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    Bioinformatics, btaa909, https://doi.org/10.1093/bioinformatics/btaa909 Abstract Summary: Polypeptides are exposed to changing environmental conditions that modulate their intrinsic aggregation propensities. Intrinsically disordered proteins (IDPs) constitutively expose their aggregation determinants to the solvent, thus being especially sensitive to its fluctuations. However, solvent conditions are often disregarded in computational aggregation predictors. We recently developed a phenomenological model to predict IDPs' solubility as a function of the solution pH, which is based on the assumption that both protein lipophilicity and charge depend on this parameter. The model anticipated solubility changes in different IDPs accurately. In this application note, we p

https://doi.org/10.1016/j.tplants.2020.10.001 https://www.sciencedirect.com/science/article/pii/S1360138520303253#f0005 First identified in human disorders, amyloids serve biological functions in bacteria, archaea, fungi, and animals; however, their role in plants has remained unexplored. Recently, Antonets et al. identified a functional amyloid in plants, with a crucial role in seed longevity, confirming that amyloids are universally exploited for organisms’ adaptation. Keywords functional amyloids plants garden pea seed storage vicilin seed longevity

Front. Bioeng. Biotechnol., 16 October 2020 | https://doi.org/10.3389/fbioe.2020.588947 Synucleinopathies are a group of disorders characterized by the accumulation of α-Synuclein amyloid inclusions in the brain. Preventing α-Synuclein aggregation is challenging because of the disordered nature of the protein and the stochastic nature of fibrillogenesis, but, at the same time, it is a promising approach for therapeutic intervention in these pathologies. A high-throughput screening initiative allowed us to discover ZPDm, the smallest active molecule in a library of more than 14.000 compounds. Although the ZPDm structure is highly related to that of the previously described ZPD-2 aggregation inhibitor, we show here that their mechanisms of action are entirely different. ZPDm inhibits the

Les tendències actuals en el mercat alimentari apunten a un increment de nombre de consumidors que, per raons ètiques o ambientals, abandonen el consum de carn, per passar a un tipus d'alimentació basada en vegetals. No obstant això, el mercat no disposa d’una oferta de productes de base vegetal que mantinguin els atributs nutricionals i organolèptics desitjables de la carn (anàlegs carnis) i que suposin una alternativa satisfactòria als productes carnis que s’estiguin consumint. Així, molts anàlegs carnis, com ara els discos a base de proteïna vegetal (p.ex., soja), un cop cuinats, disten d'oferir l'aspecte, sabor i color típic d'una hamburguesa de boví. És conegut que la leghemoglobina, una proteïna vegetal derivada dels nòduls de la soja, és capaç de conferir color i base de gust carni

https://www.nature.com/articles/s41467-020-18777-y Vizarraga, D., Kawamoto, A., Matsumoto, U. et al. Immunodominant proteins P1 and P40/P90 from human pathogen Mycoplasma pneumoniae. Nat Commun 11, 5188 (2020). https://doi.org/10.1038/s41467-020-18777-y Abstract Mycoplasma pneumoniae is a bacterial human pathogen that causes primary atypical pneumonia. M. pneumoniae motility and infectivity are mediated by the immunodominant proteins P1 and P40/P90, which form a transmembrane adhesion complex. Here we report the structure of P1, determined by X-ray crystallography and cryo-electron microscopy, and the X-ray structure of P40/P90. Contrary to what had been suggested, the binding site for sialic acid was found in P40/P90 and not in P1. Genetic and clinical variability concentrates on

 https://doi.org/10.1016/j.dci.2020.103848 Abstract Infections are able to trigger epigenetic modifications; however, epigenetic-mediating infections in the immune system in fish is currently unavailable. Within this purpose, zebrafish were immune-stimulated with three lipopolysaccharides (LPS) during sex differentiation. Methylation patterns of three immune genes were studied by a candidate gene approach together with gene expression analysis, and in adulthood, sex ratios were determined. It was shown that the entrance of LPS was through the gills and accumulated in the pronephros. Significant hypomethylation levels of CASP9 and a significant CpG site for IL1β after Pseudomonas aeruginosa LPS exposure were found. No methylation difference was observed for TNFα. Gene expression a

Protocols for rational design of protein solubility and aggregation properties using Aggrescan3D standalone Aleksander Kuriata, Aleksandra E. Badaczewska-Dawid, Jordi Pujols, Salvador Ventura, Sebastian Kmiecik bioRxiv 2020.09.09.276915.   doi: https://doi.org/10.1101/2020.09.09.276915 https://www.biorxiv.org/content/10.1101/2020.09.09.276915v1.full Summary Protein aggregation is a major hurdle in the development and manufacturing of protein-based therapeutics. Development of aggregation-resistant and stable protein variants can be guided by rational redesign using computational tools. Here, we describe the architecture and functionalities of the Aggrescan3D (A3D) standalone package for the rational design of protein solubility and aggregation properties based on three-dimensi

doi:10.1016/j.bbamcr.2020.118727 Abstract The Ser/Thr protein phosphatase Ppz1 from Saccharomyces cerevisiae is the best characterized member of a family of enzymes only found in fungi. Ppz1 is regulated in vivo by two inhibitory subunits, Hal3 and Vhs3, which are moonlighting proteins also involved in the decarboxylation of the 4-phosphopantothenoylcysteine (PPC) intermediate required for coenzyme A biosynthesis. It has been reported that, when overexpressed, Ppz1 is the most toxic protein in yeast. However, the reasons for such toxicity have not been elucidated. Here we show that the detrimental effect of excessive Ppz1 expression is due to an increase in its phosphatase activity and not to a plausible down-titration of the PPC decarboxylase components. We have identified several

/doi/full/10.1080/14756366.2020.1816999 Abstract Parkinson’s disease is one of the most common neurodegenerative disorders in elderly age. One of the mechanisms involved in the neurodegeneration appears related to the aggregation of the presynaptic protein alpha synuclein (α-syn) into toxic oligomers and fibrils. To date, no highly effective treatment is currently available; therefore, there is an increasing interest in the search of new therapeutic tools. The modulation of α-syn aggregation represents an emergent and promising disease-modifying strategy for reducing or blocking the neurodegenerative process. Herein, by combining in silico and in vitro screenings we initially identified 3-(cinnamylsulfanyl)-5-(4-pyridinyl)-1,2,4-triazol-4-amine (3) as α-syn aggregation inhibitor that

https://doi.org/10.1093/dnares/dsaa019   Abstract Transmission Ratio Distortion (TRD), the uneven transmission of an allele from a parent to its offspring, can be caused by allelic differences affecting gametogenesis, fertilization or embryogenesis. However, TRD remains vaguely studied at a genomic scale. We sequenced the diploid and haploid genomes of 3 boars from leukocytes and spermatozoa at 50x to shed light into the genetic basis of spermatogenesis-caused Allelic Ratio Distortion (ARD). We first developed a binomial model to identify ARD by simultaneously analysing all three males. This led to the identification of 55 ARD SNPs, most of which were animal-specific. We then evaluated ARD individually within each pig by a Fisher Exact Test and identified 2 shared genes (TOP3A ...