bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACTBackground: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

AbstractThis 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.
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

AbstractThe 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

AbstractExisting 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

AbstractChloride 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

AbstractThe 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.
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

AbstractMucosal 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

AbstractMost 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

AbstractEven 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

AbstractNuclear 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

AbstractThe 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

AbstractEdentulism 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

AbstractInorganic 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

AbstractPathologic 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

AbstractThe 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

AbstractElectrokinetic 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.