A bifunctional baculovirus homologous region (hr1) sequence: enhancer and orginal of replication functions reside within the same sequence element

Analysis of the synergy between transcription regulation and DNA replication as well as the mechanisms of enhancer action has been of interest to us. Our studies on the Autographa californica multi-nucleocapsid nuclear polyhedrosis virus (AcMNPV) have revealed that the viral homologous region sequence, hr1, can function as an enhancer of polyhedron promoter-driven transcription as well as an origin of DNA replication in transfected host insect cells. Minimal sequence requirements for both these activities of hr1 have been delineated. A host factor that interacts at multiple sites within hr1 has also been implicated in the enhancer function of this sequence. While demonstrating the dual function of hr1, our observations also indicate the importance of host factor(s) in regulating crucial processes in the viral infection cycle

A bifunctional baculovirus homologous region (hrl) sequence: Enhancer and origin of replication

Analysis of the synergy between transcription regulation and DNA replication as well as the mechanisms of enhancer action has been of interest to us. Our studies on the Autographa califomica multinucleocapsid nuclear polyhedrosis virus (AcMNPV) have revealed that the viral homologous region se-quence, hrl, can function as an enhancer of polyhedrin promoter-driven transcription as well as an origin of DNA replication in transfected host insect cells. Minimal sequence requirements for both these activities of hrl have been delineated. A host factor that interacts at multiple sites within hrl has also been implicated in the enhancer function of this sequence. While demonstrating the duel function of hr1, our observations also indicate the importance of host factor(s) in regulating crucial processes in the viral infection cycle

The host factor polyhedrin promoter binding protein (PPBP) is involved in transcription from the baculovirus polyhedrin gene promoter

Hypertranscription and temporal expression from the Autographa californica nuclear polyhedrosis (AcNPV) baculovirus polyhedrin promoter involves an α-amanitin-resistant RNA polymerase and requires a trans-acting viral factor(s). We previously reported that a 30-kDa host factor, polyhedrin promoter binding protein (PPBP), binds with unusual affinity, specificity, and stability to the transcriptionally important motif AATAAATAAGTATT within the polyhedrin (polh) initiator promoter and also displays coding strand-specific single-stranded DNA (ssDNA)-binding activity (S. Burma, B. Mukherjee, A. Jain, S. Habib, and S. E. Hasnain, J. Biol. Chem. 269:2750-2757, 1994; B. Mukherjee, S. Burma, and S. E. Hasnain, J. Biol. Chem. 270:4405-4411, 1995). We now present evidence which indicates that an additional factor(s) is involved in stabilizing PPBP-duplex promoter and PPBP-ssDNA interactions. TBP (TATA box binding protein) present in Spodoptera frugiperda (Sf9) cells is characteristically distinct from PPBP and does not interact directly with the polh promoter. Replacement of PPBP cognate sequences within the polh promoter with random nucleotides abolished PPBP binding in vitro and also failed to express the luciferase reporter gene in vivo. Phosphocellulose fractions of total nuclear extract from virus-infected cells which support in vitro transcription from the polh promoter contain PPBP activity. When PPBP was sequestered by the presence of oligonucleotides containing PPBP cognate sequence motifs, in vitro transcription of a C-free reporter cassette was affected but was restored by the exogenous addition of nuclear extract containing PPBP. When PPBP was mopped out in vivo by a plasmid carrying PPBP cognate sequence present in trans, polh promoter-driven expression of the luciferase reporter was abolished, demonstrating that binding of PPBP to the polh promoter is essential for transcription

Genetic differentiation of populations residing in areas of high malaria endemicity in India

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Drivers of food waste reduction behaviour in the household context

Studies on the drivers of household consumer engagement in various food waste reduction strategies have been limited. We thus address this gap by developing a research model that utilises two well-known theories, namely, the Theory of Interpersonal Behaviour (TIB) and the Comprehensive Model of Environmental Psychology (CMEP), to explain food waste reduction behaviour in household consumers. The model hypothesises positive associations between emotional, social, and cognitive factors and food waste reduction behaviour, as conceptualised using the 3Rs (reuse, reduce, and recycle). A total of 515 U.S. household consumers participated in the cross-sectional survey. The results suggest that emotional (anticipated guilt), social (sense of community), and cognitive factors (awareness about consequences and environmental knowledge) were positively associated with food waste reduction behaviour. However, the study results did not support the association between a sense of community and reuse intentions. Moreover, anticipated guilt and awareness of consequences were significant drivers of the reuse and reduce food waste behaviours, respectively. The age of the study participants also had a significant controlling influence on the reduce intentions. The study findings have significant implications for governments, policymakers, marketers, and academics that are interested in developing strategies to mitigate the impact of food waste.publishedVersio

Drivers of food waste reduction behaviour in the household context

Studies on the drivers of household consumer engagement in various food waste reduction strategies have been limited. We thus address this gap by developing a research model that utilises two well-known theories, namely, the Theory of Interpersonal Behaviour (TIB) and the Comprehensive Model of Environmental Psychology (CMEP), to explain food waste reduction behaviour in household consumers. The model hypothesises positive associations between emotional, social, and cognitive factors and food waste reduction behaviour, as conceptualised using the 3Rs (reuse, reduce, and recycle). A total of 515 U.S. household consumers participated in the cross-sectional survey. The results suggest that emotional (anticipated guilt), social (sense of community), and cognitive factors (awareness about consequences and environmental knowledge) were positively associated with food waste reduction behaviour. However, the study results did not support the association between a sense of community and reuse intentions. Moreover, anticipated guilt and awareness of consequences were significant drivers of the reuse and reduce food waste behaviours, respectively. The age of the study participants also had a significant controlling influence on the reduce intentions. The study findings have significant implications for governments, policymakers, marketers, and academics that are interested in developing strategies to mitigate the impact of food waste.publishedVersio

CDR1, a multidrug resistance gene from Candida albicans, contains multiple regulatory domains in its promoter and the distal AP-1 element mediates its induction by miconazole

We previously demonstrated that the CDR1 gene, encoding a multidrug transporter in Candida albicans, is differentially upregulated by various drugs and steroids. In order to get an insight into the molecular basis of the induction of this gene we analyzed its promoter region. The transcription start site was mapped to 63 nucleotides upstream of the initiating ATG. Reporter assays revealed the presence of four upstream activating and four upstream repressing sequence domains along the entire promoter. Like the native gene, promoter-luciferase recombinants showed enhanced activity in response to various stresses like drugs, human steroid hormones and heavy metals. Mutational analysis demonstrated that while the proximal promoter (−345/+1) contains all the regulatory domains required for its induction by various other stresses, the miconazole response is mediated via the distal promoter (−857/−1147), harboring an AP-1 site. The involvement of the AP-1 element in mediating the latter effect was evident by an increase in AP-1 binding activity following miconazole treatment

Frequency of pregnancy induced hypertension and its association with elevated serum beta human chorionic gonadotropin levels during mid trimester of pregnancy

Objective: To determine the frequency of PIH amongst elevated beta-hCG levels and non-elevated beta-hCG in the mid-trimester of pregnancy. Materials and Methods: It was Descriptive case series conducted for six months (02-12-2019 to 02-06-2020) in OPD of Gynae Unit-II, Holy Family Hospital, Rawalpindi. A total of one hundred and twenty-two (n=122) normotensive pregnant females at 13-20 weeks gestational age and 18-35 years of maternal age were selected in this study after informed consent from every patient. The frequency of PIH in patients with elevated serum beta-hCG was measured. Data were analyzed using SPSS version 20. Effect modifiers were controlled by stratification. A p-value of ≤ 0.05 was considered significant. Results: Mean beta-hCG levels in the total study population were found to be 7305.09±3900.64 IU/mL. Median b-hCG levels in our study population were noted as 6936.15 IU/mL. Pregnancy-induced hypertension was found positive in 16 (13.1%) patients. Raised beta-hCG levels were present in 10 (8.2%) patients. The frequency of PIH in raised beta-HCG levels was found in 7/10 (70%) of patients. We found a statistically significant (p-value ≤ 0.05) difference in the frequency of PIH among patients with elevated and not-elevated beta-hCG levels. Conclusion: It is evident from my study that patients with raised levels of serum β-hCG during mid-trimester pregnancy are at increased risk to develop hypertensive disorders of pregnancy. We further elaborated that there is a statistically significant difference in various effect modifiers such as maternal age, gestational age, residential status, and BMI  for developing  PIH among patients with elevated and non-elevated beta-hCG levels

Housekeeping and other metabolic functions of the Plasmodium plastid

The malaria parasite carries a plastid called the apicoplast that has been the subject of intense study in the last 15 years. Having originated from red-algal plastids, the apicoplast has lost its ability to photosynthesize, but carries out other essential functions such as type-II fatty acid synthesis, biosynthesis of haem and isoprenoid synthesis; the DOXP pathway for isoprenoid synthesis has recently been demonstrated to be the only pathway critical for parasite survival in the erythrocytic stage. The apicoplast also has a functional Suf system for assembly of (Fe–S) complexes on target proteins. The organelle has a 35 kb, double-stranded DNA genome that encodes a set of RNAs and proteins, the latter being translated from organellar mRNA by an active translation machinery, a major component of which is encoded by the nucleus. This article reviews current knowledge of housekeeping functions of the Plasmodium apicoplast and its (Fe–S) assembly system and discusses these components as sites for drug intervention against malaria

Variations in host genes encoding adhesion molecules and susceptibility to falciparum malaria in India

<p>Abstract</p> <p>Background</p> <p>Host adhesion molecules play a significant role in the pathogenesis of <it>Plasmodium falciparum </it>malaria and changes in their structure or levels in individuals can influence the outcome of infection. The aim of this study was to investigate the association of SNPs of three adhesion molecule genes, <it>ICAM1</it>, <it>PECAM1 </it>and <it>CD36</it>, with severity of falciparum malaria in a malaria-endemic and a non-endemic region of India.</p> <p>Methods</p> <p>The frequency distribution of seven selected SNPs of <it>ICAM1</it>, <it>PECAM1 </it>and <it>CD36 </it>was determined in 552 individuals drawn from 24 populations across India. SNP-disease association was analysed in a case-control study format. Genotyping of the population panel was performed by Sequenom mass spectroscopy and patient/control samples were genotyped by SNaPshot method. Haplotypes and linkage disequilibrium (LD) plots were generated using PHASE and Haploview, respectively. Odds-ratio (OR) for risk assessment was estimated using EpiInfo™ version 3.4.</p> <p>Results</p> <p>Association of the ICAM1 rs5498 (exon 6) G allele and the CD36 exon 1a A allele with increased risk of severe malaria was observed (severe versus control, OR = 1.91 and 2.66, P = 0.02 and 0.0012, respectively). The CD36 rs1334512 (-53) T allele as well as the TT genotype associated with protection from severe disease (severe versus control, TT versus GG, OR = 0.37, P = 0.004). Interestingly, a SNP of the <it>PECAM1 </it>gene (rs668, exon 3, C/G) with low minor allele frequency in populations of the endemic region compared to the non-endemic region exhibited differential association with disease in these regions; the G allele was a risk factor for malaria in the endemic region, but exhibited significant association with protection from disease in the non-endemic region.</p> <p>Conclusion</p> <p>The data highlights the significance of variations in the <it>ICAM1</it>, <it>PECAM1 </it>and <it>CD36 </it>genes in the manifestation of falciparum malaria in India. The <it>PECAM1 </it>exon 3 SNP exhibits altered association with disease in the endemic and non-endemic region.</p