Gastroesophageal reflux disease and tooth erosion

The increasing prevalence of gastroesophageal reflux disease (GERD) in children and adults, and of “silent refluxers” in particular, increases the responsibility of dentists to be alert to this potentially severe condition when observing unexplained instances of tooth erosion. Although gastroesophageal reflux is a normal physiologic occurrence, excessive gastric and duodenal regurgitation combined with a decrease in normal protective mechanisms, including an adequate production of saliva, may result in many esophageal and extraesophageal adverse conditions. Sleep-related GERD is particularly insidious as the supine position enhances the proximal migration of gastric contents, and normal saliva production is much reduced. Gastric acid will displace saliva easily from tooth surfaces, and proteolytic pepsin will remove protective dental pellicle. Though increasing evidence of associations between GERD and tooth erosion has been shown in both animal and human studies, relatively few clinical studies have been carried out under controlled trial conditions. Suspicion of an endogenous source of acid being associated with observed tooth erosion requires medical referral and management of the patient as the primary method for its prevention and control.Sarbin Ranjitkar, John A. Kaidonis, and Roger J. Smale

Regulation of the Centromeric Histone H3 Variant Cse4 by the E3 Ubiquitin Ligase, Pshl

Aneuploidy, one of the most common hallmarks of cancer, results from defects in chromosome segregation during cell division. Once cells replicate their genome, sister chromatids must be accurately segregated into daughter cells during mitosis in order to ensure genomic stability. Chromosome segregation IS directed by the kinetochore, a multi-protein complex that assembles onto specialized chromosomal locus called the centromere. Because centromere DNA is not conserved, there are epigenetic mechanisms that ensure its propagation. Cenp-A, a conserved histone H3 variant appears to be the epigenetic mark that specifies centromere identity and is essential for kinetochore assembly and function. Exclusive localization of Cenp-A to the centromere is critical to prevent formation of di-centric chromosome that can be broken during segregation. Proteolysis is one of the mechanisms that cells utilize to regulate Cenp-A levels and prevent its mislocalization to non-centromeric loci in budding yeast and flies. However, the molecular machinery and the underlying mechanisms are not known. In my research, I focused on identifying proteins involved in degradation of Cenp-A and elucidate the meehanism by which the proteolytic machinery prevents eetopic localization of Cenp-A using budding yeast as a model system. Cse4 is the Cenp-A homolog in budding yeast. To identify Cse4 degradation machinery, I focused on known and novel Cse4 interacting proteins that were previously identified in the lab. Of the various candidates, I focused on Pshl, a protein of unknown function. Pshl contains a R1NG domain, a hallmark of all ruNG type E3 ligases. I demonstrated that Pshl is a bonafide E3 ligase in vitro and functions to ubiquitinate and degrade Cse4 in vivo. Moreover, Pshl mediated degradation of Cse4 prevents mislocalization of Cse4 to non-centromeric loci. Consistent with this, overexpression of Cse4 is toxic to pshl 11 cells and leads to mislocaliztion of Cse4 to the euchromatin. The toxicity of Cse4 overexpression is correlated with the levels of Cse4 protein and can be partly attributed to the activation of the spindle checkpoint. Since Cse4 is about 60% identical to the canonical H3, I also investigated if Pshl is a specific E3 ligase for Cse4 and how it is able to discriminate between the two histones. Pshl co-purifies with Cse4 but fails to interact with histone H3. Consistent with a specific function of Pshl for Cse4 proteolysis, overexpression of H3 had no effect on the viability of pshl 11 cells. Domain swap experiments reveal the centromere targeting domain (CATD) in Cse4, which is absent in H3, to be the recognition motif by which Pshl distinguishes Cse4 from H3. In addition, this domain appears to be required and sufficient for Pshl mediated degradation. Taken together, my work has shown that the CA TD has a previously unknown role in maintaining the exclusive localization of Cse4 by preventing its misloealization to euchromatin via Pshl-mediated degradation

Intra-gender differences and women’s participation in climate change adaptation programs: An intersectional study of gender, caste, and ethnicity in the rural plains of Nepal

GLODE33

Participation in climate change adaptation programs in Nepal: an intersectional study

In the social discourses of climate change, women are perceived both as vulnerable victims and as active players in adaptation. These perceptions of women along with inclusion policies have led climate change adaptation programs to seek women’s participation. However, ‘women’ is not a homogenous category. Intra-gender power differences in terms of castes and ethnicities can play an important role, especially in Nepal with its long history of institutionalized disparities. Using qualitative methodology, this study explores the relationships between gender, caste and ethnicity in shaping women’s participation in climate change adaptation programs in the southern plains of Nepal. We conclude that women’s gender identities generally facilitated their participation and that affirmative action for marginalized groups, to some extent, gave women from these groups spaces to participate in climate change adaptation programs. However, power relations associated with caste/ethnic identity created hindrances for marginalized women, implying that they had more restricted access than women from the majority groups.publishedVersio

Intergenic Transcription in In Vivo Developed Bovine Oocytes and Pre-Implantation Embryos

Background Intergenic transcription, either failure to terminate at the transcription end site (TES), or transcription initiation at other intergenic regions, is present in cultured cells and enhanced in the presence of stressors such as viral infection. Transcription termination failure has not been characterized in natural biological samples such as pre-implantation embryos which express more than 10,000 genes and undergo drastic changes in DNA methylation. Results Using Automatic Readthrough Transcription Detection (ARTDeco) and data of in vivo developed bovine oocytes and embryos, we found abundant intergenic transcripts that we termed as read-outs (transcribed from 5 to 15 kb after TES) and read-ins (transcribed 1 kb up-stream of reference genes, extending up to 15 kb up-stream). Read-throughs (continued transcription from TES of expressed reference genes, 4–15 kb in length), however, were much fewer. For example, the numbers of read-outs and read-ins ranged from 3,084 to 6,565 or 33.36–66.67% of expressed reference genes at different stages of embryo development. The less copious read-throughs were at an average of 10% and significantly correlated with reference gene expression (P \u3c 0.05). Interestingly, intergenic transcription did not seem to be random because many intergenic transcripts (1,504 read-outs, 1,045 read-ins, and 1,021 read-throughs) were associated with common reference genes across all stages of pre-implantation development. Their expression also seemed to be regulated by developmental stages because many were differentially expressed (log2 fold change ≥ 2, P \u3c 0.05). Additionally, while gradual but un-patterned decreases in DNA methylation densities 10 kb both up- and down-stream of the intergenic transcribed regions were observed, the correlation between intergenic transcription and DNA methylation was insignificant. Finally, transcription factor binding motifs and polyadenylation signals were found in 27.2% and 12.15% of intergenic transcripts, respectively, suggesting considerable novel transcription initiation and RNA processing. Conclusion In summary, in vivo developed oocytes and pre-implantation embryos express large numbers of intergenic transcripts, which are not related to the overall DNA methylation profiles either up- or down-stream

Depression among patients undergoing maintenance hemodialysis at a tertiary care center in Kathmandu, Nepal

Introductions: Patients with chronic kidney disease have a high burden of somatic symptoms which may be due to depression. This study analyses occurrence of depression in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD) at a tertiary care center in Kathmandu, Nepal. Methods: This is a retrospective study done at Patan Hospital, a tertiary care teaching hospital of Patan Academy of Health sciences, Lalitpur, Nepal. Translated in Nepali language and validated Beck Depression Inventory (BDI) was used. A cut-off of 16/17 was used to define depression.  Results: Altogether 56 patients were included, mean age 54.375±17.87 years, time on HD 25.06±21.58 months, BDI score 19.18±10.16. The prevalence of depression was 51.8%. There was no significant differences of BDI score and rate of depression in genders, housing status, education level, alcohol intake, presence of co-morbidity and shift of HD. However, there was a significant association of BDI score and the employment status, p=0.026 and the affordability of erythropoiesis stimulating agent, p=0.033. Conclusions: Depression was common in patients undergoing hemodialysis treatment and the rate of depression was significantly lower in the patients who were employed and used of erythropoiesis stimulating agent. Keywords: chronic kidney disease, depression, hemodialysi

Dasatinib tyrosine kinase inhibitor as second and third line therapy in chronic myeloid leukemia: outcome of a Nepalese study

Introductions: Dasatinib is indicated as a first line, second line and third line tyrosine kinase inhibitor (TKI) in chronic myeloid leukemia (CML). In our center it is used as a second line or third line therapy in BCR-ABL gene positive CML. Methods: It is a retrospective observational therapy done from June 2015 to May 2018.   The purpose of the study is to see the response rates using the second line and third line dasatinib after failing or not tolerating imatinib alone or following a sequential therapy with imatinib and nilotinib. Results: A total of 31 (male 56.3%) patients were included in our study. In eighteen patients it was used as a second line TKI and in 13 a third line TKI. Complete Hematologic Response (CHR) was achieved in 93.55%. Best optimal responses were 46.66% and 61.53% in second and third line dasatinib respectively. Major Molecular Response (MMR) was achieved in 35.71% (26.66% and 46.14% in second line and third line dasatinib respectively). For both the groups, the overall survival was 92% and 94 % at 20 months and the event free survival was 70% at 10 months. Conclusions:  Dasatinib is effective in achieving MMR and inducing survival benefit in the patients who failed imatinib alone and imatinib and nilotinib. Keywords: chronic myeloid leukemia, dasatinib, imatinib failure or intolerance, imatinib and nilotinib failure or intoleranc

Determining the Correlation Between Helminth Parasite Prevalence in Wisconsin Felis rufus Populations

Felis rufus (bobcat) populations are declining throughout some of their range in Wisconsin, while expanding in others (Personal Communication, WI DNR)1. Many theories exist as to why this is happening, including the possibility of disease. Our lab wanted to determine the helminth parasite population prevalence and intensity in Wisconsin bobcat and determine if there was a correlation with sex, age or geographic location of these animals. One hundred and fifteen bobcat intestines were collected March 5, 2012 at a Department of Natural Resources (DNR) Facility, Madison, WI. These animals were legally harvested by trapping/hunting and the carcasses were made available for scientific use by the WI DNR. Each intestine was analyzed by first washing the digesta through different pore sized screens or sieves, and then observing the retentate for parasites. Parasites were sorted and counted by species and gender and stored in 70% ethanol for further processing. Some parasites were stained or cleared and mounted for species determination. Currently, prevalence and intensity of infection are being determined and correlated with the geographic range, age, and gender of the animals

Model-based design of coordinated traffic controllers

Modern transportation systems optimize traffic flows in road networks by allowing intersection-level traffic controllers to communicate and synchronize. Typically they are distributed systems, with multiple nodes (intersections) communicating with each other in real time. This paper proposes a design process for traffic coordination systems using model driven engineering (MDE), a paradigm used to design complex embedded systems in automotive and aerospace. The approach combines a conventional micro-simulator (AIMSUN) with a state of the art control modelling tool (Simulink) following a model-view-controller approach. The MDE approach allows for both micro-simulation (on a PC) and emulation (using embedded controllers). Once the model is validated, automatic code generation can be used to generate the implementation of the system on embedded devices. As a case study, the authors designed a SCATS-inspired coordinated intersection control system. To the authors' knowledge, the proposed approach is the first, fully automated approach for the design of complex intelligent transportation systems (ITS)