X-Ray Crystallography for Macromolecular Complexes.

X-ray crystallography has for most of the last century been the standard technique to determine the high-resolution structure of biological macromolecules, including multi-subunit protein-protein and protein-nucleic acids as large as the ribosome and viruses. As such, the successful application of X-ray crystallography to many biological problems revolutionized biology and biomedicine by solving the structures of small molecules and vitamins, peptides and proteins, DNA and RNA molecules, and many complexes-affording a detailed knowledge of the structures that clarified biological and chemical mechanisms, conformational changes, interactions, catalysis and the biological processes underlying DNA replication, translation, and protein synthesis. Now reaching well into the first quarter of the twenty-first century, X-ray crystallography shares the structural biology stage with cryo-electron microscopy and other innovative structure determination methods, as relevant and central to our understanding of biological function and structure as ever.

Protein-Protein Binding Kinetics by Biolayer Interferometry.

The specific kinetics and thermodynamics of protein-protein interactions underlie the molecular mechanisms of cellular functions; hence the characterization of these interaction parameters is central to the quantitative understanding of physiological and pathological processes. Many methods have been developed to study protein-protein interactions, which differ in various features including the interaction detection principle, the sensitivity, whether the method operates in vivo, in vitro, or in silico, the temperature control, the use of labels, immobilization, the amount of sample required, the number of measurements that can be accomplished simultaneously, or the cost. Bio-Layer Interferometry (BLI) is a label-free biophysical method to measure the kinetics of protein-protein interactions.

Decoding anaphylatoxins: unveiling the molecular mechanisms of complement receptor activation and signaling.

Recent advances in cryo-electron microscopy (Cryo-EM) have revolutionized our understanding of the complement C5a/C3a receptors that are crucial in inflammation. A recent report by Yadav et al. has elucidated the activation, ligand binding, selectivity, and signaling bias of these receptors, thereby enhancing structure-guided drug discovery.

Silencing of Amylomyces rouxii aspartic II protease by siRNA to increase tyrosinase activity.

Amylomyces rouxii is a zygomycete that produces extracellular protease and tyrosinase. The tyrosinase activity is negatively regulated by the proteases and, which attempts to purify the tyrosinase (tyr) enzyme that has been hampered by the presence of a protease that co-purified with it. In this work we identified genes encoding aspartic protease II (aspII) and VI of A.

Technologies for Managing the Health of Older Adults with Multiple Chronic Conditions: A Systematic Literature Review.

Multimorbidity is defined as the presence of two or more chronic medical conditions in a person, whether physical, mental or long-term infectious diseases. This is especially common in older populations, affecting their quality of life and emotionally impacting their caregivers and family. Technology can allow for monitoring, managing, and motivating older adults in their self-care, as well as supporting their caregivers.

Gene as a dynamical notion: An extensive and integrative vision. Redefining the gene concept, from traditional to genic-interaction, as a new dynamical version.

The current concept of gene has been very useful during the 20th and 21st centuries. However, recent advances in molecular biology and bioinformatics, which have further diversified the functional and adaptive profile of genetic information and its integration with cell physiology and environmental response, have contributed to focusing on additional new gene properties besides the traditional definition. Considering the inherent complexity of gene expression, whose adaptive objective must be referred to the Tortoise-Hare model, in which two tendencies converge, one focused on rapid adaptation to achieve survival, and the other that prevents an over-adaptation effect.

C4BP(β-)-mediated immunomodulation attenuates inflammation in DSS-induced murine colitis and in myeloid cells from IBD patients.

The most recent and promising therapeutic strategies for inflammatory bowel disease (IBD) have engaged biologics targeting single effector components involved in major steps of the immune-inflammatory processes, such as tumor necrosis factor, interleukins or integrins. Nevertheless, these molecules have not yet met expectations regarding efficacy and safety, resulting in a significant percentage of refractory or relapsing patients. Thus, novel treatment options are urgently needed.

Structural biology of complement receptors.

The complement system plays crucial roles in a wide breadth of immune and inflammatory processes and is frequently cited as an etiological or aggravating factor in many human diseases, from asthma to cancer. Complement receptors encompass at least eight proteins from four structural classes, orchestrating complement-mediated humoral and cellular effector responses and coordinating the complex cross-talk between innate and adaptive immunity. The progressive increase in understanding of the structural features of the main complement factors, activated proteolytic fragments, and their assemblies have spurred a renewed interest in deciphering their receptor complexes.

The structure of GAPDH sheds light into an immunoevasion factor that can target the anaphylatoxin C5a of innate immunity.

Leptospirosis is a neglected worldwide zoonosis involving farm animals and domestic pets caused by the Gram-negative spirochete . This bacterium deploys a variety of immune evasive mechanisms, some of them targeted at the complement system of the host's innate immunity. In this work, we have solved the X-ray crystallographic structure of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to 2.

Silencing of the Laccase () Gene from Causes Important Effects on the Formation of Toxocyst-like Structures and Fruiting Body.

A wide variety of biological functions, including those involved in the morphogenesis process of basidiomycete fungi, have been attributed to laccase enzymes. In this work, RNA interference (RNAi) was used to evaluate the role of the laccase () gene of PoB. Previously, transformant strains of were obtained and according to their level of silencing they were classified as light (T7), medium (T21) or severe (T26 and T27).

Soluble endoglin reduces thrombus formation and platelet aggregation via interaction with αIIbβ3 integrin.

Background: The circulating form of human endoglin (sEng) is a cleavage product of membrane-bound endoglin present on endothelial cells. Because sEng encompasses an RGD motif involved in integrin binding, we hypothesized that sEng would be able to bind integrin αIIbβ3, thereby compromising platelet binding to fibrinogen and thrombus stability.

Methods: In vitro human platelet aggregation, thrombus retraction, and secretion-competition assays were performed in the presence of sEng.

The crystal structure of iC3b-CR3 αI reveals a modular recognition of the main opsonin iC3b by the CR3 integrin receptor.

Complement activation on cell surfaces leads to the massive deposition of C3b, iC3b, and C3dg, the main complement opsonins. Recognition of iC3b by complement receptor type 3 (CR3) fosters pathogen opsonophagocytosis by macrophages and the stimulation of adaptive immunity by complement-opsonized antigens. Here, we present the crystallographic structure of the complex between human iC3b and the von Willebrand A inserted domain of the α chain of CR3 (αI).

Endophytic Fungal Terpenoids: Natural Role and Bioactivities.

Endophytic fungi are a highly diverse group of fungi that intermittently colonize all plants without causing symptoms of the disease. They sense and respond to physiological and environmental changes of their host plant and microbiome. The inter-organism interactions are largely driven by chemical networks mediated by specialized metabolites.

adaptation in cystic fibrosis patients increases C5a levels and promotes neutrophil recruitment.

Cystic fibrosis (CF) disease is characterized by an intense airway inflammatory response mediated by neutrophils and chronic respiratory infections caused by . High levels of the complement component C5a, the strongest neutrophil chemoattractant molecule, are commonly found in the CF lung and have been associated with a worsening of the disease. In this study, we investigated how the isolates from CF patients modulate the levels of C5a and identified the bacterial factors involved.

Surface-enhanced Raman spectroscopy and ultrastructural analysis of penicillin-producing Penicillium rubens strains.

Raman spectroscopy, transmission electron microscopy (TEM) and atomic force microscopy (AFM) techniques can perform chemical analyses and acquire high-resolution images of cell samples. For this reason, in this study, semi-thin sections of a single Penicillium rubens cell were analysed by Raman enhanced surface spectroscopy. The spectra showed peaks corresponding to the macromolecules that make up the cellular components.

Progressive Functional and Neuroretinal Affectation in Patients With Multiple Sclerosis Treated With Fingolimod.

Background: To evaluate the effect of fingolimod in visual function and neuroretinal structures in patients with multiple sclerosis (MS) for a period of 1 year.

Methods: This longitudinal and observational cohort study included 78 eyes of 78 patients with MS treated with fingolimod. All subjects were evaluated every 3 months during 12 months and compared with 32 patients treated with interferon beta.

Long-chain fatty acids alter transcription of virulence and regulatory genes.

Infection with is one of the most important risk factors for developing gastric cancer (GC). The type IV secretion system (T4SS) encoded in the pathogenicity island is the main virulence factor of associated with GC. Additionally, other virulence factors have been shown to play a role in the virulence, such as vacuolizing cytotoxin (VacA), urease, flagella, and adhesins.

Generation of a Soluble Form of Human Endoglin Fused to Green Fluorescent Protein.

Endoglin (Eng, CD105) is a type I membrane glycoprotein that functions in endothelial cells as an auxiliary receptor for transforming growth factor β (TGF-β)/bone morphogenetic protein (BMP) family members and as an integrin ligand, modulating the vascular pathophysiology. Besides the membrane-bound endoglin, there is a soluble form of endoglin (sEng) that can be generated by the action of the matrix metalloproteinase (MMP)-14 or -12 on the juxtamembrane region of its ectodomain. High levels of sEng have been reported in patients with preeclampsia, hypercholesterolemia, atherosclerosis and cancer.

Gaps, biases, and future directions in research on the impacts of anthropogenic land-use change on aquatic ecosystems: a topic-based bibliometric analysis.

Anthropogenic land use change (ALUC) satisfies human needs but also impacts aquatic ecosystems. Aquatic ecosystems are intrinsically linked with terrestrial landscapes, an association that is already recognized as a key factor to address future research and effective governance. However, the complexity and range of the impact of ALUC in aquatic ecosystems have been fundamental challenges and have implicitly routed the analysis to particular segments, drivers, management, or effects of the theme.

High-Efficiency Electroporation for Genetic Improvement of Fungal Strains.

Electroporation is a method for the introduction of molecules (usually nucleic acids) into a cell, consisting of submitting the cells to high-voltage and short electric pulses in the presence of the exogenous DNA/molecule. It is a versatile method, adaptable to different types of cells, from bacteria to cultured cells to higher eukaryotes, and thus has applications in many diverse fields, such as environmental biology, biotechnology, genetic engineering, and medicine. Electroporation has some advantages over other genetic transformation strategies, including the simplicity of the method, a wide range of adjustable parameters (possibility of optimization), high reproducibility and avoidance of the use of chemicals toxic to cells.

Lack of almagate interference in breath test results for Helicobacter pylori diagnosis (Almatest study).

Objective: The C-urea breath test (UBT) is the most widely used non-invasive diagnostic test for Helicobacter pylori. Debate continues to surround the possible interference of antacid intake on its result. This study aims to confirm the non-interference of almagate in the determination of H.

Food groups, diet quality and colorectal cancer risk in the Basque Country.

Background: The results obtained to date concerning food groups, diet quality and colorectal cancer (CRC) risk vary according to criteria used and the study populations.

Aim: To study the relationships between food groups, diet quality and CRC risk, in an adult population of the Basque Country (North of Spain).

Methods: This observational study included 308 patients diagnosed with CRC and 308 age- and sex-matched subjects as controls.