bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of transforming growth factor-β signaling promotes collective cancer cell invasion through tumor-stromal crosstalk
Authors: Matise Lauren A , Palmer Trenis D , Ashby William J , Nashabi Abudi , Chytil Anna , Aakre Mary , Pickup Michael W , Gorska Agnieszka E , Zijlstra Andries , Moses Harold L 
Published: July 2012

Abstract
Introduction
Transforming growth factor beta (TGF-β) has a dual role during tumor progression, initially as a suppressor and then as a promoter. Epithelial TGF-β signaling regulates fibroblast recruitment and activation. Concurrently, TGF-β signaling in stromal fibroblasts suppresses tumorigenesis in adjacent epithelia, while its ablation potentiates tumor formation. Much is known about the contribution of TGF-β signaling to tumorigenesis, yet the role of TGF-β in epithelial-stromal migration during tumor progression is poorly understood. We hypothesize that TGF-β is a critical regulator of tumor-stromal interactions that promote mammary tumor cell migration and invasion.

Methods
Fluorescently labeled murine mammary carcinoma cells, isolated from either MMTV-PyVmT transforming growth factor-beta receptor II knockout (TβRII KO) or TβRIIfl/fl control mice, were combined with mammary fibroblasts and xenografted onto the chicken embryo chorioallantoic membrane. These combinatorial xenografts were used as a model to study epithelial-stromal crosstalk. Intravital imaging of migration was monitored ex ovo, and metastasis was investigated in ovo. Epithelial RNA from in ovo tumors was isolated by laser capture microdissection and analyzed to identify gene expression changes in response to TGF-β signaling loss.

Results
Intravital microscopy of xenografts revealed that mammary fibroblasts promoted two migratory phenotypes dependent on epithelial TGF-β signaling: single cell/strand migration or collective migration. At epithelial-stromal boundaries, single cell/strand migration of TβRIIfl/fl carcinoma cells was characterized by expression of α-smooth muscle actin and vimentin, while collective migration of TβRII KO carcinoma cells was identified by E-cadherin+/p120+/β-catenin+ clusters. TβRII KO tumors also exhibited a twofold greater metastasis than TβRIIfl/fl tumors, attributed to enhanced extravasation ability. In TβRII KO tumor epithelium compared with TβRIIfl/fl epithelium, Igfbp4 and Tspan13 expression was upregulated while Col1α2, Bmp7, Gng11, Vcan, Tmeff1, and Dsc2 expression was downregulated. Immunoblotting and quantitative PCR analyses on cultured cells validated these targets and correlated Tmeff1 expression with disease progression of TGF-β-insensitive mammary cancer.

Conclusion
Fibroblast-stimulated carcinoma cells utilize TGF-β signaling to drive single cell/strand migration but migrate collectively in the absence of TGF-β signaling. These migration patterns involve the signaling regulation of several epithelial-to-mesenchymal transition pathways. Our findings concerning TGF-β signaling in epithelial-stromal interactions are important in identifying migratory mechanisms that can be targeted as recourse for breast cancer treatment.
Conserved rules govern genetic interaction degree across species
Authors: Koch Elizabeth N , Costanzo Michael , Bellay Jeremy , Deshpande Raamesh , Chatfield-Reed Kate , Chua Gordon , D'Urso Gennaro , Andrews Brenda J , Boone Charles , Myers Chad L 
Published: July 2012

Abstract
Background
Synthetic genetic interactions have recently been mapped on a genome scale in the budding yeast Saccharomyces cerevisiae, providing a functional view of the central processes of eukaryotic life. Currently, comprehensive genetic interaction networks have not been determined for other species, and we therefore sought to model conserved aspects of genetic interaction networks in order to enable the transfer of knowledge between species.

Results
Using a combination of physiological and evolutionary properties of genes, we built models that successfully predicted the genetic interaction degree of S. cerevisiae genes. Importantly, a model trained on S. cerevisiae gene features and degree also accurately predicted interaction degree in the fission yeast Schizosaccharomyces pombe, suggesting that many of the predictive relationships discovered in S. cerevisiae also hold in this evolutionarily distant yeast. In both species, high single mutant fitness defect, protein disorder, pleiotropy, protein-protein interaction network degree, and low expression variation were significantly predictive of genetic interaction degree. A comparison of the predicted genetic interaction degrees of S. pombe genes to the degrees of S. cerevisiae orthologs revealed functional rewiring of specific biological processes that distinguish these two species. Finally, predicted differences in genetic interaction degree were independently supported by differences in co-expression relationships of the two species.

Conclusions
Our findings show that there are common relationships between gene properties and genetic interaction network topology in two evolutionarily distant species. This conservation allows use of the extensively mapped S. cerevisiae genetic interaction network as an orthology-independent reference to guide the study of more complex species.
Whole-genome sequencing and analysis of the Malaysian cynomolgus macaque (Macaca fascicularis) genome
Authors: Higashino Atsunori , Sakate Ryuichi , Kameoka Yosuke , Takahashi Ichiro , Hirata Makoto , Tanuma Reiko , Masui Tohru , Yasutomi Yasuhiro , Osada Naoki 
Published: July 2012

Abstract
Background
The genetic background of the cynomolgus macaque (Macaca fascicularis) is made complex by the high genetic diversity, population structure, and gene introgression from the closely related rhesus macaque (Macaca mulatta). Herein we report the whole-genome sequence of a Malaysian cynomolgus macaque male with more than 40-fold coverage, which was determined using a resequencing method based on the Indian rhesus macaque genome.

Results
We identified approximately 9.7 million single nucleotide variants (SNVs) between the Malaysian cynomolgus and the Indian rhesus macaque genomes. Compared with humans, a smaller nonsynonymous/synonymous SNV ratio in the cynomolgus macaque suggests more effective removal of slightly deleterious mutations. Comparison of two cynomolgus (Malaysian and Vietnamese) and two rhesus (Indian and Chinese) macaque genomes, including previously published macaque genomes, suggests that Indochinese cynomolgus macaques have been more affected by gene introgression from rhesus macaques. We further identified 60 nonsynonymous SNVs that completely differentiated the cynomolgus and rhesus macaque genomes, and that could be important candidate variants for determining species-specific responses to drugs and pathogens. The demographic inference using the genome sequence data revealed that Malaysian cynomolgus macaques have experienced at least three population bottlenecks.

Conclusions
This list of whole-genome SNVs will be useful for many future applications, such as an array-based genotyping system for macaque individuals. High-quality whole-genome sequencing of the cynomolgus macaque genome may aid studies on finding genetic differences that are responsible for phenotypic diversity in macaques and may help control genetic backgrounds among individuals.
Internet sex addiction: a licence to lust?
Authors: Dunn Nick , Seaburne-May Matthew , Gatter Philip 
Published: July 2012

SummaryIn this article we ask what kind of phenomenon is internet sex addiction. From the perspectives of two practising psychiatrists, one of whom has worked in a weekly sexual disorders clinic for 12 years, and an anthropologist we explore whether a moral panic is emerging over sexual behaviour and the internet, and whether internet sex addiction forms part of any such panic. We ask whether many individuals who diagnose themselves as addicted to internet-based sex do so more out of a media-activated sensibility than a clinical reality. We also consider what developments in DSM-5 hold for this area.
Simulation in psychiatric teaching
Authors: Dave Subodh 
Published: July 2012

SummaryThe use of simulated patients in medicine offers students a standardised learning experience and a reproducible way of exploring attitudes and teaching communication skills. This would seem to be particularly relevant to psychiatry with its focus on attitudes and interpersonal skills, but doubts have been raised about the utility of simulated patients in teaching skills such as empathy and the generalisability of this learning to the real world. This, tempered with cost implications, may have limited the use of simulated patients to assessment through objective structured clinical examinations rather than to teaching and to learning. This article examines the educational advantages and disadvantages of the use of simulated patients in psychiatric teaching and argues that their judicious use complements undergraduate and postgraduate training in psychiatry. The article offers practical tips on writing simulated patient scenarios to deliver specific learning objectives and discusses the potential use of novel simulation techniques in psychiatric education.
Benzodiazepines for anxiety disorders: maximising the benefits and minimising the risks
Authors: Starcevic Vladan 
Published: July 2012

SummaryBenzodiazepines still play an important role in the management of anxiety disorders but dependence is associated with their therapeutic use. The key to effective and safe long-term use of benzodiazepines is: the careful selection of patients who might benefit from them; administration in clinical situations in which they are more likely to be beneficial; use of lower doses and in conjunction with an antidepressant, if possible; monitoring and managing their side-effects; and minimising the risk of withdrawal symptoms and relapse, mainly through tapering the dose and/or combining with effective psychological interventions.
Why benzodiazepines are not going away
Authors: Tyrer Peter 
Published: July 2012

SummaryBenzodiazepines are still widely prescribed in psychiatry, mainly for the treatment of anxiety-related disorders. This is not because they are only taken by a hard core component of patients who are addicted and do not need them; it is because they remain the most effective and rapid acting of all drug treatments. Strategies for practitioners to use them more confidently are described.
Arthur Conan Doyle: the many faces of Sherlock Holmes
Authors: Reed James 
Published: July 2012

SummarySir Arthur Conan Doyle trained as a doctor and practised in a number of areas, but found real success only as an author. He is best known as the creator of the Sherlock Holmes stories. This article considers the individuals in Doyles' life that seem to have inspired the character of Holmes, a flawed genius with dark aspects (including intravenous drug use and instability of mood).
How does psychotherapy work? The self and its disorders
Authors: Adshead Gwen , Fonagy Peter 
Published: July 2012

SummaryThere is now extensive evidence that different types of psychological therapy are effective for various psychiatric disorders, both in terms of symptom reduction and in improving the patient's capacity to function adaptively. In two articles, we set out some current ideas of how psychological therapies might ‘work’, drawing on neurobiological studies of brain plasticity and therapeutic efficacy. In this first article, we review the evidence that disorders of self-experience are common to many psychiatric disorders, and that psychological therapies ‘work’ on those disorders. The second article will appear in the next issue ofAdvances.
Grief as a psychiatric disorder
Authors: Bryant Richard A. 
Published: July 2012

SummaryThe revisions DSM-5 and ICD-11 are attempting to describe psychopathological reactions to bereavement. The delineation between depressive disorder and normal bereavement-related depressed state lacks sufficient data to guide diagnostic development. In contrast, there is strong evidence for a diagnosis of prolonged grief that is distinguished from depression and involves marked impairment.
Magnetic resonance imaging in late-life depression: vascular and glucocorticoid cascade hypotheses
Authors: Sexton Claire E. , Masurier Marisa Le , Allan Charlotte L. , Jenkinson Mark , McDermott Lisa , Kalu Ukwuori G. , Herrmann Lucie L. , Bradley Kevin M. , Mackay Clare E. , Ebmeier Klaus P. 
Published: July 2012

BackgroundLate-life depression is a common and heterogeneous illness, associated with structural abnormalities in both grey and white matter.AimsTo examine the relationship between age at onset and magnetic resonance imaging (MRI) measures of grey and white matter to establish whether they support particular hypotheses regarding the anatomy and aetiology of network disruption in late-life depression.MethodWe studied 36 participants with late-life depression. Grey matter was examined usingT1-weighted MRI and analysed using voxel-based morphometry. The hippocampus was automatically segmented and volume and shape analysis performed. White matter was examined using diffusion tensor imaging and analysed using tract-based spatial statistics.ResultsLater age at onset was significantly associated with reduced fractional anisotropy of widespread tracts, in particular the anterior thalamic radiation and superior longitudinal fasciculus. Earlier age at onset was associated with reduced hippocampal volume normalised to whole brain size bilaterally. However, no significant correlations were detected using hippocampal shape analysis or voxel-based morphometry.ConclusionsOverall, the results were compatible with the vascular hypothesis, and provided some support for the glucocorticoid cascade hypothesis.
Psychometric properties of the Mental Health Recovery Star
Authors: Killaspy Helen , White Sarah , Taylor Tatiana L. , King Michael 
Published: July 2012

BackgroundThe Mental Health Recovery Star (MHRS) is a popular outcome measure rated collaboratively by staff and service users, but its psychometric properties are unknown.AimsTo assess the MHRS's acceptability, reliability and convergent validity.MethodA total of 172 services users and 120 staff from in-patient and community services participated. Interrater reliability of staff-only ratings and test–retest reliability of staff-only and collaborative ratings were assessed using intraclass correlation coefficients (ICCs). Convergent validity between MHRS ratings and standardised measures of social functioning and recovery was assessed using Pearson correlation. The influence of collaboration on ratings was assessed using descriptive statistics and ICCs.ResultsThe MHRS was relatively quick and easy to use and had good test–retest reliability, but interrater reliability was inadequate. Collaborative ratings were slightly higher than staff-only ratings. Convergent validity suggests it assesses social function more than recovery.ConclusionsThe MHRS cannot be recommended as a routine clinical outcome tool but may facilitate collaborative care planning.
Neuroimaging in psychiatry: bringing neuroscience into clinical practice
Authors: Phillips Mary L. 
Published: July 2012

SummaryThe past 20 years have seen a remarkable development of neuroimaging methodologies that allow fine-tuned examination of abnormalities in the structure and function of neural circuitry, supporting cognition and emotion in individuals with psychiatric disorders. This editorial highlights the potential of neuroimaging to address major challenges in psychiatric clinical practice.
Regional Timber Bridge Girder Reliability: Structural Health Monitoring and Reliability Strategies
Authors: Moore John C , Glenncross-Grant Rex , Mahini Seyed Saeed , Patterson Robert 
Published: July 2012

Many short span timber beam bridges in regional New South Wales are of unknown reliability, have high traffic loadings and were designed according to codes, many of which have since been superseded. Because asset managers are delaying their maintenance for fiscal reasons, a high proportion of these bridges are structurally degraded and potentially unsafe when excessively loaded. In regional areas, a prioritised maintenance program can be a cost effective alternative to bridge replacement. Such older bridges will require continuous monitoring by low cost methods to assess the temporal probability of their failure. This paper examines the potential for measuring the mid-span deflections of girders caused by high traffic loads to obtain continually updated indicators of the structural health of girders. The mid-span deflection data of a case study bridge were continuously measured using a laser based measuring system, recently developed by the first author. An analysis of the deflection data is used to obtain a reliability index and the probability of bridge failure. Reliability indicators such as these can be used, in conjunction with continuous deflection monitoring, to prioritise cost effective maintenance of older timber bridges in regional New South Wales.
A Comparative Study of Entrepreneurs' Attitudes to Failure in Technology Ventures
Authors: Cotterill Keith 
Published: July 2012

Entrepreneurs develop new technology ventures in uncertain conditions with unproven technologies and limited resources. The majority of such ventures fail. Examining entrepreneurs' attitudes to failure may reveal much about how entrepreneurs learn and how they identify subsequent opportunities.There is much literature on entrepreneurial failure [1-7] but relatively little that is focused on attitudes to failure [8, 9], the high-technology industry, or international comparisons. Pioneering work by the late Jason Cope applied methodologies derived from qualitative psychology to investigate attitudes to failure in entrepreneurs with recent experience of failed ventures in the aftermath of the ‘dot-com’ crash in 2001. We develop this work further, examining a wider range of geographic regions, a less intense period and focusing entirely on attitudes of the entrepreneur.This paper examines how entrepreneurs' attitudes to failure in early stage technology companies differ in the USA (Silicon Valley), UK (Cambridge) and Germany (Munich), and what this might reveal about entrepreneurial learning and opportunity identification in these countries. Using a qualitative approach, interviews with habitual entrepreneurs explore their experiences of failure. Techniques from qualitative psychology, including Interpretative Phenomenological Analysis are employed in the gathering and analysis of interview-based case studies to reveal emergent trends, which are then used to compare attitudes to failure within and between each country.Based on preliminary analysis of interview transcripts and a review of the literature, a conceptual model of how to analyze failure is proposed. Emergent trends are identified within each country and then evaluated to draw comparisons between different countries. Failure represents a frequent and important component of the entrepreneurial experience. Attitudes to failure reveal insights into how entrepreneurs respond and how they identify future opportunities.It is hoped this research will add to existing knowledge and theory of entrepreneurial failure, especially through the comparative (regional) approach and the industry-specific (high-technology) focus. It may also improve the preparedness of new entrepreneurs, with positive implications for future entrepreneurial success.
Experimental Investigation of Aluminum Foam Lined Suppressive Shield Containment Vessels
Authors: Braimah Abass , Elshafey Mohamed , Halim Abd El Halim O. Abd El , Contestabile Ettore 
Published: July 2012

Manufacture, transport, and storage of dangerous goods, especially energetic materials, in Canada and around the world pose serious challenges to explosives regulators and inspectors. Currently siting of manufacturing and storage facilities are in accordance with quantity-distance principles designed to mitigate effects of accidental explosions. The land requirements to satisfy these principles are imposing financial burdens on the explosives sector. This paper presents an experimental program designed to investigate the effectiveness of suppressive shield containers in reducing the blast pressure outside of the container while eliminating fragments thus reducing the distance requirement for the stored amount of explosives. Several suppressive shield panels including aluminium foam-lined panels were tested to study their effect on blast pressure and impulse. In addition computational fluid dynamics techniques were used to study suppressive shields effects on blast environment. The results show reduction of the incident peak blast pressure by 60% and the incident impulse by 58%. The aluminium foam-lined suppressive shield panels attenuated the peak incident pressure and impulse by 80%.
Abortion‐Seeking Minors’ Views on the Illinois Parental Notification Law: A Qualitative Study
Authors: Kavanagh Erin K. , Hasselbacher Lee A. , Betham Brittany , Tristan Sigrid , Gilliam Melissa L. 
Published: July 2012

CONTEXTThirty‐seven states have laws in effect that mandate parental involvement in adolescent abortion decisions. Little is known about minors’ opinions of parental involvement laws.METHODSIn‐depth interviews were conducted with 30 minors presenting for an abortion at one of three Chicago‐area clinics in 2010. Interviewers described the Illinois parental notification law (which was passed in 1995 but is not in effect because of legal challenges) and a corresponding judicial bypass option to the minors and asked their opinions about them. Interviews were coded and analyzed using content analysis and grounded theory methods.RESULTSMost minors perceived the law negatively, citing fears that it would lead to diminished reproductive autonomy for minors, forced continuation of pregnancies, adverse parental reactions (including emotional or physical abuse) and damaged parental relationships. A few held positive or ambivalent opinions, concluding that notifying a trusted adult could provide an adolescent with needed support, but that parental involvement should not be mandated. Most participants held negative opinions of judicial bypass, describing it as overwhelming and logistically complicated, and worrying that some minors might go to extreme lengths to avoid the process.CONCLUSIONSMany minors have deep concerns about the potential harm that could result from parental involvement laws. These opinions provide a valuable addition to the debate on such laws, which purportedly are intended to ensure minors’ best interests.