The RNA-binding protein LARP1 is a post-transcriptional regulator of survival and tumorigenesis in ovarian cancer

RNA-binding proteins (RBPs) are increasingly identified as post-transcriptional drivers of cancer progression. The RBP LARP1 is an mRNA stability regulator, and elevated expression of the protein in hepatocellular and lung cancers is correlated with adverse prognosis. LARP1 associates with an mRNA interactome that is enriched for oncogenic transcripts. Here we explore the role of LARP1 in epithelial ovarian cancer, a disease characterized by the rapid acquisition of resistance to chemotherapy through the induction of pro-survival signalling. We show, using ovarian cell lines and xenografts, that LARP1 is required for cancer cell survival and chemotherapy resistance. LARP1 promotes tumour formation in vivo and maintains cancer stem cell-like populations. Using transcriptomic analysis following LARP1 knockdown, cross-referenced against the LARP1 interactome, we identify BCL2 and BIK as LARP1 mRNA targets. We demonstrate that, through an interaction with the 3 untranslated regions (3 UTRs) of BCL2 and BIK, LARP1 stabilizes BCL2 but destabilizes BIK with the net effect of resisting apoptosis. Together, our data indicate that by differentially regulating the stability of a selection of mRNAs, LARP1 promotes ovarian cancer progression and chemotherapy resistance

Influence of Time Dependent Factors To The Phases and Poisson's Ratio of Cholesteryl Ester liquid crystals

Liquid crystal based biosensors detect physical restructuring of cells via changes in the birefringence property or orientation order of the liquid crystal molecules. The strain induced in the liquid crystal molecules is closely associated with the liquid crystalline phases and Poisson’s ratio of the liquid crystals. Cholesteryl ester liquid crystals (CELC) and CELC based lyotropic liquid crystals (LLC) that were regarded as viscoelastic materials are subjected to time-dependent factors (a fluidic environment, incubation time, and temperature). The effects of these factors, qualitatively and quantitatively, were investigated by using cross-polarising microscopy and a uniaxial micro-tensile technique. More lyotropic phases were observed in the liquid crystals as the incubation time in cell culture media was increased. Poisson’s ratio of approximately 0.58 and 0.6 were determined for CELC and LLC, respectively, at room (25 oC) and incubation (37 oC) temperatures over a period of 3 days

Sector well-being differences among UK police custody staff

The research explores a new model of staff well-being across UK police custodial services (public and private). These services are unique for the fact that police sergeant custody officers are supported by detention officers who can be publicly or privately contracted, with the latter providing a heterogeneous mix never previously researched. The model informs a survey approach conducted across four English police forces. Drawing on a diverse literature which compares health and criminal justice professions, this study explores the possibility that private sector detention officers will report lower levels of emotional exhaustion and workplace stress and higher levels of personal accomplishment than their public sector counterparts. Multilevel analyses, supplemented by ANOVA and t tests, detected statistically significant differences for private sector detention officers regarding higher levels of emotional exhaustion and lower levels of personal accomplishment and workplace stress (with the stress result the only one in the predicted direction). However, results should be interpreted as sample specific linked to privately contracted detention officer disquiet with their then employer (since replaced). That said, the results provide a good exploration of the model's utility together with important lessons for model and survey development in the future

Subcellular mRNA Localization Regulates Ribosome Biogenesis in Migrating Cells

Translation of ribosomal protein-coding mRNAs (RP-mRNAs) constitutes a key step in ribosome biogenesis, but the mechanisms that modulate RP-mRNA translation in coordination with other cellular processes are poorly defined. Here, we show that subcellular localization of RP-mRNAs acts as a key regulator of their translation during cell migration. As cells migrate into their surroundings, RP-mRNAs localize to the actin-rich cell protrusions. This localization is mediated by La-related protein 6 (LARP6), an RNA-binding protein that is enriched in protrusions. Protrusions act as hotspots of translation for RP-mRNAs, enhancing RP synthesis, ribosome biogenesis, and the overall protein synthesis in migratory cells. In human breast carcinomas, epithelial-to-mesenchymal transition (EMT) upregulates LARP6 expression to enhance protein synthesis and support invasive growth. Our findings reveal LARP6-mediated mRNA localization as a key regulator of ribosome biogenesis during cell migration and demonstrate a role for this process in cancer progression downstream of EMT

The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5′TOP sequence

La-related protein 1 (LARP1) regulates the stability of many mRNAs. These include 5′TOPs, mTOR-kinase responsive mRNAs with pyrimidine-rich 5′ UTRs, which encode ribosomal proteins and translation factors. We determined that the highly conserved LARP1-specific C-terminal DM15 region of human LARP1 directly binds a 5′TOP sequence. The crystal structure of this DM15 region refined to 1.86 Å resolution has three structurally related and evolutionarily conserved helix-turn-helix modules within each monomer. These motifs resemble HEAT repeats, ubiquitous helical protein-binding structures, but their sequences are inconsistent with consensus sequences of known HEAT modules, suggesting this structure has been repurposed for RNA interactions. A putative mTORC1-recognition sequence sits within a flexible loop C-terminal to these repeats. We also present modelling of pyrimidine-rich single-stranded RNA onto the highly conserved surface of the DM15 region. These studies lay the foundation necessary for proceeding toward a structural mechanism by which LARP1 links mTOR signaling to ribosome biogenesis

Recommended terminology concerning people with a criminal conviction

This guide to terminology has been created to support staff and students in understanding helpful and appropriate ways to refer to people who have previously been convicted of a criminal offence. It has been put together with input from a survey of NTU Psychology staff, best practice guidance from the American Psychological Association, The Marshall (Language) Project, Her Majesty’s Prison and Probation Service, academic journals, research, and individuals with a vested interest in the use of language that supports rather than excludes

New Asian and Nearctic Hypechiniscus species (Heterotardigrada: Echiniscidae) signalize a pseudocryptic horn of plenty

The cosmopolitan echiniscid genus Hypechiniscus contains exclusively rare species. In this contribution, by combining statistical morphometry and molecular phylogeny, we present qualitative and quantitative aspects of Hypechiniscus diversity, which remained hidden under the two purportedly cosmopolitan species: H. gladiator and H. exarmatus. A neotype is designated for H. gladiator from Creag Meagaidh (Scotland), and an informal re-description is provided for H. exarmatus based on animals from Creag Meagaidh and the Isle of Skye (Inner Hebrides). Subspecies/forms of H. gladiator are suppressed due to the high developmental variability of the cirrus dorsalis. At the same time, four species of the genus are described: H. daedalus sp. nov. from Roan Mountain and the Great Smoky Mountains (Southern Appalachian Mountains, USA), H. flavus sp. nov. and H. geminus sp. nov. from the Yatsugatake Mountains (Honshu, Japan), and H. cataractus sp. nov. from the Malay Archipelago (Borneo and the Moluccas). Dorsal and ventral sculpturing, together with morphometric traits, are shown to be the key characters that allow for the phenotypic discrimination of species within the genus. Furthermore, the morphology of Hypechiniscus is discussed and compared to that of the most similar genera, Pseudechiniscus and Stellariscus. Finally, a diagnostic key to all recognized Hypechiniscus species is provided

Serendipitous isolation of a disappearing conformational polymorph of succinic acid challenges computational polymorph prediction

A conformational polymorph (γ) of succinic acid was discovered in an attempt to purify a leucine dipeptide by cocrystallization from a methanol solution in the presence of various impurities, such as trifluoroacetic acid. The new γ form was found to have crystallized concomitantly with the most stable β form. In light of this situation, a crystal structure prediction study was undertaken to examine the polymorph landscape. These studies reveal that the γ polymorph is thermodynamically competitive with the other observed polymorphs; having a more stable folded conformation than the planar crystalline conformation in the β form, but being stabilized less by the intermolecular interactions. Simulations and experiment show that the folded conformation is dominant in solution, but that trapping long-lived crystals of the new metastable polymorph may be challenging. Thus the γ polymorph provides a stringent test of theories for predicting which thermodynamically plausible structures may be practically important polymorphs

"It’s sort of reaffirmed to me that I'm not a monster, I'm not a terrible person": sex offenders’ movements toward desistance via peer-support roles in prison

Individuals incarcerated in prisons across the United Kingdom and abroad are able to volunteer for a variety of peer-support roles, which are characterized by prisoner-to-prisoner helping. Some research has found that such roles can represent turning points in the lives of those who have offended and encourage movements toward desistance. This proposed redemptive influence is argued to result from the prosocial behaviors that such roles appear to elicit in their holders. The present study aims to explore the mechanics of this claimed influence. While a limited amount of research has attempted this on a general offending population, no research has done so with a sample of sexual offenders. Given the intensive treatment programs involved in such contexts, and the requirements for sexual offenders to demonstrate reduced risk, the authors believe those serving time for sexual offenses represent an important sample on which to explore the potentially redemptive properties of peer-support roles. To this end, 13 peer supporters participated in semistructured interviews. Transcripts were analyzed using a phenomenologically oriented thematic analysis. Results suggest that sexual offenders who adopt peer-support roles are able to live up to desired selves by “doing good” in prison, “giving back,” and consequently resisting negative labels. These benefits have been theoretically linked with better reintegration outcomes for sexual offenders, who are publicly denigrated in the extreme and find it especially difficult to (re)integrate. Suggestions regarding the future utility of such schemes are offered