Male reproductive health and environmental xenoestrogens

EHP is a publication of the U.S. government. Publication of EHP lies in the public domain and is therefore without copyright. Research articles from EHP may be used freely; however, articles from the News section of EHP may contain photographs or figures copyrighted by other commercial organizations and individuals that may not be used without obtaining prior approval from both the EHP editors and the holder of the copyright. Use of any materials published in EHP should be acknowledged (for example, "Reproduced with permission from Environmental Health Perspectives") and a reference provided for the article from which the material was reproduced.Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.Supported by EU Contract BMH4-CT96-0314

Gynaecologists estimate and experience laparoscopic hysterectomy as more difficult compared with abdominal hysterectomy

The level of difficulty of various types of hysterectomy differs and may influence the choice of either approach. When surgeons consider one specific approach to hysterectomy as more difficult, they may be reluctant to perform this type of hysterectomy. The main objective of this study was to investigate the potential different levels of difficulty for laparoscopic and abdominal hysterectomy. Furthermore, the accuracy of estimating the level of difficulty was examined. In a randomized controlled trial between laparoscopic hysterectomy (LH) and abdominal hysterectomy (AH), gynaecologists were asked to record the preoperatively estimated and postoperatively experienced level of difficulty on a Visual Analogue Scale (VAS). Differences between LH and AH were examined and the correlation between the estimated uterine weight on bimanual palpation and the actual uterine weight was calculated. A difference on the VAS of three points or more (ΔVAS ≥ 3) was considered clinically relevant. In 72 out of 76 cases, both VAS scores were recorded. LH was estimated and experienced as significantly more difficult as compared with AH. In 13 (18%) cases, ΔVAS was ≥3, equally distributed between LH (n = 6) and AH (n = 7). Eleven of these 13 cases had a positive ΔVAS ≥3, meaning that surgery was experienced as more difficult than it was estimated. Surgeon’s estimation of uterine size correlated well with the actual uterine weight. LH is considered as more difficult than AH, which might be a reason for its slow implementation. In a large proportion of cases, gynaecologists seem to be able to estimate the level of difficulty of hysterectomy accurately

Hazardous explosive eruptions of a recharging multi-cyclic island arc caldera

Caldera-forming eruptions of silicic volcanic systems are among the most devastating events on Earth. By contrast, post-collapse volcanic activity initiating new caldera cycles is generally considered less hazardous. Formed after Santorini’s latest caldera-forming eruption of ~1600 bce, the Kameni Volcano in the southern Aegean Sea enables the eruptive evolution of a recharging multi-cyclic caldera to be reconstructed. Santorini’s eruptive record has been documented by onshore products and historical descriptions of mainly effusive eruptions dating back to 197 bce. Here we combine high-resolution seismic reflection data with cored lithologies from International Ocean Discovery Program Expedition 398 at four sites to determine the submarine architecture and volcanic history of intra-caldera deposits from Kameni. Our shore-crossing analysis reveals the deposits of a submarine explosive eruption that produced up to 3.1 km3 of pumice and ash, which we relate to a historical eruption in 726 ce. The estimated volcanic explosivity index of magnitude 5 exceeds previously considered worst-case eruptive scenarios for Santorini. Our finding that the Santorini caldera is capable of producing large explosive eruptions at an early stage in the caldera cycle implies an elevated hazard potential for the eastern Mediterranean region, and potentially for other recharging silicic calderas

A novel pancoronavirus RT-PCR assay: frequent detection of human coronavirus NL63 in children hospitalized with respiratory tract infections in Belgium

BACKGROUND: Four human coronaviruses are currently known to infect the respiratory tract: human coronaviruses OC43 (HCoV-OC43) and 229E (HCoV-229E), SARS associated coronavirus (SARS-CoV) and the recently identified human coronavirus NL63 (HCoV-NL63). In this study we explored the incidence of HCoV-NL63 infection in children diagnosed with respiratory tract infections in Belgium. METHODS: Samples from children hospitalized with respiratory diseases during the winter seasons of 2003 and 2004 were evaluated for the presence of HCoV-NL63 using a optimized pancoronavirus RT-PCR assay. RESULTS: Seven HCoV-NL63 positive samples were identified, six were collected during January/February 2003 and one at the end of February 2004. CONCLUSIONS: Our results support the notation that HCoV-NL63 can cause serious respiratory symptoms in children. Sequence analysis of the S gene showed that our isolates could be classified into two subtypes corresponding to the two prototype HCoV-NL63 sequences isolated in The Netherlands in 1988 and 2003, indicating that these two subtypes may currently be cocirculating

Rapid in vivo analysis of synthetic promoters for plant pathogen phytosensing

<p>Abstract</p> <p>Background</p> <p>We aimed to engineer transgenic plants for the purpose of early detection of plant pathogen infection, which was accomplished by employing synthetic pathogen inducible promoters fused to reporter genes for altered phenotypes in response to the pathogen infection. Toward this end, a number of synthetic promoters consisting of inducible regulatory elements fused to a red fluorescent protein (RFP) reporter were constructed for use in phytosensing.</p> <p>Results</p> <p>For rapid analysis, an <it>Agrobacterium</it>-mediated transient expression assay was evaluated, then utilized to assess the inducibility of each synthetic promoter construct <it>in vivo</it>. Tobacco (<it>Nicotiana tabacum </it>cv. Xanthi) leaves were infiltrated with <it>Agrobacterium </it>harboring the individual synthetic promoter-reporter constructs. The infiltrated tobacco leaves were re-infiltrated with biotic (bacterial pathogens) or abiotic (plant defense signal molecules salicylic acid, ethylene and methyl jasmonate) agents 24 and 48 hours after initial agroinfiltration, followed by RFP measurements at relevant time points after treatment. These analyses indicated that the synthetic promoter constructs were capable of conferring the inducibility of the RFP reporter in response to appropriate phytohormones and bacterial pathogens, accordingly.</p> <p>Conclusions</p> <p>These observations demonstrate that the <it>Agrobacterium</it>-mediated transient expression is an efficient method for <it>in vivo </it>assays of promoter constructs in less than one week. Our results provide the opportunity to gain further insights into the versatility of the expression system as a potential tool for high-throughput <it>in planta </it>expression screening prior to generating stably transgenic plants for pathogen phytosensing. This system could also be utilized for temporary phytosensing; e.g., not requiring stably transgenic plants.</p

High-throughput gene and SNP discovery in Eucalyptus grandis, an uncharacterized genome

<p>Abstract</p> <p>Background</p> <p>Benefits from high-throughput sequencing using 454 pyrosequencing technology may be most apparent for species with high societal or economic value but few genomic resources. Rapid means of gene sequence and SNP discovery using this novel sequencing technology provide a set of baseline tools for genome-level research. However, it is questionable how effective the sequencing of large numbers of short reads for species with essentially no prior gene sequence information will support contig assemblies and sequence annotation.</p> <p>Results</p> <p>With the purpose of generating the first broad survey of gene sequences in <it>Eucalyptus grandis</it>, the most widely planted hardwood tree species, we used 454 technology to sequence and assemble 148 Mbp of expressed sequences (EST). EST sequences were generated from a normalized cDNA pool comprised of multiple tissues and genotypes, promoting discovery of homologues to almost half of <it>Arabidopsis</it> genes, and a comprehensive survey of allelic variation in the transcriptome. By aligning the sequencing reads from multiple genotypes we detected 23,742 SNPs, 83% of which were validated in a sample. Genome-wide nucleotide diversity was estimated for 2,392 contigs using a modified theta (θ) parameter, adapted for measuring genetic diversity from polymorphisms detected by randomly sequencing a multi-genotype cDNA pool. Diversity estimates in non-synonymous nucleotides were on average 4x smaller than in synonymous, suggesting purifying selection. Non-synonymous to synonymous substitutions (Ka/Ks) among 2,001 contigs averaged 0.30 and was skewed to the right, further supporting that most genes are under purifying selection. Comparison of these estimates among contigs identified major functional classes of genes under purifying and diversifying selection in agreement with previous researches.</p> <p>Conclusion</p> <p>In providing an abundance of foundational transcript sequences where limited prior genomic information existed, this work created part of the foundation for the annotation of the <it>E. grandis </it>genome that is being sequenced by the US Department of Energy. In addition we demonstrated that SNPs sampled in large-scale with 454 pyrosequencing can be used to detect evolutionary signatures among genes, providing one of the first genome-wide assessments of nucleotide diversity and Ka/Ks for a non-model plant species.</p

Transcriptional Regulation of Ribosome Components Are Determined by Stress According to Cellular Compartments in Arabidopsis thaliana

Plants have to coordinate eukaryotic ribosomes (cytoribosomes) and prokaryotic ribosomes (plastoribosomes and mitoribosomes) production to balance cellular protein synthesis in response to environmental variations. We identified 429 genes encoding potential ribosomal proteins (RP) in Arabidopsis thaliana. Because cytoribosome proteins are encoded by small nuclear gene families, plastid RP by nuclear and plastid genes and mitochondrial RP by nuclear and mitochondrial genes, several transcriptional pathways were attempted to control ribosome amounts. Examining two independent genomic expression datasets, we found two groups of RP genes showing very different and specific expression patterns in response to environmental stress. The first group represents the nuclear genes coding for plastid RP whereas the second group is composed of a subset of cytoribosome genes coding for RP isoforms. By contrast, the other cytoribosome genes and mitochondrial RP genes show less constraint in their response to stress conditions. The two subsets of cytoribosome genes code for different RP isoforms. During stress, the response of the intensively regulated subset leads to dramatic variation in ribosome diversity. Most of RP genes have same promoter structure with two motifs at conserved positions. The stress-response of the nuclear genes coding plastid RP is related with the absence of an interstitial telomere motif known as telo box in their promoters. We proposed a model for the “ribosome code” that influences the ribosome biogenesis by three main transcriptional pathways. The first pathway controls the basal program of cytoribosome and mitoribosome biogenesis. The second pathway involves a subset of cytoRP genes that are co-regulated under stress condition. The third independent pathway is devoted to the control of plastoribosome biosynthesis by regulating both nuclear and plastid genes

Digital strategies to a local cultural tourism development: Project e-Carnide

Digital humanities and smart economy strategies are being seen as an important link between tourism and cultural heritage, as they may contribute to differentiate the audiences and to provide different approaches. Carnide is a peripheral neighbourhood of Lisbon with an elderly population, visible traces of rurality, and strong cultural and religious traditions. The academic project e-Carnide concerns its tangible and intangible cultural heritage and the data dissemination through a website and a mobile app, with textual and visual information. The project aims to analyse the impact of technological solutions on cultural tourism development in a sub-region, involving interdisciplinary research in heritage, history of art, ethnography, design communication and software engineering and the collaboration between the university and local residents in a dynamic and innovative way. Framed by a theoretical approach about the role of smart economy for the cultural tourism development in peripheral areas, this paper focuses on a case study, dealing with documents, interviews and observations, in order to understand how the e-Carnide project evolves. The study comprises an analysis about the strengths, weaknesses, opportunities and threats (SWOT analysis) of the project in view to realize its social and cultural implications and to appreciate how it can be applied in other similar and enlarged projects. Results of the research indicates that the new technological strategies can promote the involvement of the population in the knowledge of its own heritage as a factor of cultural and creative tourism development centred on an authentic and immersive experience of the places

Expression of cell cycle proteins in male breast carcinoma

<p>Abstract</p> <p>Introduction</p> <p>Male breast cancer (MBC) is a rare, yet potentially aggressive disease. Although literature regarding female breast cancer (FBC) is extensive, little is known about the etiopathogenesis of male breast cancer. Studies from our laboratory show that MBCs have a distinct immunophenotypic profile, suggesting that the etiopathogenesis of MBC is different from FBCs. The aim of this study was to evaluate and correlate the immunohistochemical expression of cell cycle proteins in male breast carcinoma to significant clinico-biological endpoints.</p> <p>Methods</p> <p>75 cases of MBC were identified using the records of the Saskatchewan Cancer Agency over 26 years (1970-1996). Cases were reviewed and analyzed for the immunohistochemical expression of PCNA, Ki67, p27, p16, p57, p21, cyclin-D1 and c-myc and correlated to clinico-biological endpoints of tumor size, node status, stage of the disease, and disease free survival (DFS).</p> <p>Results</p> <p>Decreased DFS was observed in the majority of tumors that overexpressed PCNA (98%, p = 0.004). The overexpression of PCNA was inversely correlated to the expression of Ki67 which was predominantly negative (78.3%). Cyclin D1 was overexpressed in 83.7% of cases. Cyclin D1 positive tumors were smaller than 2 cm (55.6%, p = 0.005), had a low incidence of lymph node metastasis (38.2%, p = 0.04) and were associated with increased DFS of >150 months (p = 0.04). Overexpression of c-myc (90%) was linked with a higher incidence of node negativity (58.3%, p = 0.006) and increased DFS (p = 0.04). p27 over expression was associated with decreased lymph node metastasis (p = 0.04). P21 and p57 positive tumors were related to decreased DFS (p = 0.04). Though p16 was overexpressed in 76.6%, this did not reach statistical significance with DFS (p = 0.06) or nodal status (p = 0.07).</p> <p>Conclusion</p> <p>Aberrant cell cycle protein expression supports our view that these are important pathways involved in the etiopathogenesis of MBC. Tumors with overexpression of Cyclin D1 and c-myc had better outcomes, in contrast to tumors with overexpression of p21, p57, and PCNA with significantly worse outcomes. P27 appears to be a predictive marker for lymph nodal status. Such observation strongly suggests that dysregulation of cell cycle proteins may play a unique role in the initiation and progression of disease in male breast cancer. Such findings open up new avenues for the treatment of MBC as a suitable candidate for novel CDK-based anticancer therapies in the future.</p