HIV-1 Reverse Transcriptase (RT) is a multifunctional enzyme responsible for the transcription of the RNA genome of the HIV virus into DNA suitable for incorporation within the DNA of human host cells. Its crucial role in the viral life cycle has made it one of the major targets for antiretroviral drug therapy. The Non-Nucleoside RT Inhibitor (NNRTI) class of drugs binds allosterically to the enzyme, affecting many aspects of its activity. We use both coarse grained network models and atomistic molecular dynamics to explore the changes in protein dynamics induced by NNRTI binding. We identify changes in the flexibility and conformation of residue Glu396 in the RNaseH primer grip which could provide an explanation for the acceleration in RNaseH cleavage rate observed experimentally in NNRTI bound HIV-1 RT. We further suggest a plausible path for conformational and dynamic changes to be communicated from the vicinity of the NNRTI binding pocket to the RNaseH at the other end of the enzyme. Full article

Due to a mutation in the Foxp3 transcription factor, Scurfy mice lack regulatory T-cells that maintain self-tolerance of the immune system. They develop multi-organ inflammation (MOI) and die around four weeks old. The affected organs are skin, tail, lungs and liver. In humans, endocrine and gastrointestinal inflammation are also observed, hence the disease is termed IPEX (Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked) syndrome. The three week period of fatal MOI offers a useful autoimmune model in which the controls by genetics, T-cell subsets, cytokines, and effector mechanisms could be efficiently investigated. In this report, we will review published work, summarize our recent studies of Scurfy double mutants lacking specific autoimmune-related genes, discuss the cellular and cytokine controls by these genes on MOI, the organ-specificities of the MOI controlled by environments, and the effector mechanisms regulated by specific Th cytokines, including several newly identified control mechanisms for organ-specific autoimmune response. Full article

Soil flooding in wetlands is accompanied by changes in soil physical and chemical characteristics. These changes include the lowering of soil redox potential (Eh) leading to increasing demand for oxygen within the soil profile as well as production of soil phytotoxins that are by-products of soil reduction and thus, imposing potentially severe stress on plant roots. Various methods are utilized for quantifying plant responses to reducing soil conditions that include measurement of radial oxygen transport, plant enzymatic responses, and assessment of anatomical/morphological changes. However, the chemical properties and reducing nature of soil environment in which plant roots are grown, including oxygen demand, and other associated processes that occur in wetland soils, pose a challenge to evaluation and comparison of plant responses that are reported in the literature. This review emphasizes soil-plant interactions in wetlands, drawing attention to the importance of quantifying the intensity and capacity of soil reduction for proper evaluation of wetland plant responses, particularly at the process and whole-plant levels. Furthermore, while root oxygen-deficiency may partially account for plant stress responses, the importance of soil phytotoxins, produced as by-products of low soil Eh conditions, is discussed and the need for development of methods to allow differentiation of plant responses to reduced or anaerobic soil conditions vs. soil phytotoxins is emphasized. Full article

Discovery of prognostic and diagnostic biomarker gene signatures for diseases, such as cancer, is seen as a major step towards a better personalized medicine. During the last decade various methods, mainly coming from the machine learning or statistical domain, have been proposed for that purpose. However, one important obstacle for making gene signatures a standard tool in clinical diagnosis is the typical low reproducibility of these signatures combined with the difficulty to achieve a clear biological interpretation. For that purpose in the last years there has been a growing interest in approaches that try to integrate information from molecular interaction networks. Here we review the current state of research in this field by giving an overview about so-far proposed approaches. Full article