Internet of Things for Water Sustainability

The water is a finite resource. The issue of sustainable withdrawal of freshwater is a vital concern being faced by the community. There is a strong connection between the energy, food, and water which is referred to as water-food-energy nexus. The agriculture industry and municipalities are struggling to meet the demand of water supply. This situation is particularly exacerbated in the developing countries. The projected increase in world population requires more fresh water resources. New technologies are being developed to reduce water usage in the field of agriculture (e.g., sensor guided autonomous irrigation management systems). Agricultural water withdrawal is also impacting ground and surface water resources. Although the importance of reduction in water usage cannot be overemphasized, major efforts for sustainable water are directed towards the novel technology development for cleaning and recycling. Moreover, currently, energy technologies require abundant water for energy production. Therefore, energy sustainability is inextricably linked to water sustainability. The water sustainability IoT has a strong potential to solve many challenges in water-food-energy nexus. In this chapter, the architecture of IoT for water sustainability is presented. An in-depth coverage of sensing and communication technologies and water systems is also provided

Can Non-lytic CD8+T Cells Drive HIV-1 Escape?

The CD8+ T cell effector mechanisms that mediate control of HIV-1 and SIV infections remain poorly understood. Recent work suggests that the mechanism may be primarily non-lytic. This is in apparent conflict with the observation that SIV and HIV-1 variants that escape CD8+ T cell surveillance are frequently selected. Whilst it is clear that a variant that has escaped a lytic response can have a fitness advantage compared to the wild-type, it is less obvious that this holds in the face of non-lytic control where both wild-type and variant infected cells would be affected by soluble factors. In particular, the high motility of T cells in lymphoid tissue would be expected to rapidly destroy local effects making selection of escape variants by non-lytic responses unlikely. The observation of frequent HIV-1 and SIV escape poses a number of questions. Most importantly, is the consistent observation of viral escape proof that HIV-1- and SIV-specific CD8+ T cells lyse infected cells or can this also be the result of non-lytic control? Additionally, the rate at which a variant strain escapes a lytic CD8+ T cell response is related to the strength of the response. Is the same relationship true for a non-lytic response? Finally, the potential anti-viral control mediated by non-lytic mechanisms compared to lytic mechanisms is unknown. These questions cannot be addressed with current experimental techniques nor with the standard mathematical models. Instead we have developed a 3D cellular automaton model of HIV-1 which captures spatial and temporal dynamics. The model reproduces in vivo HIV-1 dynamics at the cellular and population level. Using this model we demonstrate that non-lytic effector mechanisms can select for escape variants but that outgrowth of the variant is slower and less frequent than from a lytic response so that non-lytic responses can potentially offer more durable control

PI3Kinase signaling in glioblastoma

Glioblastoma (GBM) is the most common primary tumor of the CNS in the adult. It is characterized by exponential growth and diffuse invasiveness. Among many different genetic alterations in GBM, e.g., mutations of PTEN, EGFR, p16/p19 and p53 and their impact on aberrant signaling have been thoroughly characterized. A major barrier to develop a common therapeutic strategy is founded on the fact that each tumor has its individual genetic fingerprint. Nonetheless, the PI3K pathway may represent a common therapeutic target to most GBM due to its central position in the signaling cascade affecting proliferation, apoptosis and migration. The read-out of blocking PI3K alone or in combination with other cancer pathways should mainly focus, besides the cytostatic effect, on cell death induction since sublethal damage may induce selection of more malignant clones. Targeting more than one pathway instead of a single agent approach may be more promising to kill GBM cells

Increased motion and travel, rather than stable docking, characterize the last moments before secretory granule fusion

The state of secretory granules immediately before fusion with the plasma membrane is unknown, although the granules are generally assumed to be stably bound (docked). We had previously developed methods using total internal reflection fluorescence microscopy and image analysis to determine the position of chromaffin granules immediately adjacent to the plasma membrane with high precision, often to within ≈10 nm, or <5% of the granule diameter (300 nm). These distances are of the dimensions of large proteins and are comparable with the unitary step sizes of molecular motors. Here we demonstrate with quantitative measures of granule travel in the plane parallel to the plasma membrane that secretory granules change position within several hundred milliseconds of nicotinic agonist-induced fusion. Furthermore, just before fusion, granules frequently move to areas that they have rarely visited. The movement of granules to new areas is most evident for granules that fuse later during the stimulus. The movement may increase the probability of productive interactions of the granule with the plasma membrane or may reflect the pull of molecular interactions between the granule and the plasma membrane that are part of the fusion process. Thus, instead of being stably docked before exocytosis, granules undergo molecular-scale motions and travel immediately preceding the fusion event

The Structural and Functional Implications of Linked SNARE Motifs in SNAP25

We investigated the functional and structural implications of SNAP25 having two SNARE motifs (SN1 and SN2). A membrane-bound, intramolecular FRET probe was constructed to report on the folding of N-terminal SN1 and C-terminal SN2 in living cells. Membrane-bound constructs containing either or both SNARE motifs were also singly labeled with donor or acceptor fluorophores. Interaction of probes with other SNAREs was monitored by the formation of SDS-resistant complexes and by changes in FRET measured in vitro using spectroscopy and in the plasma membrane of living cells using TIRF microscopy. The probes formed the predicted SDS-resistant SNARE complexes. FRET measurements revealed that syntaxin induced a close association of the N-termini of SN1 and SN2. This association required that the SNARE motifs reside in the same molecule. Unexpectedly, the syntaxin-induced FRET was prevented by VAMP. Both full-length SNAP25 constructs and the combination of its separated, membrane-bound constituent chains supported secretion in permeabilized chromaffin cells that had been allowed to rundown. However, only full-length SNAP25 constructs enabled robust secretion from intact cells or permeabilized cells before rundown. The experiments suggest that the bidentate structure permits specific conformations in complexes with syntaxin and VAMP and facilitates the function of SN1 and SN2 in exocytosis