Project description:Water is essential for metabolism, substrate transport across membranes, cellular homeostasis, temperature regulation, and circulatory function. Although nutritional and physiological research teams and professional organizations have described the daily total water intakes (TWI, L/24h) and Adequate Intakes (AI) of children, women, and men, there is no widespread consensus regarding the human water requirements of different demographic groups. These requirements remain undefined because of the dynamic complexity inherent in the human water regulatory network, which involves the central nervous system and several organ systems, as well as large inter-individual differences. The present review analyzes published evidence that is relevant to these issues and presents a novel approach to assessing the daily water requirements of individuals in all sex and life-stage groups, as an alternative to AI values based on survey data. This empirical method focuses on the intensity of a specific neuroendocrine response (e.g., plasma arginine vasopressin (AVP) concentration) employed by the brain to regulate total body water volume and concentration. We consider this autonomically-controlled neuroendocrine response to be an inherent hydration biomarker and one means by which the brain maintains good health and optimal function. We also propose that this individualized method defines the elusive state of euhydration (i.e., water balance) and distinguishes it from hypohydration. Using plasma AVP concentration to analyze multiple published data sets that included both men and women, we determined that a mild neuroendocrine defense of body water commences when TWI is ?1.8 L/24h, that 19?71% of adults in various countries consume less than this TWI each day, and consuming less than the 24-h water AI may influence the risk of dysfunctional metabolism and chronic diseases.
Project description:The aquaporins transport water through membranes of numerous tissues, but the molecular mechanisms for sensing changes in extracellular osmolality and regulating water balance in brain are unknown. We have isolated a brain aquaporin by homology cloning. Like aquaporin 1 (AQP1, also known as CHIP, channel-forming integral membrane protein of 28 kDa), the deduced polypeptide has six putative transmembrane domains but lacks cysteines at the known mercury-sensitive sites. Two initiation sites were identified encoding polypeptides of 301 and 323 amino acids; expression of each in Xenopus oocytes conferred a 20-fold increase in osmotic water permeability not blocked by 1 mM HgCl2, even after substitution of cysteine at the predicted mercury-sensitive site. Northern analysis and RNase protection demonstrated the mRNA to be abundant in mature rat brain but only weakly detectable in eye, kidney, intestine, and lung. In situ hybridization of brain localized the mRNA to ependymal cells lining the aqueduct, glial cells forming the edge of the cerebral cortex and brainstem, vasopressin-secretory neurons in supraoptic and paraventricular nuclei of hypothalamus, and Purkinje cells of cerebellum. Its distinctive expression pattern implicates this fourth mammalian member of the aquaporin water channel family (designated gene symbol, AQP4) as the osmoreceptor which regulates body water balance and mediates water flow within the central nervous system.
Project description:The glucokinase (GCK) gene was one of the first candidate genes to be identified as a human "diabetes gene". Subsequently, important advances were made in understanding the impact of GCK in the regulation of glucose metabolism. Structure elucidation by crystallography provided insight into the kinetic properties of GCK. Protein interaction partners of GCK were discovered. Gene expression studies revealed new facets of the tissue distribution of GCK, including in the brain, and its regulation by insulin in the liver. Metabolic control analysis coupled to gene overexpression and knockout experiments highlighted the unique impact of GCK as a regulator of glucose metabolism. Human GCK mutants were studied biochemically to understand disease mechanisms. Drug development programs identified small molecule activators of GCK as potential antidiabetics. These advances are summarized here, with the aim of offering an integrated view of the role of GCK in the molecular physiology and medicine of glucose homeostasis.
Project description:BackgroundMangroves are a group of highly salt-tolerant woody plants. The high water use efficiency of mangroves under saline conditions suggests that regulation of water transport is a crucial component of their salinity tolerance.ScopeThis review focuses on the processes that contribute to the ability of mangroves to maintain water uptake and limit water loss to the soil and the atmosphere under saline conditions, from micro to macro scales. These processes include: (1) efficient filtering of the incoming water to exclude salt; (2) maintenance of internal osmotic potentials lower than that of the rhizosphere; (3) water-saving properties; and (4) efficient exploitation of less-saline water sources when these become available.ConclusionsMangroves are inherently plastic and can change their structure at the root, leaf and stand levels in response to salinity in order to exclude salt from the xylem stream, maintain leaf hydraulic conductance, avoid cavitation and regulate water loss (e.g. suberization of roots and alterations of leaf size, succulence and angle, hydraulic anatomy and biomass partitioning). However, much is still unknown about the regulation of water uptake in mangroves, such as how they sense and respond to heterogeneity in root zone salinity, the extent to which they utilize non-stomatally derived CO2 as a water-saving measure and whether they can exploit atmospheric water sources.
Project description:In vivo imaging techniques are powerful tools for evaluating biological systems. Relating image signals to precise molecular phenomena can be challenging, however, due to limitations of the existing optical, magnetic and radioactive imaging probe mechanisms. Here we demonstrate a concept for molecular imaging which bypasses the need for conventional imaging agents by perturbing the endogenous multimodal contrast provided by the vasculature. Variants of the calcitonin gene-related peptide artificially activate vasodilation pathways in rat brain and induce contrast changes that are readily measured by optical and magnetic resonance imaging. CGRP-based agents induce effects at nanomolar concentrations in deep tissue and can be engineered into switchable analyte-dependent forms and genetically encoded reporters suitable for molecular imaging or cell tracking. Such artificially engineered physiological changes, therefore, provide a highly versatile means for sensitive analysis of molecular events in living organisms.
Project description:The Syrian crisis caused a massive influx of displaced people into neighboring countries, with Lebanon hosting the highest per capita number of refugees (3:10). Water remains the most critical natural resource that influences the resilience of host and refugee communities. We provide a new GIS-based updated water balance and water scarcity analysis at the national and the watershed level in Lebanon by comparing current conditions to no-refugee levels. Results show a small (6%) increase in water stress in an average water year at the national level that masks hot spots of water scarcity at the local geography. While domestic water use increased by 20%, we find that refugees' water use is only 10% of agricultural water use in summer. We also show that interventions to rehabilitate the water networks can reduce water stress to better than pre-conflict levels (3% less stress).
Project description:PremisePoikilohydric plants respond to hydration by undergoing dry-wet-dry cycles. Carbon balance represents the net gain or loss of carbon from each cycle. Here we present the first standard protocol for measuring carbon balance, including a custom-modified chamber system for infrared gas analysis, 12-h continuous monitoring, resolution of plant-substrate relationships, and in-chamber specimen hydration.Methods and resultsWe applied the carbon balance technique to capture responses to water stress in populations of the moss Syntrichia caninervis, comparing 19 associated physiological variables. Carbon balance was negative in desiccation-acclimated (field-collected) mosses, which exhibited large respiratory losses. Contrastingly, carbon balance was positive in hydration-acclimated (lab-cultivated) mosses, which began exhibiting net carbon uptake <15 min following hydration.ConclusionsCarbon balance is a functional trait indicative of physiological performance, hydration stress, and survival in poikilohydric plants, and the carbon balance method can be applied broadly across taxa to test hypotheses related to environmental stress and global change.
Project description:PurposeThis review recalls the principles developed over a century to describe trans-capillary fluid exchanges concerning in particular the lung during exercise, a specific condition where dyspnea is a leading symptom, the question being whether this symptom simply relates to fatigue or also implies some degree of lung edema.MethodData from experimental models of lung edema are recalled aiming to: (1) describe how extravascular lung water is strictly controlled by "safety factors" in physiological conditions, (2) consider how waning of "safety factors" inevitably leads to development of lung edema, (3) correlate data from experimental models with data from exercising humans.ResultsExercise is a strong edemagenic condition as the increase in cardiac output leads to lung capillary recruitment, increase in capillary surface for fluid exchange and potential increase in capillary pressure. The physiological low microvascular permeability may be impaired by conditions causing damage to the interstitial matrix macromolecular assembly leading to alveolar edema and haemorrhage. These conditions include hypoxia, cyclic alveolar unfolding/folding during hyperventilation putting a tensile stress on septa, intensity and duration of exercise as well as inter-individual proneness to develop lung edema.ConclusionData from exercising humans showed inter-individual differences in the dispersion of the lung ventilation/perfusion ratio and increase in oxygen alveolar-capillary gradient. More recent data in humans support the hypothesis that greater vasoconstriction, pulmonary hypertension and slower kinetics of alveolar-capillary O2 equilibration relate with greater proneness to develop lung edema due higher inborn microvascular permeability possibly reflecting the morpho-functional features of the air-blood barrier.
Project description:To prevent dehydration, terrestrial animals and humans have developed a sensitive and versatile system to maintain their water homeostasis. In states of hypernatremia or hypovolemia, the antidiuretic hormone vasopressin (AVP) is released from the pituitary and binds its type-2 receptor in renal principal cells. This triggers an intracellular cAMP signaling cascade, which phosphorylates aquaporin-2 (AQP2) and targets the channel to the apical plasma membrane. Driven by an osmotic gradient, pro-urinary water then passes the membrane through AQP2 and leaves the cell on the basolateral side via AQP3 and AQP4 water channels. When water homeostasis is restored, AVP levels decline, and AQP2 is internalized from the plasma membrane, leaving the plasma membrane watertight again. The action of AVP is counterbalanced by several hormones like prostaglandin E2, bradykinin, dopamine, endothelin-1, acetylcholine, epidermal growth factor, and purines. Moreover, AQP2 is strongly involved in the pathophysiology of disorders characterized by renal concentrating defects, as well as conditions associated with severe water retention. This review focuses on our recent increase in understanding of the molecular mechanisms underlying AVP-regulated renal water transport in both health and disease.
Project description:Atmospheric humidity and soil moisture in the Amazon forest are tightly coupled to the region's water balance, or the difference between two moisture fluxes, evapotranspiration minus precipitation (ET-P). However, large and poorly characterized uncertainties in both fluxes, and in their difference, make it challenging to evaluate spatiotemporal variations of water balance and its dependence on ET or P. Here, we show that satellite observations of the HDO/H2O ratio of water vapor are sensitive to spatiotemporal variations of ET-P over the Amazon. When calibrated by basin-scale and mass-balance estimates of ET-P derived from terrestrial water storage and river discharge measurements, the isotopic data demonstrate that rainfall controls wet Amazon water balance variability, but ET becomes important in regulating water balance and its variability in the dry Amazon. Changes in the drivers of ET, such as above ground biomass, could therefore have a larger impact on soil moisture and humidity in the dry (southern and eastern) Amazon relative to the wet Amazon.