Rare and Frequent Promoter Methylation, Respectively, of TSHZ2 and 3 Genes That Are Both Downregulated in Expression in Breast and Prostate Cancers

Neoplastic cells harbor both hypomethylated and hypermethylated regions of DNA. Whereas hypomethylation is found mainly in repeat sequences, regional hypermethylation has been linked to the transcriptional silencing of certain tumor suppressor genes. We attempted to search for candidate genes involved in breast/prostate carcinogenesis, using the criteria that they should be expressed in primary cultures of normal breast/prostate epithelial cells but are frequently downregulated in breast/prostate cancer cell lines and that their promoters are hypermethylated.We identified several dozens of candidates among 194 homeobox and related genes using Systematic Multiplex RT-PCR and among 23,000 known genes and 23,000 other expressed sequences in the human genome by DNA microarray hybridization. An additional examination, by real-time qRT-PCR of clinical specimens of breast cancer, further narrowed the list of the candidates. Among them, the most frequently downregulated genes in tumors were NP_775756 and ZNF537, from the homeobox gene search and the genome-wide search, respectively. To our surprise, we later discovered that these genes belong to the same gene family, the 3-member Teashirt family, bearing the new names of TSHZ2 and TSHZ3. We subsequently determined the methylation status of their gene promoters. The TSHZ3 gene promoter was found to be methylated in all the breast/prostate cancer cell lines and some of the breast cancer clinical specimens analyzed. The TSHZ2 gene promoter, on the other hand, was unmethylated except for the MDA-MB-231 breast cancer cell line. The TSHZ1 gene was always expressed, and its promoter was unmethylated in all cases.TSHZ2 and TSHZ3 genes turned out to be the most interesting candidates for novel tumor suppressor genes. Expression of both genes is downregulated. However, differential promoter methylation suggests the existence of distinctive mechanisms of transcriptional inactivation for these genes

Whole Genomes of Chandipura Virus Isolates and Comparative Analysis with Other Rhabdoviruses

The Chandipura virus (CHPV) belonging to the Vesiculovirus genus and Rhabdoviridae family, has recently been associated with a number of encephalitis epidemics, with high mortality in children, in different parts of India. No full length genome sequences of CHPV isolates were available in GenBank and little is known about the molecular markers for pathogenesis. In the present study, we provide the complete genomic sequences of four isolates from epidemics during 2003–2007. These sequences along with the deduced sequence of the prototype isolate of 1965 were analysed using phylogeny, motif search, homology modeling and epitope prediction methods. Comparison with other rhaboviruses was also done for functional extrapolations. All CHPV isolates clustered with the Isfahan virus and maintained several functional motifs of other rhabdoviruses. A notable difference with the prototype vesiculovirus, Vesicular Stomatitis Virus was in the L-domain flanking sequences of the M protein that are known to be crucial for interaction with host proteins. With respect to the prototype isolate, significant additional mutations were acquired in the 2003–2007 isolates. Several mutations in G mapped onto probable antigenic sites. A mutation in N mapped onto regions crucial for N-N interaction and a putative T-cell epitope. A mutation in the Casein kinase II phosphorylation site in P may attribute to increased rates of phosphorylation. Gene junction comparison revealed changes in the M-G junction of all the epidemic isolates that may have implications on read-through and gene transcription levels. The study can form the basis for further experimental verification and provide additional insights into the virulence determinants of the CHPV

3D analysis of thermal and stress evolution during laser cladding of bioactive glass coatings

Thermal and strain-stress transient fields during laser cladding of bioactive glass coatings on the Ti6Al4V alloy basement were numerically calculated and analysed. Conditions leading to micro-cracking susceptibility of the coating have been investigated using the finite element based modelling supported by experimental results of microscopic investigation of the sample coatings. Consecutive temperature and stress peaks are developed within the cladded material as a result of the laser beam moving along the complex trajectory, which can lead to micro-cracking. The preheated to 500oC base plate allowed for decrease of the laser power and lowering of the cooling speed between the consecutive temperature peaks contributing in such way to achievement of lower cracking susceptibility. The cooling rate during cladding of the second and the third layer was lower than during cladding of the first one, in such way, contributing towards improvement of cracking resistance of the subsequent layers due to progressive accumulation of heat over the process

Towards a new phenotype for tick resistance in beef and dairy cattle:a review

About 80% of the world's cattle are affected by ticks and tick-borne diseases, both of which cause significant production losses. Cattle host resistance to ticks is the most important factor affecting the economics of tick control, but it is largely neglected in tick-control programs due to technical difficulties and costs associated with identifying individual-animal variation in resistance. The present paper reviews the scientific literature to identify factors affecting resistance of cattle to ticks and the biological mechanisms of host tick resistance, to develop alternative phenotype(s) for tick resistance. If new cost-effective phenotype(s) can be developed and validated, then tick resistance of cattle could be genetically improved using genomic selection, and incorporated into breeding objectives to simultaneously improve cattle productive attributes and tick resistance. The phenotype(s) could also be used to improve tick control by using cattle management. On the basis of the present review, it is recommended that three possible phenotypes (haemolytic analysis measures of skin hypersensitivity reactions simplified artificial tick infestations) be further developed to determine their practical feasibility for consistently, cost-effectively and reliably measuring cattle tick resistance in thousands of individual animals in commercial and smallholder farmer herds in tropical and subtropical areas globally. During evaluation of these potential new phenotypes, additional measurements should be included to determine the possibility of developing a volatile-based resistance phenotype, to simultaneously improve cattle resistance to both ticks and biting flies. Because the current measurements of volatile chemistry do not satisfy the requirements of a simple, cost-effective phenotype for use in commercial cattle herds, consideration should also be given to inclusion of potentially simpler measures to enable indirect genetic selection for volatile-based resistance to ticks

Nurses' Caring Behaviors for Dying Patients in Southern Thailand

Background: Nowadays, the end-of-life care becomes an indicator of the quality of care in a hospital. However, current nursing standards and quality of care related to the end of life do not meet the desired expectations of both dying patients and their families. Therefore, caring behaviors of nurses need to be described.Purpose: The purpose of this descriptive research was to describe the level of nurses' caring behaviors for dying patients in southern Thailand. Method: Proportionate stratified random sampling was used to select 360 registered nurses who had been working in general hospitals and regional/university hospitals in southern Thailand for at least one year. Instruments used in the study included the Demographic Data Questionnaire (DDQ) and the Nurse's Caring Behavior for Dying Patients Questionnaire (NCBDQ). The questionnaires were content validated by three experts. The reliability of the NCBDQ was tested with 30 nurses yielding a Cronbach's alpha coefficient of .97. The data were analyzed by using frequency, percentage, mean and standard deviation.Results: The level of nurses' caring behaviors for dying patients was high (M = 2.12, SD = .43). The five dimensions of the nurses' caring behaviors including compassion, confidence, conscience, commitment and comportment were also at a high level. However, the competence dimension was at a moderate level (M = 1.82, SD = .51). Conclusion: The results of this study indicated that nurses perceived themselves as having a moderate level of competency in taking care of dying patients. Therefore, educational intervention on enhancing nurses' competency for end of life care is recommended. In addition, factors relating to nurses' caring behavior for dying patients should be further explored