Phosphorus Recovery from Phosphate Rocks Using Phosphate-Solubilizing Bacteria

In this paper, we are presenting a biological process to recover phosphorus by solubilizing low-grade phosphate rocks. To this end, the efficiency of different phosphate-solubilizing microorganism (PSM) species for solubilizing P from phosphate rocks using both pure cultures and associations. Nutritional conditions, phosphate rock concentrations, and reactor designs were tested. The genus Bacillus, especially Bacillus megaterium (ATCC 14581), was found to be the most promising PSM for solubilizing P. Production of organic acids and acidic pH values were shown to be directly related to P solubilizing. However, associations between tested microorganisms did not significantly enhance process efficiency. We conclude that nutritional factors of the medium are important to solubilization, and lower phosphate rock concentrations lead to better solubilization. The Air Lift reactor was promising for B. megaterium (ATCC 14581), but adaptations are needed for further tests.     

Proposal of 28 GHz In Vitro Exposure System Based on Field Uniformity for Three‐Dimensional Cell Culture Experiments

This paper proposes a novel in vitro exposure system operating at millimeter‐wave (mmWave) 28 GHz, one of the frequency bands under consideration for fifth generation (5G) communication. We employed the field uniformity concept along cross‐sectional observation planes at shorter distances from the radiation antenna for better efficiency and a small‐size system. A choke‐ring antenna was designed for this purpose in consideration of a wider beamwidth (BW) and a symmetric far‐field pattern across three principal planes. The permittivity of Dulbecco's modified Eagle's medium solution was measured to examine the specific absorption rate (SAR) of the skin cell layer inside a Petri dish model for a three‐dimensional (3D) cell culture in vitro experiment. The best deployment of Petri dishes, taking into account a geometrical field symmetry, was proposed. Local SAR values within the cell layer among the Petri dishes were determined with different polarization angles. It was determined that this polarization effect should be considered when the actual exposure and deployment were conducted. We finally proposed an in vitro exposure system based on the field uniformity including downward exposure from an antenna for 3D cell culture experiments. A small‐size chamber system was obtained, and the size was estimated using the planar near‐field chamber design rule. Bioelectromagnetics. 2019;40:445–457. © 2019 Bioelectromagnetics Society     

TrioMDR: Detecting SNP interactions in trio families with model-based multifactor dimensionality reduction

Single nucleotide polymorphism (SNP) interactions can explain the missing heritability of common complex diseases. Many interaction detection methods have been proposed in genome-wide association studies, and they can be divided into two types: population-based and family-based. Compared with population-based methods, family-based methods are robust vs. population stratification. Several family-based methods have been proposed, among which Multifactor Dimensionality Reduction (MDR)-based methods are popular and powerful. However, current MDR-based methods suffer from heavy computational burden. Furthermore, they do not allow for main effect adjustment. In this work we develop a two-stage model-based MDR approach (TrioMDR) to detect multi-locus interaction in trio families (i.e., two parents and one affected child). TrioMDR combines the MDR framework with logistic regression models to check interactions, so TrioMDR can adjust main effects. In addition, unlike consuming permutation procedures used in traditional MDR-based methods, TrioMDR utilizes a simple semi-parameter P-values correction procedure to control type I error rate, this procedure only uses a few permutations to achieve the significance of a multi-locus model and significantly speeds up TrioMDR. We performed extensive experiments on simulated data to compare the type I error and power of TrioMDR under different scenarios. The results demonstrate that TrioMDR is fast and more powerful in general than some recently proposed methods for interaction detection in trios. The R codes of TrioMDR are available at: https://github.com/TrioMDR/TrioMDR.     

Co(II)‐salen catalyzed stereoselective cyclopropanation of fluorinated styrenes

Three cis‐selective Co(II)‐salen complexes have been developed for the asymmetric cyclopropanation of para‐fluorinated styrenes with ethyl diazoacetate. Increasing the steric reach of the C₂‐symmetric ligand side chains improved the enantiomeric ratio of the reaction from 28:1 to 66:1. The methodology was exemplified by the gram‐scale synthesis of a lead compound for the treatment of castration‐resistant prostate cancer (CRPC), as well as a structurally related analog.     

The role of mitochondria in sepsis-induced cardiomyopathy

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Myocardial dysfunction, often termed sepsis-induced cardiomyopathy, is a frequent complication and is associated with worse outcomes. Numerous mechanisms contribute to sepsis-induced cardiomyopathy and a growing body of evidence suggests that bioenergetic and metabolic derangements play a central role in its development; however, there are significant discrepancies in the literature, perhaps reflecting variability in the experimental models employed or in the host response to sepsis. The condition is characterised by lack of significant cell death, normal tissue oxygen levels and, in survivors, reversibility of organ dysfunction. The functional changes observed in cardiac tissue may represent an adaptive response to prolonged stress that limits cell death, improving the potential for recovery. In this review, we describe our current understanding of the pathophysiology underlying myocardial dysfunction in sepsis, with a focus on disrupted mitochondrial processes.     

PKM2-regulated STAT3 promotes esophageal squamous cell carcinoma progression via TGF-β1-induced EMT

Recent studies have demonstrated pleiotropic roles of pyruvate kinase isoenzyme type M2 (PKM2) in tumor progression. However, the precise mechanisms underlying the effects of PKM2 on esophageal squamous cell carcinoma (ESCC) metastasis and transforming growth factor β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) remain to be established. In this study, we observed upregulation of PKM2 in ESCC tissues that was markedly associated with lymph node metastasis and poor prognosis. High PKM2 expression in tumor tissues frequently coincided with the high pSTAT3Tyr705 expression and low E-cadherin expression. Furthermore, altered PKM2 expression was significantly associated with proliferation, migration, and invasion of ESCC cells, in addition to expression patterns of EMT markers (Snail, E-cadherin, and vimentin) and pSTAT3^Tyr705/STAT3 ratio. Overexpression of STAT3 significantly attenuated the effects of PKM2 knockdown on cell proliferation and motility as well as expression of pSTAT3 ^Tyr705 and EMT markers. Consistently, stable short hairpin RNA (shRNA)-mediated silencing of PKM2 reversed the effects of TGF-β1 treatment, specifically, upregulation of PKM2, phosphorylation of STAT3 at Tyr705, and increased EMT, migration, and invasion. We propose that PKM2 regulates cell proliferation, migration, and invasion via phosphorylation of STAT3 through TGF-β1-induced EMT. Our findings collectively provide mechanistic insights into the tumor-promoting role of PKM2, supporting its prognostic value and the therapeutic utility of PKM2 inhibitors as potential antitumor agents in ESCC.     

Simulation of protein diffusion: a sensitive probe of protein–solvent interactions

Aqueous solutions of Candida antarctica lipase B (CALB) were simulated considering three different water models (SPC/E, TIP3P, TIP4P) by a series of molecular dynamics (MD) simulations of three different box sizes (L = 9, 14, and 19 nm) to determine the diffusion coefficient, the water viscosity and the protein density. The protein–water systems were equilibrated for 500 ns, followed by 100 ns production runs which were analysed. The diffusional properties of CALB were characterized by the Stokes radius (R_S), which was derived from the diffusion coefficient and the viscosity. R_S was compared to the geometric radius (R_G) of CALB, which was derived from the protein density. R_S and R_G differed by 0.27 nm for SPC/E and by 0.40 and 0.39 nm for TIP3P and TIP4P, respectively, which characterizes the thickness of the diffusive hydration layer on the protein surface. The simulated hydration layer of CALB resulted in agreement with those experimentally determined for other seven different proteins of comparable size. By avoiding the most common pitfalls, protein diffusion can be reliably simulated: simulating different box sizes to account for the finite size effect, equilibrating the protein–water system sufficiently, and using the complete production run for the determination of the diffusion coefficient.     

Human p38α mitogen-activated protein kinase in the Asp168-Phe169-Gly170-in (DFG-in) state can bind allosteric inhibitor Doramapimod

Doramapimod (BIRB-796) is widely recognized as one of the most potent and selective type II inhibitors of human p38α mitogen-activated protein kinase (MAPK); however, the understanding of its binding mechanism remains incomplete. Previous studies indicated high affinity of the ligand to a so-called allosteric pocket revealed only in the ‘out’ state of the DFG motif (i.e. Asp168-Phe169-Gly170) when Phe169 becomes fully exposed to the solvent. The possibility of alternative binding in the DFG-in state was hypothesized, but the molecular mechanism was not known. Methods of bioinformatics, docking and long-time scale classical and accelerated molecular dynamics have been applied to study the interaction of Doramapimod with the human p38α MAPK. It was shown that Doramapimod can bind to the protein even when the Phe169 is fully buried inside the allosteric pocket and the kinase activation loop is in the DFG-in state. Orientation of the inhibitor in such a complex is significantly different from that in the known crystallographic complex formed by the kinase in the DFG-out state; however, the Doramapimod’s binding is followed by the ligand-induced conformational changes, which finally improve accommodation of the inhibitor. Molecular modelling has confirmed that Doramapimod combines the features of type I and II inhibitors of p38α MAPK, i.e. can directly and indirectly compete with the ATP binding. It can be concluded that optimization of the initial binding in the DFG-in state and the final accommodation in the DFG-out state should be both considered at designing novel efficient type II inhibitors of MAPK and homologous proteins.

Communicated by Ramaswamy H. Sarma