Diastereoselective ZnCl-Mediated Joullié-Ugi Three-Component Reaction for the Preparation of Phosphorylated -Acylaziridines from 2-Azirines.

We disclose a direct approach to the diastereoselective synthesis of phosphorus substituted -acylaziridines based on a one-pot ZnCl-catalyzed Joullié-Ugi three-component reaction of phosphorylated 2-azirines, carboxylic acids and isocyanides. Hence, this robust protocol offers rapid access to an array of -acylaziridines in moderate-to-good yields and up to 98:2 dr for substrates over a wide scope. The relevance of this synthetic methodology was achieved via a gram-scale reaction and the further derivatization of the nitrogen-containing three-membered heterocycle.

Development, Optimisation and Validation of a Novel Multiplex Real-Time PCR Method for the Simultaneous Detection of spp., and .

The enteric protozoan parasites spp., and are-to various extents-contributors to the burden of gastrointestinal illness in high-income countries. Detection of these pathogens by microscopy examination is challenging because of the limited sensitivity and need for specific staining procedures.

[Treatment protocol for COVID-19 in patients with and without an indication for hospital admission].

SARS-CoV-2 infection causes a wide spectrum of symptoms with varying degrees of severity, from asymptomatic cases or cases in the form of self-limiting influenza-like illness to cases of rapidly progressing respiratory distress syndrome due to an anomalous immune system response in the form of a cytokine storm. Thrombotic complications are also common. Multiple antiviral treatments have been tested in COVID-19 without favorable outcomes.

[Viral pneumonia. COVID-19 pneumonia].

Viruses are becoming more and more important as etiological agents of pneumonia, mainly due to improvements in diagnostic techniques. At present, they account for approximately one-third of community-acquired pneumonia cases. They tend to occur in children and elderly patients, causing anything from mild cases to severe cases which require intubation and intensive care.

Predictors of mediastinal staging and usefulness of pet in patients with stage IIIA (N2) or IIIB (N3) lung cancer.

Objective: To analyze which factors predict mediastinal N2/N3 lymph node staging and diagnostic accuracy of PET and CT to determine it.

Patients And Methods: We analyzed data collected prospectively in a database that included patients with non-small cell lung cancer (NSCLC) who underwent EBUS-TBNA. Prior to EBUS-TBNA, CT and PET were used to define the radiographic N stage and lymph nodes with short axis ≥ 1 cm by CT or with ratio between maximum standardized uptake value (maxSUV), by PET, of lymph node and primary tumor greater than 0.

Timing of implant-removal in late acute periprosthetic joint infection: A multicenter observational study.

Objectives: We evaluated the treatment outcome in late acute (LA) periprosthetic joint infections (PJI) treated with debridement and implant retention (DAIR) versus implant removal.

Methods: In a large multicenter study, LA PJIs of the hip and knee were retrospectively evaluated. Failure was defined as: PJI related death, prosthesis removal or the need for suppressive antibiotic therapy.

Development of a multicellular pancreatic tumor microenvironment system using patient-derived tumor cells.

The development of drugs to treat cancer is hampered by the inefficiency of translating pre-clinical in vitro monoculture and mouse studies into clinical benefit. There is a critical need to improve the accuracy of evaluating pre-clinical drug efficacy through the development of more physiologically relevant models. In this study, a human triculture 3D in vitro tumor microenvironment system (TMES) was engineered to accurately mimic the tumor microenvironment.

[Popliteal Artery Aneurysms: Literature Review and presentation of case.].

Introduction: The popliteal artery aneurysm (AAP) is localized and irreversible walls of the popliteal artery dilation. It is rare pathology is the second most common location of true aneurysms after aortic, and the first location within the peripheral aneurysms. It is characterized by affecting mainly men at an average age of 65, whose manifestations are mainly ischemic, finishing lower limb amputation in a frequency ranging as appropriate between 7 and 20 percent.

[Perception of Psychiatry among Undergraduate Students of a School of Medicine].

Objective: Learn about perceptions and beliefs regarding psychiatry among undergraduate medicine students and compare their conceptions and appreciations concerning positive and negative aspects, before and after specific training in psychiatry.

Methods: Observational, cross-sectional study; qualitative and quantitative research with application of a survey for undergraduate medicine students of the Universidad de La Sabana, before and after a specific psychiatry course. 90 students answered the survey in two groups: one of them before the course, and the other one afterwards;

Results: 52,2% corresponded to semesters prior to the course of psychiatry; 25.

Autophosphorylation of carboxy-terminal residues inhibits the activity of protein kinase CK1alpha.

CK1 constitutes a protein kinase subfamily that is involved in many important physiological processes. However, there is limited knowledge about mechanisms that regulate their activity. Isoforms CK1delta and CK1epsilon were previously shown to autophosphorylate carboxy-terminal sites, a process which effectively inhibits their catalytic activity.

CK2alpha/CK1alpha chimeras are sensitive to regulation by the CK2beta subunit.

The effect of CK2beta on the activity of CK2alpha and other protein kinases that can bind this regulatory subunit is not fully understood. In an attempt to improve our understanding of this effect, chimeras of CK2alpha and CK1alpha have been constructed. These chimeras contain different portions of the CK2alpha amino terminal region that are involved in the interaction with CK2beta to form CK2 tetramers.

Protein kinase CK2 as an ectokinase: the role of the regulatory CK2beta subunit.

Protein kinase CK2 (also known as casein kinase 2) is present in the cytoplasm, nuclei, and several other organelles. In addition, this enzyme has been found bound to the external side of the cell membrane where it acts as an ectokinase phosphorylating several extracellular proteins. Previous experiments with transfection of HEK-293T cells demonstrated that expression of both subunits, CK2alpha (catalytic) and CK2beta (regulatory), was necessary for the appearance of the ectopic enzyme as an ectokinase.

A new mathematical model to evaluate simazine removal in three different immobilized-biomass reactors.

A new mathematical model based on the cinetical Langmuir equation is developed to interpret and predict the effectiveness of simazine (SZ) removal in immobilized-biomass reactor (IBR), to consider herbicide-support affinity (Cx), and herbicide-cell affinity (Cy). Three solid supports: sepiolite monolith, granular sepiolite, and alginate were used in pilot-scale reactors that were inoculated with Klebsiella planticola DSZ. The abiotic process was analysed by measuring the SZ sorption capacity of the reactor supports.

Chemical dissection of the APC Repeat 3 multistep phosphorylation by the concerted action of protein kinases CK1 and GSK3.

A crucial event in machinery controlled by Wnt signaling is the association of beta-catenin with the adenomatous polyposis coli (APC) protein, which is essential for the degradation of beta-catenin and requires the multiple phosphorylation of APC at six serines (1501, 1503, 1504, 1505, 1507, and 1510) within its repeat three (R3) region. Such a phosphorylation is believed to occur by the concerted action of two protein kinases, CK1 and GSK3, but its mechanistic aspects are a matter of conjecture. Here, by combining the usage of variably phosphorylated peptides reproducing the APC R3 region and Edman degradation assisted localization of residues phosphorylated by individual kinases, we show that the process is initiated by CK1, able to phosphorylate S1510 and S1505, both specified by non-canonical determinants.

Impaired hyperphosphorylation of rotavirus NSP5 in cells depleted of casein kinase 1alpha is associated with the formation of viroplasms with altered morphology and a moderate decrease in virus replication.

The rotavirus (RV) non-structural protein 5, NSP5, is encoded by the smallest of the 11 genomic segments and localizes in 'viroplasms', cytoplasmic inclusion bodies in which viral RNA replication and packaging take place. NSP5 is essential for the replicative cycle of the virus because, in its absence, viroplasms are not formed and viral RNA replication and transcription do not occur. NSP5 is produced early in infection and undergoes a complex hyperphosphorylation process, leading to the formation of proteins differing in electrophoretic mobility.

The first armadillo repeat is involved in the recognition and regulation of beta-catenin phosphorylation by protein kinase CK1.

Multiple phosphorylation of beta-catenin by glycogen synthase kinase 3 (GSK3) in the Wnt pathway is primed by CK1 through phosphorylation of Ser-45, which lacks a typical CK1 canonical sequence. Synthetic peptides encompassing amino acids 38-64 of beta-catenin are phosphorylated by CK1 on Ser-45 with low affinity (K(m) approximately 1 mM), whereas intact beta-catenin is phosphorylated at Ser-45 with very high affinity (K(m) approximately 200 nM). Peptides extended to include a putative CK1 docking motif (FXXXF) at 70-74 positions or a F74AA mutation in full-length beta-catenin had no significant effect on CK1 phosphorylation efficiency.

Identifying interaction motifs in CK2beta--a ubiquitous kinase regulatory subunit.

Casein kinase 2 (CK2) is probably the most ubiquitous serine/threonine kinase found in eukaryotes: it phosphorylates >300 cellular proteins, ranging from transcription factors to proteins involved in chromatin structure and cell division. CK2 is a heterotetrameric enzyme that induces neoplastic growth when overexpressed. The beta subunit of CK2 (CK2beta) functions as the regulator of the catalytic CK2alpha and CK2alpha' subunits, enhancing their stability, activity and specificity.

Casein kinase 2-dependent serine phosphorylation of MuSK regulates acetylcholine receptor aggregation at the neuromuscular junction.

The release of Agrin by motoneurons activates the muscle-specific receptor tyrosine kinase (MuSK) as the main organizer of subsynaptic specializations at the neuromuscular junction. MuSK downstream signaling is largely undefined. Here we show that protein kinase CK2 interacts and colocalizes with MuSK at post-synaptic specializations.

Minimal CK2 activity required for yeast growth.

Protein kinase CK2 is essential for the growth of Saccharomyces cerevisiae. Yeast cells that lack the functional genes coding for both the catalytic subunits of protein kinase CK2 can grow only if they are complemented by exogenous cDNAs coding for this subunit. A series of deletion mutants of CK2alpha from Xenopus laevis was constructed.

Generation of protein kinase Ck1alpha mutants which discriminate between canonical and non-canonical substrates.

Protein kinase CK1 denotes a family of pleiotropic serine/threonine protein kinases implicated in a variety of cellular functions. Typically, CK1 acts as a 'phosphate-directed' kinase whose targeting is primed by a single phosphorylated side chain at position n-3 or n-4 relative to serine/threonine, but increasing evidence is accumulating that CK1 can also engage some of its substrates at sites that do not conform to this canonical consensus. In the present paper, we show that CK1a phosphorylates with the same efficiency phosphopeptides primed by a phosphoserine residue at either n-3 [pS(-3)] or n-4 [pS(-4)] positions.