Biology subjects

Reddy, A.

Publications and source records attributed to Reddy, A..

23 records · Page 2Linked to original sources

bioRxiv2020

Temporal evolution of single-cell transcriptomes of Drosophila olfactory projection neurons

Neurons undergo substantial morphological and functional changes during development to form precise synaptic connections and acquire specific physiological features. What are the underlying transcriptomic bases? Here, we obtained the single-cell transcriptomes of Drosophila olfactory projection neurons (PNs) at four developmental stages. We decoded the identity of 21 transcriptomic clusters corresponding to 20 PN types and developed methods to match transcriptomic clusters representing the same PN type across development. We discovered that PN transcriptomes reflect unique biological processes unfolding at each stage--neurite growth and pruning during metamorphosis at an early pupal stage; peaked transcriptomic diversity during olfactory circuit assembly at mid-pupal stages; and neuronal signaling in adults. At early developmental stages, PN types with adjacent birth order share similar transcriptomes. Together, our work reveals principles of cellular diversity during brain development and provides a resource for future studies of neural development in PNs and other neuronal types.

neuroscience↗

bioRxiv2019

Recent evolutionary history of tigers highlights contrasting roles of genetic drift and selection

Formulating strategies for species conservation requires knowledge of evolutionary and genetic history. Tigers are among the most charismatic of endangered species and garner significant conservation attention. However, the evolutionary history and genomic variation of tigers remain poorly known. With 70% of the worlds wild tigers living in India, such knowledge is critical for tiger conservation. We re-sequenced 65 individual tiger genomes across their extant geographic range, representing most extant subspecies with a specific focus on tigers from India. As suggested by earlier studies, we found strong genetic differentiation between the putative tiger subspecies. Despite high total genomic diversity in India, individual tigers host longer runs of homozygosity, potentially suggesting recent inbreeding, possibly because of small and fragmented protected areas. Surprisingly, demographic models suggest recent divergence (within the last 10,000 years) between populations, and strong population bottlenecks. Amur tiger genomes revealed the strongest signals of selection mainly related to metabolic adaptation to cold, while Sumatran tigers show evidence of evolving under weak selection for genes involved in body size regulation. Depending on conservation objectives, our results support the isolation of Amur and Sumatran tigers, while geneflow between Malayan and South Asian tigers may be considered. Further, the impacts of ongoing connectivity loss on the health and persistence of tigers in India should be closely monitored.

genomics↗

bioRxiv2019

Role of ethnicity and socio-economic status (SES) in the presentation of retinoblastoma: findings from the UK

PurposeThe aim of this study was to investigate if there was a relationship between ethnicity or socioeconomic status and the presentation of advanced non-familial retinoblastoma in the UK.\n\nMethodsA cross sectional study based at the two centres providing retinoblastoma care in the UK. Non-familial cases of retinoblastoma (Rb) presenting between January 2006 and December 2011 were included. Data collected included: age at diagnosis, gender, childs ethnicity, International Intraocular Retinoblastoma Classification (IIRC) stage with Groups D and E being considered advanced, laterality, treatment, and postcodes. Individual postcode (ZIP code) data was used to obtain the Index of Multiple Deprivation (IMD) score. A postal questionnaire was sent to participants parents to collect further, person-level, information on languages spoken and household socioeconomic position. Measures of severity of retinoblastoma also included: requirement for primary enucleation; the use of adjuvant chemotherapy; and mortality.\n\nResults189 cases were analyzed. 98 (52%) male and 91 (48%) female. Median age at diagnosis was 16 months [IQR 8 - 34 months]. 153/189 (81%) of cases presented with advanced retinoblastoma; 75 (40%) group E, 78 (41%) group D. 134 (72%) of cases were treated with enucleation.\n\nMultivariable analysis showed that older age at presentation was associated with enucleation and bilateral disease was associated with adjuvant chemotherapy. There was some indication that South Asian ethnicity and being in the most deprived IMD quintile were associated with a higher likelihood of presentation with advanced disease, but these estimates did not reach statistical significance.\n\nConclusionsIn this first national UK study of patients with non-familial retinoblastoma, there was no evidence of an association of ethnicity or socio-economic status and the risk of presenting with advanced disease. This may reflect equality in access of health care in the UK. As a result, awareness campaigns should continue.

epidemiology↗

bioRxiv2017

Development of an in vitro pre-mRNA splicing assay using plant nuclear extract

BackgroundPre-mRNA splicing is an essential post-transcriptional process in all eukaryotes. In vitro splicing systems using nuclear or cytoplasmic extracts from mammalian cells, yeast, and Drosophila have provided a wealth of mechanistic insights into assembly and composition of the spliceosome, splicing regulatory proteins and mechanisms of pre-mRNA splicing in non-plant systems. The lack of an in vitro splicing system prepared from plant cells has been a major limitation in splicing research in plants.\n\nResultsHere we report an in vitro splicing assay system using plant nuclear extract. Several lines of evidence indicate that nuclear extract (NE) derived from Arabidopsis seedlings can convert pre-mRNA substrate (LHCB3) into a spliced product. These include: i) generation of an RNA product that corresponds to the size of expected mRNA, ii) a junction-mapping assay using S1 nuclease revealed that the two exons are spliced together, iii) the reaction conditions are similar to those found with non-plant extracts and iv) finally mutations in conserved donor and acceptor sites abolished the production of the spliced product.\n\nConclusionsThis first report on the plant in vitro splicing assay opens new avenues to investigate plant spliceosome assembly and composition, and splicing regulatory mechanisms specific to plants.

plant biology↗

bioRxiv2017

Id proteins suppress E2A-driven innate-like T cell development prior to TCR selection

Id proteins have been shown to promote the differentiation of conventional {beta} and {gamma}{delta}T cells, and to suppress the expansion of invariant Natural Killer T (iNKT) cells and innate-like {gamma}{delta}NKT within their respective cell lineages. However, it remains to be determined whether Id proteins regulate lineage specification in developing T cells that give rise to these distinct cell fates. Here we report that in the absence of Id2 and Id3 proteins, E2A prematurely activates genes critical for the iNKT cell lineage prior to TCR expression. Enhanced iNKT development in Id3-deficient mice lacking {gamma}{delta} NKT cells suggests that Id3 regulates the lineage competition between these populations. RNA-Seq analysis establishes E2A as the transcriptional regulator of both iNKT and {gamma}{delta}NKT development. In the absence of pre-TCR signaling, Id2/Id3 deletion gives rise to a large population of iNKT cells and a unique innate-like DP population, despite the block in conventional {beta} T cell development. The transcriptional profile of these unique DP cells reflects enrichment of innate-like signature genes, including PLZF (Zbtb16) and Granzyme A (Gzma). Results from these genetic models and genome-wide analyses suggest that Id proteins suppress E2A-driven innate-like T cell programs prior to TCR selection to enforce predominance of conventional T cells.

immunology↗