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Purpose Administration of hyperosmolar formula is regarded as a risk factor for the development of necrotizing enterocolitis (NEC). However, there are limited number of reports about the relationship between formula osmolality and NEC. The aim of this study is to evaluate the effects of formula concentration in an experimental model of NEC. Methods We studied experimental NEC in C57BL/6 mice. NEC was induced by giving hypoxia, gavage administration of lipopolysaccharide and gavage formula feeding from postnatal day 5–9. We used two types of formula: (1) hyperosmolar formula (HF): 15 g Similac + 75 ml Esbilac (849 mOsm/kg); (2) diluted formula (DF): dilute hyperosmolar formula with an equal amount of water (325 mOsm/kg). Controls were fed by the mother. On postnatal day 9, the ileum was harvested and evaluated for severity of mucosal injury (hematoxylin/eosin staining) and inflammation (PCR for IL6 and TNFα mRNA expression). Results The incidence of NEC was same in both HF and DF (80%). The intestinal inflammatory response was similar between HF and DF (IL6: p  = 0.26, TNFα: p  = 0.69). Conclusions This study indicates the osmolality of enteral formula does not affect incidence of experimental NEC. This experimental study provides new insights into the relationship between formula feeding and NEC.

To impart directionality to the motions of a molecular mechanism, one must overcome the random thermal forces that are ubiquitous on such small scales and in liquid solution at ambient temperature. In equilibrium without energy supply, directional motion cannot be sustained without violating the laws of thermodynamics. Under conditions away from thermodynamic equilibrium, directional motion may be achieved within the framework of Brownian ratchets, which are diffusive mechanisms that have broken inversion symmetry 1 – 5 . Ratcheting is thought to underpin the function of many natural biological motors, such as the F 1 F 0 -ATPase 6 – 8 , and it has been demonstrated experimentally in synthetic microscale systems (for example, to our knowledge, first in ref.  3 ) and also in artificial molecular motors created by organic chemical synthesis 9 – 12 . DNA nanotechnology 13 has yielded a variety of nanoscale mechanisms, including pivots, hinges, crank sliders and rotary systems 14 – 17 , which can adopt different configurations, for example, triggered by strand-displacement reactions 18 , 19 or by changing environmental parameters such as pH, ionic strength, temperature, external fields and by coupling their motions to those of natural motor proteins 20 – 26 . This previous work and considering low-Reynolds-number dynamics and inherent stochasticity 27 , 28 led us to develop a nanoscale rotary motor built from DNA origami that is driven by ratcheting and whose mechanical capabilities approach those of biological motors such as F 1 F 0 -ATPase. A nanoscale rotary motor made of DNA origami, driven by ratcheting and powered by an external electric field, shows the ability to wind up a spring and has mechanical capabilities approaching those of biological motors.

Optimum protein function and biochemical activity critically depends on water availability because solvent thermodynamics drive protein folding and macromolecular interactions 1 . Reciprocally, macromolecules restrict the movement of ‘structured’ water molecules within their hydration layers, reducing the available ‘free’ bulk solvent and therefore the total thermodynamic potential energy of water, or water potential. Here, within concentrated macromolecular solutions such as the cytosol, we found that modest changes in temperature greatly affect the water potential, and are counteracted by opposing changes in osmotic strength. This duality of temperature and osmotic strength enables simple manipulations of solvent thermodynamics to prevent cell death after extreme cold or heat shock. Physiologically, cells must sustain their activity against fluctuating temperature, pressure and osmotic strength, which impact water availability within seconds. Yet, established mechanisms of water homeostasis act over much slower timescales 2 , 3 ; we therefore postulated the existence of a rapid compensatory response. We find that this function is performed by water potential-driven changes in macromolecular assembly, particularly biomolecular condensation of intrinsically disordered proteins. The formation and dissolution of biomolecular condensates liberates and captures free water, respectively, quickly counteracting thermal or osmotic perturbations of water potential, which is consequently robustly buffered in the cytoplasm. Our results indicate that biomolecular condensation constitutes an intrinsic biophysical feedback response that rapidly compensates for intracellular osmotic and thermal fluctuations. We suggest that preserving water availability within the concentrated cytosol is an overlooked evolutionary driver of protein (dis)order and function. Water thermodynamics drive changes in macromolecular assembly that rapidly restore intracellular water availability in response to physiological fluctuations in temperature, pressure and osmotic strength.

Mechanically activated (MA) ion channels convert physical forces into electrical signals, and are essential for eukaryotic physiology. Despite their importance, few bona-fide MA channels have been described in plants and animals. Here, we show that various members of the OSCA and TMEM63 family of proteins from plants, flies, and mammals confer mechanosensitivity to naïve cells. We conclusively demonstrate that OSCA1.2, one of the Arabidopsis thaliana OSCA proteins, is an inherently mechanosensitive, pore-forming ion channel. Our results suggest that OSCA/TMEM63 proteins are the largest family of MA ion channels identified, and are conserved across eukaryotes. Our findings will enable studies to gain deep insight into molecular mechanisms of MA channel gating, and will facilitate a better understanding of mechanosensory processes in vivo across plants and animals.

Zeta potential is often used to approximate a nanoparticle’s surface charge, i.e., cationic, anionic, or neutral character, and has become a standard characterization technique to evaluate nanoparticle surfaces. While useful, zeta potential values provide only very general conclusions about surface charge character. Without a thorough understanding of the measurement parameters and limitations of the technique, these values can become meaningless. This case study attempts to explore the sensitivity of zeta potential measurement using specifically formulated cationic, anionic, and neutral liposomes. This study examines zeta potential dependence on pH and ionic strength, resolving power, and highlights the sensitivity of zeta potential to charged liposomes. Liposomes were prepared with cholesterol, 1,2-distearoyl- sn -glycero-3-phosphocholine (DSPC), and varying amounts of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or 1,2-dioleoyl- sn -glycero-3-phospho- l -serine (DOPS). A strong linear relationship was noted between zeta potential values and the mole percentage of charged lipids within a liposome (e.g., cationic DOTAP or anionic DOPS). This finding could be used to formulate similar liposomes to a specific zeta potential, potentially of importance for systems sensitive to highly charged species. In addition, cationic and anionic liposomes were titrated with up to two mole percent of the neutral lipid 1,2-distearoyl- sn -glycero-3-phosphoethanolamine- N -[methoxy(polyethylene glycol)-2000] (lipid-PEG; LP). Very small amounts of the lipid-PEG (<0.2 mol%) were found to impart stability to the DOTAP- and DOPS-containing liposomes without significantly affecting other physicochemical properties of the formulation, providing a simple approach to making stable liposomes with cationic and anionic surface charge.

Susceptibility of plants to abiotic stresses, including extreme temperatures, salinity and drought, poses an increasing threat to crop productivity worldwide. Here the drought-induced response of maize was modulated by applications of methyl jasmonate (MeJA) and salicylic acid (SA) to seeds prior to sowing and to leaves prior to stress treatment. Pot experiments were conducted to ascertain the effects of exogenous applications of these hormones on maize growth, physiology and biochemistry under drought stress and well-watered (control) conditions. Maize plants were subjected to single as well as combined pre-treatments of MeJA and SA. Drought stress severely affected maize morphology and reduced relative water content, above and below-ground biomass, rates of photosynthesis, and protein content. The prolonged water deficit also led to increased relative membrane permeability and oxidative stress induced by the production of malondialdehyde (from lipid peroxidation), lipoxygenase activity (LOX) and the production of H2O2. The single applications of MeJA and SA were not found to be effective in maize for drought tolerance while the combined pre-treatments with exogenous MeJA+SA mitigated the adverse effects of drought-induced oxidative stress, as reflected in lower levels of lipid peroxidation, LOX activity and H2O2. The same pre-treatment also maintained adequate water status of the plants under drought stress by increasing osmolytes including proline, total carbohydrate content and total soluble sugars. Furthermore, exogenous applications of MeJA+SA approximately doubled the activities of the antioxidant enzymes catalase, peroxidase and superoxide dismutase. Pre-treatment with MeJA alone gave the highest increase in drought-induced production of endogenous abscisic acid (ABA). Pre-treatment with MeJA+SA partially prevented drought-induced oxidative stress by modulating levels of osmolytes and endogenous ABA, as well as the activities of antioxidant enzymes. Taken together, the results show that seed and foliar pre-treatments with exogenous MeJA and/or SA can have positive effects on the responses of maize seedlings to drought.

Biomolecular condensates that form via phase separation are increasingly regarded as coordinators of cellular reactions that regulate a wide variety of biological phenomena. Mounting evidence suggests that multiple steps of the RNA life cycle are organized within RNA-binding protein-rich condensates. In this Review, we discuss recent insights into the influence of phase separation on RNA biology, which has implications for basic cell biology, the pathogenesis of human diseases and the development of novel therapies. The organization of multiple steps of the RNA life cycle in phase-separated condensates presents a framework for understanding how sequestration of RNA-binding proteins and RNAs modulates gene expression.

Oligomeric species arising during the aggregation of α -synuclein are implicated as a major source of toxicity in Parkinson’s disease, and thus a major potential drug target. However, both their mechanism of formation and role in aggregation are largely unresolved. Here we show that, at physiological pH and in the absence of lipid membranes, α -synuclein aggregates form by secondary nucleation, rather than simple primary nucleation, and that this process is enhanced by agitation. Moreover, using a combination of single molecule and bulk level techniques, we identify secondary nucleation on the surfaces of existing fibrils, rather than formation directly from monomers, as the dominant source of oligomers. Our results highlight secondary nucleation as not only the key source of oligomers, but also the main mechanism of aggregate formation, and show that these processes take place under conditions which recapitulate the neutral pH and ionic strength of the cytosol. The formation of protein aggregates is a hallmark of Parkinson’s disease, with small oligomeric species implicated as a major source of toxicity. In this work, Xu et al. determine their mechanism of formation and role in aggregation.

No fish have been found in the deepest 25% of the ocean (8,400—11,000 m). This apparent absence has been attributed to hydrostatic pressure, although direct evidence is wanting because of the lack of deepest-living species to study. The common osmolyte trimethylamine N-oxide (TMAO) stabilizes proteins against pressure and increases with depth, going from 40 to 261 mmol/kg in teleost fishes from 0 to 4,850 m. TMAO accumulation with depth results in increasing internal osmolality (typically 350 mOsmol/kg in shallow species compared with seawater's 1,100 mOsmol/kg). Preliminary extrapolation of osmolalities of predicted isosmotic state at 8,000—8,500 m may indicate a possible physiological limit, as greater depths would require reversal of osmotic gradients and, thus, osmoregulatory systems. We tested this prediction by capturing five of the second-deepest known fish, the hadal snailfish (Notoliparis kermadecensis; Liparidae), from 7,000 m in the Kermadec Trench. We found their muscles to have a TMAO content of 386 ± 18 mmol/kg and osmolality of 991 ± 22 mOsmol/kg. These data fit previous extrapolations and, combined with new osmolalities from bathyal and abyssal fishes, predict isosmotic state at 8,200 m. This is previously unidentified evidence that biochemistry could constrain the depth of a large, complex taxonomic group.

This article reviews the methods of monitoring and treating traumatic intracranial hypertension in intensive care settings. An elevation in intracranial pressure can be a medical or surgical emergency. There are many possible conditions that can lead to elevated intracranial pressure on either an acute or a chronic basis (Table 1). In this article, we focus on the increased intracranial pressure that occurs in patients after traumatic brain injury, since this is an area in which there are both physiological and clinical data. Traumatic brain injury is a medical and social problem worldwide, with an estimated 10 million cases leading to hospitalization or death each year. 1 In low- and medium-income countries, in which the use of motor-powered . . .