DOT1L Methyltransferase Regulates Calcium Influx in Erythroid Progenitor Cells in Response to Erythropoietin

Erythropoietin (EPO) signaling plays a vital role in erythropoiesis by regulating proliferation and lineage-specific differentiation of murine hematopoietic progenitor cells (HPCs). An important downstream response of EPO signaling is calcium (Ca²⁺) influx, which is regulated by transient receptor potential channel (TRPC) proteins, particularly TRPC2 and TRPC6. While EPO induces Ca²⁺ influx through TRPC2, TRPC6 inhibits the function of TRPC2. Thus, interactions between TRPC2 and TRPC6 regulate the rate of Ca²⁺ influx in EPO-induced erythropoiesis. In this study, we observed that the expression of TRPC6 in KIT-positive erythroid progenitor cells was regulated by DOT1L. DOT1L is a methyltransferase that plays an important role in many biological processes during embryonic development including early erythropoiesis. We previously reported that Dot1l knockout (Dot1l^KO) HPCs in the yolk sac failed to develop properly, which resulted in lethal anemia. In this study, we detected a marked downregulation of Trpc6 gene expression in Dot1l^KO progenitor cells in the yolk sac compared to the wild type (WT). The promoter and the proximal regions of the Trpc6 gene locus exhibited an enrichment of H3K79 methylation, which is mediated solely by DOT1L. However, the expression of Trpc2, the positive regulator of Ca²⁺ influx, remained unchanged, resulting in an increased TRPC2/TRPC6 ratio. As the loss of DOT1L decreased TRPC6, which inhibited Ca²⁺ influx by TRPC2, Dot1l^KO HPCs in the yolk sac exhibited accelerated and sustained elevated levels of Ca²⁺ influx. Such heightened Ca²⁺ levels might have detrimental effects on the growth and proliferation of HPCs in response to EPO.     

Hybrid polymer networks of unsaturated polyester–urethane as composite matrices for jute reinforcement

Reactions of unsaturated polyester resin and 4,4′ diphenyl methane diisocyanate were carried out at different NCO/OH ratios in presence of catalysts to form the hybrid polymer networks. Chain extender (1,4 butanediol) added in the hybrid network (NCO/OH ratio: 0.76) was optimized at a level of ～ 3 wt % only of the polyester resin. The curing of these networks was studied by a rigid body pendulum type (RPT) method in terms of reduced damping ratio and increased frequency. Lack of multiple glass transition temperatures, sharp Tan delta peak, and particulate composite type morphology clearly demonstrated the formation of phase mixed domains in the hybrid networks. The storage modulus and loss modulus master curves obtained by dynamic mechanical analysis indicate that hybrid polymer networks retained higher modulus at lower and intermediate frequencies over the polyester resin showing their superior time‐dependent response. Efficacy of these hybrid network resins was examined as matrices in the jute composites and compared with those of polyester resin and unsaturated polyester–polyurethane interpenetrating network matrices. It is found that the hybrid polymer network matrix composites exhibited superior physicomechanical properties under both dry and boiling water age test. Fractographic evidences such as fiber–matrix adhesion, hackle markings, and fiber breakage also supported their superior behavior over other composite matrices. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Thermal Mixing of Impinging Laminar Streams of Shear-Thinning Fluids

Abstract

Thermal mixing behavior of shear-thinning fluids with the specified heat flux boundary condition at mixing zone walls is studied numerically to investigate the effect of Reynolds number (10 to 50), power-law index (0.6161 to 1), Nusselt number (10⁴ to 10⁶) for external air flows and dimensionless ambient temperature (?2.7 to 1.3). The temperature is a passive tracer that quantifies the degree of mixing in this study. Detailed kinematics shows the formation of recirculation zones at the mixing channel walls. Length required to achieve the well mixed condition (i.e., a flat temperature profile across the channel height) is shorter at low Reynolds number, convective heat transfer coefficient and ambient temperature, and high power-law index values. In the impingement zone, a faster reduction in mixing index has been observed with respect to mixing length at high power-law index and low Reynolds numbers, while Nusselt number and ambient temperature exert only a weak influence. Under appropriate conditions, significant energy exchange between the system and surroundings can occur and has been analyzed in detail in this work. This work finds its applications in the improved mixing as practiced in the processing and production of food-stuffs, fine chemicals, personal care products, etc.     

Breaking a Couple: Disulfide Reducing Agents

Cysteine is present in a large number of natural and synthetic (bio)molecules. Although the thiol side chain of Cys can be in a free form, in most cases it forms a disulfide bond either with a second Cys (bridge) or with another thiol, as in the case of protecting groups. Efficient reduction of these disulfide bridges is a requirement for many applications of Cys-containing molecules in the fields of chemistry and biochemistry. Here we review reducing methods for disulfide bonds, taking into consideration the solubility of the substrates when selecting the appropriate reducing reagent.     

Optimization of fermentation condition for co-production of ethanol and 2,3-butanediol (2,3-BD) from hemicellolosic hydrolysates by Klebsiella oxytoca XF7

Microbial production of ethanol and 2,3-butanediol (2,3-BD) from agro-residues has been attracting interest because of their applications in various industries, including generation of biofuel molecules. In the present investigation, the hemicellulosic fraction of corncob was hydrolyzed by indigenous holocellulase from novel psychrotolerant Aspergillus niger SH3 resulting in high xylose release (34.61?g?L^?1), followed by the bioconversion of xylose to ethanol and 2,3-BD. Taguchi design was adopted to optimize the process which resulted in 5.25- and 3.31-fold increase in 2,3-BD (12.18?±?0.53?g?L^?1) and ethanol (4.08?±?0.03?g?L^?1), as compared with un-optimized condition. For the first time, co-production of ethanol and 2,3-BD from the corncob hemicellulosic hydrolysate was performed using a newly isolated Klebsiella oxytoca XF7 strain, under the optimized fermentation conditions. These results suggest that K. oxytoca XF7 is a promising candidate for co-production of ethanol and 2,3-BD, with high xylose conversion efficiency (96.65%), facilitating the economical production of biofuel molecules.     

Meshfree method for fluctuating hydrodynamics

In the current study a meshfree Lagrangian particle method for the Landau–Lifshitz Navier–Stokes (LLNS) equations is developed. The LLNS equations incorporate thermal fluctuation into macroscopic hydrodynamics by the addition of white noise fluxes whose magnitudes are set by a fluctuation–dissipation theorem. The study focuses on capturing the correct variance and correlations computed at equilibrium flows, which are compared with available theoretical values. Moreover, a numerical test for the random walk of standing shock wave has been considered for capturing the shock location.     

Optimized ensemble of regression tree-based location of evolving faults in dual-circuit line

Neural Computing and Applications - In a dual-circuit transmission line, the location of evolving faults (EVFs) is more tiresome due to its multifaceted nature. In this paper, a novel...     

Handwritten signature verification using shallow convolutional neural network

Multimedia Tools and Applications - Handwritten signatures are an undeniable and unique way to prove the identity of persons. Owing to the simplicity and uniqueness, it finds an essential place in...     

Chitosan: Application in tissue engineering and skin grafting

Tissue Engineering and skin grafting, an essential part of regenerative medicine is one of the fastest growing biomedical fields which could offer an important therapeutic strategy for management of hard to heal wounds. 2D and 3D polymeric scaffolds are prerequisites in this field to promote cell adhesion, proliferation and tissue regeneration. Convergence of technology and research has successfully unveiled unknown properties of Chitosan as a bioactive polymer. Natural abundance, cost effectiveness, biodegradability, biocompatibility and wound healing capabilities of chitosan and its derivatives has drawn the attention of many researchers for its use as an alternative for fabrication of a scaffold in tissue engineering and skin graft. However lower mechanical strength and solubility has limited its application in the biomedical field. It has been found that the derivatization and combination with other polymers can successfully overcome these limitations. This review focuses on the applicability of chitosan and its derivatives in combination with other polymers in tissue engineering and skin grafting along with the novel scaffold fabrication techniques. Studies so far have demonstrated the potential of chitosan and its derivative as a scaffold in the field of regenerative medicine. However, even if the promising results obtained from in-vitro and preclinical studies prove the efficacy of chitosan scaffolds it still has a long way to go to be used in clinical set ups.