Reduction In Cell Volume Research Articles

Origin of pressure-induced insulator-to-metal transition in the van der Waals compound FePS3 from first-principles calculations.

Pressure-induced insulator-to-metal transition (IMT) has been studied in the van der Waals compound iron thiophosphate (FePS3 ) using first-principles calculations within the periodic linear combination of atomic orbitals method with hybrid Hartree-Fock-DFT B3LYP functional. Our calculations reproduce correctly the IMT at ∼15 GPa, which is accompanied by a reduction of the unit cell volume and of the vdW gap. We found from the detailed analysis of the projected density of states that the 3p states of phosphorus atoms contribute significantly at the bottom of the conduction band. As a result, the collapse of the band gap occurs due to changes in the electronic structure of FePS3 induced by relative displacements of phosphorus or sulfur atoms along the c-axis direction under pressure.

Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space

Mortality of glioblastoma multiforme (GBM) has not improved over the last two decades despite medical breakthroughs in the treatment of other types of cancers. Nanoparticles hold tremendous promise to overcome the pharmacokinetic challenges and off-target adverse effects. However, an inhibitory effect of nanoparticles by themselves on metastasis has not been explored. In this study, we developed transferrin-conjugated porous silicon nanoparticles (Tf@pSiNP) and studied their effect on inhibiting GBM migration by means of a microfluidic-based migration chip. This platform, designed to mimic the tight extracellular migration tracts in brain parenchyma, allowed high-content time-resolved imaging of cell migration. Tf@pSiNP were colloidally stable, biocompatible, and their uptake into GBM cells was enhanced by receptor-mediated internalisation. The migration of Tf@pSiNP-exposed cells across the confined microchannels was suppressed, but unconfined migration was unaffected. The pSiNP-induced destabilisation of focal adhesions at the leading front may partially explain the migration inhibition. More corroborating evidence suggests that pSiNP uptake reduced the plasticity of GBM cells in reducing cell volume, an effect that proved crucial in facilitating migration across the tight confined tracts. We believe that the inhibitory effect of Tf@pSiNP on cell migration, together with the drug-delivery capability of pSiNP, could potentially offer a disruptive strategy to treat GBM.

Volume Adaptation Controls Stem Cell Mechanotransduction.

Recent studies have found discordant mechanosensitive outcomes when comparing 2D and 3D, highlighting the need for tools to study mechanotransduction in 3D across a wide spectrum of stiffness. A gelatin methacryloyl (GelMA) hydrogel with a continuous stiffness gradient ranging from 5 to 38 kPa was developed to recapitulate physiological stiffness conditions. Adipose-derived stem cells (ASCs) were encapsulated in this hydrogel, and their morphological characteristics and expression of both mechanosensitive proteins (Lamin A, YAP, and MRTFa) and differentiation markers (PPARγ and RUNX2) were analyzed. Low-stiffness regions (∼8 kPa) permitted increased cellular and nuclear volume and enhanced mechanosensitive protein localization in the nucleus. This trend was reversed in high stiffness regions (∼30 kPa), where decreased cellular and nuclear volumes and reduced mechanosensitive protein nuclear localization were observed. Interestingly, cells in soft regions exhibited enhanced osteogenic RUNX2 expression, while those in stiff regions upregulated the adipogenic regulator PPARγ, suggesting that volume, not substrate stiffness, is sufficient to drive 3D stem cell differentiation. Inhibition of myosin II (Blebbistatin) and ROCK (Y-27632), both key drivers of actomyosin contractility, resulted in reduced cell volume, especially in low-stiffness regions, causing a decorrelation between volume expansion and mechanosensitive protein localization. Constitutively active and inactive forms of the canonical downstream mechanotransduction effector TAZ were stably transfected into ASCs. Activated TAZ resulted in higher cellular volume despite increasing stiffness and a consistent, stiffness-independent translocation of YAP and MRTFa into the nucleus. Thus, volume adaptation as a function of 3D matrix stiffness can control stem cell mechanotransduction and differentiation.

Nucleoplasmin is a limiting component in the scaling of nuclear size with cytoplasmic volume.

How nuclear size is regulated relative to cell size is a fundamental cell biological question. Reductions in both cell and nuclear sizes during Xenopus laevis embryogenesis provide a robust scaling system to study mechanisms of nuclear size regulation. To test if the volume of embryonic cytoplasm is limiting for nuclear growth, we encapsulated gastrula-stage embryonic cytoplasm and nuclei in droplets of defined volume using microfluidics. Nuclei grew and reached new steady-state sizes as a function of cytoplasmic volume, supporting a limiting component mechanism of nuclear size control. Through biochemical fractionation, we identified the histone chaperone nucleoplasmin (Npm2) as a putative nuclear size effector. Cellular amounts of Npm2 decrease over development, and nuclear size was sensitive to Npm2 levels both in vitro and in vivo, affecting nuclear histone levels and chromatin organization. We propose that reductions in cell volume and the amounts of limiting components, such as Npm2, contribute to developmental nuclear size scaling.

Thermally Induced Spin Transition in a 2D Ferrous Nitroprusside

This study reports the intercalation of pyridine molecules between neighboring layers of two‐dimensional (2D) ferrous nitroprusside. In the material under study, the stacking of neighboring layers results in the formation of a long range ordered solid, where the 3D structure is supported by dipole‐dipole attractive interactions between neighboring pyridine molecules in the interlayer region. No chemical interactions were observed between layers, which preserve their identity as a 2D material. In this hybrid inorganic–organic solid, a thermal induced spin transitions from high to low spin on cooling and then from low to high spin on heating were observed. Such thermal induced spin crossover transition takes place with a pronounced hysteresis of 18 K, according to the magnetic and DSC measurements. That spin crossover transition is characterized by an extremely small structural change, involved a unit cell volume reduction from the high to low spin states of only 0.7 % and a related Fe–NPyridine distance shortening of 0.10 Å. The two spin states and the transition between them were additionally characterized from magnetic and DSC data and, Raman and Mössbauer spectra.

First-principles investigation of structural, electronic, optical and thermal properties of Zinc doped SrTiO3

This work reports the first-principles study, based on the density functional theory (DFT), by using generalized gradient approximation (GGA) and ultra-soft pseudo-potential (USP), to explore effects of zinc (Zn) doping on structural, electronic, optical and thermal properties of cuboctahedral SrTiO3. We observe significant reduction in unit cell volume upon doping Zn into SrTiO3. Furthermore, Zn doping introduces new sates at Brillouin zone symmetry points turning the indirect band gap of host material into direct one. Replacement of Zn with Sr in host lattice repositions density of states at lower energies resulting in stronger interactions between Zn-atom and its neighbors as compared to interactions between Sr-atom and its surroundings. This refers to substantial modification in electronic band structure of host material by Zn doping. Physical properties of SrTiO3 also change significantly upon Zn doping in accordance with the electronic band structure. Significant changes in electronic structure and properties of SrTiO3 by Zn doping opens new prospects for potential applications of these materials in optoelectronics.

Annealing environment dependent electrical and chemical state correlation of Li-doped NiO

The effects of annealing environments and dopants on the structural, chemical, optical, and electrical properties of NiO are investigated. Pristine NiO exhibits electrically insulating behavior regardless of the annealing environments (e.g., vacuum and O2 environments). On the other hand, Li-doped NiO exhibits electrical resistivities of ∼350 Ω cm and ∼9 Ω cm for the ceramics annealed under vacuum and O2, respectively with reduced optical band-gap. The structural analysis revealed that all the samples exhibit a cubic structure (Fm-3m, SG 225) without any measurable secondary phases. However, Li-doped NiO samples showed a reduction in the unit cell volume as compared to the undoped NiO samples. X-ray photoelectron spectroscopy revealed different residual Li content depending on the annealing environments, and the presence of induced Ni3+ state in the Li-doped NiO. These induced Ni3+ states and doped Li are responsible for the observed change in the structural and electrical properties of the Li-doped NiO samples.

Antimalarial Activity of Tinospora baenzigeri against Plasmodium berghei-Infected Mice.

Plant species of the genus Tinospora (Menispermaceae) possess several pharmacological properties, and T. crispa has been reported to have antimalarial activity. T. baenzigeri (Chingcha Chalee) is a rich source of terpenes and quinoline alkaloids; however, it still has not yet been investigated the antimalarial activity of this plant extract. Hence, this study was aimed to evaluate the antimalarial activity of T. baenzigeri stem extract against Plasmodium berghei-infected mice. The aqueous crude extract of T. baenzigeri stem was prepared using a microwave-assisted method and tested for acute toxicity in mice. For evaluating the antimalarial activity in vivo, the standard 4-day test was carried out using groups of ICR mice infected with P. berghei ANKA administered orally by gavage with the extract (100, 250, and 500 mg/kg) for 4 consecutive days. Parasitemia, body weight, packed cell volume, and mean survival time were then measured. It was found that the aqueous crude extract of T. baenzigeri stem did not exhibit any sign of toxicity up to the dose of 2,000 mg/kg. The extract significantly (P < 0.01) inhibited parasitemia in a dose-dependent manner, with 22.02%, 50.81%, and 74.95% inhibition. Moreover, the marked prevention of body weight loss and packed cell volume reduction was observed at doses of 100, 250, and 500 mg/kg of extract-treated mice. Additionally, the extract prolonged the mean survival time of P. berghei-infected mice, compared to the untreated group. In conclusion, the aqueous crude extract of T. baenzigeri stem has demonstrated potent antimalarial activity against P. berghei-infected mice with prolonged mean survival time and prevention of body weight loss and packed cell volume reduction.

Tailoring the Permittivity in Tellurium Dioxide By Co-Doping

Tellurium oxide (TeO2) due to its glass-forming characteristics, highly non-linear optical properties, good chemical resistivity, low UV- IR absorption, etc. are widely used in a variety of application like acoustic optical devices, radiation detectors, gas sensors. Apart from these applications very little studies emphasize on the dielectric property and its application. Prime aspect for the interest of this material is that the dielectric constant of about 17-25 have been reported for α-TeO2. Such a high dielectric constant may be considered as a potential characteristic sprouting the possibility of TeO2 in the microelectronic industry. In the present study (In0.5Nb0.5) x Te1-xO2 (x=0, 1, 3, 5 %) ceramics were prepared by the solid-state method by co-doping indium oxide and niobium pentoxide with TeO2 and we studied the composition dependence of doping on the dielectric properties (e.g., permittivity, dielectric loss, temperature, and frequency stability) of TeO2 ceramic. The crystal structure and vibrational modes were determined by XRD and Raman spectra respectively. SEM micrographs were used to view the morphology of the sample. XRD and Raman data shows the co-existence of the tetragonal phase of (In0.5 Nb0.5) x Te1-xO2 with space group P41212 along with highly symmetric cubic phase of In0.5 Nb0.5 Te3O8 with space group Ia-3 in the doped samples. From the quantification of XRD data, it is evident that by increasing the doping concentration evolution of the cubic phase is enhanced. Also, decrease in intensity of major Raman vibration modes related to TeO4 unit and the existence of new modes of vibration indicates the new bonding bridges formed which in turn has an effect on the basic structure of TeO2. Dielectric measurement of co-doped samples was carried out over frequency range 500 Hz to 1 MHz and temperature range 90 K to 420 K. Dielectric measurement shows a relevant enhancement of the dielectric constant for co-doped samples with ten times decline in loss (tan δ). As shown in the figure, it can be observed that with 1%, 3%, 5% doping there is an enhancement in ε value are 21.5, 22 and 27.5 respectively (at room temperature) with respect to un-doped TeO2. (ε =21). Also, the temperature and frequency dependence of dielectric constant shows a stable response. The incorporation of the cubic phase does influence the dielectric constant of the co-doped TeO2. By increasing the doping concentration, there is a proportional increase in the cubic phase and from XRD correspondingly the characteristic peak for TeO2 tetragonal phase gradually shifts towards larger diffraction angles indicating the reduction of unit cell volume [1]. This observation is a clear association reciting to the relation between the lattice constant from the XRD peaks and the dielectric constant of the co-doped TeO2. From the Clausius-Mossotti relation, it is can be interpreted that the dielectric constant enhancement through the cubic phase appearance accounts from the molar volume shrinkage [2]. Figure 1. Dielectric constant ε and tan δ of (In0.5 Nb0.5) x Te1-xO2 the samples as a function of indium and niobium co-doping. Reference: [1] Tomida K, Kita K, Toriumi A (2006) Dielectric constant enhancement due to Si incorporation into HfO2. Appl Phys Lett. 89:142902 [2] Shi F et al (2017) Crystal structure characteristics, dielectric properties and vibrational spectra of Nb-rich non-stoichiometric Ba[(Zn1/3Nb2/3)1−xNbx] O3 ceramics J. Mater. Sci., Mater. Electron. 2811455–63 Figure 1

Cell spread area and traction forces determine myosin-II-based cortex thickness regulation

Actomyosin network under the plasma membrane of cells forms a cortical layer that regulates cellular deformations during different processes. What regulates the cortex? Characterized by its thickness, it is believed to be regulated by actin dynamics, filament-length regulators and myosin motor proteins. However, its regulation by cellular morphology (e.g. cell spread area) or mechanical microenvironment (e.g. substrate stiffness) has remained largely unexplored. In this study, super- and high-resolution imaging of actin in CHO cells demonstrates that at high spread areas (>450 μm2), the cortex is thinner, better separated as layers, and sensitive to deactivation of myosin II motors or reduction of substrate stiffness (and traction forces). In less spread cells (<400 μm2) such perturbations do not elicit a response. Myosin IIA's mechanosensing is limited here due to its lowered actin-bound fraction and higher turnover rate. Cofilin, in line with its competitive inhibitory role, is found to be overexpressed in these cells. To establish the causal relation, we initiate a spread area drop by de-adhesion and find enhanced actin dynamics and fragmentation along with oscillations and increase in thickness. This is more correlated to the reduction of traction forces than the endocytosis-based reduction in cell volume. Cortex thickness control by spread area is also found be true during differentiation of THP-1 monocytes to macrophages. Thus, we propose that spread area regulates cortex and its thickness by traction-based mechanosensing of myosin II.

Redetermination of the crystal structure of tetrammineplatinum(II) dichloride – A microporous hydrogen-bonded 3D network exhibiting a temperature-dependent order-disorder phase transition

The title compound [Pt(NH3)4]Cl2 (1), prepared by reaction of (NH4)2[PtCl4] with an excess of NH3 in aqueous solution, was crystallized from water and its structure redetermined by single-crystal X-ray diffraction at four different temperatures in the range from 273 K down to 100 K. 1 is composed of square-planar [Pt(NH3)4]2+ complex cations and Cl− anions and crystallizes in the tetragonal crystal system. Remarkably, the solid state structure is porous (approx. 18% of the crystal volume is void space) and features one-dimensional open channels of a diameter of ∼3–4 Å. Unexpectedly, these channels are free of solvent molecules, although the crystals were obtained from aqueous solutions. NH⋯Cl hydrogen bonding interactions between the square-planar [Pt(NH3)4]2+ dications and the Cl− counter ions result in a three-dimensional hydrogen bonding network that stabilizes the porous solid state structure. The hydrogen atoms of the ammonia ligands and their corresponding NH⋯Cl hydrogen bonds are localized at low temperature (space group I4/mmm) but disorder dynamically above 173 K (space group P4/mmm). The order-disorder transition is accompanied by significant changes in the Pt–Pt stacking distances and a fourfold reduction of the unit cell volume.

Effect of Mg2+ substitution on the crystal structure and microwave dielectric properties of Ca5Mn4(VO4)6 ceramics

The influence of Mg2+ substitution for Mn2+ on the crystal structure and microwave dielectric properties of Ca5Mn4-xMgx(VO4)6 (0 ≤ x ≤ 2) ceramics was investigated. Ca5Mn4-xMgx(VO4)6 (0 ≤ x ≤ 2) ceramics were synthesized by a solid-state reaction. XRD and EDS analyses confirmed that a continuous solid solution with a garnet structure was formed for x values in the range of 0 ˜ 2. Rietveld refinement revealed that the occupation of Mn sites by Mg ions resulted in a reduction in the unit cell volume. The microwave dielectric properties closely depended on the ionic polarizability, Raman shift, packing fraction, average grain size, and bond valence. Ca5Mn2.4Mg1.6(VO4)6 ceramics sintered at 860 °C possessed the best microwave dielectric properties of the samples considered in this study: εr = 10.9, Q × f = 60,444 GHz, and τf = -76.5 ppm/°C.

Hydrogen-bond-mediated structural variation of metal guanidinium formate hybrid perovskites under pressure.

The hybrid perovskites are coordination frameworks with the same topology as the inorganic perovskites, but with properties driven by different chemistry, including host-framework hydrogen bonding. Like the inorganic perovskites, these materials exhibit many different phases, including structures with potentially exploitable functionality. However, their phase transformations under pressure are more complex and less well understood. We have studied the structures of manganese and cobalt guanidinium formate under pressure using single-crystal X-ray and powder neutron diffraction. Under pressure, these materials transform to a rhombohedral phase isostructural to cadmium guanidinium formate. This transformation accommodates the reduced cell volume while preserving the perovskite topology of the framework. Using density-functional theory calculations, we show that this behaviour is a consequence of the hydrogen-bonded network of guanidinium ions, which act as struts protecting the metal formate framework against compression within their plane. Our results demonstrate more generally that identifying suitable host–guest hydrogen-bonding geometries may provide a route to engineering hybrid perovskite phases with desirable crystal structures.This article is part of the theme issue ‘Mineralomimesis: natural and synthetic frameworks in science and technology’.

Thermal decomposition of calcium carbonate (calcite polymorph) as examined by in-situ high-temperature X-ray powder diffraction

The temperature dependence of composition, unit cell parameters, thermal expansion coefficients and microstructure during complete thermal decomposition of calcite has been investigated by in-situ high-temperature X-ray powder diffraction. The respective X-ray diffractograms were obtained from 675 to 800 °C at 25 °C intervals. Results indicate that the thermal conversion of calcite to calcium oxide is initiated at a slow rate and rapidly decomposed beyond the temperature of 750 °C. During the period of thermal decomposition, positive and negative expansion of the unit cell is detected parallel to c-axis and perpendicular to a-axis, respectively. A substantial reduction in unit cell volume by 69% is observed during the conversion from trigonal calcite to cubic calcium oxide. It is also found that the rapid composition change and unit cell volume reduction simultaneously accounted for polynomial behavior of thermal expansion coefficients of calcite. Both crystallite size and lattice strain of calcite are increased simultaneously during thermal decomposition. A considerably higher lattice strain is observed for calcite compared to calcium oxide at all decomposition temperatures. The uniform arrangement of small cubic unit cells in newly materialized calcium oxide is accounted for moderate crystallite size and lowest lattice strain at the completion of thermal decomposition.

Optimization of Design Parameters and Operating Conditions of Electrochemical Capacitors for High Energy and Power Performances

Theoretical expressions for performance parameters of different electrochemical capacitors (ECs) were optimized by writing MATLAB scripts to solve them and also via MATLAB R2014a optimization tool box. Performance of different kind of ECs at given circumstances were compared through theoretical equations and simulation of various models subject to conditions of device components, using optimal coefficient associated to battery-kind material and constant associated to electrolyte material KBMopt and KEopt , as well as our symmetric electric double layer capacitor (EDLC) experimental data. Estimations of performance parameters were feasible and achievable once details of electrodes mass ratio, operating potential range ratio and specific capacitance of electrolyte are known. Performances of asymmetric EC with suitable electrode mass and operating potential range ratios using aqueous electrolytes, and that with suitable electrode mass and operating potential range ratios using organic electrolyte with appropriate operating potential range and specific capacitance were factors of 2.2 and 5.56, respectively, greater than those of symmetric EDLC and asymmetric EC using the same aqueous electrolyte, respectively. This enhancement came along with reduction in cell mass and volume. Also, storable and deliverable energies of asymmetric EC with suitable electrode mass and operating potential range ratios using proper organic electrolyte were factor of 12.9 greater than those of symmetric EDLC using aqueous electrolyte, with reduction in cell mass and volume. Storable energy, energy density and power density of asymmetric EDLC with suitable electrode mass and operating potential range ratios using proper organic electrolyte were factor of 5.56 higher than those of similar symmetric EDLC using aqueous electrolyte with reduction in cell mass and volume by a factor 1.77. Also, introduction of asymmetric EDLC with the same type of electrode, and suitable electrodes mass ratio, working potential range ratios and proper organic electrolyte enhanced performance of conventional symmetric EDLC using aqueous electrolyte with reduction in cell mass and volume. These results can obviously reduce number of experiments to determine optimum manufacturing state of EC, and also demonstrated that institution of asymmetric electrode and organic electrolyte was very successful in improving performance of EC with reduction in cell mass and volume. These results can as well be a guideline for design, fabrication and operation of electrochemical capacitor with outstanding storable energy, energy and power densities. Key words: Electrodes symmetry; Modelling and simulation; Performance parameters; Electrolytes type; Working potential range; Asymmetric capacitors.

A coarse-grained red blood cell membrane model to study stomatocyte-discocyte-echinocyte morphologies.

An improved red blood cell (RBC) membrane model is developed based on the bilayer coupling model (BCM) to accurately predict the complete sequence of stomatocyte-discocyte-echinocyte (SDE) transformation of a RBC. The coarse-grained (CG)–RBC membrane model is proposed to predict the minimum energy configuration of the RBC from the competition between lipid-bilayer bending resistance and cytoskeletal shear resistance under given reference constraints. In addition to the conventional membrane surface area, cell volume and bilayer-leaflet-area-difference constraints, a new constraint: total-membrane-curvature is proposed in the model to better predict RBC shapes in agreement with experimental observations. A quantitative evaluation of several cellular measurements including length, thickness and shape factor, is performed for the first time, between CG-RBC model predicted and three-dimensional (3D) confocal microscopy imaging generated RBC shapes at equivalent reference constraints. The validated CG-RBC membrane model is then employed to investigate the effect of reduced cell volume and elastic length scale on SDE transformation, to evaluate the RBC deformability during SDE transformation, and to identify the most probable RBC cytoskeletal reference state. The CG-RBC membrane model can predict the SDE shape behaviour under diverse shape-transforming scenarios, in-vitro RBC storage, microvascular circulation and flow through microfluidic devices.

ABO-mismatched marrow processing for transplantation: Comparative results of 80 procedures performed with Cobe Spectra and Spectra Optia

Backgroundremoval of incompatible red blood cells (RBCs) or plasma is usually required to avoid hemolysis during infusion of ABO incompatible bone marrow (BM) allogeneic transplants. This process often involves separation of buffy coat (BC) by centrifugation in automated devices. We have evaluated the Spectra Optia™ (Optia) apheresis system to determine its effectiveness in BC concentration, volume reduction and RBCs depletion of ABO-incompatible BM compared with our previous method using Cobe Spectra™ (Cobe). Materials and methods28 processes were performed with Optia and 52 with Cobe. We compared volume reduction, RBCs depletion, and recovery of total nucleated cells (TNCs), mononuclear cells (MNCs), CD34+ and CD3+ cells in the final product. Hematopoietic engraftment was ascertained. We used Saphiro-Wilks and Kolmorgorov- Smirnov tests to test normality and Mann-Whitney’s U test to compare means between both groups. ResultsWe found statistically significant differences favoring Optia versus Cobe in TNCs recovery (62% vs. 37%), CD34+ cell recovery (98 vs 84%), volume reduction (91 vs 84%), and RBCs depletion (99 vs. 97%), but not in processing time or time to engraftment. ConclusionOptia achieves high RBCs and volume depletion of BM, while providing excellent CD34+ recovery in clinical routine. Some parameters compare favorably with Cobe Spectra.

Structural phase transition in Al-substituted Fe2MnGa Heusler alloy

In this work, we have systematically investigated the face centered cubic (FCC) to body centered cubic (BCC) transition and its influence on hyperfine and magnetic properties of Al-substituted Fe2MnGa laminated metallic ribbons (non-annealed and annealed) prepared by arc-melting. X-ray diffraction results of non-annealed ribbons show the formation of the atomically disordered FCC (A1) phase in low Al-content (&amp;lt;30 at. %), while a full atomically disordered BCC phase (A2) is found for high Al-content (≥50 at. %). An ordered cubic phase (L21-structure) is established in plastically deformed Al-substituted alloys annealed at 573 K for a few hours. In the L21 state, the Al content increase induces a linear reduction of the cubic cell volume, which influence s and d-electron charge and spin densities at Fe atoms. These changes are responsible for the modifications in hyperfine and magnetic properties of the studied alloys, as confirmed by first principles calculation. We have also demonstrated that the L21 state can be obtained when small percentages (5 at. %) of Al replace Ga atoms and the structural transition is basically explained by an enhancement of chemical pressure in the Al isoelectronically substituted Fe2MnGa system.

Effect of acute hypohydration on glycemic regulation in healthy adults: a randomized crossover trial.

The aim of this study was to investigate the acute effect of hydration status on glycemic regulation in healthy adults and explore underlying mechanisms. In this randomized crossover trial, 16 healthy adults (8 men, 8 women) underwent an oral glucose tolerance test (OGTT) when hypohydrated and rehydrated after 4 days of pretrial standardization. One day before OGTT, participants were dehydrated for 1 h in a heat tent with subsequent fluid restriction (HYPO) or replacement (RE). The following day, an OGTT was performed with metabolic rate measurements and pre- and post-OGTT muscle biopsies. Peripheral quantitative computer tomography thigh scans were taken before and after intervention to infer changes in cell volume. HYPO (but not RE) induced 1.9% (SD 1.2) body mass loss, 2.9% (SD 2.7) cell volume reduction, and increased urinary hydration markers, serum osmolality, and plasma copeptin concentration (all P ≤ 0.007). Fasted serum glucose [HYPO 5.10 mmol/l (SD 0.42), RE 5.02 mmol/l (SD 0.40); P = 0.327] and insulin [HYPO 27.1 pmol/l (SD 9.7), RE 27.6 pmol/l (SD 9.2); P = 0.809] concentrations were similar between HYPO and RE. Hydration status did not alter the serum glucose ( P = 0.627) or insulin ( P = 0.200) responses during the OGTT. Muscle water content was lower before OGTT after HYPO compared with RE [761 g/kg wet wt (SD 13) vs. 772 g/kg wet wt (SD 18) RE] but similar after OGTT [HYPO 779 g/kg wet wt (SD 15) vs. RE 780 g/kg wet wt (SD 20); time P = 0.011; trial × time P = 0.055]. Resting energy expenditure was similar between hydration states (stable between -1.21 and 5.94 kJ·kg-1·day-1; trial P = 0.904). Overall, despite acute mild hypohydration increasing plasma copeptin concentrations and decreasing fasted cell volume and muscle water, we found no effect on glycemic regulation. NEW & NOTEWORTHY We demonstrated for the first time that an acute bout of hypohydration does not impact blood sugar control in healthy adults. Physiological responses to mild hypohydration (<2% body mass loss) caused an elevation in copeptin concentrations similar to that seen in those with diabetes as well as reducing cell volume by ~3%; both of these changes had been hypothesized to cause a higher blood sugar response.

Cytoplasmic Volume and Limiting Nucleoplasmin Scale Nuclear Size During &lt;i&gt;Xenopus Laevis&lt;/i&gt; Development

How nuclear size is regulated relative to cell size is a fundamental cell biological question. Reductions in both cell and nuclear sizes during Xenopus laevis embryogenesis provide a robust scaling system to study mechanisms of nuclear size regulation. To test if the volume of embryonic cytoplasm is limiting for nuclear growth, we encapsulated gastrula stage embryonic cytoplasm and nuclei in droplets of defined volume using microfluidics. Nuclei grew and reached new steady-state sizes as a function of cytoplasmic volume, supporting a limiting component mechanism of nuclear size control. Through biochemical fractionation, we identified the histone chaperone nucleoplasmin (Npm2) as a putative nuclear size-scaling factor. Cellular amounts of Npm2 decrease over development, and nuclear size was sensitive to Npm2 levels both in vitro and in vivo, affecting nuclear histone levels and chromatin organization. Thus, reductions in cell volume with concomitant decreases in Npm2 amounts represent a developmental mechanism of nuclear size-scaling that may also be relevant to cancers with increased nuclear size.