Subcellular fractionation of primary chronic lymphocytic leukemia cells to monitor nuclear/ cytoplasmic protein trafficking

Nuclear export of macromolecules is often deregulated in cancer cells. Tumor suppressor proteins, such as p53, can be rendered inactive due to aberrant cellular localization disrupting their mechanism of action. The survival of chronic lymphocytic leukaemia (CLL) cells, among other cancer cells, is assisted by the deregulation of nuclear to cytoplasmic shuttling, at least in part through deregulation of the transport receptor XPO1 and the constitutive activation of PI3K-mediated signaling pathways. It is essential to understand the role of individual proteins in the context of their intracellular location to gain a deeper understanding of the role of such proteins in the pathobiology of the disease. Furthermore, identifying processes that underlie cell stimulation and the mechanism of action of specific pharmacological inhibitors, in the context of subcellular protein trafficking, will provide a more comprehensive understanding of the mechanism of action. The protocol described here enables the optimization and subsequent efficient generation of nuclear and cytoplasmic fractions from primary chronic lymphocytic leukemia cells. These fractions can be used to determine changes in protein trafficking between the nuclear and cytoplasmic fractions upon cell stimulation and drug treatment. The data can be quantified and presented in parallel with immunofluorescent images, thus providing robust and quantifiable data

Pilot Study of Skin Cancer Risk Reduction Behaviors, Cancer Communication, and Skin Cancer Beliefs in Hispanics

Purpose: Given rising rates of deadly melanoma skin cancer in Hispanics, the study objective was to examine skin cancer-related risk reduction behaviors and beliefs to dictate content for culturally targeted skin cancer prevention strategies for Hispanics. Methods/Data Source: An anonymous survey was administered to waiting room volunteers in a primary care facility in Albuquerque, New Mexico to assess skin cancer risk reduction behaviors, screening, cancer information seeking and communication, as well as skin cancer beliefs in Hispanics (n=48) and Non-Hispanic Whites (n=36). Results: We found lower levels of sun protection clothing use among Hispanics compared to Non-Hispanic Whites, but comparable use of sunscreen and shade-seeking among these groups. Hispanic ethnicity was the most important predictor of skin cancer misconceptions, with skin cancer information overload and misconceptions reported more often in Hispanics. Conclusions: This study demonstrates the need for culturally relevant information for ethnic minority populations such as Hispanics who have shown an increased risk of presenting with later stage, more aggressive melanoma skin cancer

mTORC1 activity is essential for erythropoiesis and B cell lineage commitment

Mechanistic target of rapamycin (mTOR) is a serine/threonine protein kinase that mediates phosphoinositide-3-kinase (PI3K)/AKT signalling. This pathway is involved in a plethora of cellular functions including protein and lipid synthesis, cell migration, cell proliferation and apoptosis. In this study, we proposed to delineate the role of mTORC1 in haemopoietic lineage commitment using knock out (KO) mouse and cell line models. Mx1-cre and Vav-cre expression systems were used to specifically target Raptorfl/fl (mTORC1), either in all tissues upon poly(I:C) inoculation, or specifically in haemopoietic stem cells, respectively. Assessment of the role of mTORC1 during the early stages of development in Vav-cre+Raptorfl/fl mice, revealed that these mice do not survive post birth due to aberrations in erythropoiesis resulting from an arrest in development at the megakaryocyte-erythrocyte progenitor stage. Furthermore, Raptor-deficient mice exhibited a block in B cell lineage commitment. The essential role of Raptor (mTORC1) in erythrocyte and B lineage commitment was confirmed in adult Mx1-cre+Raptorfl/fl mice upon cre-recombinase induction. These studies were supported by results showing that the expression of key lineage commitment regulators, GATA1, GATA2 and PAX5 were dysregulated in the absence of mTORC1-mediated signals. The regulatory role of mTOR during erythropoiesis was confirmed in vitro by demonstrating a reduction of K562 cell differentiation towards RBCs in the presence of established mTOR inhibitors. While mTORC1 plays a fundamental role in promoting RBC development, we showed that mTORC2 has an opposing role, as Rictor-deficient progenitor cells exhibited an elevation in RBC colony formation ex vivo. Collectively, our data demonstrate a critical role played by mTORC1 in regulating the haemopoietic cell lineage commitment

Ketamine as the anaesthetic for electroconvulsive therapy:the KANECT randomised controlled trial

C.AS. reports grants from Vifor Pharma, outside the submitted work. I.C.R. (deceased) declared personal fees from AstraZeneca, Sanofi Aventis and Sunovion, and non-financial support from Lundbeck, between 2009 and 2014 and all outside the submitted work. Volume 212, Issue 5 May 2018 , p. 323 Ketamine as the anaesthetic for electroconvulsive therapy: the KANECT randomised controlled trial – CORRIGENDUM Gordon Fernie, James Currie, Jennifer S. Perrin, Caroline A. Stewart... https://doi.org/10.1192/bjp.2018.76 Published online: 06 April 2018 Summary: This notice describes a correction to the above mentioned paper.Peer reviewedPublisher PD

Weight goals, disordered eating behaviors, and BMI trajectories in US young adults

BACKGROUND: Community sample data indicate that weight control efforts in young adulthood may have associations with greater increases in body mass index (BMI) over time. OBJECTIVE: To determine the prospective associations between weight goals and behaviors in young adults and BMI trajectories over 15-year follow-up using a nationally representative sample. DESIGN: Longitudinal cohort data collected from 2001 to 2018 of the National Longitudinal Study of Adolescent to Adult Health. PARTICIPANTS: Young adults aged 18–26 years old at baseline stratified by gender and BMI category. MAIN MEASURES: Predictors: weight goals, any weight loss/maintenance behaviors, dieting, exercise, disordered eating behaviors. Outcomes: BMI at 7- and 15-year follow-up. KEY RESULTS: Of the 12,155 young adults in the sample (54% female, 32% non-White), 33.2% reported a goal to lose weight, 15.7% to gain weight, and 14.6% to maintain weight. In unadjusted models, all groups have higher mean BMI at 7- and 15-year follow-up. In mixed effect models, goals to lose weight in men with BMI < 18.5 (5.94 kg/m2 ; 95% CI 2.58, 9.30) and goals to maintain weight in men with BMI ≥ 25 (0.44; 95% CI 0.15, 0.72) were associated with greater BMI increase compared to no weight goal. Engaging in disordered eating behaviors was associated with greater BMI increase in men with BMI < 18.5 (5.91; 2.96, 8.86) and women with 18.5 ≤ BMI < 25 (0.40; 0.16, 0.63). Dieting (− 0.24; − 0.41, − 0.06) and exercise (− 0.31; − 0.45, − 0.17) were associated with lower BMI increase in women with 18.5 ≤ BMI < 25. In women with BMI < 18.5, dieting was associated with greater BMI increase (1.35; 0.33, 2.37). CONCLUSIONS: Weight control efforts may have variable effects on BMI over time by gender and BMI category. These findings underscore the need to counsel patients on the effectiveness of weight control efforts and long-term weight management

Developing graduate attributes through participation in undergraduate research conferences

© 2016 Taylor & Francis. Abstract: Graduate attributes are a framework of skills, attitudes, values and knowledge that graduates should develop by the end of their degree programmes. Adopting a largely qualitative approach and using semi-structured interviews, this paper outlines students’ experiences at a national undergraduate research conference over three years and evidences the graduate attributes developed. The students demonstrated intellectual autonomy, repurposing their work for presentation to a multidisciplinary audience through conversation with and benchmarking against peers. They gained confidence in expressing their identity as researchers and moved towards self-authorship, consciously balancing the contextual nature of their disciplinary knowledge with intra-personally grounded goals and values

Interdisciplinary Perspectives on Sun Safety and Skin Cancer Risk: achieving consensus

Overexposure to the sun is associated with an increased risk of melanoma and nonmelanoma skin cancer, but indications of improvements in sun protection behavior are poor. Attempts to identify emerging themes in skin cancer control have largely been driven by groups of experts from a single field. In December 2016, 19 experts from various disciplines convened for Interdisciplinary Perspectives on Skin Cancer, a 2-day meeting hosted by the National Academy of Sciences. The group discussed knowledge gaps, perspectives on sun exposure, implications for skin cancer risk and other health outcomes, and new directions. Five themes emerged from the discussion: (1) The definition of risk must be expanded, and categories for skin physiology must be refined to incorporate population diversities. (2) Risky sun exposure often co-occurs with other health-related behaviors. (3) Messages must be nuanced to target at-risk populations. (4) Persons at risk for tanning disorder must be recognized and treated. (5) Sun safety interventions must be scalable. Efficient use of technologies will be required to sharpen messages to specific populations and to integrate them within multilevel interventions. Further interdisciplinary research should address these emerging themes to build effective and sustainable approaches to large-scale behavior change