Regional assessment of articular cartilage gene expression and small proteoglycan metabolism in an animal model of osteoarthritis

Osteoarthritis (OA), the commonest form of arthritis and a major cause of morbidity, is characterized by progressive degeneration of the articular cartilage. Along with increased production and activation of degradative enzymes, altered synthesis of cartilage matrix molecules and growth factors by resident chondrocytes is believed to play a central role in this pathological process. We used an ovine meniscectomy model of OA to evaluate changes in chondrocyte expression of types I, II and III collagen; aggrecan; the small leucine-rich proteoglycans (SLRPs) biglycan, decorin, lumican and fibromodulin; transforming growth factor-β; and connective tissue growth factor. Changes were evaluated separately in the medial and lateral tibial plateaux, and were confirmed for selected molecules using immunohistochemistry and Western blotting. Significant changes in mRNA levels were confined to the lateral compartment, where active cartilage degeneration was observed. In this region there was significant upregulation in expession of types I, II and III collagen, aggrecan, biglycan and lumican, concomitant with downregulation of decorin and connective tissue growth factor. The increases in type I and III collagen mRNA were accompanied by increased immunostaining for these proteins in cartilage. The upregulated lumican expression in degenerative cartilage was associated with increased lumican core protein deficient in keratan sulphate side-chains. Furthermore, there was evidence of significant fragmentation of SLRPs in both normal and arthritic tissue, with specific catabolites of biglycan and fibromodulin identified only in the cartilage from meniscectomized joints. This study highlights the focal nature of the degenerative changes that occur in OA cartilage and suggests that altered synthesis and proteolysis of SLRPs may play an important role in cartilage destruction in arthritis

Strategies to optimize the impact of nutritional surveys and epidemiological studies

The development of nutrition and health guidelines and policies requires reliable scientific information. Unfortunately, theoretical considerations and empirical evidence indicate that a large percentage of science-based claims rely on studies that fail to replicate. The session "Strategies to Optimize the Impact of Nutrition Surveys and Epidemiological Studies" focused on the elements of design, interpretation, and communication of nutritional surveys and epidemiological studies to enhance and encourage the production of reliable, objective evidence for use in developing dietary guidance for the public. The speakers called for more transparency of research, raw data, consistent data-staging techniques, and improved data analysis. New approaches to collecting data are urgently needed to increase the credibility and utility of findings from nutrition epidemiological studies. Such studies are critical for furthering our knowledge and understanding of the effects of diet on health

Near-island biological hotspots in barren ocean basins

Phytoplankton production drives marine ecosystem trophic-structure and global fisheries yields. Phytoplankton biomass is particularly influential near coral reef islands and atolls that span the oligotrophic tropical oceans. The paradoxical enhancement in phytoplankton near an island-reef ecosystem—Island Mass Effect (IME)—was first documented 60 years ago, yet much remains unknown about the prevalence and drivers of this ecologically important phenomenon. Here we provide the first basin-scale investigation of IME. We show that IME is a near-ubiquitous feature among a majority (91%) of coral reef ecosystems surveyed, creating near-island ‘hotspots' of phytoplankton biomass throughout the upper water column. Variations in IME strength are governed by geomorphic type (atoll vs island), bathymetric slope, reef area and local human impacts (for example, human-derived nutrient input). These ocean oases increase nearshore phytoplankton biomass by up to 86% over oceanic conditions, providing basal energetic resources to higher trophic levels that support subsistence-based human populations

Sex and sport: chlamydia screening in rural sporting clubs

BACKGROUND: Chlamydia trachomatis is the most common notifiable disease in Australia, mainly affecting those aged 15 to 29 years. Testing rates are low in Australia and considerably lower in rural areas, with access and confidentiality of sexual health services being problematic in rural and regional areas. This study aimed to determine the feasibility of establishing a pilot chlamydia testing outreach program among 16-25 year old males and females in rural Victoria (Australia) undertaken at local sporting clubs and to determine the prevalence of chlamydia and acceptability of the program in this population. METHODS: We aimed to recruit young people from the Loddon Mallee region of Victoria, Australia between May and September 2007. After a night of sporting practice, participants provided a first pass urine sample, completed a brief questionnaire regarding risk taking behaviour and were then provided with condoms and health promotion materials about sexually transmitted infections (STIs). Those positive for chlamydia were managed by telephone consultation with a practitioner from Melbourne Sexual Health Centre. RESULTS: A total of 709 young people participated (77% male, 23% female), 77% being sexually active. All provided a urine sample and completed the questionnaire. Participation rate on recruitment nights was over 95%. Overall chlamydia prevalence in those sexually active was 5.1% (95%CI: 3.4-7.3), 7.4% in females (95%CI: 3.5-13.6) and 4.5% in males (95%CI: 2.7-6.9). CONCLUSION: Sporting clubs represent a feasible, acceptable and innovative community based setting to screen, treat and educate young people in a rural and regional setting, especially for males

Nuclear genome of Bulinus truncatus, an intermediate host of the carcinogenic human blood fluke Schistosoma haematobium

Some snails act as intermediate hosts (vectors) for parasitic flatworms (flukes) that cause neglected tropical diseases, such as schistosomiases. Schistosoma haematobium is a blood fluke that causes urogenital schistosomiasis and induces bladder cancer and increased risk of HIV infection. Understanding the molecular biology of the snail and its relationship with the parasite could guide development of an intervention approach that interrupts transmission. Here, we define the genome for a key intermediate host of S. haematobium—called Bulinus truncatus—and explore protein groups inferred to play an integral role in the snail’s biology and its relationship with the schistosome parasite. Bu. truncatus shared many orthologous protein groups with Biomphalaria glabrata—the key snail vector for S. mansoni which causes hepatointestinal schistosomiasis in people. Conspicuous were expansions in signalling and membrane trafficking proteins, peptidases and their inhibitors as well as gene families linked to immune response regulation, such as a large repertoire of lectin-like molecules. This work provides a sound basis for further studies of snail-parasite interactions in the search for targets to block schistosomiasis transmission

Bridging Alone: Religious Conservatism, Marital Homogamy, and Voluntary Association Membership

This study characterizes social insularity of religiously conservative American married couples by examining patterns of voluntary associationmembership. Constructing a dataset of 3938 marital dyads from the second wave of the National Survey of Families and Households, the author investigates whether conservative religious homogamy encourages membership in religious voluntary groups and discourages membership in secular voluntary groups. Results indicate that couples’ shared affiliation with conservative denominations, paired with beliefs in biblical authority and inerrancy, increases the likelihood of religious group membership for husbands and wives and reduces the likelihood of secular group membership for wives, but not for husbands. The social insularity of conservative religious groups appears to be reinforced by homogamy—particularly by wives who share faith with husbands

USP6 oncogene promotes Wnt signaling by deubiquitylating Frizzleds

Ubiquitin-specific protease 6 (USP6) is a deubiquitylase that is overexpressed by chromosome translocation in two human neoplasms, aneurysmal bone cyst and nodular fasciitis. The relevant substrates of this ubiquitin-specific protease are not clear. Here, we identify the Wnt receptor Frizzled (Fzd) as a key target of the USP6 oncogene. Increased expression of USP6 increases the membrane abundance of Fzd, and hence increases cellular sensitivity to Wnts. USP6 opposes the activity of the ubiquitin ligase and tumor suppressor ring finger protein 43 (RNF43). This study identifies a new mechanism for pathological Wnt pathway activation in human disease and suggests a new approach to regulate Wnt activity therapeutically

Chromosome-level genome of Schistosoma haematobium underpins genome-wide explorations of molecular variation.

Urogenital schistosomiasis is caused by the blood fluke Schistosoma haematobium and is one of the most neglected tropical diseases worldwide, afflicting \u3e 100 million people. It is characterised by granulomata, fibrosis and calcification in urogenital tissues, and can lead to increased susceptibility to HIV/AIDS and squamous cell carcinoma of the bladder. To complement available treatment programs and break the transmission of disease, sound knowledge and understanding of the biology and ecology of S. haematobium is required. Hybridisation/introgression events and molecular variation among members of the S. haematobium-group might effect important biological and/or disease traits as well as the morbidity of disease and the effectiveness of control programs including mass drug administration. Here we report the first chromosome-contiguous genome for a well-defined laboratory line of this blood fluke. An exploration of this genome using transcriptomic data for all key developmental stages allowed us to refine gene models (including non-coding elements) and annotations, discover \u27new\u27 genes and transcription profiles for these stages, likely linked to development and/or pathogenesis. Molecular variation within S. haematobium among some geographical locations in Africa revealed unique genomic \u27signatures\u27 that matched species other than S. haematobium, indicating the occurrence of introgression events. The present reference genome (designated Shae.V3) and the findings from this study solidly underpin future functional genomic and molecular investigations of S. haematobium and accelerate systematic, large-scale population genomics investigations, with a focus on improved and sustained control of urogenital schistosomiasis

Identification of a small molecule yeast TORC1 inhibitor with a flow cytometry-based multiplex screen

TOR (target of rapamycin) is a serine/threonine kinase, evolutionarily conserved from yeast to human, which functions as a fundamental controller of cell growth. The moderate clinical benefit of rapamycin in mTOR-based therapy of many cancers favors the development of new TOR inhibitors. Here we report a high throughput flow cytometry multiplexed screen using five GFPtagged yeast clones that represent the readouts of four branches of the TORC1 signaling pathway in budding yeast. Each GFP-tagged clone was differentially color-coded and the GFP signal of each clone was measured simultaneously by flow cytometry, which allows rapid prioritization of compounds that likely act through direct modulation of TORC1 or proximal signaling components. A total of 255 compounds were confirmed in dose-response analysis to alter GFP expression in one or more clones. To validate the concept of the high throughput screen, we have characterized CID 3528206, a small molecule most likely to act on TORC1 as it alters GFP expression in all five GFP clones in an analogous manner to rapamycin. We have shown that CID 3528206 inhibited yeast cell growth, and that CID 3528206 inhibited TORC1 activity both in vitro and in vivo with EC50s of 150 nM and 3.9 μM, respectively. The results of microarray analysis and yeast GFP collection screen further support the notion that CID 3528206 and rapamycin modulate similar cellular pathways. Together, these results indicate that the HTS has identified a potentially useful small molecule for further development of TOR inhibitors