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Ballesteros, J.

Publications and source records attributed to Ballesteros, J..

3 recordsLinked to original sources

Coordination of Anle138b to Silver Results in Selective Reduction of a C-terminal truncated Alpha-synuclein Protein and Increased Aggregate Size

Parkinsons disease (PD) is a prevalent age-related neurodegenerative syndrome, partially thought to be caused by a decrease in alpha-synuclein proteostasis. Anle138b = 5-(1,3-benzodioxol-5-yl)-3-(3-bromophenyl)-1H-pyrazole (HL), is undergoing clinical trials as a promising mitigator of alpha-synuclein aggregation. Because complexation to metals is known to modulate the activity of several drugs, we have prepared and characterized: H2L(ClO4), [CuI({micro}-L)]3, and [AgI({micro}-L)]3. To better understand the bioviability of these compounds, we monitored their effects in a cell culture model of alpha-synuclein protein aggregation using human alpha-synuclein pre-formed fibrils (PFFs). Using two different anti-alpha-synuclein antibodies, our data suggests that [AgI({micro}-L)]3 decreases a C-terminal truncated protein that is approximately 12.4 kDa, as well as increases the size and alters the shape of PFF-induced aggregates. This indicates that [AgI({micro}-L)]3 impacts aggregation in a manner different from HL and may serve as a novel tool for studying C-terminal truncation related aggregation chemistry. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/679869v1_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@4bbda5org.highwire.dtl.DTLVardef@8fc0b7org.highwire.dtl.DTLVardef@1b561f5org.highwire.dtl.DTLVardef@1322902_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

Machine learning approaches to assess microendemicity and conservation risk in cave-dwelling arachnofauna

The biota of cave habitats faces heightened conservation risks, due to geographic isolation and high levels of endemism. Molecular datasets, in tandem with ecological surveys, have the potential to delimit precisely the nature of cave endemism and identify conservation priorities for microendemic species. Here, we sequenced ultraconserved elements of Tegenaria within, and at the entrances of, 25 cave sites to test phylogenetic relationships, combined with an unsupervised machine learning approach to delimit species. Our data identified clear species limits, as well as the incidence of previously unidentified, potential cryptic species. We employed the R package canaper and Categorical Analysis of Neo- and Paleo-Endemism (CANAPE) to generate conservation metrics that are informative for future policy, in tandem with conservation assessments for the troglobitic Israeli species of this genus.

evolutionary biology↗

Neglected no longer: Phylogenomic resolution of higher-level relationships in Solifugae

Considerable progress has been achieved in resolving higher-level relationships of Arthropoda in the past two decades, largely precipitated by advances in sequencing technology. Yet, dark branches persist in the arthropod tree of life, principally among groups that are difficult to collect, occur in cryptic habitats, or are characterized by minute body size. Among chelicerates, the mesodiverse order Solifugae (commonly called camel spiders or sun spiders) is one of the last orders of Arachnida that lacks a higher-level phylogeny altogether and has long been characterized as one of the "neglected cousins", a lineage of arachnid orders that are comparatively poorly studied with respect to evolutionary relationships. Though renowned for their aggression, remarkable running speed, and adaptation to arid habitats, inferring solifuge relationships has been hindered by inaccessibility of diagnostic characters in most ontogenetic stages for morphological datasets, whereas molecular investigations to date have been limited to one of the 12 recognized families. In this study we generated a phylogenomic dataset via capture of ultraconserved elements (UCEs) and sampled all extant families. We recovered a well-resolved phylogeny of solifuge families, with two distinct groups of New World taxa nested within a broader Paleotropical radiation. To provide a temporal context to solifuge diversification, we estimated molecular divergence times using fossil calibrations within a least-squares framework. Solifugae were inferred to have radiated by the Permian, with divergences of most families dating to the post Paleogene-Cretaceous extinction. These results accord with a diversification history largely driven by vicariance as a result of continental breakup.

evolutionary biology↗