Phosphorylation of amyloid-β peptide at serine 8 attenuates its clearance via insulin-degrading and angiotensin-converting enzymes

Accumulation of amyloid-β peptides (Aβ) in the brain is a common pathological feature of Alzheimer disease (AD). Aggregates of Aβ are neurotoxic and appear to be critically involved in the neurodegeneration during AD pathogenesis. Accumulation of Aβ could be caused by increased production, as indicated by several mutations in the amyloid precursor protein or the γ-secretase components presenilin-1 and presenilin-2 that cause familial early-onset AD. However, recent data also indicate a decreased clearance rate of Aβ in AD brains. We recently demonstrated that Aβ undergoes phosphorylation by extracellular or cell surface-localized protein kinase A, leading to increased aggregation. Here, we provide evidence that phosphorylation of monomeric Aβ at Ser-8 also decreases its clearance by microglial cells. By using mass spectrometry, we demonstrate that phosphorylation at Ser-8 inhibited the proteolytic degradation of monomeric Aβ by the insulin-degrading enzyme, a major Aβ-degrading enzyme released from microglial cells. Phosphorylation also decreased the degradation of Aβ by the angiotensin-converting enzyme. In contrast, Aβ degradation by plasmin was largely unaffected by phosphorylation. Thus, phosphorylation of Aβ could play a dual role in Aβ metabolism. It decreases its proteolytic clearance and also promotes its aggregation. The inhibition of extracellular Aβ phosphorylation, stimulation of protease expression and/or their proteolytic activity could be explored to promote Aβ degradation in AD therapy or prevention.     

Efficacy of natural products against Callosobruchus chinensis (Coleoptera: Bruchidae) in Nepal

This study was conducted to determine the efficacy of local natural products against the beetle, Callosobruchus chinensis L. (Coleoptera: Bruchidae), in stored chickpea Cicer arietinum L. (Fabaceae) in Chitwan, Nepal. Five natural products and one synthetic pesticide (Malathion) and two storage regimes (aluminum sheet bin vs. jute bags with plastic lining) were tested for their effect on stored pulse with respect to damage by C. chinensis. The five natural products included Xanthoylum armatum DC (Rutaceae) fruit powder, Acorus calamus L. (Araceae) rhizome powder, Cinnamom camphora L. (Lauraceae) balls, oil of Sesamum indicum L. (Pedaliaceae), and leaf powder of Azadirachta indica A. Juss. (Meliaceae). Treatments of stored pulses with natural products or with Malathion all caused significantly higher mortality of C. chinensis at 15 d after treatment (DAT) than stored pulses receiving no treatments. The balls of C. camphora, rhizome powder of A. calamus and sesame oil outperformed all other treatments, including the Malathion at 45 and 75 DAT and resulted in significantly reduced damage or deterioration of stored pulses compared with other treatments. Storage regimes performed similarly, although the jute bags did protect seed integrity for some treatments. Our results indicate that incorporating these natural products into stored pulses can protect the seeds from C. chinensis for up to two generations, something that Malathion cannot do. These products are readily available to most farmers in the region and their use will lead to 1) reduction of losses to significant stored product pests, and 2) a reduction of contamination of foodstuffs and the environment by synthetic pesticides like Malathion.     

Trypanosoma brucei: Reduction of GPI-phospholipase C protein during differentiation is dependent on replication of newly transformed cells

The protozoan parasite Trypanosoma brucei lives in the bloodstream of vertebrates or in a tsetse fly. Expression of a GPI-phospholipase C polypeptide (GPI-PLCp) in the parasite is restricted to the bloodstream form. Events controlling the amount of GPI-PLCp expressed during differentiation are not completely understood. Our metabolic “pulse-chase” analysis reveals that GPI-PLCp is stable in bloodstream form. However, during differentiation of bloodstream to insect stage (procyclic) T. brucei, translation GPI-PLC mRNA ceases within 8 h of initiating transformation. GPI-PLCp is not lost precipitously from newly transformed procyclic trypanosomes. Nascent procyclics contain 400-fold more GPI-PLCp than established insect stage T. brucei. Reduction of GPI-PLCp in early-stage procyclics is linked to parasite replication. Sixteen cell divisions are required to reduce the amount of GPI-PLCp in newly differentiated procyclics to levels present in the established procyclic. GPI-PLCp is retained in strains of T. brucei that fail to replicate after differentiation of the bloodstream to the procyclic form. Thus, at least two factors control levels of GPI-PLCp during differentiation of bloodstream T. brucei; (i) repression of GPI-PLC mRNA translation, and (ii) sustained replication of newly transformed procyclic T. brucei. These studies illustrate the importance of repeated cell divisions in controlling the steady-state amount of GPI-PLCp during differentiation of the African trypanosome.     

Antimicrobial Peptide from <Emphasis Type="Italic">Bacillus</Emphasis> Strain K1R Exhibits Ameliorative Potential Against Vancomycin-Resistant <Emphasis Type="Italic">Enterococcus</Emphasis> Group of Organisms

Microorganisms secrete antimicrobial peptides (AMPs) which are part of the innate immune system and rapidly increase in concentration in the host upon challenge by pathogens, which they produce themselves. Kimchi, a traditional Korean food fermented by Bacillus organisms, is found to be ideal for AMP production. Our aim was to investigate the therapeutic potential of antimicrobial substances produced by Bacillus species. Peptide K1R was subjected to fermentation in a culture media containing carbon and nitrogen sources and metal ions. A protein band around 4.6 kDa was detected in tricine-SDS-PAGE and confirmed by in situ inhibitory activity of the gel. Peptide K1R was stable over a broad range of pH (6.5–9), thermo tolerant up to 60?°C and showed unaltered activity at low temperatures (0–4?°C). The complete amino acid sequence of peptide K1R was AVQGTLEDALNLSKGALNQVQKAIQNGDXLTVXGXLGTIXLAVSX. The antagonistic effect of peptide K1R against multiple drug resistant (MDR) pathogens such as Salmonella Typhimurium and Enterococcus sp. verified its potential application in treating MDR cases. The antioxidant activity of peptide K1R was also comparable to that of standard ascorbic acid.     

<Emphasis Type="Italic">Phytophthora colocasiae</Emphasis> from Vietnam,China, Hawaii and Nepal: intra- and inter-genomic variations in ploidy and a long-lived,diploid Hawaiian lineage.

Phytophthora colocasiae is an important pathogen of taro and is widely distributed. Our goal was to develop whole genome sequence and single nucleotide polymorphism (SNP) markers to characterize historical and current populations from Hawaii (2010 and 2016, HA), historical isolates from Vietnam and China (2010, VN and CH) and current isolates from Nepal (2016, NEP). Seven isolates (VN = 2, CH = 1, HA = 1, NEP = 3) were sequenced (NCBI BioProject PRJNA378784) and compared using the reference genome of the closely related vegetable pathogen P. capsici. Genome-wide SNP analysis using 27,537 markers revealed genomes of diploid, triploid, tetraploid and higher ploidy. Ploidy varied within and between populations, with HA being primarily diploid, CH primarily triploid, VN containing diploid and triploid isolates, and NEP having predominantly triploid, tetraploid and higher ploidy. A total of 37 SNP markers were genotyped in 89 samples (grown in culture or directly from infected tissue) using targeted-sequencing. Analyses indicate a single clonal lineage dominated populations in HA from 2010 to 2016 and targeted-sequencing was useful to estimate ploidy. The implications for adaptation and evolution of P. colocasiae are discussed, as well as consequences for selection and breeding of resistant taro cultivars.     

Will Delaying Breakfast Mitigate the Metabolic Health Benefits of Time‐Restricted Eating?

Eating out of phase with the biological clock induces circadian misalignment in peripheral organs and impairs glucose tolerance in preclinical models. Time‐restricted eating (TRE) is a dietary approach that consolidates energy intake to 6 to 10 hours during the biologically active phase of the day, without necessarily altering diet quality and quantity. TRE induces pleiotropic metabolic benefits in mice, flies, and humans. Most studies have initiated TRE early in the biological morning. This perspective discusses the potential challenges in translating early TRE to the community and considers the potential metabolic consequences of delaying TRE.     

Spatial and temporal movement of the Bearded Vulture using GPS telemetry in the Himalayas of Nepal

This study addresses for the first time the movement patterns of the globally near-threatened Bearded Vulture Gypaetus barbatus in its most important stronghold, the high-altitude mountain ranges of Asia. Tracked individuals (n = 8) in the Annapurna Himalayan range (Nepal) foraged over a vast range of 60 715.9 km² and our results indicated age-class differences in the use of space. Territorial adults showed very small annual home-ranges (K90 = 150.3 km²), whereas immatures wandered extensively and covered vast ranges of the mountains (K90 = 23 930.8 km²). For adults and immatures, these values are notably larger than the other two studied populations in the world (Pyrenees and South Africa). This suggests that the studied Annapurna population might exhibit lower breeding density than in the Pyrenees or South Africa, possibly due to lower food availability.