Small irrigation tanks as a source of malaria mosquito vectors: a study in north-central Sri Lanka

Watersheds / Tank irrigation / Rehabilitation / Malaria / Waterborne diseases / Disease vectors / Sri Lanka / Yan Oya

Dissecting the sharp response of a canonical developmental enhancer reveals multiple sources of cooperativity.

Developmental enhancers integrate graded concentrations of transcription factors (TFs) to create sharp gene expression boundaries. Here we examine the hunchback P2 (HbP2) enhancer which drives a sharp expression pattern in the Drosophila blastoderm embryo in response to the transcriptional activator Bicoid (Bcd). We systematically interrogate cis and trans factors that influence the shape and position of expression driven by HbP2, and find that the prevailing model, based on pairwise cooperative binding of Bcd to HbP2 is not adequate. We demonstrate that other proteins, such as pioneer factors, Mediator and histone modifiers influence the shape and position of the HbP2 expression pattern. Comparing our results to theory reveals how higher-order cooperativity and energy expenditure impact boundary location and sharpness. Our results emphasize that the bacterial view of transcription regulation, where pairwise interactions between regulatory proteins dominate, must be reexamined in animals, where multiple molecular mechanisms collaborate to shape the gene regulatory function

The Dynamics of Zeroth-Order Ultrasensitivity: A Critical Phenomenon in Cell Biology

It is well known since the pioneering work of Goldbeter and Koshland [Proc. Natl. Acad. Sci. USA, vol. 78, pp. 6840-6844 (1981)] that cellular phosphorylation- dephosphorylation cycle (PdPC), catalyzed by kinase and phosphatase under saturated condition with zeroth order enzyme kinetics, exhibits ultrasensitivity, sharp transition. We analyse the dynamics aspects of the zeroth order PdPC kinetics and show a critical slowdown akin to the phase transition in condensed matter physics. We demonstrate that an extremely simple, though somewhat mathematically "singular" model is a faithful representation of the ultrasentivity phenomenon. The simplified mathematical model will be valuable, as a component, in developing complex cellular signaling network theory as well as having a pedagogic value.Comment: 8 pages, 3 figure

Geometric Path Integrals. A Language for Multiscale Biology and Systems Robustness

In this paper we suggest that, under suitable conditions, supervised learning can provide the basis to formulate at the microscopic level quantitative questions on the phenotype structure of multicellular organisms. The problem of explaining the robustness of the phenotype structure is rephrased as a real geometrical problem on a fixed domain. We further suggest a generalization of path integrals that reduces the problem of deciding whether a given molecular network can generate specific phenotypes to a numerical property of a robustness function with complex output, for which we give heuristic justification. Finally, we use our formalism to interpret a pointedly quantitative developmental biology problem on the allowed number of pairs of legs in centipedes

Filling in the gaps: a road map to establish a model system to study developmental programmed cell death

Only a handful of model systems for studying programmed cell death (PCD) exist. The model Arabidopsis thaliana has generated a plethora of knowledge, but it is essential to introduce new models to broaden our understanding of the commonalities of PCD. This review focuses on Aponogeton madagascariensis (the lace plant) as a choice model to study PCD in vivo. PCD plays a key role in plant development and defence. Thus, identifying key regulators across plants is a priority in the field. The formation of perforations in lace plant leaves in areas called areoles is a striking example of PCD. Cells undergoing PCD within areoles can be easily identified from a loss of their anthocyanin pigmentation. In contrast, cells adjacent to veins, non-PCD cells, retain anthocyanins, creating a gradient of cell death. The spatiotemporal pattern of perforation formation, a gradient of cell death within areoles, and the availability of axenic cultures provide an excellent in vivo system to study mechanisms of developmental PCD. The priorities to further develop this model involve sequencing the genome, establishing transformation protocols, and identifying anthocyanin species to determine their medicinal properties. We discuss practical methodologies and challenges associated with developing the lace plant as a model to study PCD

Genetic association study of NF-κB genes in UK Caucasian adult and juvenile onset idiopathic inflammatory myopathy

Treatment-resistant muscle wasting is an increasingly recognized problem in idiopathic inflammatory myopathy (IIM). TNF-α is thought to induce muscle catabolism via activation of nuclear factor-kappa B (NF-κB). Several genes share homology with the NF-κB family of proteins. This study investigated the role of NF-κB-related genes in disease susceptibility in UK Caucasian IIM