Pathway-based expression profiling of benign prostatic hyperplasia and prostate cancer delineates an immunophilin molecule associated with cancer progression

Aberrant restoration of AR activity is linked with prostate tumor growth, therapeutic failures and development of castrate-resistant prostate cancer. Understanding the processes leading to ARreactivation should provide the foundation for novel avenues of drug discovery. A differential gene expression study was conducted using biopsies from CaP and BPH patients to identify the components putatively responsible for reinstating AR activity in CaP. From the set of genes upregulated in CaP, FKBP52, an AR co-chaperone, was selected for further analysis. Expression of FKBP52 was positively correlated with that of c-Myc. The functional cross-talk between c-Myc and FKBP52 was established using c-Myc specific-siRNA to LNCaP cells that resulted in reduction of FKBP52. A non-canonical E-box sequence housing a putative c-Myc binding site was detected on the FKBP4 promoter using in silico search. LNCaP cells transfected with the FKBP52 promoter cloned in pGL3 basic showed increased luciferase activity which declined considerably when the promoter-construct was co-transfected with c-Myc specific-siRNA. ChIP-PCR confirmed the binding of c-Myc with the conserved E-box located in the FKBP52 promoter. c-Myc downregulation concomitantly affected expression of FGF8. Since expression of FGF8 is controlled by AR, our study unveiled a novel functional axis between c-Myc, AR and FGF8 operating through FKBP52

Blue carbon stock of the Bangladesh Sundarban mangroves: what could be the scenario after a century?

The total blue carbon stock of the Bangladesh Sundarban mangroves was evaluated and the probable future status after a century was predicted based on the recent trend of changes in the last 30 years and implementing a hybrid model of Markov Chain and Cellular automata. At present 36.24 Tg C and 54.95 Tg C are stored in the above-ground and below-ground compartments respectively resulting in total blue carbon stock of 91.19 Tg C. According to the prediction 15.88 Tg C would be lost from this region by the year 2115. The low saline species composition classes dominated mainly by Heritiera spp. accounts for the major portion of the carbon sock at present (45.60 Tg C), while the highly saline regions stores only 14.90 Tg C. The prediction shows that after a hundred years almost 22.42 Tg C would be lost from the low saline regions accompanied by an increase of 8.20 Tg C in the high saline regions dominated mainly by Excoecaria sp. and Avicennia spp. The net carbon loss would be due to both mangrove area loss (~ 510 km2) and change in species composition leading to 58.28 Tg of potential CO2 emission within the year 2115

Impact of Rapid Urbanization on the Rates of Infection by Vibrio cholerae O1 and Enterotoxigenic Escherichia coli in Dhaka, Bangladesh

Bangladesh is a country where acute dehydrating diarrhea or cholera is common and is seen at least two times every year and additionally in natural disasters. In addition cholera cases have increased in the country, especially in urban settings such as in the capital city, Dhaka, where the number of hospitalized patients with more severe disease has tremendously increased. In the present observation, we have concentrated on determining the occurrence of diarrhoea caused by the two most common bacterial agents V. cholerae O1 and enterotoxigenic Escherichia coli (ETEC) in a densely populated, disease prone area Mirpur in Dhaka for two years from March 2008 to February 2010. Stool or rectal specimens from diarrheal patients coming to the ICDDR,B hospital from Mirpur were tested for the two bacterial pathogens. We found that V. cholerae O1 was the major bacterial pathogen and a cause of severe cholera disease in 23% of patients (2,647 of a total of 11,395 patients) from Mirpur. We surmise that cholera vaccines, as well as other public health tools that can target such high risk groups in the country, will be able to reduce the disease morbidity and the transmission of pathogens to improve the quality of life in urban settings

Pandemics, pathogenicity and changing molecular epidemiology of cholera in the era of global warming

BACKGROUND: Vibrio cholerae, a Gram-negative, non-spore forming curved rod is found in diverse aquatic ecosystems around the planet. It is classified according to its major surface antigen into around 206 serogroups, of which O1 and O139 cause epidemic cholera. A recent spatial modelling technique estimated that around 2.86 million cholera cases occur globally every year, and of them approximately 95,000 die. About 1.3 billion people are currently at risk of infection from cholera. Meta-analysis and mathematical modelling have demonstrated that due to global warming the burden of vector-borne diseases like malaria, leishmaniasis, meningococcal meningitis, viral encephalitis, dengue and chikungunya will increase in the coming years in the tropics and beyond. CHOLERA AND CLIMATE: This review offers an overview of the interplay between global warming and the pathogenicity and epidemiology of V. cholerae. Several distinctive features of cholera survival (optimal thriving at 15% salinity, 30 °C water temperature, and pH 8.5) indicate a possible role of climate change in triggering the epidemic process. Genetic exchange (ctxAB, zot, ace, cep, and orfU) between strains and transduction process allows potential emergence of new toxigenic clones. These processes are probably controlled by precise environmental signals such as optimum temperature, sunlight and osmotic conditions. Environmental influences on phytoplankton growth and chitin remineralization will be discussed alongside the interplay of poor sanitary conditions, overcrowding, improper sewage disposal and global warming in promoting the growth and transmission of this deadly disease. CONCLUSION: The development of an effective early warning system based on climate data could help to prevent and control future outbreaks. It may become possible to integrate real-time monitoring of oceanic regions, climate variability and epidemiological and demographic population dynamics to predict cholera outbreaks and support the design of cost-effective public health strategies

Multifactorial Regulation of a Hox Target Gene

Hox proteins play fundamental roles in controlling morphogenetic diversity along the anterior–posterior body axis of animals by regulating distinct sets of target genes. Within their rather broad expression domains, individual Hox proteins control cell diversification and pattern formation and consequently target gene expression in a highly localized manner, sometimes even only in a single cell. To achieve this high-regulatory specificity, it has been postulated that Hox proteins co-operate with other transcription factors to activate or repress their target genes in a highly context-specific manner in vivo. However, only a few of these factors have been identified. Here, we analyze the regulation of the cell death gene reaper (rpr) by the Hox protein Deformed (Dfd) and suggest that local activation of rpr expression in the anterior part of the maxillary segment is achieved through a combinatorial interaction of Dfd with at least eight functionally diverse transcriptional regulators on a minimal enhancer. It follows that context-dependent combinations of Hox proteins and other transcription factors on small, modular Hox response elements (HREs) could be responsible for the proper spatio-temporal expression of Hox targets. Thus, a large number of transcription factors are likely to be directly involved in Hox target gene regulation in vivo

Bioaccumulation and ecotoxicity of carbon nanotubes

Carbon nanotubes (CNT) have numerous industrial applications and may be released to the environment. In the aquatic environment, pristine or functionalized CNT have different dispersion behavior, potentially leading to different risks of exposure along the water column. Data included in this review indicate that CNT do not cross biological barriers readily. When internalized, only a minimal fraction of CNT translocate into organism body compartments. The reported CNT toxicity depends on exposure conditions, model organism, CNT-type, dispersion state and concentration. In the ecotoxicological tests, the aquatic organisms were generally found to be more sensitive than terrestrial organisms. Invertebrates were more sensitive than vertebrates. Single-walled CNT were found to be more toxic than double-/multi-walled CNT. Generally, the effect concentrations documented in literature were above current modeled average environmental concentrations. Measurement data are needed for estimation of environmental no-effect concentrations. Future studies with benchmark materials are needed to generate comparable results. Studies have to include better characterization of the starting materials, of the dispersions and of the biological fate, to obtain better knowledge of the exposure/effect relationships

Ultra high diluted arsenic reduces spore germination of Alternaria brassicicola and dark leaf spot in cauliflower

ABSTRACT A major problem in cauliflower crop is the fungus Alternaria brassicicola, which causes dark leaf spot on Brassicaceae family. The current use of copper salts in agriculture is questioned. In fact, these products present some disadvantages, connected mainly with their deposits in the soil and toxicity on plants. This work investigated the effects of arsenic treatments, in ultra high diluted form (UHD), prepared by a process of repeated dilution and succussion (shaking), through: 1) in vitro germination experiments, where spores of A. brassicicola were suspended in the treatments; 2) in planta experiments and 3) a field trial, where cauliflower plants infected by the fungus were sprayed with treatments. The results showed that ultra high dilutions of arsenic (where no more molecules of this substance are present) were effective in all the experiments, inhibiting spore germination by 60.0%, controlling fungal disease in in planta experiments (relative efficacy of 42.1%), and, in field trial, decreasing the mean infection level in cauliflower heads by 45.7% and 41.6% in artificially inoculated and naturally infected plants, respectively. This is the first study to demonstrate that ultra high dilutions effectively reduce in vitro spore germination and infection of A. brassicicola in cauliflower plants, both under controlled conditions and in the field. Our research is still very experimental, however, in light of the significant results obtained with ultra-diluted arsenic, and given that its extreme high dilution level precludes any toxicity or accumulation in the environment, the use of UHDs could be considered a potential and reliable approach for sustainable agriculture

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research