Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

Regulation of human intestinal T-cell responses by type 1 interferon-STAT1 signaling is disrupted in inflammatory bowel disease

This work was supported by a research fellowship grant from the Crohn’s and Colitis in Childhood Research Association (CICRA) and a small project grant from Crohn’s and Colitis UK (CCUK). We would like to acknowledge Professor Ian Sanderson, who helped with the initial design of this work, and provided important support throughout. We would also like to thank Dr Gary Warne for his advice and assistance in the use of the sorting by flow cytometry. We would also like to thank Dr Raj Lahiri and Professor Graham Foster for the kind gift of the primers for the ISGs (2’5’ OAS and MxA)

Classification of behaviour in housed dairy cows using an accelerometer-based activity monitoring system

Background Advances in bio-telemetry technology have made it possible to automatically monitor and classify behavioural activities in many animals, including domesticated species such as dairy cows. Automated behavioural classification has the potential to improve health and welfare monitoring processes as part of a Precision Livestock Farming approach. Recent studies have used accelerometers and pedometers to classify behavioural activities in dairy cows, but such approaches often cannot discriminate accurately between biologically important behaviours such as feeding, lying and standing or transition events between lying and standing. In this study we develop a decision-tree algorithm that uses tri-axial accelerometer data from a neck-mounted sensor to both classify biologically important behaviour in dairy cows and to detect transition events between lying and standing. Results Data were collected from six dairy cows that were monitored continuously for 36 h. Direct visual observations of each cow were used to validate the algorithm. Results show that the decision-tree algorithm is able to accurately classify three types of biologically relevant behaviours: lying (77.42 % sensitivity, 98.63 % precision), standing (88.00 % sensitivity, 55.00 % precision), and feeding (98.78 % sensitivity, 93.10 % precision). Transitions between standing and lying were also detected accurately with an average sensitivity of 96.45 % and an average precision of 87.50 %. The sensitivity and precision of the decision-tree algorithm matches the performance of more computationally intensive algorithms such as hidden Markov models and support vector machines. Conclusions Biologically important behavioural activities in housed dairy cows can be classified accurately using a simple decision-tree algorithm applied to data collected from a neck-mounted tri-axial accelerometer. The algorithm could form part of a real-time behavioural monitoring system in order to automatically detect dairy cow health and welfare status

Effects of university affiliation and “school spirit” on color preferences: Berkeley versus Stanford

The ecological valence theory (EVT) posits that preference for a color is determined by people’s average affective response to everything associated with it (Palmer & Schloss, Proceedings of the National Academy of Sciences, 107, 8877–8882, 2010). The EVT thus implies the existence of sociocultural effects: Color preference should increase with positive feelings (or decrease with negative feelings) toward an institution strongly associated with a color. We tested this prediction by measuring undergraduates’ color preferences at two rival universities, Berkeley and Stanford, to determine whether students liked their university’s colors better than their rivals did. Students not only preferred their own colors more than their rivals did, but the degree of their preference increased with self-rated positive affect (“school spirit”) for their university. These results support the EVT’s claim that color preference is caused by learned affective responses to associated objects and institutions, because it is unlikely that students choose their university or develop their degree of school spirit on the basis of preexisting color preferences

Transcriptional Activation of c3 and hsp70 as Part of the Immune Response of Acropora millepora to Bacterial Challenges

The impact of disease outbreaks on coral physiology represents an increasing concern for the fitness and resilience of reef ecosystems. Predicting the tolerance of corals to disease relies on an understanding of the coral immune response to pathogenic interactions. This study explored the transcriptional response of two putative immune genes (c3 and c-type lectin) and one stress response gene (hsp70) in the reef building coral, Acropora millepora challenged for 48 hours with bacterial strains, Vibrio coralliilyticus and Alteromonas sp. at concentrations of 106 cells ml-1. Coral fragments challenged with V. coralliilyticus appeared healthy while fragments challenged with Alteromonas sp. showed signs of tissue lesions after 48 hr. Coral-associated bacterial community profiles assessed using denaturing gradient gel electrophoresis changed after challenge by both bacterial strains with the Alteromonas sp. treatment demonstrating the greatest community shift. Transcriptional profiles of c3 and hsp70 increased at 24 hours and correlated with disease signs in the Alteromonas sp. treatment. The expression of hsp70 also showed a significant increase in V. coralliilyticus inoculated corals at 24 h suggesting that even in the absence of disease signs, the microbial inoculum activated a stress response in the coral. C-type lectin did not show a response to any of the bacterial treatments. Increase in gene expression of c3 and hsp70 in corals showing signs of disease indicates their potential involvement in immune and stress response to microbial challenges

Immunological mechanism of action and clinical profile of disease-modifying treatments in multiple sclerosis.

Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the central nervous system (CNS). MS is considered to be an immune-mediated disease, and the presence of autoreactive peripheral lymphocytes in CNS compartments is believed to be critical in the process of demyelination and tissue damage in MS. Although MS is not currently a curable disease, several disease-modifying therapies (DMTs) are now available, or are in development. These DMTs are all thought to primarily suppress autoimmune activity within the CNS. Each therapy has its own mechanism of action (MoA) and, as a consequence, each has a different efficacy and safety profile. Neurologists can now select therapies on a more individual, patient-tailored basis, with the aim of maximizing potential for long-term efficacy without interruptions in treatment. The MoA and clinical profile of MS therapies are important considerations when making that choice or when switching therapies due to suboptimal disease response. This article therefore reviews the known and putative immunological MoAs alongside a summary of the clinical profile of therapies approved for relapsing forms of MS, and those in late-stage development, based on published data from pivotal randomized, controlled trials

Intrauterine exposures, pregnancy estrogens and breast cancer risk: where do we currently stand?

Since 1990, when a hypothesis on intrauterine influences on breast cancer risk was published, several studies have provided supportive, indirect evidence by documenting associations of birth weight and other correlates of the prenatal environment with breast cancer risk in offspring. Recent results from a unique cohort of women with documented exposure to diethylstilbestrol in utero have provided direct evidence in support of a potential role of pregnancy oestrogens on breast cancer risk in offspring

The textual characteristics of traditional and Open Access scientific journals are similar

<p>Abstract</p> <p>Background</p> <p>Recent years have seen an increased amount of natural language processing (NLP) work on full text biomedical journal publications. Much of this work is done with Open Access journal articles. Such work assumes that Open Access articles are representative of biomedical publications in general and that methods developed for analysis of Open Access full text publications will generalize to the biomedical literature as a whole. If this assumption is wrong, the cost to the community will be large, including not just wasted resources, but also flawed science. This paper examines that assumption.</p> <p>Results</p> <p>We collected two sets of documents, one consisting only of Open Access publications and the other consisting only of traditional journal publications. We examined them for differences in surface linguistic structures that have obvious consequences for the ease or difficulty of natural language processing and for differences in semantic content as reflected in lexical items. Regarding surface linguistic structures, we examined the incidence of conjunctions, negation, passives, and pronominal anaphora, and found that the two collections did not differ. We also examined the distribution of sentence lengths and found that both collections were characterized by the same mode. Regarding lexical items, we found that the Kullback-Leibler divergence between the two collections was low, and was lower than the divergence between either collection and a reference corpus. Where small differences did exist, log likelihood analysis showed that they were primarily in the area of formatting and in specific named entities.</p> <p>Conclusion</p> <p>We did not find structural or semantic differences between the Open Access and traditional journal collections.</p