DDX3X loss is an adverse prognostic marker in diffuse large B-cell lymphoma and is associated with chemoresistance in aggressive non-Hodgkin lymphoma subtypes.

Funder: addenbrooke's charitable trust, cambridge university hospital

Role of DDX3X in T-lymphocyte migration and haematolymphoid malignancies

The DEAD-box family of proteins are a highly conserved group of RNA helicases and participate in a plethora of cellular processes. Amongst them, DDX3X is one of the most functionally multi-faceted subgroup with diverse roles in gene regulation and cellular signal transduction. While recent reports have implicated DDX3X in cancer progression, its role in lymphoid cancer progression is poorly understood. Studies on DDX3X have yielded conflicting conclusions, with findings of both oncogenic and tumour suppressive effects in various tumour models. This study aims to examine the potential involvement of DDX3X in regulating integrin-mediated T-cell migration and in haematolymphoid malignancies. Migration is a crucial feature of T- lymphocytes required for its’ function to mount an adaptive immune response. Hence, the mechanisms involved in T-cell locomotory behaviour would be of considerable relevance to understanding immunological diseases. Here, we utilise RNA interference technique to knockdown DDX3X expression (<80%) and show that the depletion of DDX3X does not interfere with T-cell viability. Intriguingly, we demonstrated that DDX3X depletion causes concomitant increase in T-cells migratory ability. Our findings thus have implications in the understanding of haematological cancers and metastasis.Bachelor of Science in Biological Science

Mechanosensing Potentials Gate Fuel Consumption in a Bipedal DNA Nanowalker

A bipedal DNA nanowalker was recently reported to convert chemical energy into directional motion autonomously and efficiently. To elucidate its chemomechanical coupling mechanisms, three-dimensional molecular modeling is used to obtain coarse-grained foot-track binding potentials of the DNA nanowalker via unbiased and biased sampling techniques (for the potentials’ basin and high-energy edges, respectively). The binding state that is protected against fuel-induced dissociation responds asymmetrically to forward versus backward forces, unlike the unprotected state, demonstrating a mechanosensing capability to gate fuel binding. Despite complex DNA mechanics, the foot-track potential exhibits a surprisingly neat three-part profile, offering some general guidelines to rationally design efficient nanowalkers. Subsequent modeling of the bipedal walker attached to the track gives estimates of the free energy for each bipedal state, showing how the mechanosensing foot-track binding breaks the symmetry between the rear and front feet, enabling the rear foot to be selectively dissociated by fuel and generating efficient chemomechanical coupling

Gender differences in fasting and postprandial metabolic traits predictive of subclinical atherosclerosis in an asymptomatic Chinese population

The prediction utility of Framingham Risk Score in populations with low conventional cardiovascular risk burden is limited, particularly among women. Gender-specific markers to predict cardiovascular risk in overtly healthy people are lacking. In this study we hypothesize that postprandial responses triggered by a high-calorie meal test differ by gender in their ability to triage asymptomatic subjects into those with and without subclinical atherosclerosis. A total of 101 healthy Chinese subjects (46 females, 55 males) at low risk of coronary heart disease completed the study. Subjects underwent cardiovascular imaging and postprandial blood phenotyping after consuming a standardized macronutrient meal. Prediction models were developed using logistic regression and subsequently subjected to cross-validation to obtain a de-optimized receiver operating characteristic (ROC) curve. Distinctive gender differences in postprandial trajectories of glucose, lipids and inflammatory markers were observed. We used gender-specific association with different combinations of postprandial predictors to develop 2 models for predicting risk of subclinical atherosclerosis in males (ROC AUC = 0.7867, 95% CI 0.6567, 0.9166) and females (ROC AUC = 0.9161, 95% CI 0.8340, 0.9982) respectively. We report novel postprandial models for predicting subclinical atherosclerosis in apparently healthy Asian subjects using a gender-specific approach, complementing the conventional Framingham Risk Score.Clinical Trial Registration: The trial was registered at clinicaltrials.gov as NCT03531879.Agency for Science, Technology and Research (A*STAR)Published versionTis work was supported fnancially by the Agency for Science, Technology and Research (A*STAR); I-1701E0B15 and Société des Produits Nestlé SA, Lausanne, Switzerland

DDX3X loss is an adverse prognostic marker in diffuse large B-cell lymphoma and is associated with chemoresistance in aggressive non-Hodgkin lymphoma subtypes

10.1186/s12943-021-01437-0MOLECULAR CANCER20