73 research outputs found

    TheEnvelope Glycoproteins of Gammaretroviruses and Type-D Betaretroviruses are Tetherin Antagonists:

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    Thesis advisor: Welkin E. JohnsonTetherin/BST2 is an interferon-inducible antiviral factor that restricts the egress of numerous enveloped viruses including HIV-1. Consequently, many viruses have evolved mechanisms to actively or passively evade restriction by tetherin. Most studies conducted to date focused on the tetherin-evasion mechanism of complex retroviruses like HIV and SIV, which encode accessory proteins like Vpu and Nef respectively to counteract tetherin-mediated restriction. However, there is a wide gap in knowledge in understanding how simple retroviruses (that includes alpharetroviruses, some betaretroviruses and gammaretroviruses) that lack obvious accessory proteins like HIV-1 Vpu and SIV-Nef, evade restriction by tetherin. In this dissertation, I have established that Simian retrovirus type-3, a prototypical type-D betaretrovirus, isolated from Asian macaques, is restricted by human tetherin but not by rhesus macaque tetherin. This differential sensitivity indicated that SRV-3 has a mechanism to evade tetherin-mediated restriction. I have identified the SRV-3 envelope (Env) glycoprotein as the viral determinant of tetherin antagonism, and have also found that SRV-3 envelope expression in-trans was sufficient to rescue a heterologous virus from tetherin. SRV-3 Env resulted in cell-surface down-modulation of rhesus tetherin, and this mechanism of tetherin-antagonism is independent of the SRV-3 Env trafficking pathway. The target specificity of SRV-3 Env overlapped a stretch of five residues (G14DIWK18) in the rhesus tetherin cytoplasmic tail that are absent from human tetherin. Additionally, I was able to show that SRV-3 Env physically interacts with rhesus tetherin by targeting the G14DIWK18 motif. SRV-3 belongs to a large supergroup of retroviruses, called the RDR Interference Supergroup. Due to this reason, I screened additional RDR envelope glycoproteins for their ability to antagonize a panel of tetherin homologs. All the RDR envelopes tested were sensitive to human tetherin but exhibited anti-tetherin activity when tested against a panel of tetherin homologs from squirrel monkey, baboon, dog and cat. I also found that several non-RDR gammaretroviral envelope glycoproteins also have anti-tetherin function. Thus, tetherin-antagonism is not just restricted to the envelope glycoproteins of retroviruses in the RDR interference supergroups but extends to other non-RDR gammaretroviruses as well. To my knowledge, this is the first characterization of gamma-type envelopes as tetherin antagonists. Thus, in the absence of a dedicated tetherin antagonist, many simple retroviruses in the beta- and gammaretrovirus genera may evade tetherin-mediated restriction through neo-functionalization of their envelope glycoproteins. We speculate that the evolutionary success of the gamma-type envelope may be due, at least in part, to this anti-tetherin function.Thesis (PhD) — Boston College, 2018.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Biology

    Cystathionine β-synthase T833C/844INS68 polymorphism: a family-based study on mentally retarded children

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    BACKGROUND: Cystathionine β-synthase (CBS) mediates conversion of homocysteine to cystathionine and deficiency in enzyme activity may lead to hyperhomocysteinemia/homocystinuria, which are often associated with mental retardation (MR). A large number of polymorphisms have been reported in the CBS gene, some of which impair its activity and among these, a T833C polymorphism in cis with a 68 bp insertion at 844 in the exon 8 is found to be associated with mild hyperhomocysteinemia in different ethnic groups. METHODS: The present study is aimed at investigating the association between T833C/844ins68 polymorphism and MR. One hundred and ninety MR cases were recruited after psychometric evaluation. Hundred and thirty-eight control subjects, two hundred and sixty-seven parents of MR probands and thirty cardiovascular disorder (CVD) patients were included for comparison. Peripheral blood was collected after obtaining informed written consent. The T833C/844ins68 polymorphism was investigated by PCR amplification of genomic DNA and restriction fragment length polymorphism analysis, followed by statistical analysis. RESULTS: The genotypic distribution of the polymorphism was within the Hardy-Weinberg equilibrium. A slightly increased genotypic frequency was observed in the Indian control population as compared to other Asian populations. Both haplotype-based haplotype relative risk analysis and transmission disequilibrium test reveled lack of association of the T833C/844ins68 polymorphism with MR; nevertheless, the relative risk calculated was higher (>1) and in a limited number of informative MR families, preferential transmission of the double mutant from heterozygous mothers to the MR probands was noticed (χ(2 )= 4.00, P < 0.05). CONCLUSION: This is the first molecular genetic study of CBS gene dealing with T833C/844ins68 double mutation in MR subjects. Our preliminary data indicate lack of association between T833C/844ins68 polymorphism with MR. However, higher relative risk and biased transmission of the double mutation from heterozygous mothers to MR probands are indicative of a risk of association between this polymorphism with mental retardation

    Congenital Extrahepatic Portosystemic Shunts: Spectrum of Findings on Ultrasound, Computed Tomography, and Magnetic Resonance Imaging

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    Congenital extrahepatic portosystemic shunt (CEPS) is a rare disorder characterised by partial or complete diversion of portomesenteric blood into systemic veins via congenital shunts. Type I is characterised by complete lack of intrahepatic portal venous blood flow due to an end to side fistula between main portal vein and the inferior vena cava. Type II on the other hand is characterised by partial preservation of portal blood supply to liver and side to side fistula between main portal vein or its branches and mesenteric, splenic, gastric, and systemic veins. The presentation of these patients is variable. Focal liver lesions, most commonly nodular regenerative hyperplasia, are an important clue to the underlying condition. This pictorial essay covers imaging characteristics in abdominopelvic region

    Fertility transition in North-East India: Historical and comparative perspectives

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    This thesis looks into the process of fertility transition in the North-Eastern Region of India (NER) from a historical and comparative perspective vis-à-vis India beginning 1901, using available data from standard secondary sources such as the Census, Sample Registration System and the National Family Health Surveys. Analysis of census data for the colonial period (1901-1941) reveals that the relatively higher population growth rates evinced by the region and its constituent states throughout the pre-Independence period as compared to the all-India average, was largely the result of incessant and relatively huge immigration into the Brahmaputra Valley initiated by the importation of ‘coolies’ and agriculturists from the over-populated areas of Bengal Province. More interestingly perhaps, indirect fertility estimates for the concerned period are indicative of an actual reproductive differential between NER (Assam) and all-India, with the former eliciting significantly higher fertility rates as compared to the latter during the pre-Independence period. Examination of socio-economic differences between Assam and India provide clues as to why such differentials might have existed during that time. Availability of a much greater amount of data for the post-colonial period allows for a greater flexibility of approach to examine fertility in NER and its constituent states. While we find that population growth rates for most of the period following 1951, continued to remain higher among the states of NER as compared to the all-India average at least partly due to continuing high migration into the region, there was a drastic change in the destination of the immigratory population- from the plain areas during the colonial period to the tribal dominated regions/states of NER in the Independent era. No doubt, this has been one of the primary reasons behind the continuing socio-political turmoil in the region during most of the period following Independence. One of the rather important findings for this period, and especially the period after the 1990s, has been the stalling of fertility decline among the states of NER. Even though there have been discrepancies between the SRS and the NFHS, regarding the trend of fertility among the states of NER, indirect estimates based on census data corroborate the findings from the latter in that there has been insignificant reduction in fertility among the states of NER in the period following the 1990s till mid 2000s. Analysis of the determinants of fertility for NER and states presents several important results. The examination of the proximate determinants of fertility for the period 1990 to 2005, finds that as in the case of all-India and the major states, contraception is the most important proximate determinant of fertility. Interestingly, nuptiality has been also found to be a proximate determinant of much importance and its effect had been mostly towards reducing fertility as was seen in the case of Tripura and Nagaland. Results from the regression analyses (cross-sectional and panel data models) for the period 1991 and 2001 finds that women’s status/autonomy as captured, for instance, by female literacy has significant fertility depressing effects. However, tribal status, at least as far as NER is concerned, is no longer a socio-cultural protection against the burden of repeated child-bearing for women. Indeed, to the contrary, ST status is associated with higher fertility rates in NER. Increasing son preference and broadly speaking, ‘Sansktitzation’ of the tribes, reflected for instance, in the relatively earlier and exogamous marriages among them, provide clues as to why such trends may have surfaced. Interestingly, we find that adherence to Christianity leads to lower fertility, possibly due to the higher age at marriage in this community. Also important has been the factor of ethnic diversity in influencing fertility in NER. Indeed, we find that region or context specific factors may have significant impact on fertility differentials. For example, in our analysis we find that greater ethnic diversity leads to lower fertility, possibly due to the fact that these numerically smaller groups have been already assimilated to a great extent into the larger ethnic groups in the respective regions, and demographic war (or war on the basis of population strength) does not hold any significant promise for greater access to socio-political and economic power for these communities

    Incidence of Ovarian Pregnancy is in the increasing trend? Two case reports

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    Ovarian pregnancy is a rare event occurring in 1-3% of all ectopic pregnancies. Increased reporting might be due to the wider use of intra-uterine devices, ovulatory drugs and assisted reproductive techniques. Though ovarian pregnancy has a distinct pathology, it can be a source of clinical and intraoperative diagnostic difficulty. We report two cases of ovarian pregnancy – one primary and one secondary – that came to our notice within six months span. Unlike tubal ectopic and secondary ovarian pregnancies, patients with primary ovarian pregnancy are likely to experience success in future intra-uterine conception and negligible risk

    Automatic scan triggering software "confused": Computed tomography angiography in foot arteriovenous malformation!

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    Multidetector computed tomography angiography (MDCTA) has become a well-established modality for limb angiography for a variety of indications. The technique of MDCTA depends on the scanner features including the number of detector rows, rotation speeds and single or dual source energy. Integral to a diagnostic quality CTA is the acquisition timing. Various techniques are available for determining the appropriate timing of scan acquisition which includes fixed delay, test bolus and the bolus tracking technique. The transit times of contrast from the aorta to the peripheral arteries shows a wide variability and is dependent upon the inter individual hemodynamic states. The bolus tracking technique is the most preferred one which allows reliable scan timing with acceptable contrast volume and radiation dose. Pitfalls with all these techniques are well described and we report one such technical pitfall in a case of left foot arteriovenous malformation (AVM) where the bolus tracking technique employed for scan triggering failed to initiate acquisition

    Gastric Duplication Cyst with Macroscopic Serosal Heterotopic Pancreas

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    Context Gastric duplication cysts are often associated with microscopic evidence of ectopic pancreatic tissue on their submucosal surface and, less commonly, on the subserosal surface. Case report We present an unusual case of a gastric duplication cyst with finger-like projections and a large heterotopic pancreas on the serosal surface of the cyst in a 30-year-old female. Conclusion We point out the unusual imaging findings which helped in the preoperative diagnosis.Image: A two-layered pattern of the wall of the duplication cyst

    Discerning non-disjunction in down syndrome patients by means of GluK1-(AGAT) n and D21S2055-(GATA) n microsatellites on chromosome 21

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    Introduction: Down syndrome (DS), the leading genetic cause of mental retardation, stems from non-disjunction of chromosome 21. Aim: Our aim was to discern non-disjunction in DS patients by genotyping GluK1-(AGAT) n and D21S2055-(GATA) n microsatellites on chromosome 21 using a family-based study design. Materials and Methods: We have used a PCR and automated DNA sequencing followed by appropriate statistical analysis of genotype data for the present study Results and Discussion: We show that a high power of discrimination and a low probability of matching indicate that both markers may be used to distinguish between two unrelated individuals. That the D21S2055-(GATA) n allele distribution is evenly balanced, is indicated by a high power of exclusion [PE=0.280]. The estimated values of observed heterozygosity and polymorphism information content reveal that relative to GluK1-(AGAT) n [H obs =0.286], the D21S2055- (GATA) n [H obs =0.791] marker, is more informative. Though allele frequencies for both polymorphisms do not conform to Hardy-Weinberg equilibrium proportions, we were able to discern the parental origin of non-disjunction and also garnered evidence for triallelic (1:1:1) inheritance. The estimated proportion of meiosis-I to meiosis-II errors is 2:1 in maternal and 4:1 in paternal cases for GluK1-(AGAT) n , whereas for D21S2055-(GATA) n , the ratio is 2:1 in both maternal and paternal cases. Results underscore a need to systematically evaluate additional chromosome 21-specific markers in the context of non-disjunction DS

    Barium esophagogram in various esophageal diseases: A pictorial essay

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    Recent years have seen a decline in number of barium procedures due to wider availability of cross sectional imaging modalities. Though use of barium esophagography/barium swallow has decreased in day to day clinical practice, it still remains a valuable test for structural and functional evaluation of esophagus. It can be performed as single or double contrast examination or as a multiphasic examination comprising upright double contrast views followed by prone single contrast views. This pictorial essay demonstrates imaging features of various esophageal diseases on barium esophagogram
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