Measurement of absolute abundance of crystallins in human and αA N101D transgenic mouse lenses using N-labeled crystallin standards.

Stable isotope labeled standards of all major human lens crystallins were created to measure the abundance of lens endogenous crystallins from birth to adulthood. All major human crystallins (αA, αB, βA2, βA3/A1, βA4, βB1, βB2, βB3, γA, γB, γC, γD, γS) were cloned with N-terminal 6 x His tagged SUMO for ease of purification and the ability to generate natural N-termini by SUMO protease cleavage when producing crystallins for structure/function studies. They were then expressed in N-enriched media, quantified by mass spectrometry, and mixed in proportions found in young human lens to act as an artificial lens standard.

Dysregulation of Autophagy Occurs During Congenital Cataract Development in βA3ΔG91 Mice.

Purpose: To examine lens phenotypic characteristics in βA3ΔG91 mice and determine if βA3ΔG91 affects autophagy in the lens.

Methods: We generated a βA3ΔG91 mouse model using CRISPR/Cas9 methodology. Comparative phenotypic and biochemical characterizations of lenses from postnatal day 0 (P0), P15, and 1-month-old βA3ΔG91 and wild-type (WT) mice were performed.

Immunofluorescence analysis of human eosinophils.

A prominent inflammatory cell type in allergic diseases is the eosinophil, a granulated white blood cell that releases pro-inflammatory cytokines. Eosinophil-derived cytokines, including interleukin-9 (IL-9) and interleukin-13 (IL-13), can skew the immune response towards an allergic phenotype. Unfortunately, it is challenging to immunolabel and collect quantifiable images of eosinophils given their innate autofluorescence and ability to nonspecifically bind to antibodies.

Role of Fibroblast Growth Factor Receptor 2 (FGFR2) in Corneal Stromal Thinning.

Purpose: To determine the role of fibroblast growth factor receptor 2 (FGFR2)-mediated signaling in keratocytes during corneal development, a keratocyte-specific FGFR2-knockout (named FGFR2cKO) mouse model was generated, and its phenotypic characteristics were determined.

Methods: A FGFR2cKO mouse model was generated by the following method: FGFR2 flox mice were crossed with the inducible keratocyte specific-Cre mice (Kera-rtTA/tet-O-Cre). Both male and female FGFR2cKO- and control mice (1 to 3-months-old) were analyzed for changes in corneal topography and pachymetry maps using the optical coherence tomography (OCT) method.

Lens-specific βA3/A1-conditional knockout mice: Phenotypic characteristics and calpain activation causing protein degradation and insolubilization.

βA3/A1-crystallin is a lens structural protein that plays an important role in maintaining lens transparency via interactions with other crystallins. While the function of βA3/A1-crystallin in the retina is well studied, its functions in the lens, other than as a structural protein, remain unclear. In the current study, we generated the lens-specific βA3/A1-crystallin conditional knockout mouse (named βA3/A1ckO) and explored phenotypic changes and the function of the crystallin in the lens.

Outcomes of Second-Line Intravitreal Anti-VEGF Switch Therapy in Radiation Retinopathy Secondary to Uveal Melanoma: Moving from Bevacizumab to Aflibercept.

Introduction: Radiation retinopathy is a dose-dependent complication of the retina following exposure to ionizing radiation. The objective of this prospective case series is to determine the clinical efficacy of intravitreal aflibercept for radiation retinopathy secondary to radiotherapy for uveal melanoma in those that failed intravitreal bevacizumab treatment.

Methods: A case series of 30 patients with a mean age of 57 ± 15 years with radiation retinopathy were enrolled.

Organophotoredox-mediated Formal [3+2]-Cycloaddition of 2H-Azirines with Aryldiazonium Salts: Direct Access to Trisubstituted 1,2,4-Triazoles.

The present work documents an organophotoredox-mediated formal [3+2]-cycloaddition of 2H-azirines with aryl diazonium tetrafluoroborate salts to furnish 1,3,5-trisubstituted 1,2,4-triazoles. The reaction furnishes a regioisomeric mixture of 1,2,4-triazoles in case of unsymmetrically substituted azirines. It is noteworthy that aryl radical generation from diazonium salt under visible light photoredox conditions could be successfully avoided by carefully selecting the reaction conditions.

Resolution of Fulminant Idiopathic Intracranial Hypertension Treated with Acetazolamide.

Idiopathic intracranial hypertension (IIH) is a condition of elevated intracranial pressure commonly seen in obese women of childbearing age. Fulminant IIH is a rare subset of IIH that is characterized by rapidly progressive vision loss in less than 4 weeks, and typically requires surgical intervention for treatment. We describe a 36-year-old man with a 3-week history of acute onset vision loss and fulminant IIH in whom severe bilateral hemorrhagic optic disk edema was identified.

Artificial intelligence and machine learning in ophthalmology: A review.

Since the introduction of artificial intelligence (AI) in 1956 by John McCarthy, the field has propelled medicine, optimized efficiency, and led to technological breakthroughs in clinical care. As an important frontier in healthcare, AI has implications on every subspecialty within medicine. This review highlights the applications of AI in ophthalmology: a specialty that lends itself well to the integration of computer algorithms due to the high volume of digital imaging, data, and objective metrics such as central retinal thickness.

αA and αB peptides from human cataractous lenses show antichaperone activity and enhance aggregation of lens proteins.

Purpose: To identify and characterize properties of αA- and αB-crystallins' low molecular weight peptides (molecular weight [Mr] < 5 kDa) that were present in a 62-year-old human nuclear cataract, but not in normal 62-year-old human lenses.

Methods: Low molecular weight peptides (< 5 kDa) were isolated with a trichloroacetic acid (TCA) solubilization method from water-soluble (WS) and water-insoluble (WI) proteins of nuclear cataractous lenses of a 62-year-old donor and normal human lenses from an age-matched donor. Five commercially synthesized peptides (found only in cataractous lenses and not in normal lenses) were used to determine their chaperone and antichaperone activity and aggregation properties.

Progressive Neurochemical Abnormalities in Cognitive and Motor Subgroups of Amyotrophic Lateral Sclerosis: A Prospective Multicenter Study.

Objective: To evaluate progressive cerebral degeneration in amyotrophic lateral sclerosis (ALS) by assessing alterations in -acetylaspartate (NAA) ratios in the motor and prefrontal cortex within clinical subgroups of ALS.

Methods: Seventy-six patients with ALS and 59 healthy controls were enrolled in a prospective, longitudinal, multicenter study in the Canadian ALS Neuroimaging Consortium. Participants underwent serial clinical evaluations and magnetic resonance spectroscopy at baseline and 4 and 8 months using a harmonized protocol across 5 centers.

Evolution from sinusoidal to collinear A-type antiferromagnetic spin-ordered magnetic phase transition in TbPrMnOsolid solution.

The present study reports on the structural and magnetic phase transitions in Pr-doped polycrystalline TbPrMnO, using high-resolution neutron powder diffraction (NPD) collected at SINQ spallation source, to emphasize the suppression of the sinusoidal magnetic structure of pure TbMnOand the evolution to a collinear A-type antiferromagnetic ordering. The phase purity, Jahn-Teller distortion, and one-electron bandwidth for eorbital of Mncation have been calculated for polycrystalline TbPrMnOin comparison to the parent materials TbMnOand PrMnO, through the Rietveld refinement study from x-ray diffraction data at room temperature, which reveals the GdFeOtype orthorhombic structure of TbPrMnOhavingspace group symmetry. The temperature-dependent zero field-cooled and field-cooled dc magnetization study at low temperature down to 5 K reveals a variation in the magnetic phase transition due to the effect of Prsubstitution at the Tbsite, which gives the signature of the antiferromagnetic nature of the sample, with a weak ferromagnetic component at low temperature-induced by an external magnetic field.

Increased Association of Deamidated αA- with Lens membrane of transgenic αA vs. wild type αA mice: potential effects on intracellular ionic imbalance and membrane disorganization.

Unlabelled: We have generated two mouse models, in one by inserting the human lens αAN101D transgene in CRYαA mice, and in the other by inserting human wild-type αA-transgene in CRYαA mice. The CRYαA mice developed cortical cataract at about 7-months of age relative to CRYαA mice. The objective of the study was to determine the following relative changes in the lenses of CRYαA- vs.

Nanodiagnostics in leishmaniasis: A new frontiers for early elimination.

Visceral leishmaniasis (VL) is still a major public health concern in developing countries having the highest outbreak and mortality potential. While the treatment of VL has greatly improved in recent times, the current diagnostic tools are limited for use in the post-elimination setting. Although conventional serological methods of detection are rapid, they can only differentiate between active disease in strict combination with clinical criteria, and thus are not sufficient enough to diagnose relapse patients.

Cytokine trafficking of IL-9 and IL-13 through TfnRc vesicles in activated human eosinophils.

Eosinophils are granulocytes that are elevated in lung mucosa in approximately half of patients with allergic asthma. These highly granulated cells can synthesize and secrete many cytokines, including IL-9 and IL-13. We hypothesized that IL-9 and IL-13 are found as preformed mediators in crystalloid granules and secreted using distinct trafficking pathways.

Evaluation of Safety and Antileishmanial Efficacy of Amine Functionalized Carbon-Based Composite Nanoparticle Appended With Amphotericin B: An and Preclinical Study.

Visceral leishmaniasis (VL) has been a major health concern in the developing world, primarily affecting impoverished people. It is caused by a protozoan parasite and is characterized by immune dysfunction that can lead to deadly secondary infections. Several adverse side effects limit the existing treatment options; hence, the need of the hour is some drug option with high efficacy and no toxicity.

Extraction of Two-Dimensional Aluminum Alloys from Decagonal Quasicrystals.

Atomically thin metallic alloys are receiving increased attention due to their prospective applications as interconnects/contacts in two-dimensional (2D) circuits, sensors, and catalysts, among others. In this work, we demonstrate an easily scalable technique for the synthesis of 2D metallic alloys from their 3D quasicrystalline precursors. We have used aluminum (Al)-based single-phase decagonal quasicrystal AlCoCu alloy to extract the corresponding 2D alloy structure.

Immobilization of fenugreek β-amylase onto functionalized graphene quantum dots (GQDs) using Box-Behnken design: Its biochemical, thermodynamic and kinetic studies.

β-Amylase was immobilized onto GQDs using 3-aminopropyltriethoxysilane and glutaraldehyde. Optimization was carried out by Box-Behnken design and binding was confirmed by SEM, AFM, FTIR and fluorescence microscopy. Predicted optimum immobilization efficiency (88.

Cerebral degeneration in amyotrophic lateral sclerosis: A prospective multicenter magnetic resonance spectroscopy study.

Background: We investigated cerebral degeneration and neurochemistry in patients with amyotrophic lateral sclerosis (ALS) using magnetic resonance spectroscopy (MRS).

Methods: We prospectively studied 65 patients and 43 age-matched healthy controls. Participants were recruited from 4 centers as part of a study in the Canadian ALS Neuroimaging Consortium.

Lens epithelial cells-induced pluripotent stem cells as a model to study epithelial-mesenchymal transition during posterior capsular opacification.

The overall goal was to generate an epithelial-mesenchymal transition (EMT) model using lens epithelial cells-induced pluripotent stem cells to elucidate EMT-regulatory factors during posterior capsular opacification (PCO). For this purpose, the mouse lens epithelial cells-derived mesenchymal cells were reprogrammed to induced pluripotent stem cells (iPSC) and differentiated to lens epithelial cells to be used to determine regulatory factors during EMT. Lens epithelial cells from one-month-old C57BL/6 mice were transitioned to mesenchymal cells in culture, and were reprogrammed to iPSC by delivering reprogramming factors in a single polycistronic lentiviral vector (co-expressing four transcription factors, Oct 4, Sox2, Klf4, and Myc).

Envisioning the innovations in nanomedicine to combat visceral leishmaniasis: for future theranostic application.

Visceral leishmaniasis (VL) is a life-threatening parasitic disease affecting impoverished people of the developing world; and much effort has been spent on the early case detection and treatment. However, current diagnostics and treatment options are not sufficient for appropriate surveillance in VL elimination setting. Hence, there is a dire need to develop highly sensitive diagnostics and less toxic effective treatments for proper management of cases and to achieve the sustained disease elimination.

A dual borohydride (Li and Na borohydride) catalyst/additive together with intermetallic FeTi for the optimization of the hydrogen sorption characteristics of Mg(NH)/2LiH.

The present study deals with the material tailoring of Mg(NH)-2LiH through dual borohydrides: the reactive LiBH and the non-reactive NaBH. Furthermore, a pulverizer, as well as a catalyst FeTi, has been added in order to facilitate hydrogen sorption. Addition of LiBH to LiNH in a 1 : 3 molar ratio leads to the formation of Li(BH)(NH) which also acts as a catalyst.

A Facile Synthesis of Alkaline Electrolyte Based Graphene Sheets, Their Functionalization and Attachment of Some Drugs.

High-quality graphene is highly enviable material due to its seminal role amongst several areas in modern technology including its role as nanocarrier for site selective drug grafting and delivery applications. Here, we report a facile, cost-effective and single-step method to produce high-quality graphene through customised electrochemical exfoliation of graphite anode in alkaline electrolyte medium. The quality of graphene sheets (GS) were investigated by Raman, TEM/HRTEM, AFM, and FTIR techniques.