Network Analysis of Breast Cancer Progression and Reversal Using a Tree-Evolving Network Algorithm

The HMT3522 progression series of human breast cells have been used to discover how tissue architecture, microenvironment and signaling molecules affect breast cell growth and behaviors. However, much remains to be elucidated about malignant and phenotypic reversion behaviors of the HMT3522-T4-2 cells of this series. We employed a "pan-cell-state" strategy, and analyzed jointly microarray profiles obtained from different state-specific cell populations from this progression and reversion model of the breast cells using a tree-lineage multi-network inference algorithm, Treegl. We found that different breast cell states contain distinct gene networks. The network specific to non-malignant HMT3522-S1 cells is dominated by genes involved in normal processes, whereas the T4-2-specific network is enriched with cancer-related genes. The networks specific to various conditions of the reverted T4-2 cells are enriched with pathways suggestive of compensatory effects, consistent with clinical data showing patient resistance to anticancer drugs. We validated the findings using an external dataset, and showed that aberrant expression values of certain hubs in the identified networks are associated with poor clinical outcomes. Thus, analysis of various reversion conditions (including non-reverted) of HMT3522 cells using Treegl can be a good model system to study drug effects on breast cancer. © 2014 Parikh et al

Establishing comprehensive oral assessments for children with safeguarding concerns.

The dental profession is well placed to contribute important information in child protection cases but no previous research has been reported that assesses the volume or impact of this information. Comprehensive oral assessment clinics were introduced and established as an integral part of comprehensive medical assessments for children with welfare concerns in Greater Glasgow and Clyde. An assessment protocol and standardised paperwork for comprehensive oral assessments were developed to enhance information sharing and patient access to appropriate care. Two cases are presented and discussed to demonstrate the value of dental input

Actinopolyspora algeriensis sp. nov., a novel halophilic actinomycete isolated from a Saharan soil

A halophilic actinomycete strain designated H19T, was isolated from a Saharan soil in the Bamendil region (Ouargla province, South Algeria) and was characterized taxonomically by using a polyphasic approach. The morphological and chemotaxonomic characteristics of the strain were consistent with those of members of the genus Actinopolyspora, and 16S rRNA gene sequence analysis confirmed that strain H19T was a novel species of the genus Actinopolyspora. DNA–DNA hybridization value between strain H19T and the nearest Actinopolyspora species, A. halophila, was clearly below the 70 % threshold. The genotypic and phenotypic data showed that the organism represents a novel species of the genus Actinopolyspora for which the name Actinopolyspora algeriensis sp. nov. is proposed, with the type strain H19T (= DSM 45476T = CCUG 62415T)

Helium reionization and the thermal proximity effect

We examine the temperature structure of the intergalactic medium IGM) surounding a hard radiation source, such as a Quasi-Stellar Object (QSO), as it responds to the onset of helium reionization by the source. We model the reionization using a radiative transfer (RT) code coupled to a particle-mesh (PM) N-body code. Neutral hydrogen and helium are initially ionized by a starburst spectrum, which is allowed to gradually evolve into a power law spectrum (fnu ~ nu^(-0.5)). Multiple simulations were performed with different times for the onset and dominance of the hard spectrum, with onset redshifts ranging from z = 3.5 to 5.5. The source is placed in a high-density region to mimic the expected local environment of a QSO. Simulations with the source placed in a low-density environment were also performed as control cases to explore the role of the environment on the properties of the surrounding IGM. We find in both cases that the IGM temperature within the HeIII region produced exceeds the IGM temperature before full helium reionization, resulting in a "thermal proximity effect", but that the temperature in the HeIII region increases systematically with distance from the source. With time the temperature relaxes with a reduced spread as a function of impact parameter along neighbouring lines of sight, although the trend continues to persist until z = 2. Such a trend could be detected using the widths of intervening metal absorption systems using high resolution, high signal-to-noise ratio spectra.Comment: 17 pages, 12 figures, for publication in MNRA

The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission

1Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this report, we analyzed a critical component of the GSH biosynthesis pathway using reverse genetics. Plasmodium berghei parasites lacking expression of gamma-glutamylcysteine synthetase (γ-GCS), the rate limiting enzyme in de novo synthesis of GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, that γ-GCS is not essential for blood stage development. Despite a significant reduction in GSH levels, blood stage forms of pbggcs− parasites showed only a defect in growth as compared to wild type. In contrast, a dramatic effect on development of the parasites in the mosquito was observed. Infection of mosquitoes with pbggcs− parasites resulted in reduced numbers of stunted oocysts that did not produce sporozoites. These results have important implications for the design of drugs aiming at interfering with the GSH redox-system in blood stages and demonstrate that de novo synthesis of GSH is pivotal for development of Plasmodium in the mosquito

Interface modification of clay and graphene platelets reinforced epoxy nanocomposites: a comparative study

The interface between the matrix phase and dispersed phase of a composite plays a critical role in influencing its properties. However, the intricate mecha-nisms of interface are not fully understood, and polymer nanocomposites are no exception. This study compares the fabrication, morphology, and mechanical and thermal properties of epoxy nanocomposites tuned by clay layers (denoted as m-clay) and graphene platelets (denoted as m-GP). It was found that a chemical modification, layer expansion and dispersion of filler within the epoxy matrix resulted in an improved interface between the filler mate-rial and epoxy matrix. This was confirmed by Fourier transform infrared spectroscopy and transmission electron microscope. The enhanced interface led to improved mechanical properties (i.e. stiffness modulus, fracture toughness) and higher glass transition temperatures (Tg) compared with neat epoxy. At 4 wt% m-GP, the critical strain energy release rate G1c of neat epoxy improved by 240 % from 179.1 to 608.6 J/m2 and Tg increased from 93.7 to 106.4 �C. In contrast to m-clay, which at 4 wt%, only improved the G1c by 45 % and Tg by 7.1 %. The higher level of improvement offered by m-GP is attributed to the strong interaction of graphene sheets with epoxy because the covalent bonds between the carbon atoms of graphene sheets are much stronger than silicon-based clay

Effect of peri-implant mucosal thickness on esthetic outcomes and the efficacy of soft tissue augmentation procedures: Consensus report of group 2 of the SEPA/DGI/OF workshop

OBJECTIVES: The aim of this study was to comprehensively assess the literature in terms of the effect of peri‐implant mucosal thickness on esthetic outcomes and the efficacy of soft tissue augmentation procedures to increase the mucosal thickness with autogenous grafts or soft tissue substitutes. MATERIAL AND METHODS: Two systematic reviews (SR) were performed prior to the consensus meeting to assess the following questions. Review 1, focused question: In systemically healthy patients with an implant‐supported fixed prosthesis, what is the influence of thin as compared to thick peri‐implant mucosa on esthetic outcomes? Review 2, focused question 1: In systemically healthy humans with at least one dental implant (immediate or staged implant), what is the efficacy of connective tissue graft (CTG), as compared to absence of a soft tissue grafting procedure, in terms of gain in peri‐implant soft tissue thickness (STT) reported by randomized controlled clinical trials (RCTs) or controlled clinical trials (CCTs)? Review 2, focused question 2: In systemically healthy humans with at least one dental implant (immediate or staged implant), what is the efficacy of CTG, as compared to soft tissue substitutes, in terms of gain in peri‐implant STT reported by RCTs or CCTs? The outcomes of the two SRs, the consensus statements, the clinical implications, and the research recommendations were discussed and subsequently approved at the consensus meeting during the group and plenary sessions. CONCLUSIONS: There was a tendency of superior esthetic outcomes in the presence of a thick mucosa. The connective tissue graft remains the standard of care in terms of increasing mucosa thickness

Cranial osteopathy: its fate seems clear

BACKGROUND: According to the original model of cranial osteopathy, intrinsic rhythmic movements of the human brain cause rhythmic fluctuations of cerebrospinal fluid and specific relational changes among dural membranes, cranial bones, and the sacrum. Practitioners believe they can palpably modify parameters of this mechanism to a patient's health advantage. DISCUSSION: This treatment regime lacks a biologically plausible mechanism, shows no diagnostic reliability, and offers little hope that any direct clinical effect will ever be shown. In spite of almost uniformly negative research findings, "cranial" methods remain popular with many practitioners and patients. SUMMARY: Until outcome studies show that these techniques produce a direct and positive clinical effect, they should be dropped from all academic curricula; insurance companies should stop paying for them; and patients should invest their time, money, and health elsewhere

The Relationship Between HR Practices and Firm Performance: Examining Causal Order

Significant research attention has been devoted to examining the relationship between HR practices and firm performance, and the research support has assumed HR as the causal variable. Using data from 45 business units (with 62 data points), this study examines how measures of HR practices correlate with past, concurrent, and future operational performance measures. The results indicate that correlations with performance measures at all three times are both high and invariant, and that controlling for past or concurrent performance virtually eliminates the correlation of HR with future performance. Implications are discussed