Autophagic dysfunction in Alzheimer’s disease: Cellular and molecular mechanistic approaches to halt Alzheimer’s pathogenesis

Autophagy is a preserved cytoplasmic self-degradation process and endorses recycling of intracellular constituents into bioenergetics for the controlling of cellular homeostasis. Functional autophagy process is essential in eliminating cytoplasmic waste components and helps in the recycling of some of its constituents. Studies have revealed that neurodegenerative disorders may be caused by mutations in autophagy-related genes and alterations of autophagic flux. Alzheimer’s disease (AD) is an irrevocable deleterious neurodegenerative disorder characterized by the formation of senile plaques and neurofibrillary tangles (NFTs) in the hippocampus and cortex. In the central nervous system of healthy people, there is no accretion of amyloid β (Aβ) peptides due to the balance between generation and degradation of Aβ. However, for AD patients, the generation of Aβ peptides is higher than lysis that causes accretion of Aβ. Likewise, the maturation of autophagolysosomes and inhibition of their retrograde transport creates favorable conditions for Aβ accumulation. Furthermore, increasing mammalian target of rapamycin (mTOR) signaling raises tau levels as well as phosphorylation. Alteration of mTOR activity occurs in the early stage of AD. In addition, copious evidence links autophagic/lysosomal dysfunction in AD. Compromised mitophagy is also accountable for dysfunctional mitochondria that raises Alzheimer’s pathology. Therefore, autophagic dysfunction might lead to the deposit of atypical proteins in the AD brain and manipulation of autophagy could be considered as an emerging therapeutic target. This review highlights the critical linkage of autophagy in the pathogenesis of AD, and avows a new insight to search for therapeutic target for blocking Alzheimer’s pathogenesis.     

Poly(dG)-poly(dC) DNA appears shorter than poly(dA)-poly(dT) and possibly adopts an A-related conformation on a mica surface under ambient conditions

Three types of DNA: approximately 2700 bp polydeoxyguanylic olydeoxycytidylic acid [poly(dG)-poly(dC)], approximately 2700 bp polydeoxyadenylic polydeoxythymidylic acid [poly(dA)-poly(dT)] and 2686 bp linear plasmid pUC19 were deposited on a mica surface and imaged by atomic force microscopy. Contour length measurements show that the average length of poly(dG)-poly(dC) is approximately 30% shorter than that of poly(dA)-poly(dT) and the plasmid. This led us to suggest that individual poly(dG)-poly(dC) molecules are immobilized on mica under ambient conditions in a form which is likely related to the A-form of DNA in contrast to poly(dA)-poly(dT) and random sequence DNA which are immobilized in a form that is related to the DNA B-form.     

Enzymatic pre‐treatment of microalgae cells for enhanced extraction of proteins

Crude proteins and pigments were extracted from different microalgae strains, both marine and freshwater. The effectiveness of enzymatic pre‐treatment prior to protein extraction was evaluated and compared to conventional techniques, including ultrasonication and high‐pressure water extraction. Enzymatic pre‐treatment was chosen as it could be carried out at mild shear conditions and does not subject the proteins to high temperatures, as with the ultrasonication approach. Using enzymatic pre‐treatment, the extracted proteins yields of all tested microalgae strains were approximately 0.7 mg per mg of dry cell weight. These values were comparable to those achieved using a commercial lytic kit. Ultrasonication was not very effective for proteins extraction from Chlorella sp., and the extracted proteins yields did not exceed 0.4 mg per mg of dry cell weight. For other strains, similar yields were achieved by both treatment methods. The time‐course effect of enzymatic incubation on the proteins extraction efficiency was more evident using laccase compared to lysozyme, which suggested that the former enzyme has a slower rate of cell disruption. The crude extracted proteins were fractionated using an ion exchange resin and were analyzed by the electrophoresis technique. They were further tested for their antioxidant activity, the highest of which was about 60% from Nannochloropsis sp. The total phenolic contents in the selected strains were also determined, with Chlorella sp. showing the highest content reaching 17 mg/g. Lysozyme was also found to enhance the extraction of pigments, with Chlorella sp. showing the highest pigments contents of 16.02, 4.59 and 5.22 mg/g of chlorophyll a, chlorophyll b and total carotenoids, respectively.     

Evaluation and selection of tandem repeat loci for a Brucella MLVA typing assay

Background  

The classification of Brucella into species and biovars relies on phenotypic characteristics and sometimes raises difficulties in the interpretation of the results due to an absence of standardization of the typing reagents. In addition, the resolution of this biotyping is moderate and requires the manipulation of the living agent. More efficient DNA-based methods are needed, and this work explores the suitability of multiple locus variable number tandem repeats analysis (MLVA) for both typing and species identification.     

NADH oxidase activity of Bacillus subtilis nitroreductase NfrA1: Insight into its biological role

NfrA1 nitroreductase from the Gram-positive bacterium Bacillus subtilis is a member of the NAD(P)H/FMN oxidoreductase family. Here, we investigated the reactivity, the structure and kinetics of NfrA1, which could provide insight into the unclear biological role of this enzyme. We could show that NfrA1 possesses an NADH oxidase activity that leads to high concentrations of oxygen peroxide and an NAD⁺ degrading activity leading to free nicotinamide. Finally, we showed that NfrA1 is able to rapidly scavenge H₂O₂ produced during the oxidative process or added exogenously.

Structured summary

MINT-7990140: nfrA1 (uniprotkb:P39605) and nfrA1 (uniprotkb:P39605) bind (MI:0407) by X-ray crystallography (MI:0114)     

Tabanidae (Diptera) of Saudi Arabia

Samples were collected from southern, central and eastern regions of Saudi Arabia using Malaise traps and sweep nets. Nine species of Tabanidae were identified, two for the first time from Saudi Arabia, Hybomitra peculiaris (Szilády) and Atylotus pulchellus (Loew).Therefore, the total number of Tabanidae in Saudi Arabia is 31 species. Remarks of the species recorded in this study were given. A key to the genera of Tabanidae occurring in the Arabian Peninsula is also provided. Available literature for Saudi Arabian Tabanidae is summarized and provided. It is concluded that the tabanid fauna of Saudi Arabia is more similar to that of the Palaearctic region than to the Afrotropical region.     

Larvicidal potential of gold and silver nanoparticles synthesized using Acalypha fruticosa leaf extracts against Culex pipiens (Culicidae: Diptera)

Plant secondary metabolites have been recently used for the synthesis of different nanoparticles. The present investigation aimed at evaluating the effect of gold (AuNPs) and silver (AgNPs) nanoparticles synthesized using Acalypha fruticosa leaf extracts to control the mosquito Culex pipiens. The A. fruticosa AuNPs and AgNPs spectra displayed their maximum absorption at 550 nm and 440 nm, respectively. The infrared spectra revealed different functional groups related to different chemical compounds. The larval mortality of aqueous leaf extract of A. fruticosa was 499.54 ppm (LC₅₀) and 1734.06 ppm (LC₉₀) after 24 h of treatment. This study revealed that AuNP (LC₅₀, 30.2 and LC₉₀, 104.83 ppm) and AgNP (LC₅₀, 52.86 and LC₉₀, 157.227 ppm) preparations were highly effective compared to the A. fruticosa extract alone and also more affordable, as a smaller amount was required. The present findings show the potential larvicidal effect of the synthesized AuNPs and AgNPs for the control of mosquito-mediated disease transmission.     

Bayesian Estimation Using Ranked Set Sampling

Bayesian Estimation of the parameter of a distribution is considered using Ranked set sampling (RSS). It is shown that for at least one RSS plan, the Bayes estimator has smaller Bayes risk than the Bayes estimator using simple random sampling (SRS). Furthermore, for exponential family with conjugate prior, the Bayes estimator of the mean using balanced RSS dominates, in terms of its Bayes risk, the Bayes estimator of the mean using SRS. This procedure is used to estimate the average Milk yield of four hundreds and two sheep. The empirical efficiency supports the theoretical findings.     

How to efficiently determine the size at maturity of small-sized tropical fishes: A case study based on 144 species identified via DNA barcoding from southwestern Madagascar

In order to provide biological evidence of the real impact of mosquito seine nets in southwestern Madagascar, an efficient procedure for determining the size at maturity of small-sized tropical fishes was developed. The fishes caught by two small-scale fishermen were studied between October 2017 and April 2018. One catch per day was analyzed three days per month during the full-moon period. In the laboratory, fishes were all sorted by morphospecies, photographed and measured. One individual per morphospecies was selected for being identified using CO1 DNA barcoding. A total of 34,051 individual fishes belonging to 144 DNA bacoded species from 48 families was obtained from 42 samples, 467 individuals from 22 morphospecies that had not been successfully barcoded were excluded from the analyses. The macroscopic observations of 8,143 individuals between 0.7 and 10 cm SL indicated the proportion of individuals with clearly observable gonads was 15% only.Among the 144 species identified via DNA barcoding, 83 consisted of individuals that were all without clearly observable gonads, seven of individuals that were all with clearly observable gonads and 54 included of individuals with and without clearly observable gonads. As the determination of L₅₀ using logistic general linear models failed for most species, the minimum size at maturity was retained to determine the proportion of juveniles and adults for these 54 species. Compared to the data available in FishBase, the minimum size at maturity appears more adequate to discrimine juvenile from adult fish of small-sized tropical species.     

Whole Mitochondrial and Plastid Genome SNP Analysis of Nine Date Palm Cultivars Reveals Plastid Heteroplasmy and Close Phylogenetic Relationships among Cultivars

Date palm is a very important crop in western Asia and northern Africa, and it is the oldest domesticated fruit tree with archaeological records dating back 5000 years. The huge economic value of this crop has generated considerable interest in breeding programs to enhance production of dates. One of the major limitations of these efforts is the uncertainty regarding the number of date palm cultivars, which are currently based on fruit shape, size, color, and taste. Whole mitochondrial and plastid genome sequences were utilized to examine single nucleotide polymorphisms (SNPs) of date palms to evaluate the efficacy of this approach for molecular characterization of cultivars. Mitochondrial and plastid genomes of nine Saudi Arabian cultivars were sequenced. For each species about 60 million 100 bp paired-end reads were generated from total genomic DNA using the Illumina HiSeq 2000 platform. For each cultivar, sequences were aligned separately to the published date palm plastid and mitochondrial reference genomes, and SNPs were identified. The results identified cultivar-specific SNPs for eight of the nine cultivars. Two previous SNP analyses of mitochondrial and plastid genomes identified substantial intra-cultivar ( = intra-varietal) polymorphisms in organellar genomes but these studies did not properly take into account the fact that nearly half of the plastid genome has been integrated into the mitochondrial genome. Filtering all sequencing reads that mapped to both organellar genomes nearly eliminated mitochondrial heteroplasmy but all plastid SNPs remained heteroplasmic. This investigation provides valuable insights into how to deal with interorganellar DNA transfer in performing SNP analyses from total genomic DNA. The results confirm recent suggestions that plastid heteroplasmy is much more common than previously thought. Finally, low levels of sequence variation in plastid and mitochondrial genomes argue for using nuclear SNPs for molecular characterization of date palm cultivars.