Systems Biology

Longitudinal landscape of immune reconstitution after acute SARS-CoV-2 infection at single-cell resolution

Tue, 2024-08-06 06:00

Sci Bull (Beijing). 2024 Jul 15:S2095-9273(24)00488-2. doi: 10.1016/j.scib.2024.07.011. Online ahead of print.

NO ABSTRACT

PMID:39107149 | DOI:10.1016/j.scib.2024.07.011

Categories: Literature Watch

Chloroplastic ascorbate modifies plant metabolism and may act as a metabolite signal regardless of oxidative stress

Tue, 2024-08-06 06:00

Plant Physiol. 2024 Aug 6:kiae409. doi: 10.1093/plphys/kiae409. Online ahead of print.

ABSTRACT

Ascorbate is a major plant metabolite that plays crucial roles in various processes, from reactive oxygen scavenging to epigenetic regulation. However, to what extent and how ascorbate modulates metabolism is largely unknown. We investigated the consequences of chloroplastic and total cellular ascorbate-deficiencies by studying chloroplastic ascorbate-transporter mutant lines lacking PHOSPHATE TRANSPORTER 4; 4 (PHT4; 4) , and the ascorbate-deficient vtc2-4 mutant of Arabidopsis (Arabidopsis thaliana). Under regular growth conditions, both ascorbate deficiencies caused minor alterations in photosynthesis, with no apparent signs of oxidative damage. In contrast, metabolomics analysis revealed global and largely overlapping alterations in the metabolome profiles of both ascorbate-deficiency mutants, suggesting that chloroplastic ascorbate modulates plant metabolism. We observed significant alterations in amino acid metabolism, particularly in arginine metabolism, activation of nucleotide salvage pathways, and changes in secondary metabolism. In addition, proteome-wide analysis of thermostability revealed that ascorbate may interact with enzymes involved in arginine metabolism, the Calvin-Benson cycle, and several photosynthetic electron transport components. Overall, our results suggest that, independently of oxidative stress, chloroplastic ascorbate modulates the activity of diverse metabolic pathways in vascular plants and may act as an internal metabolic signal.

PMID:39106412 | DOI:10.1093/plphys/kiae409

Categories: Literature Watch

Adiponectin suppresses stiffness-dependent, pro-fibrotic activation of lung fibroblasts

Tue, 2024-08-06 06:00

Am J Physiol Lung Cell Mol Physiol. 2024 Aug 6. doi: 10.1152/ajplung.00037.2024. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible respiratory disease with limited therapeutic options. A hallmark of IPF is excessive fibroblast activation and extracellular matrix (ECM) deposition. The resulting increase in tissue stiffness amplifies fibroblast activation and drives disease progression. Dampening stiffness-dependent activation of fibroblasts could slow disease progression. We performed an unbiased, next generation sequencing (NGS) screen to identify signaling pathways involved in stiffness-dependent lung fibroblast activation. Adipocytokine signaling was downregulated in primary lung fibroblasts (PFs) cultured on stiff matrices. Re-activating adipocytokine signaling with adiponectin suppressed stiffness-dependent activation of human PFs. Adiponectin signaling depended on CDH13 expression and p38 mitogen-activated protein kinase gamma (p38MAPKγ) activation. CDH13 expression and p38MAPKγ activation were strongly reduced in lungs from IPF donors. Our data suggest that adiponectin-signaling via CDH13 and p38MAPKγ activation suppresses pro-fibrotic activation of fibroblasts in the lung. Targeting of the adiponectin signaling cascade may provide therapeutic benefits in IPF.

PMID:39104319 | DOI:10.1152/ajplung.00037.2024

Categories: Literature Watch

Combining distribution modelling and phylogeography to understand present, past and future of an endangered spider

Mon, 2024-08-05 06:00

BMC Ecol Evol. 2024 Aug 5;24(1):106. doi: 10.1186/s12862-024-02295-2.

ABSTRACT

BACKGROUND: Understanding how endangered species respond to climatic changes is fundamental for their conservation. Due to its restricted geographic range, its sensitivity to the ongoing global warming and its continuing decline, the Southwestern-Alpine endemic wolf spider Vesubia jugorum is currently classified as Endangered in the IUCN Red List. Here, we combined species distribution modelling (SDM) and phylogeographic inference to describe the present, the past and the future of this species in light of the mtDNA genetic structure of extant populations.

RESULTS: Phylogenetic and network analyses show a high level of genetic differentiation and a strong genetic structure of the populations, likely explicable by a long history of isolation and survival in separate refugia. The SDM projection into past climatic conditions supports these results by showing a smaller distribution range compared to present, mostly restricted to the Maritime and Ligurian Alps, which possibly served as main refugium. Future forecast shows a significant shift in the bioclimatic range towards higher altitudes and latitudes, with a drastic decrease of habitat suitability in the central and south-eastern parts of the range, with consequent general loss of haplotype diversity.

CONCLUSION: SDM and phylogeographic inference support the hypothesis that the current distribution and the genetic structure of the extant populations mirror the survival in situ of Vesubia jugorum across repeated glacial and interglacial phases, in line with the 'long-term stability hypothesis'. Future predictions show a significant shift in the bioclimatic range that V. jugorum will be likely unable to track, with profound impact on its long-term survival and its genetic diversity. Our considerations have implication for conservation genetics, highlighting the pivotal role of the transboundary protected areas of the SW-Alps in promoting conservation efforts for this species.

PMID:39103753 | DOI:10.1186/s12862-024-02295-2

Categories: Literature Watch

Barcoded overexpression screens in gut Bacteroidales identify genes with roles in carbon utilization and stress resistance

Mon, 2024-08-05 06:00

Nat Commun. 2024 Aug 5;15(1):6618. doi: 10.1038/s41467-024-50124-3.

ABSTRACT

A mechanistic understanding of host-microbe interactions in the gut microbiome is hindered by poorly annotated bacterial genomes. While functional genomics can generate large gene-to-phenotype datasets to accelerate functional discovery, their applications to study gut anaerobes have been limited. For instance, most gain-of-function screens of gut-derived genes have been performed in Escherichia coli and assayed in a small number of conditions. To address these challenges, we develop Barcoded Overexpression BActerial shotgun library sequencing (Boba-seq). We demonstrate the power of this approach by assaying genes from diverse gut Bacteroidales overexpressed in Bacteroides thetaiotaomicron. From hundreds of experiments, we identify new functions and phenotypes for 29 genes important for carbohydrate metabolism or tolerance to antibiotics or bile salts. Highlights include the discovery of a D-glucosamine kinase, a raffinose transporter, and several routes that increase tolerance to ceftriaxone and bile salts through lipid biosynthesis. This approach can be readily applied to develop screens in other strains and additional phenotypic assays.

PMID:39103350 | DOI:10.1038/s41467-024-50124-3

Categories: Literature Watch

Comprehensive lipidomic insights of differentially accumulating lipids in large pigmented rice sprout collection and the changes in the starch composition upon germination

Mon, 2024-08-05 06:00

Food Chem. 2024 Jul 31;460(Pt 2):140677. doi: 10.1016/j.foodchem.2024.140677. Online ahead of print.

ABSTRACT

Germination represents a vital bioprocess characterized by numerous biochemical transformations that significantly influence the nutritional characteristics of rice. The mobilization of starch and lipids during germination plays a pivotal role in altering the dietary profile of rice, thus potentially addressing the nutritional requirements of populations heavily reliant on rice as a staple food. To explore this potential, a comprehensive analysis encompassing lipidomics and starch composition was conducted on a diverse collection of pigmented rice sprouts. High-resolution mass spectrometry unveiled substantial shifts in the lipidome of pigmented rice sprouts, showcasing a notable enrichment in carotenoids and unsaturated triglycerides, with potential human health benefits. Notably, purple rice sprouts exhibited heightened levels of alpha- and beta-carotene. Analysis of starch composition revealed slight changes in amylose and amylopectin content; however, a consistent increase in digestible carbohydrates was observed across all rice varieties. Germination also led to a reduction in resistant starch content, with purple rice sprouts demonstrating a pronounced two-fold decrease (p < 0.05). These changes were corroborated by a 1.33% decrease in gelatinization enthalpy and a 0.40% reduction in the melting of the amylose-lipid complex. Furthermore, pasting property analysis indicated a substantial 42% decrease in the complexation index post-germination. We posit that the insights garnered from this study hold significant promise for the development of novel products enriched with health-promoting lipids and characterized by unique flour properties.

PMID:39102764 | DOI:10.1016/j.foodchem.2024.140677

Categories: Literature Watch

DepoScope: Accurate phage depolymerase annotation and domain delineation using large language models

Mon, 2024-08-05 06:00

PLoS Comput Biol. 2024 Aug 5;20(8):e1011831. doi: 10.1371/journal.pcbi.1011831. Online ahead of print.

ABSTRACT

Bacteriophages (phages) are viruses that infect bacteria. Many of them produce specific enzymes called depolymerases to break down external polysaccharide structures. Accurate annotation and domain identification of these depolymerases are challenging due to their inherent sequence diversity. Hence, we present DepoScope, a machine learning tool that combines a fine-tuned ESM-2 model with a convolutional neural network to identify depolymerase sequences and their enzymatic domains precisely. To accomplish this, we curated a dataset from the INPHARED phage genome database, created a polysaccharide-degrading domain database, and applied sequential filters to construct a high-quality dataset, which is subsequently used to train DepoScope. Our work is the first approach that combines sequence-level predictions with amino-acid-level predictions for accurate depolymerase detection and functional domain identification. In that way, we believe that DepoScope can greatly enhance our understanding of phage-host interactions at the level of depolymerases.

PMID:39102416 | DOI:10.1371/journal.pcbi.1011831

Categories: Literature Watch

Oxidative stress-induced YAP1 expression is regulated by NCE102, CDA2, and BCS1

Mon, 2024-08-05 06:00

FEBS J. 2024 Aug 5. doi: 10.1111/febs.17243. Online ahead of print.

ABSTRACT

Maintaining cellular homeostasis in the face of stress conditions is vital for the overall well-being of an organism. Reactive oxygen species (ROS) are among the most potent cellular stressors and can disrupt the internal redox balance, giving rise to oxidative stress. Elevated levels of ROS can severely affect biomolecules and have been associated with a range of pathophysiological conditions. In response to oxidative stress, yeast activator protein-1 (Yap1p) undergoes post-translation modification that results in its nuclear accumulation. YAP1 has a key role in oxidative detoxification by promoting transcription of numerous antioxidant genes. In this study, we identified previously undescribed functions for NCE102, CDA2, and BCS1 in YAP1 expression in response to oxidative stress induced by hydrogen peroxide (H2O2). Deletion mutant strains for these candidates demonstrated increased sensitivity to H2O2. Our follow-up investigation linked the activity of these genes to YAP1 expression at the level of translation. Under oxidative stress, global cap-dependent translation is inhibited, prompting stress-responsive genes like YAP1 to employ alternative modes of translation. We provide evidence that NCE102, CDA2, and BCS1 contribute to cap-independent translation of YAP1 under oxidative stress.

PMID:39102301 | DOI:10.1111/febs.17243

Categories: Literature Watch

Oleic acid enriched diet affects the metabolome composition of the hybrid grouper infected with vibriosis

Mon, 2024-08-05 06:00

Fish Physiol Biochem. 2024 Aug 5. doi: 10.1007/s10695-024-01389-4. Online ahead of print.

ABSTRACT

This study focuses in investigating the fatty acid contents of surviving infected hybrid grouper fed with oleic acid immunostimulant. After a 6-week feeding trial, Epinephelus fuscoguttatus × Epinephelus lanceolatus fingerlings were infected with Vibrio vulnificus. One week after bacterial challenge, fish oil was extracted from body tissue of surviving infected fingerlings using the Soxhlet extraction method. The extracted samples were then sent for GC-MS analysis. The raw GC-MS data were analyzed using software programs and databases (i.e., MetaboAnalyst, SIMCA-P, NIST Library, and KEGG). A total of 39 metabolites were putatively identified, with 18 metabolites derived from the fatty acid group. Our further analysis revealed that most metabolites were highly abundant in the oleic acid dietary samples, including oleic acid (4.56%), 5,8,11-eicosatrienoic acid (3.45%), n-hexadecenoic acid (3.34%), cis-erucic acid (2.76%), and 9-octadecenoic acid (2.5%). Worthy of note, we observed a greater abundance of α-linoleic acid (15.57%) in the control diet samples than in the oleic acid diet samples (14.59%) with no significant difference in their results. The results obtained from this study revealed that surviving infected hybrid grouper expressed more immune-related fatty acids due to the effect of oleic acid immunostimulant. Therefore, in this study, we propose oleic acid as a potential immunostimulant in enhancing fish immunity in aquaculture industry.

PMID:39102011 | DOI:10.1007/s10695-024-01389-4

Categories: Literature Watch

Chromosome-scale assembly and annotation of eight Arabidopsis thaliana ecotypes

Mon, 2024-08-05 06:00

Genome Biol Evol. 2024 Aug 5:evae169. doi: 10.1093/gbe/evae169. Online ahead of print.

ABSTRACT

The plant Arabidopsis thaliana is a model system used by researchers through much of plant research. Recent efforts have focused on discovering the genomic variation found in naturally occurring ecotypes isolated from around the world. These ecotypes have come from diverse climates and therefore have faced and adapted to a variety of abiotic and biotic stressors. The sequencing and comparative analysis of these genomes can offer insight into the adaptive strategies of plants. While there are a large number of ecotype genome sequences available, the majority were created using short-read technology. Mapping of short-reads containing structural variation to a reference genome bereft of that variation leads to incorrect mapping of those reads, resulting in a loss of genetic information and introduction of false heterozygosity. For this reason, long-read de novo sequencing of genomes is required to resolve structural variation events. In this paper, we sequenced the genomes of eight natural variants of A. thaliana using nanopore sequencing. This resulted in highly contiguous assemblies with >95% of the genome contained within 5 contigs. The sequencing results from this study include 5 ecotypes from relict and African populations, an area of untapped genetic diversity. With this study, we increase the knowledge of diversity we have across A. thaliana ecotypes and contribute to ongoing production of an A. thaliana pan-genome.

PMID:39101619 | DOI:10.1093/gbe/evae169

Categories: Literature Watch

Varying selection pressure for a Na+ sensing site in epithelial Na+ channel subunits reflect divergent roles in Na+ homeostasis

Mon, 2024-08-05 06:00

Mol Biol Evol. 2024 Aug 5:msae162. doi: 10.1093/molbev/msae162. Online ahead of print.

ABSTRACT

The epithelial Na+ channel (ENaC) emerged early in vertebrates and has played a role in Na+ and fluid homeostasis throughout vertebrate evolution. We previously showed that proteolytic activation of the channel evolved at the water to land transition of vertebrates. Sensitivity to extracellular Na+, known as Na+ self-inhibition, reduces ENaC function when Na+ concentrations are high and is a distinctive feature of the channel. A fourth ENaC subunit, δ, emerged in jawed fishes from an α subunit gene duplication. Here, we analyzed 849 α and δ subunit sequences and found that a key Asp in a postulated Na+ binding site was nearly always present in the α subunit, but frequently lost in the δ subunit (e.g., human). Analysis of site evolution and codon substitution rates provide evidence that the ancestral α subunit had the site and that purifying selection for the site relaxed in the δ subunit after its divergence from the α subunit, coinciding with a loss of δ subunit expression in renal tissues. We also show that the proposed Na+ binding site in the α subunit is a bona fide site by conferring novel function to channels comprising human δ subunits. Together, our findings provide evidence that ENaC Na+ self-inhibition improves fitness through its role in Na+ homeostasis in vertebrates.

PMID:39101592 | DOI:10.1093/molbev/msae162

Categories: Literature Watch

Photosynthetic capacity in middle-aged larch and spruce acclimates independently to experimental warming and elevated CO<sub>2</sub>

Mon, 2024-08-05 06:00

Plant Cell Environ. 2024 Aug 5. doi: 10.1111/pce.15068. Online ahead of print.

ABSTRACT

Photosynthetic acclimation to both warming and elevated CO2 of boreal trees remains a key uncertainty in modelling the response of photosynthesis to future climates. We investigated the impact of increased growth temperature and elevated CO2 on photosynthetic capacity (Vcmax and Jmax) in mature trees of two North American boreal conifers, tamarack and black spruce. We show that Vcmax and Jmax at a standard temperature of 25°C did not change with warming, while Vcmax and Jmax at their thermal optima (Topt) and growth temperature (Tg) increased. Moreover, Vcmax and Jmax at either 25°C, Topt or Tg decreased with elevated CO2. The Jmax/Vcmax ratio decreased with warming when assessed at both Topt and Tg but did not significantly vary at 25°C. The Jmax/Vcmax increased with elevated CO2 at either reference temperature. We found no significant interaction between warming and elevated CO2 on all traits. If this lack of interaction between warming and elevated CO2 on the Vcmax, Jmax and Jmax/Vcmax ratio is a general trend, it would have significant implications for improving photosynthesis representation in vegetation models. However, future research is required to investigate the widespread nature of this response in a larger number of species and biomes.

PMID:39101396 | DOI:10.1111/pce.15068

Categories: Literature Watch

The <em>Zea mays</em> PeptideAtlas: A New Maize Community Resource

Mon, 2024-08-05 06:00

J Proteome Res. 2024 Aug 5. doi: 10.1021/acs.jproteome.4c00320. Online ahead of print.

ABSTRACT

This study presents the Maize PeptideAtlas resource (www.peptideatlas.org/builds/maize) to help solve questions about the maize proteome. Publicly available raw tandem mass spectrometry (MS/MS) data for maize collected from ProteomeXchange were reanalyzed through a uniform processing and metadata annotation pipeline. These data are from a wide range of genetic backgrounds and many sample types and experimental conditions. The protein search space included different maize genome annotations for the B73 inbred line from MaizeGDB, UniProtKB, NCBI RefSeq, and for the W22 inbred line. 445 million MS/MS spectra were searched, of which 120 million were matched to 0.37 million distinct peptides. Peptides were matched to 66.2% of proteins in the most recent B73 nuclear genome annotation. Furthermore, most conserved plastid- and mitochondrial-encoded proteins (NCBI RefSeq annotations) were identified. Peptides and proteins identified in the other B73 genome annotations will improve maize genome annotation. We also illustrate the high-confidence detection of unique W22 proteins. N-terminal acetylation, phosphorylation, ubiquitination, and three lysine acylations (K-acetyl, K-malonyl, and K-hydroxyisobutyryl) were identified and can be inspected through a PTM viewer in PeptideAtlas. All matched MS/MS-derived peptide data are linked to spectral, technical, and biological metadata. This new PeptideAtlas is integrated in MaizeGDB with a peptide track in JBrowse.

PMID:39101213 | DOI:10.1021/acs.jproteome.4c00320

Categories: Literature Watch

What are the 100 most cited fungal genera?

Mon, 2024-08-05 06:00

Stud Mycol. 2024 Jul;108:1-411. doi: 10.3114/sim.2024.108.01. Epub 2024 Jul 15.

ABSTRACT

The global diversity of fungi has been estimated between 2 to 11 million species, of which only about 155 000 have been named. Most fungi are invisible to the unaided eye, but they represent a major component of biodiversity on our planet, and play essential ecological roles, supporting life as we know it. Although approximately 20 000 fungal genera are presently recognised, the ecology of most remains undetermined. Despite all this diversity, the mycological community actively researches some fungal genera more commonly than others. This poses an interesting question: why have some fungal genera impacted mycology and related fields more than others? To address this issue, we conducted a bibliometric analysis to identify the top 100 most cited fungal genera. A thorough database search of the Web of Science, Google Scholar, and PubMed was performed to establish which genera are most cited. The most cited 10 genera are Saccharomyces, Candida, Aspergillus, Fusarium, Penicillium, Trichoderma, Botrytis, Pichia, Cryptococcus and Alternaria. Case studies are presented for the 100 most cited genera with general background, notes on their ecology and economic significance and important research advances. This paper provides a historic overview of scientific research of these genera and the prospect for further research. Citation: Bhunjun CS, Chen YJ, Phukhamsakda C, Boekhout T, Groenewald JZ, McKenzie EHC, Francisco EC, Frisvad JC, Groenewald M, Hurdeal VG, Luangsa-ard J, Perrone G, Visagie CM, Bai FY, Błaszkowski J, Braun U, de Souza FA, de Queiroz MB, Dutta AK, Gonkhom D, Goto BT, Guarnaccia V, Hagen F, Houbraken J, Lachance MA, Li JJ, Luo KY, Magurno F, Mongkolsamrit S, Robert V, Roy N, Tibpromma S, Wanasinghe DN, Wang DQ, Wei DP, Zhao CL, Aiphuk W, Ajayi-Oyetunde O, Arantes TD, Araujo JC, Begerow D, Bakhshi M, Barbosa RN, Behrens FH, Bensch K, Bezerra JDP, Bilański P, Bradley CA, Bubner B, Burgess TI, Buyck B, Čadež N, Cai L, Calaça FJS, Campbell LJ, Chaverri P, Chen YY, Chethana KWT, Coetzee B, Costa MM, Chen Q, Custódio FA, Dai YC, Damm U, de Azevedo Santiago ALCM, De Miccolis Angelini RM, Dijksterhuis J, Dissanayake AJ, Doilom M, Dong W, Alvarez-Duarte E, Fischer M, Gajanayake AJ, Gené J, Gomdola D, Gomes AAM, Hausner G, He MQ, Hou L, Iturrieta-González I, Jami F, Jankowiak R, Jayawardena RS, Kandemir H, Kiss L, Kobmoo N, Kowalski T, Landi L, Lin CG, Liu JK, Liu XB, Loizides M, Luangharn T, Maharachchikumbura SSN, Makhathini Mkhwanazi GJ, Manawasinghe IS, Marin-Felix Y, McTaggart AR, Moreau PA, Morozova OV, Mostert L, Osiewacz HD, Pem D, Phookamsak R, Pollastro S, Pordel A, Poyntner C, Phillips AJL, Phonemany M, Promputtha I, Rathnayaka AR, Rodrigues AM, Romanazzi G, Rothmann L, Salgado-Salazar C, Sandoval-Denis M, Saupe SJ, Scholler M, Scott P, Shivas RG, Silar P, Souza-Motta CM, Silva-Filho AGS, Spies CFJ, Stchigel AM, Sterflinger K, Summerbell RC, Svetasheva TY, Takamatsu S, Theelen B, Theodoro RC, Thines M, Thongklang N, Torres R, Turchetti B, van den Brule T, Wang XW, Wartchow F, Welti S, Wijesinghe SN, Wu F, Xu R, Yang ZL, Yilmaz N, Yurkov A, Zhao L, Zhao RL, Zhou N, Hyde KD, Crous PW (2024). What are the 100 most cited fungal genera? Studies in Mycology 108: 1-411. doi: 10.3114/sim.2024.108.01.

PMID:39100921 | PMC:PMC11293126 | DOI:10.3114/sim.2024.108.01

Categories: Literature Watch

Genome-wide expression analysis in a Fabry disease human podocyte cell line

Mon, 2024-08-05 06:00

Heliyon. 2024 Jul 9;10(14):e34357. doi: 10.1016/j.heliyon.2024.e34357. eCollection 2024 Jul 30.

ABSTRACT

Fabry disease (FD) is an X-linked lysosomal disease caused by an enzyme deficiency of alpha-galactosidase A (α-gal A). This deficiency leads to the accumulation of glycosphingolipids in lysosomes, resulting in a range of clinical symptoms. The complex pathogenesis of FD involves lysosomal dysfunction, altered autophagy, and mitochondrial abnormalities. Omics sciences, particularly transcriptomic analysis, comprehensively understand molecular mechanisms underlying diseases. This study focuses on genome-wide expression analysis in an FD human podocyte model to gain insights into the underlying mechanisms of podocyte dysfunction. Human control and GLA-edited podocytes were used. Gene expression data was generated using RNA-seq analysis, and differentially expressed genes were identified using DESeq2. Principal component analysis and Spearman correlation have explored gene expression trends. Functional enrichment and Reporter metabolite analyses were conducted to identify significantly affected metabolites and metabolic pathways. Differential expression analysis revealed 247 genes with altered expression levels in GLA-edited podocytes compared to control podocytes. Among these genes, 136 were underexpressed, and 111 were overexpressed in GLA-edited cells. Functional analysis of differentially expressed genes showed their involvement in various pathways related to oxidative stress, inflammation, fatty acid metabolism, collagen and extracellular matrix homeostasis, kidney injury, apoptosis, autophagy, and cellular stress response. The study provides insights into molecular mechanisms underlying Fabry podocyte dysfunction. Integrating transcriptomics data with genome-scale metabolic modeling further unveiled metabolic alterations in GLA-edited podocytes. This comprehensive approach contributes to a better understanding of Fabry disease and may lead to identifying new biomarkers and therapeutic targets for this rare lysosomal disorder.

PMID:39100494 | PMC:PMC11295972 | DOI:10.1016/j.heliyon.2024.e34357

Categories: Literature Watch

Characterization of Olive Oil Phenolic Extracts and Their Effects on the Aggregation of the Alzheimer's Amyloid-β Peptide and Tau

Mon, 2024-08-05 06:00

ACS Omega. 2024 Jul 17;9(30):32557-32578. doi: 10.1021/acsomega.4c01281. eCollection 2024 Jul 30.

ABSTRACT

The dietary consumption of extra virgin olive oil (EVOO) is believed to slow the progression of Alzheimer's disease (AD) symptoms. Its protective mechanisms are unclear, but specific EVOO phenolic compounds can individually impede the aggregation of amyloid-β (Aβ) peptides and the microtubule-associated protein tau, two important pathological manifestations of AD. It is unknown, however, whether the numerous and variable phenolic compounds that are consumed in dietary EVOO can collectively alter tau and Aβ aggregation as effectively as the individual compounds. The activity of these complex mixtures against Aβ and tau may be moderated by competition between active and nonactive phenolic components and by extensive derivatizations and isomerization. Here, phenolic mixtures extracted from two different EVOO sources are characterized and tested for how they modulate the aggregation of Aβ40 peptide and tau peptides in vitro. The chromatographic and NMR analysis of Greek and Saudi Arabian EVOO phenolic extracts reveals that they have different concentration profiles, and over 30 compounds are identified. Thioflavin T fluorescence and circular dichroism measurements show that relatively low concentrations (<20 μg/mL) of the Greek and Saudi extracts reduce the rate of Aβ40 aggregation and fibril mass, despite the extracts having different phenolic profiles. By contrast, the Greek extract reduces the rate of tau aggregation only at very high phenolic concentrations (>100 μg/mL). Most compounds in the extracts bind to preformed Aβ40 fibrils and release soluble Aβ oligomers that are mildly toxic to SH-SY5Y cells. Much higher (500 μg/mL) extract concentrations are required to remodel tau filaments into oligomers, and a minimal binding of phenolic compounds to the preformed filaments is observed. It is concluded that EVOO extracts having different phenol profiles are similarly capable of modulating Aβ40 aggregation and fibril morphology in vitro at relatively low concentrations but are less efficient at modulating tau aggregation. Over 2 M tonnes of EVOO are consumed globally each year as part of the Mediterranean diet, and the results here provide motivation for further clinical interrogation of the antiaggregation properties of EVOO as a potential protective mechanism against AD.

PMID:39100310 | PMC:PMC11292642 | DOI:10.1021/acsomega.4c01281

Categories: Literature Watch

Unlocking rivers' hidden diversity and ecological status using DNA metabarcoding in Northwest Spain

Mon, 2024-08-05 06:00

Ecol Evol. 2024 Aug 1;14(8):e70110. doi: 10.1002/ece3.70110. eCollection 2024 Aug.

ABSTRACT

Rivers are crucial ecosystems supporting biodiversity and human well-being, yet they face increasing degradation globally. Traditional river biomonitoring methods based on morphological identification of macroinvertebrates present challenges in terms of taxonomic resolution and scalability. This study explores the application of DNA metabarcoding analysis in both bulk and environmental DNA (eDNA) samples for comprehensive assessment of macrozoobenthic biodiversity, detection of invasive and endangered species, and evaluation of river ecological status in northwestern Spain. DNA metabarcoding of homogenized bulk samples and water eDNA revealed a mean of 100 and 87 macrozoobenthos species per sample respectively. However, the specific composition was significantly different with only 27.3% of the total species being shared. It was not possible to identify all the OTUs to species level; only 17.43% and 49.4% of the OTUs generated could be identified to species level in the bulk and eDNA samples, respectively. Additionally, a total of 11 exotic species (two first records for the Iberian Peninsula and another three first records for Asturias region) and one endangered species were detected by molecular tools. Molecular methods showed significant correlations with morphological identification for EQR values (Ecological Quality Ratio) of IBMWP index, yet differences in inferred river ecological status were noted, with bulk samples tending to indicate higher status. Overall, DNA metabarcoding offers a promising approach for river biomonitoring, providing insights into biodiversity, invasive species, and ecological status within a single analysis. Further optimization and intercalibration are required for its implementation in routine biomonitoring programmes, but its scalability and multi-tasking capabilities position it as a valuable tool for integrated monitoring of river ecosystems.

PMID:39100209 | PMC:PMC11294579 | DOI:10.1002/ece3.70110

Categories: Literature Watch

Proximity labeling reveals dynamic changes in the SQSTM1 protein network

Sun, 2024-08-04 06:00

J Biol Chem. 2024 Aug 2:107621. doi: 10.1016/j.jbc.2024.107621. Online ahead of print.

ABSTRACT

Sequestosome1 (SQSTM1) is an autophagy receptor that mediates degradation of intracellular cargo, including protein aggregates, through multiple protein interactions. These interactions form the SQSTM1 protein network, and these interactions are mediated by SQSTM1 functional interaction domains, which include LIR, PB1, UBA and KIR. Technological advances in cell biology continue to expand our knowledge of the SQSTM1 protein network and of the relationship of the actions of the SQSTM1 protein network in cellular physiology and disease states. Here we apply proximity profile labeling to investigate the SQSTM1 protein interaction network by fusing TurboID with the human protein SQSTM1 (TurboID::SQSTM1). This chimeric protein displayed well-established SQSTM1 features including production of SQSTM1 intracellular bodies, binding to known SQSTM1 interacting partners, and capture of novel SQSTM1 protein interactors. Strikingly, aggregated tau protein altered the protein interaction network of SQSTM1 to include many stress-associated proteins. We demonstrate the importance of the PB1 and/or UBA domains for binding network members, including the K18 domain of tau. Overall, our work reveals the dynamic landscape of the SQSTM1 protein network and offers a resource to study SQSTM1 function in cellular physiology and disease state.

PMID:39098523 | DOI:10.1016/j.jbc.2024.107621

Categories: Literature Watch

The natural variance of Arabidopsis secondary metabolism on extended darkness

Sat, 2024-08-03 06:00

Sci Data. 2024 Aug 3;11(1):841. doi: 10.1038/s41597-024-03694-2.

ABSTRACT

In plants due to their sessile nature, secondary metabolites are important components against different abiotic and biotic stress, such as extended darkness. For this reason, the variation of secondary metabolite content of the Arabidopsis thaliana HapMap natural population following 0-and 6-d darkness treatment were detected and the raw data of different accessions at two timepoints were deposited in the Zenodo database. Moreover, the annotated secondary metabolites of these samples are presented in this data descriptor, which we believe will be a usefully re-usable resource for future integrative analysis with dark-treated transcripts, proteins or other phenotypic data in order to comprehensively illustrate the multiomic landscape of Arabidopsis in response to the stresses exerted by extended darkness.

PMID:39097666 | DOI:10.1038/s41597-024-03694-2

Categories: Literature Watch

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