Different Patterns of White Matter Degeneration Using Multiple Diffusion Indices and Volumetric Data in Mild Cognitive Impairment and Alzheimer Patients

Alzheimeŕs disease (AD) represents the most prevalent neurodegenerative disorder that causes cognitive decline in old age. In its early stages, AD is associated with microstructural abnormalities in white matter (WM). In the current study, multiple indices of diffusion tensor imaging (DTI) and brain volumetric measurements were employed to comprehensively investigate the landscape of AD pathology. The sample comprised 58 individuals including cognitively normal subjects (controls), amnestic mild cognitive impairment (MCI) and AD patients. Relative to controls, both MCI and AD subjects showed widespread changes of anisotropic fraction (FA) in the corpus callosum, cingulate and uncinate fasciculus. Mean diffusivity and radial changes were also observed in AD patients in comparison with controls. After controlling for the gray matter atrophy the number of regions of significantly lower FA in AD patients relative to controls was decreased; nonetheless, unique areas of microstructural damage remained, e.g., the corpus callosum and uncinate fasciculus. Despite sample size limitations, the current results suggest that a combination of secondary and primary degeneration occurrs in MCI and AD, although the secondary degeneration appears to have a more critical role during the stages of disease involving dementia.     

WNK1 is an assembly factor for the human ER membrane protein complex

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Influenza Vaccine Manufacturing: Effect of Inactivation,Splitting and Site of Manufacturing. Comparison of Influenza Vaccine Production Processes

The aim of this study was to evaluate the impact of different inactivation and splitting procedures on influenza vaccine product composition, stability and recovery to support transfer of process technology. Four split and two whole inactivated virus (WIV) influenza vaccine bulks were produced and compared with respect to release criteria, stability of the bulk and haemagglutinin recovery. One clarified harvest of influenza H3N2 A/Uruguay virus prepared on 25.000 fertilized eggs was divided equally over six downstream processes. The main unit operation for purification was sucrose gradient zonal ultracentrifugation. The inactivation of the virus was performed with either formaldehyde in phosphate buffer or with beta-propiolactone in citrate buffer. For splitting of the viral products in presence of Tween^®, either Triton^™ X-100 or di-ethyl-ether was used. Removal of ether was established by centrifugation and evaporation, whereas removal of Triton-X100 was performed by hydrophobic interaction chromatography. All products were sterile filtered and subjected to a 5 months real time stability study. In all processes, major product losses were measured after sterile filtration; with larger losses for split virus than for WIV. The beta-propiolactone inactivation on average resulted in higher recoveries compared to processes using formaldehyde inactivation. Especially ether split formaldehyde product showed low recovery and least stability over a period of five months.     

Induction of N–malonyl–D–tryptophan by drought stress. Is D–tryptophan the only D–amino acid appeared in wilted leaves?

D-amino acid were searched in wilted tomato leaves. D-Isomers of free amino acids were not revealed by the treatment with L- and D-amino acid oxidases. The noncationic fraction of the extract contained N-malonyl-D-tryptophan and no other N-acylated amino acids. A special search for endogenous N-malonyl-D-phenylalanine gave negative results. Exogenous¹⁴C-malonate was only incorporated in one Chromatographic zone corresponding to N-malonyl-D-tryptophan. It is concluded that drought stress does not induce the appearance of D-amino acids except for D-tryptophan which is accumulated in the malonylated form.     

γ-Lactam-Based Antifungal Compounds against the Wheat Pathogen Zymoseptoria tritici

As new environmentally friendly and effective antifungal agents are deeply needed, efficient ecofriendly strategies were designed to access two series of compounds inspired from natural γ-lactams. Designed compounds were fully characterized and evaluated as antifungal candidates against Zymoseptoria tritici, the main pathogen on wheat crops. The targeted derivatives were prepared from natural resources using green solvents, simple procedures, and limited purification steps. These bio-inspired compounds revealed as good candidates for further development of efficient crop protection products. Indeed, the HIT compounds exhibited IC₅₀ around 1 μg/mL and were more active than the references tebuconazole and bixafen towards some multidrug-resistant strains. Two dozen of derivatives have been obtained for each series and allowed to establish early structure-activity relationships useful for the development of next generation of γ-lactam derivatives with improved efficacy.     

Spontaneous aneuploidy level in blood cells of fertile females

In this study, we presented results of molecular cytogenetic assay of blood cells of fertile women of reproductive age. Cultivated and uncultivated cells and two sets of FISH probes with direct and indirect labeling were used. The middle level of aneuploidy for four chromosomes and statistical limits for aneuploidy detection were estimated. Aneuploidy determined with direct multicolor FISH in cultivated lymphocytes varied from 0.1 to 1.3%. The middle level of aneuploidy for all four chromosomes (13, 18, 21, and X) was 1.39%. The limit of mutation detection was 3.4%. We found differences in results with direct and indirect labeling. It was shown that the cultivation process influenced the level of aneuploidy. The absolute error in FISH technique was 0.13% and the relative error was 4.08%.     

Biological Instability in a Chlorinated Drinking Water Distribution Network

The purpose of a drinking water distribution system is to deliver drinking water to the consumer, preferably with the same quality as when it left the treatment plant. In this context, the maintenance of good microbiological quality is often referred to as biological stability, and the addition of sufficient chlorine residuals is regarded as one way to achieve this. The full-scale drinking water distribution system of Riga (Latvia) was investigated with respect to biological stability in chlorinated drinking water. Flow cytometric (FCM) intact cell concentrations, intracellular adenosine tri-phosphate (ATP), heterotrophic plate counts and residual chlorine measurements were performed to evaluate the drinking water quality and stability at 49 sampling points throughout the distribution network. Cell viability methods were compared and the importance of extracellular ATP measurements was examined as well. FCM intact cell concentrations varied from 5×10³ cells mL⁻¹ to 4.66×10⁵ cells mL⁻¹ in the network. While this parameter did not exceed 2.1×10⁴ cells mL⁻¹ in the effluent from any water treatment plant, 50% of all the network samples contained more than 1.06×10⁵ cells mL⁻¹. This indisputably demonstrates biological instability in this particular drinking water distribution system, which was ascribed to a loss of disinfectant residuals and concomitant bacterial growth. The study highlights the potential of using cultivation-independent methods for the assessment of chlorinated water samples. In addition, it underlines the complexity of full-scale drinking water distribution systems, and the resulting challenges to establish the causes of biological instability.     

Citrate usage in the leading causes of blindness: new possibilities for the old metabolite

Introduction

Citrate is an old metabolite which is best known for the role in the Krebs cycle. Citrate is widely used in many branches of medicine. In ophthalmology citrate is considered as a therapeutic agent and an useful diagnostic tool—biomarker.

Objectives

To summarize the published literature on citrate usage in the leading causes of blindness and highlight the new possibilities for this old metabolite.

Methods

We conducted a systematic search of the scientific literature about citrate usage in ophthalmology up to January 2018. The reference lists of identified articles were searched for providing in-depth information.

Results

This systematic review included 30 articles. The role of citrate in the leading causes of blindness is presented.

Conclusions

Citrate might help inhibit cataract progression, in case of questions confirm glaucoma diagnosis or improve cornea repair treatment as adjuvant agent (therapy of ulcerating cornea after alkali injury, crosslinking procedure). However, the knowledge about possible citrate usage in ophthalmology is not widely known. Promoting recent scientific knowledge about citrate usage in ophthalmology may not only benefit of medical improvement but may also limit economic costs caused by leading causes of blindness. Further studies on citrate usage in ophthalmology should continuously be the field of scientific interest.