Gene expression and splicing alterations analyzed by high throughput RNA sequencing of chronic lymphocytic leukemia specimens.

BackgroundTo determine differentially expressed and spliced RNA transcripts in chronic lymphocytic leukemia specimens a high throughput RNA-sequencing (HTS RNA-seq) analysis was performed.MethodsTen CLL specimens and five normal peripheral blood CD19+ B cells were analyzed by HTS RNA-seq. The library preparation was performed with Illumina TrueSeq RNA kit and analyzed by Illumina HiSeq 2000 sequencing system.ResultsAn average of 48.5 million reads for B cells, and 50.6 million reads for CLL specimens were obtained with 10396 and 10448 assembled transcripts for normal B cells and primary CLL specimens respectively. With the Cuffdiff analysis, 2091 differentially expressed genes (DEG) between B cells and CLL specimens based on FPKM (fragments per kilobase of transcript per million reads and false discovery rate, FDR q < 0.05, fold change >2) were identified. Expression of selected DEGs (n = 32) with up regulated and down regulated expression in CLL from RNA-seq data were also analyzed by qRT-PCR in a test cohort of CLL specimens. Even though there was a variation in fold expression of DEG genes between RNA-seq and qRT-PCR; more than 90 % of analyzed genes were validated by qRT-PCR analysis. Analysis of RNA-seq data for splicing alterations in CLL and B cells was performed by Multivariate Analysis of Transcript Splicing (MATS analysis). Skipped exon was the most frequent splicing alteration in CLL specimens with 128 significant events (P-value <0.05, minimum inclusion level difference >0.1).ConclusionThe RNA-seq analysis of CLL specimens identifies novel DEG and alternatively spliced genes that are potential prognostic markers and therapeutic targets. High level of validation by qRT-PCR for a number of DEG genes supports the accuracy of this analysis. Global comparison of transcriptomes of B cells, IGVH non-mutated CLL (U-CLL) and mutated CLL specimens (M-CLL) with multidimensional scaling analysis was able to segregate CLL and B cell transcriptomes but the M-CLL and U-CLL transcriptomes were indistinguishable. The analysis of HTS RNA-seq data to identify alternative splicing events and other genetic abnormalities specific to CLL is an added advantage of RNA-seq that is not feasible with other genome wide analysis

Wealth-related inequalities of women’s knowledge of cervical cancer screening and service utilisation in 18 resource-constrained countries: evidence from a pooled decomposition analysis

Introduction: Resource-constrained countries (RCCs) have the highest burden of cervical cancer (CC) in the world. Nonetheless, although CC can be prevented through screening for precancerous lesions, only a small proportion of women utilise screening services in RCCs. The objective of this study was to examine the magnitude of inequalities of women’s knowledge and utilisation of cervical cancer screening (CCS) services in RCCs. Methods: A total of 1,802,413 sample observations from 18 RCC’s latest national-level Demographic and Health Surveys (2008 to 2017–18) were analysed to assess wealth-related inequalities in terms of women’s knowledge and utilisation of CCS services. Regression-based decomposition analyses were applied in order to compute the contribution to the inequality disparities of the explanatory variables for women’s knowledge and utilisation of CCS services. Results: Overall, approximately 37% of women had knowledge regarding CCS services, of which, 25% belonged to the poorest quintile and approximately 49% from the richest. Twenty-nine percent of women utilised CCS services, ranging from 11% in Tajikistan, 15% in Cote d’Ivoire, 17% in Tanzania, 19% in Zimbabwe and 20% in Kenya to 96% in Colombia. Decomposition analyses determined that factors that reduced inequalities in women’s knowledge of CCS services were male-headed households (− 2.24%; 95% CI: − 3.10%, − 1.59%; P < 0.01), currently experiencing amenorrhea (− 1.37%; 95% CI: − 2.37%, − 1.05%; P < 0.05), having no problems accessing medical assistance (− 10.00%; 95% CI: − 12.65%, − 4.89%; P < 0.05), being insured (− 6.94%; 95% CI: − 9.58%, − 4.29%; P < 0.01) and having an urban place of residence (− 9.76%; 95% CI: − 12.59%, − 5.69%; P < 0.01). Similarly, factors that diminished inequality in the utilisation of CCS services were being married (− 8.23%; 95% CI: − 12.46%, − 5.80%; P < 0.01), being unemployed (− 14.16%; 95% CI: − 19.23%, − 8.47%; P < 0.01) and living in urban communities (− 9.76%; 95% CI: − 15.62%, − 5.80%; P < 0.01). Conclusions: Women’s knowledge and utilisation of CCS services in RCCs are unequally distributed. Significant inequalities were identified among socioeconomically deprived women in the majority of countries. There is an urgent need for culturally appropriate community-based awareness and access programs to improve the uptake of CCS services in RCCs

Reappraising David Livingstone's The Geographical Tradition from complex locations: more‐than‐contextual historiographies

This paper reflects on The Geographical Tradition through the lens of feminist and other critical historiographies of geography, linking therein to recent discussion on the relative merits of canonical status and the dilemmas and legacies of wide‐ranging, selective, and partial histories. It argues for inclusive, more‐than‐contextual historiographies, and reflects on what these mean epistemologically, methodologically, and in terms of the contemporary experience of the discipline

Discovery of novel herpes simplexviruses in wild gorillas, bonobos, and chimpanzees supports zoonotic origin of HSV-2

Viruses closely related to human pathogens can reveal the origins of human infectious diseases. Human herpes simplexvirus type 1 (HSV-1) and type 2 (HSV-2) are hypothesized to have arisen via host-virus codivergence and cross-species transmission. We report the discovery of novel herpes simplexviruses during a large-scale screening of fecal samples from wild gorillas, bonobos, and chimpanzees. Phylogenetic analysis indicates that, contrary to expectation, simplexviruses from these African apes are all more closely related to HSV-2 than to HSV-1. Molecular clock-based hypothesis testing suggests the divergence between HSV-1 and the African great ape simplexviruses likely represents a codivergence event between humans and gorillas. The simplexviruses infecting African great apes subsequently experienced multiple cross-species transmission events over the past 3 My, the most recent of which occurred between humans and bonobos around 1 Ma. These findings revise our understanding of the origins of human herpes simplexviruses and suggest that HSV-2 is one of the earliest zoonotic pathogens

Naturally-Acquired Influenza-Specific CD4+ T-Cell Proliferative Responses Are Impaired in HIV-Infected African Adults

BACKGROUND Seasonal influenza has been associated with greater morbidity and mortality in AIDS patients. Highly-active antiretroviral therapy (HAART) has led to some reduction in influenza-related complications but the nature of naturally-acquired T-cell immunity to influenza virus in an African setting, and how this changes with immune reconstitution following HAART is unknown. We measured influenza-specific CD4(+) T-cell immunity in unimmunized HIV-infected Malawian adults and then investigated immune reconstitution following HAART. METHODS Peripheral blood mononuclear cells were isolated from HIV-infected and HIV-uninfected Malawian adults. CFSE proliferation and CD154 expression flow cytometry-based assays were used to measure influenza-specific CD4(+) T-cell immunity. RESULTS We found lower naturally-acquired proliferative influenza-specific CD4(+) T-cell responses in AIDS patients that was also present in asymptomatic HIV-infected adults with relatively high CD4 counts (>350 cells/µl). Influenza-specific CD4(+) T-cell immune reconstitution in HIV-infected patients on HAART for 12 months was poor despite a marked reduction in viral load and an increase in CD4 count. This poor immune reconstitution was characterised by a low influenza-specific proliferative CD4(+) T-cell response and reduced proportions of CD154-expressing influenza-specific CD4(+) T-cells in peripheral blood. CONCLUSION Our data suggest that asymptomatic HIV-infected adults may also be at risk of influenza-related complications and that HAART alone may not circumvent this risk in AIDS patients. This study highlights the need to identify possible interventions early in HIV infection to reduce the risk of influenza and to intensify influenza surveillance in these susceptible African populations

Tackling health inequalities: moving theory to action

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Marine recreational fishing and the implications of climate change

Marine recreational fishing is popular globally and benefits coastal economies and people's well-being. For some species, it represents a large component of fish landings. Climate change is anticipated to affect recreational fishing in many ways, creating opportunities and challenges. Rising temperatures or changes in storms and waves are expected to impact the availability of fish to recreational fishers, through changes in recruitment, growth and survival. Shifts in distribution are also expected, affecting the location that target species can be caught. Climate change also threatens the safety of fishing. Opportunities may be reduced owing to rougher conditions, and costs may be incurred if gear is lost or damaged in bad weather. However, not all effects are expected to be negative. Where weather conditions change favourably, participation rates could increase, and desirable species may become available in new areas. Drawing on examples from the UK and Australia, we synthesize existing knowledge to develop a conceptual model of climate-driven factors that could impact marine recreational fisheries, in terms of operations, participation and motivation. We uncover the complex pathways of drivers that underpin the recreational sector. Climate changes may have global implications on the behaviour of recreational fishers and on catches and local economies

Culturally valuable minority crops provide a succession of floral resources for flower visitors in traditional orchard gardens

Agricultural intensification typically has detrimental effects on pollinator communities, but diverse cropping systems that contain sequentially-flowering crops have the potential to benefit pollinators through the provision of additional floral resources. In this study we investigate the importance of cultivated flora for flower visitors in ten agricultural gardens in South Sinai, Egypt. Insect-flower interactions in gardens and unmanaged plots were surveyed across a four-month period in two environmentally distinct years (pre-flood and post-flood). Despite containing an equal abundance and diversity of wild plants as unmanaged habitat, gardens supported a higher abundance and diversity of flower visitors due to the additional presence of cultivated flora. Visitation networks exhibited dramatic intra-annual changes in composition, with cultivated plants becoming increasingly important in later months. Trends were highly conserved across 2 years despite highly contrasting rainfall. Several key crop species were strongly involved in shaping the structure of the networks, the majority of which were herbs with strong cultural significance (fennel, rosemary, mint) and grown incidentally alongside the primary orchard crops. Minority crops are frequently overlooked in agricultural systems due to their low economic value, but we show that they can have a dramatic influence upon the structure of visitation networks, increasing both pollinator abundance and diversity, and emphasising the link between cultural practices and biodiversity conservation

National prevalence and trends of HIV transmitted drug resistance

Abstract Background: Transmitted drug resistance (TDR) remains an important concern for the management of HIV infection, especially in countries that have recently scaled-up antiretroviral treatment (ART) access