bluuebunny/crossref_metadata_2025 huggingface dataset:
Mid- to late-Holocene climate change in central Turkey: The Tecer Lake record
Authors: Kuzucuoğlu Catherine , Dörfler Walter , Kunesch Stéphane , Goupille Franck
Published: January 2011

The mineralogy and grain-size distribution of sediments from Tecer Lake in central Anatolia provides a 6000 year record of mid- to late-Holocene climate trends and events. Correspondences between key measured parameters allow a reconstruction of variations in lake level, evaporation intensity (summer droughts) and humidity (triggering erosion in winter and spring). They also indicate, occasionally, seasonal contrasts (e.g. phases with high winter rainfall). The Tecer sequence is divided into two main periods: (a) the mid-Holocene transition (from sixth to third millennia BP) characterised by the alternation of multicentenial wet and dry phases, and (b) shorter alternations during the last two millennia. During the mid-Holocene transition, intense droughts occur at the end of the sixth, fifth and fourth millennia BP. The characteristics of some climatic phases at Tecer seem specific to the location of the sequence which, when compared with other sites in the eastern Mediterranean, may record variations in the extent of different climatic systems (NE Atlantic, polar, east Mediterranean, Indian monsoon).
Circum-Mediterranean fire activity and climate changes during the mid-Holocene environmental transition (8500-2500 cal. BP)
Authors: Vannière B. , Power M.J. , Roberts N. , Tinner W. , Carrión J. , Magny M. , Bartlein P. , Colombaroli D. , Daniau A.L. , Finsinger W. , Gil-Romera G. , Kaltenrieder P. , Pini R. , Sadori L. , Turner R. , Valsecchi V. , Vescovi E.
Published: January 2011

A mid- to late-Holocene synthesis of fire activity from the Mediterranean basin explores the linkages among fire, climate variability and seasonality through several climatic and ecological transitions. Regional fire histories were created from 36 radiocarbon-dated sedimentary charcoal records, available from the Global Charcoal Database. During the mid-Holocene ‘Thermal Maximum’ around 7500—4500 cal. BP, charcoal records from the northern Mediterranean suggest an increase in fire while records from the southern Mediterranean indicate a decrease associated with wetter-than-present summers. A North—South partition between 40° and 43°N latitude is apparent in the central and western Mediterranean. Relatively abrupt changes in fire activity are observed c. 5500—5000 cal. BP. Records of Holocene fire activity appear sensitive to both orbitally forced climate changes and shorter-lived excursions which may be related to North Atlantic cold events, possibly modulated by an NAO-like climate mechanism. In cases where human—fire interactions have been documented, the regional coherency between fire occurrence and climate forcing suggests a dominant fire—climate relationship during the early—mid Holocene. The human influence on regional fire activity became increasingly important after c. 4000—3000 cal. BP. Results also suggest that: (1) teleconnections between the Mediterranean area and other climatic regions, in particular the North Atlantic and the low latitudes monsoon areas, influenced past fire activity; (2) gradual forcing, such as changes in orbital parameters, may have triggered abrupt shifts in fire activity; (3) regional fire reconstructions contradict former notions of a gradual (mid- to late-Holocene) aridification of the entire region due to climate and/or human activities and the importance of shorter-term events; (4) Mediterranean fire activity appears hightly sensitive to climate dynamics and thus could be considerably impacted by future climate changes.
Propensity scores: From naïve enthusiasm to intuitive understanding
Authors: Williamson Elizabeth , Morley Ruth , Lucas Alan , Carpenter James
Published: January 2011

Estimation of the effect of a binary exposure on an outcome in the presence of confounding is often carried out via outcome regression modelling. An alternative approach is to use propensity score methodology. The propensity score is the conditional probability of receiving the exposure given the observed covariates and can be used, under the assumption of no unmeasured confounders, to estimate the causal effect of the exposure. In this article, we provide a non-technical and intuitive discussion of propensity score methodology, motivating the use of the propensity score approach by analogy with randomised studies, and describe the four main ways in which this methodology can be implemented. We carefully describe the population parameters being estimated — an issue that is frequently overlooked in the medical literature. We illustrate these four methods using data from a study investigating the association between maternal choice to provide breast milk and the infant's subsequent neurodevelopment. We outline useful extensions of propensity score methodology and discuss directions for future research. Propensity score methods remain controversial and there is no consensus as to when, if ever, they should be used in place of traditional outcome regression models. We therefore end with a discussion of the relative advantages and disadvantages of each.
Does the Portrayal of Tanning in Australian Women’s Magazines Relate to Real Women’s Tanning Beliefs and Behavior?
Authors: Dixon Helen G. , Warne Charles D. , Scully Maree L. , Wakefield Melanie A. , Dobbinson Suzanne J.
Published: January 2011

Content analysis data on the tans of 4,422 female Caucasian models sampled from spring and summer magazine issues were combined with readership data to generate indices of potential exposure to social modeling of tanning via popular women’s magazines over a 15-year period (1987 to 2002). Associations between these indices and cross-sectional telephone survey data from the same period on 5,675 female teenagers’ and adults’ tanning attitudes, beliefs, and behavior were examined using logistic regression models. Among young women, greater exposure to tanning in young women’s magazines was associated with increased likelihood of endorsing pro-tan attitudes and beliefs. Among women of all ages, greater exposure to tanned models via the most popular women’s magazines was associated with increased likelihood of attempting to get a tan but lower likelihood of endorsing pro-tan attitudes. Popular women’s magazines may promote and reflect real women’s tanning beliefs and behavior.
Identifying economically potential inbound markets for Malaysian tourism industry
Authors: Mazumder Mohammad Nurul Huda , Ahmed Elsadig Musa , Murad Md. Wahid , Al-Amin Abul Quasem
Published: January 2011

The key objective of this study is to determine and analyze the impacts of inbound tourism on the Malaysian economy using an input-output analysis. With the view of accomplishing the key objective, this study also explores the economic potential of inbound markets for the Malaysian tourism industry. As central to any economic impact analysis, tourism multipliers are estimated from the inverse of Leontief’s input-output matrix. The empirical results reveal two interesting observations concerning inbound tourism impacts on Malaysian economy. These are, firstly, tourism sectors that produce larger multipliers do not generate larger total economic impact, and secondly, inbound markets with highest per capita do not yield highest economic impact. Therefore, this study concludes that an economic sector with lower multipliers should not be neglected and that the contribution of inbound tourism market generating lower per capita expenditure should not be ignored when preparing appropriate tourism marketing and public policies for developing economies.
Dubai outbound tourism: An exploratory study of Emiratis and expatriates
Authors: Michael Ian , Armstrong Anona , Badran Badran , King Brian
Published: January 2011

This research investigates the perceptions of residents of Dubai, United Arab Emirates (UAE) towards the state of Victoria, Australia as a destination and assesses their knowledge of Victoria’s tourism attributes. Focus groups were undertaken with UAE nationals (referred to as Emiratis), expatriate residents and travel agents. In the case of the former group it was found that the previous travel experiences of most respondents involved travelling in family groups with the wife and mother making the key travel-related decisions. The responses appeared to be broadly representative of attitudes prevalent more widely within their relevant families. Of the expatriate respondents, all were experienced travellers who had previously visited Australia. Their tourism interests, in such things as outdoor activities and music, differed from those of the Emiratis. All but one of the respondents in the focus group of travel agents had previously visited Australia. The study fills a gap in researching immature markets. The use of the focus group method illustrates how investigating the perceptions of emerging target markets can provide a useful input to shape future industry development.
Gender differences in factors associated with sexual intercourse among Estonian adolescents
Authors: Part Kai , Rahu Kaja , Rahu Mati , Karro Helle
Published: January 2011

Aims: To examine factors associated with early sexual intercourse among 15 to 16-year-old adolescents by gender. Methods: The data were collected from a random sample of Estonian basic schools’ ninth grade pupils in 1999 using self-completed questionnaires. A multivariate logistic regression analysis for boys and girls was used to test for associations between sexual intercourse, and personal gender role-related attitudes, attitudes towards sexual intercourse, pubertal timing, smoking status and experience of drunkenness. Results: Of the respondents, 14.6% of boys and 13.1% of girls had experienced sexual intercourse. Traditional gender role-related attitudes were associated with sexual intercourse among girls, but not among boys. Smoking and experience of drunkenness was strongly associated with sexual intercourse for both genders. Conclusions: Gender differences in the association between gender role-related attitudes and early sexual intercourse were observed among 15 to 16-year-olds in Estonia. Smoking and experience of drunkenness were strongly related to sexual intercourse for both genders.
Municipal variation in health and social service use in the last 2 years of life among old people
Authors: Forma Leena , Jylhä Marja , Aaltonen Mari , Raitanen Jani , Rissanen Pekka
Published: January 2011

Aims: To describe and analyse municipal differences in health and social service use among old people in the last 2 years of life. Methods: The data were derived from national registers. All those who died in 2002 or 2003 at the age of ≥70 years were included except those who lived in very small municipalities. The services included were different types of hospitals, long-term care, and home care. The variation in service use was described by coefficients of variation (CV). To analyse local differences, three-level (individual, municipal, and regional) binary logistic and Poisson regression analyses were performed. Results: A total of 67,027 decedents from 315 municipalities in 20 hospital districts were included. There was considerable variation in service use between residents of different municipalities, especially in the types of hospital used. Of the individual-level variables age and use of other services were associated (p < 0.05) with use of all services. Of the municipal-level variables, indicators describing the service pattern in the municipality were associated with use of all services and average age of decedents with most of the services. The presence of a university hospital in the hospital district increased the probability of using university and general hospitals, but among the users increased days in university hospital and decreased days in general hospital. Conclusions: Considerable differences between municipalities exist, but these cannot be exhaustively explained. Behind the differences are probably factors which are difficult to describe and quantify, such as historical developments and political realities.
The life and career of a great surgeon: Sir Archibald McIndoe CBE, MD, MSc, FRCS, FRCSI (Hon), FACS (Hon)1900-1960
Authors: Ashwood Neil , Philpott Matthew
Published: January 2011

Sir Archibald McIndoe is undoubtedly one of the greatest surgeons of the twentieth century. He is widely regarded as being one of the founding fathers of plastic surgery. Throughout his early career McIndoe had shown signs of his potential by winning numerous prizes and being awarded various scholarships. During the Second World War McIndoe was appointed civilian consultant plastic surgeon to the Royal Air Force, at the East Grinstead hospital. Here he worked with RAF servicemen who had suffered horrific burns. McIndoe not only pioneered new techniques for treating and reconstructing these servicemen’s injuries, he also developed new methods for reducing the risk and preventing them from happening to other servicemen. McIndoe was renowned not only for his technical brilliance and innovations in plastic surgery but also for the huge dedication he made towards his patient’s rehabilitation and return to society. McIndoe was able to inspire the staff at the East Grinstead hospital to help him achieve this goal by emphasising the importance of teamwork and total patient care. For his outstanding work McIndoe received numerous accolades at home and abroad and was knighted in 1947.
Alternative journalism as active citizenship
Authors: Harcup Tony
Published: January 2011

This article explores relationships between alternative forms of journalism and political concepts such as democracy and citizenship; in the process of doing so, it explores the role and purpose of alternative media. By means of an exploratory empirical study, utilizing qualitative research methods with a sample group of alternative media practitioners within the UK, the article discusses differing concepts of alternative media, paying particular attention to the journalistic methods and outputs of such media and the ways in which they can be seen as supportive of citizenship. The findings are discussed within the context of the work of international scholars on issues such as alternative media and democratic participation. The article concludes that, although a precise and universal definition of alternative media remains elusive, there appears to be a considerable degree of agreement amongst practitioners and scholars of alternative journalism alike that such media can play a role in reflecting, nurturing and demonstrating what can be identified as active citizenship.
The fight for ‘how to think’: Traditional media, social networks, and issue interpretation
Authors: Meraz Sharon
Published: January 2011

This study tested social influence theories against traditional media attribute agenda setting theory within 18 ideologically diverse political blogs, two elite traditional media entities, and the latter’s 11 political newsroom blogs across three issues in 2007. Results reveal significant correlations in left-leaning network agendas ranging from 0.64 to 0.91 through all issue periods. Social influence did not homogenize interpretative agendas within the right-leaning network through two of the three issue periods. As predicted, partisan blog networks showed insignificant correlations in attribute agendas, and unlike the left-leaning and moderate blog networks, the right-leaning blog network bore little similarity to traditional media’s issue interpretation across two of the three issues.These findings point to two significant trends: the growing power of social influence among partisan blog networks and the weakening influence of elite, traditional media as a singular power in influencing issue interpretation within networked political environments.
Multiperspectival news revisited: Journalism and representative democracy
Authors: Gans Herbert J
Published: January 2011

Thirty years ago, I published an ethnographic study of four mainstream national news organizations entitled Deciding What’s News (Gans, 2004 [1979]). In a final chapter devoted to news policy, I urged that the news become more multiperspectival, that national news depend less on top down news from high level government and other official and authoritative sources. Instead, the news media should do more reporting from and about other levels and sectors of society and how these see and interpret the country and its problems.

The mainstream news media as well as the economy and polity in which the news media are embedded have changed over the past decades and the arrival of the internet offers a chance to add different kinds of news. These changes justify a revisit to multiperspectival news which focuses particularly on the journalists’ role in representative democracy.
Experiments with autonomous mobile radios for wireless tethering in tunnels
Authors: Moore Kevin L , Weiss Manoja D , Steele John P , Meehan Chris , Hulbert Jesse , Larson Eric , Weinstein Alejandro
Published: January 2011

Tunnels are a challenging environment for radio communications. In this paper we consider the use of autonomous mobile radio nodes (AMRs) to provide wireless tethering between a base station and a leader in a tunnel exploration scenario. We propose a tethering algorithm for AMR motion control based on a consensus variable protocol. Using radio signal strength measurements, the AMRs autonomously space themselves so as to achieve equal radio distance between each entity in the chain from the base station to the leader. Experimental results show the feasibility of our ideas.
Randomized trials of alcohol-use interventions with college students and their parents: lessons from the Transitions Project
Authors: Fernandez AC , Wood MD , Laforge R , Black JT
Published: January 2011

Background Matriculation from high school to college is typified by an increase in alcohol use and related harm for many students. Therefore, this transition period is an ideal time for preventive interventions to target alcohol use and related problems.

Purpose The purpose of this report is to describe the design and methods used in the Transitions Project, a randomized controlled trial of two interventions designed to prevent and reduce heavy episodic drinking and alcohol-related negative consequences among incoming college students.

Methods This study used a 2 × 2 factorial design to investigate the effects of a two-session brief motivational intervention delivered to students and a handbook-based parent intervention. Interventions were administered to students and parents. Follow-up assessment took place at 10- and 22-months post-baseline.

Results The Transitions Project successfully recruited and retained participants across a major transition period (i.e., entering college), administered and compared two distinct but complementary interventions, and collected and analyzed highly skewed data. The application of a factorial design and two-part latent growth curve modeling allowed us to examine main and interactive intervention effects in terms of both initiation and growth in heavy drinking and alcohol-related problems.

Limitations While we conducted successful tests of our primary and secondary study hypotheses over a lengthy follow-up period, our study design did not permit full interpretation of null findings. We suggest that researchers carefully consider assessment timing, tests of assessment reactivity, and ensure objective tests of intervention efficacy when conducting clinical trials of motivational interventions.

Conclusions The lessons we learned while conducting this trial have the potential to assist other researchers designing and conducting future preventive interventions targeting parents and college students. The data analytic procedures presented can also help guide trials that plan to analyze zero-inflated non-normal outcome data.
Enhancement of nicotinic receptors alleviates cytotoxicity in neurological disease models
Authors: Kawamata Jun , Suzuki Syuuichirou , Shimohama Shun
Published: January 2011

The common pathological mechanisms among the spectrum of neurodegenerative diseases are supposed to be shared. Multiple lines of evidence, from molecular and cellular to epidemiological, have implicated nicotinic transmission in the pathology of the two most common neurodegenerative disorders, namely Alzheimer’s disease (AD) and Parkinson’s disease (PD). In this review article we present evidence of nicotinic acetylcholine receptor (nAChR)-mediated protection against neurotoxicity induced by β amyloid (Aβ), glutamate, rotenone, and 6-hydroxydopamine (6-OHDA) and the signal transduction involved in this mechanism. Our studies have clarified that survival signal transduction, the α7 nAChR/Src family/PI3K/AKT pathway and subsequent upregulation of Bcl-2 and Bcl-x, would lead to neuroprotection. In addition to the PI3K/AKT pathway, two other survival pathways, JAK2/STAT3 and MEK/ERK, are proposed by other groups. In rotenone- and 6-OHDA-induced PD models, nAChR-mediated neuroprotection was also observed, and the effect was blocked not only by α7 but also by α4β2 nAChR antagonists. We also document that nAChR stimulation blocks glutamate neurotoxicity in spinal cord motor neurons. These findings suggest that nAChR-mediated neuroprotection is achieved through subtypes of nAChRs and common signal cascades. An early diagnosis and protective therapy with nAChR stimulation could be effective in delaying the progression of neurodegenerative diseases such as AD, PD and amyotrophic lateral sclerosis.
E47 regulates hematopoietic stem cell proliferation and energetics but not myeloid lineage restriction
Authors: Yang Qi , Esplin Brandt , Borghesi Lisa
Published: January 2011

The immune system is replenished by self-renewing hematopoietic stem cells (HSCs) that produce multipotent progenitors (MPPs) with little renewal capacity. E-proteins, the widely expressed basic helix-loop-helix transcription factors, contribute to HSC and MPP activity, but their specific functions remain undefined. Using quantitative in vivo and in vitro approaches, we show that E47 is dispensable for the short-term myeloid differentiation of HSCs but regulates their long-term capabilities. E47-deficient progenitors show competent myeloid production in short-term assays in vitro and in vivo. However, long-term myeloid and lymphoid differentiation is compromised because of a progressive loss of HSC self-renewal that is associated with diminished p21 expression and hyperproliferation. The activity of E47 is shown to be cell-intrinsic. Moreover, E47-deficient HSCs and MPPs have altered expression of genes associated with cellular energy metabolism, and the size of the MPP pool but not downstream lymphoid precursors in bone marrow or thymus is rescued in vivo by antioxidant. Together, these observations suggest a role for E47 in the tight control of HSC proliferation and energy metabolism, and demonstrate that E47 is not required for short-term myeloid differentiation.
KNG1 Ile581Thr and susceptibility to venous thrombosis
Authors: Morange Pierre-Emmanuel , Oudot-Mellakh Tiphaine , Cohen William , Germain Marine , Saut Noémie , Antoni Guillemette , Alessi Marie-Christine , Bertrand Marion , Dupuy Anne-Marie , Letenneur Luc , Lathrop Mark , Lopez Lorna M. , Lambert Jean-Charles , Emmerich Joseph , Amouyel Philippe , Trégouët David-Alexandre
Published: January 2011

Three single nucleotide polymorphisms (SNPs) were recently found to be associated with activated partial thromboplastin time (aPTT). Because shortened aPTT levels have been observed in patients experiencing venous thrombosis (VT), we investigated the effects of these 3 aPTT-associated SNPs, rs2731672, rs9898, and rs710446, on the risk of VT in a sample of 1110 healthy patients and 1542 patients with VT. Among the 3 tested SNPs, only rs710446 was associated with VT risk; the rs710446-C allele was associated with an increased risk of VT (odds ratio 1.196, 95% confidence interval 1.071-1.336, P = .0012). This association also was observed in an independent sample of 590 controls and 596 patients (odds ratio 1.171, 95% confidence interval 0.889-1.541, P = .059). We also confirmed that the rs710446-C allele was associated with decreased aPTT levels, making this nonsynonymous Ile581Thr variant a new genetic risk factor for VT.
ASPDock: protein-protein docking algorithm using atomic solvation parameters model
Authors: Li Lin , Guo Dachuan , Huang Yangyu , Liu Shiyong , Xiao Yi
Published: January 2011

Background

Atomic Solvation Parameters (ASP) model has been proven to be a very successful method of calculating the binding free energy of protein complexes. This suggests that incorporating it into docking algorithms should improve the accuracy of prediction. In this paper we propose an FFT-based algorithm to calculate ASP scores of protein complexes and develop an ASP-based protein-protein docking method (ASPDock).

Results

The ASPDock is first tested on the 21 complexes whose binding free energies have been determined experimentally. The results show that the calculated ASP scores have stronger correlation (r ≈ 0.69) with the binding free energies than the pure shape complementarity scores (r ≈ 0.48). The ASPDock is further tested on a large dataset, the benchmark 3.0, which contain 124 complexes and also shows better performance than pure shape complementarity method in docking prediction. Comparisons with other state-of-the-art docking algorithms showed that ASP score indeed gives higher success rate than the pure shape complementarity score of FTDock but lower success rate than Zdock3.0. We also developed a softly restricting method to add the information of predicted binding sites into our docking algorithm. The ASP-based docking method performed well in CAPRI rounds 18 and 19.

Conclusions

ASP may be more accurate and physical than the pure shape complementarity in describing the feature of protein docking.
Conservation genetics and phylogeography of endangered and endemic shrub Tetraena mongolica (Zygophyllaceae) in Inner Mongolia, China
Authors: Ge Xue-Jun , Hwang Chi-Chuan , Liu Zin-Huang , Huang Chi-Chun , Huang Wei-Hsiang , Hung Kuo-Hsiang , Wang Wei-Kuang , Chiang Tzen-Yuh
Published: January 2011

Background

Tetraena mongolica (Zygophyllaceae), an endangered endemic species in western Inner Mongolia, China. For endemic species with a limited geographical range and declining populations, historical patterns of demography and hierarchical genetic structure are important for determining population structure, and also provide information for developing effective and sustainable management plans. In this study, we assess genetic variation, population structure, and phylogeography of T. mongolica from eight populations. Furthermore, we evaluate the conservation and management units to provide the information for conservation.

Results

Sequence variation and spatial apportionment of the atp B-rbc L noncoding spacer region of the chloroplast DNA were used to reconstruct the phylogeography of T. mongolica. A total of 880 bp was sequenced from eight extant populations throughout the whole range of its distribution. At the cpDNA locus, high levels of genetic differentiation among populations and low levels of genetic variation within populations were detected, indicating that most seed dispersal was restricted within populations.

Conclusions

Demographic fluctuations, which led to random losses of genetic polymorphisms from populations, due to frequent flooding of the Yellow River and human disturbance were indicated by the analysis of BEAST skyline plot. Nested clade analysis revealed that restricted gene flow with isolation by distance plus occasional long distance dispersal is the main evolutionary factor affecting the phylogeography and population structure of T. mongolica. For setting a conservation management plan, each population of T. mongolica should be recognized as a conservation unit.
Genome-wide patterns of promoter sharing and co-expression in bovine skeletal muscle
Authors: Gu Quan , Nagaraj Shivashankar H , Hudson Nicholas J , Dalrymple Brian P , Reverter Antonio
Published: January 2011

Background

Gene regulation by transcription factors (TF) is species, tissue and time specific. To better understand how the genetic code controls gene expression in bovine muscle we associated gene expression data from developing Longissimus thoracis et lumborum skeletal muscle with bovine promoter sequence information.

Results

We created a highly conserved genome-wide promoter landscape comprising 87,408 interactions relating 333 TFs with their 9,242 predicted target genes (TGs). We discovered that the complete set of predicted TGs share an average of 2.75 predicted TF binding sites (TFBSs) and that the average co-expression between a TF and its predicted TGs is higher than the average co-expression between the same TF and all genes. Conversely, pairs of TFs sharing predicted TGs showed a co-expression correlation higher that pairs of TFs not sharing TGs. Finally, we exploited the co-occurrence of predicted TFBS in the context of muscle-derived functionally-coherent modules including cell cycle, mitochondria, immune system, fat metabolism, muscle/glycolysis, and ribosome. Our findings enabled us to reverse engineer a regulatory network of core processes, and correctly identified the involvement of E2F1, GATA2 and NFKB1 in the regulation of cell cycle, fat, and muscle/glycolysis, respectively.

Conclusion

The pivotal implication of our research is two-fold: (1) there exists a robust genome-wide expression signal between TFs and their predicted TGs in cattle muscle consistent with the extent of promoter sharing; and (2) this signal can be exploited to recover the cellular mechanisms underpinning transcription regulation of muscle structure and development in bovine. Our study represents the first genome-wide report linking tissue specific co-expression to co-regulation in a non-model vertebrate.
TNFA deletion alters apoptosis as well as caspase 3 and 4 expression during otitis media
Authors: Ebmeyer Joerg , Leichtle Anke , Hernandez Michelle , Ebmeyer Umay , Husseman Jacob , Pak Kwang , Sudhoff Holger , Broide David , Wasserman Stephen I , Ryan Allen F
Published: January 2011

Background

Tumor necrosis factor (TNFA) is the canonical member of the TNF superfamily, which plays a major role in both inflammation and apoptosis. To evaluate the role of TNFs in otitis media (OM), the most common disease of childhood, we evaluated middle ear (ME) expression of genes encoding the TNF and TNF receptor superfamilies during bacterial OM in the mouse, characterized OM in TNFA-deficient mice, and assessed apoptosis during OM in normal versus TNF-deficient MEs.

Results

TNFs and TNF receptors were broadly regulated during OM, with TNFA showing the highest level of up-regulation. TNF deficient mice exhibited mucosal hyperplasia even in the absence of infection and exuberant growth of the mucosa during OM, including the formation of mucosal polyps. Mucosal recovery during OM was also delayed, in parallel with a delay in mucosal apoptosis and reduced caspase gene expression.

Conclusions

The TNF and TNF receptor superfamilies mediate both inflammation and apoptosis during OM. TNF appears to be critical for the maintenance of mucosal architecture in both the normal and infected ME, since excessive accumulation of mucosal tissue is seen in TNFA-/- MEs both before and after bacterial inoculation of the ME. TNFA is also required for appropriate regulation of caspase genes.
Bimanual training in stroke: How do coupling and symmetry-breaking matter?
Authors: Sleimen-Malkoun Rita , Temprado Jean-Jacques , Thefenne Laurent , Berton Eric
Published: January 2011

Background

The dramatic consequences of stroke on patient autonomy in daily living activities urged the need for new reliable therapeutic strategies. Recently, bimanual training has emerged as a promising tool to improve the functional recovery of upper-limbs in stroke patients. However, who could benefit from bimanual therapy and how it could be used as a part of a more complete rehabilitation protocol remain largely unknown. A possible reason explaining this situation is that coupling and symmetry-breaking mechanisms, two fundamental principles governing bimanual behaviour, have been largely under-explored in both research and rehabilitation in stroke.

Discussion

Bimanual coordination emerges as an active, task-specific assembling process where the limbs are constrained to act as a single unit by virtue of mutual coupling. Consequently, exploring, assessing, re-establishing and exploiting functional bimanual synergies following stroke, require moving beyond the classical characterization of performance of each limb in separate and isolated fashion, to study coupling signatures at both neural and behavioural levels. Grounded on the conceptual framework of the dynamic system approach to bimanual coordination, we debated on two main assumptions: 1) stroke-induced impairment of bimanual coordination might be anticipated/understood by comparing, in join protocols, changes in coupling strength and asymmetry of bimanual discrete movements observed in healthy people and those observed in stroke; 2) understanding/predicting behavioural manifestations of decrease in bimanual coupling strength and/or increase in interlimb asymmetry might constitute an operational prerequisite to adapt therapy and better target training at the specific needs of each patient. We believe that these statements draw new directions for experimental and clinical studies and contribute in promoting bimanual training as an efficient and adequate tool to facilitate the paretic upper-limb recovery and to restore spontaneous bimanual synergies.

Since bimanual control deficits have scarcely been systematically investigated, the eventual benefits of bimanual coordination practice in stroke rehabilitation remains poorly understood. In the present paper we argued that a better understanding of coupling and symmetry-breaking mechanisms in both the undamaged and stroke-lesioned neuro-behavioral system should provide a better understanding of stroke-related alterations of bimanual synergies, and help clinicians to adapt therapy in order to maximize rehabilitation benefits.
Identification and Regulation of c-Myb Target Genes in MCF-7 Cells
Authors: Quintana Anita M , Liu Fan , O'Rourke John P , Ness Scott A
Published: January 2011

Background

The c-Myb transcription factor regulates differentiation and proliferation in hematopoietic cells, stem cells and epithelial cells. Although oncogenic versions of c-Myb were first associated with leukemias, over expression or rearrangement of the c-myb gene is common in several types of solid tumors, including breast cancers. Expression of the c-myb gene in human breast cancer cells is dependent on estrogen stimulation, but little is known about the activities of the c-Myb protein or what genes it regulates in estrogen-stimulated cells.

Methods

We used chromatin immunoprecipitation coupled with whole genome promoter tiling microarrays to identify endogenous c-Myb target genes in human MCF-7 breast cancer cells and characterized the activity of c-Myb at a panel of target genes during different stages of estrogen deprivation and stimulation.

Results

By using different antibodies and different growth conditions, the c-Myb protein was found associated with over 10,000 promoters in MCF-7 cells, including many genes that encode cell cycle regulators or transcription factors and more than 60 genes that encode microRNAs. Several previously identified c-Myb target genes were identified, including CCNB1, MYC and CXCR4 and novel targets such as JUN, KLF4, NANOG and SND1. By studying a panel of these targets to validate the results, we found that estradiol stimulation triggered the association of c-Myb with promoters and that association correlated with increased target gene expression. We studied one target gene, CXCR4, in detail, showing that c-Myb associated with the CXCR4 gene promoter and activated a CXCR4 reporter gene in transfection assays.

Conclusions

Our results show that c-Myb associates with a surprisingly large number of promoters in human cells. The results also suggest that estradiol stimulation leads to large-scale, genome-wide changes in c-Myb activity and subsequent changes in gene expression in human breast cancer cells.
Differential molecular information of maurotoxin peptide recognizing IKCa and Kv1.2 channels explored by computational simulation
Authors: Yi Hong , Qiu Su , Wu Yingliang , Li Wenxin , Wang Baoshan
Published: January 2011

Background

Scorpion toxins are invaluable tools for ion channel research and are potential drugs for human channelopathies. However, it is still an open task to determine the molecular basis underlying the diverse interactions between toxin peptides and ion channels. The inhibitory peptide Maurotoxin (MTX) recognized the distantly related IKCa and Kv1.2 channel with approximately the same potency and using the same functional residues, their differential binding mechanism remain elusive. In this study, we applied computational methods to explore the differential binding modes of MTX to Kv1.2 and IKCa channels, which would help to understand the diversity of channel-toxin interactions and accelerate the toxin-based drug design.

Results

A reasonably stable MTX-IKCa complex was obtained by combining various computational methods and by in-depth comparison with the previous model of the MTX-Kv1.2 complex. Similarly, MTX adopted the β-sheet structure as the interacting surface for binding both channels, with Lys23 occluding the pore. In contrast, the other critical residues Lys27, Lys30, and Tyr32 of MTX adopted distinct interactions when associating with the IKCa channel. In addition, the residues Gln229, Ala230, Ala233, and Thr234 on the IKCa channel turret formed polar and non-polar interactions with MTX, whereas the turret of Kv1.2 was almost not involved in recognizing MTX. In all, the pairs of interacting residues on MTX and the IKCa channel of the bound complex indicated that electrostatic and Van der Waal interactions contributed equally to the formation of a stable MTX-IKCa complex, in contrast to the MTX-Kv1.2 binding that is dominantly mediated by electrostatic forces.

Conclusions

Despite sharing similar pharmacological profiles toward both IKCa and Kv1.2 channels, MTX adopted totally diverging modes in the two association processes. All the molecular information unveiled here could not only offer a better understanding about the structural differences between the IKCa and Kv1.2 channels, but also provide novel structural clews that will help in the designing of more selective molecular probes to discriminate between these two channels.
Socio-demographic factors and processes associated with stages of change for smoking cessation in pregnant versus non-pregnant women
Authors: Buja Alessandra , Guarnieri Emanuela , Forza Giovanni , Tognazzo Federica , Sandonà Paolo , Zampieron Alessandra
Published: January 2011

Background

The tobacco control community assumes that the most effective interventions are personalized. Nevertheless, little attention is paid to understanding differences between pregnant and non-pregnant European women in terms of the social factors that influence tobacco use and the processes of change used to quit smoking.

Methods

The study consecutively enrolled 177 pregnant women who acknowledged smoking the year before pregnancy and 177 non-pregnant women who acknowledged smoking the year before their clinic visit for a Pap test.

Results

With respect to socio-demographic factors, the stages of change in pregnant women were associated with level of education, marital status, and the presence of roommates, partners and friends who smoke. In pregnant women, there was no statistically significant difference in the processes used to stop smoking among the stages of change. Furthermore, behavioral processes were higher in non-pregnant women than in pregnant women, and the difference was statistically significant in the advanced stages of behavioral change. Both pregnant and non-pregnant women showed higher levels of acceptance towards smoking in the earlier stages of change, but the acceptability of smoking in the pre-contemplative stage was higher in non-pregnant women. Greater craving was detected in non-pregnant vs. pregnant women at all stages and reached a statistically significant level at the pre-contemplative stage.

Conclusion

Pregnancy is a favorable time to stop smoking since pregnant women are more likely to be in an advanced stage of behavioral change. Pregnant and non-pregnant women are distinct populations in the types and processes of change involved in smoking cessation. The intervention programs to promote smoking cessation and prevent relapses will need to take these differences into account.
Differential effects of frozen storage on the molecular detection of bacterial taxa that inhabit the nasopharynx
Authors: Kwambana Brenda A , Mohammed Nuredin I , Jeffries David , Barer Mike , Adegbola Richard A , Antonio Martin
Published: January 2011

Background

Frozen storage often precedes metagenomic analysis of biological samples; however, the freezing process can have adverse effects on microbial composition. The effect of freezing on the detection of bacteria inhabiting the infant nasopharynx, a major reservoir of bacterial pathogens, was investigated.

Methods

16S ribosomal RNA (rRNA) gene-based terminal restriction fragment length polymorphism (T-RFLP) analysis of nasopharyngeal (NP) swabs from twelve Gambian infants was employed. NP swabs were analysed within hours of collection and then after 30 days of storage at -70°C.

Results

There was substantial heterogeneity among subjects with respect to the effect of freezing on the number of operational taxonomic units (OTUs) detected. Nevertheless, the mean number of OTUs decreased after frozen storage and the relative abundance for 72% of the OTUs changed by less than 0.5% after deep frozen storage. There were differences in the odds of detection and relative abundance of OTUs matched with Moraxella sp., Haemophilus sp./Burkholderia sp., and Pseudomonas sp. A strong interaction between sex and the effect of freezing was found, whereby there was no significant change observed for males while the mean number of OTUs significantly declined among female infants following frozen storage.

Conclusions

Although frozen storage of biological samples is often necessary for archiving and logistic purposes, the potential effects on the number of taxa (composition) detected in microbial community studies are significant and should not be overlooked. Moreover, genetic factors such as sex may influence the integrity of nucleic acids during the freezing process.
LIM kinase1 modulates function of membrane type matrix metalloproteinase 1: implication in invasion of prostate cancer cells
Authors: Tapia Tenekua , Ottman Richard , Chakrabarti Ratna
Published: January 2011

Background

LIM kinase 1 (LIMK1) is an actin and microtubule cytoskeleton modulatory protein that is overexpressed in a number of cancerous tissues and cells and also promotes invasion and metastasis of prostate and breast cancer cells. Membrane type matrix metalloproteinase 1 (MT1-MMP) is a critical modulator of extracellular matrix (ECM) turnover through pericellular proteolysis and thus plays crucial roles in neoplastic cell invasion and metastasis. MT1-MMP and its substrates pro-MMP-2 and pro-MMP-9 are often overexpressed in a variety of cancers including prostate cancer and the expression levels correlate with the grade of malignancy in prostate cancer cells. The purpose of this study is to determine any functional relation between LIMK1 and MT1-MMP and its implication in cell invasion.

Results

Our results showed that treatment with the hydroxamate inhibitor of MT1-MMP, MMP-2 and MMP-9 ilomastat inhibited LIMK1-induced invasion of benign prostate epithelial cells. Over expression of LIMK1 resulted in increased collagenolytic activity of MMP-2, and secretion of pro-MMP2 and pro-MMP-9. Cells over expressing LIMK1 also exhibited increased expression of MT1-MMP, transcriptional activation and its localization to the plasma membrane. LIMK1 physically associates with MT1-MMP and is colocalized with it to the Golgi vesicles. We also noted increased expression of both MT1-MMP and LIMK1 in prostate tumor tissues.

Conclusion

Our results provide new information on regulation of MT1-MMP function by LIMK1 and showed for the first time, involvement of MMPs in LIMK1 induced cell invasion.
Plasmid-encoded NP73-102 modulates atrial natriuretic peptide receptor signaling and plays a critical role in inducing tolerogenic dendritic cells
Authors: Zhang Weidong , Cao Xueqin , Chen Dongqing , Wang Jia-wang , Yang Hong , Wang Wenshi , Mohapatra Subhra , Hellermann Gary , Kong Xiaoyuan , Lockey Richard F , Mohapatra Shyam S
Published: January 2011

Background

Atrial natriuretic peptide (ANP) is an important endogenous hormone that controls inflammation and immunity by acting on dendritic cells (DCs); however, the mechanism remains unclear.

Objective

We analyzed the downstream signaling events resulting from the binding of ANP to its receptor, NPRA, and sought to determine what aspects of this signaling modulate DC function.

Methods

We utilized the inhibitory peptide, NP73-102, to block NPRA signaling in human monocyte-derived DCs (hmDCs) and examined the effect on DC maturation and induced immune responses. The potential downstream molecules and interactions among these molecules involved in NPRA signaling were identified by immunoprecipitation and immunoblotting. Changes in T cell phenotype and function were determined by flow cytometry and BrdU proliferation ELISA. To determine if adoptively transferred DCs could alter the in vivo immune response, bone marrow-derived DCs from wild-type C57BL/6 mice were incubated with ovalbumin (OVA) and injected i.v. into C57BL/6 NPRA-/- knockout mice sensitized and challenged with OVA. Lung sections were stained and examined for inflammation and cytokines were measured in bronchoalveolar lavage fluid collected from parallel groups of mice.

Results

Inhibition of NPRA signaling in DCs primes them to induce regulatory T cells. Adoptive transfer of wild type DCs into NPRA-/- mice reverses the attenuation of lung inflammation seen in the NPRA-knockout model. NPRA is associated with TLR-2, SOCS3 and STAT3, and inhibiting NPRA alters expression of IL-6, IL-10 and TGF-β, but not IL-12.

Conclusions

Modulation of NPRA signaling in DCs leads to immune tolerance and TLR2 and SOCS3 are involved in this induction.
Circular polarization in a non-magnetic resonant tunneling device
Authors: dos Santos Lara F , Gobato Yara Galvão , Teodoro Márcio D , Lopez-Richard Victor , Marques Gilmar E , Brasil Maria JSP , Orlita Milan , Kunc Jan , Maude Duncan K , Henini Mohamed , Airey Robert J
Published: January 2011

We have investigated the polarization-resolved photoluminescence (PL) in an asymmetric n-type GaAs/AlAs/GaAlAs resonant tunneling diode under magnetic field parallel to the tunnel current. The quantum well (QW) PL presents strong circular polarization (values up to -70% at 19 T). The optical emission from GaAs contact layers shows evidence of highly spin-polarized two-dimensional electron and hole gases which affects the spin polarization of carriers in the QW. However, the circular polarization degree in the QW also depends on various other parameters, including the g-factors of the different layers, the density of carriers along the structure, and the Zeeman and Rashba effects.