bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment-Associated Changes in Body Composition, Health Behaviors, and Mood as Predictors of Change in Body Satisfaction in Obese Women
Authors: Annesi James J. , Tennant Gisèle A. , Mareno Nicole
Published: April 2014

A lack of satisfaction with one’s body is common among women with obesity, often prompting unhealthy “dieting.” Beyond typically slow improvements in weight and body composition, behavioral factors might also affect change in body satisfaction. Age and race/ethnicity (African American vs. White) might moderate such change. Obese women ( N = 246; Mage = 43 years; MBMI = 39 kg/m2) initiating a 6-month cognitive-behaviorally based physical activity and nutrition treatment were assessed on possible predictors of body satisfaction change. At baseline, African American and younger women had significantly higher body satisfaction. The treatment was associated with significant within-group improvements in mood, health behaviors (physical activity and fruit/vegetable intake), and body composition (waist circumference). A multiple regression analysis indicated that mood, health behavior, and body composition changes explained a significant 27% of the variance in body satisfaction change. Of these predictors, changes in mood (β = −.36, p < .001) and health behaviors (β = .18, p = .01) made significant, unique contributions to the variance in change in body satisfaction that was accounted for, while only the measure of actual physiological change (body composition) did not. Neither age nor race/ethnicity was a significant moderator when each was entered separately into the multiple regression equation. Practical implications for leveraging manageable changes in behavioral factors for improving body satisfaction were discussed.
Generative Insights From the Eleanor Chelimsky Forum on Evaluation Theory and Practice
Authors: Leviton Laura C.
Published: April 2014

Both speakers at the Eleanor Chelimsky Forum on Theory and Practice in Evaluation pointed out the complexity and messiness of evaluation practice, and thus potential limits on theory and generalizable knowledge. The concept of reflective practice offers one way forward to build evaluation theory. Building generalizable knowledge about practice depends on the ability of expert practitioners to dialogue at greater length about the issues they encounter. On that basis they can better develop the implications of their practice experiences for evaluation theory. By renewing attention to what program managers and service practitioners know, we can also build evaluation theory, because their reflective practice can inform both the program and knowledge (external validity) dimensions of theory.
Formulation of the tangential velocity slip problem in terms of variational inequalities
Authors: Strozzi Antonio , Giacopini Matteo , Bertocchi Enrico , Dini Daniele
Published: April 2014

This contribution deals with a modelling of the tangential velocity slip problem in terms of variational inequalities. In particular, various technical situations for which the slippage problem appears to play an important role are first reviewed. Then, a mathematical formulation in terms of variational inequalities is developed where the critical shear stress criterion is considered. The theoretical conditions under which a unique solution exists are also discussed and an algebraic description based upon a complementarity approach is presented. Preliminary numerical results end the paper and a validation versus an analytical solution is proposed.
Discrepancy between parents and children in reporting of distress and impairment: Association with critical symptoms
Authors: Bein Laura A , Petrik Megan L , Saunders Stephen M , Wojcik James V
Published: April 2014

Background:

We examined discrepant parent–child reports of subjective distress and psychosocial impairment.

Method:

Parent–child pairs ( N = 112 pairs) completed the Health Dynamics Inventory at intake for outpatient therapy.

Results:

Average parent scores were significantly higher than average child scores on distress, impairment, and externalizing symptoms, but not internalizing symptoms. There were significant associations between parent–child discrepancy (i.e. children who reported greater distress or impairment than parents or vice versa) and child endorsement of several notable symptoms (rapid mood swings, panic, nightmares, and suicidal ideation).

Conclusion:

Parents tended to report more externalizing symptoms, distress, and impairment than children reported; however, when children report more distress and impairment than parents, this may indicate serious psychological problems.
Stendhal’s Gaze: Towards an hermeneutic approach of the tourist
Authors: Welten Ruud
Published: April 2014

Is travel inherently beneficial to human character? This is one of the principal questions to the practice of tourism from a philosophical viewpoint and posed as such by Dean MacCannell. But it is also a question with a long tradition. In this article, I aim to elaborate on MacCannell’s initial understandings of Stendhal’s work as a starting point for the philosophical deepening of tourism studies. MacCannell has criticised John Urry and argued for an analysis by replacing the term ‘the tourist gaze’ by ‘tourist agency’. MacCannell’s alternative version of the gaze is based on the non-representational discourse of the tourist-subject. Based on the work of the French writer Stendhal, MacCannell argues that the tourist gaze presumes a second gaze which ‘turns back onto the gazing subject an ethical responsibility for the construction of its own existence’. Although this notion makes the tourist not only a passive spectator but also an active narrator, the narration is nonetheless never a formal, ‘factual’ description of the things visited and experienced by the tourist. Instead of objectively representing the world, travel in this respect becomes a way of constructing the self.
The limits of a ‘heritage at risk’ framework: The construction of post-disaster cultural heritage in Banda Aceh, Indonesia
Authors: Rico Trinidad
Published: April 2014

This paper discusses what it means to label heritage as being ‘at risk’ in post-disaster landscapes in the city of Banda Aceh, Indonesia, following the 2004 Indian Ocean tsunami. It questions the relevance of a ‘heritage at risk’ framework, pointing out the issues associated with starting from this popular threat-based model of preservation in the aftermath of near or total destruction. By challenging the hegemony of a ‘heritage at risk’ rhetorical device that constructs heritage typologies, this debate focuses instead on the emergence and mastering of new heritage in post-tsunami Aceh, and the ways in which a shift in focus is able to document and preserve the emergence of unique heritage constructs and priorities. This paper promotes the study of heritage as a performance that transcends an emphasis on victimhood, toward framing a heritage construct that is productive and dynamic, a steward for post-disaster identities.
Singularizing the past: The history and archaeology of the small and ordinary
Authors: Mímisson Kristján , Magnússon Sigurður Gylfi
Published: April 2014

Recently a fierce criticism has been aimed at social history and how it has been directed by various forms of grand narratives. Some microhistorians have lent this critique a voice from where a new theoretical framework, the singularization of history, has arisen. It rejects the notion that fragments of historical data can be put together into rational and coherent metanarratives but emphasizes the need for an inward focus on the material at hand and interpretations free from the idealized perspectives on the past. Consequently, it involves scrutinizing the details of each event and object of research, looking for meaning within them rather than in larger contexts. In this paper, we intend to pose the question of if or how the idea of the singularization of history may apply to archaeology. Furthermore, we want to reflect upon the possibilities of a ‘singularized archaeology' that regards the things at hand by honouring the nature of singularities, their relations and ontological constitution and how they reassemble into composite entities like practices, events or persons.
What do we want from a discipline-based education? What do we need?
Authors: Edmond Jennifer
Published: April 2014

This article presents the research context for a 2013 investigation of how discipline of study at undergraduate level contributes to the development of generic problem solving skills. Inspired by a number of recent higher education policy developments in Ireland, it takes a different approach to the utility debate that seems to plague discussions of the arts and humanities as disciplines of study, looking into the economic and policy research underpinning what we know about the outcomes that can be expected from these courses of study, as well as the very small amount of evidence for medium to long term success in career formation. As might be expected, it exposes significant gaps between the research evidence for utility, the opinions of employer representatives and the policy positions taken, suggesting that common perceptions of all disciplines require a reevaluation.
Paradoxes of ethically branded bottled water: constituting the solution to the world water crisis
Authors: Hawkins Roberta , Emel Jody
Published: April 2014

This paper draws attention to the growing role of corporate marketing in the cultural production of crisis narratives. We examine ethically branded bottled water products that encourage the purchase of bottled water as one means of solving the global water crisis. The brands make a donation to a development organization addressing water issues each time a bottle of water is purchased. Through this process consumers are encouraged to ‘save lives’ and ‘engage’ in ‘alleviating the world water crisis’ through buying one brand of bottled water over another. These brands are somewhat paradoxical because they portray the consumption of products that many consider environmentally, economically and socially harmful as an ethical practice. We undertake a discourse analysis of the marketing materials for Ethos Water (one such ethically branded water product) in order to examine how a version of the world water crisis is constituted by the brand. Using the concept of problem closure, we argue that the cultural production of the world water crisis as natural and apolitical; as dislocated from specific places and environments; and as an opportunity for ethical awakening among consumers, results in the consumption of Ethos Water being constituted as a viable solution to such a crisis.
Local knowledge, early warning and coastal hazards: Participatory inquiry among fishworkers in Kerala, India
Authors: Santha Sunil D , Gahana P , Aswin VS
Published: April 2014

This paper demonstrates that local knowledge systems are inherent elements of people's capacity to forecast natural hazards and thereby reduce disaster risk. It describes the local knowledge systems prevalent among traditional fishworkers in Kerala to predict and forecast coastal hazards. Apart from diverse techniques of participatory inquiry, in-depth interviews were carried out with 400 fishing households across 20 marine fishing villages of the state. The socially constructed nature of coastal hazards is demonstrated as a holistic phenomenon namely kolu. The empirical knowledge related to forecasting and prediction of kolu is thus explained in terms of biotic, oceanic, atmospheric and celestial spheres. This paper asserts the need for effective community-based early warning systems that are deeply embedded in the livelihood struggles and life-world of marginalised resource-dependent communities.
Discomfort glare for white LED light sources with different spatial arrangements
Authors: Tashiro T , Kawanobe S , Kimura-Minoda T , Kohko S , Ishikawa T , Ayama M
Published: April 2014

Quantitative relations between discomfort glare evaluation and photometric quantities such as illuminance at the observer’s eye, average luminance of the source area, average luminance of the effective area and effective glare luminance for white LED sources having a variety of spatial luminance distributions have been investigated. Effective glare luminance, which is the sum of luminances in the luminaire area divided by the effective area, explains the scaling results of all sources in the same way. In addition, a new equation modified from the Commission Internationale de l'Éclairage Unified Glare Rating formula using the effective glare luminance showed a strong correlation with the scaling results. It is thus suggested that effective glare luminance is a useful index of discomfort glare for light sources having different spatial luminance distributions.
Effects of Tracking Technology on Daily Life of Persons With Dementia
Authors: Olsson Annakarin , Engström Maria , Åsenlöf Pernilla , Skovdahl Kirsti , Lampic Claudia
Published: April 2014

Objectives:

To investigate the effects of using tracking technology on independent outdoor activities and psychological well-being in 3 persons with dementia (PwDs) and their spouses.

Methods:

Three experimental single-case studies with an A1B1A2B2 design. The intervention entailed access to a passive positioning alarm and technical support. Continual daily measures of independent outdoor activities among PwDs’ and spouses’ worries about these activities were made during all phases.

Results:

Access to a tracking technology consistently increased the independent outdoor activities of 2 PwDs. One of the spouses consistently reported decreased worry during B phases, another’s worry decreased only in B2, and the third showed little variability in worrying across all phases.

Conclusion:

Tracking technology may support PwDs to engage in independent outdoor activities and decrease spouses’ worries; however, randomized controlled group studies are needed to investigate whether these results can be replicated on a group level.
Dementia and Cognitive Impairment in Patients With Parkinson’s Disease From India
Authors: Sanyal Jaya , Banerjee Tapas Kumar , Rao Vadlamudi Raghavendra
Published: April 2014

Depression and cognitive impairment are frequent manifestations in Parkinson’s disease (PD). Although a few longitudinal studies have reported on depression and dementia in PD, there is a yet a lack of such studies in India. This 7-year longitudinal study is a hospital-based prospective case (n = 250)–control (n = 280) study. In all, 36.8% had PD with no cognitive impairment (PD-Normal), 27.2% of the patients with PD were affected by dementia (PDD), and 36% of the remaining patients with PD had mild cognitive impairment (PD-MCI) at baseline. After 7 years of evaluation, 32 new patients, 12 patients from the PD-MCI group and 9 patients from the PD-Normal group, were diagnosed with dementia. The 7-year prevalence rate for dementia was estimated to be 49.28%. In the Indian population, an early onset of dementia is noted among patients with PD, with the age of onset being less than 55 years. Patients with early-onset PDD showed depression symptoms that differed significantly from the controls of the same age-group. There was a major difference in verbal fluency, word list recall, constructional praxis and recall, word list recognition, abridged Boston Naming Test, word list memory with repetition, and Mini-Mental State Examination between PD-MCI and PDD groups. Hallucinations before baseline (odds ratio [OR] = 4.427, 95% confidence interval [CI] = 2.122-9.373), akinetic/tremor dominancy (OR = 0.380, 95%CI = 0.149-0.953), and asymmetrical disease onset (OR = 0.3285, 95%CI = 0.1576-0.685) can be considered as risk factors for patients with dementia. Patients with early-onset PD might be more prone to complex depression and dementia. As the disease progresses, akinetic-dominant PD, early hallucinations, and asymmetrical disease onset are the potential risk factors for the development of dementia in patients with PD.
The Rehabilitation Engineering Research Center for the Advancement of Cognitive Technologies
Authors: Heyn Patricia Cristine , Cassidy Joy Lucille , Bodine Cathy
Published: April 2014

Barring few exceptions, allied health professionals, engineers, manufacturers of assistive technologies (ATs), and consumer product manufacturers have developed few technologies for individuals with cognitive impairments (CIs). In 2004, the National Institute on Disability Rehabilitation Research (NIDRR) recognized the need to support research in this emergent field. They funded the first Rehabilitation Engineering Research Center for the Advancement of Cognitive Technologies (RERC-ACT). The RERC-ACT has since designed and evaluated existing and emerging technologies through rigorous research, improving upon existing AT devices, and creating new technologies for individuals with CIs. The RERC-ACT has contributed to the development and testing of AT products that assist persons with CIs to actively engage in tasks of daily living at home, school, work, and in the community. This article highlights the RERC-ACT’s engineering development and research projects and discusses how current research may impact the quality of life for an aging population.
Articulating the Case for the Longevity Dividend
Authors: Olshansky S. Jay
Published: April 2014

In the past century, the average duration of life of people living in developed countries rose by 30 years. Most of this gain was a result of advances in public health that saved the young by warding off communicable diseases. However, in the latter half of the 20th century, improvements in lifestyle modification and advances in biomedical technology enabled people at middle and older ages to experience extended lives. Thus, aging as we know it today is a new phenomenon—experienced by a small but rapidly growing segment of our world. As appealing as our longer lives may be, there was a price to pay for life extension—the rise of noncommunicable fatal and disabling diseases. It was a fair exchange, but now humanity is left with the difficult task of dealing with this Faustian trade. A new approach to public health in a rapidly aging world has been proposed (the longevity dividend), with the idea that extending healthy life by slowing aging may prove to be the most efficient way to combat the fatal and disabling diseases that plague us today. Here, I articulate the case for why we now need to turn our attention to combating aging itself.
Evaluation of Tarsal Navicular Stress Fracture Fixation Using Intraoperative O-arm Computed Tomography
Authors: Hsu Andrew R. , Lee Simon
Published: April 2014

Stress fractures of the tarsal navicular are high-risk injuries that can result in displacement, avascular necrosis, malunion, and nonunion. Delayed diagnosis and improper treatment can lead to long-term functional impairments and poor clinical outcomes. Increased shear stress and decreased vascularity in the central third of the navicular can complicate bony healing with often unpredictable return times to activity using conservative management in a non-weight-bearing cast. There recently has been increasing debate regarding the effectiveness of treatment options with a trend toward surgical management to anatomically reduce and stabilize navicular stress fractures in athletes. However, anatomic reduction and fixation of the navicular can be difficult despite direct visualization and intraoperative fluoroscopy. We report a case of a chronic navicular stress fracture in a high-level teenage athlete treated with open reduction internal fixation (ORIF) and calcaneus autograft using intraoperative computed tomography (CT) (O-arm®, Medtronic, Minneapolis, MN) for real-time evaluation of fracture reduction and fixation. Intraoperative CT was fast, reliable, and allowed for confirmation of guide wire orientation, alignment, and length across the fracture site. Anatomic fixation of navicular stress fractures can be challenging, and it is important for surgeons to be aware of the potential advantages of using intraoperative CT when treating these injuries.

Levels of Evidence: Therapeutic, Level IV: Case Report
Future Ethical Issues Involving Reproduction—With Examples from Star Trek
Authors: Savona-Ventura Charles , Grech Victor
Published: April 2014

Science fiction narratives are regularly used to explore the consequences of contemporary and envisaged future scientific innovations along with the ensuing novel ethical and moral concepts. The television series Star Trek has dealt with aspects of reproductive health, often based on extrapolations from significant real-world breakthroughs in artificial reproductive technology and genetic engineering. This article assesses episodes that addressed such vexing ethical questions as choices affecting pregnancy after rape, advances in obstetrics including surrogate motherhood, and novel delivery techniques designed to protect the health of the mother and baby. However, the most significant ethical challenges may be those involving choices of deliberate genetic enhancements and/or frank physical alterations in non-life-threatening situations. The authors argue that responsible use of the popular science fiction genre, as exemplified by the various Star Trek series, cannot only provide advanced warning of problems and issues that science may eventually unleash but also suggest potential solutions to such problems.
Injury Rate and Patterns Among CrossFit Athletes
Authors: Weisenthal Benjamin M. , Beck Christopher A. , Maloney Michael D. , DeHaven Kenneth E. , Giordano Brian D.
Published: April 2014

Background:

CrossFit is a type of competitive exercise program that has gained widespread recognition. To date, there have been no studies that have formally examined injury rates among CrossFit participants or factors that may contribute to injury rates.

Purpose:

To establish an injury rate among CrossFit participants and to identify trends and associations between injury rates and demographic categories, gym characteristics, and athletic abilities among CrossFit participants.

Study Design:

Descriptive epidemiology study.

Methods:

A survey was conducted, based on validated epidemiologic injury surveillance methods, to identify patterns of injury among CrossFit participants. It was sent to CrossFit gyms in Rochester, New York; New York City, New York; and Philadelphia, Pennsylvania, and made available via a posting on the main CrossFit website. Participants were encouraged to distribute it further, and as such, there were responses from a wide geographical location. Inclusion criteria included participating in CrossFit training at a CrossFit gym in the United States. Data were collected from October 2012 to February 2013. Data analysis was performed using Fisher exact tests and chi-square tests.

Results:

A total of 486 CrossFit participants completed the survey, and 386 met the inclusion criteria. The overall injury rate was determined to be 19.4% (75/386). Males (53/231) were injured more frequently than females (21/150; P = .03). Across all exercises, injury rates were significantly different ( P < .001), with shoulder (21/84), low back (12/84), and knee (11/84) being the most commonly injured overall. The shoulder was most commonly injured in gymnastic movements, and the low back was most commonly injured in power lifting movements. Most participants did not report prior injury (72/89; P < .001) or discomfort in the area (58/88; P < .001). Last, the injury rate was significantly decreased with trainer involvement ( P = .028).

Conclusion:

The injury rate in CrossFit was approximately 20%. Males were more likely to sustain an injury than females. The involvement of trainers in coaching participants on their form and guiding them through the workout correlates with a decreased injury rate. The shoulder and lower back were the most commonly injured in gymnastic and power lifting movements, respectively. Participants reported primarily acute and fairly mild injuries.
How I treat renal complications in sickle cell disease
Authors: Sharpe Claire C. , Thein Swee Lay
Published: April 2014

Renal disease is one of the most frequent and severe complications experienced by patients with sickle cell disease; its prevalence is likely to increase as the patient population ages. We recommend regular monitoring for early signs of renal involvement and a low threshold for the use of hydroxyurea as preventative measures for end-stage renal disease. Once renal complications are detected, a careful assessment of the patient is required to rule out other causes of renal disease. Proteinuria and hypertension should be managed aggressively and the patient referred to a specialist nephrology center when progressive decline in renal function is noted. For the few patients who develop advanced chronic kidney disease, timely planning for dialysis and transplantation can significantly improve outcome, and we recommend an exchange blood transfusion policy for all patients on the transplant waiting list and for those with a functioning graft. Alongside the invasive treatment regimes, it is important to remember that renal failure in conjunction with sickle cell disease does carry a significant burden of morbidity and that focusing on symptom control has to be central to good patient care.
CC-Chemokine receptor CCR7: a key molecule for lymph node metastasis in esophageal squamous cell carcinoma
Authors: Irino Tomoyuki , Takeuchi Hiroya , Matsuda Sachiko , Saikawa Yoshiro , Kawakubo Hirofumi , Wada Norihito , Takahashi Tsunehiro , Nakamura Rieko , Fukuda Kazumasa , Omori Tai , Kitagawa Yuko
Published: April 2014

Background

CC-chemokine receptor 7 (CCR7), a known lymph node homing receptor for immune cells, has been reported as a key molecule in lymph node metastasis. We hypothesized a clinicopathological correlation and functional causality between CCR7 expression and lymph node metastasis in patients with esophageal squamous cell carcinoma (ESCC).

Methods

We performed immunohistochemical analysis of 105 consecutive and 61 exclusive pathological T1 ESCC patients, followed by adhesion assay and in vivo experiment using a newly developed lymph node metastasis mouse model. The adhesive ability in response to CC-chemokine ligand 21/secondary lymphoid-tissue chemokine (CCL21/SLC) was assessed in the presence or absence of lymphatic endothelial cells and anti-CCR7 antibody. We established a heterotopic transplantation mouse model and analyzed lymph node metastasis by quantitative real-time RT-PCR.

Results

Positive CCR7 expression in immunohistochemistory was detected in 28 (27%) of 105 consecutive patients and 17 (28%) of 61 T1 patients, which significantly correlated with lymph node metastasis (p = 0.037 and p = 0.040, respectively) and poor five-year survival (p = 0.013 and p = 0.012, respectively). Adhesion assay revealed an enhanced adhesive ability of CCR7-expressing cells in response to CCL21/SLC, in particular, in the presence of lymphatic endothelial cells (p = 0.005). In the mouse model, lymph nodes from mice transplanted with CCR7-expressing cells showed significantly higher DNA levels at 5 weeks (p = 0.019), indicating a high metastatic potential of CCR7-expressing cells.

Conclusion

These results demonstrated the significant clinicopathological relationship and functional causality between CCR7 expression and lymph node metastasis in ESCC patients.
A role for PAX8 in the tumorigenic phenotype of ovarian cancer cells
Authors: Di Palma Tina , Lucci Valeria , de Cristofaro Tiziana , Filippone Maria Grazia , Zannini Mariastella
Published: April 2014

Background

PAX8 is a member of the paired box (Pax) multigene family of transcription factors, which are involved in the developmental and tissue-specific control of the expression of several genes in both vertebrates and invertebrates. Previously, several studies reported that PAX8 is expressed at high levels in specific types of tumors. In particular, PAX8 has been recently reported to be conspicuously expressed in human ovarian cancer, but the functional role of PAX8 in the carcinogenesis of this type of tumor has not been addressed. In this study, we investigated the contribution of PAX8 in ovarian cancer progression.

Methods

Stable PAX8 depleted ovarian cancer cells were generated using short hairpin RNA (shRNA) constructs. PAX8 mRNA and protein were detected by RT-PCR, immunoblot and immunofluorescence. Cell proliferation, motility and invasion potential of PAX8 silenced cells were analyzed by means of growth curves, wound healing and Matrigel assays. In addition, PAX8 knockdown and control cells were injected into nude mice for xenograft tumorigenicity assays. Finally, qPCR was used to detect the expression levels of EMT markers in PAX8-overexpressing and control cells.

Results

Here, we show that PAX8 plays a critical role in the migration, invasion and tumorigenic ability of ovarian cancer cells. Our results show that RNA interference-mediated knockdown of PAX8 expression in SKOV-3 ovarian cancer cells produces a significant reduction of cell proliferation, migration ability and invasion activity compared with control parental SKOV-3 cells. Moreover, PAX8 silencing strongly suppresses anchorage-independent growthin vitro. Notably, tumorigenesisin vivoin a nude mouse xenograft model is also significantly inhibited.

Conclusions

Overall, our results indicate that PAX8 plays an important role in the tumorigenic phenotype of ovarian cancer cells and identifies PAX8 as a potential new target for the treatment of ovarian cancer.
WNT5A induces release of exosomes containing pro-angiogenic and immunosuppressive factors from malignant melanoma cells
Authors: Ekström Elin J , Bergenfelz Caroline , von Bülow Verena , Serifler Filiz , Carlemalm Eric , Jönsson Göran , Andersson Tommy , Leandersson Karin
Published: April 2014

Background

Wnt proteins are important for developmental processes and certain diseases. WNT5A is a non-canonical Wnt protein that previously has been shown to play a role in the progression of malignant melanoma. High expression of WNT5A in melanoma tumors correlates to formation of distant metastasis and poor prognosis. This has partly been described by the findings that WNT5A expression in melanoma cell lines increases migration and invasion.

Methods

Malignant melanoma cell lines were treated with rWNT5A or WNT5A siRNA, and mRNA versus protein levels of soluble mediators were measured using RT-PCR, cytokine bead array and ELISA. The induced signaling pathways were analyzed using inhibitors, Rho-GTPase pull down assays and western blot. Ultracentrifugation and electron microscopy was used to analyze microvesicles. Gene expression microarray data obtained from primary malignant melanomas was used to verify our data.

Results

We show that WNT5A signaling induces a Ca2+-dependent release of exosomes containing the immunomodulatory and pro-angiogenic proteins IL-6, VEGF and MMP2 in melanoma cells. The process was independent of the transcriptional machinery and depletion of WNT5A reduced the levels of the exosome-derived proteins. The WNT5A induced exosomal secretion was neither affected by Tetanus toxin nor Brefeldin A, but was blocked by the calcium chelator Bapta, inhibited by a dominant negative version of the small Rho-GTPase Cdc42 and was accompanied by cytoskeletal reorganization. Co-cultures of melanoma/endothelial cells showed that depletion of WNT5A in melanoma cells decreased endothelial cell branching, while stimulation of endothelial cells with isolated rWNT5A-induced melanoma exosomes increased endothelial cell branching in vitro. Finally, gene expression data analysis of primary malignant melanomas revealed a correlation between WNT5A expression and the angiogenesis marker ESAM.

Conclusions

These data indicate that WNT5A has a broader function on tumor progression and metastatic spread than previously known; by inducing exosome-release of immunomodulatory and pro-angiogenic factors that enhance the immunosuppressive and angiogenic capacity of the tumors thus rendering them more aggressive and more prone to metastasize.
E. coli O157 on Scottish cattle farms: Evidence of local spread and persistence using repeat cross-sectional data
Authors: Herbert Liam J , Vali Leila , Hoyle Deborah V , Innocent Giles , McKendrick Iain J , Pearce Michael C , Mellor Dominic , Porphyre Thibaud , Locking Mary , Allison Lesley , Hanson Mary , Matthews Louise , Gunn George J , Woolhouse Mark EJ , Chase-Topping Margo E
Published: April 2014

Background

Escherichia coli (E. coli) O157 is a virulent zoonotic strain of enterohaemorrhagic E. coli. In Scotland (1998-2008) the annual reported rate of human infection is 4.4 per 100,000 population which is consistently higher than other regions of the UK and abroad. Cattle are the primary reservoir. Thus understanding infection dynamics in cattle is paramount to reducing human infections.

A large database was created for farms sampled in two cross-sectional surveys carried out in Scotland (1998 - 2004). A statistical model was generated to identify risk factors for the presence of E. coli O157 on farms. Specific hypotheses were tested regarding the presence of E. coli O157 on local farms and the farms previous status. Pulsed-field gel electrophoresis (PFGE) profiles were further examined to ascertain whether local spread or persistence of strains could be inferred.

Results

The presence of an E. coli O157 positive local farm (average distance: 5.96km) in the Highlands, North East and South West, farm size and the number of cattle moved onto the farm 8 weeks prior to sampling were significant risk factors for the presence of E. coli O157 on farms. Previous status of a farm was not a significant predictor of current status (p = 0.398). Farms within the same sampling cluster were significantly more likely to be the same PFGE type (p < 0.001), implicating spread of strains between local farms. Isolates with identical PFGE types were observed to persist across the two surveys, including 3 that were identified on the same farm, suggesting an environmental reservoir. PFGE types that were persistent were more likely to have been observed in human clinical infections in Scotland (p < 0.001) from the same time frame.

Conclusions

The results of this study demonstrate the spread of E. coli O157 between local farms and highlight the potential link between persistent cattle strains and human clinical infections in Scotland. This novel insight into the epidemiology of Scottish E. coli O157 paves the way for future research into the mechanisms of transmission which should help with the design of control measures to reduce E. coli O157 from livestock-related sources.
Experimental validation of FINDSITEcomb virtual ligand screening results for eight proteins yields novel nanomolar and micromolar binders
Authors: Srinivasan Bharath , Zhou Hongyi , Kubanek Julia , Skolnick Jeffrey
Published: April 2014

Background

Identification of ligand-protein binding interactions is a critical step in drug discovery. Experimental screening of large chemical libraries, in spite of their specific role and importance in drug discovery, suffer from the disadvantages of being random, time-consuming and expensive. To accelerate the process, traditional structure- or ligand-based VLS approaches are combined with experimental high-throughput screening, HTS. Often a single protein or, at most, a protein family is considered. Large scale VLS benchmarking across diverse protein families is rarely done, and the reported success rate is very low. Here, we demonstrate the experimental HTS validation of a novel VLS approach, FINDSITEcomb, across a diverse set of medically-relevant proteins.

Results

For eight different proteins belonging to different fold-classes and from diverse organisms, the top 1% of FINDSITEcomb’s VLS predictions were tested, and depending on the protein target, 4%-47% of the predicted ligands were shown to bind with μM or better affinities. In total, 47 small molecule binders were identified. Low nanomolar (nM) binders for dihydrofolate reductase and protein tyrosine phosphatases (PTPs) and micromolar binders for the other proteins were identified. Six novel molecules had cytotoxic activity (<10 μg/ml) against the HCT-116 colon carcinoma cell line and one novel molecule had potent antibacterial activity.

Conclusions

We show that FINDSITEcombis a promising new VLS approach that can assist drug discovery.
Brain-derived neurotrophic factor levels and bipolar disorder in patients in their first depressive episode: 3-year prospective longitudinal study
Authors: Li Zezhi , Zhang Chen , Fan Jinbo , Yuan Chengmei , Huang Jia , Chen Jun , Yi Zhenghui , Wang Zuowei , Hong Wu , Wang Yong , Lu Weihong , Guan Yangtai , Wu Zhiguo , Su Yousong , Cao Lan , Hu Yingyan , Hao Yong , Liu Mingyuan , Yu Shunying , Cui Donghong , Xu Lin , Song Yanyan , Fang Yiru
Published: April 2014

Background

Early identification of patients with bipolar disorder during their first depressive episode is beneficial to the outcome of the disorder and treatment, but traditionally this has been a great challenge to clinicians. Recently, brain-derived neurotrophic factor (BDNF) has been suggested to be involved in the pathophysiology of bipolar disorder and major depressive disorder (MDD), but it is not clear whether BDNF levels can be used to predict bipolar disorder among patients in their first major depressive episode.

Aims

To explore whether BDNF levels can differentiate between MDD and bipolar disorder in the first depressive episode.

Method

A total of 203 patients with a first major depressive episode as well as 167 healthy controls were recruited. After 3 years of bi-annual follow-up, 164 patients with a major depressive episode completed the study, and of these, 21 were identified as having bipolar disorder and 143 patients were diagnosed as having MDD. BDNF gene expression and plasma levels at baseline were compared among the bipolar disorder, MDD and healthy control groups. Logistic regression and decision tree methods were applied to determine the best model for predicting bipolar disorder at the first depressive episode.

Results

At baseline, patients in the bipolar disorder and MDD groups showed lower BDNF mRNA levels (P<0.001 andP= 0.02 respectively) and plasma levels (P= 0.002 andP= 0.01 respectively) compared with healthy controls. Similarly, BDNF levels in the bipolar disorder group were lower than those in the MDD group. These results showed that the best model for predicting bipolar disorder during a first depressive episode was a combination of BDNF mRNA levels with plasma BDNF levels (receiver operating characteristics (ROC) = 0.80, logistic regression; ROC = 0.84, decision tree).

Conclusions

Our findings suggest that BDNF levels may serve as a potential differential diagnostic biomarker for bipolar disorder in a patient's first depressive episode.
Organizational Networks and Recovery following the Canterbury Earthquakes
Authors: Stevenson J. R. , Chang-Richards Y. , Conradson D. , Wilkinson S. , Vargo J. , Seville E. , Brunsdon D.
Published: April 2014

Following a disaster, the recovery of organizations is influenced by the flow of resources and information through organizational networks. The 2010–2011 earthquakes in Canterbury, New Zealand, had major direct and indirect impacts on local organizations and the regional economy. This paper utilizes 47 organizational case studies to assess the role of organizations’ networks in their response and short-term recovery activities, and to explore the effects of networks on regional reconstruction and related sectors. The results are organized around four thematic analyses, focusing on organizations’ support network characteristics, the types of support mobilized to aid recovery, network adaptations for new post-quake demands, and the economic impacts of organizational networks in reconstruction. The paper discusses how organizations managed and utilized networks to reduce the impacts of the earthquakes and to adapt to altered post-quake environments. These empirical observations of post-quake organizational behavior can also inform regional economic impact and resilience modeling.
Drag, but not buoyancy, affects swim speed in captive Steller sea lions
Authors: Suzuki Ippei , Sato Katsufumi , Fahlman Andreas , Naito Yasuhiko , Miyazaki Nobuyuki , Trites Andrew W.
Published: April 2014

Swimming at an optimal speed is critical for breath-hold divers seeking to maximize the time they can spend foraging underwater. Theoretical studies have predicted that the optimal swim speed for an animal while transiting to and from depth is independent of buoyancy, but is dependent on drag and metabolic rate. However, this prediction has never been experimentally tested. Our study assessed the effects of buoyancy and drag on the swim speed of three captive Steller sea lions (Eumetopias jubatus) that made 186 dives. Our study animals were trained to dive to feed at fixed depths (10–50 m) under artificially controlled buoyancy and drag conditions. Buoyancy and drag were manipulated using a pair of polyvinyl chloride (PVC) tubes attached to harnesses worn by the sea lions, and buoyancy conditions were designed to fall within the natural range of wild animals (∼12–26% subcutaneous fat). Drag conditions were changed with and without the PVC tubes, and swim speeds were recorded and compared during descent and ascent phases using an accelerometer attached to the harnesses. Generalized linear mixed-effect models with the animal as the random variable and five explanatory variables (body mass, buoyancy, dive depth, dive phase, and drag) showed that swim speed was best predicted by two variables, drag and dive phase (AIC = −139). Consistent with a previous theoretical prediction, the results of our study suggest that the optimal swim speed of Steller sea lions is a function of drag, and is independent of dive depth and buoyancy.
Aldehyde dehydrogenase, Ald4p, is a major component of mitochondrial fluorescent inclusion bodies in the yeast Saccharomyces cerevisiae
Authors: Misonou Yoshiko , Kikuchi Maiko , Sato Hiroshi , Inai Tomomi , Kuroiwa Tsuneyoshi , Tanaka Kenji , Miyakawa Isamu
Published: April 2014

When Saccharomyces cerevisiae strain 3626 was cultured to the stationary phase in a medium that contained glucose, needle-like structures that emitted autofluorescence were observed in almost all cells by fluorescence microscopy under UV excitation. The needle-like structures completely overlapped with the profile of straight elongated mitochondria. Therefore, these structures were designated as mitochondrial fluorescent inclusion bodies (MFIBs). The MFIB-enriched mitochondrial fractions were successfully isolated and 2D-gel electrophoresis revealed that a protein of 54 kDa was only highly concentrated in the fractions. Determination of the N-terminal amino acid sequence of the 54-kDa protein identified it as a mitochondrial aldehyde dehydrogenase, Ald4p. Immunofluorescence microscopy showed that anti-Ald4p antibody specifically stained MFIBs. Freeze-substitution electron microscopy demonstrated that cells that retained MFIBs had electron-dense filamentous structures with a diameter of 10 nm in straight elongated mitochondria. Immunoelectron microscopy showed that Ald4p was localized to the electron-dense filamentous structures in mitochondria. These results together showed that a major component of MFIBs is Ald4p. In addition, we demonstrate that MFIBs are common features that appear in mitochondria of many species of yeast.
The Wnt/JNK signaling target gene alcam is required for embryonic kidney development
Authors: Cizelsky Wiebke , Tata Aleksandra , Kühl Michael , Kühl Susanne J.
Published: April 2014

Proper development of nephrons is essential for kidney function. β-Catenin-independent Wnt signaling through Fzd8, Inversin, Daam1, RhoA and Myosin is required for nephric tubule morphogenesis. Here, we provide a novel mechanism through which non-canonical Wnt signaling contributes to tubular development. Using Xenopus laevis as a model system, we found that the cell-adhesion molecule Alcam is required for proper nephrogenesis and functions downstream of Fzd3 during embryonic kidney development. We found alcam expression to be independent of Fzd8 or Inversin, but to be transcriptionally regulated by the β-Catenin-independent Wnt/JNK pathway involving ATF2 and Pax2 in a direct manner. These novel findings indicate that several branches of Wnt signaling are independently required for proximal tubule development. Moreover, our data indicate that regulation of morphogenesis by non-canonical Wnt ligands also involves direct transcriptional responses in addition to the effects on a post-translational level.
Role of insulin impairment, adiponectin and dyslipidemia in peripheral and central neuropathy in mice
Authors: Anderson Nicholas J. , King Matthew R. , Delbruck Lina , Jolivalt Corinne G.
Published: April 2014

One of the tissues/organs affected by diabetes is the nervous system, predominantly the peripheral system (peripheral polyneuropathy and/or painful peripheral neuropathy) but also the central system with impaired learning, memory and mental flexibility. The aim of this study was to test the hypothesis that the pre-diabetic or diabetic condition caused by a high fat diet (HFD) can damage both the peripheral and central nervous systems. Groups of C57Bl6 and Swiss Webster mice were fed a diet containing 60% fat for 8 months and compared to control and STZ-diabetic groups that were fed a standard diet containing 10% fat. Aspects of peripheral nerve function (conduction velocity, thermal sensitivity) and central nervous system function (learning ability, memory) were measured at assorted times during the study. Both strains of mice on HFD developed impaired glucose tolerance, indicative of insulin resistance, but only the C57Bl6 showed statistically significant hyperglycemia. STZ-diabetic C57Bl6 mice developed learning deficits in the Barnes maze after 8 weeks of diabetes while neither C57Bl6 or Swiss Webster mice fed a HFD showed signs of defects at that time point. By 6 months on HFD, Swiss Webster mice developed learning and memory deficits in the Barnes maze test, whereas their peripheral nervous system remained normal. In contrast, C57Bl6 mice fed the HFD developed peripheral nerve dysfunction, as indicated by nerve conduction slowing and thermal hyperalgesia, but showed normal learning and memory functions. Our data indicate that STZ-diabetes or high fat diet can damage both peripheral and central nervous systems but learning deficits develop more rapidly in insulin-deficient than in insulin-resistant conditions and only in Swiss Webster mice. In addition to insulin impairment, dyslipidemia or adiponectinemia may determine the neuropathy phenotype.