bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuity and density results for a one-phase nonlocal free boundary problem
Authors: Dipierro Serena , Valdinoci Enrico
Published: November 2016

We consider a one-phase nonlocal free boundary problem obtained by the superposition of a fractional Dirichlet energy plus a nonlocal perimeter functional. We prove that the minimizers are Hölder continuous and the free boundary has positive density from both sides.

For this, we also introduce a new notion of fractional harmonic replacement in the extended variables and we study its basic properties.
Growth under Extractive Institutions? Latin American Per Capita GDP in Colonial Times
Authors: Abad Leticia Arroyo , van Zanden Jan Luiten
Published: November 2016

This article presents new estimations of per capita GDP in colonial times for the two pillars of the Spanish empire: Mexico and Peru. We find dynamic economies as evidenced by increasing real wages, urbanization, and silver mining. Their growth trajectories are such that both regions reduced the gap with respect to Spain; Mexico even achieved parity at times. While experiencing swings in growth, the notable turning point is in 1780s as bottlenecks in production and later, the independence wars reduced economic activity. Our results question the notion that colonial institutions impoverished Latin America.
Colonial New Jersey Paper Money, 1709–1775: Value Decomposition and Performance
Authors: Grubb Farley
Published: November 2016

I decompose the market value of Colonial New Jersey's paper money into its component parts, namely its real-asset present value and transaction premium. Its market value was predominately determined by its real-asset present value. I also find a small transaction premium that is positively associated with the quantity of paper money in circulation and with the land-bank method of paper money injection. This paper money was not a fiat currency. It traded below face value due to time-discounting not depreciation.
Constructing Arctic security: an inter-disciplinary approach to understanding security in the Barents region
Authors: Hossain Kamrul , Zojer Gerald , Greaves Wilfrid , Roncero J. Miguel , Sheehan Michael
Published: November 2016

The field of Security Studies traditionally focused on military threats to states' survival, however, since the end of the Cold War the concept of security has widened and individuals and communities have gradually become viewed as appropriate referent objects of security: Multifaceted challenges facing communities at the sub-state level are increasingly regarded as security threats, including their potential to cause instability for the larger society, thus affecting states’ security. In the Arctic region, a central challenge is that inhabitants are exposed to multiple non-traditional and non-military threats resulting from environmental, economic, and societal changes, which can be understood as threats tohuman security. We argue that a comprehensive approach to human security overlaps with the concept ofsocietal security, and must therefore consider threats to collective identity and the essential conditions necessary for the maintenance and preservation of a distinct society. We see the human security framework as a suitable analytical tool to study the specific challenges that threaten the Arctic population, and in turn the well-being of Arctic societies. Therefore, we argue that utilising the concept of human security can promote societal security in the context of the Arctic, and in particular, its sub-regions, for example, the Barents region.
Trading accuracy for speed in approximate consensus
Authors: Beal Jacob
Published: November 2016

Approximate consensus is an important building block for distributed systems, used overtly or implicitly in applications as diverse as formation control, sensor fusion, and synchronization. Laplacian-based consensus, the current dominant approach, is extremely accurate and resilient, but converges slowly. Comparing Laplacian-based consensus to exact consensus algorithms, relaxing the requirements for accuracy and resilience should enable a spectrum of algorithms that incrementally tradeoff accuracy and/or resilience for speed. This manuscript demonstrates that may be so by beginning to populate this spectrum with a new approach to approximate consensus, Power-Law-Driven Consensus (PLD-consensus), which accelerates consensus by sending values across long distances using a self-organizing overlay network. Both a unidirectional and bidirectional algorithm based on this approach are studied. Although both have the same asymptotic O(diameter) convergence time (vs. O(diameter2) for Laplacian-based), unidirectional PLD-consensus is faster and more resilient than bidirectional PLD-consensus, but exhibits higher variance in the converged value.
MULTIPLE REGRESSION AS A FLEXIBLE ALTERNATIVE TO ANOVA IN L2 RESEARCH
Authors: Plonsky Luke , Oswald Frederick L.
Published: November 2016

Second language (L2) research relies heavily and increasingly on ANOVA (analysis of variance)-based results as a means to advance theory and practice. This fact alone should merit some reflection on the utility and value of ANOVA. It is possible that we could use this procedure more appropriately and, as argued here, other analyses such as multiple regression may prove to be more illuminating in certain research contexts. We begin this article with an overview of problems associated with ANOVA; some of them are inherent to the procedure, and others are tied to the way it is applied in L2 research. We then present three rationales for when researchers might turn to multiple regression in place of ANOVA. Output from ANOVA and multiple regression analyses based on published and mock-up studies are used to illustrate major points.
Public preferences for species conservation: choosing between lethal control, habitat protection and no action
Authors: LUTE MICHELLE L. , ATTARI SHAHZEEN Z.
Published: November 2016

Despite increasing support for conservation efforts, humans exert strong negative forces on nature and disagree over the management of these effects. Conflicts over conservation policy may reflect evolving opinions about how people ought to conserve species and whether to intervene in various processes. To understand public preferences for conservation in the USA, we measured support for various strategies in five case studies, where we pitted one species against another in simplified but realistic scenarios. Among our online convenience sample of 1040 participants, we found the majority of participants favoured habitat protection in all but one case, and there was little acceptance of lethal control across all cases. The results reveal that habitat protection preferences positively relate to considerations of moral principles and ecosystems and negatively relate to economic and practical considerations. Older, conservative and male participants were less likely to support habitat protection and more likely to support no action. The results suggest broad support for holistic nature conservation that benefits both people and nature and highlight areas where current wildlife management may not align with public preferences. Controversy may continue until wildlife management policies are consistent with societal values and address moral and ecosystem considerations at multiple levels.
The association between attending specialized day care centers and the quality of life of people with dementia
Authors: Rokstad Anne Marie Mork , Engedal Knut , Kirkevold Øyvind , Šaltytė Benth Jūratė , Barca Maria Lage , Selbæk Geir
Published: November 2016

Background:

Day care that is designed for people with dementia aims to increase the users’ quality of life (QoL). The objective of the study was to compare the QoL of people with dementia attending day care with those not attending day care.

Methods:

The study is based on baseline data from a project using a quasi-experimental design, including a group of day care users (n = 183) and a comparison group not receiving day care (n = 78). Quality of Life-Alzheimer's Disease (QoL-AD) was used as the primary outcome, to collect both self-reported and proxy-based information from family carers on the users’ QoL. A linear mixed model was used to examine the differences between groups.

Results:

Attending day care was significantly associated with higher mean scores of self-reported QoL. There was no difference between the groups in proxy-reported QoL. Analyses of the interaction between group belonging and awareness of memory loss revealed that the participants with shallow or no awareness who attended day care had significant higher mean scores of QoL-AD compared to those not attending day care.

Conclusions:

Higher self-reported QoL was found among people attending day care designed for people with dementia compared to the comparison group. The difference in QoL ratings was found in the group of day care users with shallow or no awareness of their memory loss. Hence, day care designed for people with dementia might have the potential to increase QoL as it is experienced by the users.
It's Institutions, Not Theology! Muslim Actors’ Influence on Democratization in Mali
Authors: Leininger Julia
Published: November 2016

This article aims at explaining religious actors' influence on democratic transition in Mali (1987–1992). It argues that it takes more than political theology to effectively influence democratization processes. Although Muslim actors used their political theology during democratization, they had neither the organizational means nor the legitimization to convince others of their preferences for a post-authoritarian institutional set-up. They had very limited influence on the institutions that today are supposed to regulate the relations between religion and the state under democratic rule. In fact, this high path-dependency of institutional factors since the colonial era led to an informalization of non-liberal Muslim politics in the 2000s. It is likely that accepting Muslim actors' demands for institutionalized cooperation between the state and religion during democratic transition would have caused fewer problems for democracy in the long run. The article concludes with general lessons for the study of religion in democratization.
Psychiatric rehabilitation in Latin America: challenges and opportunities
Authors: Uribe-Restrepo J. M. , Escobar M. L. , Cubillos L.
Published: November 2016

Comprehensive psychiatric rehabilitation programs in Latin America have been designed across several countries in the region without yet achieving full implementation. Facing an increasing burden of disease due to mental disorders, including alcohol and substance use disorders, the region has responded unevenly to the challenge. Moreover, low priority for mental health in national policies and insufficient funding for mental health services are common barriers for the much-needed mental health services reforms. Reestablishing a primary care community-based model of care has been a shared aspiration for most countries during the last two decades. Comprehensive models of psychiatric rehabilitation developed predominantly in high-income countries need to be culturally adapted to local contexts, while strengthening health systems research will provide evidence on the efficiency of locally designed interventions and on the critical milestones to succeed in the scaling up strategies. Increasing participation of patients and their families in the mental health delivery system is another key factor in order to ensure comprehensive patient-centred psychosocial rehabilitation programs in Latin America.
De-ubiquitinating enzyme, USP11, promotes transforming growth factor β-1 signaling through stabilization of transforming growth factor β receptor II
Authors: Jacko A M , Nan L , Li S , Tan J , Zhao J , Kass D J , Zhao Y
Published: November 2016

The transforming growth factorβ-1 (TGFβ-1) signaling pathway plays a central role in the pathogenesis of pulmonary fibrosis. Two TGFβ-1 receptors, TβRI and TβRII, mediate this pathway. TβRI protein stability, as mediated by the ubiquitin/de-ubiquitination system, has been well studied; however, the molecular regulation of TβRII still remains unclear. Here we reveal that a de-ubiquitinating enzyme, USP11, promotes TGFβ-1 signaling through de-ubiquitination and stabilization of TβRII. We elucidate the role that mitoxantrone (MTX), an USP11 inhibitor, has in the attenuation of TGFβ-1 signaling. Inhibition or downregulation of USP11 results in increases in TβRII ubiquitination and reduction of TβRII stability. Subsequently, TGFβ-1 signaling is greatly attenuated, as shown by the decreases in phosphorylation of SMAD2/3 levels as well as that of fibronectin (FN) and smooth muscle actin (SMA). Overexpression of USP11 reduces TβRII ubiquitination and increases TβRII stabilization, thereby elevating phosphorylation of SMAD2/3 and the ultimate expression of FN and SMA. Further, elevated expression of USP11 and TβRII were detected in lung tissues from bleomycin-challenged mice and IPF patients. Therefore, USP11 may contribute to the pathogenesis of pulmonary fibrosis by stabilization of TβRII and promotion of TGFβ-1 signaling. This study provides mechanistic evidence for development of USP11 inhibitors as potential antifibrotic drugs for pulmonary fibrosis.
Near-infrared uncaging or photosensitizing dictated by oxygen tension
Authors: Anderson Erin D. , Gorka Alexander P. , Schnermann Martin J.
Published: November 2016

Existing strategies that use tissue-penetrant near-infrared light for the targeted treatment of cancer typically rely on the local generation of reactive oxygen species. This approach can be impeded by hypoxia, which frequently occurs in tumour microenvironments. Here we demonstrate that axially unsymmetrical silicon phthalocyanines uncage small molecules preferentially in a low-oxygen environment, while efficiently generating reactive oxygen species in normoxic conditions. Mechanistic studies of the uncaging reaction implicate a photoredox pathway involving photoinduced electron transfer to generate a key radical anion intermediate. Cellular studies demonstrate that the biological mechanism of action is O2-dependent, with reactive oxygen species-mediated phototoxicity in normoxic conditions and small molecule uncaging in hypoxia. These studies provide a near-infrared light-targeted treatment strategy with the potential to address the complex tumour landscape through two distinct mechanisms that vary in response to the local O2 environment.
Cl-out is a novel cooperative optogenetic tool for extruding chloride from neurons
Authors: Alfonsa Hannah , Lakey Jeremy H. , Lightowlers Robert N. , Trevelyan Andrew J.
Published: November 2016

Chloride regulation affects brain function in many ways, for instance, by dictating the GABAergic reversal potential, and thereby influencing neuronal excitability and spike timing. Consistent with this, there is increasing evidence implicating chloride in a range of neurological conditions. Investigations about these conditions, though, are made difficult by the limited range of tools available to manipulate chloride levels. In particular, there has been no way to actively remove chloride from neurons; we now describe an optogenetic strategy, ‘Cl-out’, to do exactly this. Cl-out achieves its effect by the cooperative action of two different component opsins: the proton pump, Archaerhodopsin and a chloride channel opsin. The removal of chloride happens when both are activated together, using Archaerhodopsin as an optical voltage clamp to provide the driving force for chloride removal through the concurrently opened, chloride channels. We further show that this novel optogenetic strategy can reverse an in vitro epileptogenic phenotype.
Silica deposits on Mars with features resembling hot spring biosignatures at El Tatio in Chile
Authors: Ruff Steven W. , Farmer Jack D.
Published: November 2016

The Mars rover Spirit encountered outcrops and regolith composed of opaline silica (amorphous SiO2·nH2O) in an ancient volcanic hydrothermal setting in Gusev crater. An origin via either fumarole-related acid-sulfate leaching or precipitation from hot spring fluids was suggested previously. However, the potential significance of the characteristic nodular and mm-scale digitate opaline silica structures was not recognized. Here we report remarkably similar features within active hot spring/geyser discharge channels at El Tatio in northern Chile, where halite-encrusted silica yields infrared spectra that are the best match yet to spectra from Spirit. Furthermore, we show that the nodular and digitate silica structures at El Tatio that most closely resemble those on Mars include complex sedimentary structures produced by a combination of biotic and abiotic processes. Although fully abiotic processes are not ruled out for the Martian silica structures, they satisfy an a priori definition of potential biosignatures.
Correction: Corrigendum: Pathway on demand: automated reconstruction of human signaling networks
Authors: Ritz Anna , Poirel Christopher L , Tegge Allison N , Sharp Nicholas , Simmons Kelsey , Powell Allison , Kale Shiv D , Murali TM
Published: November 2016

Correction to: npj Systems Biology and Applications (2016) 2, 16002; doi:10.1038/npjsba.2016.2; published online 3 March 2016 After online publication of this article, the authors noticed an error in the input files used for running the Prize Collecting Steiner Forest algorithm for Figure 2 (panels 2(a) and 2(b)) and Supplementary Figure S1 in the Supplementary Information.
Mucosal vaccination with a live recombinant rhinovirus followed by intradermal DNA administration elicits potent and protective HIV-specific immune responses
Authors: Tomusange Khamis , Wijesundara Danushka , Gummow Jason , Wesselingh Steve , Suhrbier Andreas , Gowans Eric J. , Grubor-Bauk Branka
Published: November 2016

Mucosal immunity is deemed crucial to control sexual transmission of human immunodeficiency virus (HIV). Herein we report the efficacy of a mucosal HIV vaccine strategy comprising intranasal (IN) vaccination with a cocktail of live recombinant human rhinoviruses (HRVs) encoding overlapping fragments of HIV Gag and full length Tat (rHRV-Gag/Tat) followed by intradermal (ID) vaccination with DNA vaccines encoding HIV Gag and Tat (pVAX-Gag-Tat). This heterologous prime-boost strategy will be referred to hereafter as rHRV-DNA. As a control, IN vaccination with wild type (wt)-HRV-A1 followed by a single ID dose of pVAX (wt-HRV-A1/pVAX vaccination) was included. rHRV-DNA vaccination elicited superior multi-functional CD8+T cell responses in lymphocytes harvested from mesenteric lymph nodes and spleens, and higher titres of Tat-specific antibodies in blood and vaginal lavages, and reduced the viral load more effectively after challenge with EcoHIV, a murine HIV challenge model, in peritoneal macrophages, splenocytes and blood compared compared with wt-HRV-A1/pVAX vaccination or administration of 3 ID doses of pVAX-Gag-Tat (3X pVAX-Gag-Tat vaccination). These data provide the first evidence that a rHRV-DNA vaccination regimen can induce HIV-specific immune responses in the gut, vaginal mucosa and systemically, and supports further testing of this regimen in the development of an effective mucosally-targeted HIV-1 vaccine.
Activated hepatic stellate cells play pivotal roles in hepatocellular carcinoma cell chemoresistance and migration in multicellular tumor spheroids
Authors: Song Yeonhwa , Kim Se-hyuk , Kim Kang Mo , Choi Eun Kyung , Kim Joon , Seo Haeng Ran
Published: November 2016

Most Hepatocellular carcinoma (HCC) are resistant to conventional chemotherapeutic agents and remain an unmet medical need. Recently, multiple studies on the crosstalk between HCC and their tumor microenvironment have been conducted to overcome chemoresistance in HCC. In this study, we formed multicellular tumor spheroids (MCTS) to elucidate the mechanisms of environment-mediated chemoresistance in HCC. We observed that hepatic stellate cells (HSCs) in MCTS significantly increased the compactness of spheroids and exhibited strong resistance to sorafenib and cisplatin relative to other types of stromal cells. Increased collagen 1A1 (COL1A1) expression was apparent in activated HSCs but not in fibroblasts or vascular endothelial cells in MCTS. Additionally, COL1A1 deficiency, which was increased by co-culture with HSCs, decreased the cell-cell interactions and thereby increased the therapeutic efficacy of anticancer therapies in MCTS. Furthermore, losartan, which can inhibit collagen I synthesis, attenuated the compactness of spheroids and increased the therapeutic efficacy of anticancer therapies in MCTS. Meanwhile, activated HSCs facilitated HCC migration by upregulating matrix metallopeptidase 9 (MMP9) in MCTS. Collectively, crosstalk between HCC cells and HSCs promoted HCC chemoresistance and migration by increasing the expression of COL1A1 and MMP9 in MCTS. Hence, targeting HSCs might represent a promising therapeutic strategy for liver cancer therapy.
Multi-species collapses at the warm edge of a warming sea
Authors: Rilov Gil
Published: November 2016

Even during the current biodiversity crisis, reports on population collapses of highly abundant, non-harvested marine species were rare until very recently. This is starting to change, especially at the warm edge of species’ distributions where populations are more vulnerable to stress. The Levant basin is the southeastern edge of distribution of most Mediterranean species. Coastal water conditions are naturally extreme, and are fast warming, making it a potential hotspot for species collapses. Using multiple data sources, I found strong evidence for major, sustained, population collapses of two urchins, one large predatory gastropod and a reef-building gastropod. Furthermore, of 59 molluscan species once-described in the taxonomic literature as common on Levant reefs, 38 were not found in the present-day surveys, and there was a total domination of non-indigenous species in molluscan assemblages. Temperature trends indicate an exceptional warming of the coastal waters in the past three decades. Though speculative at this stage, the fast rise in SST may have helped pushing these invertebrates beyond their physiological tolerance limits leading to population collapses and possible extirpations. If so, these collapses may indicate the initiation of a multi-species range contraction at the Mediterranean southeastern edge that may spread westward with additional warming.
Intestinal PPARγ signalling is required for sympathetic nervous system activation in response to caloric restriction
Authors: Duszka Kalina , Picard Alexandre , Ellero-Simatos Sandrine , Chen Jiapeng , Defernez Marianne , Paramalingam Eeswari , Pigram Anna , Vanoaica Liviu , Canlet Cécile , Parini Paolo , Narbad Arjan , Guillou Hervé , Thorens Bernard , Wahli Walter
Published: November 2016

Nuclear receptor PPARγ has been proven to affect metabolism in multiple tissues, and has received considerable attention for its involvement in colon cancer and inflammatory disease. However, its role in intestinal metabolism has been largely ignored. To investigate this potential aspect of PPARγ function, we submitted intestinal epithelium-specific PPARγ knockout mice (iePPARγKO) to a two-week period of 25% caloric restriction (CR), following which iePPARγKO mice retained more fat than their wild type littermates. In attempting to explain this discrepancy, we analysed the liver, skeletal muscle, intestinal lipid trafficking, and the microbiome, none of which appeared to contribute to the adiposity phenotype. Interestingly, under conditions of CR, iePPARγKO mice failed to activate their sympathetic nervous system (SNS) and increase CR-specific locomotor activity. These KO mice also manifested a defective control of their body temperature, which was overly reduced. Furthermore, the white adipose tissue of iePPARγKO CR mice showed lower levels of both hormone-sensitive lipase, and its phosphorylated form. This would result from impaired SNS signalling and possibly cause reduced lipolysis. We conclude that intestinal epithelium PPARγ plays an essential role in increasing SNS activity under CR conditions, thereby contributing to energy mobilization during metabolically stressful episodes.
Lineage mapper: A versatile cell and particle tracker
Authors: Chalfoun Joe , Majurski Michael , Dima Alden , Halter Michael , Bhadriraju Kiran , Brady Mary
Published: November 2016

The ability to accurately track cells and particles from images is critical to many biomedical problems. To address this, we developed Lineage Mapper, an open-source tracker for time-lapse images of biological cells, colonies, and particles. Lineage Mapper tracks objects independently of the segmentation method, detects mitosis in confluence, separates cell clumps mistakenly segmented as a single cell, provides accuracy and scalability even on terabyte-sized datasets, and creates division and/or fusion lineages. Lineage Mapper has been tested and validated on multiple biological and simulated problems. The software is available in ImageJ and Matlab at isg.nist.gov.
Population prevalence of edentulism and its association with depression and self-rated health
Authors: Tyrovolas Stefanos , Koyanagi Ai , Panagiotakos Demosthenes B. , Haro Josep Maria , Kassebaum Nicholas J. , Chrepa Vanessa , Kotsakis Georgios A.
Published: November 2016

Edentulism is associated with various adverse health outcomes but treatment options in low- and middle-income countries (LMICs) are limited. Data on its prevalence and its effect on mental health and overall-health is lacking, especially from LMICs. Self-reported data on complete edentulism obtained by standardized questionnaires on 201,953 adults aged ≥18 years from 50 countries which participated in the World Health Survey (WHS) 2002–2004 were analyzed. Age and sex-standarized edentulism prevalence ranged from 0.1% (95% CI = 0.0–0.3) (Myanmar) to 14.5% (95% CI = 13.1–15.9) (Zimbabwe), and 2.1% (95% CI = 1.5–3.0) (Ghana) to 32.3% (95% CI = 29.0–35.8) (Brazil) in the younger and older age groups respectively. Edentulism was significantly associated with depression (OR 1.57, 95% CI = 1.23–2.00) and poor self-rated health (OR 1.38, 95% CI = 1.03–1.83) in the younger group with no significant associations in the older age group. Our findings highlight the edentulism-related health loss in younger persons from LMICs. The relative burden of edentulism is likely to grow as populations age and live longer. Given its life-long nature and common risk factors with other NCDs, edentulism surveillance and prevention should be an integral part of the global agenda of NCD control.
Regulation of Sirt1/Nrf2/TNF-α signaling pathway by luteolin is critical to attenuate acute mercuric chloride exposure induced hepatotoxicity
Authors: Yang Daqian , Tan Xiao , Lv Zhanjun , Liu Biying , Baiyun Ruiqi , Lu Jingjing , Zhang Zhigang
Published: November 2016

Inorganic mercury, though a key component of pediatric vaccines, is an environmental toxicant threatening human health via accumulating oxidative stress in part. Luteolin has been of great interest because of its antiinflammatory, anticarcinogenic and antioxidative effects. Here we hypothesized that luteolin would attenuate hepatotoxicity induced by acute inorganic mercury exposure. Kunming mice were treated with luteolin (100 mg/kg) 24 h after administration of 4 mg/kg mercuric chloride (HgCl2). The results showed that luteolin ameliorated HgCl2 induced anemia and hepatotoxicity, regulating radical oxygen species (ROS) production and hepatocyte viability in vitro and oxidative stress and apoptosis in vivo. Furthermore, luteolin reversed the changes in levels of inflammation- and apoptosis-related proteins involving NF-κB, TNF-α, Sirt1, mTOR, Bax, p53, and Bcl-2, and inhibited p38 MAPK activation. Luteolin enhanced antioxidant defense system based on Keap1, Nrf2, HO-1, NQO1, and KLF9. Moreover, luteolin did not affect miRNA-146a expression. Collectively, our findings, for the first time, elucidate a precise mechanism for attenuation of HgCl2-induced liver dysfunction by dietary luteolin via regulating Sirt1/Nrf2/TNF-α signaling pathway, and provide a foundation for further study of luteolin as a novel therapeutic agent against inorganic mercury poisoning.
Cinaciguat prevents the development of pathologic hypertrophy in a rat model of left ventricular pressure overload
Authors: Németh Balázs Tamás , Mátyás Csaba , Oláh Attila , Lux Árpád , Hidi László , Ruppert Mihály , Kellermayer Dalma , Kökény Gábor , Szabó Gábor , Merkely Béla , Radovits Tamás
Published: November 2016

Pathologic myocardial hypertrophy develops when the heart is chronically pressure-overloaded. Elevated intracellular cGMP-levels have been reported to prevent the development of pathologic myocardial hypertrophy, therefore we investigated the effects of chronic activation of the cGMP producing enzyme, soluble guanylate cyclase by Cinaciguat in a rat model of pressure overload-induced cardiac hypertrophy. Abdominal aortic banding (AAB) was used to evoke pressure overload-induced cardiac hypertrophy in male Wistar rats. Sham operated animals served as controls. Experimental and control groups were treated with 10 mg/kg/day Cinaciguat (Cin) or placebo (Co) p.o. for six weeks, respectively. Pathologic myocardial hypertrophy was present in the AABCo group following 6 weeks of pressure overload of the heart, evidenced by increased relative heart weight, average cardiomyocyte diameter, collagen content and apoptosis. Cinaciguat did not significantly alter blood pressure, but effectively attenuated all features of pathologic myocardial hypertrophy, and normalized functional changes, such as the increase in contractility following AAB. Our results demonstrate that chronic enhancement of cGMP signalling by pharmacological activation of sGC might be a novel therapeutic approach in the prevention of pathologic myocardial hypertrophy.
Loss of NMDA receptors in dopamine neurons leads to the development of affective disorder-like symptoms in mice
Authors: Jastrzębska Kamila , Walczak Magdalena , Cieślak Przemysław Eligiusz , Szumiec Łukasz , Turbasa Mateusz , Engblom David , Błasiak Tomasz , Parkitna Jan Rodriguez
Published: November 2016

The role of changes in dopamine neuronal activity during the development of symptoms in affective disorders remains controversial. Here, we show that inactivation of NMDA receptors on dopaminergic neurons in adult mice led to the development of affective disorder-like symptoms. The loss of NMDA receptors altered activity and caused complete NMDA-insensitivity in dopamine-like neurons. Mutant mice exhibited increased immobility in the forced swim test and a decrease in social interactions. Mutation also led to reduced saccharin intake, however the preference of sweet taste was not significantly decreased. Additionally, we found that while mutant mice were slower to learn instrumental tasks, they were able to reach the same performance levels, had normal sensitivity to feedback and showed similar motivation to exert effort as control animals. Taken together these results show that inducing the loss of NMDA receptor-dependent activity in dopamine neurons is associated with development of affective disorder-like symptoms.
Observation and experimental investigation of confinement effects on ion transport and electrokinetic flows at the microscale
Authors: Benneker Anne M. , Wood Jeffery A. , Tsai Peichun A. , Lammertink Rob G. H.
Published: November 2016

Electrokinetic effects adjacent to charge-selective interfaces (CSI) have been experimentally investigated in microfluidic platforms in order to gain understanding on underlying phenomena of ion transport at elevated applied voltages. We experimentally investigate the influence of geometry and multiple array densities of the CSI on concentration and flow profiles in a microfluidic set-up using nanochannels as the CSI. Particle tracking obtained under chronoamperometric measurements show the development of vortices in the microchannel adjacent to the nanochannels. We found that the direction of the electric field and the potential drop inside the microchannel has a large influence on the ion transport through the interface, for example by inducing immediate wall electroosmotic flow. In microfluidic devices, the electric field may not be directed normal to the interface, which can result in an inefficient use of the CSI. Multiple vortices are observed adjacent to the CSI, growing in size and velocity as a function of time and dependent on their location in the microfluidic device. Local velocities inside the vortices are measured to be more than 1.5 mm/s. Vortex speed, as well as flow speed in the channel, are dependent on the geometry of the CSI and the distance from the electrode.
Comparison of high-titer lactic acid fermentation from NaOH- and NH3-H2O2-pretreated corncob by Bacillus coagulans using simultaneous saccharification and fermentation
Authors: Zhang Zhenting , Xie Yuejiao , He Xiaolan , Li Xinli , Hu Jinlong , Ruan Zhiyong , Zhao Shumiao , Peng Nan , Liang Yunxiang
Published: November 2016

Lignocellulose is one of the most abundant renewable feedstocks that has attracted considerable attention as a substrate for biofuel and biochemical production. One such biochemical product, lactic acid, is an important fermentation product because of its great potential for the production of biodegradable and biocompatible polylactic acid. High-titer lactic acid production from lignocellulosic materials has been achieved recently; however, it requires biodetoxification or results in large amounts of waste washing water. In this study, we employed two alkaline pretreatment methods and compared their effects on lactic acid fermentation of pretreated corncob by Bacillus coagulans LA204 using fed-batch simultaneous saccharification and fermentation under non-sterile conditions. The lactic acid titer, yield, and productivity from 16% (w/w) NaOH-pretreated and washed corncob were 122.99 g/L, 0.77 g/g corncob, and 1.37 g/L/h, respectively, and from 16% NH3-H2O2-pretreated and washed corncob were 118.60 g/L, 0.74 g/g corncob, and 1.32 g/L/h, respectively. Importantly, the lactic acid titer, yield, and productivity from 18.4% NH3-H2O2-pretreated and unwashed corncob by using fed-batch simultaneous saccharification and fermentation reached 79.47 g/L, 0.43 g/g corncob, and 1.10 g/L/h, respectively, demonstrating that this method is possible for industrial applications and saves washing water.
Labeling and analysis of chicken taste buds using molecular markers in oral epithelial sheets
Authors: Rajapaksha Prasangi , Wang Zhonghou , Venkatesan Nandakumar , Tehrani Kayvan F. , Payne Jason , Swetenburg Raymond L. , Kawabata Fuminori , Tabata Shoji , Mortensen Luke J. , Stice Steven L. , Beckstead Robert , Liu Hong-Xiang
Published: November 2016

In chickens, the sensory organs for taste are the taste buds in the oral cavity, of which there are ~240–360 in total number as estimated by scanning electron microscopy (SEM). There is not an easy way to visualize all taste buds in chickens. Here, we report a highly efficient method for labeling chicken taste buds in oral epithelial sheets using the molecular markers Vimentin and α-Gustducin. Immediate tissue fixation following incubation with sub-epithelially injected proteases enabled us to peel off whole epithelial sheets, leaving the shape and integrity of the tissue intact. In the peeled epithelial sheets, taste buds labeled with antibodies against Vimentin and α-Gustducin were easily identified and counted under a light microscope and many more taste buds, patterned in rosette-like clusters, were found than previously reported with SEM. Broiler-type, female-line males have more taste buds than other groups and continue to increase the number of taste buds over stages after hatch. In addition to ovoid-shaped taste buds, big tube-shaped taste buds were observed in the chicken using 2-photon microscopy. Our protocol for labeling taste buds with molecular markers will factilitate future mechanistic studies on the development of chicken taste buds in association with their feeding behaviors.
Electronic Properties of Cyclacenes from TAO-DFT
Authors: Wu Chun-Shian , Lee Pei-Yin , Chai Jeng-Da
Published: November 2016

Owing to the presence of strong static correlation effects, accurate prediction of the electronic properties (e.g., the singlet-triplet energy gaps, vertical ionization potentials, vertical electron affinities, fundamental gaps, symmetrized von Neumann entropy, active orbital occupation numbers, and real-space representation of active orbitals) of cyclacenes with n fused benzene rings (n = 4–100) has posed a great challenge to traditional electronic structure methods. To meet the challenge, we study these properties using our newly developed thermally-assisted-occupation density functional theory (TAO-DFT), a very efficient method for the study of large systems with strong static correlation effects. Besides, to examine the role of cyclic topology, the electronic properties of cyclacenes are also compared with those of acenes. Similar to acenes, the ground states of cyclacenes are singlets for all the cases studied. In contrast to acenes, the electronic properties of cyclacenes, however, exhibit oscillatory behavior (for n ≤ 30) in the approach to the corresponding properties of acenes with increasing number of benzene rings. On the basis of the calculated orbitals and their occupation numbers, the larger cyclacenes are shown to exhibit increasing polyradical character in their ground states, with the active orbitals being mainly localized at the peripheral carbon atoms.
Generation of metastatic melanoma specific antibodies by affinity purification
Authors: Schütz Birgit , Koppensteiner Anita , Schörghofer David , Kinslechner Katharina , Timelthaler Gerald , Eferl Robert , Hengstschläger Markus , Missbichler Albert , Hundsberger Harald , Mikula Mario
Published: November 2016

Melanoma is the most aggressive type of skin cancer and one of the most frequent tumours in young adults. Identification of primary tumours prone to develop metastasis is of paramount importance for further patient stratification. However, till today, no markers exist that are routinely used to predict melanoma progression. To ameliorate this problem, we generated antiserum directed against metastatic melanoma tissue lysate and applied a novel approach to purify the obtained serum via consecutive affinity chromatography steps. The established antibody, termed MHA-3, showed high reactivity against metastatic melanoma cell lines both in vitro and in vivo. We also tested MHA-3 on 227 melanoma patient samples and compared staining with the melanoma marker S100b. Importantly, MHA-3 was able to differentiate between metastatic and non-metastatic melanoma samples. By proteome analysis we identified 18 distinct antigens bound by MHA-3. Combined expression profiling of all identified proteins revealed a significant survival difference in melanoma patients. In conclusion, we developed a polyclonal antibody, which is able to detect metastatic melanoma on paraffin embedded sections. Hence, we propose that this antibody will represent a valuable additional tool for precise melanoma diagnosis.
Supplementation with D-serine prevents the onset of cognitive deficits in adult offspring after maternal immune activation
Authors: Fujita Yuko , Ishima Tamaki , Hashimoto Kenji
Published: November 2016

Prenatal maternal infection contributes to the etiology of schizophrenia, with D-serine, an endogenous co-agonist of the N-methyl-D-aspartate (NMDA) receptor, playing a role in the pathophysiology of this disease. We examined whether supplementation with D-serine during juvenile and adolescent stages could prevent the onset of cognitive deficits, prodromal and the core symptoms of schizophrenia in adult offspring after maternal immune activation (MIA). Juvenile offspring exposed prenatally to poly(I:C) showed reduced expression of NMDA receptor subunits in the hippocampus. Supplementing drinking water with D-serine (600 mg/L from P28 to P56) prevented the onset of cognitive deficits in adult offspring after MIA, in a significant manner. This study shows that supplementing offspring with D-serine during juvenile and adolescent stages could prevent the onset of psychosis in adulthood, after MIA. Therefore, early intervention with D-serine may prevent the occurrence of psychosis in high-risk subjects.
The archaeal “7 kDa DNA-binding” proteins: extended characterization of an old gifted family
Authors: Kalichuk Valentina , Béhar Ghislaine , Renodon-Cornière Axelle , Danovski Georgi , Obal Gonzalo , Barbet Jacques , Mouratou Barbara , Pecorari Frédéric
Published: November 2016

The “7 kDa DNA-binding” family, also known as the Sul7d family, is composed of chromatin proteins from the Sulfolobales archaeal order. Among them, Sac7d and Sso7d have been the focus of several studies with some characterization of their properties. Here, we studied eleven other proteins alongside Sac7d and Sso7d under the same conditions. The dissociation constants of the purified proteins for binding to double-stranded DNA (dsDNA) were determined in phosphate-buffered saline at 25 °C and were in the range from 11 μM to 22 μM with a preference for G/C rich sequences. In accordance with the extremophilic origin of their hosts, the proteins were found highly stable from pH 0 to pH 12 and at temperatures from 85.5 °C to 100 °C. Thus, these results validate eight putative “7 kDa DNA-binding” family proteins and show that they behave similarly regarding both their function and their stability among various genera and species. As Sac7d and Sso7d have found numerous uses as molecular biology reagents and artificial affinity proteins, this study also sheds light on even more attractive proteins that will facilitate engineering of novel highly robust reagents.
Genetic Epidemiology of Glucose-6-Phosphate Dehydrogenase Deficiency in the Arab World
Authors: Doss C. George Priya , Alasmar Dima R. , Bux Reem I. , Sneha P. , Bakhsh Fadheela Dad , Al-Azwani Iman , Bekay Rajaa El , Zayed Hatem
Published: November 2016

A systematic search was implemented using four literature databases (PubMed, Embase, Science Direct and Web of Science) to capture all the causative mutations of Glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDD) in the 22 Arab countries. Our search yielded 43 studies that captured 33 mutations (23 missense, one silent, two deletions, and seven intronic mutations), in 3,430 Arab patients with G6PDD. The 23 missense mutations were then subjected to phenotypic classification usingin silicoprediction tools, which were compared to the WHO pathogenicity scale as a reference. Thesein silico toolswere tested for their predicting efficiency using rigorous statistical analyses. Of the 23 missense mutations, p.S188F, p.I48T, p.N126D, and p.V68M, were identified as the most common mutations among Arab populations, but were not unique to the Arab world, interestingly, our search strategy found four other mutations (p.N135T, p.S179N, p.R246L, and p.Q307P) that are unique to Arabs. These mutations were exposed to structural analysis and molecular dynamics simulation analysis (MDSA), which predicting these mutant forms as potentially affect the enzyme function. The combination of the MDSA, structural analysis, andin silicopredictions and statistical tools we used will provide a platform for future prediction accuracy for the pathogenicity of genetic mutations.
Plasma selenium levels and nonalcoholic fatty liver disease in Chinese adults: a cross-sectional analysis
Authors: Yang Zhen , Yan Chonghuai , Liu Gang , Niu Yixin , Zhang Weiwei , Lu Shuai , Li Xiaoyong , Zhang Hongmei , Ning Guang , Fan Jiangao , Qin Li , Su Qing
Published: November 2016

Selenium exposure can induce liver insulin resistance and increased liver triglyceride concentrations in animals, which may link to an increased risk of nonalcoholic fatty liver disease (NAFLD). However, epidemiological studies investigating the association between elevated plasma selenium levels and NAFLD were not available. We aimed to investigate the association of selenium levels with the prevalence of NAFLD in Chinese adults. This was a cross-sectional study of 8550 Chinese adults aged 40 yr or older in Shanghai, China. A questionnaire, anthropometric measurements, and laboratory tests were conducted. NAFLD was diagnosed by hepatic ultrasound after the exclusion of alcohol abuse and other liver diseases. Plasma selenium concentration was assessed by inductively coupled plasma mass spectroscopy. The median concentration of plasma selenium was 213.0 μg/L. Elevated plasma selenium levels were associated with higher triglycerides, LDL-cholesterol, fasting plasma glucose, post-loading plasma glucose, A1c, HOMA-IR, as well as ALT, AST and γ-GT (all P < 0.05). The odds ratios were substantially higher for NAFLD (OR = 1.54, 95% CI 1.13–2.18) in the highest selenium quartile compared with those in the lowest quartile, after adjustment for potential cofounder. The results of this study provided epidemiological evidence that increased plasma selenium level is associated with elevated prevalence of NAFLD.
The association between meteorological factors and road traffic injuries: a case analysis from Shantou city, China
Authors: Gao Jinghong , Chen Xiaojun , Woodward Alistair , Liu Xiaobo , Wu Haixia , Lu Yaogui , Li Liping , Liu Qiyong
Published: November 2016

Few studies examined the associations of meteorological factors with road traffic injuries (RTIs). The purpose of the present study was to quantify the contributions of meteorological factors to RTI cases treated at a tertiary level hospital in Shantou city, China. A time-series diagram was employed to illustrate the time trends and seasonal variation of RTIs, and correlation analysis and multiple linear regression analysis were conducted to investigate the relationships between meteorological parameters and RTIs. RTIs followed a seasonal pattern as more cases occurred during summer and winter months. RTIs are positively correlated with temperature and sunshine duration, while negatively associated with wind speed. Temperature, sunshine hour and wind speed were included in the final linear model with regression coefficients of 0.65 (t = 2.36, P = 0.019), 2.23 (t = 2.72, P = 0.007) and −27.66 (t = −5.67, P < 0.001), respectively, accounting for 19.93% of the total variation of RTI cases. The findings can help us better understand the associations between meteorological factors and RTIs, and with potential contributions to the development and implementation of regional level evidence-based weather-responsive traffic management system in the future.
Efficacy of cupping therapy in patients with the fibromyalgia syndrome-a randomised placebo controlled trial
Authors: Lauche Romy , Spitzer Julia , Schwahn Barbara , Ostermann Thomas , Bernardy Kathrin , Cramer Holger , Dobos Gustav , Langhorst Jost
Published: November 2016

This study aimed to test the efficacy of cupping therapy to improve symptoms and quality of life in patients diagnosed with the fibromyalgia syndrome. Participants were randomly assigned to cupping therapy, sham or usual care. Cupping was administered five times at twice weekly intervals on the upper and lower back. The primary outcome measure was pain intensity at day 18. Secondary outcomes included functional disability, quality of life, fatigue and sleep quality as well as pressure pain sensitivity, satisfaction and safety at day 18 and 6 months. Altogether 141 patients were included in this study (139 females, 55.8 ± 9.1 years). After 18 days patients reported significant less pain after cupping compared to usual care (difference −12.4; 95% CI: −18.9; −5.9, p < 0.001) but not compared to sham (difference −3.0; 95% CI: −9.9, 3.9, p = 0.396). Further effects were found for quality of life compared to usual care. Patients were mildly satisfied with cupping and sham cupping; and only minor side effects were observed. Despite cupping therapy being more effective than usual care to improve pain intensity and quality of life, effects of cupping therapy were small and comparable to those of a sham treatment, and as such cupping cannot be recommended for fibromyalgia at the current time.