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Nature Sep 2023Many animal- and plant-pathogenic bacteria use a type III secretion system to deliver effector proteins into host cells. Elucidation of how these effector proteins...
Many animal- and plant-pathogenic bacteria use a type III secretion system to deliver effector proteins into host cells. Elucidation of how these effector proteins function in host cells is critical for understanding infectious diseases in animals and plants. The widely conserved AvrE-family effectors, including DspE in Erwinia amylovora and AvrE in Pseudomonas syringae, have a central role in the pathogenesis of diverse phytopathogenic bacteria. These conserved effectors are involved in the induction of 'water soaking' and host cell death that are conducive to bacterial multiplication in infected tissues. However, the exact biochemical functions of AvrE-family effectors have been recalcitrant to mechanistic understanding for three decades. Here we show that AvrE-family effectors fold into a β-barrel structure that resembles bacterial porins. Expression of AvrE and DspE in Xenopus oocytes results in inward and outward currents, permeability to water and osmolarity-dependent oocyte swelling and bursting. Liposome reconstitution confirmed that the DspE channel alone is sufficient to allow the passage of small molecules such as fluorescein dye. Targeted screening of chemical blockers based on the predicted pore size (15-20 Å) of the DspE channel identified polyamidoamine dendrimers as inhibitors of the DspE/AvrE channels. Notably, polyamidoamines broadly inhibit AvrE and DspE virulence activities in Xenopus oocytes and during E. amylovora and P. syringae infections. Thus, we have unravelled the biochemical function of a centrally important family of bacterial effectors with broad conceptual and practical implications in the study of bacterial pathogenesis.
Topics: Animals; Bacterial Proteins; Cell Death; Fluorescein; Liposomes; Oocytes; Plant Cells; Plant Diseases; Porins; Protein Folding; Solutions; Water; Xenopus laevis; Osmolar Concentration
PubMed: 37704725
DOI: 10.1038/s41586-023-06531-5 -
Age and Ageing Oct 2023Hydration is a fundamental aspect of clinical practice and yet it is an under-researched topic, particularly in older people, leading to many areas of uncertainty. There...
Hydration is a fundamental aspect of clinical practice and yet it is an under-researched topic, particularly in older people, leading to many areas of uncertainty. There are two types of dehydration; hypertonic, which is a water deficit, and isotonic, which is a deficit of both water and salt. Individual clinical signs and bedside tests are poor diagnostic tools, making dehydration difficult to identify. However, the diagnostic value of a holistic clinical approach is not known. The gold-standard clinical test for dehydration is serum osmolality, but this cannot diagnose isotonic dehydration and may delay diagnosis in acute situations. Salivary osmolality point-of-care testing is a promising and rapid new diagnostic test capable of detecting both hypertonic and isotonic dehydration in older people, but further evidence to support its clinical utility is needed. Daily fluid requirements may be less than previously thought in adults, but the evidence specific to older people remains limited. Hydration via the subcutaneous route is safer and easier to initiate than the intravenous route but is limited by infusion speed and volume. Prompting older adults more frequently to drink, offering a wider selection of drinks and using drinking vessels with particular features can result in small increases in oral intake in the short-term. The ongoing clinically-assisted hydration at end of life (CHELsea II) trial will hopefully provide more evidence for the emotive issue of hydration at the end of life.
Topics: Humans; Aged; Dehydration; Water; Osmolar Concentration; Death
PubMed: 37847795
DOI: 10.1093/ageing/afad193 -
PloS One 2024Urine osmolality is used throughout research to determine hydration levels. Prior studies have found black individuals to have elevated urine creatinine and osmolality,... (Observational Study)
Observational Study
Urine osmolality is used throughout research to determine hydration levels. Prior studies have found black individuals to have elevated urine creatinine and osmolality, but it remains unclear which factors explain these findings. This cross-sectional, observational study sought to understand the relationship of self-reported race to urine creatinine and urine osmolality after accounting for age, socioeconomic status, and fluid intake. Data from 1,386 participants of the 2009-2012 National Health and Nutrition Examination Survey were utilized. Age, poverty-to-income ratio (PIR), urine flow rate (UFR), fluid intake, estimated lean body mass (LBM), urine creatinine, and urine osmolality were measured. In a sex-specific manner, black and white participants were matched on age, dietary moisture, UFR, and PIR. Urine creatinine was greater in black men (171 mg/dL) than white men (150 mg/dL) and greater in black women (147 mg/dL) than white women (108 mg/dL) (p < .001). Similarly, urine osmolality was greater in black women than white women (723 vs. 656 mOsm/kg, p = .001), but no difference was observed between white and black men (737 vs. 731 mOsm/kg, p = .417). Estimated LBM was greater in black men (61.8 kg) and women (45.5 kg) than in white men (58.9 kg) and women (42.2 kg) (p≤.001). The strongest correlate of urine osmolality in all race-sex groups was urine creatinine (Spearman ρ = .68-.75). These results affirm that individuals identifying as black produce higher urine creatinine concentrations and, in women, higher urine osmolality after matching for age, fluid intake, and socioeconomic status. The findings suggest caution when comparing urine hydration markers between racial groups.
Topics: Humans; Female; Male; Creatinine; Osmolar Concentration; White People; Adult; Middle Aged; Black or African American; Cross-Sectional Studies; Social Class; Nutrition Surveys; Aged; Age Factors; Drinking
PubMed: 38820483
DOI: 10.1371/journal.pone.0304803 -
Global Change Biology Sep 2023Climate change is fundamentally altering marine and coastal ecosystems on a global scale. While the effects of ocean warming and acidification on ecology and ecosystem... (Review)
Review
Climate change is fundamentally altering marine and coastal ecosystems on a global scale. While the effects of ocean warming and acidification on ecology and ecosystem functions and services are being comprehensively researched, less attention is directed toward understanding the impacts of human-driven ocean salinity changes. The global water cycle operates through water fluxes expressed as precipitation, evaporation, and freshwater runoff from land. Changes to these in turn modulate ocean salinity and shape the marine and coastal environment by affecting ocean currents, stratification, oxygen saturation, and sea level rise. Besides the direct impact on ocean physical processes, salinity changes impact ocean biological functions with the ecophysiological consequences are being poorly understood. This is surprising as salinity changes may impact diversity, ecosystem and habitat structure loss, and community shifts including trophic cascades. Climate model future projections (of end of the century salinity changes) indicate magnitudes that lead to modification of open ocean plankton community structure and habitat suitability of coral reef communities. Such salinity changes are also capable of affecting the diversity and metabolic capacity of coastal microorganisms and impairing the photosynthetic capacity of (coastal and open ocean) phytoplankton, macroalgae, and seagrass, with downstream ramifications on global biogeochemical cycling. The scarcity of comprehensive salinity data in dynamic coastal regions warrants additional attention. Such datasets are crucial to quantify salinity-based ecosystem function relationships and project such changes that ultimately link into carbon sequestration and freshwater as well as food availability to human populations around the globe. It is critical to integrate vigorous high-quality salinity data with interacting key environmental parameters (e.g., temperature, nutrients, oxygen) for a comprehensive understanding of anthropogenically induced marine changes and its impact on human health and the global economy.
Topics: Humans; Ecosystem; Aquatic Organisms; Salinity; Climate Change; Coral Reefs; Seawater
PubMed: 37435759
DOI: 10.1111/gcb.16859 -
Soft Matter Jul 2023Small angle neutron scattering (SANS) measurements are reported for DNA gels under near physiological conditions in which the concentration of monovalent and divalent...
Small angle neutron scattering (SANS) measurements are reported for DNA gels under near physiological conditions in which the concentration of monovalent and divalent counter-ions and the pH are varied. The scattering intensity () is described by a two-term equation, one due to osmotic concentration fluctuations and the other coming from static inhomogeneities frozen in by the cross-links. SANS in the low range indicates the presence of large clusters and the size of which exceeds the resolution of the experiment. In the intermediate -range, the intensity increases with the CaCl concentration and the slope approaches -1, corresponding to linear (rod-like) scatterers. In the highest region, the scattering response is governed by the local chain geometry. Screening of electrostatic interactions by sodium chloride causes a moderate increase in the SANS intensity that is accompanied by an increase in the mesh size of the network. Addition of calcium chloride, or a decrease in pH, produces similar trends, and ultimately leads to phase separation. The scattering intensity at = 0, estimated from independent measurements of the osmotic pressure , is in excellent agreement with (0) from the SANS measurements. Anomalous small angle X-ray scattering (ASAXS) measurements on the uncross-linked DNA show that the monovalent ion cloud is only weakly influenced by the addition of divalent ions. Conversely, the divalent counter-ion cloud tightly follows the contour of polymer chains.
Topics: Ions; DNA; Sodium Chloride; Osmotic Pressure; Gels
PubMed: 37427607
DOI: 10.1039/d3sm00666b -
Cryobiology Dec 2023Oocyte cryopreservation has notably increased in recent times, to become an essential part of clinical infertility treatment. Since the 1980s, many improvements in... (Review)
Review
Oocyte cryopreservation has notably increased in recent times, to become an essential part of clinical infertility treatment. Since the 1980s, many improvements in oocyte cryopreservation (OC) have been adopted, including the great advance with the application of vitrification. The commonly used vitrification protocol applies different cryoprotectants (Ethylene glycol and/or DMSO and/or PROH and sucrose and/or Trehalose) and two different steps: firstly, exposure in equilibration solution for 5-15 min, followed by a vitrification solution for 60-90 s at room temperature. The warming method includes a first step for 1 min at 37 °C and 3 subsequent steps at room temperature to remove the cryoprotectant for a total of 9-12 min. In addition, biosafety is a critical aspect to mention, and it is related to devices used during the vitrification, mainly in terms of whether the biological vitrified material comes in direct contact with liquid nitrogen (open vitrification) or not (closed vitrification), where LN may contain potentially contaminating viruses or pathogens. Furthermore, during early development major waves of epigenetic reprogramming take place. Recent literature suggests that epigenetic and transcriptomic profiles are sensitive to the stress induced by vitrification, including osmotic shock, temperature, rapid changes of pH and toxicity of cryoprotectants. It is, therefore, important to better understand the potential perturbations of epigenetic modifications that may be associated with the globally used vitrification methods. Therefore, we here discuss the benefits and efficiency of human oocyte vitrification; we also review the evidence surrounding oocyte cryopreservation-related epigenetic modifications and potential epigenetic dysregulations, together with long-term consequences for offspring health.
Topics: Humans; Cryopreservation; Vitrification; Cryoprotective Agents; Osmotic Pressure; Oocytes
PubMed: 37804949
DOI: 10.1016/j.cryobiol.2023.104590 -
Pharmaceutical Research Feb 2024Highly concentrated monoclonal antibody (mAb) formulations for subcutaneous administration are becoming increasingly preferred within the biopharmaceutical industry for...
PURPOSES
Highly concentrated monoclonal antibody (mAb) formulations for subcutaneous administration are becoming increasingly preferred within the biopharmaceutical industry for ease of use and improved patient compliance. A common phenomenon observed in the industry is that osmolality detected via freezing-point depression (FPD) in high-concentration mAb formulations is much higher than the theoretical concentrations, yet the occurrence of this phenomenon and its possible safety issues have been rarely reported.
METHODS
The current study summarized theoretical osmolality of U.S. Food and Drug Administration approved high-concentration mAb formulations and evaluated effects of high osmolality on safety using hemolysis experiments for the first time. Two mAbs formulated at 150 mg/mL were used as models and configured into two isotonic solutions: a, a theoretically calculated molarity in the isotonic range (H) and b, an osmolality value measured via the FPD in the isotonic range (I). The H and I formulations of each mAb were individually subjected to hemolysis experiments, and the hemolysis rates of the two formulations of the same mAb were compared. Besides, the effect of mAb concentration on osmolality detected by FPD was explored as well.
RESULTS
The results indicated that the hemolysis rates were similar between the H and I formulations of mAbs at the same sample addition volume, and the osmolality values increased approximately linearly with the increase in mAb concentration.
CONCLUSIONS
High osmolality for high-concentration mAb formulations would not affect product safety and the excipients could be added at relatively high levels to maintain product stability, especially for labile products.
Topics: Humans; Hemolysis; Drug Compounding; Antibodies, Monoclonal; Excipients; Osmolar Concentration
PubMed: 38172366
DOI: 10.1007/s11095-023-03650-6 -
Trends in Plant Science Jul 2023Osmotic stress limits plant growth and productivity. The downstream signaling components involved in osmotic adjustments are well known, but our knowledge of the...
Osmotic stress limits plant growth and productivity. The downstream signaling components involved in osmotic adjustments are well known, but our knowledge of the perception of osmotic stress is far too limited. Wang et al. have recently identified a lesser-known mechanism of bimolecular condensation that underlies osmotic stress perception in plants.
Topics: Plants; Signal Transduction; Osmotic Pressure; Gene Expression Regulation, Plant
PubMed: 37061375
DOI: 10.1016/j.tplants.2023.04.001 -
The sources, leaching, remediation, and environmental concerns associated with groundwater salinity.Environmental Science and Pollution... Oct 2023Water resources management and sustainable development depend on the quality of groundwater as a major source of fresh water. As a result of rising water demand in... (Review)
Review
Water resources management and sustainable development depend on the quality of groundwater as a major source of fresh water. As a result of rising water demand in emerging nations and overexploitation, groundwater quality has declined globally in many aquifers. One of the most significant elements that lower the quality of the groundwater is salinization. This review is to provide an overview of various materials that are used in the design and development of innovative chitosan-based nanocomposite polymeric membranes for desalination. Biodegradable, non-toxic, affordable, and easily available, with film-forming ability and poly-functionality, chitosan is an ideal material for a sustainable future. Membrane preparation for desalination using chitosan helps to provide antibacterial and antioxidant activities, great chelating capabilities, and strong adsorption capacity. In this research, we discuss a variety of concepts concerning the different sources of elevated salinity and available desalination methods. A comprehensive framework was also developed to understand the leaching and percolation of salt in groundwater, an essential component of managing risks and ensuring safety. Additionally, we explain the various remediation strategies for reducing groundwater's salt concentration and explore the best method for desalination specifically focused on chitosan.
Topics: Salinity; Chitosan; Seawater; Groundwater; Fresh Water; Sodium Chloride; Sodium Chloride, Dietary; Environmental Monitoring; Water Pollutants, Chemical
PubMed: 37698790
DOI: 10.1007/s11356-023-29601-7 -
Environmental Research Oct 2023Salinized land is slowly spreading across the world. Reduced crop yields and quality due to salt stress threaten the ability to feed a growing population. We discussed... (Review)
Review
Salinized land is slowly spreading across the world. Reduced crop yields and quality due to salt stress threaten the ability to feed a growing population. We discussed the mechanisms behind nano-enabled antioxidant enzyme-mediated plant tolerance, such as maintaining reactive oxygen species (ROS) homeostasis, enhancing the capacity of plants to retain K and eliminate Na, increasing the production of nitric oxide, involving signaling pathways, and lowering lipoxygenase activities to lessen oxidative damage to membranes. Frequently used techniques were highlighted like protecting cells from oxidative stress and keeping balance in ionic state. Salt tolerance in plants enabled by nanotechnology is also discussed, along with the potential role of physiobiochemical and molecular mechanisms. As a whole, the goal of this review is meant to aid researchers in fields as diverse as plant science and nanoscience in better-comprehending potential with novel solutions to addressing salinity issues for sustainable agriculture.
Topics: Antioxidants; Salt Stress; Oxidative Stress; Nanoparticles; Defense Mechanisms; Salinity
PubMed: 37437867
DOI: 10.1016/j.envres.2023.116585