Molecular medicine of microRNAs: structure, function and implications for diabetes

MicroRNAs (miRNAs) are a family of endogenous small noncoding RNA molecules, of 19–28 nucleotides in length. In humans, up to 3% of all genes are estimated to encode these evolutionarily conserved sequences. miRNAs are thought to control expression of thousands of target mRNAs. Mammalian miRNAs generally negatively regulate gene expression by repressing translation, possibly through effects on mRNA stability and compartmentalisation, and/or the translation process itself. An extensive range of in silico and experimental techniques have been applied to our understanding of the occurrence and functional relevance of such sequences, and antisense technologies have been successfully used to control miRNA expression in vitro and in vivo. Interestingly, miRNAs have been identified in both normal and pathological conditions, including differentiation and development, metabolism, proliferation, cell death, viral infection and cancer. Of specific relevance and excitement to the area of diabetes research, miRNA regulation has been implicated in insulin secretion from pancreatic β-cells, diabetic heart conditions and nephropathy. Further analyses of miRNAs in vitro and in vivo will, undoubtedly, enable us determine their potential to be exploited as therapeutic targets in diabetes

Molecular medicine: an overview

Editorialpublished_or_final_versio

Data collection methods for task-based information access in molecular medicine

An important area of improving access to health information is the study of task-based information access in the health domain. This is a significant challenge towards developing focused information retrieval (IR) systems. Due to the complexities of this context, its study requires multiple and often tedious means of data collection, which yields a lot of data for analysis, but also allows triangulation so as to increase the reliability of the findings. In addition to traditional means of data collection, such as questionnaires, interviews and observation, there are novel opportunities provided by lifelogging technologies such as the SenseCam. Together they yield an understanding of information needs, the sources used, and their access strategies. The present paper examines the strengths and weaknesses of the traditional and the more novel means of data collection and addresses the challenges in their application in molecular medicine, which intensively uses digital information sources

Molecular Medicine Select

From Alzheimer's disease and the obesity epidemic to the chronic health effects of certain viral infections, scientists in academia and big pharma are seeking new therapeutic targets and strategies to tackle these diseases. However, as discussed in this Molecular Medicine Select, designing more effective drugs with fewer side effects that fight the disease itself and not just the symptoms requires a thorough understanding of the underlying mechanisms of disease pathogenesis

Tensions and Opportunities in Convergence: Shifting Concepts of Disease in Emerging Molecular Medicine

The convergence of biomedical sciences with nanotechnology as well as ICT has created a new wave of biomedical technologies, resulting in visions of a ‘molecular medicine’. Since novel technologies tend to shift concepts of disease and health, this paper investigates how the emerging field of molecular medicine may shift the meaning of ‘disease’ as well as the boundary between health and disease. It gives a brief overview of the development towards and the often very speculative visions of molecular medicine. Subsequently three views of disease often used in the philosophy of medicine are briefly discussed: the ontological or neo-ontological, the physiological and the normative/holistic concepts of disease. Against this background two tendencies in the field of molecular medicine are highlighted: (1) the use of a cascade model of disease and (2) the notion of disease as a deviation from an individual pattern of functioning. It becomes clear that molecular medicine pulls conceptualizations of disease and health in several, partly opposed directions. However, the resulting tensions may also offer opportunities to steer the future of medicine in more desirable directions

The Master Observational Trial: A New Class of Master Protocol to Advance Precision Medicine.

This commentary introduces a new clinical trial construct, the Master Observational Trial (MOT), which hybridizes the power of molecularly based master interventional protocols with the breadth of real-world data. The MOT provides a clinical venue to allow molecular medicine to rapidly advance, answers questions that traditional interventional trials generally do not address, and seamlessly integrates with interventional trials in both diagnostic and therapeutic arenas. The result is a more comprehensive data collection ecosystem in precision medicine

MicroRNA-433 Dampens Glucocorticoid Receptor Signaling, Impacting Circadian Rhythm and Osteoblastic Gene Expression

FUNDING This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [AR44877]; the National Institutes for Dental and Craniofacial Research [5T90DE21989]; a Grant-in-Aid award from the American Society for Bone and Mineral Research; the UConn Health Center Research Advisory council; and the Center for Molecular Medicine at UConn Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Peer reviewedPublisher PD

Suppressing nonsense--a surprising function for 5-azacytidine.

In this issue of EMBO Molecular Medicine, Bhuvanagiri et al report on a chemical means to convert molecular junk into gold. They identify a chemical inhibitor of a quality control pathway that is best known for its ability to clear cells of rubbish, but that in certain cases can be detrimental because it eliminates “useful” garbage. The chemical inhibitor identified by Bhuvanagiri et al perturbs Nonsense‐Mediated RNA Decay (NMD), a RNA surveillance pathway that targets mRNAs harboring premature termination codons (PTCs) for degradation (Kervestin & Jacobson, 2012)

The value proposition of molecular medicine.

Individualized patient management is rapidly evolving, driven by the emergence of insights in discovery, development, regulatory, and comparative effectiveness sciences.1-4 The pace of discovery is accelerating, enabled by platforms, including “omics”, stem cell biology, network medicine, and medical and biological informatics that provide unanticipated insights into pathophysiology.2, 4-6 The integration of these paradigms has established a model for identifying the mechanistic underpinnings of disease, offering novel opportunities to individualize diagnostics that shape how modern therapies are deployed, including markers of disease prognosis, clinical predictors of therapeutic responses, and molecular determinants that optimize clinical management.7-10 Importantly, deconvolution of physiological circuits is producing a new vanguard of molecular therapies that target corrupted pathways at the center of disease pathogenesis, individualizing patient care algorithms that optimize benefits and minimize adverse effects