Electrostatic Preorganization in Three Distinct Heterogeneous Proteasome β-Subunits.

The origin of the enzyme's powerful role in accelerating chemical reactions is one of the most critical and still widely discussed questions. It is already accepted that enzymes impose an electrostatic field onto their substrates by adopting complex three-dimensional structures; therefore, the preorganization of electric fields inside protein active sites has been proposed as a crucial contributor to catalytic mechanisms and rate constant enhancement. In this work, we focus on three catalytically active β-subunits of 20S proteasomes with low sequence identity (∼30%) whose active sites, although situated in an electrostatically miscellaneous environment, catalyze the same chemical reaction with similar catalytic efficiency.

Thrombus Burden, Caval Thrombosis, and Retrieval of the Denali Inferior Vena Cava Filter.

The purpose of this study was to evaluate outcomes of the Denali inferior vena cava filter (Bard Peripheral Vascular, Tempe, Arizona). Five hundred patients had 508 filters placed between 2015 and 2022. Filters were retrieved at the study site in 284 patients: 159 (31.

Biochemical and Structural Characterization of a Novel Psychrophilic Laccase (Multicopper Oxidase) Discovered from 229 (ENOLAB 4002).

Recently, prokaryotic laccases from lactic acid bacteria (LAB), which can degrade biogenic amines, were discovered. A laccase enzyme has been cloned from , a very important LAB in winemaking, and it has been expressed in . This enzyme has similar characteristics to those previously isolated from LAB as the ability to oxidize canonical substrates such as 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,6-dimethoxyphenol (2,6-DMP), and potassium ferrocyanide K[Fe(CN)], and non-conventional substrates as biogenic amines.

Intranasal Versus Intravenous Dexamethasone to Treat Hospitalized COVID-19 Patients: A Randomized Multicenter Clinical Trial.

Background: SARS-CoV2 induces flu-like symptoms that can rapidly progress to severe acute lung injury and even death. The virus also invades the central nervous system (CNS), causing neuroinflammation and death from central failure. Intravenous (IV) or oral dexamethasone (DXM) reduced 28 d mortality in patients who required supplemental oxygen compared to those who received conventional care alone.

How to increase noninvasive ventilation effectiveness in bulbar amyotrophic lateral sclerosis patients.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease in which the respiratory muscles are also affected, leading to respiratory failure. Bulbar impairment develops in almost all cases during the course of the disease, becoming severe in the late stages of disease. Noninvasive ventilation (NIV) has been shown to increase survival in ALS; however, severe bulbar dysfunction has a negative impact on NIV tolerance and effectiveness.

A fast magnetic vector characterization method for quasi two-dimensional systems and heterostructures.

The use of magnetic vector tomography/laminography has opened a 3D experimental window to access the magnetization at the nanoscale. These methods exploit the dependence of the magnetic contrast in transmission to recover its 3D configuration. However, hundreds of different angular projections are required leading to large measurement times.

Spatial magnetic imaging of non-axially symmetric vortex domains in cylindrical nanowire by transmission X-ray microscopy.

The spatial magnetization texture of a cylindrical nanowire has been determined by Transmission X-ray Microscopy (TXM) and X-ray magnetic circular dichroism (XMCD). For this purpose, nanowires with designed geometry, consisting of CoNi/Ni periodic segments, have been grown by designed electrodeposition into alumina templates. Experimental data allow one to conclude the presence of mono- and trivortex magnetic domains in CoNi segments but, unusually, these states are characterized by an asymmetric XMCD contrast across the nanowire's section.

Waveforms Analysis in Patients With Amyotrophic Lateral Sclerosis for Enhanced Efficacy of Mechanically Assisted Coughing.

Background: Effectiveness of mechanical assisted coughing with insufflation-exsufflation (MI-E) in amyotrophic lateral sclerosis (ALS) depends largely on severity of bulbar dysfunction, which can generate different upper-airway responses. The aim of the study was to evaluate the use of graphs generated by MI-E in ALS to detect airway obstruction and set parameters to achieve an effective mechanically assisted coughing.

Methods: This was a prospective study enrolling patients with ALS.

Wine yeast selection in the Iberian Peninsula: and non- as drivers of innovation in Spanish and Portuguese wine industries.

Yeast selection for the wine industry in Spain started in 1950 for the understanding of the microbial ecology, and for the selection of optimal strains to improve the performance of alcoholic fermentation and the overall wine quality. This process has been strongly developed over the last 30 years, firstly on , and, lately, with intense activity on non-. Several thousand yeast strains have been isolated, identified and tested to select those with better performance and/or specific technological properties.

Covalent Inhibition of the 20S Proteasome with Homobelactosin C Inquired by QM/MM Studies.

20S proteasome is a main player in the protein degradation pathway in the cytosol, thus intervening in multiple pivotal cellular processes. Over the years the proteasome has emerged as a crucial target for the treatment of many diseases such as neurodegenerative diseases, cancer, autoimmune diseases, developmental disorders, cystic fibrosis, diabetes, cardiac diseases, atherosclerosis, and aging. In this work, the mechanism of proteasome covalent inhibition with bisbenzyl-protected homobelactosin C (hBelC) was explored using quantum mechanics/molecular mechanics (QM/MM) methods.

Prediction of lung exposure to anti-tubercular drugs using plasma pharmacokinetic data: Implications for dose selection.

The development of novel candidate molecules for tuberculosis remains challenging, as drug distribution into the target tissue is not fully characterised in preclinical models of infection. Often antitubercular human dose selection is derived from pharmacokinetic data in plasma. Here, we explore whether whole-body physiologically-based pharmacokinetic (PBPK) modelling enables the prediction of lung exposure to anti-tubercular drugs in humans.

Halobenzene Clathrates of the Porous Metal-Organic Spin-Crossover Framework [Fe(tvp)(NCS)]. Stabilization of a Four-Step Transition.

Here we show that the porous metal-organic spin crossover (SCO) framework [Fe(tvp)(NCS)]@4(CHCN·HO) [] is an excellent precursor material for the systematic synthesis, via single-crystal to single-crystal transformation, of a series of halobenzene clathrates. Immersion of samples constituted of single crystals of in the liquid halobenzenes PhX, X = F ( = 1-6), X = Cl ( = 1, 2), and X = Br ( = 1) at room temperature induces complete replacement of the guest molecules by PhX to afford . Single-crystal analyses of the new clathrates confirm the integrity of the porous framework with the PhX guests being organized by pairs via π-stacking filling the nanochannels.

Two-Step Resist Deposition of E-Beam Patterned Thick Py Nanostructures for X-ray Microscopy.

Patterned elements of permalloy (Py) with a thickness as large as 300 nm have been defined by electron beam lithography on X-ray-transparent 50 nm thick membranes in order to characterize their magnetic structure via Magnetic Transmission X-ray Microscopy (MTXM). To avoid the situation where the fragility of the membranes causes them to break during the lithography process, it has been found that the spin coating of the resist must be applied in two steps. The MTXM results show that our samples have a central domain wall, as well as other types of domain walls, if the nanostructures are wide enough.

: attentional bias, emotional and psychophysiological response by pure exposure treatment in women with obesity.

Unlabelled: Obesity is one of the most important health problems nowadays. In addition to the direct physical consequences, it is also a risk factor in the development of psychological (Eating disorders, body dissatisfaction, depression, anxiety, etc.) and social problems.

The intriguing role of USP30 inhibitors as deubiquitinating enzymes from the patent literature since 2013.

Introduction: Ubiquitin specific peptidase 30 (USP30) is a mitochondrial deubiquitinase that antagonizes ubiquitination-mediated mitophagy of damaged or impaired mitochondria driven by the activity of PARK2/Parkin ubiquitin ligase and PINK1 protein kinase. Researchers have related low levels of USP30 to enhanced mitophagy and therefore have been pursuing mitophagy activation utilizing USP30 inhibitors as an alternative approach to target neurodegenerative disorders and other human diseases associated with defective mitophagy.

Areas Covered: This review covers the research and patent literature on the discovery and development of USP30 inhibitors since 2013.

ROX index as predictor of high flow nasal cannula therapy success in acute respiratory failure due to SARS-CoV-2.

Background: High-Flow Nasal Cannula (HFNC) therapy is useful treatment in patients with acute respiratory failure (ARF). The ROX index (ratio of pulse oximetry/fraction of inspired oxygen to respiratory rate) has been evaluated to predict success of HFNC in patients with pneumonia.

Objective: The aim of this study was to determine whether the ROX Index could predict HFNC therapy success in patients with ARF due to SARS-CoV-2 pneumonia.

A randomized phase II study comparing consolidation with a single dose of Y ibritumomab tiuxetan maintenance with rituximab for two years in patients with newly diagnosed follicular lymphoma responding to R-CHOP. Long-term follow-up results.

This is a randomized phase-2 trial aimed to compare consolidation vs. maintenance in untreated patients with follicular lymphoma (FL) responding to induction. 146 patients were enrolled from 25 Spanish institutions (ZAR2007; ClinicalTrials.

Effect of one-year dextromethorphan/quinidine treatment on management of respiratory impairment in amyotrophic lateral sclerosis.

Unlabelled: Treatment with Dextromethorphan/Quinidine (DM/Q) has demonstrated benefit on pseudobulbar affect and bulbar function in amyotrophic lateral sclerosis (ALS). The aim of this study was to assess whether DM/Q could provide long-term improvement in bulbar function and thereby prolong noninvasive respiratory management in ALS.

Materials And Methods: This prospective, case-cohort study, recruited ALS patients with bulbar dysfunction.

[Euthanasia: is this the law we need?].

The Spanish Euthanasia Law introduces a new right that is added to the portfolio of services provided by the Spanish health system and whose application is guaranteed within a period of 40 days. From the perspective of clinical experience, it is argued that without the effective right to quality palliative care and given the current shortcomings in dependant care, this law may send a threatening message to particularly fragile and dependant individuals that will lead to them feeling like a burden to their families and society. It is reasoned that basing the right to die on the dignity of the individual may have unexpected social repercussions.

Structural analysis and biochemical properties of laccase enzymes from two Pediococcus species.

Prokaryotic laccases are emergent biocatalysts. However, they have not been broadly found and characterized in bacterial organisms, especially in lactic acid bacteria. Recently, a prokaryotic laccase from the lactic acid bacterium Pediococcus acidilactici 5930, which can degrade biogenic amines, was discovered.

Tracheostomy in patients with COVID-19: predictors and clinical features.

Background: Around 20% of patients hospitalized for COVID-19 need mechanical ventilation (MV). MV may be prolonged, thus warranting tracheostomy.

Methods: Observational cohort study enrolling patients admitted due to COVID-19.

Revealing 3D magnetization of thin films with soft X-ray tomography: magnetic singularities and topological charges.

The knowledge of how magnetization looks inside a ferromagnet is often hindered by the limitations of the available experimental methods which are sensitive only to the surface regions or limited in spatial resolution. Here we report a vector tomographic reconstruction based on soft X-ray transmission microscopy and magnetic dichroism data, which has allowed visualizing the three-dimensional magnetization in a ferromagnetic thin film heterostructure. Different non-trivial topological textures have been resolved and the determination of their topological charge has allowed us to identify a Bloch point and a meron-like texture.