Low Phosphate Diet Exacerbates Hypercalciuria in the Jimbee Mouse Model of SGLT2 Loss-of Function

Selective sodium-dependent glucose co-transporter 2 inhibitors (SGLT2is) are a class of anti-hyperglycemic drugs that lower blood glucose in an insulin-independent manner by inhibiting renal glucose reabsorption and promoting glucosuria. In persons with chronic kidney disease, a potential therapeutic target group for such SGLT2i treatment, dietary phosphate restriction is a mainstay of treatment for metabolic bone disease. We investigated the impact of a low phosphate (LP) diet on the physiology of Jimbee mice which, via deletion in exon 10 of the sglt2 gene, provide a model of SGLT2 loss-of-function, albeit with otherwise normal renal function. Male (M) and female (F), 12-week (wk) old, C57BL/6J (genetic control) and Jimbee mice were randomized 1:1 to a kcal/g equivalent 0.1% phosphate (LP) or 0.4% phosphate (normal P = NP) diet and monitored for 12 wks (n=9–12 per group x 8 groups). At study end (~24 wks of age), male Jimbee vs. C57BL/6J mice had lower body mass (BM: p<0.0001), more-so on LP diet (C57BL/6J vs. Jimbee; (M) NP: 31.4 ± 2.1 vs. 28.6 ± 2.0. LP: 30.8 ± 2.0 vs. 26.0 ± 1.6 g). Female mice exhibited no differences in BM. By MRI, male mice demonstrated proportionate decrements in body composition of Jimbees, as the % fat vs. lean mass and % total body water were comparable between genotypes. HbA1c and random blood glucose were no different between groups, while glucosuria was increased in M and F Jimbee mice (p<0.0001) on either diet [C57BL/6J vs. Jimbee; (M) NP: 0.2 ± 0.2 vs. 10.2 ± 4.5. LP: 0.2 ± 0.2 vs. 7.8 ± 2.0 mg/g (body weight)/day. (F) NP: 0.5 ± 0.5 vs. 8.2 ± 2.7. LP: 0.4 ± 0.3 vs. 7.0 ± 2.9 mg/g/day]. Serum calcium and phosphorus were no different between any groups. However, Jimbee mice also exhibited hypercalciuria and hyperphosphaturia (p<0.001 for both). Hypercalciuria was amplified by LP diet in both strains, with a significant diet x strain interaction in males (p=0.01) [C57BL/6J vs. Jimbee; (M) NP: 4.7 ± 2.3 vs. 15.5 ± 8.2. LP: 27.8 ± 31.5 vs. 73.4 ± 25.8 µg/g/day of urine calcium (Ca2+). (F) NP: 4.9 ± 2.8 vs. 22.7 ± 16.9. LP: 45.8 ± 29.5 vs. 62.6 ± 39.8 µg/g/day]. In contrast, hyperphosphaturia was attenuated by LP diet [C57BL/6J vs. Jimbee; (M) NP: 8.7 ± 8.5 vs. 14.7 ± 10.4. LP: 0.9 ± 0.5 vs. 3.2 ± 2.9 µg/g/day of urine phosphate (PO4). (F) NP: 4.4 ± 6.1 vs. 16.3 ± 9.7. LP: 1.2 ± 0.8 vs. 2.9 ± 1.0 µg/g/day]. Plasma PTH levels were significantly lower (p<0.001) in male Jimbee mice on either diet (C57BL/6J vs. Jimbee; NP: 81.1 ± 31.0 vs. 41.3 ± 10.7. LP: 38.2 ± 1.9 vs. 24.1 ± 6.2 pg/mL) and negatively correlated with daily urine Ca2+ (r = -0.62; p=0.006). Consistent with PTH, renal 1-α hydroxylase gene expression was decreased by ~60% in Jimbee males, specifically on LP diet (p=0.02). Together, these data suggest that, in mice, dietary phosphate restriction might exacerbate SGLT2i-related hypercalciuria during prolonged treatment, independent of PTH, becoming potentially detrimental to bone mineralization and growth over time.

Genetic Interaction Studies Reveal Superior Performance of Rhizobium tropici CIAT899 on a Range of Diverse East African Common Bean (Phaseolus vulgaris L.) Genotypes

ABSTRACT We studied symbiotic performance of factorial combinations of diverse rhizobial genotypes (GR) and East African common bean varieties (GL) that comprise Andean and Mesoamerican genetic groups. An initial wide screening in modified Leonard jars (LJ) was followed by evaluation of a subset of strains and genotypes in pots (contained the same, sterile medium) in which fixed nitrogen was also quantified. An additive main effect and multiplicative interaction (AMMI) model was used to identify the contribution of individual strains and plant genotypes to the GL × GR interaction. Strong and highly significant GL × GR interaction was found in the LJ experiment but with little evidence of a relation to genetic background or growth habits. The interaction was much weaker in the pot experiment, with all bean genotypes and Rhizobium strains having relatively stable performance. We found that R. etli strain CFN42 and R. tropici strains CIAT899 and NAK91 were effective across bean genotypes but with the latter showing evidence of positive interaction with two specific bean genotypes. This suggests that selection of bean varieties based on their response to inoculation is possible. On the other hand, we show that symbiotic performance is not predicted by any a priori grouping, limiting the scope for more general recommendations. The fact that the strength and pattern of GL × GR depended on growing conditions provides an important cautionary message for future studies. IMPORTANCE The existence of genotype-by-strain (GL × GR) interaction has implications for the expected stability of performance of legume inoculants and could represent both challenges and opportunities for improvement of nitrogen fixation. We find that significant genotype-by-strain interaction exists in common bean (Phaseolus vulgaris L.) but that the strength and direction of this interaction depends on the growing environment used to evaluate biomass. Strong genotype and strain main effects, combined with a lack of predictable patterns in GL × GR, suggests that at best individual bean genotypes and strains can be selected for superior additive performance. The observation that the screening environment may affect experimental outcome of GL × GR means that identified patterns should be corroborated under more realistic conditions.

On the role of return to isotropy in wall-bounded turbulent flows with buoyancy

High Reynolds number wall-bounded turbulent flows subject to buoyancy forces are fraught with complex dynamics originating from the interplay between shear generation of turbulence ($S$) and its production or destruction by density gradients ($B$). For horizontal walls, $S$ augments the energy budget of the streamwise fluctuations, while $B$ influences the energy contained in the vertical fluctuations. Yet, return to isotropy remains a tendency of such flows where pressure–strain interaction redistributes turbulent energy among all three velocity components and thus limits, but cannot fully eliminate, the anisotropy of the velocity fluctuations. A reduced model of this energy redistribution in the inertial (logarithmic) sublayer, with no tuneable constants, is introduced and tested against large eddy and direct numerical simulations under both stable ($B<0$) and unstable ($B>0$) conditions. The model links key transitions in turbulence statistics with flux Richardson number (at $Ri_{f}=-B/S\approx$$-2$, $-1$ and $-0.5$) to shifts in the direction of energy redistribution. Furthermore, when coupled to a linear Rotta-type closure, an extended version of the model can predict individual variance components, as well as the degree of turbulence anisotropy. The extended model indicates a regime transition under stable conditions when $Ri_{f}$ approaches $Ri_{f,max}\approx +0.21$. Buoyant destruction $B$ increases with increasing stabilizing density gradients when $Ri_{f}<Ri_{f,max}$, while at $Ri_{f}\geqslant Ri_{f,max}$ limitations on the redistribution into the vertical component throttle the highest attainable rate of buoyant destruction, explaining the ‘self-preservation’ of turbulence at large positive gradient Richardson numbers. Despite adopting a ‘framework of maximum simplicity’, the model results in novel and insightful findings on how the interacting roles of energy redistribution and buoyancy modulate the variance budgets and the energy exchange among the components.

Identification of Collision Mechanism at Seismogenic Fault Interface Using Finite Element Analysis Involving Plate Bending Applications Using Ant Colony Optimization

Understanding space-time correlation in equilibrium matrix when force of collision involving earthquake stress strain interaction. The proposed study shows that non-linear dynamics of earthquake behaviour simulated with ant colony optimization in short timescale deformation by analysis of the stiffness matrix and the stress strain interaction process of the rock pattern. An improved ant colony optimization combined with local search is proposed for solving this complex optimization problem of finding trigger zones for earthquake occurrences. The disturbances at trigger basins for any system cause the collapse of a subsystem leading to stress evolution and slip due to strain nucleation. The stress strain network based on redistribution of stress accumulation are discretized into four states of low stress and strain and a finite element model is established to identify vertices for the stress-strain component and edges for global coupling effects have been constructed for dynamic monitoring of stress and strain behaviour at triggering zones. In this paper, an efficient algorithm is developed for the formation of null basis of triangular and rectangular plate bending finite element models, corresponding to highly sparse flexibility matrices. Triggering basins serve as harbingers of large earthquake where stress-strain interactions have been analyzed by the quasi-static mechanics of seismic precursory stress-strain propagation in the crustal lithosphere. The simulation framework shows that with time, spatial triggering points as stress varies from one point to another to identify the external influences for the body forces and the surface forces for geodynamic frameworks.

Cooling a mechanical resonator with nitrogen-vacancy centres using a room temperature excited state spin–strain interaction

Cooling a mechanical resonator mode to a sub-thermal state has been a long-standing challenge in physics. This pursuit has recently found traction in the field of optomechanics in which a mechanical mode is coupled to an optical cavity. An alternate method is to couple the resonator to a well-controlled two-level system. Here we propose a protocol to dissipatively cool a room temperature mechanical resonator using a nitrogen-vacancy centre ensemble. The spin ensemble is coupled to the resonator through its orbitally-averaged excited state, which has a spin–strain interaction that has not been previously studied. We experimentally demonstrate that the spin–strain coupling in the excited state is 13.5±0.5 times stronger than the ground state spin–strain coupling. We then theoretically show that this interaction, combined with a high-density spin ensemble, enables the cooling of a mechanical resonator from room temperature to a fraction of its thermal phonon occupancy.

On the Theory of Tetragonality of Martensite Crystals Surrounded with Elastic Matrix

The paper is dedicated to the study of thermodynamic stability of tetragonal and cubic states of dilute Fe–C interstitial solid solutions. The combination of the thermodynamic theory and atomistic simulations results was used. This approach allowed us to analyze a widespread theory of carbon ordering in martensite crystal lattice enclosed in an elastic matrix developed by A.G. Khachaturyan. The key parameter of the theory is λ0, the strain interaction parameter. The value of λ0 calculated by A.G. Khachaturyan for a free martensite crystal (2.73 eV/atom ) yields the critical concentration of carbon ccrit=0,55 wt. % for room temperature. In fact, according to the experimental works this concentrations is close to 0.25 wt. %. A.G. Khachaturyan offered an improved theory of carbon ordering based on the assumption that decreasing the sizes of crystals along z axis will cause elastic resistance from surrounding crystals. The stresses arising when the martensite crystal is enclosed in an elastic matrix causes the appearance of a “tail” of order parameter at concentrations below the ccr for free crystal, which explained the discrepancy between Khachaturian’s theory and the experimental data. However our analysis shows the absence of this “tail” that means incorrect calculation of λ0 parameter. Over the last ten years the calculations of the strain interaction parameter λ0 have been made. The values of the parameter λ0 range from 5 to 10 eV/atom, in contrast to 2.73 eV/atom as defined by A.G. Khachaturyan. This fact has a great effect on the estimates of the critical carbon concentration at room temperature. This concentration becomes close to 0.2 wt. %, the value previously indicated by G.V. Kurdjumov. The reasons of abnormal tetragonality observed in the 0.2–0.6 wt. %C range are also considered.

Electronic Properties of CdTe/CdS Solar Cells as Influenced by a Buffer Layer

ABSTRACTWe considered modification of the defect density of states in CdTe as influenced by a buffer layer in ZnO(ZnS, SnSe)/CdS/CdTe solar cells. Compared to the solar cells employing ZnO buffer layers, implementation of ZnSe and ZnS resulted in the lower net ionized acceptor concentration and the energy shift of the dominant deep trap levels to the midgap of CdTe. The results clearly indicated that the same defect was responsible for the inefficient doping and the formation of recombination centers in CdTe. This observation can be explained taking into account the effect of strain on the electronic properties of the grain boundary interface states in polycrystalline CdTe. In the conditions of strain, interaction of chlorine with the grain boundary point defects can be altered.