Neural and Onconeural Autoantibodies and Blood-Brain Barrier Disruption Markers in Patients Undergoing Radiotherapy for High-Grade Primary Brain Tumour.

Unlabelled: Radiotherapy (RT) plays a key role in brain tumours but can negatively impact functional outcomes and quality of life. The aim of this study was to analyse anti-neural and onconeural autoantibodies and markers of blood-brain barrier (BBB) disruption in patients with primary brain cancer undergoing RT.

Materials And Methods: A prospective study was conducted on 45 patients with a brain tumour scheduled for intensity-modulated radiotherapy.

The influence of various endocrine disruptors on the reproductive system.

Various stimulants (VS) are chemicals that disrupt the endocrine system - endocrine homeostasis of the reproductive system - which also known as endocrine-disrupting chemicals (EDCs). These substances are found in the human body, in both the blood and urine, amniotic fluid, or, among others, the adipose tissue. This article presents the current state of knowledge of the effect of EDCs and additional factors such as smoking, alcohol consumption, and cannabis on the gonads.

Maternal SARS-CoV-2 Infection at Delivery Increases IL-6 Concentration in Umbilical Cord Blood.

Background: SARS-CoV-2 infection in pregnant women may induce inflammation within the amniotic cavity and/or an increase in proinflammatory cytokines in fetal circulation. The aim was to investigate levels of IL-6 in maternal blood, umbilical cord blood, and amniotic fluid in pregnant women infected with SARS-CoV-2 at delivery.

Methods: A single-center prospective observational case-control study of pregnant women diagnosed with SARS-CoV-2 infection at delivery was conducted.

Glioblastoma Multiforme: The Latest Diagnostics and Treatment Techniques.

Background: Glioblastoma multiforme (GBM) is a WHO grade 4 glioma and the most common malignant primary brain tumour. Recently, there has been outstanding progress in the treatment of GBM. In addition to the newest form of GBM removal using fluorescence, three-dimensional (3D) imaging, tomoradiotherapy, moderate electro-hyperthermia, and adjuvant temozolomide (post-operative chemotherapy), new developments have been made in the fields of immunology, molecular biology, and virotherapy.

The association between lymph node metastases and long-term survival in patients with epithelial ovarian cancer.

Introduction: A key survival prognosis factor for patients treated for ovarian cancer is complete cytoreductive surgery where all macroscopic neoplastic implants, including enlarged metastatic lymph nodes, are removed. We presume that investigating the involvement of the lymphatic system can result in a more individualized approach to the treatment of ovarian cancer patients. The main aim of our study was to analyze the relationship between the presence, number and types of lymph node metastases and ovarian cancer patient prognosis.

Wilms' tumor 1 antigen immunoreactivity in epithelial ovarian cancer - diagnostic and prognostic value.

Objectives: Ovarian cancer is a heterogeneous disease, with a number of different histological subtypes with various responses to treatment. Wilms' tumor 1 (WT1) immunoreactivity is used to distinguish between OC's various subtypes. However, little is known about the protein's role as a prognostic factor.

Analysis of long-term outcomes in 44 patients following pelvic exenteration due to cervical cancer.

Background: Pelvic exenteration (PE) may be associated with prolonged overall survival (OS) in selected patients with advanced or recurrent cervical cancer. However, the factors related to improved survival following PE are not clearly defined. The aim of this study was to perform a retrospective analysis of OS rates in a group of patients undergoing PE in order to identify the factors related to improved long-term outcomes.

Assessment of Impact of Aramid Fibre Addition on the Mechanical Properties of Selected Asphalt Mixtures.

Various additives to asphalt binders and asphalt mixtures improving their properties are being used more and more frequently in order to improve the durability of road pavements. Such additives include various types of fibres, including aramid fibres. Tests concerning the impact of aramid fibre addition on the properties of selected asphalt mixtures have been described herein.

Psychiatric disorders and changes in immune response in labor and postpartum.

Women may present with psychiatric disorders during pregnancy, normal labor, following delivery by caesarean section, or in the postpartum period. The accumulating evidence suggests that these disorders may be due to changes in immune responses. During pregnancy complications such as the prolongation of cervical ripening or descent, placental abruption, premature labor, and preeclampsia increase the risk of postpartum psychiatric disorders.

An Analysis of Long-Term Outcomes in Patients Treated by Extensive Bowel Resection Due to Advanced Ovarian Cancer Relative to the Effectiveness of Surgery.

Introduction: Surgery for advanced ovarian cancer (AOC) often requires bowel resections. However, the impact of bowel surgery on patient overall survival (OS) has not yet been precisely determined.

Objective: The aim of the study was to analyze the OS rates in a group of AOC patients undergoing bowel resection.

Lithiation Substitution of Unprotected Benzyltetrazoles.

1-Tetrazoles occupy an important role in modern medicinal chemistry, but few methods for their modification exist. Many extant protocols require the use of a difficult to remove -alkyl-protecting group, precluding the products from use as carboxylate bioisosteres, the major role of tetrazoles in pharmaceuticals. We herein report a convenient, protecting-group-free lithiation-substitution protocol for benzylic tetrazoles.

A comparison of biological activity of commercially available purified native botulinum neurotoxin serotypes A1 to F1 in vitro, ex vivo, and in vivo.

Botulinum neurotoxin (BoNT) is a major therapeutic agent. Of seven native BoNT serotypes (A to G), only A and B are currently used in the clinic. Here we compared the potency of commercially available purified native serotypes A1 to F1 across in vitro, ex vivo, and in vivo assays.

Miro1-mediated mitochondrial positioning shapes intracellular energy gradients required for cell migration.

It has long been postulated, although never directly demonstrated, that mitochondria are strategically positioned in the cytoplasm to meet local requirements for energy production. Here we show that positioning of mitochondria in mouse embryonic fibroblasts (MEFs) determines the shape of intracellular energy gradients in living cells. Specifically, the ratio of ATP to ADP was highest at perinuclear areas of dense mitochondria and gradually decreased as more-peripheral sites were approached.

A Maximum-Likelihood Approach to Force-Field Calibration.

A new approach to the calibration of the force fields is proposed, in which the force-field parameters are obtained by maximum-likelihood fitting of the calculated conformational ensembles to the experimental ensembles of training system(s). The maximum-likelihood function is composed of logarithms of the Boltzmann probabilities of the experimental conformations, calculated with the current energy function. Because the theoretical distribution is given in the form of the simulated conformations only, the contributions from all of the simulated conformations, with Gaussian weights in the distances from a given experimental conformation, are added to give the contribution to the target function from this conformation.

Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease.

Defective mitochondrial distribution in neurons is proposed to cause ATP depletion and calcium-buffering deficiencies that compromise cell function. However, it is unclear whether aberrant mitochondrial motility and distribution alone are sufficient to cause neurological disease. Calcium-binding mitochondrial Rho (Miro) GTPases attach mitochondria to motor proteins for anterograde and retrograde transport in neurons.

Mitochondrial association, protein phosphorylation, and degradation regulate the availability of the active Rab GTPase Ypt11 for mitochondrial inheritance.

The Rab GTPase Ypt11 is a Myo2-binding protein implicated in mother-to-bud transport of the cortical endoplasmic reticulum (ER), late Golgi, and mitochondria during yeast division. However, its reported subcellular localization does not reflect all of these functions. Here we show that Ypt11 is normally a low-abundance protein whose ER localization is only detected when the protein is highly overexpressed.

Gem1 and ERMES do not directly affect phosphatidylserine transport from ER to mitochondria or mitochondrial inheritance.

In yeast, a protein complex termed the ER-Mitochondria Encounter Structure (ERMES) tethers mitochondria to the endoplasmic reticulum. ERMES proteins are implicated in a variety of cellular functions including phospholipid synthesis, mitochondrial protein import, mitochondrial attachment to actin, polarized mitochondrial movement into daughter cells during division, and maintenance of mitochondrial DNA (mtDNA). The mitochondrial-anchored Gem1 GTPase has been proposed to regulate ERMES functions.

Like-charged residues at the ends of oligoalanine sequences might induce a chain reversal.

We have examined the effect of like-charged residues on the conformation of an oligoalanine sequence. This was facilitated by circular dichroism (CD) and NMR spectroscopic and differential scanning calorimetric (DSC) measurements, and molecular dynamics calculations of the following three alanine-based peptides: Ac-K-(A)(5) -K-NH(2) (KAK5), Ac-K-(A)(4) -K-NH(2) (KAK4), Ac-K-(A)(3) -K-NH(2) (KAK3), where A and K denote alanine and lysine residues, respectively. Our earlier studies suggested that the presence of like-charged residues at the end of a short polypeptide chain composed of nonpolar residues can induce a chain reversal.

Identification of the epitope for anti-cystatin C antibody.

Human cystatin C (hCC), like many other amyloidogenic proteins, has been shown to form dimers by exchange of subdomains of the monomeric protein. Considering the model of hCC fibrillogenesis by propagated domain swapping, it seems possible that inhibition of this process should also suppress the entire process of dimerization and fibrillogenesis which leads to specific amyloidosis (hereditary cystatin C amyloid angiopathy (HCCAA)). It was reported that exogenous agents like monoclonal antibody against cystatin C are able to suppress formation of cystatin C dimers.

beta-hairpin-forming peptides; models of early stages of protein folding.

Formation of beta-hairpins is considered the initial step of folding of many proteins and, consequently, peptides constituting the beta-hairpin sequence of proteins (the beta-hairpin-forming peptides) are considered as models of early stages of protein folding. In this article, we discuss the results of experimental studies (circular-dichroism, infrared and nuclear magnetic resonance spectroscopy, and differential scanning calorimetry) of the structure of beta-hairpin-forming peptides excised from the B1 domain of protein G, which are known to fold on their own. We demonstrate that local interactions at the turn sequence and hydrophobic interactions between nonpolar residues are the dominant structure-determining factors, while there is no convincing evidence that stable backbone hydrogen bonds are formed in these peptides in aqueous solution.

Mechanism of formation of the C-terminal beta-hairpin of the B3 domain of the immunoglobulin-binding protein G from Streptococcus. IV. Implication for the mechanism of folding of the parent protein.

A 34-residue alpha/beta peptide [IG(28-61)], derived from the C-terminal part of the B3 domain of the immunoglobulin binding protein G from Streptoccocus, was studied using CD and NMR spectroscopy at various temperatures and by differential scanning calorimetry. It was found that the C-terminal part (a 16-residue-long fragment) of this peptide, which corresponds to the sequence of the beta-hairpin in the native structure, forms structure similar to the beta-hairpin only at T = 313 K, and the structure is stabilized by non-native long-range hydrophobic interactions (Val47-Val59). On the other hand, the N-terminal part of IG(28-61), which corresponds to the middle alpha-helix in the native structure, is unstructured at low temperature (283 K) and forms an alpha-helix-like structure at 305 K, and only one helical turn is observed at 313 K.

Mechanism of formation of the C-terminal beta-hairpin of the B3 domain of the immunoglobulin binding protein G from Streptococcus. III. Dynamics of long-range hydrophobic interactions.

A 20-residue peptide, IG(42-61), derived from the C-terminal beta-hairpin of the B3 domain of the immunoglobulin binding protein G from Streptoccocus was studied using circular dichroism, nuclear magnetic resonance (NMR) spectroscopy at various temperatures and by differential scanning calorimetry (DSC). Unlike other related peptides studied so far, this peptide displays two heat capacity peaks in DSC measurements (at a scanning rate of 1.5 deg/min at a peptide concentration of 0.

Chaperones in control of protein disaggregation.

The chaperone protein network controls both initial protein folding and subsequent maintenance of proteins in the cell. Although the native structure of a protein is principally encoded in its amino-acid sequence, the process of folding in vivo very often requires the assistance of molecular chaperones. Chaperones also play a role in a post-translational quality control system and thus are required to maintain the proper conformation of proteins under changing environmental conditions.