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.     

Positive Maternal Attitude to the Family Eating Together Decreases the Risk of Adolescent Overweight

Objectives: To determine whether maternal attitude towards the family regularly eating together and maternal report of how often the family eat together are associated with adolescent offspring overweight. Research Methods and Procedures: A cross‐sectional mother‐child‐linked analysis was carried out using 14‐year follow‐up data from a population‐based prospective birth cohort of 3795 children (52% males) who were participants in the Mater‐University study of pregnancy, Brisbane, Australia. Maternal reports on family eating pattern reported at age 14 were used. Results: The prevalence of overweight at age 14 was 24.1% (95% confidence interval (CI), 22.3, 26.1) for males and 27.1% (CI, 25.1, 29.2) for females. The majority of mothers (78%) reported that the family ate together at least once a day, but only 43% reported that they felt that family eating together was important. The offspring of women who felt that the family eating together was not important had increased odds of being overweight at age 14 (odds ratio, 1.27; 95% CI, 1.05, 1.53) in age‐ and sex‐adjusted models. Adjustment for potential confounding factors had no substantive effect on the association. There was no association between maternal reports of how often the family actually did eat together and overweight at age 14 in the offspring. Discussion: These findings suggest that maternal attitude towards family eating patterns, but not maternal report of how often the family do eat together, are associated with childhood overweight status. Maternal attitude towards family eating (as opposed to a report of actual frequency at one time‐point) may reflect broader maternal influences (beyond family eating pattern) on their child's diet and eating patterns over a long time course.     

Estimation of 16S rRNA gene copy number in several probiotic Lactobacillus strains isolated from the gastrointestinal tract of chicken

The copy numbers of 16S rRNA genes in 12 probiotic Lactobacillus strains of poultry origin were analyzed. Genomic DNA of the strains was digested with restriction endonucleases that do not cut within the 16S rRNA gene of the strains. This was followed by Southern hybridization with a biotinylated probe complementary to the 16S rRNA gene. The copy number of the 16S rRNA gene within a Lactobacillus species was found to be conserved. From the hybridization results, Lactobacillus salivarius I 24 was estimated to have seven copies of the 16S rRNA gene, Lactobacillus panis C 17 to have five copies and Lactobacillus gallinarum strains I 16 and I 26 four copies. The 16S rRNA gene copy numbers of L. gallinarum and L. panis reported in the present study are the first record. Lactobacillus brevis strains I 12, I 23, I 25, I 211, I 218 and Lactobacillus reuteri strains C 1, C 10, C 16 were estimated to have at least four copies of the 16S rRNA gene. In addition, distinct rRNA restriction patterns which could discriminate the strains of L. reuteri and L. gallinarum were also detected. Information on 16S rRNA gene copy number is important for physiological, evolutionary and population studies of the bacteria.     

Contrasting genetic and morphological differentiation among geographical lineages of a stenotopic miniature rasborine,Boraras maculatus,in Peninsular Malaysia

The variability in the stenotopic miniature rasborine Boraras maculatus (Cypriniformes: Danionidae: Rasborinae) across acidic-water habitats of Peninsular Malaysia (PM) was investigated using two molecular markers (the mitochondrial cytochrome c oxidase subunit I [COI] gene and the nuclear rhodopsin gene), as well as morphological evidence. Molecular phylogenetic analyses revealed differentiation among populations of B. maculatus in PM with the distinction of four allopatric lineages. Each of them was recognized as a putative species by automatic species delimitation methods. These lineages diverged from each other between 7.4 and 1.9 million years ago. A principal component analysis (PCA) was conducted to examine the multivariate variation in 11 morphometric measurements among three of these lineages. PCA results showed a significant overlap in morphological characteristics among these lineages. Additionally, a photograph-based machine learning approach failed to fully differentiate these lineages, suggesting limited morphological differentiation. B. maculatus represents a case of morphological stasis in a stenotopic miniature species. Strong habitat preference, coupled with long-term habitat fragmentation, may explain why each lineage of B. maculatus has a restricted distribution and did not disperse to other regions within and outside of PM, despite ample possibilities when the Sunda shelf was emerged and drained by large paleodrainages for most of the past 7 million years. The conservation status of B. maculatus and its peat swamp habitats are discussed, and it is concluded that peat swamps comprise several evolutionary units. Each of these units is considered a conservation unit and deserves appropriate protection.     

Assessment of probiotic potential and anticancer activity of newly isolated vaginal bacterium Lactobacillus plantarum 5BL

Numerous bacteria in and on its external parts protect the human body from harmful threats. This study aimed to investigate the potential beneficial effects of the vaginal ecosystem microbiota. A type of bacteria was isolated from vaginal secretions of adolescent and young adult women, cultured on an appropriate specific culture medium, and then molecularly identified through 16S rDNA gene sequencing. Results of 16S rDNA sequencing revealed that the isolate belongs to the Lactobacillus plantarum species. The isolated strain exhibited probiotic properties such as low pH and high bile salt concentration tolerance, antibiotic susceptibility and antimicrobial activity against some pathogenic bacteria. The anticancer effects of the strain on human cancer cell lines (cervical, HeLa; gastric, AGS; colon, HT‐29; breast, MCF‐7) and on a human normal cell line (human umbilical vein endothelial cells [HUVEC]) were investigated. Toxic side effects were assessed by studying apoptosis in the treated cells. The strain exhibited desirable probiotic properties and remarkable anticancer activity against the tested human cancer cell lines (P ≤ 0.05) with no significant cytotoxic effects on HUVEC normal cells (P ≤ 0.05). Overall, the isolated strain showed favorable potential as a bioactive therapeutic agent. Therefore, this strain should be subjected to the other required tests to prove its suitability for clinical therapeutic application.     

Expression Analysis of Fatty Acid Biosynthetic Pathway Genes during Interactions of Oil Palm (Elaeis guineensis Jacq.) with the Pathogenic Ganoderma boninense and Symbiotic Trichoderma harzianum Fungal Organisms

The fatty acid (FA) signaling pathway is emerging as an important mechanism in plant responses during interactions with microbial organisms. For a comprehensive evaluation of key FA biosynthetic pathway genes during interactions of oil palm (Elaeis guineensis Jacq.) with the pathogenic Ganoderma boninense and symbiotic Trichoderma harzianum fungal organisms, a lane-based array analysis of gene expression in artificially inoculated oil palm seedlings was performed. The results obtained demonstrated that acetyl-CoA carboxylase (ACC), β-ketoacyl-ACP synthases (KAS) II and III, palmitoyl-ACP thioesterase (PTE), oleoyl-ACP thioesterase (OTE) and glycerol-3-phosphate acyltransferase (ACT) showed identical responses in root and leaf tissues for the same fungi. The expression of these genes was up-regulated in both root and leaf tissues at 21 days post-inoculation (dpi) during interaction of oil palm with G. boninense. Thereafter, production of physical symptoms occurred at 42 and 63 dpi concomitantly with suppression of expression of these genes. An increase in the expression level of these genes was observed in both tissues at 3–63 dpi, which correlated with the colonization of roots and promotion of plant growth by T. harzianum. These data suggest that FA biosynthetic pathway genes are involved in the defense response of oil palm to infection. Identical plant responses by FA biosynthetic pathway genes may lead to enhanced resistance against G. boninense and could be a useful marker to contribute towards early detection of infection. The distinct expression profile during symbiotic interaction demonstrated its role in plant resistance mechanisms and growth promotion by T. harzianum.     

Conformational Switching in PolyGln Amyloid Fibrils Resulting from a Single Amino Acid Insertion

The established correlation between neurodegenerative disorders and intracerebral deposition of polyglutamine aggregates motivates attempts to better understand their fibrillar structure. We designed polyglutamines with a few lysines inserted to overcome the hindrance of extreme insolubility and two D-lysines to limit the lengths of β-strands. One is 33 amino acids long (PolyQKd-33) and the other has one fewer glutamine (PolyQKd-32). Both form well-dispersed fibrils suitable for analysis by electron microscopy. Electron diffraction confirmed cross-β structures in both fibrils. Remarkably, the deletion of just one glutamine residue from the middle of the peptide leads to substantially different amyloid structures. PolyQKd-32 fibrils are consistently 10–20% wider than PolyQKd-33, as measured by negative staining, cryo-electron microscopy, and scanning transmission electron microscopy. Scanning transmission electron microscopy analysis revealed that the PolyQKd-32 fibrils have 50% higher mass-per-length than PolyQKd-33. This distinction can be explained by a superpleated β-structure model for PolyQKd-33 and a model with two β-solenoid protofibrils for PolyQKd-32. These data provide evidence for β-arch-containing structures in polyglutamine fibrils and open future possibilities for structure-based drug design.