bluuebunny/crossref_metadata_2025 huggingface dataset:
The Epigenetic Regulator HDAC1 Modulates Transcription of a Core Cardiogenic Program in Human Cardiac Mesenchymal Stromal Cells Through a p53-Dependent Mechanism
Authors: Moore Joseph B. , Zhao John , Keith Matthew C. L. , Amraotkar Alok R. , Wysoczynski Marcin , Hong Kyung U. , Bolli Roberto
Published: August 2016

Histone deacetylase (HDAC) regulation is an essential process in myogenic differentiation. Inhibitors targeting the activity of specific HDAC family members have been shown to enhance the cardiogenic differentiation capacity of discrete progenitor cell types; a key property of donor cell populations contributing to their afforded benefits in cardiac cell therapy applications. The influence of HDAC inhibition on cardiac-derived mesenchymal stromal cell (CMC) transdifferentiation or the role of specific HDAC family members in dictating cardiovascular cell lineage specification has not been investigated. In the current study, the consequences of HDAC inhibition on patient-derived CMC proliferation, cardiogenic program activation, and cardiovascular differentiation/cell lineage specification were investigated using pharmacologic and genetic targeting approaches. Here, CMCs exposed to the pan-HDAC inhibitor sodium butyrate exhibited induction of a cardiogenic transcriptional program and heightened expression of myocyte and endothelial lineage-specific markers when coaxed to differentiate in vitro. Further, shRNA knockdown screens revealed CMCs depleted of HDAC1 to promote the induction of a cardiogenic transcriptional program characterized by enhanced expression of cardiomyogenic- and vasculogenic-specific markers, a finding which depended on and correlated with enhanced acetylation and stabilization of p53. Cardiogenic gene activation and elevated p53 expression levels observed in HDAC1-depleted CMCs were associated with improved aptitude to assume a cardiomyogenic/vasculogenic cell-like fate in vitro. These results suggest that HDAC1 depletion-induced p53 expression alters CMC cell fate decisions and identify HDAC1 as a potential exploitable target to facilitate CMC-mediated myocardial repair in ischemic cardiomyopathy.
Setting the Stage: The Intersection of Leadership and Assessment
Authors: Roberts Darby M. , Bailey Krista J.
Published: August 2016

This chapter provides an overview of leadership and assessment and addresses the complexity of assessing leadership.
Developing a Comprehensive Assessment Plan
Authors: Piatt Kimberly A. , Woodruff Tearney R.
Published: August 2016

This chapter provides practical advice for developing a comprehensive assessment plan. Two examples from institutions that have created both individual and program‐level assessment plans for leadership programs are shared.
Exploring the Language of Leadership Learning and Education
Authors: Allen Scott J. , Shehane Melissa R.
Published: August 2016

This chapter examines the importance of language in the emerging field of leadership, especially when establishing and maintaining partnerships and when designing pedagogical practices for leadership learning.
Large soft‐tissue masses in an adult patient with Gaucher disease
Authors: Mahajan Neha , Brynes Russell , Yano Shoji
Published: August 2016

Extra‐osseous masses are rarely seen in Gaucher disease. Here we present a case of a 30‐year‐old patient with Gaucher disease type 3, receiving β‐glucocerebrosidase enzyme replacement therapy, who presented with slowly enlarging masses along her back. There was no osseous extension seen on imaging. Biopsy of the mass ultimately showed extensive soft tissue infiltration by Gaucher cells. No other cases of soft‐tissue masses of this extent have been described in the literature, and therefore management remains unclear.
Synthesis of Fatty Acetoacetates Under Microwave Irradiation Catalysed by Sulfamic Acid in a Solvent‐Free System
Authors: Weber Andressa C. H. , Batista Thaís C. , Gonçalves Bruno , Hack Carolina R. L. , Porciuncula Larissa M. , Treptow Tamara G. M. , D'Oca Caroline Da R. Montes , Russowsky Dennis , D'Oca Marcelo G. Montes
Published: August 2016

The 1,3‐dicarbonyl compounds are important building blocks to obtain products with various biological activities and technological applications. In this work, we used a simple transesterification method to develop fatty acetoacetates in a solvent‐free medium using a green catalyst, sulfamic acid (NH2SO3H), under microwave irradiation. The experimental results demonstrate good yields in a short reaction time (13 min), which makes this method an efficient approach to synthesize fatty acetoacetates from a wide range of saturated, unsaturated, and polyunsaturated long chain fatty alcohols, and ricinoleic derivatives. Experiments of recycling of the catalyst were performed and no decrease in catalytic activity of sulfamic acid was observed.
Liquefaction Potential Evaluation for Subsurface Soil Layers of Delhi Region
Authors: Thoithoi L. , Dubey C. S. , Ningthoujam P. S. , Shukla D. P. , Singh R. P. , Naorem S. S.
Published: August 2016

The study area Delhi is second most populous city and third largest urban area in the world. Though the area lies in seismic high damage risk zone, number of high rise building and construction of mega structure at several sites of the city increase rapidly. In this study field Standard Penetration Test (SPT) values of soil collected from 750 boreholes data were analyzed to identify liquefiable sub-surface soil layers. Finally, liquefaction susceptible sub-surface maps of the region at various depth (20 m, 15 m, 12 m, 9 m, 6 m and 3 m) from ground level is prepared. The outcome of this study will be useful input for preliminary foundation and designing of earthquake resistant high rise building and seismic microzonation studies of Delhi.
Geochemical Behaviour of LREE, Y and Zr in Uranium Mineralized and Non-Mineralized Granite from Darshanapur Area, in the Gogi-Kurlagere Fault Zone, Bhima Basin, Yadgiri District, Karnataka
Authors: Patnaik Sikta , Hegde G. N. , Panneerselvam A. , Verma M. B. , Mohanty R. , Rai A. K.
Published: August 2016

Granite core samples (n=14) from the Gogi-Kurlagere fault zone in the central part of the Bhima basin were studied in terms of LREE, Y and Zr mobility during uranium mineralization. LREE, Zr and Y along with LILE (Ba, Rb) and P show behavioral differences in the mineralised and the non-mineralised samples. Average ∑LREE in mineralised granite (240 ppm) is higher than in non-mineralised samples (157 ppm). The average Zr and Y in the mineralised granite are 193 ppm and 17 ppm, while the corresponding abundances of these elements in non-mineralised portion are 148 ppm and 11 ppm respectively. Besides enrichment of U, Th, Ba, Pb and Rb and depletion of Sr are observed in mineralized granite in comparison to non-mineralized granite. Hydrothermal alteration has led to the mobility of these elements, which again dependent on the overall geochemical behavior of the migrating fluid. REE and Y in association with uranyl [(UO 2)2+] ion were transported as carbonate complexes like [UO2 (CO3)3]4- and [REE (CO3)3]3- and were later incorporated into favourable structural loci by precipitating minerals like pitchblende and coffinite.
Prioritization of Sub-Watersheds for Conservation Measures in a Semi Arid Watershed Using Remote Sensing and GIS
Authors: Khanday Mohd Yousuf , Javed Akram
Published: August 2016

Land and water resources development plans are generally adopted at watershed level. Delineation of watersheds and their prioritization within large river basins requires host of terrain parameters to be studied and analysed. Chopan watershed in Central India has been studied for sub-watershed delineation and prioritization based on drainage morphometry, land use/land cover and sediment yield index analysis using remote sensing and GIS techniques. The watershed was demarcated into five sub-watersheds on the basis of drainage flow directions, contour value, slope, elevation. Geocoded satellite data of 1989 and 2001 on 1:50 000 scale were visually interpreted to prepare land use/land cover and drainage maps which were later digitized using Arcview/ArcGIS. Linear and shape aspects of the sub-watersheds were computed and used for prioritization. The results show widespread variation in drainage characteristics, land cover changes and sediment yield rates across sub-watersheds. On the basis of morphometric, land use/land cover change and sediment yield index, sub-watersheds were grouped into low, medium and high priority. A correlation of results show that SW1 and SW5 are common sub-watersheds falling under high and low priority based on morphometric, land use change analysis and SYI. The priority list of sub-watersheds will be crucial for decision making and implementation of land and water resource conservation projects.
Dynamicity of the Himalayan Landslide - A Tectono-Geotechnical Appraisal of the 13th Mile Landslide, Sikkim
Authors: Hindayar J. N. , Dasarwar P. , Srivastava S. P. , Thrideep Kumar N. , Mohan Murali , Som S. K.
Published: August 2016

Understanding the causes of slope development with movement initiation of land sliding requires knowledge on dynamicity, displacement, strain concentration and factor of safety. The 13th mile landslide on Gangtok-Nathula road of the Sikkim Himalaya has seriously affected the Indo-China trade route. To quantify the spatial movement pattern, strain analysis and identification of zones of safety were attempted which indicates that differential movement activity of the landslide zone is co-relatable with differential strain pattern with an overall imprint of the Himalaya collision tectonics.
Statistical and Analytical Evaluation of Groundwater Quality of Tirupati Area, Chittoor District, Andhra Pradesh, South India
Authors: Nagaraju A. , Sharifi Z. , Balaji E.
Published: August 2016

The multivariate statistical analysis, hydrogeochemical modelling using visual MINTEQ software, indices of base exchange and Gibbs ratio were simultaneously applied to groundwater hydrochemical data of the Tirupati area. These techniques were applied to know the principal processes controlling the water chemistry. Fifty groundwater samples were analyzed for pH, electrical conductivity (EC), Ca, Mg, Na, K, HCO3, CO3, Cl, and SO4. The results showed that the abundance of the major ions in the water samples is in following order: Na > Ca > Mg > K and HCO3 > Cl > SO4 > CO3 > F. From this study, it is clear that there are five main processes that are responsible for this hydrochemistry namely: (1) weathering of silicate minerals, (2) dissolution of chloride salts, (3) Ion exchange between (sodium, potassium) and (calcium, magnesium) during the infiltration of reclaimed water, (4) precipitation of carbonate minerals and (5) anthropogenic activities (agricultural activities such as irrigation practices and fertilizers). Further, this study clearly demonstrates that the multivariate statistical techniques are potential tools and provide with greater precision clues to the processes that control water chemistry.
Clusterorganisationen in der Praxis
Authors: Häfner Karl
Published: August 2016

Cluster organizations implement cluster policies and affect the outcome of them to a high degree. Their work is influenced by interactions with the promoted firms, political and other actors. A sound consultancy of cluster promotion should know these influences and take them seriously, because they shape the strengths, weaknesses and potentials of cluster organizations. This article examines how cluster organizations in Bavaria translate cluster theory into practical activities and how other actors influence them in the process. The influences are subdivided into institutional and structural factors. Institutional factors refer to social institutions that other actors impose on the organizations. It will be shown that these factors shape the work of cluster organizations to a high degree, but only seldom restrain it. The organizations positions and tasks within the wider economic promotion system constitute the structural factors. They confine the organizations towards networking activities and force them to cooperate with other promotional actors, if they want to provide a comprehensive cluster promotion.
Fetal Growth Restriction (FGR): How the Differences Between Early and Late FGR Impact on Clinical Management?
Authors: Monaghan Caitriona , Thilaganathan Baskaran
Published: August 2016

Fetal growth restriction (FGR) is associated with significantly increased perinatal mortality as well as immediate and long-term morbidity. One of the most challenging aspects of this condition is the ability to accurately define and adequately diagnose it in order to determine appropriate clinical management. Within a common pathogenesis of placental insufficiency, two phenotypes, early and late FGR, have emerged. Early FGR is easier to diagnose, however, as a consequence of extreme prematurity at presentation it can be extremely challenging to manage. Late fetal growth restriction is much more problematic to diagnose but relatively straightforward to manage as delivery is a reasonable option. Areas of research with regards to FGR, which require further evaluation, include the development of more accurate screening tools in order to identify those women at risk and validation of the role of aspirin in the prevention of this condition in a prospective adequately powered trial.
Locus coeruleus volume and cell population changes during Alzheimer's disease progression: A stereological study in human postmortem brains with potential implication for early‐stage biomarker discovery
Authors: Theofilas Panos , Ehrenberg Alexander J. , Dunlop Sara , Di Lorenzo Alho Ana T. , Nguy Austin , Leite Renata Elaine Paraizo , Rodriguez Roberta Diehl , Mejia Maria B. , Suemoto Claudia K. , Ferretti-Rebustini Renata Eloah De Lucena , Polichiso Livia , Nascimento Camila F. , Seeley William W. , Nitrini Ricardo , Pasqualucci Carlos Augusto , Jacob Filho Wilson , Rueb Udo , Neuhaus John , Heinsen Helmut , Grinberg Lea T.
Published: August 2016

Introduction

Alzheimer's disease (AD) progression follows a specific spreading pattern, emphasizing the need to characterize those brain areas that degenerate first. The brainstem's locus coeruleus (LC) is the first area to develop neurofibrillary changes (neurofibrillary tangles [NFTs]).

Methods

The methods include unbiased stereological analyses in human brainstems to estimate LC volume and neuronal population in controls and individuals across all AD stages.

Results

As the Braak stage increases by 1 unit, the LC volume decreases by 8.4%. Neuronal loss started only midway through AD progression. Age‐related changes spare the LC.

Discussion

The long gap between NFT accumulation and neuronal loss suggests that a second trigger may be necessary to induce neuronal death in AD. Imaging studies should determine whether LC volumetry can replicate the stage‐wise atrophy observed here and how these changes are specific to AD. LC volumetry may develop into a screening biomarker for selecting high‐yield candidates to undergo expensive and less accessible positron emission tomography scans and to monitor AD progression from presymptomatic stages.
Wholesome Nutrition: an example for a sustainable diet
Authors: von Koerber Karl , Bader Nadine , Leitzmann Claus
Published: August 2016

‘Wholesome Nutrition’ is a concept of sustainable nutrition that was developed at the University of Giessen in the 1980s. In this concept, health and the ecologic, economic, social and cultural dimensions of nutrition are equally important. In 1992 at the UN-Conference on Environment and Development in Rio de Janeiro the definition of ‘Sustainable Development’ comprised the dimensions environment, economy and society. Additionally to these three ‘classical’ dimensions of sustainability, we included ‘health’ as the fourth dimension because nutrition has far reaching effects on human health. The fifth dimension, ‘culture’, became part of the sustainability dialogue since many years; the respective cultural background influences food habits. Presently, mankind has to cope with huge global challenges such as poverty and food insecurity in low-income countries as well as climate change. Therefore the objective is to identify prospects for actions to respond to these global challenges. The concept of ‘Sustainable Nutrition’ analyses the food supply chain at all stages from input-production and primary production to processing, distribution, preparation, consumption and waste disposal. The present analysis leads to the following seven principles: preference of plant-based foods, organic foods, regional and seasonal products, preference of minimally processed foods, Fair Trade products, resource-saving housekeeping and enjoyable eating culture. This concept is based on holistic thinking and has the potential to reduce the global challenges in the field of nutrition. Scientists, stakeholders, multipliers and consumers are asked to consider environmental, economic, social and cultural aspects in addition to the biological (health) aspects.
Motivating factors and barriers towards exercise in severe mental illness: a systematic review and meta-analysis
Authors: Firth J. , Rosenbaum S. , Stubbs B. , Gorczynski P. , Yung A. R. , Vancampfort D.
Published: August 2016

Exercise can improve clinical outcomes in people with severe mental illness (SMI). However, this population typically engages in low levels of physical activity with poor adherence to exercise interventions. Understanding the motivating factors and barriers towards exercise for people with SMI would help to maximize exercise participation. A search of major electronic databases was conducted from inception until May 2016. Quantitative studies providing proportional data on the motivating factors and/or barriers towards exercise among patients with SMI were eligible. Random-effects meta-analyses were undertaken to calculate proportional data and 95% confidence intervals (CI) for motivating factors and barriers toward exercise. From 1468 studies, 12 independent studies of 6431 psychiatric patients were eligible for inclusion. Meta-analyses showed that 91% of people with SMI endorsed ‘improving health’ as a reason for exercise (N = 6, n = 790, 95% CI 80–94). Among specific aspects of health and well-being, the most common motivations were ‘losing weight’ (83% of patients), ‘improving mood’ (81%) and ‘reducing stress’ (78%). However, low mood and stress were also identified as the most prevalent barriers towards exercise (61% of patients), followed by ‘lack of support’ (50%). Many of the desirable outcomes of exercise for people with SMI, such as mood improvement, stress reduction and increased energy, are inversely related to the barriers of depression, stress and fatigue which frequently restrict their participation in exercise. Providing patients with professional support to identify and achieve their exercise goals may enable them to overcome psychological barriers, and maintain motivation towards regular physical activity.
An improved FastSLAM 2.0 algorithm based on FC&ASD-PSO
Authors: Lv Taizhi , Feng Maoyan
Published: August 2016

FastSLAM 2.0 is a popular framework which uses a Rao-Blackwellized particle filter to solve the simultaneous localization and mapping problem. The sampling process is one of the most important phases in the FastSLAM 2.0 framework. Its estimation accuracy depends heavily on a correct prior knowledge about the control and observation noise statistics (the covariance matrices Q and R). Without the correct prior knowledge about these matrices, the estimation accuracy of the robot path and landmark positions may degrade seriously. However in many applications, the prior knowledge is unknown, or these noises are non-stationary. In this paper, these covariance matrices are supposed to be dynamic and denoted as Qt and Rt. Since there are noises, time-adjacent observations are inconsistent with each other. This inconsistency can reflect the real value of the covariance matrices. By the inconsistency, an extra step is introduced to the FastSLAM 2.0 framework. This step makes Qt and Rt match with their real value by using a particle swarm optimization method based on fractional calculus and alpha stable distribution (FC&ASD-PSO). Both simulation and experimental results show that the proposed algorithm improves the accuracy by the more accurate estimation on the noise covariance matrices.
Self-deployment of mobile robotic networks: an algorithm for decentralized sweep boundary coverage
Authors: Semakova Anna A. , Ovchinnikov Kirill S. , Matveev Alexey S.
Published: August 2016

Several non-holonomic Dubins-car-like robots travel over paths with bounded curvatures in a plane that contains an a priori unknown region. The robots are anonymous to one another and do not use communication facilities. Any of them has access to the current minimum distance to the region and can determine the relative positions and orientations of the other robots within a finite and given visibility range. We present a distributed navigation and guidance strategy under which every robot autonomously converges to the desired minimum distance to the region with always respecting a given safety margin, the robots do not collide with one another and do not get into clusters, and the entire team ultimately sweeps over the respective equidistant curve at a speed exceeding a given threshold, thus forming a kind of a sweeping barrier at the perimeter of the region. Moreover, this strategy provides effective sub-uniform distribution of the robots over the equidistant curve. Mathematically rigorous justification of the proposed strategy is offered; its effectiveness is confirmed by extensive computer simulations and experiments with real wheeled robots.
crAssphage is not associated with diarrhoea and has high genetic diversity
Authors: LIANG Y. Y. , ZHANG W. , TONG Y. G. , CHEN S. P.
Published: August 2016

crAssphage is a newly discovered gut bacteriophage. However, its pathogenicity and molecular epidemiology in humans are as yet unclear. In this study, we investigated the association between crAssphage and diarrhoea, as well as the molecular epidemiology of crAssphage in Chinese patients from our hospital. Our results indicated that there were no significant differences in the crAssphage-positive ratio and viral loads in faecal supernatants between adults with diarrhoea and healthy adults. Of infants and children with diarrhoea, 2·8% were found to be crAssphage-positive, including two infants aged <1 month. Markedly, of all confirmed crAssphage-positive strains, 100% had the ORF00039 deletion and 77·8% had low identity of ORF00018 compared to crAssphage (GenBank accession no. NC_024711, designated genotype 1). Thus, crAssphage was not associated with diarrhoea and most strains of crAssphage in Chinese patients (designated genotype 2) were characterized by the ORF00039 deletion and low identity of ORF00018.
Cognitive leisure activities and future risk of cognitive impairment and dementia: systematic review and meta-analysis
Authors: Yates Lauren A , Ziser Shier , Spector Aimee , Orrell Martin
Published: August 2016

Background:

As life expectancies continue to rise, modifiable lifestyle factors that may prevent cognitive decline and dementia in later life become increasingly important in order to maintain quality of life in old age.

Methods:

Five meta-analyses were conducted on data from papers identified in a systematic review. Studies were grouped according to outcomes (dementia, cognitive impairment including amnestic Mild Cognitive Impairment (aMCI), Mild Cognitive Impairment (MCI), and cognitive decline) and output (risk (RR), odds (OR), or hazard ratios (HR)).

Results:

Nineteen studies met our inclusion criteria and quality assessments. Four of five meta-analyses showed significant associations between participation in cognitive leisure activities and reduced risk of cognitive impairment (OR = 0.69, 95% CI: 0.56–0.85) and dementia (HR = 0.58, 95% CI: 0.46–0.74; RR = 0.61, 95% CI: 0.42–0.90; OR = 0.78, 95% CI: 0.67–0.90). However, one pooled analysis of cognitive impairment studies did not reach significance (HR = 0.85, 95% CI: 0.71–1.02). Mentally stimulating leisure activities were significantly associated with later life cognition (β = 0.11, p = 0.05), better memory (β = 0.20, 95% CI: 0.11–0.29), speed of processing (β = 0.37, 95% CI: 0.29–0.45), and executive functioning (β = 0.23, 95% CI: 0.15–0.29), and less decline in overall cognition (β = −0.23, p < 0.01), language (β = −0.11, p < 0.05), and executive functioning (β = −0.13, p < 0.05). Activities were also shown to reduce rate of cognitive decline (estimate = 0.03, SE = 0.01, p = 0.00).

Conclusions:

There is increasing evidence that participation in cognitively stimulating leisure activities may contribute to a reduction of risk of dementia and cognitive impairment in later life. Promoting involvement in such activities across lifespan could be an important focus for primary prevention strategies for governments and health services.
Changes in Mortality Rates and Humanitarian Conditions in Darfur, Sudan 2003–2007
Authors: Garfield Richard , Polonsky Jonny
Published: August 2016

The Darfur region of Sudan has been an intense focus of humanitarian concern since rebellions began there early in 2003. In 2004, the US Secretary of State declared that conflict in Darfur represented genocide. Since 2003, many sample surveys and various mortality estimates for Darfur have been made. Nonetheless, confusion and controversy surrounding mortality levels and trends have continued. For this project, results were reviewed from the highest quality field surveys on mortality in Darfur conducted between 2003 and 2008. Trend analysis demonstrated a dramatic decline in mortality over time in Darfur. By 2005, mortality levels had fallen below emergency levels and have continued to decline. Deaths directly due violence have declined as a proportion of all of the deaths in Darfur. Declining mortality in Darfur was not associated with other proximate improvements in well-being, such as improved nutrition. Without large-scale, humanitarian intervention, continuing high rates of mortality due to violence likely would have occurred. If mortality had continued at the high rate documented in 2004, by January 2009, there would have been 330,000 additional deaths. With the humanitarian assistance provided through the United Nations and non-governmental organizations, these people are alive today. A focus on excess deaths among non-combatants may draw attention away from other needs, such as establishing better security, improving service delivery to the displaced, and advocating for internally displaced persons to be reached today and to re-establish their lives and livelihoods tomorrow.
Mechanism of action of pimavanserin in Parkinson’s disease psychosis: targeting serotonin 5HT2A and 5HT2C receptors
Authors: Stahl Stephen M.
Published: August 2016

Pimavanserin, a novel agent approved for the treatment of Parkinson’s disease psychosis, has potent actions as an antagonist/inverse agonist at serotonin 5HT2A receptors and less potent antagonist/inverse agonist actions at 5HT2C receptors.
Evolution of Microstructure and Microtexture in Friction Stir Welded Oxide Dispersion Strengthened Steel
Authors: Baker B.W. , Menon S. , Brewer L.N.
Published: August 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
Nepali Bhutanese Refugees Reap Support Through Community Gardening
Authors: Gerber Monica M. , Callahan Jennifer L. , Moyer Danielle N. , Connally Melissa L. , Holtz Pamela M. , Janis Beth M.
Published: August 2016

Effectively addressing psychological needs of refugees is a challenge for service providers operating within an expensive health care system based on Western constructs of mental health. In response to this challenge, refugee resettlement agencies throughout the United States use community gardens to promote psychological healing, self-sufficiency, community engagement, and a return of human dignity. Although the success of these programs has been reported in the popular press, they have not been studied systematically. The present exploratory mixed methods study drew upon quantitative and qualitative data to explore perspectives on participating in a community garden among Nepali Bhutanese refugees ( N = 50; 62% female). Participants self-selected to engage in gardening prior to research ( n = 22), or were part of the nongardening comparison group ( n = 28). Results revealed no significant group differences in regard to symptoms of depression, anxiety, somatic complaints, or adjustment to life in the United States. Quantitative results indicated that community gardening was significantly positively associated with social support, a key contributor to optimal functioning within communal cultures. Qualitative data provided additional context within which to understand these results, and further supported the role of social support in community gardening. Implications for clinical research, advocacy, and community care are discussed and suggestions for further research are provided.
The methanogenic redox cofactor F420 is widely synthesized by aerobic soil bacteria
Authors: Ney Blair , Ahmed F Hafna , Carere Carlo R , Biswas Ambarish , Warden Andrew C , Morales Sergio E , Pandey Gunjan , Watt Stephen J , Oakeshott John G , Taylor Matthew C , Stott Matthew B , Jackson Colin J , Greening Chris
Published: August 2016

F420 is a low-potential redox cofactor that mediates the transformations of a wide range of complex organic compounds. Considered one of the rarest cofactors in biology, F420 is best known for its role in methanogenesis and has only been chemically identified in two phyla to date, the Euryarchaeota and Actinobacteria. In this work, we show that this cofactor is more widely distributed than previously reported. We detected the genes encoding all five known F420 biosynthesis enzymes (cofC, cofD, cofE, cofG and cofH) in at least 653 bacterial and 173 archaeal species, including members of the dominant soil phyla Proteobacteria, Chloroflexi and Firmicutes. Metagenome datamining validated that these genes were disproportionately abundant in aerated soils compared with other ecosystems. We confirmed through high-performance liquid chromatography analysis that aerobically grown stationary-phase cultures of three bacterial species, Paracoccus denitrificans, Oligotropha carboxidovorans and Thermomicrobium roseum, synthesized F420, with oligoglutamate sidechains of different lengths. To understand the evolution of F420 biosynthesis, we also analyzed the distribution, phylogeny and genetic organization of the cof genes. Our data suggest that although the Fo precursor to F420 originated in methanogens, F420 itself was first synthesized in an ancestral actinobacterium. F420 biosynthesis genes were then disseminated horizontally to archaea and other bacteria. Together, our findings suggest that the cofactor is more significant in aerobic bacterial metabolism and soil ecosystem composition than previously thought. The cofactor may confer several competitive advantages for aerobic soil bacteria by mediating their central metabolic processes and broadening the range of organic compounds they can synthesize, detoxify and mineralize.
Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma
Authors: Shiraishi Kouya , Okada Yukinori , Takahashi Atsushi , Kamatani Yoichiro , Momozawa Yukihide , Ashikawa Kyota , Kunitoh Hideo , Matsumoto Shingo , Takano Atsushi , Shimizu Kimihiro , Goto Akiteru , Tsuta Koji , Watanabe Shun-ichi , Ohe Yuichiro , Watanabe Yukio , Goto Yasushi , Nokihara Hiroshi , Furuta Koh , Yoshida Akihiko , Goto Koichi , Hishida Tomoyuki , Tsuboi Masahiro , Tsuchihara Katsuya , Miyagi Yohei , Nakayama Haruhiko , Yokose Tomoyuki , Tanaka Kazumi , Nagashima Toshiteru , Ohtaki Yoichi , Maeda Daichi , Imai Kazuhiro , Minamiya Yoshihiro , Sakamoto Hiromi , Saito Akira , Shimada Yoko , Sunami Kuniko , Saito Motonobu , Inazawa Johji , Nakamura Yusuke , Yoshida Teruhiko , Yokota Jun , Matsuda Fumihiko , Matsuo Keitaro , Daigo Yataro , Kubo Michiaki , Kohno Takashi
Published: August 2016

Lung adenocarcinoma driven by somatic EGFR mutations is more prevalent in East Asians (30–50%) than in European/Americans (10–20%). Here we investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls. Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA class II at 6p21.32 (rs2179920; P =5.1 × 10−17, per-allele OR=1.36) and 6p21.1 (FOXP4) (rs2495239; P=3.9 × 10−9, per-allele OR=1.19) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma. This study indicates that multiple genetic factors underlie the risk of lung adenocarcinomas with EGFR mutations.
Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding
Authors: Suyama Shigetomo , Maekawa Fumihiko , Maejima Yuko , Kubota Naoto , Kadowaki Takashi , Yada Toshihiko
Published: August 2016

Adiponectin regulates glucose and lipid metabolism, acting against metabolic syndrome and atherosclerosis. Accumulating evidence suggest that adiponectin acts on the brain including hypothalamic arcuate nucleus (ARC), where proopiomelanocortin (POMC) neurons play key roles in feeding regulation. Several studies have examined intracerebroventricular (ICV) injection of adiponectin and reported opposite effects, increase or decrease of food intake. These reports used different nutritional states. The present study aimed to clarify whether adiponectin exerts distinct effects on food intake and ARC POMC neurons depending on the glucose concentration. Adiponectin was ICV injected with or without glucose for feeding experiments and administered to ARC slices with high or low glucose for patch clamp experiments. We found that adiponectin at high glucose inhibited POMC neurons and increased food intake while at low glucose it exerted opposite effects. The results demonstrate that glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding.
2-(Maleimidomethyl)-1,3-Dioxanes (MD): a Serum-Stable Self-hydrolysable Hydrophilic Alternative to Classical Maleimide Conjugation
Authors: Dovgan Igor , Kolodych Sergii , Koniev Oleksandr , Wagner Alain
Published: August 2016

The vast majority of antibody-drug conjugates (ADC) are prepared through amine-to-thiol conjugation. To date, N-Succinimidyl-4-(maleimidomethyl) cyclohexanecarboxylate (SMCC) has been one of the most frequently applied reagents for the preparation of ADC and other functional conjugates. However, SMCC-based conjugates suffer from limited stability in blood circulation and from a hydrophobic character of the linker, which may give rise to major pharmacokinetic implications. To address this issue, we have developed a heterobifunctional analogue of a SMCC reagent, i.e., sodium 4-(maleimidomethyl)-1,3-dioxane-5-carbonyl)oxy)-2,3,5,6- tetrafluorobenzenesulfonate (MDTF) for amine-to-thiol conjugation. By replacing the cyclohexyl ring in the SMCC structure with the 1,3-dioxane, we increased the hydrophilicity of the linker. A FRET probe based on MD linker was prepared and showed superior stability compared to the MCC linker in human plasma, as well as in a variety of aqueous buffers. A detailed investigation demonstrated an accelerated succinimide ring opening for MD linker, resulting in stabilized conjugates. Finally, the MDTF reagent was applied for the preparation of serum stable antibody-dye conjugate.
Change in atmospheric deposition during last half century and its impact on lichen community structure in Eastern Himalaya
Authors: Bajpai Rajesh , Mishra Seema , Dwivedi Sanjay , Upreti Dalip Kumar
Published: August 2016

Climatic fluctuations largely affects species turnover and cause major shifts of terrestrial ecosystem. In the present study the five decade old herbarium specimens of lichens were compared with recent collection from Darjeeling district with respect to elements, PAHs accumulation and carbon isotope composition (δ13C) to explore the changes in climatic conditions and its impact on lichen flora. The δ13C has increased in recent specimens which is in contrast to the assumption that anthropogenic emission leads to δ13C depletion in air and increased carbon discrimination in flora. Study clearly demonstrated an increase in anthropogenic pollution and drastic decrease in precipitation while temperature showed abrupt changes during the past five decades resulting in significant change in lichen community structure. The Usneoid and Pertusorioid communities increased, while Physcioid and Cyanophycean decreased, drastically. Lobarian abolished from the study area, however, Calcicoid has been introduced in the recent past. Probably, post-industrial revolution, the abrupt changes in the environment has influenced CO2 diffusion and/C fixation of (lower) plants either as an adaptation strategy or due to toxicity of pollutants. Thus, the short term studies (≤5 decades) might reflect recent micro-environmental condition and lichen community structure can be used as model to study the global climate change.
Breaking through the strength-ductility trade-off dilemma in an Al-Si-based casting alloy
Authors: Dang B. , Zhang X. , Chen Y. Z. , Chen C. X. , Wang H. T. , Liu F.
Published: August 2016

Al-Si-based casting alloys have a great potential in various industrial applications. Common strengthening strategies on these alloys are accompanied inevitably by sacrifice of ductility, known as strength-ductility trade-off dilemma. Here, we report a simple route by combining rapid solidification (RS) with a post-solidification heat treatment (PHT), i.e. a RS + PHT route, to break through this dilemma using a commercial Al-Si-based casting alloy (A356 alloy) as an example. It is shown that yield strength and elongation to failure of the RS + PHT processed alloy are elevated simultaneously by increasing the cooling rate upon RS, which are not influenced by subsequent T6 heat treatment. Breaking through the dilemma is attributed to the hierarchical microstructure formed by the RS + PHT route, i.e. highly dispersed nanoscale Si particles in Al dendrites and nanoscale Al particles decorated in eutectic Si. Simplicity of the RS + PHT route makes it being suitable for industrial scaling production. The strategy of engineering microstructures offers a general pathway in tailoring mechanical properties of other Al-Si-based alloys. Moreover, the remarkably enhanced ductility of A356 alloy not only permits strengthening further the material by work hardening but also enables possibly conventional solid-state forming of the material, thus extending the applications of such an alloy.
Baicalin promotes hippocampal neurogenesis via SGK1- and FKBP5-mediated glucocorticoid receptor phosphorylation in a neuroendocrine mouse model of anxiety/depression
Authors: Zhang Kuo , Pan Xing , Wang Fang , Ma Jie , Su Guangyue , Dong Yingxu , Yang Jingyu , Wu Chunfu
Published: August 2016

Antidepressants increase hippocampal neurogenesis by activating the glucocorticoid receptor (GR), but excessive GR activation impairs hippocampal neurogenesis, suggesting that normal GR function is crucial for hippocampal neurogenesis. Baicalin was reported to regulate the expression of GR and facilitate hippocampal neurogenesis, but the underlying molecular mechanisms are still unknown. In this study, we used the chronic corticosterone (CORT)-induced mouse model of anxiety/depression to assess antidepressant-like effects of baicalin and illuminate possible molecular mechanisms by which baicalin affects GR-mediated hippocampal neurogenesis. We found that oral administration of baicalin (40, 80 or 160 mg/kg) for 4 weeks alleviated several chronic CORT-induced anxiety/depression-like behaviors. Baicalin also increased Ki-67- and DCX-positive cells to restore chronic CORT-induced suppression of hippocampal neurogenesis. Moreover, baicalin normalized the chronic CORT-induced decrease in GR protein levels, the increase in GR nuclear translocation and the increase in GR phosphorylation at Ser203 and Ser211. Finally, chronic CORT exposure increased the level of FK506-binding protein 51 (FKBP5) and of phosphorylated serum- and glucocorticoid-inducible kinase 1 (SGK1) at Ser422 and Thr256, whereas baicalin normalized these changes. Together, our findings suggest that baicalin improves anxiety/depression-like behaviors and promotes hippocampal neurogenesis. We propose that baicalin may normalize GR function through SGK1- and FKBP5-mediated GR phosphorylation.
A novel role for β2-microglobulin: a precursor of antibacterial chemokine in respiratory epithelial cells
Authors: Chiou Shean-Jaw , Wang Chan-Chi , Tseng Yan-Shen , Lee Yen-Jung , Chen Shih-Chieh , Chou Chi-Hsien , Chuang Lea-Yea , Hong Yi-Ren , Lu Chi-Yu , Chiu Chien-Chih , Chignard Michel
Published: August 2016

We analyzed a panel of cationic molecules secreted in the culture medium of human respiratory epithelial cells (REC) upon activation by IL-1β and different pathogen-associated molecular patterns. A 9 kDa fragment derived from β2-microglobulin (B2M) was identified and named shed 9 kDa B2M (sB2M-9). The primary structure of sB2M-9 was revealed to increase its pI value that potentially could play an important role in innate defense. sB2M-9 exhibits antibacterial activity against Gram positive Staphylococcus aureus (SA) but not against Gram negative Klebsiella pneumonia (KP). Upon its binding to SA, sB2M-9 induces clumps, a phenomenon not observed with B2M. Migration of THP-1 monocytes exposed to SA clumps was significantly greater than that to SA without clumps. sB2M-9 binds to SA, more likely as a chemokine, to facilitate THP-1 migration. As a whole, we demonstrated that REC release a novel chemokine with antibacterial activity that is shed from B2M to facilitate THP-1 migration.
Discovery of potential prognostic long non-coding RNA biomarkers for predicting the risk of tumor recurrence of breast cancer patients
Authors: Zhou Meng , Zhong Lei , Xu Wanying , Sun Yifan , Zhang Zhaoyue , Zhao Hengqiang , Yang Lei , Sun Jie
Published: August 2016

Deregulation of long non-coding RNAs (lncRNAs) expression has been proven to be involved in the development and progression of cancer. However, expression pattern and prognostic value of lncRNAs in breast cancer recurrence remain unclear. Here, we analyzed lncRNA expression profiles of breast cancer patients who did or did not develop recurrence by repurposing existing microarray datasets from the Gene Expression Omnibus database, and identified 12 differentially expressed lncRNAs that were closely associated with tumor recurrence of breast cancer patients. We constructed a lncRNA-focus molecular signature by the risk scoring method based on the expression levels of 12 relapse-related lncRNAs from the discovery cohort, which classified patients into high-risk and low-risk groups with significantly different recurrence-free survival (HR = 2.72, 95% confidence interval 2.07–3.57; p = 4.8e-13). The 12-lncRNA signature also represented similar prognostic value in two out of three independent validation cohorts. Furthermore, the prognostic power of the 12-lncRNA signature was independent of known clinical prognostic factors in at least two cohorts. Functional analysis suggested that the predicted relapse-related lncRNAs may be involved in known breast cancer-related biological processes and pathways. Our results highlighted the potential of lncRNAs as novel candidate biomarkers to identify breast cancer patients at high risk of tumor recurrence.
Identification of the earliest collagen- and plant-based coatings from Neolithic artefacts (Nahal Hemar cave, Israel)
Authors: Solazzo Caroline , Courel Blandine , Connan Jacques , van Dongen Bart E. , Barden Holly , Penkman Kirsty , Taylor Sheila , Demarchi Beatrice , Adam Pierre , Schaeffer Philippe , Nissenbaum Arie , Bar-Yosef Ofer , Buckley Michael
Published: August 2016

Mortuary practices in human evolution record cognitive, social changes and technological innovations. The Neolithic Revolution in the Levant was a watershed in this domain that has long fascinated the archaeological community. Plaster modelled skulls are well known at Jericho and several other Neolithic sites, and in Nahal Hemar cave (Israel, ca. 8200 −7300 cal. BC) excavations yielded six unique human skulls covered with a black organic coating applied in a net pattern evoking a headdress. This small cave was used as storage for paraphernalia in the semi-arid area of the Judean desert and the dry conditions preserved other artefacts such as baskets coated with a similar dark substance. While previous analysis had revealed the presence of amino acids consistent with a collagen signature, in the present report, specific biomarkers were characterised using combined proteomic and lipid approaches. Basket samples yielded collagen and blood proteins of bovine origin (Bos genus) and a large sequence coverage of a plant protein charybdin (Charybdis genus). The skull residue samples were dominated by benzoate and cinnamate derivatives and triterpenes consistent with a styrax-type resin (Styrax officinalis), thus providing the earliest known evidence of an odoriferous plant resin used in combination with an animal product.
Nanometal Skin of Plasmonic Heterostructures for Highly Efficient Near-Field Scattering Probes
Authors: Zito Gianluigi , Rusciano Giulia , Vecchione Antonio , Pesce Giuseppe , Di Girolamo Rocco , Malafronte Anna , Sasso Antonio
Published: August 2016

In this work, atomic force microscopy probes are functionalized by virtue of self-assembling monolayers of block copolymer (BCP) micelles loaded either with clusters of silver nanoparticles or bimetallic heterostructures consisting of mixed species of silver and gold nanoparticles. The resulting self-organized patterns allow coating the tips with a sort of nanometal skin made of geometrically confined nanoislands. This approach favors the reproducible engineering and tuning of the plasmonic properties of the resulting structured tip by varying the nanometal loading of the micelles. The newly conceived tips are applied for experiments of tip-enhanced Raman scattering (TERS) spectroscopy and scattering-type scanning near-field optical microscopy (s-SNOM). TERS and s-SNOM probe characterizations on several standard Raman analytes and patterned nanostructures demonstrate excellent enhancement factor with the possibility of fast scanning and spatial resolution <12 nm. In fact, each metal nanoisland consists of a multiscale heterostructure that favors large scattering and near-field amplification. Then, we verify the tips to allow challenging nongap-TER spectroscopy on thick biosamples. Our approach introduces a synergistic chemical functionalization of the tips for versatile inclusion and delivery of plasmonic nanoparticles at the tip apex, which may promote the tuning of the plasmonic properties, a large enhancement and the possibility of adding new degrees of freedom for tip functionalization.