circRNAs arise from back splicing events during mRNA processing, and when deregulated can play an active role in cancer. Here we characterize a new circRNA (circPOK) encoded by the Zbtb7a gene (also kown as POKEMON, LRF) in the context of mesenchymal tumor progression. circPOK functions as a non-coding proto-oncogenic RNA independently and antithetically to its linear transcript counterpart, which acts as a tumor suppressor by encoding the Pokemon transcription factor. We find that circPOK regulates proproliferative and pro-angiogenic factors by co-activation of the ILF2/3 complex. Importantly, the expression of Pokemon protein and circRNA is aberrantly uncoupled in cancer through differential post-transcriptional regulation. Thus, we identify a novel type of genetic unit, the iRegulon, that yields biochemically distinct RNA products, circular and linear, with diverse and antithetical functions. Our findings further expand the cellular repertoire towards the control of normal biological outputs, while aberrant expression of such components may underlie disease pathogenesis including cancer.

The purpose of this study was to investigate the effects of body size, foraging mode, and parental care on the relationship between clutch size and egg size in spiders. Specifically, covariation of egg size and clutch size with body size was investigated, using data from the literature, in 156 species of North American spiders from 22 families. Variance in clutch size and egg size was found to be mainly attributed to differences among genera. I therefore conducted a comparative analysis at the generic level. Results indicated that clutch and egg size were influenced by body size. Spiders from genera with larger body sizes produced larger offspring and more offspring per reproductive event than spiders from genera with smaller sized species. Relative egg number was inversely related to size of eggs produced, indicating a reproductive trade—off. Web building spiders produced more and smaller eggs than cursorial hunting spiders of a similar body size. Furthermore, cursorial spiders that guard and carry their young produced more young than those that only guard the eggs before hatching or do not guard. However, residual clutch size or residual egg size (residuals from regressions of clutch size and egg size, respectively, against female body size) did not differ among parental care groups. This study suggests that the method of food acquisition and type of parental care contributed to the offspring are associated with clutch size and egg size in spiders.

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Using qualitative biographical data from a longitudinal study of youth transitions, criminal careers and desistance, this paper casts doubt on the veracity and predictive power of risk assessment devices such as Asset and OASys. These devices, and the research on which they are based, suggest that earlier and current childhood and teenage influences trigger and sustain later re-offending. In contrast, we argue that focus must be shifted to contingent risk factors that accrue in late teenage and young adulthood. Secondly, risk assessment and criminal career research has ignored the influence that unforeseen and unforeseeable processes of neighbourhood destabilization and life events have in criminal careers and their cessation.

Connections between epigenetic reprogramming and transcription or splicing create novel mechanistic networks that can be targeted with tailored therapies. Multiple subunits of the chromatin remodeling BAF complex, including ARID1A, play a role in oncogenesis, either as tumor suppressors or oncogenes. Recent work demonstrated that EWS–FLI1, the oncogenic driver of Ewing sarcoma (ES), plays a role in chromatin regulation through interactions with the BAF complex. However, the specific BAF subunits that interact with EWS–FLI1 and the precise role of the BAF complex in ES oncogenesis remain unknown. In addition to regulating transcription, EWS–FLI1 also alters the splicing of many mRNA isoforms, but the role of splicing modulation in ES oncogenesis is not well understood. We have identified a direct connection between the EWS–FLI1 protein and ARID1A isoform protein variant ARID1A-L. We demonstrate here that ARID1A-L is critical for ES maintenance and supports oncogenic transformation. We further report a novel feed-forward cycle in which EWS–FLI1 leads to preferential splicing of ARID1A-L, promoting ES growth, and ARID1A-L reciprocally promotes EWS–FLI1 protein stability. Dissecting this interaction may lead to improved cancer-specific drug targeting.

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This comparative analysis suggests that in this community setting, the use of postal HIV DBS kits resulted in a significantly improved RRR compared with MT. The biggest factor was the large number of MT samples not analysed due to inadequate blood volumes. The unexpected level of false positive results in the MT samples needs confirming in larger studies.