A mutation in transmembrane protein 135 impairs lipid metabolism in mouse eyecups

Aging is a significant factor in the development of age-related diseases but how aging disrupts cellular homeostasis to cause age-related retinal disease is unknown. Here, we further our studies on transmembrane protein 135 (Tmem135), a gene involved in retinal aging, by examining the transcriptomic profiles of wild-type, heterozygous and homozygous Tmem135 mutant posterior eyecup samples through RNA sequencing (RNA-Seq). We found significant gene expression changes in both heterozygous and homozygous Tmem135 mutant mouse eyecups that correlate with visual function deficits. Further analysis revealed that expression of many genes involved in lipid metabolism are changed due to the Tmem135 mutation. Consistent with these changes, we found increased lipid accumulation in mutant Tmem135 eyecup samples. Since mutant Tmem135 mice have similar ocular pathologies as human age-related macular degeneration (AMD) eyes, we compared our homozygous Tmem135 mutant eyecup RNA-Seq dataset with transcriptomic datasets of human AMD donor eyes. We found similar changes in genes involved in lipid metabolism between the homozygous Tmem135 mutant eyecups and AMD donor eyes. Our study suggests that the Tmem135 mutation affects lipid metabolism as similarly observed in human AMD eyes, thus Tmem135 mutant mice can serve as a good model for the role of dysregulated lipid metabolism in AMD

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Plant Growth-Promoting Microbes from Herbal Vermicompost

Overreliance on chemical pesticides and fertilizers has resulted in problems including safety risks, outbreaks of secondary pests normally held in check by natural enemies, insecticide resistance, environmental contamination, and decrease in biodiversity. The increasing costs and negative effects of pesticides and fertilizers necessitate the idea of biological options of crop protection and production. This includes the use of animal manure, crop residues, microbial inoculum, and composts. They provide natural nutrition, reduce the use of inorganic fertilizers, develop biodiversity, increase soil biological activity, maintain soil physical properties, and improve environmental health

Mixed convective-radiative dissipative magnetized micropolar nanofluid flow over a stretching surface in porous media with double stratification and chemical reaction effects : ADM-Padé computation

The present study deals with the electrically conducting micropolar nanofluid flow from a vertical stretching surface adjacent to a porous medium under a transverse magnetic field. Eringen’s micropolar model is deployed for non-Newtonian characteristics and the Buongiorno nanofluid model employed for nanoscale effects (thermophoresis and Brownian motion). The model includes double stratification (thermal and solutal) and also chemical reaction effects, heat source and viscous dissipation. Darcy’s model is employed for the porous medium and a Rosseland diffusion flux approximation for nonlinear thermal radiation. The nonlinear governing partial differential conservation equations are rendered into nonlinear ordinary differential equations via relevant transformations. An innovative semi-numerical methodology combining the Adomian decomposition method (ADM) with Padé approximants and known as ADM-Padé is deployed to solve the emerging nonlinear ordinary differential boundary value problem with appropriate wall and free stream conditions in MATLAB software. A detailed parametric study of the influence of key parameters on stream function, velocity, microrotation (angular velocity), temperature and nanoparticle concentration profiles are conducted. Furthermore, skin friction coefficient, wall couple stress coefficient, Nusselt number and Sherwood number are displayed in tables. The validation of both numerical techniques used i. e. ADM and ADM-Padé against a conventional numerical 4 th order Runge Kutta method is also included and significant acceleration in convergence of solutions achieved with the ADM-Padé approach. The flow is decelerated with greater buoyancy ratio parameter whereas microrotation (angular velocity) is enhanced. Increasing thermal and solutal stratification suppresses micro-rotation. Concentration magnitudes are boosted with greater chemical reaction parameter and Lewis number. Temperatures are significantly enhanced with radiative parameter. Increasing Brownian motion parameter depletes concentration values. The study finds applications in thermo-magnetic coating processes involving nanomaterials with microstructural characteristics

Axisymmetric radiative titanium dioxide magnetic nanofluid flow on a stretching cylinder with homogeneous/ heterogeneous reactions in Darcy-Forchheimer porous media : intelligent nanocoating simulation

Modern nanomaterials coating processes feature high temperature environments and complex chemical reactions required for the precise synthesis of bespoke designs. Such flow processes are extremely complex and feature both heat and mass transfer in addition to viscous behaviour. Intelligent nanocoatings exploit magnetic nanoparticles and can be manipulated by external magnetic fields. Mathematical models provide an inexpensive insight into the inherent characteristics of such coating dynamics processes. Motivated by this, in the current work, a novel mathematical model is developed for dual catalytic reactive species diffusion in axisymmetric coating enrobing forced convection boundary layer flow from a linearly axially stretching horizontal cylinder immersed in a homogenous non-Darcy porous medium saturated with magnetic nanofluid. Homogeneous and heterogeneous reactions, heat source (e.g. laser source) and non-linear radiative transfer are included. The Tiwari-Das nanoscale model is deployed. A Darcy-Forchheimer drag force formulation is utilized to simulate both bulk porous drag and second order inertial drag of the porous medium fibres. The magnetic nanofluid is an aqueous electroconductive polymer comprising base fluid water and magnetic TiO2 nanoparticles. The TiO2 nanoparticles are one chemically reacting species (A) and a second species (B) is also present (e.g. oxygen) which also reacts chemically. Viscous heating and Ohmic dissipation are also included to produce a more physically realistic thermal analysis. The non-linear conservation equations proposed here with species diffusion (species A and B) are transformed via an appropriate stream function and scaling variables into a set of non-linear united multi-degree ODEs. The rising nonlinear ordinary differential boundary value problem is solved with four-point Gauss-Lobotto formulae in the MATLAB bvp5c routine. Validation is conducted with an Adams-Moulton predictorcorrector numerical scheme (AM2 coded in Unix). The widespread visualization of velocity, temperature, species A concentration, species B concentration, skin friction, local Nusselt number and species A and B local Sherwood numbers is included

A Method to Discriminate Strain and Temperature in Fiber Bragg Grating Sensors

A significant limitation to the applications of fiber Bragg gratings (FBG) sensors is the sensitivity of the Bragg wavelength to both temperature and strain, complicating the independent measurement of these paremeters. In this letter, we explore a new method to discriminate strain and temperature in FBG sensors, which utilises the additioanl wavelength dependent phase introduced by Fiber Bragg grating written on sensing arm of Mach Zehnder Interferometer (MZI). The intensity variations of the MZI output at the wavelength outside the Bragg resonance provide an additional parameter along with the Bragg wavelength shift observed at the input end for simultaneous measurement of strain and temperature

Fusogenic peptide as diagnostic marker for detection of flaviviruses

Background: Dengue, Japanese encephalitis, West Nile encephalitis, yellow fever are the common flaviviral diseases associated with high morbidity and mortality. The initial symptoms of most of the flaviviral infections are similar to each other as well as to some other viral diseases. Making clinical diagnosis, therefore, becomes a challenging task for the clinician. Several studies have been reported on using detection of serum antibodies against flavivirus for the diagnosis of specific flaviviral disease; no field-based pan-flavi virus detection system is available, which can be used in low-endemicity areas for differentiation of flaviviral disease from other viral diseases. Aim: To identify a conserved amino acid sequence among all flaviviruses and evaluate the antibody formed against the conserved peptide to develop pan-flavivirus detection system. Materials and Methods: In the present study we have compared amino acid sequences of several flaviviruses and identified a conserved amino acid sequence lying in domain II of envelope protein. Results : A peptide having the conserved amino acid sequence was used to generate polyclonal antibodies and these antibodies were used to detect several flaviviruses. Anti-peptide polyclonal antibodies selectively recognized flaviviruses and did not detect non-flaviviruses. Anti-peptide antibodies detected presence of virus in serum spiked with pure virus preparations. Conclusion: The study offers a rationale for development of pan-flavivirus capture assay suitable for low endemic areas

Magnetic resonance imaging of cerebral malaria patients reveals distinct pathogenetic processes in different parts of the brain.

The mechanisms underlying the rapidly reversible brain swelling described in patients with cerebral malaria (CM) are unknown. Using a 1.5-Tesla (T) magnetic resonance imaging (MRI) scanner, we undertook an observational study in Rourkela, India, of 11 Indian patients hospitalized with CM and increased brain volume. Among the 11 cases, there were 5 adults and 6 children. All patients had reduced consciousness and various degrees of cortical swelling at baseline. The latter was predominately posterior in distribution. The findings on diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps were consistent with vasogenic edema in all cases. Reversibility after 48 to 72 h was observed in >90% of cases. DWI/ADC mismatch suggested the additional presence of cytotoxic edema in the basal nuclei of 5 patients; all of these had perfusion parameters consistent with vascular engorgement and not with ischemic infarcts. Our results suggest that an impairment of the blood-brain barrier is responsible for the brain swelling in CM. In 5 cases, vasogenic edema occurred in conjunction with changes in the basal nuclei consistent with venous congestion, likely to be caused by the sequestration of Plasmodium falciparum-infected erythrocytes. While both mechanisms have been individually postulated to play an important role in the development of CM, this is the first demonstration of their concurrent involvement in different parts of the brain. The clinical and radiological characteristics observed in the majority of our patients are consistent with posterior reversible encephalopathy syndrome (PRES), and we show for the first time a high frequency of PRES in the context of CM. IMPORTANCE The pathophysiology and molecular mechanisms underlying cerebral malaria (CM) are still poorly understood. Recent neuroimaging studies demonstrated that brain swelling is a common feature in CM and a major contributor to death in pediatric patients. Consequently, determining the precise mechanisms responsible for this swelling could open new adjunct therapeutic avenues in CM patients. Using an MRI scanner with a higher resolution than the ones used in previous reports, we identified two distinct origins of brain swelling in both adult and pediatric patients from India, occurring in distinct parts of the brain. Our results support the hypothesis that both endothelial dysfunction and microvascular obstruction by Plasmodium falciparum-infected erythrocytes make independent contributions to the pathogenesis of CM, providing opportunities for novel therapeutic interventions

Brain magnetic resonance imaging reveals different courses of disease in pediatric and adult cerebral malaria

BackgroundCerebral malaria is a common presentation of severe Plasmodium falciparum infection and remains an important cause of death in the tropics. Key aspects of its pathogenesis are still incompletely understood, but severe brain swelling identified by magnetic resonance imaging (MRI) was associated with a fatal outcome in African children. In contrast, neuroimaging investigations failed to identify cerebral features associated with fatality in Asian adults.MethodsQuantitative MRI with brain volume assessment and apparent diffusion coefficient (ADC) histogram analyses were performed for the first time in 65 patients with cerebral malaria to compare disease signatures between children and adults from the same cohort, as well as between fatal and nonfatal cases.ResultsWe found an age-dependent decrease in brain swelling during acute cerebral malaria, and brain volumes did not differ between fatal and nonfatal cases across both age groups. In nonfatal disease, reversible, hypoxia-induced cytotoxic edema occurred predominantly in the white matter in children, and in the basal ganglia in adults. In fatal cases, quantitative ADC histogram analyses also demonstrated different end-stage patterns between adults and children: Severe hypoxia, evidenced by global ADC decrease and elevated plasma levels of lipocalin-2 and microRNA-150, was associated with a fatal outcome in adults. In fatal pediatric disease, our results corroborate an increase in brain volume, leading to augmented cerebral pressure, brainstem herniation, and death.ConclusionsOur findings suggest distinct pathogenic patterns in pediatric and adult cerebral malaria with a stronger cytotoxic component in adults, supporting the development of age-specific adjunct therapies