Aggregation-Inhibiting scFv-Based Therapies Protect Mice against AAV1/2-Induced A53T-α-Synuclein Overexpression.

To date, there is no cure for Parkinson's disease (PD). There is a pressing need for anti-neurodegenerative therapeutics that can slow or halt PD progression by targeting underlying disease mechanisms. Specifically, preventing the build-up of alpha-synuclein (αSyn) and its aggregated and mutated forms is a key therapeutic target.

Identifying SARS-COV-2 infected patients through canine olfactive detection on axillary sweat samples; study of observed sensitivities and specificities within a group of trained dogs.

There is an increasing need for rapid, reliable, non-invasive, and inexpensive mass testing methods as the global COVID-19 pandemic continues. Detection dogs could be a possible solution to identify individuals infected with SARS-CoV-2. Previous studies have shown that dogs can detect SARS-CoV-2 on sweat samples.

Quantum diffusion in spin chains with phase space methods.

Connecting short-time microscopic dynamics with long-time hydrodynamics in strongly correlated quantum systems is one of the outstanding questions. In particular, it is hard to determine various hydrodynamic coefficients such as the diffusion constant or viscosity starting from a microscopic model: exact quantum simulations are limited to either small system sizes or to short times, which are insufficient to reach asymptotic behavior and so various approximations must be applied. We show that these difficulties, at least for particular models, can be circumvented by using the cluster truncated Wigner approximation (CTWA), which maps quantum Hamiltonian dynamics into classical Hamiltonian dynamics in auxiliary high-dimensional phase space.

Topical Tranexamic Acid Increases Early Postoperative Pain After Total Hip Arthroplasty.

Background: Tranexamic acid (TXA) has reduced blood transfusion following total hip arthroplasty (THA). However, non-human studies have linked TXA exposure with increased pain and decreased periarticular cell viability and cell death. This study evaluated early pain following THA performed with and without topical TXA.

Chemical-Reaction-Controlled Phase Separated Drops: Formation, Size Selection, and Coarsening.

Phase separation under nonequilibrium conditions is exploited by biological cells to organize their cytoplasm but remains poorly understood as a physical phenomenon. Here, we study a ternary fluid model in which phase-separating molecules can be converted into soluble molecules, and vice versa, via chemical reactions. We elucidate using analytical and simulation methods how drop size, formation, and coarsening can be controlled by the chemical reaction rates, and categorize the qualitative behavior of the system into distinct regimes.

A randomised, controlled, non-inferiority trial comparing the performance of a soft silicone-coated wound contact layer (Mepitel One) with a lipidocolloid wound contact layer (UrgoTul) in the treatment of acute wounds.

Wound contact layer (WCL) dressings are intended to protect tissue during the healing process. A randomised controlled trial was undertaken to compare 2 such dressings. Outpatients with acute wounds were randomly allocated to treatment with either a soft silicone-coated WCL (intervention group, n = 59) or a lipidocolloid-impregnated WCL (control group, n = 62).

Functional insights from high resolution structures of mouse protein arginine methyltransferase 6.

PRMT6 is a protein arginine methyltransferase involved in transcriptional regulation, human immunodeficiency virus pathogenesis, DNA base excision repair, and cell cycle progression. Like other PRMTs, PRMT6 is overexpressed in several cancer types and is therefore considered as a potential anti-cancer drug target. In the present study, we described six crystal structures of PRMT6 from Mus musculus, solved and refined at 1.

Assessment of a fast generated analytical matrix for rotating slat collimation iterative reconstruction: a possible method to optimize the collimation profile.

In SPECT imaging, improvement or deterioration of performance is mostly due to collimator design. Classical SPECT systems mainly use parallel hole or pinhole collimators. Rotating slat collimators (RSC) can be an interesting alternative to optimize the tradeoff between detection efficiency and spatial resolution.

Structural insight into arginine methylation by the mouse protein arginine methyltransferase 7: a zinc finger freezes the mimic of the dimeric state into a single active site.

Protein arginine methyltransferase 7 (PRMT7) is a type III arginine methyltransferase which has been implicated in several biological processes such as transcriptional regulation, DNA damage repair, RNA splicing, cell differentiation and metastasis. PRMT7 is a unique but less characterized member of the family of PRMTs. The crystal structure of full-length PRMT7 from Mus musculus refined at 1.

Trends in meat science and technology: the future looks bright, but the journey will be long.

With an increasing world population, an increase in affluence and a substantial growth in the demand for high quality protein, the meat sector faces a fantastic but challenging century. New scientific knowledge, technology and creative minds are the main ingredients in order to reach out for this great opportunity. Efficiency all the way from breeding and farming to processing and dispatch is crucial for success.

Molecular basis for the antiparasitic activity of a mercaptoacetamide derivative that inhibits histone deacetylase 8 (HDAC8) from the human pathogen schistosoma mansoni.

Schistosomiasis, caused by the parasitic flatworm Schistosoma mansoni and related species, is a tropical disease that affects over 200 million people worldwide. A new approach for targeting eukaryotic parasites is to tackle their dynamic epigenetic machinery that is necessary for the extensive phenotypic changes during the life cycle of the parasite. Recently, we identified S.

Cysteine mapping in conformationally distinct kinase nucleotide binding sites: application to the design of selective covalent inhibitors.

Kinases have emerged as one of the most prolific therapeutic targets. An important criterion in the therapeutic success of inhibitors targeting the nucleotide binding pocket of kinases is the inhibitor residence time. Recently, covalent kinase inhibitors have attracted attention since they confer terminal inhibition and should thus be more effective than reversible inhibitors with transient inhibition.

Characterization of a rotating slat collimator system dedicated to small animal imaging.

Some current investigations based on small animal models are dedicated to functional cerebral imaging. They represent a fundamental tool to understand the mechanisms involved in neurodegenerative diseases. In the radiopharmaceutical development approach, the main challenge is to measure the radioactivity distribution in the brain of a subject with good temporal and spatial resolutions.

Defining and characterizing protein surface using alpha shapes.

The alpha shape of a molecule is a geometrical representation that provides a unique surface decomposition and a means to filter atomic contacts. We used it to revisit and unify the definition and computation of surface residues, contiguous patches, and curvature. These descriptors are evaluated and compared with former approaches on 85 proteins for which both bound and unbound forms are available.

Histone H3 tails containing dimethylated lysine and adjacent phosphorylated serine modifications adopt a specific conformation during mitosis and meiosis.

Condensation of chromatin, mediated in part by posttranslational modifications of histones, is essential for cell division during mitosis. Histone H3 tails are dimethylated on lysine (Kme2) and become phosphorylated on serine (Sp) residues during mitosis. We have explored the possibility that these double modifications are involved in the establishment of H3 tail conformations during the cell cycle.

Critical role of desolvation in the binding of 20-hydroxyecdysone to the ecdysone receptor.

The insect steroid hormone 20-hydroxyecdysone (20E) binds to its cognate nuclear receptor composed of the ecdysone receptor (EcR) and Ultraspiracle (USP) and triggers the main developmental transitions, in particular molting and metamorphosis. We present the crystal structure of the ligand-binding domains of EcR/USP in complex with 20E at 2.4A resolution and compare it with published structures of EcR/USP bound to ponasterone A (ponA).

The loss of transcriptional inhibition by the photoreceptor-cell specific nuclear receptor (NR2E3) is not a necessary cause of enhanced S-cone syndrome.

Purpose: To investigate functional consequence on photoreceptor-cell specific nuclear receptor (NR2E3) transcriptional activity of enhanced S-cone syndrome (ESCS) mutations localized in ligand binding domain (LBD).

Methods: Point mutations were introduced into the LBD of full length and Gal4 chimeric NR2E3 receptors and transcriptional activity was investigated by using transient co-transfection assay on corresponding luciferase reporters. Expression and DNA binding properties of transfected mutant and wild-type receptors were tested by Western blotting and gel shift assay.

Raloxifene and ICI182,780 increase estrogen receptor-alpha association with a nuclear compartment via overlapping sets of hydrophobic amino acids in activation function 2 helix 12.

The basis for the differential repressive effects of antiestrogens on transactivation by estrogen receptor-alpha (ERalpha) remains incompletely understood. Here, we show that the full antiestrogen ICI182,780 and, to a lesser extent, the selective ER modulator raloxifene (Ral), induce accumulation of exogenous ERalpha in a poorly soluble fraction in transiently transfected HepG2 or stably transfected MDA-MB231 cells and of endogenous receptor in MCF7 cells. ERalpha remained nuclear in HepG2 cells treated with either compound.

Partial defects in transcriptional activity of two novel DAX-1 mutations in childhood-onset adrenal hypoplasia congenita.

Objective: Mutations in DAX-1, an X-linked gene encoding an orphan nuclear receptor, have been associated with adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Here we describe two novel DAX-1 mutations, Y214X and I361T, associated with childhood-onset primary adrenal failure. We aimed at analysing their effects on protein localization, transcriptional activity and propose a structural-function relationship.

A new species of Procamallanus (Nematoda: Camallanidae) from Pacific eels (Anguilla spp.).

A new species of parasitic nematode, Procamallanus (Procamallanus) pacificus n. sp., is described from the stomach of the Pacific shortfinned eel, Anguilla obscura (type host), and from the speckled longfin eel, Anguilla reinhardtii, from northern New Caledonia (Melanesia, South Pacific); from Anguilla sp.

Unfaithfulness and promiscuity of a mutant androgen receptor in a hormone-refractory prostate cancer.

Missense mutations in the androgen receptor (AR) contribute to the failure of hormonal therapy for prostate cancer (PCa), but the underlying molecular bases remain uncharacterized. Here, we describe a new AR variant found in a hormone-refractory metastatic PCa, in which threonine 575 in the DNA binding domain, and threonine 877 in the ligand-binding domain, were both replaced by an alanine. Using gene reporter assays, we demonstrate that the T575A mutation weakened transcriptional activity from promoters containing AR-specific responsive elements, while activity from promoters with AR-non-specific elements was enhanced.

Cucullanus oceaniensis sp. n. (Nematoda: Cucullanidae) from Pacific eels (Anguilla spp.).

A new species of parasitic nematode, Cucullanus oceaniensis sp. n., is described from the intestine of the giant mottled eel Anguilla marmorata (type host) from Futuna Island (Wallis and Futuna Islands, Polynesia) and from A.

The monomeric orphan nuclear receptor Schistosoma mansoni Ftz-F1 dimerizes specifically and functionally with the schistosome RXR homologue, SmRXR1.

In an attempt to understand development and differentiation processes of the parasitic blood fluke Schistosoma mansoni, several members of the nuclear receptor superfamily were cloned, including SmFtz-F1 (S. mansoni Fushi Tarazu-factor 1). The Ftz-F1 nuclear receptor subfamily only contains orphan receptors that bind to their response element as monomers.

Structure-based analysis of the ultraspiracle protein and docking studies of putative ligands.

The ultraspiracle protein (USP) is the insect ortholog of the mammalian retinoid X receptor (RXR). Fundamental questions concern the functional role of USP as the heterodimerization partner of insect nuclear receptors such as the ecdysone receptor. The crystallographic structures of the ligand binding domain of USPs of Heliothis virescens and Drosophila melanogaster solved recently show that helix 12 is locked in an antagonist conformation raising the question whether USPs could adopt an agonist conformation as observed in RXRalpha.