Clinical and radiologic criteria to predict endoscopic third ventriculostomy success in non-communicating pediatric hydrocephalus.

Objective: Endoscopic third ventriculocisternostomy (ETV) became the relevant treatment option for non-communicating pediatric hydrocephalus. ETV success was predicted in relation to age, diagnosis, and previous shunt implantation. Radiological factors are usually taken for indication decision-making.

A PDZ tandem repeat folds and unfolds via different pathways.

Protein folding and unfolding experiments are interpreted under the assumption of microscopic reversibility, that is, that at equilibrium one process is the reverse of the other. Single-domain proteins illustrate the validity of such an interpretation, although reversibility does not necessarily hold under the different conditions typically used for folding and unfolding experiments. In fact, more complex proteins, which often exhibit irreversible unfolding, are generally considered not amenable to folding kinetics studies.

Stented endoscopic third ventriculostomy: technique, safety, and indications-a multicenter multinational study.

Purpose: Endoscopic third ventriculostomy (ETV) is an effective treatment for obstructive hydrocephalus. Secondary stoma closure may be life threatening and is the most common reason for late ETV failure, mostly secondary to local scarring. Local stents intended to maintain patency are rarely used.

Folding and Binding Kinetics of the Tandem of SH2 Domains from SHP2.

The SH2 domains of SHP2 play a crucial role in determining the function of the SHP2 protein. While the folding and binding properties of the isolated NSH2 and CSH2 domains have been extensively studied, there is limited information about the tandem SH2 domains. This study aims to elucidate the folding and binding kinetics of the NSH2-CSH2 tandem domains of SHP2 through rapid kinetic experiments, complementing existing data on the isolated domains.

PDZ2-conjugated-PLGA nanoparticles are tiny heroes in the battle against SARS-CoV-2.

The COVID-19 pandemic caused by SARS-CoV-2 has highlighted the urgent need for innovative antiviral strategies to fight viral infections. Although a substantial part of the overall effort has been directed at the Spike protein to create an effective global vaccination strategy, other proteins have also been examined and identified as possible therapeutic targets. Among them, although initially underestimated, there is the SARS-CoV-2 E-protein, which turned out to be a key factor in viral pathogenesis due to its role in virus budding, assembly and spreading.

The Mechanism of Folding of Human Frataxin in Comparison to the Yeast Homologue - Broad Energy Barriers and the General Properties of the Transition State.

The funneled energy landscape theory suggests that the folding pathway of homologous proteins should converge at the late stages of folding. In this respect, proteins displaying a broad energy landscape for folding are particularly instructive, allowing inferring both the early, intermediate and late stages of folding. In this paper we explore the folding mechanisms of human frataxin, an essential mitochondrial protein linked to the neurodegenerative disorder Friedreich's ataxia.

The binding selectivity of the C-terminal SH3 domain of Grb2, but not its folding pathway, is dictated by its contiguous SH2 domain.

The adaptor protein Grb2, or growth factor receptor-bound protein 2, possesses a pivotal role in the transmission of fundamental molecular signals in the cell. Despite lacking enzymatic activity, Grb2 functions as a dynamic assembly platform, orchestrating intracellular signals through its modular structure. This study delves into the energetic communication of Grb2 domains, focusing on the folding and binding properties of the C-SH3 domain linked to its neighboring SH2 domain.

Exploring the short linear motif-mediated protein-protein interactions of CrkL through ProP-PD.

Adaptor proteins play a pivotal role in cellular signaling mediating a multitude of protein-protein interaction critical for cellular homeostasis. Dysregulation of these interactions has been linked to the onset of various cancer pathologies and exploited by viral pathogens during host cell takeover. CrkL is an adaptor protein composed of an N-terminal SH2 domain followed by two SH3 domains that mediate interactions with diverse partners through the recognition of specific binding motifs.

Addressing the Binding Mechanism of the Meprin and TRAF-C Homology Domain of the Speckle-Type POZ Protein Using Protein Engineering.

Protein-protein interactions play crucial roles in a wide range of biological processes, including metabolic pathways, cell cycle progression, signal transduction, and the proteasomal system. For PPIs to fulfill their biological functions, they require the specific recognition of a multitude of interacting partners. In many cases, however, protein-protein interaction domains are capable of binding different partners in the intracellular environment, but they require precise regulation of the binding events in order to exert their function properly and avoid misregulation of important molecular pathways.

Characterization of the folding and binding properties of the PTB domain of FRS2 with phosphorylated and unphosphorylated ligands.

PTB (PhosphoTyrosine Binding) domains are protein domains that exert their function by binding phosphotyrosine residues on other proteins. They are commonly found in a variety of signaling proteins and are important for mediating protein-protein interactions in numerous cellular processes. PTB domains can also exhibit binding to unphosphorylated ligands, suggesting that they have additional binding specificities beyond phosphotyrosine recognition.

An intramolecular energetic network regulates ligand recognition in a SH2 domain.

In an effort to investigate the molecular determinants of ligand recognition of the C-terminal SH2 domain of the SHP2 protein, we conducted extensive site-directed mutagenesis and kinetic binding experiments with a peptide mimicking a specific portion of a physiological ligand (the scaffold protein Gab2). Obtained data provided an in-depth characterization of the binding reaction, allowing us to pinpoint residues topologically far from the binding pocket of the SH2 domain to have a role in the recognition and binding of the peptide. The presence of a sparse energetic network regulating the interaction with Gab2 was identified and characterized through double mutant cycle analysis, performed by challenging all the designed site-directed variants of C-SH2 with a Gab2 peptide mutated at +3 position relative to its phosphorylated tyrosine, a key residue for C-SH2 binding specificity.

Biophysical Characterization of the Binding Mechanism between the MATH Domain of SPOP and Its Physiological Partners.

SPOP (Speckle-type POZ protein) is an E3 ubiquitin ligase adaptor protein that mediates the ubiquitination of several substrates. Furthermore, SPOP is responsible for the regulation of both degradable and nondegradable polyubiquitination of a number of substrates with diverse biological functions. The recognition of SPOP and its physiological partners is mediated by two protein-protein interaction domains.

Monomeric and dimeric states of human ZO1-PDZ2 are functional partners of the SARS-CoV-2 E protein.

The Envelope (E) protein of SARS-CoV-2 plays a key role in virus maturation, assembly, and virulence mechanisms. The E protein is characterized by the presence of a PDZ-binding motif (PBM) at its C-terminus that allows it to interact with several PDZ-containing proteins in the intracellular environment. One of the main binding partners of the SARS-CoV-2 E protein is the PDZ2 domain of ZO1, a protein with a crucial role in the formation of epithelial and endothelial tight junctions (TJs).

Biopsies of Caudal Brainstem Tumors in Pediatric Patients-A Single-Center Retrospective Case Series.

Objective: The indication for performing biopsies in patients with diffuse lesions in the brain stem is controversial. The possible risks associated with the technically challenging interventions must be balanced against clarifying the diagnosis and the possible therapeutic options. We reviewed the feasibility, risk profile, and diagnostic yield of different biopsy techniques in a pediatric cohort.

Different electrostatic forces drive the binding kinetics of SARS-CoV, SARS-CoV-2 and MERS-CoV Envelope proteins with the PDZ2 domain of ZO1.

The Envelope protein (E) is a structural protein encoded by the genome of SARS-CoV, SARS-CoV-2 and MERS-CoV Coronaviruses. It is poorly present in the virus but highly expressed in the host cell, with prominent role in virus assembly and virulence. The E protein possesses a PDZ-binding motif (PBM) at its C terminus that allows it to interact with host PDZ domain containing proteins.

Understanding the molecular basis of folding cooperativity through a comparative analysis of a multidomain protein and its isolated domains.

Although cooperativity is a well-established and general property of folding, our current understanding of this feature in multidomain folding is still relatively limited. In fact, there are contrasting results indicating that the constituent domains of a multidomain protein may either fold independently on each other or exhibit interdependent supradomain phenomena. To address this issue, here we present the comparative analysis of the folding of a tandem repeat protein, comprising two contiguous PDZ domains, in comparison to that of its isolated constituent domains.

SH2 Domains: Folding, Binding and Therapeutical Approaches.

SH2 (Src Homology 2) domains are among the best characterized and most studied protein-protein interaction (PPIs) modules able to bind and recognize sequences presenting a phosphorylated tyrosine. This post-translational modification is a key regulator of a plethora of physiological and molecular pathways in the eukaryotic cell, so SH2 domains possess a fundamental role in cell signaling. Consequently, several pathologies arise from the dysregulation of such SH2-domains mediated PPIs.

Exploring the effect of tethered domains on the folding of Grb2 protein.

Two thirds of eukaryotic proteins have evolved as multidomain constructs, and in vivo, domains fold within a polypeptide chain, with inter-domain interactions possibly crucial for correct folding. However, to date, most of the experimental folding studies are based on domains in isolation. In an effort to better understand multidomain folding, in this work we analyzed, through equilibrium and kinetic folding experiments, the folding properties of the Growth factor receptor-bound protein 2 (Grb2), composed by one SRC homology 2 domain flanked by two SRC homology 3 domains.

Maneuver protocol for outpatient telemetric intracranial pressure monitoring in hydrocephalus patients.

Introduction: Telemetric intracranial pressure measurement (tICPM) offers new opportunities to acquire objective information in shunted and non-shunted patients. The sensor reservoir (SR) provides tICPM modality at a decent sampling rate as an integrated component of the CSF shunt system. The aim of this study is to perform tICPM during a defined protocol of maneuvers in an outpatient setting as feasibility study including either shunt-dependent patients or candidates for possible shunt therapy.

Folding and Binding Mechanisms of the SH2 Domain from Crkl.

SH2 domains are structural modules specialized in the recognition and binding of target sequences containing a phosphorylated tyrosine residue. They are mostly incorporated in the 3D structure of scaffolding proteins that represent fundamental regulators of several signaling pathways. Among those, Crkl plays key roles in cell physiology by mediating signals from a wide range of stimuli, and its overexpression is associated with several types of cancers.

Characterization of early and late transition states of the folding pathway of a SH2 domain.

Albeit SH2 domains are abundant protein-protein interaction modules with fundamental roles in the regulation of several physiological and molecular pathways in the cell, the available information about the determinants of their thermodynamic stability and folding properties are still very limited. In this work, we provide a quantitative characterization of the folding pathway of the C-terminal SH2 domain of SHP2, conducted through a combination of site-directed mutagenesis and kinetic (un)folding experiments (Φ-value analysis). The energetic profile of the folding reaction of the C-SH2 domain is described by a three-state mechanism characterized by the presence of two transition states and a high-energy intermediate.

Retrospective single-center historical comparative study between proGAV and proGAV2.0 for surgical revision and implant duration.

Objective: Cerebrospinal fluid (CSF) diversion shunt systems remain to be the most common treatment for pediatric hydrocephalus. Different valve systems are used to regulate CSF diversion. Preventing complications such as occlusions, ruptures, malpositioning, and over- or underdrainage are the focus for further developments.