Towards third generation matrix metalloproteinase inhibitors for cancer therapy

The failure of matrix metalloproteinase (MMP) inhibitor drug clinical trials in cancer was partly due to the inadvertent inhibition of MMP antitargets that counterbalanced the benefits of MMP target inhibition. We explore how MMP inhibitor drugs might be developed to achieve potent selectivity for validated MMP targets yet therapeutically spare MMP antitargets that are critical in host protection

DIPPER, a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics

The spatiotemporal proteome of the intervertebral disc (IVD) underpins its integrity and function. We present DIPPER, a deep and comprehensive IVD proteomic resource comprising 94 genome-wide profiles from 17 individuals. To begin with, protein modules defining key directional trends spanning the lateral and anteroposterior axes were derived from high-resolution spatial proteomes of intact young cadaveric lumbar IVDs. They revealed novel region-specific profiles of regulatory activities and displayed potential paths of deconstruction in the level- and location-matched aged cadaveric discs. Machine learning methods predicted a 'hydration matrisome' that connects extracellular matrix with MRI intensity. Importantly, the static proteome used as point-references can be integrated with dynamic proteome (SILAC/degradome) and transcriptome data from multiple clinical samples, enhancing robustness and clinical relevance. The data, findings, and methodology, available on a web interface (http://www.sbms.hku.hk/dclab/DIPPER/), will be valuable references in the field of IVD biology and proteomic analytics

Are lay people good at recognising the symptoms of schizophrenia?

©2013 Erritty, Wydell. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Aim: The aim of this study was to explore the general public’s perception of schizophrenia symptoms and the need to seekhelp for symptoms. The recognition (or ‘labelling’) of schizophrenia symptoms, help-seeking behaviours and public awareness of schizophrenia have been suggested as potentially important factors relating to untreated psychosis. Method: Participants were asked to rate to what extent they believe vignettes describing classic symptoms (positive and negative) of schizophrenia indicate mental illness. They were also asked if the individuals depicted in the vignettes required help or treatment and asked to suggest what kind of help or treatment. Results: Only three positive symptoms (i.e., Hallucinatory behaviour, Unusual thought content and Suspiciousness) of schizophrenia were reasonably well perceived (above 70%) as indicating mental illness more than the other positive or negative symptoms. Even when the participants recognised that the symptoms indicated mental illness, not everyone recommended professional help. Conclusion: There may be a need to improve public awareness of schizophrenia and psychosis symptoms, particularly regarding an awareness of the importance of early intervention for psychosis

The relationship between finger length ratio, masculinity, and sexual orientation in women: A correlational study.

Homosexual women are, on average, more masculine in their appearance and behavior than heterosexual women. We hypothesized that their masculinity was influenced by exposure to elevated levels of prenatal androgen during early development. We recruited 199 women (including 67 homosexual women) and measured their masculinity via self-report and observer ratings. Our measure of prenatal androgen exposure was the ratio of the index to ring finger (2D:4D), which is hypothesized to be lower in women exposed to elevated levels of androgens during prenatal development. Homosexual women were substantially more masculine than heterosexual women in both self-report and observer ratings. However, homosexual women neither had more male-typical finger length ratios, nor did their finger length ratios relate to their masculinity in any predicted direction. Thus, we found no evidence that increased prenatal androgen exposure influenced masculinity in homosexual women

Gender Nonconformity of Bisexual Men and Women

The degree to which bisexual-identified individuals are distinct from either heterosexual or homosexual individuals in their sexual orientation is an ongoing debate. We examined potential differences between these groups with respect to a strong correlate of sexual orientation, gender nonconformity (femininity in males, masculinity in females). Across pooled data, we compared self-reports of childhood gender nonconformity (n = 919) and adulthood gender nonconformity (n = 1265) and observer ratings of adulthood gender nonconformity (n = 915) between sexual orientations. Most analyses suggested a steady increase in gender nonconformity from exclusively heterosexual to exclusively homosexual. However, in some analyses, bisexual men were closer to homosexual men than to heterosexual men in their gender nonconformity. The intermediate status of bisexual people in gender nonconformity was not due to the sample having a mixture of very gender-conforming and very gender-nonconforming individuals. In total, men and women with bisexual orientations appeared neither like heterosexual nor homosexual individuals, at least with respect to their gender-related traits

Assessment for learning : a model for the development of a child’s self competence in the early years of education

In recent years policy documents, curricula and other educational initiatives have promoted a pedagogy founded on the concept of independent learning. This is broadly defined as ‘having the belief in yourself to think through learning activities, problems or challenges, make decisions about your learning and act upon those decisions (Blandford and Knowles, 2009:336). The central role of Assessment for Learning (AfL) in this process is often overlooked in practice. By considering the findings from a small scale research study this article addresses the central role of the teacher /practitioner in developing effective AfL in the early years classroom (3-5 years)

Pleiotropic functions of the tumor- and metastasis-suppressing Matrix Metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice

Matrix metalloproteinase-8 (MMP-8; neutrophil collagenase) is an important regulator of innate immunity which has onco-suppressive actions in numerous tumor types

Abortion attitudes: An overview of demographic and ideological differences

Despite being a defining issue in the culture war, the relative importance of the psychological predictors of abortion attitudes are poorly understood. We address this oversight here by reviewing existing findings and providing new evidence for the demographic and ideological correlates of abortion support. Throughout our review, we integrate new analyses of several large-scale, cross-sectional, and longitudinal datasets to provide the most complete empirical examination of abortion attitudes to date. Our review and new analyses indicate that abortion support is increasing (modestly) over time in both the US and New Zealand. We also show that a plurality of respondents (43.8%) in the US indicate that they are “pro-choice” across various elective and traumatic scenarios, whereas only 14.8% report being consistently “pro-life” regardless of why an abortion is sought. Our review and new integrative analyses then demonstrate that age, religiosity, and conservatism correlate negatively, whereas Openness to Experience correlates positively, with abortion support. New analyses of heterosexual couples also reveal that women’s and men’s religiosity uniquely decreases their romantic partner’s abortion support. Finally, noting inconsistent gender differences in abortion support, we review evidence for the impact of traditional gender role attitudes and sexism on abortion support. Our review and theoretical analyses illustrate that, rather than misogyny, benevolent sexism—the belief that women should be cherished and protected—best explains abortion opposition. We conclude that demographic and ideological variables, along with attitudes that revere women and motherhood, continue to undermine women’s interpersonal, intergroup, and societal rights

Demography and disorders of German Shepherd Dogs under primary veterinarycare in the UK

The German Shepherd Dog (GSD) has been widely used for a variety of working roles. However, concerns for the health and welfare of the GSD have been widely aired and there is evidence that breed numbers are now in decline in the UK. Accurate demographic and disorder data could assist with breeding and clinical prioritisation. The VetCompassTM Programme collects clinical data on dogs under primary veterinary care in the UK. This study included all VetCompassTM dogs under veterinary care during 2013. Demographic, mortality and clinical diagnosis data on GSDs were extracted and reported

Robust evidence for bisexual orientation among men

The question whether some men have a bisexual orientation—that is, whether they are substantially sexually aroused and attracted to both sexes—has remained controversial among both scientists and laypersons. Skeptics believe that male sexual orientation can only be homosexual or heterosexual, and that bisexual identification reflects nonsexual concerns, such as a desire to deemphasize homosexuality. Although most bisexual-identified men report that they are attracted to both men and women, self-report data cannot refute these claims. Patterns of physiological (genital) arousal to male and female erotic stimuli can provide compelling evidence for male sexual orientation. (In contrast, most women provide similar physiological responses to male and female stimuli.) We investigated whether men who self-report bisexual feelings tend to produce bisexual arousal patterns. Prior studies of this issue have been small, used potentially invalid statistical tests, and produced inconsistent findings. We combined nearly all previously published data (from eight previous studies in the United States, United Kingdom, and Canada), yielding a sample of 474 to 588 men (depending on analysis). All participants were cisgender males. Highly robust results showed that bisexual-identified men’s genital and subjective arousal patterns were more bisexual than were those who identified as exclusively heterosexual or homosexual. These findings support the view that male sexual orientation contains a range, from heterosexuality, to bisexuality, to homosexuality