Expression and subcellular localization of cyclin D1 protein in epithelial ovarian tumour cells

The expression of cyclin D1 protein in tumour sections from 81 patients with epithelial ovarian cancer was analysed using immunohistochemistry. The tumours that overexpressed cyclin D1 in more than 10% of neoplastic cells were considered positive. Thus overexpression of cyclin D1 was observed in 72/81 (89%) of the cases examined. Protein was detected in both the nucleus and the cytoplasm in 24/81 (30%) and localized exclusively in the cytoplasm in 48/81 (59%) of the tumours. Cyclin D1 was overexpressed in both borderline and invasive tumours. There was no association between protein overexpression and tumour stage and differentiation. Furthermore, no correlation between cyclin D1 expression and clinical outcome was observed. However, in tumours overexpressing cyclin D1 (n = 72), the proportion displaying exclusively cytoplasmic localization of protein was higher in those with serous compared with non-serous histology (P = 0.004, odds ratio 4.8, 95% confidence interval 1.4–19.1). Western analysis using a monoclonal antibody to cyclin D1 identified a 36 kDa protein in homogenates from seven tumours displaying cytoplasmic only and one tumour demonstrating both nuclear and cytoplasmic immunostaining. Using restriction fragment length polymorphism polymerase chain reaction and PCR-multiplex analysis, amplification of the cyclin D1 gene (CCNDI) was detected in 1/29 of the tumours demonstrating overexpression of cyclin D1 protein. We conclude that deregulation of CCND1 expression leading to both cytoplasmic and nuclear protein localization is a frequent event in ovarian cancer and occurs mainly in the absence of gene amplification. © 1999 Cancer Research Campaig

Control of the induction of type I interferon by Peste des petits ruminants virus.

Peste des petits ruminants virus (PPRV) is a morbillivirus that produces clinical disease in goats and sheep. We have studied the induction of interferon-β (IFN-β) following infection of cultured cells with wild-type and vaccine strains of PPRV, and the effects of such infection with PPRV on the induction of IFN-β through both MDA-5 and RIG-I mediated pathways. Using both reporter assays and direct measurement of IFN-β mRNA, we have found that PPRV infection induces IFN-β only weakly and transiently, and the virus can actively block the induction of IFN-β. We have also generated mutant PPRV that lack expression of either of the viral accessory proteins (V&C) to characterize the role of these proteins in IFN-β induction during virus infection. Both PPRV_ΔV and PPRV_ΔC were defective in growth in cell culture, although in different ways. While the PPRV V protein bound to MDA-5 and, to a lesser extent, RIG-I, and over-expression of the V protein inhibited both IFN-β induction pathways, PPRV lacking V protein expression can still block IFN-β induction. In contrast, PPRV C bound to neither MDA-5 nor RIG-I, but PPRV lacking C protein expression lost the ability to block both MDA-5 and RIG-I mediated activation of IFN-β. These results shed new light on the inhibition of the induction of IFN-β by PPRV

The neurobiology of mouse models syntenic to human chromosome 15q

Autism is a neurodevelopmental disorder that manifests in childhood as social behavioral abnormalities, such as abnormal social interaction, impaired communication, and restricted interest or behavior. Of the known causes of autism, duplication of human chromosome 15q11–q13 is the most frequently associated cytogenetic abnormality. Chromosome 15q11–q13 is also known to include imprinting genes. In terms of neuroscience, it contains interesting genes such as Necdin, Ube3a, and a cluster of GABAA subunits as well as huge clusters of non-coding RNAs (small nucleolar RNAs, snoRNAs). Phenotypic analyses of mice genetically or chromosomally engineered for each gene or their clusters on a region of mouse chromosome seven syntenic to human 15q11–q13 indicate that this region may be involved in social behavior, serotonin metabolism, and weight control. Further studies using these models will provide important clues to the pathophysiology of autism. This review overviews phenotypes of mouse models of genes in 15q11–q13 and their relationships to autism

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Sustainability of urban parks planning policies in Bangladesh: a comparative analysis

Urban parks, the key domain of sustainability of the community, integrate social, economic and ecological benefits. Current research are consistently concerned in planning for sustainable and resilient cities through preserving urban green areas are mainly concerned with a large, bio-diverse and relatively endangered ecosystem. While such efforts act as benchmarks for assessing progress towards sustainability and resilience goals, obviously much less attention is being paid to that type of small-scale green areas more specifically urban parks in cities and their benefits to societies. Thus, the extension of these benefits whether or not is equitably distributed across diverse urban populations in cities is a remarkable quarry in urban design policies and practices, especially in developing nations. This research, therefore, aims to analyze of conventional urban design practice on sustainability, more specifically on ecosystem services. Since ecosystem services are vary geographically, the policies even under national guidelines, need to be localized to appreciate the strength of local ecology. Hence, first, this paper develops a theoretical framework of a sustainable urban park with arguing that beyond biodiversity and socio-economic status, urban parks can also inform urban planning policy and practices to promote sustainable urbanism through practices of urban form. Second, it assesses sustainability of urban parks to compare similar urban parks in two different topographies like biodiversity with varied ecosystem services. This qualitative research adopts deductive approach and case study method to evaluate and compare the planning policies of such two parks in two different cities in Bangladesh. Thus, Hadis Park in industrial city Khulna and Biplob Uddan in coastal seaport city Chittagong respectively have taken from two different ecological viewpoints. Multi methodological approaches, including questionnaire survey, interviews with academics and professionals, observation and document policies of the urban park in terms of ecological and planning viewpoints, have been accompanied. Findings reveal that urban park planning policies in both cities mostly focus on generating social and economic activities only relatively for short-term basis rather than on promoting ecological sustainability and biodiversity for long-term maximization. The study, therefore, concludes that traditional urban design practices merely motivated, or supportive to provide sustainable urban park design policies by municipalities and professionals. Further, multi-disciplinary efforts including ecology, landscape architecture, urban planning and urban design simultaneously well informed by locals are essential to assess and develop ecologically sensitive urban design and planning policies

Sustainability of urban parks planning policies in bangladesh: a comparative analysis

Urban parks, the key domain of sustainability of the community, integrate social, economic and ecological benefits. Current research are consistently concerned in planning for sustainable and resilient cities through preserving urban green areas are mainly concerned with a large, bio-diverse and relatively endangered ecosystem. While such efforts act as benchmarks for assessing progress towards sustainability and resilience goals, obviously much less attention is being paid to that type of small-scale green areas more specifically urban parks in cities and their benefits to societies. Thus, the extension of these benefits whether or not is equitably distributed across diverse urban populations in cities is a remarkable quarry in urban design policies and practices, especially in developing nations. This research, therefore, aims to analyze of conventional urban design practice on sustainability, more specifically on ecosystem services. Since ecosystem services are vary geographically, the policies even under national guidelines, need to be localized to appreciate the strength of local ecology. Hence, first, this paper develops a theoretical framework of a sustainable urban park with arguing that beyond biodiversity and socio-economic status, urban parks can also inform urban planning policy and practices to promote sustainable urbanism through practices of urban form. Second, it assesses sustainability of urban parks to compare similar urban parks in two different topographies like biodiversity with varied ecosystem services. This qualitative research adopts deductive approach and case study method to evaluate and compare the planning policies of such two parks in two different cities in Bangladesh. Thus, Hadis Park in industrial city Khulna and Biplob Uddan in coastal seaport city Chittagong respectively have taken from two different ecological viewpoints. Multi methodological approaches, including questionnaire survey, interviews with academics and professionals, observation and document policies of the urban park in terms of ecological and planning viewpoints, have been accompanied. Findings reveal that urban park planning policies in both cities mostly focus on generating social and economic activities only relatively for short-term basis rather than on promoting ecological sustainability and biodiversity for long-term maximization. The study, therefore, concludes that traditional urban design practices merely motivated, or supportive to provide sustainable urban park design policies by municipalities and professionals. Further, multi-disciplinary efforts including ecology, landscape architecture, urban planning and urban design simultaneously well informed by locals are essential to assess and develop ecologically sensitive urban design and planning policies