sleep plays a role in consolidating hippocampal (HIPP)‐dependent memories. The effects of the SO on HIPP activity have been studied in rodents and cats both during natural sleep and during anesthetic administration titrated to mimic sleep‐like slow rhythms. In this study, we sought to document these effects in primates. First, HIPP field potentials were recorded during ketamine‐dexmedetomidine sedation and during natural sleep in three rhesus macaques. Sedation produced regionally‐specific slow and gamma (∼40 Hz) oscillations with strong coupling between the SO phase and gamma amplitude. These same features were seen in slow‐wave sleep (SWS), but the coupling was weaker and the coupled gamma oscillation had a higher frequency (∼70 Hz) during SWS. Second, electrical stimuli were delivered to HIPP afferents in the parahippocampal gyrus (PHG) during sedation to assess the effects of sleep‐like SO on excitability. Gamma bursts after the peak of SO cycles corresponded to periods of increased gain of monosynaptic connections between the PHG and HIPP. However, the two PHG‐HIPP connectivity gains during sedation were both substantially lower than when the animal was awake. We conclude that the SO is correlated with rhythmic excitation and inhibition of the PHG‐HIPP network, modulating connectivity and gamma generators intrinsic to this network. Ketamine‐dexmedetomidine sedation produces a similar effect, but with a decreased contribution of the PHG to HIPP activity and gamma generation.
Association Between Vertebral Cross-sectional Area and Vertebral Wedging in Children and Adolescents: A Cross-sectional Analysis
Authors: Wren Tishya AL , Ponrartana Skorn , Aggabao Patricia C , Poorghasamians Ervin , Gilsanz Vicente
Published: July 2017

A small vertebral cross-sectional area (CSA) imparts a mechanical disadvantage that escalates the risk for vertebral fractures in elderly populations. We examined whether a small vertebral CSA is also associated with a greater degree of vertebral wedging in children. Measurements of vertebral CSA, lumbar lordosis (LL) or thoracic scoliosis angle, and vertebral wedging were obtained in 100 healthy adolescents (50 boys and 50 girls) and 25 girls with adolescent idiopathic scoliosis (AIS) using magnetic resonance imaging. Vertebral CSA of the lumbar vertebrae negatively correlated to the degree of posteroanterior vertebral wedging at L5 (r = –0.49; p < 0.0001); this was true whether all subjects were analyzed together or boys and girls independently. In contrast, we found a positive correlation between the degree of LL and vertebral wedging (r = 0.57; p < 0.0001). Multiple regression analysis showed that the association between vertebral CSA and wedging was independent of age and body mass index. In girls with AIS, vertebral CSA negatively correlated to the degree of lateral thoracic vertebral wedging (r = –0.66; p = 0.0004), an association that persisted even after accounting for age and body mass index. Additionally, Cobb angle positively correlated to lateral thoracic vertebral wedging (r = 0.46; p = 0.021). Our cross-sectional results support the hypothesis that smaller vertebral CSA is associated with greater vertebral deformity during growth, as in adulthood. © 2017 American Society for Bone and Mineral Research.
Long-Term Effects of Severe Burn Injury on Bone Turnover and Microarchitecture
Authors: Muschitz Gabriela Katharina , Schwabegger Elisabeth , Fochtmann Alexandra , Baierl Andreas , Kocijan Roland , Haschka Judith , Gruther Wolfgang , Schanda Jakob E , Resch Heinrich , Rath Thomas , Pietschmann Peter , Muschitz Christian
Published: July 2017

Severe burn injury triggers massive alterations in stress hormone levels with a dose-dependent hypermetabolic status including increased bone resorption. This study evaluated bone microarchitecture measured by noninvasive high-resolution peripheral quantitative computed tomography (HR-pQCT). Changes of serum bone turnover markers (BTM) as well as regulators of bone signaling pathways involved in skeletal health were assessed. Standardized effect sizes as a quantitative measure regarding the impact of serum changes and the prediction of these changes on bone microarchitecture were investigated. In total, 32 male patients with a severe burn injury (median total body surface area [TBSA], 40.5%; median age 40.5 years) and 28 matched male controls (median age 38.3 years) over a period of 24 months were included. In patients who had sustained a thermal injury, trabecular and cortical bone microstructure showed a continuous decline, whereas cortical porosity (Ct.Po) and pore volume increased. Initially, elevated levels of BTM and C-reactive protein (CRP) continuously decreased over time but remained elevated. In contrast, levels of soluble receptor activator of NF-κB ligand (sRANKL) increased over time. Osteocalcin, bone-specific alkaline phosphatase (BALP), intact N-terminal type 1 procollagen propeptide (P1NP), and cross-linked C-telopeptide (CTX) acutely reflected the increase of Ct.Po at the radius (R2 = 0.41), followed by the reduction of trabecular thickness at the tibia (R2 = 0.28). In adult male patients, early and sustained changes of markers of bone resorption, formation and regulators of bone signaling pathways, prolonged inflammatory cytokine activities in conjunction with muscle catabolism, and vitamin D insufficiency were observed. These alterations are directly linked to a prolonged deterioration of bone microstructure. The probably increased risk of fragility fractures should be of clinical concern and subject to future interventional studies with bone-protective agents. © 2017 American Society for Bone and Mineral Research
Lasp2 enhances tumor invasion via facilitating phosphorylation of FAK and predicts poor overall survival of non‐small cell lung cancer patients
Authors: Zhang Xiupeng , Cai Lin , Zhou Haijing , Liu Yang , Fan Chuifeng , Wang Liang , Li Ailin , Miao Yuan , Li Qingchang , Qiu Xueshan , Wang Enhua
Published: July 2017

Lasp2, as well as Lasp1, is a member of the LIM‐protein subfamily of the nebulin group characterized by the combined presence of LIM and SH3 domains. Lasp1 and Lasp2 are highly conserved in their LIM, nebulin‐like, and SH3 domains but differ significantly at their linker regions. Lasp1 had been described as an oncogenic protein that was highly expressed in diverse cancer types and facilitated tumor proliferation, invasion, and metastasis process. However, unlike Lasp1, little is known about the functions of Lasp2. In the present study, using immunohistochemistry, we found that Lasp2 expression was significantly correlated with histological type (P = 0.012), advanced TNM stage (P = 0.024), positive regional lymph node metastasis (P = 0.035), and poor overall survival (P = 0.001). Would healing assay and transwell assay results indicated that Lasp2 promoted tumor migration and invasion in NSCLC cells. Furthermore, Lasp2 facilitated Snail expression and inhibited Zo‐1. The levels of phosphorylated FAK (Tyr397 and Tyr925) were obviously increased after overexpressing Lasp2 and were downregulated by transfecting Lasp2‐siRNA. FAK inhibitor counteracted upregulating Snail expression and downregulating of Zo‐1 expression induced by Lasp2 overexpression. Taken together, Lasp2 may facilitate tumor migration and invasion of NSCLCs through FAK‐Snail/Zo‐1 signaling pathway. Lasp2 may be a potential prognostic predictor of NSCLC patients.
Physiological mechanisms through which heat stress compromises reproduction in pigs
Authors: Ross Jason W. , Hale Benjamin J. , Seibert Jacob T. , Romoser Matthew R. , Adur Malavika K. , Keating Aileen F. , Baumgard Lance H.
Published: July 2017

Seasonal variations in environmental temperatures impose added stress on domestic species bred for economically important production traits. These heat‐mediated stressors vary on a seasonal, daily, or spatial scale, and negatively impact behavior and reduce feed intake and growth rate, which inevitably lead to reduced herd productivity. The seasonal infertility observed in domestic swine is primarily characterized by depressed reproductive performance, which manifests as delayed puberty onset, reduced farrowing rates, and extended weaning‐to‐estrus intervals. Understanding the effects of heat stress at the organismal, cellular, and molecular level is a prerequisite to identifying mitigation strategies that should reduce the economic burden of compromised reproduction. In this review, we discuss the effect of heat stress on an animal's ability to maintain homeostasis in multiple systems via several hypothalamic‐pituitary‐end organ axes. Additionally, we discuss our understanding of epigenetic programming and how hyperthermia experienced in utero influences industry‐relevant postnatal phenotypes. Further, we highlight the recent recognized mechanisms by which distant tissues and organs may molecularly communicate via extracellular vesicles, a potentially novel mechanism contributing to the heat‐stress response.
“Government Doesn't Have the Muscle”: State, NGOs, Local Politics, and Disaster Risk Governance in Malawi
Authors: Kita Stern Mwakalimi
Published: July 2017

The Sendai Framework for Disaster Risk Reduction, 2015–30, calls for countries to strengthen disaster risk governance systems as a pathway to disaster risk reduction. This paper assesses the disaster risk governance system in Malawi, Sub‐Saharan Africa, to understand how the positioning of multiple actors is contributing to the creation of an environment generating either positive or negative outcomes. The study utilizes a landscape governance analytical framework grounded within network governance theory and predominantly relies on qualitative approaches. The study finds that non‐governmental organizations are delivering the majority of disaster risk management services in the country. However, there are shortfalls within and across key actors and institutions that are frustrating progress and could reverse isolated gains that the country has made. While central government is largely detached from community‐level implementation, its incapacity is worsened by politicians and local government actors who have positioned themselves to capture risk reduction finance. The paper, therefore, questions the rationale behind the urgency in decentralizing disaster risk governance before addressing critical challenges within the local government system. These findings, while specifically for Malawi, are also pertinent to other developing countries struggling to deal with the consequences of climate variability and change.
Assessment of arterial function in pregnancy: recommendations of the International Working Group on Maternal Hemodynamics
Authors: Foo F. L. , McEniery C. M. , Lees C. , Khalil A. ,   International Working Group on Maternal Hemodynamics
Published: July 2017

There is strong evidence supporting the role of maternal arterial dysfunction in pregnancy‐specific disorders such as pre‐eclampsia and intrauterine growth restriction. As more work is focused towards this field, it is important that methods and interpretation of arterial function assessment are applied appropriately. Here, we summarize techniques and devices commonly used in maternal health studies, with consideration of their technical application in pregnant cohorts. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
An update: Epstein-Barr virus and immune evasion via microRNA regulation
Authors: Zuo Lielian , Yue Wenxin , Du Shujuan , Xin Shuyu , Zhang Jing , Liu Lingzhi , Li Guiyuan , Lu Jianhong
Published: July 2017

Epstein-Barr virus (EBV) is an oncogenic virus that ubiquitously establishes
life-long persistence in humans. To ensure its survival and maintain its B cell
transformation function, EBV has developed powerful strategies to evade host immune
responses. Emerging evidence has shown that microRNAs (miRNAs) are powerful
regulators of the maintenance of cellular homeostasis. In this review, we summarize
current progress on how EBV utilizes miRNAs for immune evasion. EBV encodes miRNAs
targeting both viral and host genes involved in the immune response. The miRNAs are
found in two gene clusters, and recent studies have demonstrated that lack of these
clusters increases the CD4+ and
CD8+ T cell response of infected cells. These reports
strongly indicate that EBV miRNAs are critical for immune evasion. In addition, EBV
is able to dysregulate the expression of a variety of host miRNAs, which influence
multiple immune-related molecules and signaling pathways. The transport via exosomes
of EBV-regulated miRNAs and viral proteins contributes to the construction and
modification of the inflammatory tumor microenvironment. During EBV immune evasion,
viral proteins, immune cells, chemokines, pro-inflammatory cytokines, and
pro-apoptosis molecules are involved. Our increasing knowledge of the role of miRNAs
in immune evasion will improve the understanding of EBV persistence and help to
develop new treatments for EBV-associated cancers and other diseases.
Existence and qualitative theory for stratified solitary water waves
Authors: Walsh Samuel , Wheeler Miles H. , Chen Robin Ming
Published: July 2017

This paper considers two-dimensional gravity solitary waves moving through a body of density stratified water lying below vacuum. The fluid domain is assumed to lie above an impenetrable flat ocean bed, while the interface between the water and vacuum is a free boundary where the pressure is constant. We prove that, for any smooth choice of upstream velocity field and density function, there exists a continuous curve of such solutions that includes large-amplitude surface waves. Furthermore, following this solution curve, one encounters waves that come arbitrarily close to possessing points of horizontal stagnation.

We also provide a number of results characterizing the qualitative features of solitary stratified waves. In part, these include bounds on the wave speed from above and below, some of which are new even for constant density flow; an a priori bound on the velocity field and lower bound on the pressure; a proof of the nonexistence of monotone bores in this physical regime; and a theorem ensuring that all supercritical solitary waves of elevation have an axis of even symmetry.
Efficient neural differentiation of mouse pluripotent stem cells in a serum‐free medium and development of a novel strategy for enrichment of neural cells
Authors: Verma Isha , Rashid Zubin , Sikdar Sujit K. , Seshagiri Polani B.
Published: July 2017

Pluripotent stem cells (PSCs) offer an excellent model to study neural development and function. Although various protocols have been developed to direct the differentiation of PSCs into desired neural cell types, many of them suffer from limitations including low efficiency, long duration of culture, and the use of expensive, labile, and undefined growth supplements. In this study, we achieved efficient differentiation of mouse PSCs to neural lineage, in the absence of exogenous molecules, by employing a serum‐free culture medium containing knockout serum replacement (KSR). Embryoid bodies (EBs) cultured in this medium predominantly produced neural cells which included neural progenitors (15–18%), immature neurons (8–24%), mature neurons (10–26%), astrocytes (27–61%), and oligodendrocytes (∼1%). Different neuronal subtypes including glutamatergic, GABAergic, cholinergic, serotonergic, and dopaminergic neurons were generated. Importantly, neurons generated in the KSR medium were electrically active. Further, the EB scooping strategy, involving the removal of the EB core region from the peripheral EB outgrowth, resulted in the enrichment of PSC‐derived neural cells. Taken together, this study provides the evidence that the KSR medium is ideal for the rapid and efficient generation of neural cells, including functional neurons, from PSCs without the requirement of any other additional molecule.
High Altitude Pulmonary Edema in a Mining Worker With an Abnormal Rise in Pulmonary Artery Pressure in Response to Acute Hypoxia Without Prior History of High Altitude Pulmonary Edema
Authors: Akunov Almaz Ch. , Sartmyrzaeva Meerim A. , Maripov Abdirashit M. , Muratali uulu Kubatbek , Mamazhakypov Argen T. , Sydykov Akylbek S. , Sarybaev Akpay Sh.
Published: July 2017

High altitude pulmonary edema (HAPE) is a potentially life-threatening form of noncardiogenic pulmonary edema that may develop in otherwise healthy individuals upon ascent to high altitude. A constitutional susceptibility has been noted in some individuals, whereas others appear not to be susceptible at all. In our report, we present a case of HAPE triggered by concurrent respiratory tract infection and strenuous exercise in a mining worker with an abnormal rise in pulmonary artery pressure in response to acute hypoxia, without a prior history of HAPE during almost a year of commuting between high altitude and lowland areas.
Unemployed? AGU Can Help
Authors: Marasco Leslie , Harwell David , Janick Nathaniel
Published: July 2017

The American Geophysical Union provides resources to minimize job loss effects and opportunities to engage with the Earth and space science community.
pVHL suppresses Akt/β-catenin-mediated cell proliferation by inhibiting 14-3-3ζ expression
Authors: Castañeda Azucena , Serrano Carolina , Hernández-Trejo José Antonio , Gutiérrez-Martínez Itzel Zenidel , Montejo-López Wilber , Gómez-Suárez Mauricio , Hernández-Ruiz Marcela , Betanzos Abigail , Candelario-Martínez Aurora , Romo-Parra Hector , Arias-Montaño José Antonio , Schnoor Michael , Meraz Ríos Marco Antonio , Gutierrez-Castillo Maria Eugenia , Martínez-Dávila Irma Alicia , Villegas-Sepúlveda Nicolás , Martinez-Fong Daniel , Nava Porfirio
Published: July 2017

The mechanisms controlling degradation of cytosolic β-catenin are important for regulating β-catenin co-transcriptional activity. Loss of von Hippel–Lindau protein (pVHL) has been shown to stabilize β-catenin, increasing β-catenin transactivation and β-catenin-mediated cell proliferation. However, the role of phosphoinositide 3-kinase (PI3K)/Akt in the regulation of β-catenin signaling downstream from pVHL has never been addressed. Here, we report that hyperactivation of PI3K/Akt in cells lacking pVHL contributes to the stabilization and nuclear accumulation of active β-catenin. PI3K/Akt hyperactivation is facilitated by the up-regulation of 14-3-3ζ and the down-regulation of 14-3-3ε, 14-3-3η and 14-3-3θ. Up-regulation of 14-3-3ζ in response to pVHL is important for the recruitment of PI3K to the cell membrane and for stabilization of soluble β-catenin. In contrast, 14-3-3ε and 14-3-3η enhanced PI3K/Akt signaling by inhibiting PI3K and PDK1, respectively. Thus, our results demonstrated that 14-3-3 family members enhance PI3K/Akt/β-catenin signaling in order to increase proliferation. Inhibition of Akt activation and/or 14-3-3 function strongly reduces β-catenin signaling and decreases cell proliferation. Thus, inhibition of Akt and 14-3-3 function efficiently reduces cell proliferation in 786-0 cells characterized by hyperactivation of β-catenin signaling due to pVHL loss.
Role of human metapneumovirus and respiratory syncytial virus in asthma exacerbations: where are we now?
Authors: Rudd Penny A. , Thomas Belinda J. , Zaid Ali , MacDonald Martin , Kan-o Keiko , Rolph Michael S. , Soorneedi Anand R. , Bardin Philip G. , Mahalingam Suresh
Published: July 2017

Since its discovery in 2001, human metapneumovirus (hMPV) has been identified as an important cause of respiratory tract infection in young children, second only to the closely related respiratory syncytial virus (RSV). Clinical evidence suggests that hMPV is associated with acute exacerbations of asthma in both children and adults, and may play a role in initiating asthma development in children. Animal models have demonstrated that airway hyperresponsiveness (AHR) and inflammation are triggered following hMPV infection, and hMPV is able to persist in vivo by inhibiting innate immune responses and causing aberrant adaptive responses. In this review, we discuss the prevalence of hMPV infection in pediatric and adult populations and its potential role in asthma exacerbation. We also review recent advances made in animal models to determine immune responses following hMPV infection, and compare to what is known about RSV.
Epilepsy and optogenetics: can seizures be controlled by light?
Authors: Tønnesen Jan , Kokaia Merab
Published: July 2017

Over the past decade, ‘optogenetics’ has been consolidated as a game-changing tool in the neuroscience field, by allowing optical control of neuronal activity with high cell-type specificity. The ability to activate or inhibit targeted neurons at millisecond resolution not only offers an investigative tool, but potentially also provides a therapeutic intervention strategy for acute correction of aberrant neuronal activity. As efficient therapeutic tools are in short supply for neurological disorders, optogenetic technology has therefore spurred considerable enthusiasm and fostered a new wave of translational studies in neuroscience. Epilepsy is among the disorders that have been widely explored. Partial epilepsies are characterized by seizures arising from excessive excitatory neuronal activity that emerges from a focal area. Based on the constricted seizure focus, it appears feasible to intercept partial seizures by acutely shutting down excitatory neurons by means of optogenetics. The availability of both inhibitory and excitatory optogenetic probes, along with the available targeting strategies for respective excitatory or inhibitory neurons, allows multiple conceivable scenarios for controlling abnormal circuit activity. Several such scenarios have been explored in the settings of experimental epilepsy and have provided encouraging translational findings and revealed interesting and unexpected new aspects of epileptogenesis. However, it has also emerged that considerable challenges persist before clinical translation becomes feasible. This review provides a general introduction to optogenetics, and an overview of findings that are relevant for understanding how optogenetics may be utilized therapeutically as a highly innovative treatment for epilepsy.
Redox theory of aging: implications for health and disease
Authors: Go Young-Mi , Jones Dean P.
Published: July 2017

Genetics ultimately defines an individual, yet the phenotype of an adult is extensively determined by the sequence of lifelong exposures, termed the exposome. The redox theory of aging recognizes that animals evolved within an oxygen-rich environment, which created a critical redox interface between an organism and its environment. Advances in redox biology show that redox elements are present throughout metabolic and structural systems and operate as functional networks to support the genome in adaptation to environmental resources and challenges during lifespan. These principles emphasize that physical and functional phenotypes of an adult are determined by gene–environment interactions from early life onward. The principles highlight the critical nature of cumulative exposure memories in defining changes in resilience progressively during life. Both plasma glutathione and cysteine systems become oxidized with aging, and the recent finding that cystine to glutathione ratio in human plasma predicts death in coronary artery disease (CAD) patients suggests this could provide a way to measure resilience of redox networks in aging and disease. The emerging concepts of cumulative gene–environment interactions warrant focused efforts to elucidate central mechanisms by which exposure memory governs health and etiology, onset and progression of disease.
Small vessel disease, neurovascular regulation and cognitive impairment: post-mortem studies reveal a complex relationship, still poorly understood
Authors: Love Seth , Miners J. Scott
Published: July 2017

The contribution of vascular disease to cognitive impairment is under-recognized and the pathogenesis is poorly understood. This information gap has multiple causes, including a lack of post-mortem validation of clinical diagnoses of vascular cognitive impairment (VCI) or vascular dementia (VaD), the exclusion of cases with concomitant neurodegenerative disease when diagnosing VCI/VaD, and a lack of standardization of neuropathological assessment protocols for vascular disease. Other contributors include a focus on end-stage destructive lesions to the exclusion of more subtle types of diffuse brain injury, on structural abnormalities of arteries and arterioles to the exclusion of non-structural abnormalities and capillary damage, and the use of post-mortem sampling strategies that are biased towards the identification of neurodegenerative pathologies. Recent studies have demonstrated the value of detailed neuropathology in characterizing vascular contributions to cognitive impairment (e.g. in diabetes), and highlight the importance of diffuse white matter changes, capillary damage and vasoregulatory abnormalities in VCI/VaD. The use of standardized, evidence-based post-mortem assessment protocols and the inclusion of biochemical as well as morphological methods in neuropathological studies should improve the accuracy of determination of the contribution of vascular disease to cognitive impairment and clarify the relative contribution of different pathogenic processes to the tissue damage.
Role of the Nrf2/HO-1 axis in bronchopulmonary dysplasia and hyperoxic lung injuries
Authors: Amata Emanuele , Pittalà Valeria , Marrazzo Agostino , Parenti Carmela , Prezzavento Orazio , Arena Emanuela , Nabavi Seyed Mohammad , Salerno Loredana
Published: July 2017

Bronchopulmonary dysplasia (BPD) is a chronic illness that usually originates in preterm newborns. Generally, BPD is a consequence of respiratory distress syndrome (RDS) which, in turn, comes from the early arrest of lung development and the lack of pulmonary surfactant. The need of oxygen therapy to overcome premature newborns’ compromised respiratory function generates an increasing amount of reactive oxygen species (ROS), the onset of sustained oxidative stress (OS) status, and inflammation in the pulmonary alveoli deputies to respiratory exchanges. BPD is a severe and potentially life-threatening disorder that in the most serious cases, can open the way to neurodevelopmental delay. More importantly, there is no adequate intervention to hamper or treat BPD. This perspective article seeks to review the most recent and relevant literature describing the very early stages of BPD and hyperoxic lung injuries focussing on nuclear factor erythroid derived 2 (Nrf2)/heme oxygenase-1 (HO-1) axis. Indeed, Nrf2/HO1 activation in response to OS induced lung injury in preterm concurs to the induction of certain number of antioxidant, anti-inflammatory, and detoxification pathways that seem to be more powerful than the activation of one single antioxidant gene. These elicited protective effects are able to counteract/mitigate all multifaceted aspects of the disease and may support novel approaches for the management of BPD.
Oxidative and inflammatory signals in obesity-associated vascular abnormalities
Authors: Reho John J. , Rahmouni Kamal
Published: July 2017

Obesity is associated with increased cardiovascular morbidity and mortality in part due to vascular abnormalities such as endothelial dysfunction and arterial stiffening. The hypertension and other health complications that arise from these vascular defects increase the risk of heart diseases and stroke. Prooxidant and proinflammatory signaling pathways as well as adipocyte-derived factors have emerged as critical mediators of obesity-associated vascular abnormalities. Designing treatments aimed specifically at improving the vascular dysfunction caused by obesity may provide an effective therapeutic approach to prevent the cardiovascular sequelae associated with excessive adiposity. In this review, we discuss the recent evidence supporting the role of oxidative stress and cytokines and inflammatory signals within the vasculature as well as the impact of the surrounding perivascular adipose tissue (PVAT) on the regulation of vascular function and arterial stiffening in obesity. In particular, we focus on the highly plastic nature of the vasculature in response to altered oxidant and inflammatory signaling and highlight how weight management can be an effective therapeutic approach to reduce the oxidative stress and inflammatory signaling and improve vascular function.
Chronic cerebral hypoperfusion alters amyloid-β peptide pools leading to cerebral amyloid angiopathy, microinfarcts and haemorrhages in Tg-SwDI mice
Authors: Salvadores Natalia , Searcy James L. , Holland Philip R. , Horsburgh Karen
Published: July 2017

Cerebral hypoperfusion is an early feature of Alzheimer’s disease (AD) that influences the progression from mild cognitive impairment to dementia. Understanding the mechanism is of critical importance in the search for new effective therapies. We hypothesized that cerebral hypoperfusion promotes the accumulation of amyloid-β (Aβ) and degenerative changes in the brain and is a potential mechanism contributing to development of dementia. To address this, we studied the effects of chronic cerebral hypoperfusion induced by bilateral carotid artery stenosis on Aβ peptide pools in a transgenic mouse model of AD (transgenic mice with Swedish, Dutch and Iowa mutations in human amyloid precursor protein (APP) (Tg-SwDI)). Cerebrovascular integrity was characterized by quantifying the occurrence of microinfarcts and haemorrhages and compared with wild-type mice without Aβ. A significant increase in soluble Aβ peptides (Aβ40/42) was detected after 1 month of hypoperfusion in the parenchyma in parallel with elevated APP and APP proteolytic products. Following 3 months, a significant increase in insoluble Aβ40/42 was determined in the parenchyma and vasculature. Microinfarct load was significantly increased in the Tg-SwDI as compared with wild-type mice and further exacerbated by hypoperfusion at 1 and 3 months. In addition, the number of Tg-SwDI hypoperfused mice with haemorrhages was increased compared with hypoperfused wild-type mice. Soluble parenchymal Aβ was associated with elevated NADPH oxidase-2 (NOX2) which was exacerbated by 1-month hypoperfusion. We suggest that in response to hypoperfusion, increased Aβ production/deposition may contribute to degenerative processes by triggering oxidative stress promoting cerebrovascular disruption and the development of microinfarcts.
Spatially-resolved star formation histories of CALIFA galaxies
Authors: González Delgado R. M. , Pérez E. , Cid Fernandes R. , García-Benito R. , López Fernández R. , Vale Asari N. , Cortijo-Ferrero C. , de Amorim A. L. , Lacerda E. A. D. , Sánchez S. F. , Lehnert M. D. , Walcher C. J.
Published: July 2017

This paper presents the spatially resolved star formation history (SFH) of nearby galaxies with the aim of furthering our understanding of the different processes involved in the formation and evolution of galaxies. To this end, we apply the fossil record method of stellar population synthesis to a rich and diverse data set of 436 galaxies observed with integral field spectroscopy in the CALIFA survey. The sample covers a wide range of Hubble types, with stellar masses ranging fromM⋆~ 109to 7 × 1011M⊙. Spectral synthesis techniques are applied to the datacubes to retrieve the spatially resolved time evolution of the star formation rate (SFR), its intensity (ΣSFR), and other descriptors of the 2D SFH in seven bins of galaxy morphology (E, S0, Sa, Sb, Sbc, Sc, and Sd) and five bins of stellar mass. Our main results are that (a) galaxies form very fast independently of their current stellar mass, with the peak of star formation at high redshift (z> 2). Subsequent star formation is driven byM⋆and morphology, with less massive and later type spirals showing more prolonged periods of star formation. (b) At any epoch in the past, the SFR is proportional toM⋆, with most massive galaxies having the highest absolute (but lowest specific) SFRs. (c) While today, the ΣSFRis similar for all spirals and significantly lower in early-type galaxies (ETG), in the past, the ΣSFRscales well with morphology. The central regions of today’s ETGs are where the ΣSFRreached the highest values (> 103M⊙Gyr-1pc-2), similar to those measured in high-redshift star-forming galaxies. (d) The evolution of ΣSFRin Sbc systems matches that of models for Milky Way-like galaxies, suggesting that the formation of a thick disk may be a common phase in spirals at early epochs. (e) The SFR and ΣSFRin outer regions of E and S0 galaxies show that they have undergone an extended phase of growth in mass betweenz= 2 and 0.4. The mass assembled in this phase is in agreement with the two-phase scenario proposed for the formation of ETGs. (f) Evidence of an early and fast quenching is found only in the most massive (M⋆> 2 × 1011M⊙) E galaxies of the sample, but not in spirals of similar mass, suggesting that halo quenching is not the main mechanism for the shut down of star formation in galaxies. Less massive E and disk galaxies show more extended SFHs and a slow quenching. (g) Evidence of fast quenching is also found in the nuclei of ETG and early spirals, with SFR and ΣSFRindicating that they can be the relic of the “red nuggets” detected at high redshift.
Proton–proton collisions prove stranger than expected
Authors: Chang Sung
Published: July 2017

Enhanced production of strange particles joins a growing body of evidence that has physicists reevaluating their assumptions about quark–gluon plasmas.
Government Intervention and Arbitrage
Authors: Pasquariello Paolo
Published: July 2017

Direct government intervention in a market may induce violations of the law of one price in other, arbitrage-related markets. I show that a government pursuing a nonpublic, partially informative price target in a model of strategic market-order trading and segmented dealership generates equilibrium price differentials among fundamentally identical assets by clouding dealers’ inference about the targeted asset’s payoff from its order flow, to an extent complexly dependent on existing price formation. I find supportive evidence using a sample of American Depositary Receipts and other cross-listings traded in the major U.S. exchanges, along with currency interventions by developed and emerging countries between 1980 and 2009.

Received May 18, 2016; editorial decision May 10, 2017 by Editor Andrew Karolyi.
Clinical Model of Exercise-Related Dyspnea in Adult Patients With Cystic Fibrosis
Authors: Stevens Daniel , Neyedli Heather F.
Published: July 2017

Purpose:

Dyspnea is a highly distressing symptom of pulmonary disease that can make performing physical activities challenging. However, little is known regarding the strongest predictors of exercise-related dyspnea in adult cystic fibrosis (CF). Therefore, the purpose of the present study was to determine the best clinical model of exercise-related dyspnea in this patient group.

Methods:

A retrospective analysis of pulmonary function and cardiopulmonary exercise testing data from patients with CF being followed up at the Adult CF Program at St Michael's Hospital, Toronto, Canada, from 2002 to 2008 were used for the analysis.

Results:

Patients (n = 88) were male 66%; aged 30.4 ± 9.4 years; body mass index (BMI) 23.1 ± 3.3 kg/m2; forced expiratory volume in 1 second (FEV1) 70% ± 19% predicted; and peak oxygen uptake 74% ± 20% predicted. A multivariate linear regression model assessing the effects of age, sex, BMI, airway obstruction (FEV1), perceived muscular leg fatigue, and dynamic hyperinflation explained 54% of the variance in dyspnea severity at peak exercise (P < .01). Relative importance analysis showed that the presence of dynamic hyperinflation and perceived muscular leg fatigue were the largest contributors.

Conclusions:

Pulmonary rehabilitation programs may consider strategies to reduce dynamic hyperinflation and promote muscular function to best improve exercise-related dyspnea in this patient group.