Recombinant cathepsins B and L promote α-synuclein clearance and restore lysosomal function in human and murine models with α-synuclein pathology.

Unlabelled: The autophagy-lysosomal pathway is crucial for maintaining homeostasis and survival of neurons, hence defects in this system have been associated with neurodegeneration, including Parkinson's disease (PD). The cysteine proteases cathepsin B (CTSB) and cathepsin L (CTSL) are involved in the clearance of various neurodegenerative disease-related proteins such as amyloid-[Formula: see text], huntingtin and the prion protein. While there are studies implicating CTSB and CTSL as mediators of α-synuclein/SNCA clearance, their exact roles remain unclear.

LIMP-2 deficiency-associated glycolipid abnormalities in mice.

Glucocerebrosidase (GCase) catalyzes the lysosomal degradation of glucosylceramide (GlcCer). GCase deficiency results in Gaucher disease (GD), a lysosomal storage disorder with characteristic hepatosplenomegaly. Transport of GCase to lysosomes is mediated by the lysosomal integral membrane protein type 2 (LIMP-2).

Application of preparative high-speed countercurrent chromatography for isolation of a bicyclo-[3.2.1]-octanoid neolignan from Piper multinodum C. DC. and determination of its absolute stereochemistry.

This study aimed to propose a straightforward approach for isolating a novel neolignan compound using high-speed countercurrent chromatography (HSCCC) in combination with spectrometric techniques. The bicycleneolignan compound was detected in the dichloromethane partition obtained from methanolic leaf extract of Piper multinodum. After evaluating several two-phase solvent systems, the n-hexane/ethyl acetate/methanol/water in ratio 3:1:1:1 (v/v/v/v) demonstrated the highest efficiency for HSCCC separation of the target compound, as evidenced by the optimal distribution coefficient K value of 1.

Anticancer Effects of Withanolides: In Silico Prediction of Pharmacological Properties.

Withanolides are a class of naturally occurring C-28 ergostane steroidal lactones with an abundance of biological activities, and their members are promising candidates for antineoplastic drug development. The ADMET properties of withanolides are still largely unknown, and in silico predictions can play a crucial role highlighting these characteristics for drug development, shortening time and resources spent on the development of a drug lead. In this work, ADMET properties of promising antitumoral withanolides were assessed.

Glucosylated cholesterol accumulates in atherosclerotic lesions and impacts macrophage immune response.

Atherosclerosis can be described as a local acquired lysosomal storage disorder (LSD), resulting from the build-up of undegraded material in lysosomes. Atherosclerotic foam cells accumulate cholesterol (Chol) and glycosphingolipids (GSLs) within lysosomes. This constitutes the ideal milieu for the formation of a side product of lysosomal storage: glucosylated cholesterol (GlcChol), previously found in several LSDs.

Giant mitogenomes in Rhynchospora are a result of nuclear gene and retrotransposon insertions in intergenic spaces.

Background And Aims: The mitochondrial genomes of plants are large, with the majority ranging between 500 and 800 kb. However, the mitochondrial genomes of Cyperaceae (sedges) species were found to be much larger, exceeding 1 Mb in size. Here, we aimed to investigate the gigantism of the mitochondrial genomes of three Rhynchospora (beak-sedges) species and one related species of the sister family Juncaceae, the common rush (Juncus effusus).

A competitive disinhibitory network for robust optic flow processing in Drosophila.

Many animals navigate using optic flow, detecting rotational image velocity differences between their eyes to adjust direction. Forward locomotion produces strong symmetric translational optic flow that can mask these differences, yet the brain efficiently extracts these binocular asymmetries for course control. In Drosophila melanogaster, monocular horizontal system neurons facilitate detection of binocular asymmetries and contribute to steering.

Same but different: Centromere regulations in holocentric insects and plants.

Centromeres are essential chromosomal regions responsible for ensuring proper chromosome segregation during cell division. Unlike monocentric chromosomes, which have a single centromeric region, holocentric chromosomes distribute centromeric activity along their entire length. This unique organization poses intriguing questions about its structure, function, and evolutionary origins.

Comparison of the Methods Fixation and Staining of Infected Macrophages with Recovery of Promastigotes in Culture to Evaluate Phagocytosis and Amastigote Proliferation of Leishmania sp. in vitro.

Purpose: Infection of macrophages is a mandatory step for Lesihmania to promote mammalian infection and the evaluation of parasites proliferating inside macrophages reveals important information about parasites virulence and leishmanicidal drugs. Here we compare macrophage phagocytosis ability and amastigote proliferation of L. major or L.

Cryoimmobilized anther analysis reveals new ultrastructural insights into (Cyperaceae) asymmetrical microsporogenesis.

Introduction: The Cyperaceae family is distinguished by holocentric chromosomes and a distinctive microsporogenesis process, which includes inverted meiosis, asymmetric tetrad formation, selective cell death, and the formation of pseudomonad pollen. Despite significant advances, the ultrastructural details of these processes remain poorly understood.

Methods: This study provides a detailed analysis of microsporogenesis in using high-pressure freezing, freeze substitution, and transmission electron microscopy, significantly enhancing ultrastructural resolution.

Centromere diversity and its evolutionary impacts on plant karyotypes and plant reproduction.

Karyotype changes are a formidable evolutionary force by directly impacting cross-incompatibility, gene dosage, genetic linkage, chromosome segregation, and meiotic recombination landscape. These changes often arise spontaneously and are commonly detected within plant lineages, even between closely related accessions. One element that can influence drastic karyotype changes after only one (or few) plant generations is the alteration of the centromere position, number, distribution, or even its strength.

Repeat competition and ecological shifts drive the evolution of the mobilome in Rhynchospora Vahl (Cyperaceae), the holocentric beaksedges.

Background And Aims: Genomic changes triggered by polyploidy, chromosomal rearrangements and/ or environmental stress are among factors that affect the activity of mobile elements, particularly long terminal repeat retrotransposons (LTR-RTs) and DNA transposons. Because these elements can proliferate and move throughout host genomes, altering the genetic, epigenetic and nucleotypic landscape, they have been recognized as a relevant evolutionary force. Beaksedges (Rhynchospora) stand out for their wide cosmopolitan distribution, high diversity (~400 species) and holocentric chromosomes related to high karyotypic diversity and a centromere-specific satDNA, Tyba.

Repeat-based holocentromeres of the woodrush Luzula sylvatica reveal insights into the evolutionary transition to holocentricity.

In most studied eukaryotes, chromosomes are monocentric, with centromere activity confined to a single region. However, the rush family (Juncaceae) includes species with both monocentric (Juncus) and holocentric (Luzula) chromosomes, where centromere activity is distributed along the entire chromosome length. Here, we combine chromosome-scale genome assembly, epigenetic analysis, immuno-FISH and super-resolution microscopy to study the transition to holocentricity in Luzula sylvatica.

An Integrated Strategy of UHPLC-ESI-MS/MS Combined with Bioactivity-Based Molecular Networking for Identification of Antitumoral Withanolides from (Vell.) I.M.C. Rodrigues & Stehmann.

Background: , a Brazilian native species from the Solanaceae family, is recognized as a promising source of bioactive withanolides, particularly Aurelianolide A and B, which exhibit significant antitumoral activities. Despite its potential, research on the chemical constituents of this species remains limited. This study aimed to dereplicate extracts and partitions of to streamline the discovery of bioactive withanolides.

A comparative analysis of planarian genomes reveals regulatory conservation in the face of rapid structural divergence.

The planarian Schmidtea mediterranea is being studied as a model species for regeneration, but the assembly of planarian genomes remains challenging. Here, we report a high-quality haplotype-phased, chromosome-scale genome assembly of the sexual S2 strain of S. mediterranea and high-quality chromosome-scale assemblies of its three close relatives, S.

Distinct patterns of satDNA distribution in holocentric chromosomes of spike-sedges (, Cyperaceae).

R. Br. (Cyperaceae) species are known for having holocentric chromosomes, which enable rapid karyotype differentiation.

Repeatome evolution across space and time: Unravelling repeats dynamics in the plant genus Erythrostemon Klotzsch (Leguminosae Juss).

Fluctuations in genomic repetitive fractions (repeatome) are known to impact several facets of evolution, such as ecological adaptation and speciation processes. Therefore, investigating the divergence of repetitive elements can provide insights into an important evolutionary force. However, it is not clear how the different repetitive element clades are impacted by the different factors such as ecological changes and/or phylogeny.

Centromere diversity: How different repeat-based holocentromeres may have evolved.

In addition to monocentric eukaryotes, which have a single localized centromere on each chromosome, there are holocentric species, with extended repeat-based or repeat-less centromeres distributed over the entire chromosome length. At least two types of repeat-based holocentromeres exist, one composed of many small repeat-based centromere units (small unit-type), and another one characterized by a few large centromere units (large unit-type). We hypothesize that the transposable element-mediated dispersal of hundreds of short satellite arrays formed the small centromere unit-type holocentromere in Rhynchospora pubera.

How diverse a monocentric chromosome can be? Repeatome and centromeric organization of Juncus effusus (Juncaceae).

Juncus is the largest genus of Juncaceae and was considered holocentric for a long time. Recent findings, however, indicated that 11 species from different clades of the genus have monocentric chromosomes. Thus, the Juncus centromere organization and evolution need to be reassessed.

KNL1 and NDC80 represent new universal markers for the detection of functional centromeres in plants.

Centromere is the chromosomal site of kinetochore assembly and microtubule attachment for chromosome segregation. Given its importance, markers that allow specific labeling of centromeric chromatin throughout the cell cycle and across all chromosome types are sought for facilitating various centromere studies. Antibodies against the N-terminal region of CENH3 are commonly used for this purpose, since CENH3 is the near-universal marker of functional centromeres.

Oligo-barcode illuminates holocentric karyotype evolution in (Cyperaceae).

Holocentric karyotypes are assumed to rapidly evolve through chromosome fusions and fissions due to the diffuse nature of their centromeres. Here, we took advantage of the recent availability of a chromosome-scale reference genome for , a model species of this holocentric genus, and developed the first set of oligo-based barcode probes for a holocentric plant. These probes were applied to 13 additional species of the genus, aiming to investigate the evolutionary dynamics driving the karyotype evolution in .