Activation Dynamics of Ubiquitin Specific Protease 7.

Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme responsible for the regulation of key human oncoproteins and tumor suppressors including Mdm2 and p53, respectively. Unlike other members of the USP family of proteases, the isolated catalytic domain of USP7 adopts an enzymatically inactive conformation that has been well characterized using X-ray crystallography. The catalytic domain also samples an active conformation, which has only been captured upon USP7 substrate-binding.

Jugular Vein Catheter Design and Cocaine Self-Administration Using Mice: A Comprehensive Method.

Intravenous self-administration (IVSA) is a behavioral method of voluntary drug intake in animal models which is used to study the reinforcing effects of drugs of abuse. It is considered to have greater face validity in the study of substance use and abuse than other assays, and thus, allows for valuable insight into the neurobiological basis of addiction, and the development of substance abuse disorders. The technique typically involves surgically inserting a catheter into the jugular vein, which enables the infusion of drug solution after the performance of a desired operant behavior.

Backbone and ILV side-chain NMR resonance assignments of the catalytic domain of human deubiquitinating enzyme USP7.

Ubiquitin specific protease 7 (USP7) is a deubiquitinating enzyme, which removes ubiquitin tag from numerous protein substrates involved in diverse cellular processes such as cell cycle regulation, apoptosis and DNA damage response. USP7 affects stability, interaction network and cellular localization of its cellular and viral substrates by controlling their ubiquitination status. The large 41 kDa catalytic domain of USP7 harbors the active site of the enzyme.

Risk of complications due to antithrombotic agents in cutaneous surgery: a systematic review and meta-analysis.

Background And Objectives: We aimed to determine the risk of complications during cutaneous surgery for the perioperative discontinuation in comparison to the continuation of antithrombotic agents and the bridging of vitamin K antagonists with heparin in comparison to their continuation.

Methods: We conducted a systematic review, searching three databases for eligible studies. Methods followed the Cochrane Handbook.

Nuclear magnetic resonance spectral data of the USP7 TRAF and UBL1-2 domains in complex with DNA polymerase ι peptides.

This data article is related to the publication 'DNA polymerase ι interacts with both the TRAF-like and UBL1-2 domains of USP7' [1]. Ubiquitin-specific protease 7 (USP7) is an essential deubiquitinating enzyme with characterized substrates in many cellular pathways. Established USP7 substrates interact with one of two major binding sites, located on the N-terminal TRAF-like (TRAF) domain and the first and second UBL domains (UBL1-2) within the C-terminal tail.

Wear of hip prostheses increases serum IGFBP-1 levels in patients with aseptic loosening.

The biological mechanisms involved in aseptic loosening include inflammation-associated and bone resorption-associated processes. Coordinated cellular actions result in biochemical imbalances with devastating consequences for the joint. Given that this condition is not known for showing systemic signs, we investigated whether circulating levels of inflammation-related proteins are altered in patients with aseptic loosening.

DNA Polymerase ι Interacts with Both the TRAF-like and UBL1-2 Domains of USP7.

Reversible protein ubiquitination is an essential signaling mechanism within eukaryotes. Deubiquitinating enzymes are critical to this process, as they mediate removal of ubiquitin from substrate proteins. Ubiquitin-specific protease 7 (USP7) is a prominent deubiquitinating enzyme, with an extensive network of interacting partners and established roles in cell cycle activation, immune responses and DNA replication.

USP7 Is a Master Regulator of Genome Stability.

Genetic alterations, including DNA mutations and chromosomal abnormalities, are primary drivers of tumor formation and cancer progression. These alterations can endow cells with a selective growth advantage, enabling cancers to evade cell death, proliferation limits, and immune checkpoints, to metastasize throughout the body. Genetic alterations occur due to failures of the genome stability pathways.

Update of the Spanish registry of haemoglobinopathies in children and adults.

Background And Objective: Patients with thalassaemia major (TM) and sickle cell disease (SCD) in Spain have been counted since the creation of the Spanish registry of haemoglobinopathies (REHem). The objective of this paper is to update the published data after the increase in cases due to the inclusion of adults and introduction of new-born screening in almost the whole country.

Material And Methods: An observational, descriptive, multicentre and ambispective study that included patients with haemoglobinopathies registered in the REHem, started in January 2014 and followed up annually.

Influence of inflammatory conditions provided by macrophages on osteogenic ability of mesenchymal stem cells.

Background: The mechanisms by which macrophage phenotype contributes to mesenchymal stem cells (MSC)-mediated bone repair remain unclear. In this work, we investigated the influence of factors released by human macrophages polarized to a pro-inflammatory or an anti-inflammatory phenotype on the ability of human MSC to attach, migrate, and differentiate toward the osteoblastic lineage. We focused on the role of TNF-α and IL-10, key pro-inflammatory and anti-inflammatory cytokines, respectively, in regulating MSC functions.

Immunoregulatory potential of mesenchymal stem cells following activation by macrophage-derived soluble factors.

Background: Immunoregulatory capacity of mesenchymal stem cells (MSC) is triggered by the inflammatory environment, which changes during tissue repair. Macrophages are essential in mediating the inflammatory response after injury and can adopt a range of functional phenotypes, exhibiting pro-inflammatory and anti-inflammatory activities. An accurate characterization of MSC activation by the inflammatory milieu is needed for improving the efficacy of regenerative therapies.

Genomes reveal marked differences in the adaptive evolution between orangutan species.

Background: Integrating demography and adaptive evolution is pivotal to understanding the evolutionary history and conservation of great apes. However, little is known about the adaptive evolution of our closest relatives, in particular if and to what extent adaptions to environmental differences have occurred. Here, we used whole-genome sequencing data from critically endangered orangutans from North Sumatra (Pongo abelii) and Borneo (P.

Publisher Correction: Paracrine interactions between mesenchymal stem cells and macrophages are regulated by 1,25-dihydroxyvitamin D3.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Publisher Correction: Paracrine interactions between mesenchymal stem cells and macrophages are regulated by 1,25-dihydroxyvitamin D3.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

Morphometric, Behavioral, and Genomic Evidence for a New Orangutan Species.

Six extant species of non-human great apes are currently recognized: Sumatran and Bornean orangutans, eastern and western gorillas, and chimpanzees and bonobos [1]. However, large gaps remain in our knowledge of fine-scale variation in hominoid morphology, behavior, and genetics, and aspects of great ape taxonomy remain in flux. This is particularly true for orangutans (genus: Pongo), the only Asian great apes and phylogenetically our most distant relatives among extant hominids [1].

Paracrine interactions between mesenchymal stem cells and macrophages are regulated by 1,25-dihydroxyvitamin D3.

Mesenchymal stem cells (MSC) modulate the macrophage-mediated inflammatory response through the secretion of soluble factors. In addition to its classical effects on calcium homeostasis, 1,25-dihydroxyvitamin D3 (1,25D3) has emerged as an important regulator of the immune system. The present study investigates whether 1,25D3 modulates the paracrine interactions between MSC and macrophages.

USP7-Specific Inhibitors Target and Modify the Enzyme's Active Site via Distinct Chemical Mechanisms.

USP7 is a deubiquitinating enzyme that plays a pivotal role in multiple oncogenic pathways and therefore is a desirable target for new anti-cancer therapies. However, the lack of structural information about the USP7-inhibitor interactions has been a critical gap in the development of potent inhibitors. USP7 is unique among USPs in that its active site is catalytically incompetent, and is postulated to rearrange into a productive conformation only upon binding to ubiquitin.

National registry of hemoglobinopathies in Spain (REPHem).

Background: Although highly prevalent throughout the world, the accurate prevalence of hemoglobinopathies in Spain is unknown.

Procedure: This study presents data on the national registry of hemoglobinopathies of patients with thalassemia major (TM), thalassemia intermedia (TI), and sickle cell disease (SCD) in Spain created in 2014. Fifty centers reported cases retrospectively.

Galactomannan Downregulates the Inflammation Responses in Human Macrophages via NFκB2/p100.

We show that galactomannan, a polysaccharide consisting of a mannose backbone with galactose side groups present on the cell wall of several fungi, induces a reprogramming of the inflammatory response in human macrophages through dectin-1 receptor. The nuclear factor kappa-light-chain-enhancer of activated B cells 2 (NFκB2)/p100 was overexpressed after galactomannan challenge. Knocking down NFκB2/p100 using small interfering RNA (siRNA) indicated that NFκB2/p100 expression is a crucial factor in the progression of the galactomannan-induced refractoriness.