Navigating from cellular phenotypic screen to clinical candidate: selective targeting of the NLRP3 inflammasome.

The NLRP3 inflammasome plays a pivotal role in host defense and drives inflammation against microbial threats, crystals, and danger-associated molecular patterns (DAMPs). Dysregulation of NLRP3 activity is associated with various human diseases, making it an attractive therapeutic target. Patients with NLRP3 mutations suffer from Cryopyrin-Associated Periodic Syndrome (CAPS) emphasizing the clinical significance of modulating NLRP3.

Enhancing melt strength and crystallization kinetics in polylactide: Influence of chain topology.

The generation of long-chain branches (LCB) in biobased and biodegradable polylactide (PLA) by adding different amounts of a chain extender is studied. The rheological and calorimetric behavior have been used to determine the effect of LCB presence and their topology on PLA melt strength and crystallization behavior. Rheological modeling of linear and non-linear viscoelastic shear and extensional properties identified several possible branched structures.

Chromosome-scale genome assembly and annotation of Paspalum notatum Flüggé var. saurae.

Paspalum notatum Flüggé is an economically important subtropical fodder grass that is widely used in the Americas. Here, we report a new chromosome-scale genome assembly and annotation of a diploid biotype collected in the center of origin of the species. Using Oxford Nanopore long reads, we generated a 557.

Binding Affinity of Trastuzumab and Pertuzumab Monoclonal Antibodies to Extracellular HER2 Domain.

The binding affinity of trastuzumab and pertuzumab to HER2 has been studied using both experimental and in silico methods. The experiments were conducted using the antibodies in their complete IgG form, as used in clinical therapy, and the extracellular domain of the HER2 protein in solution. This approach provides a precise, reproducible, and reliable view of the interaction between them in physicochemical conditions similar to those found in the tumoral environment.

TRIMETHYLGUANOSINE SYNTHASE1 mutations decanalize female germline development in Arabidopsis.

Here, we report the characterization of a plant RNA methyltransferase, orthologous to yeast trimethylguanosine synthase1 (Tgs1p) and whose downregulation was associated with apomixis in Paspalum grasses. Using phylogenetic analyses and yeast complementation, we determined that land plant genomes all encode a conserved, specific TGS1 protein. Next, we studied the role of TGS1 in female reproduction using reporter lines and loss-of-function mutants in Arabidopsis thaliana.

Magnetic resonance imaging findings of spontaneous pyomyoma in a premenopausal woman managed with myomectomy: A case report.

Background: Acute fibroid complications are rare. However, failure to recognize and treat acute complications expeditiously when they occur can lead to catastrophic, even deadly, complications. Pyomyoma is a rare but potentially fatal condition resulting from infarction and infection of a fibroid through bacterial seeding and direct, hematogenous, or lymphatic dissemination.

PET/Graphene Nanocomposite Fibers Obtained by Dry-Jet Wet-Spinning for Conductive Textiles.

The combination of polyethylene terephthalate (PET), one of the most used polymers in the textile industry, with graphene, one of the most outstanding conductive materials in recent years, represents a promising strategy for the preparation of conductive textiles. This study focuses on the preparation of mechanically stable and conductive polymer textiles and describes the preparation of PET/graphene fibers by the dry-jet wet-spinning method from nanocomposite solutions in trifluoroacetic acid. Nanoindentation results show that the addition of a small amount of graphene (2 wt.

ORIGIN OF RECOGNITION COMPLEX 3 controls the development of maternal excess endosperm in the Paspalum simplex agamic complex (Poaceae).

Pseudogamous apomixis in Paspalum simplex generates seeds with embryos genetically identical to the mother plant and endosperms deviating from the canonical 2(maternal):1(paternal) parental genome contribution into a maternal excess 4m:1p genome ratio. In P. simplex, the gene homologous to that coding for subunit 3 of the ORIGIN OF RECOGNITION COMPLEX (PsORC3) exists in three isogenic forms: PsORC3a is apomixis specific and constitutively expressed in developing endosperm whereas PsORCb and PsORCc are up-regulated in sexual endosperms and silenced in apomictic ones.

Emergency department observation of patients with acute heart failure prior to hospital admission: impact on short-term prognosis.

Objectives: To analyze whether short-term outcomes are affected when patients diagnosed with acute heart failure (AHF) spend time in an emergency department observation unit (EDOU) before hospital admission.

Material And Methods: Baseline and emergency episode data were collected for patients diagnosed with AHF in the EDs of 15 Spanish hospitals. We analyzed crude and adjusted associations between EDOU stay and 30-day mortality (primary outcome) and in-hospital mortality and a prolonged hospital stay of more than 7 days (secondary outcomes).

CroniCare: Platform for the Design and Implementation of Follow-Up, Control and Self-Management Interventions for Chronic and Multimorbidity Patients Based on Mobile Technologies.

The project proposes to facilitate the design and evaluation of interventions based on mobile technologies and information systems in order to improve the capacity for self-management, empowerment and control of chronic and multimorbidity patients. The system allows to create customizable apps according to the needs of primary care and specialized care. The project includes an evaluation of the impact of the care model, as well as the effectiveness and efficiency of the intervention through a study with 124 multimorbidity patients.

Melting Temperature Depression of Polymer Single Crystals: Application to the Eco-Design of Tie-Layers in Polyolefinic-Based Multilayered Films.

In this paper, we describe a method for determining polymer compatibility, which will aid in establishing the requirements of polyolefinic materials for the eco-design of multilayer films for mechanical recycling while avoiding the use of reactive tie layers. Our ultimate goal is to define the molecular characteristics of the polyolefinic structural layer that improve compatibility with the tie layer during mechanical recycling. We have investigated the melting temperature depression of single crystals of various polyethylenes embedded in commercial polymeric matrices with various functionalities (ester, acrylate, acetate and methacrylic acid sodium ionomer), which can be potentially used as tie layers.

Rheology of Poly(glycidyl methacrylate) Macromolecular Nano Assemblies.

A recently reported combined polymerization process of glycidyl methacrylate, mediated by homometallic and heterobimetallic aluminium complexes, naturally produces nano-sized macromolecular assemblies. In this work, the morphological features and the rheological properties of these novel nanoassemblies are studied. The hydrodynamic sizes of the nanoparticles in the solution range from 10 to 40 nm (in numbers), but on a flat surface they adopt a characteristic thin disk shape.

Scaffold Hopping to Imidazo[1,2-]pyrazin-8-one Positive Allosteric Modulators of Metabotropic Glutamate 2 Receptor.

Glutamate hyperfunction is implicated in multiple neurological and psychiatric diseases. Activation of the mGlu2 receptor results in reduced glutamate release and decreased excitability representing a promising novel therapeutic agent for the treatment of disorders such as epilepsy, schizophrenia, mood, anxiety, and other neuropsychiatric disorders. We have previously reported substantial efforts leading to potent and selective mGlu2 PAMs from different chemical series.

A Semi-Deterministic Random Walk with Resetting.

We consider a discrete-time random walk (xt) which, at random times, is reset to the starting position and performs a deterministic motion between them. We show that the quantity Prxt+1=n+1|xt=n,n→∞ determines if the system is averse, neutral or inclined towards resetting. It also classifies the stationary distribution.

Poly(glycidyl methacrylate) macromolecular assemblies as biocompatible nanocarrier for the antimicrobial lysozyme.

The antimicrobial lysozyme (Lys) was electrostatically incorporated to negatively charged crosslinked poly(glycidyl methacrylate) (c-PGMA) macromolecular assemblies. The resulting material was characterized by AFM, infrared spectra, water contact angle measurements and the staining with the primary amino specific dye fluorescamine. c-PGMA nanoparticles were successfully loaded with Lys reaching ratios of 27.

Biofilm mechanics in an extremely acidic environment: microbiological significance.

A variety of natural biofilms were collected from an extremely acidic environment at Río Tinto (Spain). In order to provide insights into the structure-function relationship, the microstructure of the biofilms was explored using low temperature scanning electron microscopy (LTSEM) in combination with rheological analysis. The creep-recovery experiment results have demonstrated the typical behaviour of viscoelastic materials that combine both elastic and viscous characters.

Diazaspirononane Nonsaccharide Inhibitors of O-GlcNAcase (OGA) for the Treatment of Neurodegenerative Disorders.

O-GlcNAcylation is a post-translational modification of tau understood to lower the speed and yield of its aggregation, a pathological hallmark of Alzheimer's disease (AD). O-GlcNAcase (OGA) is the only enzyme that removes O-linked -acetyl-d-glucosamine (O-GlcNAc) from target proteins. Therefore, inhibition of OGA represents a potential approach for the treatment of AD by preserving the O-GlcNAcylated tau protein.

Management of Large Vessel Occlusion Stroke Related to Infective Endocarditis: Is Mechanical Thrombectomy a Safe Option?

Introduction: Acute ischemic stroke is the most common neurological complication of infective endocarditis. Intravenous thrombolysis is contraindicated in these patients due to a higher risk of hemorrhagic complications. Whether mechanical thrombectomy has some benefit in these patients remains unanswered although some favorable results can be found in literature.

[Prevalence of Neisseria gonorrhoeae, amongst inmates of the Preventive Reclusion Center in Arica].

Background: Sex workers, people with drug addiction, early onset of sexual activity population, and criminal population, are considered the groups most at risk of contracting sexually transmitted infections (STIs).

Aim: To determine the prevalence of infection by Neisseria gonorrhoeae in inmates of the Preventive Detention Center (CDP) at Arica and Parinacota Region, Chile. The Scientific Ethical Committee of Universidad de Tarapacá approved this study.

Genetic contribution of endoplasmic reticulum aminopeptidase 1 polymorphisms to liver fibrosis progression in patients with HCV infection.

The endoplasmic reticulum aminopeptidase ERAP1 regulates innate and adaptive immune responses, trimming peptides and loading onto HLA class I molecules. Coding single nucleotide polymorphisms within ERAP1 are associated with autoimmune diseases, viral infections, and cancer development. Our purpose was to analyze the influence of ERAP1 variants on fibrogenesis in hepatitis C virus (HCV)-infected patients.

Optimisation in the multidisciplinary approach to patients with hepatitis C in the era of direct-acting antivirals.

The advents of current direct-acting antiviral treatments has revolutionised the therapeutic approach to hepatitis C, increasing cure rates to above 90% and substantially simplifying treatment, which translates into benefits for patients, clinicians and the health system. These new drugs allow cure to be achieved, irrespective of the patient's characteristics, with tolerability similar to that of placebo and few drug reactions with concomitant medication. This in turn improves patients' quality of life and wellbeing.

The Plecoptera of Panama. IV. Description of the last nymphal instar for two species of Anacroneuria Klapálek (Plecoptera: Perlidae) from the Caldera River, Chiriquí, Panamá.

The last nymphal instars of Anacroneuria planicollis Klapálek, 1923 and A. quetzali Gutiérrez-Fonseca and Springer, 2015 are described from the Caldera River, Chiriquí Province, Panamá. The adult female of A.

Spiro-oxindole Piperidines and 3-(Azetidin-3-yl)-1-benzimidazol-2-ones as mGlu Receptor PAMs.

Starting from two weak mGlu receptor positive allosteric modulator (PAM) HTS hits ( and ), a molecular hybridization strategy resulted in the identification of a novel spiro-oxindole piperidine series with improved activity and metabolic stability. Scaffold hopping around the spiro-oxindole core identified the 3-(azetidin-3-yl)-1-benzimidazol-2-one as bioisoster. Medicinal chemistry optimization of these two novel chemotypes resulted in the identification of potent, selective, orally bioavailable, and brain penetrant mGluR PAMs.