Medical genetics

The research efforts refer to tracking homologus loci in the chromosomes of a pair of a species. The purpose is to infer the extent of maximum syntenic correlation when an exhaustive set of orthologs of the species are searched. Relevant bioinformatic analyses use comparative mapping of conserved synteny via Oxford grid. In medical diagnostic efforts, deducing such synteny correlation can help screening chromosomal aberration in genetic disorder pathology. Objectively, the present study addresses: (i) Cytogenetic framework of syntenic correlation and, (ii) applying information-theoretics to determine entropy-dictated synteny across an exhaustive set of orthologs of the test pairs of species.

A naturally-occurring recessive lethal mutation in axolotls, Ambystoma mexicanum, is an intriguing model for studying tropomyosin expression regulation. Homozygous embryos(c/c) form hearts that are deficient in tropomyosin, lack organized myofibrils and fail to beat. Previous studies have shown that a non-coding RNA gene, MIR (Myofibril Inducing RNA), is sufficient to rescue the non-beating homozygous recessive mutant hearts by promoting sarcomeric tropomyosin expression that leads to formation of organized myofibrils and beating hearts. Real time RT-PCR reveals that mutant hearts express the same level mRNA of the alpha-tropomyosin and TM4 type tropomyosin (ATmC-3) gene as normal embryonic hearts. These genes show no differences with regard to the splicing patterns of normal and mutant. Using protease inhibitor LLnL and E-64d treatments and two-dimensional Western blots of normal and mutant hearts, it is found that mutant hearts express all tropomyosin protein isoforms as normal hearts but protein expression are at low levels. These studies suggest that there is a failure in the translational or posttranslational control mechanisms for tropomyosin protein synthesis in cardiac mutant axolotl hearts during development.

The purpose of this hermeneutic phenomenological study was to understand the essence of the lived experience of women after having an abnormal prenatal ultrasound. One hundred years ago, health disciplines had limited therapies for prenatal and neonatal disorders. During this period, the eugenics movement influenced leaders to involuntarily sterilize individuals who were sought to be "unfit" to prevent disorders in offspring. ... One of these contemporary reproductive genetic technologies is the use of ultrasound and serum bio-medical markers for detection of congenital, chromosome, and genetic disorders. When ultrasounds reveal abnormal findings, the perceived perfect pregnancy vanishes and gives way to feelings of shock, disbelief, fear, guilt, loss, and threats to self and their unborn baby. Twelve women who had an abnormal ultrasound were interviewed within the context of their cultural values and beliefs. The method of van Manen's hermeneutic phenomenology illuminated the meaning for these women in their life worlds. ... They endured this experience through their own coping mechanisms, but often felt uncertainty and emotional turmoil until the birth. The women also sought comfort through their cultural values, beliefs, and traditions. In coping with the risks found on this abnormal ultrasound, women often selected silence or blocking perceived threats. With these coping methods, they were alone in their suffering. ... Health providers, in not recognizing these women's misunderstandings and emotional fears, abandoned them in their psychosocial and cultural needs. The significance reveals that nurses and health providers need to infuse human caring ways of being, knowing, and doing within advanced technological environments.

Sjèogren's Syndrome (SS) is a chronic, inflammatory autoimmune disease affecting mostly the exocrine cells of lacrimal and salivary glands, leading to diminished secretory function and resulting in keratoconjunctivitis sicca (dry eye disease) and/or stomatitis sicca (dry mouth disease). Despite several decades of studies focusing on autoimmune diseases and dry eye diseases, the exact etiology and mechanisms of SS remain unknown. Besides the fact that SS is often unreported, unrecognized and untreated, today's therapies rely exclusively on treating the symptoms after disease progression; there exists neither prevention therapy nor cure for SS. In addition, SS has been diagnosed predominantly in post-menopausal women with the female to male ratio reaching 9:1, suggesting a role of ovarian sex hormones in the pathogenesis of SS. However, not all postmenopausal women develop SS, indicating the contribution of other factors such as a genetic background to the onset of SS. In the present study, ovariectomized (OVX) NOD.B10.H2b mice provide a model of menopause with a genetic predisposition to SS, as compared to non-predisposed C57BL/10 mice. Both strands of mice were either sham operated, OVX, OVX and treated with 17(Sb (Bestradiol (E2), or OVX and treated with dihydrotestosterone (DHT). Lacrimal glands were collected 3, 7, 21, and 30 days after surgery and processed for RNA analysis by rt-qPCR and protein assays by ELISA to evaluate cytokine expression and concentrations of IL- 1\U+fffd\, TNF-a, IFN-(Sd(B, IL-10, and IL-4 on a timeline. Overall, our results showed a significant increase in IL-1\U+fffd\ TNF-a, IL-10, and IL-4 expression and levels in the lacrimal glands of OVX NOD.B10.H2b mice as compared to sham operated animals, and treatment with E2 or DHT at time of OVX prevented the increase in cytokine expression and levels.

Cytogenetics is a study on the genetic considerations associated with structural and functional aspects of the cells with reference to chromosomal inclusions. Chromosomes are structures within the cells containing body's information in the form of strings of DNA. When atypical version or structural abnormality in one or more chromosomes prevails, it is defined as chromosomal aberrations (CA) depicting certain genetic pathogeny (known as genetic disorders). The present study assumes the presence of normal and abnormal chromosomal sets in varying proportions in the cytogenetic complex ; and, stochastical mixture theory is invoked to ascertain the information redundancy as a function of fractional abnormal chromosome population. This bioinformatic measure of redundancy is indicated as a track-parameter towards the progression of genetic disorder, for example, the growth of cancer. Lastly, using the results obtained, conclusions are enumerated, inferences are outlined and directions for future studies are considered.

Sjèogren's syndrome (S) is a chronic autoimmune disease characterized by ocular and oral dryness and primarily affects post menopausal women. In the present study we investigated the time course of lymphocytic infiltration, apoptosis, caspase-3 activity and different cytokines levels in the lacrimal glands of both genetically predisposed and control mice to elucidate immunopathological mechanism leading to dry eye. The results of our experiments showed that ovariectomy accelerated pathological findings of SS by increasing lympocytic infiltration, cytokine production, lacrimal gland cell death and cleaved caspase-3 activity, and these effects were more pronounced and persistent in the genetically predisposed mouse model of SS. In addition, we observed that lymphocytic infiltration occurred earlier compared to apoptosis which may perpetuate immune mediated destruction of lacrimal epithelial cells. Furthermore, treatment with physioloigical doses of 17-B Estradiol (E2) or DIhydrotestosterone (DHT) prevented all these pathological events observed after ovariectomy.

Tumor cells are characterized by an increase in genomic instability, brought about by both chromosomal rearrangement and chromosomal instability. Both of these broad changes can be induced by exposure to carcinogens. During mitosis, cells can exhibit early and late lagging chromosomes, multipolar spindles or anaphase bridges, all of which contribute to genomic rearrantement. We have studied the link between exposure to carcinogen and prevalence of mitotic defect in both chromosomally stable and unstable cell lines as well as ecamined the restorative effects of antioxidants in preventing mitotic defects. We have exposed MES-SA uterine cancer cells to vinyl chloride followed by exposure to an antioxidant : ascorbic acid, B-carotene, or lycopene. Treated cells were then scored for the prevalence of mitotic defects within the population and compared to controls. We have also investigated whether pre-treatment with the antioxidants will weaken the effects of carcinogen exposure in these cell lines.