bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Effects of Resistance Exercise Training on Cognition and Brain Volume in Older Women: Results from a Randomized Controlled Trial
Authors: Best John R. , Chiu Bryan K. , Liang Hsu Chun , Nagamatsu Lindsay S. , Liu-Ambrose Teresa
Published: November 2015

Aerobic exercise training has been shown to attenuate cognitive decline and reduce brain atrophy with advancing age. The extent to which resistance exercise training improves cognition and prevents brain atrophy is less known, and few studies include long-term follow-up cognitive and neuroimaging assessments. We report data from a randomized controlled trial of 155 older women, who engaged in 52 weeks of resistance training (either once- or twice-weekly) or balance-and-toning (twice-weekly). Executive functioning and memory were assessed at baseline, 1-year follow-up (i.e., immediately post-intervention), and 2-year follow-up. A subset underwent structural magnetic resonance imaging scans at those time points. At 2-year follow-up, both frequencies of resistance training promoted executive function compared to balance-and-toning (standardized difference [d]=.31–.48). Additionally, twice-weekly resistance training promoted memory (d=.45), reduced cortical white matter atrophy (d=.45), and increased peak muscle power (d=.27) at 2-year follow-up relative to balance-and-toning. These effects were independent of one another. These findings suggest resistance training may have a long-term impact on cognition and white matter volume in older women. (JINS, 2015,21, 745–756)
Age Moderates the Association of Aerobic Exercise with Initial Learning of an Online Task Requiring Cognitive Control
Authors: O’Connor Patrick J. , Tomporowski Phillip D. , Dishman Rodney K.
Published: November 2015

The aim of this study was to examine whether people differed in change in performance across the first five blocks of an online flanker task and whether those trajectories of change were associated with self-reported aerobic or resistance exercise frequency according to age. A total of 8752 men and women aged 13–89 completed a lifestyle survey and five 45-s games (each game was a block of ~46 trials) of an online flanker task. Accuracy of the congruent and incongruent flanker stimuli was analyzed using latent class and growth curve modeling adjusting for time between blocks, whether the blocks occurred on the same or different days, education, smoking, sleep, caffeinated coffee and tea use, and Lumosity training status (“free play” or part of a “daily brain workout”). Aerobic and resistance exercise were unrelated to first block accuracies. For the more cognitively demanding incongruent flanker stimuli, aerobic activity was positively related to the linear increase in accuracy [B=0.577%, 95% confidence interval (CI), 0.112 to 1.25 per day above the weekly mean of 2.8 days] and inversely related to the quadratic deceleration of accuracy gains (B=−0.619% CI, −1.117 to −0.121 per day). An interaction of aerobic activity with age indicated that active participants younger than age 45 had a larger linear increase and a smaller quadratic deceleration compared to other participants. Age moderates the association between self-reported aerobic, but not self-reported resistance, exercise and changes in cognitive control that occur with practice during incongruent presentations across five blocks of a 45-s online, flanker task. (JINS, 2015, 21, 802–815)
Improved Cardiorespiratory Fitness Is Associated with Increased Cortical Thickness in Mild Cognitive Impairment
Authors: Reiter Katherine , Nielson Kristy A. , Smith Theresa J. , Weiss Lauren R. , Alfini Alfonso J. , Smith J. Carson
Published: November 2015

Cortical atrophy is a biomarker of Alzheimer’s disease (AD) that correlates with clinical symptoms. This study examined changes in cortical thickness from before to after an exercise intervention in mild cognitive impairment (MCI) and healthy elders. Thirty physically inactive older adults (14 MCI, 16 healthy controls) underwent MRI before and after participating in a 12-week moderate intensity walking intervention. Participants were between the ages of 61 and 88. Change in cardiorespiratory fitness was assessed using residualized scores of the peak rate of oxygen consumption (V̇O2peak) from pre- to post-intervention. Structural magnetic resonance images were processed using FreeSurfer v5.1.0. V̇O2peak increased an average of 8.49%, which was comparable between MCI and healthy elders. Overall, cortical thickness was stable except for a significant decrease in the right fusiform gyrus in both groups. However, improvement in cardiorespiratory fitness due to the intervention (V̇O2peak) was positively correlated with cortical thickness change in the bilateral insula, precentral gyri, precuneus, posterior cingulate, and inferior and superior frontal cortices. Moreover, MCI participants exhibited stronger positive correlations compared to healthy elders in the left insula and superior temporal gyrus. A 12-week moderate intensity walking intervention led to significantly improved fitness in both MCI and healthy elders. Improved V̇O2peak was associated with widespread increased cortical thickness, which was similar between MCI and healthy elders. Thus, regular exercise may be an especially beneficial intervention to counteract cortical atrophy in all risk groups, and may provide protection against future cognitive decline in both healthy elders and MCI. (JINS, 2015, 21, 757–767)
Physical Activity as Protective Factor against Dementia: A Prospective Population-Based Study (NEDICES)
Authors: Llamas-Velasco Sara , Contador Israel , Villarejo-Galende Alberto , Lora-Pablos David , Bermejo-Pareja Félix
Published: November 2015

The aim of this study was to analyze whether physical activity (PA) is a protective factor for the incidence of dementia after 3 years of follow-up. The Neurological Disorders in Central Spain (NEDICES) is a prospective population-based survey of older adults (age 65 years and older) that comprised 5278 census-based participants at baseline (1994–1995). A broad questionnaire was used to assess participants’ sociodemographic characteristics, health status, and lifestyle. Subsequently, a modified version of Rosow-Breslau questionnaire was applied to classify individuals’ baseline PA into groups (i.e., sedentary, light, moderate, and high). Cox regression models adjusted for several covariates (age, sex, education, previous stroke, alcohol consumption, hypertension, health related variables) were carried out to estimate the association between the PA groups and risk of dementia at the 3-year follow-up (1997–1998). A total of 134 incident dementia cases were identified among 3105 individuals (56.6% female; mean age=73.15±6.26) after 3 years. Hazard ratios (HRs) of the light, moderate, and high PA groups (vs. sedentary group) were 0.40 (95% confidence interval {CI} [0.26, 0.62]; p<.001), 0.32 (95% CI [0.20, 0.54]; p<.001) and 0.23 (95% CI [0.13, 0.40]; p<.001), respectively. Even after controlling for covariates and the exclusion of doubtful dementia cases, HRs remained significant. However, a supplementary analysis showed that the dose-effect hypothesis did not reach statistical significance. PA is a protective factor of incident dementia in this population-based cohort. (JINS, 2015, 21, 861–867)
Physical Activity Affects Brain Integrity in HIV+ Individuals
Authors: Ortega Mario , Baker Laurie M. , Vaida Florin , Paul Robert , Basco Brian , Ances Beau M.
Published: November 2015

Prior research has suggested benefits of aerobic physical activity (PA) on cognition and brain volumes in HIV uninfected (HIV-) individuals, however, few studies have explored the relationships between PA and brain integrity (cognition and structural brain volumes) in HIV-infected (HIV+) individuals. Seventy HIV+ individuals underwent neuropsychological testing, structural neuroimaging, laboratory tests, and completed a PA questionnaire, recalling participation in walking, running, and jogging activities over the last year. A PA engagement score of weekly metabolic equivalent (MET) hr of activity was calculated using a compendium of PAs. HIV+ individuals were classified as physically active (any energy expended above resting expenditure,n=22) or sedentary (n=48). Comparisons of neuropsychological performance, grouped by executive and motor domains, and brain volumes were completed between groups. Physically active and sedentary HIV+ individuals had similar demographic and laboratory values, but the active group had higher education (14.0vs. 12.6 years,p=.034). Physically active HIV+ individuals performed better on executive (p=.040, unadjusted;p=.043, adjusted) but not motor function (p=.17). In addition, among the physically active group the amount of physical activity (METs) positively correlated with executive (Pearson’s r=0.45,p=0.035) but not motor (r=0.21;p=.35) performance. In adjusted analyses the physically active HIV+ individuals had larger putamen volumes (p=.019). A positive relationship exists between PA and brain integrity in HIV+ individuals. Results from the present study emphasize the importance to conduct longitudinal interventional investigation to determine if PA improves brain integrity in HIV+ individuals. (JINS, 2015,21, 880–889)
Association between Lifetime Physical Activity and Cognitive Functioning in Middle-Aged and Older Community Dwelling Adults: Results from theBrain in MotionStudy
Authors: Gill Stephanie J. , Friedenreich Christine M. , Sajobi Tolulope T. , Longman R. Stewart , Drogos Lauren L. , Davenport Margie H. , Tyndall Amanda V. , Eskes Gail A. , Hogan David B. , Hill Michael D. , Parboosingh Jillian S , Wilson Ben J. , Poulin Marc J.
Published: November 2015

To determine if total lifetime physical activity (PA) is associated with better cognitive functioning with aging and if cerebrovascular function mediates this association. A sample of 226 (52.2% female) community dwelling middle-aged and older adults (66.5±6.4 years) in theBrain in MotionStudy, completed theLifetime Total Physical Activity Questionnaireand underwent neuropsychological and cerebrovascular blood flow testing. Multiple robust linear regressions were used to model the associations between lifetime PA and global cognition after adjusting for age, sex, North American Adult Reading Test results (i.e., an estimate of premorbid intellectual ability), maximal aerobic capacity, body mass index and interactions between age, sex, and lifetime PA. Mediation analysis assessed the effect of cerebrovascular measures on the association between lifetime PA and global cognition.Post hocanalyses assessed past year PA and current fitness levels relation to global cognition and cerebrovascular measures. Better global cognitive performance was associated with higher lifetime PA (p=.045), recreational PA (p=.021), and vigorous intensity PA (p=.004), PA between the ages of 0 and 20 years (p=.036), and between the ages of 21 and 35 years (p<.0001). Cerebrovascular measures did not mediate the association between PA and global cognition scores (p>.5), but partially mediated the relation between current fitness and global cognition. This study revealed significant associations between higher levels of PA (i.e., total lifetime, recreational, vigorous PA, and past year) and better cognitive function in later life. Current fitness levels relation to cognitive function may be partially mediated through current cerebrovascular function. (JINS, 2015,21, 816–830)
Acute Exercise Improves Prefrontal Cortex but not Hippocampal Function in Healthy Adults
Authors: Basso Julia C. , Shang Andrea , Elman Meredith , Karmouta Ryan , Suzuki Wendy A.
Published: November 2015

The effects of acute aerobic exercise on cognitive functions in humans have been the subject of much investigation; however, these studies are limited by several factors, including a lack of randomized controlled designs, focus on only a single cognitive function, and testing during or shortly after exercise. Using a randomized controlled design, the present study asked how a single bout of aerobic exercise affects a range of frontal- and medial temporal lobe-dependent cognitive functions and how long these effects last. We randomly assigned 85 subjects to either a vigorous intensity acute aerobic exercise group or a video watching control group. All subjects completed a battery of cognitive tasks both before and 30, 60, 90, or 120 min after the intervention. This battery included the Hopkins Verbal Learning Test-Revised, the Modified Benton Visual Retention Test, the Stroop Color and Word Test, the Symbol Digit Modalities Test, the Digit Span Test, the Trail Making Test, and the Controlled Oral Word Association Test. Based on these measures, composite scores were formed to independently assess prefrontal cortex- and hippocampal-dependent cognition. A three-way mixed Analysis of Variance was used to determine whether differences existed between groups in the change in cognitive function from pre- to post-intervention testing. Acute exercise improved prefrontal cortex- but not hippocampal-dependent functioning, with no differences found between delay groups. Vigorous acute aerobic exercise has beneficial effects on prefrontal cortex-dependent cognition and these effects can last for up to 2 hr after exercise. (JINS, 2015,21, 791–801)
Aerobic and Cognitive Exercise (ACE) Pilot Study for Older Adults: Executive Function Improves with Cognitive Challenge While Exergaming
Authors: Barcelos Nicole , Shah Nikita , Cohen Katherine , Hogan Michael J. , Mulkerrin Eamon , Arciero Paul J. , Cohen Brian D. , Kramer Arthur F. , Anderson-Hanley Cay
Published: November 2015

Dementia cases are increasing worldwide; thus, investigators seek to identify interventions that might prevent or ameliorate cognitive decline in later life. Extensive research confirms the benefits of physical exercise for brain health, yet only a fraction of older adults exercise regularly. Interactive mental and physical exercise, as in aerobic exergaming, not only motivates, but has also been found to yield cognitive benefit above and beyond traditional exercise. This pilot study sought to investigate whether greater cognitive challenge while exergaming would yield differential outcomes in executive function and generalize to everyday functioning. Sixty-four community based older adults (mean age=82) were randomly assigned to pedal a stationary bike, while interactively engaging on-screen with: (1) a low cognitive demand task (bike tour), or (2) a high cognitive demand task (video game). Executive function (indices from Trails, Stroop and Digit Span) was assessed before and after a single-bout and 3-month exercise intervention. Significant group × time interactions were found after a single-bout (Color Trails) and after 3 months of exergaming (Stroop; among 20 adherents). Those in the high cognitive demand group performed better than those in the low cognitive dose condition. Everyday function improved across both exercise conditions. Pilot data indicate that for older adults, cognitive benefit while exergaming increased concomitantly with higher doses of interactive mental challenge. (JINS, 2015,21, 768–779)
Communicating Hurricane Risks: Challenges and Recommendations
Authors: Marlon Jennifer , Farmer E. , Moran Sharon
Published: November 2015

NOAA/Sea Grant Coastal Storm Awareness Program (CSAP ) Final Workshop; Newark, New Jersey, 26–27 May 2015
Lateral forces on circularly polarizable particles near a surface
Authors: Rodríguez-Fortuño Francisco J. , Engheta Nader , Martínez Alejandro , Zayats Anatoly V.
Published: November 2015

Optical forces allow manipulation of small particles and control of nanophotonic structures with light beams. While some techniques rely on structured light to move particles using field intensity gradients, acting locally, other optical forces can ‘push’ particles on a wide area of illumination but only in the direction of light propagation. Here we show that spin–orbit coupling, when the spin of the incident circularly polarized light is converted into lateral electromagnetic momentum, leads to a lateral optical force acting on particles placed above a substrate, associated with a recoil mechanical force. This counterintuitive force acts in a direction in which the illumination has neither a field gradient nor propagation. The force direction is switchable with the polarization of uniform, plane wave illumination, and its magnitude is comparable to other optical forces.
Redistribution of Kv1 and Kv7 enhances neuronal excitability during structural axon initial segment plasticity
Authors: Kuba Hiroshi , Yamada Rei , Ishiguro Go , Adachi Ryota
Published: November 2015

Structural plasticity of the axon initial segment (AIS), the trigger zone of neurons, is a powerful means for regulating neuronal activity. Here, we show that AIS plasticity is not limited to structural changes; it also occurs as changes in ion-channel expression, which substantially augments the efficacy of regulation. In the avian cochlear nucleus, depriving afferent inputs by removing cochlea elongated the AIS, and simultaneously switched the dominant Kv channels at the AIS from Kv1.1 to Kv7.2. Due to the slow activation kinetics of Kv7.2, the redistribution of the Kv channels reduced the shunting conductance at the elongated AIS during the initiation of action potentials and effectively enhanced the excitability of the deprived neurons. The results indicate that the functional plasticity of the AIS works cooperatively with the structural plasticity and compensates for the loss of afferent inputs to maintain the homeostasis of auditory circuits after hearing loss by cochlea removal.
TRPC6 specifically interacts with APP to inhibit its cleavage by γ-secretase and reduce Aβ production
Authors: Wang Junfeng , Lu Rui , Yang Jian , Li Hongyu , He Zhuohao , Jing Naihe , Wang Xiaomin , Wang Yizheng
Published: November 2015

Generation of β-amyloid (Aβ) peptide in Alzheimer’s disease involves cleavage of amyloid precursor protein (APP) by γ-secretase, a protease known to cleave several substrates, including Notch. Finding specific modulators for γ-secretase could be a potential avenue to treat the disease. Here, we report that transient receptor potential canonical (TRPC) 6 specifically interacts with APP leading to inhibition of its cleavage by γ-secretase and reduction in Aβ production. TRPC6 interacts with APP (C99), but not with Notch, and prevents C99 interaction with presenilin 1 (PS1). A fusion peptide derived from TRPC6 also reduces Aβ levels without effect on Notch cleavage. Crossing APP/PS1 mice with TRPC6 transgenic mice leads to a marked reduction in both plaque load and Aβ levels, and improvement in structural and behavioural impairment. Thus, TRPC6 specifically modulates γ-secretase cleavage of APP and preventing APP (C99) interaction with PS1 via TRPC6 could be a novel strategy to reduce Aβ formation.
Carrier-mediated ferromagnetism in the magnetic topological insulator Cr-doped (Sb,Bi)2Te3
Authors: Ye Mao , Li Wei , Zhu Siyuan , Takeda Yukiharu , Saitoh Yuji , Wang Jiajia , Pan Hong , Nurmamat Munisa , Sumida Kazuki , Ji Fuhao , Liu Zhen , Yang Haifeng , Liu Zhengtai , Shen Dawei , Kimura Akio , Qiao Shan , Xie Xiaoming
Published: November 2015

Magnetically doped topological insulators, possessing an energy gap created at the Dirac point through time-reversal-symmetry breaking, are predicted to exhibit exotic phenomena including the quantized anomalous Hall effect and a dissipationless transport, which facilitate the development of low-power-consumption devices using electron spins. Although several candidates of magnetically doped topological insulators were demonstrated to show long-range magnetic order, the realization of the quantized anomalous Hall effect is so far restricted to the Cr-doped (Sb,Bi)2Te3 system at extremely low temperature; however, the microscopic origin of its ferromagnetism is poorly understood. Here we present an element-resolved study for Cr-doped (Sb,Bi)2Te3 using X-ray magnetic circular dichroism to unambiguously show that the long-range magnetic order is mediated by the p-hole carriers of the host lattice, and the interaction between the Sb(Te) p and Cr d states is crucial. Our results are important for material engineering in realizing the quantized anomalous Hall effect at higher temperatures.
Single-molecule FRET studies on alpha-synuclein oligomerization of Parkinson’s disease genetically related mutants
Authors: Tosatto Laura , Horrocks Mathew H. , Dear Alexander J. , Knowles Tuomas P. J. , Dalla Serra Mauro , Cremades Nunilo , Dobson Christopher M. , Klenerman David
Published: November 2015

Oligomers of alpha-synuclein are toxic to cells and have been proposed to play a key role in the etiopathogenesis of Parkinson’s disease. As certain missense mutations in the gene encoding for alpha-synuclein induce early-onset forms of the disease, it has been suggested that these variants might have an inherent tendency to produce high concentrations of oligomers during aggregation, although a direct experimental evidence for this is still missing. We used single-molecule Förster Resonance Energy Transfer to visualize directly the protein self-assembly process by wild-type alpha-synuclein and A53T, A30P and E46K mutants and to compare the structural properties of the ensemble of oligomers generated. We found that the kinetics of oligomer formation correlates with the natural tendency of each variant to acquire beta-sheet structure. Moreover, A53T and A30P showed significant differences in the averaged FRET efficiency of one of the two types of oligomers formed compared to the wild-type oligomers, indicating possible structural variety among the ensemble of species generated. Importantly, we found similar concentrations of oligomers during the lag-phase of the aggregation of wild-type and mutated alpha-synuclein, suggesting that the properties of the ensemble of oligomers generated during self-assembly might be more relevant than their absolute concentration for triggering neurodegeneration.
Gγ recruitment systems specifically select PPI and affinity-enhanced candidate proteins that interact with membrane protein targets
Authors: Kaishima Misato , Ishii Jun , Fukuda Nobuo , Kondo Akihiko
Published: November 2015

Protein-protein interactions (PPIs) are crucial for the vast majority of biological processes. We previously constructed a Gγ recruitment system to screen PPI candidate proteins and desirable affinity-altered (affinity-enhanced and affinity-attenuated) protein variants. The methods utilized a target protein fused to a mutated G-protein γ subunit (Gγcyto) lacking the ability to localize to the inner leaflet of the plasma membrane. However, the previous systems were adapted to use only soluble cytosolic proteins as targets. Recently, membrane proteins have been found to form the principal nodes of signaling involved in diseases and have attracted a great deal of interest as primary drug targets. Here, we describe new protocols for the Gγ recruitment systems that are specifically designed to use membrane proteins as targets to overcome previous limitations. These systems represent an attractive approach to exploring novel interacting candidates and affinity-altered protein variants and their interactions with proteins on the inner side of the plasma membrane, with high specificity and selectivity.
Effects of Collective Histone State Dynamics on Epigenetic Landscape and Kinetics of Cell Reprogramming
Authors: Ashwin S. S. , Sasai Masaki
Published: November 2015

Cell reprogramming is a process of transitions from differentiated to pluripotent cell states via transient intermediate states. Within the epigenetic landscape framework, such a process is regarded as a sequence of transitions among basins on the landscape; therefore, theoretical construction of a model landscape which exhibits experimentally consistent dynamics can provide clues to understanding epigenetic mechanism of reprogramming. We propose a minimal gene-network model of the landscape, in which each gene is regulated by an integrated mechanism of transcription-factor binding/unbinding and the collective chemical modification of histones. We show that the slow collective variation of many histones around each gene locus alters topology of the landscape and significantly affects transition dynamics between basins. Differentiation and reprogramming follow different transition pathways on the calculated landscape, which should be verified experimentally via single-cell pursuit of the reprogramming process. Effects of modulation in collective histone state kinetics on transition dynamics and pathway are examined in search for an efficient protocol of reprogramming.
Influence of age on rat bone-marrow mesenchymal stem cells potential
Authors: Fafián-Labora J. , Fernández-Pernas P. , Fuentes I. , De Toro J. , Oreiro N. , Sangiao-Alvarellos S. , Mateos J. , Arufe M.C.
Published: November 2015

Mesenchymal stem cells promising role in cell-based therapies and tissue engineering appears to be limited due to a decline of their regenerative potential with increasing donor age. Six age groups from bone marrow mesenchymal stem cells of Wistar rats were studied (newborn, infant, young, pre-pubertal, pubertal and adult). Quantitative proteomic assay was performance by iTRAQ using an 8-plex iTRAQ labeling and the proteins differentially expressed were grouped in pluripotency, proliferative and metabolism processes. Proliferation makers, CD117 and Ki67 were measure by flow cytometry assay. Real time polymerase chain reaction analysis of pluripotency markers Rex1, Oct4, Sox2 and Nanog were done. Biological differentiation was realized using specific mediums for 14 days to induce osteogenesis, adipogenesis or chondrogenesis and immunostain analysis of differentiated cell resulting were done. Enzimoimmunoassay analysis of several enzymes as L-lactate dehydrogenase and glucose-6-phosphate isomerase were also done to validate iTRAQ data. Taking together these results indicate for the first time that mesenchymal stem cells have significant differences in their proliferative, pluripotency and metabolism profiles and those differences are age depending.
Adipose tissue macrophages induce PPARγ-high FOXP3+ regulatory T cells
Authors: Onodera Toshiharu , Fukuhara Atsunori , Jang Myoung Ho , Shin Jihoon , Aoi Keita , Kikuta Junichi , Otsuki Michio , Ishii Masaru , Shimomura Iichiro
Published: November 2015

Numerous regulatory T cells (Tregs) are present in adipose tissues compared with other lymphoid or non-lymphoid tissues. Adipose Tregs regulate inflammatory state and insulin sensitivity. However, the mechanism that maintains Tregs in adipose tissue remains unclear. Here, we revealed the contribution of adipose tissue macrophages (ATMs) to the induction and proliferation of adipose Tregs. ATMs isolated from mice under steady state conditions induced Tregs with high expression of PPARγ compared with splenic dendritic cells in vitro. Furthermore, ATMs from obese mice prompted the differentiation of PPARγ low Tregs. Adoptive transfer of ATMs induced differentiation and proliferation of Tregs, whereas depletion of ATMs by clodronate-liposome resulted in reduction of adipose Tregs, in vivo. Deficiency of anti-inflammatory adipocytokine, Adipoq, resulted in small proportions of ATMs and adipose Tregs without alteration of other immune cells in vivo. Therefore, these data suggest that the abundance of Tregs in adipose tissue could be partly attributed to the ability of ATMs to induce PPARγ-expressing Tregs.
Selective participation of c-Jun with Fra-2/c-Fos promotes aggressive tumor phenotypes and poor prognosis in tongue cancer
Authors: Gupta Shilpi , Kumar Prabhat , Kaur Harsimrut , Sharma Nishi , Saluja Daman , Bharti Alok C. , Das Bhudev C.
Published: November 2015

Tongue squamous cell carcinoma (TSCC) is most aggressive head and neck cancer often associated with HR-HPV infection. The role of AP-1 which is an essential regulator of HPV oncogene expression and tumorigenesis is not reported in tongue cancer. One hundred tongue tissue biopsies comprising precancer, cancer and adjacent controls including two tongue cancer cell lines were employed to study the role of HPV infection and AP-1 family proteins. An exclusive prevalence (28%) of HR-HPV type 16 was observed mainly in well differentiated tongue carcinomas (78.5%). A higher expression and DNA binding activity of AP-1 was observed in tongue tumors and cancer cell lines with c-Fos and Fra-2 as the major binding partners forming the functional AP-1 complex but c-Jun participated only in HPV negative and poorly differentiated carcinoma. Knocking down of Fra-2 responsible for aggressive tongue tumorigenesis led to significant reduction in c-Fos, c-Jun, MMP-9 and HPVE6/E7 expression but Fra-1 and p53 were upregulated. The binding and expression of c-Fos/Fra-2 increased as a function of severity of tongue lesions, yet selective participation of c-Jun appears to promote poor differentiation and aggressive tumorigenesis only in HPV negative cases while HPV infection leads to well differentiation and better prognosis preferably in nonsmokers.
Observed contrast changes in snow cover phenology in northern middle and high latitudes from 2001–2014
Authors: Chen Xiaona , Liang Shunlin , Cao Yunfeng , He Tao , Wang Dongdong
Published: November 2015

Quantifying and attributing the phenological changes in snow cover are essential for meteorological, hydrological, ecological and societal implications. However, snow cover phenology changes have not been well documented. Evidence from multiple satellite and reanalysis data from 2001 to 2014 points out that the snow end date (De) advanced by 5.11 (±2.20) days in northern high latitudes (52–75°N) and was delayed by 3.28 (±2.59) days in northern mid-latitudes (32–52°N) at the 90% confidence level. Dominated by changes in De, snow duration days (Dd) was shorter in duration by 5.57 (±2.55) days in high latitudes and longer by 9.74 (±2.58) days in mid-latitudes. Changes in De during the spring season were consistent with the spatiotemporal pattern of land surface albedo change. Decreased land surface temperature combined with increased precipitation in mid-latitudes and significantly increased land surface temperature in high latitudes, impacted by recent Pacific surface cooling, Arctic amplification and strengthening westerlies, result in contrasting changes in the Northern Hemisphere snow cover phenology. Changes in the snow cover phenology led to contrasting anomalies of snow radiative forcing, which is dominated by De and accounts for 51% of the total shortwave flux anomalies at the top of the atmosphere.
Topological robustness analysis of protein interaction networks reveals key targets for overcoming chemotherapy resistance in glioma
Authors: Azevedo Hátylas , Moreira-Filho Carlos Alberto
Published: November 2015

Biological networks display high robustness against random failures but are vulnerable to targeted attacks on central nodes. Thus, network topology analysis represents a powerful tool for investigating network susceptibility against targeted node removal. Here, we built protein interaction networks associated with chemoresistance to temozolomide, an alkylating agent used in glioma therapy and analyzed their modular structure and robustness against intentional attack. These networks showed functional modules related to DNA repair, immunity, apoptosis, cell stress, proliferation and migration. Subsequently, network vulnerability was assessed by means of centrality-based attacks based on the removal of node fractions in descending orders of degree, betweenness, or the product of degree and betweenness. This analysis revealed that removing nodes with high degree and high betweenness was more effective in altering networks’ robustness parameters, suggesting that their corresponding proteins may be particularly relevant to target temozolomide resistance. In silico data was used for validation and confirmed that central nodes are more relevant for altering proliferation rates in temozolomide-resistant glioma cell lines and for predicting survival in glioma patients. Altogether, these results demonstrate how the analysis of network vulnerability to topological attack facilitates target prioritization for overcoming cancer chemoresistance.
Intestinal organoids for assessing nutrient transport, sensing and incretin secretion
Authors: Zietek Tamara , Rath Eva , Haller Dirk , Daniel Hannelore
Published: November 2015

Intestinal nutrient transport and sensing are of emerging interest in research on obesity and diabetes and as drug targets. Appropriate in vitro models are lacking that allow both, studies on transport processes as well as sensing and subsequent incretin hormone secretion including intracellular signaling. We here demonstrate that murine small-intestinal organoids are the first in vitro model system enabling concurrent investigations of nutrient and drug transport, sensing and incretin hormone secretion as well as fluorescent live-cell imaging of intracellular signaling processes. By generating organoid cultures from wild type mice and animals lacking different nutrient transporters, we show that organoids preserve the main phenotypic features and functional characteristics of the intestine. This turns them into the best in vitro model currently available and opens new avenues for basic as well as medical research.
Indium-free, highly transparent, flexible Cu2O/Cu/Cu2O mesh electrodes for flexible touch screen panels
Authors: Kim Dong-Ju , Kim Hyo-Joong , Seo Ki-Won , Kim Ki-Hyun , Kim Tae-Wong , Kim Han-Ki
Published: November 2015

We report on an indium-free and cost-effective Cu2O/Cu/Cu2O multilayer mesh electrode grown by room temperature roll-to-roll sputtering as a viable alternative to ITO electrodes for the cost-effective production of large-area flexible touch screen panels (TSPs). By using a low resistivity metallic Cu interlayer and a patterned mesh structure, we obtained Cu2O/Cu/Cu2O multilayer mesh electrodes with a low sheet resistance of 15.1 Ohm/square and high optical transmittance of 89% as well as good mechanical flexibility. Outer/inner bending test results showed that the Cu2O/Cu/Cu2O mesh electrode had a mechanical flexibility superior to that of conventional ITO films. Using the diamond-patterned Cu2O/Cu/Cu2O multilayer mesh electrodes, we successfully demonstrated TSPS of the flexible film-film type and rigid glass-film-film type TSPs. The TSPs with Cu2O/Cu/Cu2O mesh electrode were used to perform zoom in/out functions and multi-touch writing, indicating that these electrodes are promising cost-efficient transparent electrodes to substitute for conventional ITO electrodes in large-area flexible TSPs.
Proteome analysis of male accessory gland secretions in oriental fruit flies reveals juvenile hormone-binding protein, suggesting impact on female reproduction
Authors: Wei Dong , Li Hui-Min , Tian Chuan-Bei , Smagghe Guy , Jia Fu-Xian , Jiang Hong-Bo , Dou Wei , Wang Jin-Jun
Published: November 2015

In insects, the accessory gland proteins (Acps) secreted by male accessory glands (MAGs) account for the majority of seminal fluids proteins. Mixed with sperm, they are transferred to the female at mating and so impact reproduction. In this project, we identified 2,927 proteins in the MAG secretions of the oriental fruit flyBactrocera dorsalis, an important agricultural pest worldwide, using LC-MS analysis and all sequences containing open reading frames were analyzed using signalP. In total, 90 Acps were identified. About one third (26) of these 90 Acps had a specific functional description, while the other two thirds (64) had no functional description including dozens of new classes of proteins. Hence, several of these novel Acps were abundant in the MAG secretions and we confirmed their MAG-specific expression by qPCR. Finally and interestingly, one of these novel proteins was functionally predicted as juvenile hormone-binding protein, suggesting the impact of Acps with reproductive events in the female. Our results will aid in the development of an experimental method to identify Acps in insects and in turn this information with new Acps inB. dorsaliswill pave the way of further exploration their function in reproduction and potential development as new insecticide targets.
Dendritic cells and macrophages neurally hard-wired in the lymph node
Authors: Wülfing Clemens , Günther Hauke S.
Published: November 2015

The neural hard-wired pathways in which the lymphoid organs are innervated by the nervous system is of special interest with respect to suggested afferent and sensory systems informing the central nervous system about the status of the immune system. Until today efferent also like afferent innervation seem to be unspecific, targeting many types of cells by affecting many cells at the same time. We for the first time show that antigen presenting cells (APC) are abundantly innervated in the T-cell enriched area, the subsinoidal layer and the cortical extrafollicular zone of lymph nodes in rats by a mesh of filamentous neurofilament positive structures originating from single nerve fibers and covering each single APC similar to a glass fishing float, so that we termed them “wired” APC (wAPC). These wAPC also found in humans seem to be restricted to the cell body, not to follow membranous extensions, they may be dynamic and receptive as MAP2 is expressed and axonal growth cones can be detected and they probably lack vesicular activity through missing synaptophysin expression. The specific innervation targeting single cells which show a distribution divided in several areas in one lymph node suggests a form of topographically organized afferent sensory system.
Increased expression of circulating miRNA-93 in women with polycystic ovary syndrome may represent a novel, non-invasive biomarker for diagnosis
Authors: Sathyapalan T. , David R. , Gooderham N. J. , Atkin S. L.
Published: November 2015

MicroRNAs (miRNA) are a novel class of small noncoding single-stranded RNA molecules that regulate gene expression. There is increasing evidence of their importance in polycystic ovary syndrome (PCOS). The objective was to determine if miRNA-93 and miRNA-223 are differentially expressed in the circulation of women with PCOS compared to age matched women. A case–control study comparing women with PCOS (n = 25) to age and weight matched controls (n = 24) without PCOS was performed. MiRNA-93 and miRNA-223 were determined by total RNA reverse transcription. Both miRNA-93 and miRNA-223 were significantly increased relative to the control group (p < 0.01, p = 0.029 respectively). In both groups there was no correlation of either miRNA-93 or miRNA-223 with insulin, HOMA-IR, HOMA-β or testosterone levels. The area under the receiver operator characteristic curve for miR-223 and miR-93 was 0.66 and 0.72 respectively, suggesting miR-93 is a more efficient biomarker than miR-223 for diagnosis of PCOS. The combination of the two miRNAs together, tested using multiple logistic regression analysis, did not improve the diagnostic potential. In conclusion, circulating miRNA-93 and miRNA-223 were higher in women with PCOS compared to age and weight matched controls independent of insulin resistance and testosterone levels and miR-93 may represent a novel diagnostic biomarker for PCOS.
DNA methylation mediated silencing of microRNA-145 is a potential prognostic marker in patients with lung adenocarcinoma
Authors: Xia Wenjie , Chen Qiang , Wang Jie , Mao Qixing , Dong Gaochao , Shi Run , Zheng YanYan , Xu Lin , Jiang Feng
Published: November 2015

The molecular mechanism of down-regulated microRNA-145 (miR-145) expression in lung adenocarcinoma (LAC) remains largely unknown. We hypothesized that aberrant hyper-methylation of the CpG sites silenced the expression of miR-145 in LAC. In consideration of its pivotal role in LAC development and progression, we also evaluated the clinical utility of miR-145 as a prognostic marker. We assessed the DNA methylation status of the miR-145 promoter region in 20 pairs of LAC and the matched non-tumor specimens. We subsequently applied our own LAC tissue microarray containing 92 pairs of tumor and non-tumor tissues with long time follow-up records to evaluate whether miR-145 is a potential prognostic marker in LAC. The Sequenom EpiTYPER MassArray analysis showed that miR-145 was down-regulated in human LAC tissues accompanied by increased DNA methylation of its upstream region, which was further validated by the data from TCGA database. Significance was observed between miR-145 expression and clinic-pathologic parameters. Univariate and multivariate analysis revealed that miR-145 expression level was an independent risk factor for both OS and DFS in LAC patients. Taken together, DNA hyper-methylation in the miR-145 promoter region reduced its expression in LAC and miR-145 expression level might serve as a novel prognostic biomarker.
Collective effects of common SNPs in foraging decisions in Caenorhabditis elegans and an integrative method of identification of candidate genes
Authors: Zhu Zuobin , Lu Qing , Wang Junjing , Huang Shi
Published: November 2015

Optimal foraging decision is a quantitative flexible behavior, which describes the time at which animals choose to abandon a depleting food supply. The total minor allele content (MAC) in an individual has been shown to correlate with quantitative variations in complex traits. We have studied the role of MAC in the decision to leave a food lawn in recombinant inbred advanced intercross lines (RIAILs) of Caenorhabditis elegans. We found a strong link between MAC and the food lawn leaving rates (Spearman r = 0.4, P = 0.005). We identified 28 genes of unknown functions whose expression levels correlated with both MAC and leaving rates. When examined by RNAi experiments, 8 of 10 tested among the 28 affected leaving rates, whereas only 2 of 9 did among genes that were only associated with leaving rates but not MAC (8/10 vs 2/9, P < 0.05). The results establish a link between MAC and the foraging behavior and identify 8 genes that may play a role in linking MAC with the quantitative nature of the trait. The method of correlations with both MAC and traits may find broad applications in high efficiency identification of target genes for other complex traits in model organisms and humans.
Responses of the Hybrid between Sphagneticola trilobata and Sphagneticola calendulacea to Low Temperature and Weak Light Characteristic in South China
Authors: Sun Zhongyu , Chen Yanqiao , Schaefer Valentin , Liang Huimiao , Li Weihua , Huang Shengqin , Peng Changlian
Published: November 2015

Hybridization between exotic and native species is of great interest to evolutionary biologists and ecologists because it usually shows a quick evolution of species and invasiveness. It has been reported that such hybridization frequently increases the adaptation and aggressiveness of the new hybrids. A hybrid between invasiveSphagneticola trilobataand its native congenerS. calendulaceawas recently found in subtropical China. S. calendulaceahas a significantly higher tolerance to low temperature and weak light stress thanS. trilobataand its range includes both tropical and temperate regions. This study examined how the tolerance of the new hybrid to low temperature and weak light conditions (LTWL), expanded its geographical range. All changes of phenotype, gas exchange parameters, chlorophyll fluorescence parameters, contents of malonaldehyde (MDA) and activity of superoxide dismutase (SOD) and peroxidase (POD) indicated that hybridization slightly catalyzed the tolerance of the hybrid to LTWL condition and the responses of the hybrid were more similar with their invasive parent. The results demonstrate that the current hybrid populations may not expand their geographical distribution ranges in a short period, but the distribution of the backcrossed generations is still uncertain. The threat of the hybrid to its native parent in subtropical region should be concerned.
Beneficial impact of Gpnmb and its significance as a biomarker in nonalcoholic steatohepatitis
Authors: Katayama Akihiro , Nakatsuka Atsuko , Eguchi Jun , Murakami Kazutoshi , Teshigawara Sanae , Kanzaki Motoko , Nunoue Tomokazu , Hida Kazuyuki , Wada Nozomu , Yasunaka Tetsuya , Ikeda Fusao , Takaki Akinobu , Yamamoto Kazuhide , Kiyonari Hiroshi , Makino Hirofumi , Wada Jun
Published: November 2015

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Gpnmb is classified as a type 1 membrane protein and its soluble form is secreted by ADAM10-mediated cleavage. Gpnmb mRNA was found in the Kupffer cells and white adipose tissues (WATs) and its upregulation in obesity was recently found. Here, we generated aP2 promoter-driven Gpnmb transgenic (Tg) mice and the overexpression of Gpnmb ameliorated the fat accumulation and fibrosis of the liver in diet-induced obesity model. Soluble form of Gpnmb in sera was elevated in Gpnmb Tg mice and Gpnmb concentrated in hepatic macrophages and stellate cells interacted with calnexin, which resulted in the reduction of oxidative stress. In the patients with non-alcoholic steatohepatitis, serum soluble GPNMB concentrations were higher compared with the patients with simple steatosis. The GPNMB is a promising biomarker and therapeutic target for the development and progression of NAFLD in obesity.
Prenatal exposure to recreational drugs affects global motion perception in preschool children
Authors: Chakraborty Arijit , Anstice Nicola S. , Jacobs Robert J. , LaGasse Linda L. , Lester Barry M. , Wouldes Trecia A. , Thompson Benjamin
Published: November 2015

Prenatal exposure to recreational drugs impairs motor and cognitive development; however it is currently unknown whether visual brain areas are affected. To address this question, we investigated the effect of prenatal drug exposure on global motion perception, a behavioural measure of processing within the dorsal extrastriate visual cortex that is thought to be particularly vulnerable to abnormal neurodevelopment. Global motion perception was measured in one hundred and forty-five 4.5-year-old children who had been exposed to different combinations of methamphetamine, alcohol, nicotine and marijuana prior to birth and 25 unexposed children. Self-reported drug use by the mothers was verified by meconium analysis. We found that global motion perception was impaired by prenatal exposure to alcohol and improved significantly by exposure to marijuana. Exposure to both drugs prenatally had no effect. Other visual functions such as habitual visual acuity and stereoacuity were not affected by drug exposure. Prenatal exposure to methamphetamine did not influence visual function. Our results demonstrate that prenatal drug exposure can influence a behavioural measure of visual development, but that the effects are dependent on the specific drugs used during pregnancy.