Effect of Cyclin-Dependent Kinase 4/6 Inhibitors on Circulating Cells in Patients with Metastatic Breast Cancer.

The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) is the standard-of-care for estrogen receptor (ER)-positive, HER2-negative (ER+/HER2- advanced/metastatic breast cancer (mBC). However, the impact of CDK4/6i on circulating immune cells and circulating tumor cells (CTCs) in patients receiving CDK4/6i and ET (CDK4/6i+ET) remains poorly understood. This was a prospective cohort study including 44 patients with ER+/HER2- mBC treated with CDK4/6i+ET in either first or second line.

Efficiency of carboxymethylcellulose in red wine tartaric stability: Effect on wine phenolic composition, chromatic characteristics and colouring matter stability.

In this work, the effect of carboxymethylcellulose structural features on the efficiency to prevent potassium hydrogen tartrate precipitation in red wines and on the phenolic composition, chromatic characteristics and colouring matter stability was studied. The degree of substitution of carboxymethylcellulose was important for its efficiency in highly unstable wines. Application of carboxymethylcellulose doesn't result in a significant change in the phenolic, monomeric anthocyanin composition, colour intensity, and chromatic characteristics of red wines.

Genetic code ambiguity modulates the activity of a C. albicans MAP kinase linked to cell wall remodeling.

The human fungal pathogen Candida albicans ambiguously decodes the universal leucine CUG codon predominantly as serine but also as leucine. C. albicans has a high capacity to survive and proliferate in adverse environments but the rate of leucine incorporation fluctuates in response to different stress conditions.

Probing the Occurrence of Soluble Oligomers through Amyloid Aggregation Scaling Laws.

Drug discovery frequently relies on the kinetic analysis of physicochemical reactions that are at the origin of the disease state. Amyloid fibril formation has been extensively investigated in relation to prevalent and rare neurodegenerative diseases, but thus far no therapeutic solution has directly arisen from this knowledge. Other aggregation pathways producing smaller, hard-to-detect soluble oligomers are increasingly appointed as the main reason for cell toxicity and cell-to-cell transmissibility.

Distribution of Amyloid-Like and Oligomeric Species from Protein Aggregation Kinetics.

Amyloid fibrils and soluble oligomers are two types of protein aggregates associated with neurodegeneration. Classic therapeutic strategies try to prevent the nucleation and spread of amyloid fibrils, whilst diffusible oligomers have emerged as promising drug targets affecting downstream pathogenic processes. We developed a generic protein aggregation model and validate it against measured compositions of fibrillar and non-fibrillar assemblies of ataxin-3, a protein implicated in Machado-Joseph disease.

SUMOylation of the brain-predominant Ataxin-3 isoform modulates its interaction with p97.

Background: Machado-Joseph Disease (MJD), a form of dominantly inherited ataxia belonging to the group of polyQ expansion neurodegenerative disorders, occurs when a threshold value for the number of glutamines in Ataxin-3 (Atx3) polyglutamine region is exceeded. As a result of its modular multidomain architecture, Atx3 is known to engage in multiple macromolecular interactions, which might be unbalanced when the polyQ tract is expanded, culminating in the aggregation and formation of intracellular inclusions, a unifying fingerprint of this group of neurodegenerative disorders. Since aggregation is specific to certain brain regions, localization-dependent posttranslational modifications that differentially affect Atx3 might also contribute for MJD.

Examination of Ataxin-3 (atx-3) Aggregation by Structural Mass Spectrometry Techniques: A Rationale for Expedited Aggregation upon Polyglutamine (polyQ) Expansion.

Expansion of polyglutamine stretches leads to the formation of polyglutamine-containing neuronal aggregates and neuronal death in nine diseases for which there currently are no treatments or cures. This is largely due to a lack in understanding of the mechanisms by which expanded polyglutamine regions contribute to aggregation and disease. To complicate matters further, several of the polyglutamine-disease related proteins, including ataxin-3, have a multistage aggregation mechanism in which flanking domain self-assembly precedes polyglutamine aggregation yet is influenced by polyglutamine expansion.

Structure of mycobacterial maltokinase, the missing link in the essential GlgE-pathway.

A novel four-step pathway identified recently in mycobacteria channels trehalose to glycogen synthesis and is also likely involved in the biosynthesis of two other crucial polymers: intracellular methylglucose lipopolysaccharides and exposed capsular glucan. The structures of three of the intervening enzymes - GlgB, GlgE, and TreS - were recently reported, providing the first templates for rational drug design. Here we describe the structural characterization of the fourth enzyme of the pathway, mycobacterial maltokinase (Mak), uncovering a eukaryotic-like kinase (ELK) fold, similar to methylthioribose kinases and aminoglycoside phosphotransferases.

Structural basis for host membrane remodeling induced by protein 2B of hepatitis A virus.

Unlabelled: The complexity of viral RNA synthesis and the numerous participating factors require a mechanism to topologically coordinate and concentrate these multiple viral and cellular components, ensuring a concerted function. Similarly to all other positive-strand RNA viruses, picornaviruses induce rearrangements of host intracellular membranes to create structures that act as functional scaffolds for genome replication. The membrane-targeting proteins 2B and 2C, their precursor 2BC, and protein 3A appear to be primarily involved in membrane remodeling.

Development and characterization of a PHB-HV-based 3D scaffold for a tissue engineering and cell-therapy combinatorial approach for spinal cord injury regeneration.

Spinal cord injury (SCI) leads to devastating neurological deficits. Several tissue engineering (TE)-based approaches have been investigated for repairing this condition. Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB-HV) is found to be particularly attractive for TE applications due to its properties, such as biodegradability, biocompatibility, thermoplasticity and piezoelectricity.

Biochemical and biophysical characterization of recombinant yeast proteasome maturation factor ump1.

Protein degradation is essential for maintaining cellular homeostasis. The proteasome is the central enzyme responsible for non-lysosomal protein degradation in eukaryotic cells. Although proteasome assembly is not yet completely understood, a number of cofactors required for proper assembly and maturation have been identified.

Benefits of spine stabilization with biodegradable scaffolds in spinal cord injured rats.

Spine stabilization upon spinal cord injury (SCI) is a standard procedure in clinical practice, but rarely employed in experimental models. Moreover, the application of biodegradable biomaterials for this would come as an advantage as it would eliminate the presence of a nondegradable prosthesis within the vertebral bone. Therefore, in the present work, we propose the use of a new biodegradable device specifically developed for spine stabilization in a rat model of SCI.

The secretome of stem cells isolated from the adipose tissue and Wharton jelly acts differently on central nervous system derived cell populations.

Introduction: It is hypothesized that administration of stromal/stem cells isolated from the adipose tissue (ASCs) and umbilical cord (HUCPVCs) can ameliorate the injured central nervous system (CNS). It is still not clear, however, whether they have similar or opposite effects on primary cultures of neuronal populations. The objective of the present work was to determine if ASCs and HUCPVCs preferentially act, or not, on specific cell populations within the CNS.

Carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles in central nervous systems-regenerative medicine: effects on neuron/glial cell viability and internalization efficiency.

The applicability of CMCht/PAMAM dendrimer nanoparticles for CNS applications was investigated. AFM and TEM observations revealed that the nanoparticles possessed a nanosphere-like shape with a size from 22.0 to 30.

Role of human umbilical cord mesenchymal progenitors conditioned media in neuronal/glial cell densities, viability, and proliferation.

It has been recently reported that mesenchymal progenitor/stem cells isolated from the Wharton's Jelly (WJ) of umbilical cords (UC) ameliorate the condition of animals suffering from central nervous system (CNS)-related conditions. However, little is known on the mechanisms that regulate these actions. Therefore, the objective of the present work was to determine how the conditioned media (CM) of a population of mesenchymal progenitors present in the UC WJ, known as human umbilical cord perivascular cells (HUCPVCs), regulate processes such as cell viability, survival, and proliferation of postnatal hippocampal neurons and glial cells.