Telomere length and risk of melanoma,squamous cell carcinoma,and basal cell carcinoma

Background: Telomeres help maintain chromosomal structure and may influence tumorigenesis. We examined the association between telomere length and skin cancer in a clinic-based case-control study of 198 melanoma cases, 136 squamous cell carcinoma (SCC) cases, 185 basal cell carcinoma (BCC) cases, and 372 healthy controls. Methods: Cases were histologically confirmed patients treated at the Moffitt Cancer Center and University of South Florida Dermatology Clinic in Tampa, FL. Controls self-reported no history of cancer and underwent a skin cancer screening exam at study enrollment to rule out the presence of skin cancer. Quantitative real time PCR was used to measure telomere length in peripheral blood samples. Results: Melanoma patients had longer telomeres than controls (odds ratio (OR) = 3.75; 95% confidence interval (CI): 2.02–6.94 for highest versus lowest tertile) (P for trend = <0.0001). In contrast, longer telomere length was significantly inversely associated with SCC (OR = 0.01; 95% CI: 0.00–0.05 for highest versus lowest tertile) (P for trend = <0.0001) and BCC (OR = 0.10; 95% CI: 0.06–0.19 for highest versus lowest tertile) (P for trend = <0.0001). Conclusion: Telomere length may be involved in the development of skin cancer, although the effect on cancer risk differs for melanoma and non-melanoma carcinomas. Our findings suggest that long telomere length is positively associated with melanoma while inversely associated with SCC and BCC.     

Hereditary nonpolyposis colorectal cancer family members' perceptions about the duty to inform and health professionals' role in disseminating genetic information

This study's aim was to ascertain hereditary nonpolyposis colorectal cancer (HNPCC) families' views on the duty to inform with particular focus on the role of health professionals in disseminating familial genetic information. Eighty members of 16 families with a clinical or molecular diagnosis of HNPCC completed qualitative interviews regarding views on family members' right to know and who should disseminate familial genetic information. Most indicated that everyone in the family should know about the presence of a mutation in the family, with family members themselves being the preferable informant, supported by health professionals who were seen as helpful in overcoming barriers. All but one respondent indicated that if a parent did not test and presumably did not inform his/her child about the family mutation, the child should be informed by other family members or by a health professional. Many were attuned to confidentiality concerns, but judged them to be outweighed by the importance of family members knowing about the mutation and undertaking proper surveillance. Respondents were more private about the disclosure of individual results to other family members, clearly distinguishing personal results from familial genetic information. These families with a hereditary colon cancer syndrome favor open sharing of genetic information within the family, and desire the supportive involvement of health care professionals in disseminating genetic information.     

The Ovicidal,Larvacidal and Adulticidal Properties of 5,5′-Dimethyl-2,2′-Bipyridyl against Drosophila melanogaster

Insecticide resistance has limited the number of available chemical options for insect pest control. Hence there is a need for new chemistries with novel modes of action. Here we investigate the mode of action for an insecticide that has not yet been released for commercial use. The ovicidal, larvacidal and adulticidal effects of 5,5′-dimethyl -2, 2′-dipyridyl (termed Ha44), which is being developed as a treatment for head lice, were evaluated in the Drosophila melanogaster model system. Ha44 demonstrated significant activity against embryos and was capable of arresting development at a number of stages of embryogenesis. The effects of Ha44 on embryos was shown to be reversible following the addition of the metal ions Fe(II) and Fe(III), Cu and Zn. When larvae were exposed to Ha44, lethality was recorded at similar concentrations to those observed for embryos. Using an eYFP reporter system it was shown that Ha44 was able to reduce the levels of both copper and zinc in the digestive tract, confirming the binding of Ha44 to these metals in vivo. Ha44 has further been shown to inhibit a zinc containing metalloproteinase in vitro. Exposure of adult flies to Ha44 resulted in lethality, but at higher concentrations than those observed for embryos and larvae. The median lethal dose in adult flies was shown to be associated with the type of exposure, with an LD-50 of 1.57 mM being recorded following the direct contact of flies with Ha44, while an LD-50 of 12.29 mM was recorded following the ingestion of the compound. The capacity of Ha44 to act on all stages of the life-cycle and potentially via a range of targets suggests that target site resistance is unlikely to evolve.     

Diabetes with hypertension as risk factors for adult dengue hemorrhagic fever in a predominantly dengue serotype 2 epidemic: a case control study

Background

Dengue hemorrhagic fever (DHF) is a severe form of dengue, characterized by bleeding and plasma leakage. A number of DHF risk factors had been suggested. However, these risk factors may not be generalized to all populations and epidemics for screening and clinical management of patients at risk of developing DHF. This study explored demographic and comorbidity risk factors for DHF in adult dengue epidemics in Singapore in year 2006 (predominantly serotype 1) and in year 2007–2008 (predominantly serotype 2).

Methods

A retrospective case-control study was conducted with 149 DHF and 326 dengue fever (DF) patients from year 2006, and 669 DHF and 1,141 DF patients from year 2007–2008. Demographic and reported comorbidity data were collected from patients previously. We performed multivariate logistic regression to assess the association between DHF and demographic and co-morbidities for year 2006 and year 2007–2008, respectively.

Results

Only Chinese (adjusted odds ratio [AOR] = 1.90; 95% confidence interval [CI]: 1.01–3.56) was independently associated with DHF in year 2006. In contrast, age groups of 30–39 years (AOR = 1.41; 95% CI:1.09–1.81), 40–49 years (AOR = 1.34; 95% CI:1.09–1.81), female (AOR = 1.57; 95% CI:1.28–1.94), Chinese (AOR = 1.67; 95% CI:1.24–2.24), diabetes (AOR = 1.78; 95% CI:1.06–2.97), and diabetes with hypertension (AOR = 2.16; 95%CI:1.18–3.96) were independently associated with DHF in year 2007–2008. Hypertension was proposed to have effect modification on the risk of DHF outcome in dengue patients with diabetes. Chinese who had diabetes with hypertension had 2.1 (95% CI:1.07–4.12) times higher risk of DHF compared with Chinese who had no diabetes and no hypertension.

Conclusions

Adult dengue patients in Singapore who were 30–49 years, Chinese, female, had diabetes or diabetes with hypertension were at greater risk of developing DHF during epidemic of predominantly serotype 2. These risk factors can be used to guide triaging of patients who require closer clinical monitoring and early hospitalization in Singapore, when confirmed in more studies.     

Controlling the mealworm Alphitobius diaperinus (Coleoptera: Tenebrionidae) in broiler and turkey houses: field trials with a combined insecticide treatment: insect growth regulator and pyrethroid

Trials were conducted during one year under field conditions to control the lesser mealworm, Alphitobius diaperinus (Panzer), in broiler and turkey houses. The tested combined treatment included an adulticidal compound (pyrethroid: cyfluthrin) and a larvicidal compound (insect growth regulator [IGR]: triflumuron). The combined insecticide treatment greatly reduced the adult and larval stocks throughout the different broiler growing periods, and control of A. diaperinus populations was achieved by the end of the second treatment. Control of the insect population in a turkey house was not similar. A reestablishment of the insect population was observed during the second turkey growing period in summer. Building characteristics and management practices of the breeding system (duration of the breeding period, management of the litter) interact with the combined insecticide treatment and lead to a different efficiency.     

N-glycome profiling of Bothrops jararaca newborn and adult venoms

Glycosylation is an important post-translational modification of snake venom proteins and contributes to venom proteome complexity. Many snake venom components are known to be glycosylated, however, very little is known about the carbohydrate structures present in venom glycoproteins. Previous studies showed that the ontogenetic shift in diet, from ectothermic prey in early life to endothermic prey in adulthood, and shift in animal size are associated with changes in the venom proteome of the snake Bothrops jararaca. In this study we explored the composition of the N-glycome released from newborn and adult B. jararaca venom proteins. We used an ion trap mass spectrometer (IT-MS) to disassemble glycan structures based on the use of several pathways of MS (MSn) and demonstrate the presence of some structural isomers in both newborn and adult venom B. jararaca N-glycans. The main N-glycans identified in both venoms are of the hybrid/complex type however some mannose-rich type structures were also detected. The N-glycan composition of newborn and adult venoms did not vary indicating that differences in the utilization of the N-glycosylation motif could be the explanation for the differences in the glycosylation levels indicated by the differential electrophoretic profiles previously reported for B. jararaca newborn and adult venoms.     

The mouths of earth: The dialectical allegories of the Kwakiutl Indians

Summary The profane condition, baxus, is generated as the antithesis of the primordial myth-state by the great transformations. Differentiation of the mutually predatory kinds of creatures, and the increase of their number, unfolds within a temporal frame created by introducing into the world, the concrete opposites of primordial of darkness, wind and water omnipresent in the myth-state. A predominantly coordinate hierarchy among the mythic protokinds turns into obligatory antagonisms among the profane kinds (of baxus). Special individuals, successors of animal and human Ancestors, are set apart to carry the diminished aura of mythic quasi-oneness through time by means of supernatural communions. Within the human social order, this is the religious origin of caste: the presumed limitation on the communions of men and spirits diminishes the communions of men; special privilege, in economy as in ceremony, is thus conferred upon the spiritually blessed.The antagonism and power asymmetry in baxus impels it always toward the dissolution of its diversity, i.e., toward tsetseqa, manifest as winter. The resurrection of baxus, and summer, out of tsetseqa, on the other hand, is miraculous and ultimately ineffable. Kwakiutls presume that something is contributed to this end by the ritual taming of the Baxbakualanuxsiwae. But in the end, it seems, they cede the mystery of regeneration to him alone: Nobody can imitate your dance... great magician...Vernon Kobrinsky is Associate Professor in the Department of Anthropology, The University of Calgary, Canada.     

Analysis of the Sarcocystis neurona microneme protein SnMIC10: protein characteristics and expression during intracellular development

Sarcocystis neurona, an apicomplexan parasite, is the primary causative agent of equine protozoal myeloencephalitis. Like other members of the Apicomplexa, S. neurona zoites possess secretory organelles that contain proteins necessary for host cell invasion and intracellular survival. From a collection of S. neurona expressed sequence tags, we identified a sequence encoding a putative microneme protein based on similarity to Toxoplasma gondii MIC10 (TgMIC10). Pairwise sequence alignments of SnMIC10 to TgMIC10 and NcMIC10 from Neospora caninum revealed approximately 33% identity to both orthologues. The open reading frame of the S. neurona gene encodes a 255 amino acid protein with a predicted 39-residue signal peptide. Like TgMIC10 and NcMIC10, SnMIC10 is predicted to be hydrophilic, highly alpha-helical in structure, and devoid of identifiable adhesive domains. Antibodies raised against recombinant SnMIC10 recognised a protein band with an apparent molecular weight of 24 kDa in Western blots of S. neurona merozoites, consistent with the size predicted for SnMIC10. In vitro secretion assays demonstrated that this protein is secreted by extracellular merozoites in a temperature-dependent manner. Indirect immunofluorescence analysis of SnMIC10 showed a polar labelling pattern, which is consistent with the apical position of the micronemes, and immunoelectron microscopy provided definitive localisation of the protein to these secretory organelles. Further analysis of SnMIC10 in intracellular parasites revealed that expression of this protein is temporally regulated during endopolygeny, supporting the view that micronemes are only needed during host cell invasion. Collectively, the data indicate that SnMIC10 is a microneme protein that is part of the excreted/secreted antigen fraction of S. neurona. Identification and characterisation of additional S. neurona microneme antigens and comparisons to orthologues in other Apicomplexa could provide further insight into the functions that these proteins serve during invasion of host cells.     

Characterisation of the Small RNAs in the Biomedically Important Green-Bottle Blowfly Lucilia sericata

Background

The green bottle fly maggot, Lucilia sericata, is a species with importance in medicine, agriculture and forensics. Improved understanding of this species’ biology is of great potential benefit to many research communities. MicroRNAs (miRNA) are a short non-protein coding regulatory RNA, which directly regulate a host of protein coding genes at the translational level. They have been shown to have developmental and tissue specific distributions where they impact directly on gene regulation. In order to improve understanding of the biology of L. sericata maggots we have performed small RNA-sequencing of their secretions and tissue at different developmental stages.

Results

We have successfully isolated RNA from the secretions of L. sericata maggots. Illumina small RNA-sequencing of these secretions and the three tissues (crop, salivary gland, gut) revealed that the most common small RNA fragments were derived from ribosomal RNA and transfer RNAs of both insect and bacterial origins. These RNA fragments were highly specific, with the most common tRNAs, such as GlyGCC, predominantly represented by reads derived from the 5’ end of the mature maggot tRNA. Each library also had a unique profile of miRNAs with a high abundance of miR-10-5p in the maggot secretions and gut and miR-8 in the food storage organ the crop and salivary glands. The pattern of small RNAs in the bioactive maggot secretions suggests they originate from a combination of saliva, foregut and hindgut tissues. Droplet digital RT-PCR validation of the RNA-sequencing data shows that not only are there differences in the tissue profiles for miRNAs and small RNA fragments but that these are also modulated through developmental stages of the insect.

Conclusions

We have identified the small-RNAome of the medicinal maggots L. sericata and shown that there are distinct subsets of miRNAs expressed in specific tissues that also alter during the development of the insect. Furthermore there are very specific RNA fragments derived from other non-coding RNAs present in tissues and in the secretions. This new knowledge has applicability in diverse research fields including wound healing, agriculture and forensics.