How important is the N-terminal acetylation of alpha-synuclein for its function and aggregation into amyloids?

N-α-acetylation is a frequently occurring post-translational modification in eukaryotic proteins. It has manifold physiological consequences on the regulation and function of several proteins, with emerging studies suggesting that it is a global regulator of stress responses. For decades, biochemical investigations into the precise role of the intrinsically disordered protein alpha-synuclein (αS) in the etiology of Parkinson's disease (PD) were performed using non-acetylated αS.

Orthostatic Myoclonic Jerks in a Case of Hashimoto's Encephalopathy.

Hashimoto's encephalopathy (HE) is an uncommon syndrome with the characteristic triad of positive antithyroid antibodies (most commonly antibodies to thyroid peroxidase), response to steroids, and clinical picture presenting either as stroke-like pattern of focal neurological deficit or slowly progressive cognitive impairment. Myoclonus or tremors, seizures, and psychosis are other associated features which can be seen in HE. Herein, we report a girl with an uncommon presentation of orthostatic axial and myoclonic jerks in bilateral lower limbs in a case of HE.

Minimally Invasive Segmental Artery Coil Embolization (MISACE) Prior to Endovascular Thoracoabdominal Aortic Aneurysm Repair.

Purpose: Minimally Invasive Segmental Artery Coil Embolization (MISACE) is a novel approach to reduce paraplegia risk in Thoracoabdominal aortic aneurysm (TAAA) repair with limited data. We report our experience with MISACE as a method of spinal cord pre-conditioning to prevent spinal cord ischemia following endovascular repair of TAAA.

Material And Methods: A retrospective analysis of 17 patients who had an attempted MISACE prior to endovascular TAAA repair with mean follow-up of 350 days (2017-2020).

Role of BRCA2 DNA-binding and C-terminal domain in its mobility and conformation in DNA repair.

Breast cancer type two susceptibility protein (BRCA2) is an essential protein in genome maintenance, homologous recombination (HR), and replication fork protection. Its function includes multiple interaction partners and requires timely localization to relevant sites in the nucleus. We investigated the importance of the highly conserved DNA-binding domain (DBD) and C-terminal domain (CTD) of BRCA2.

Conformational flexibility and oligomerization of BRCA2 regions induced by RAD51 interaction.

BRCA2 is a key breast cancer associated protein that is predicted to have interspersed regions of intrinsic disorder. Intrinsic disorder coupled with large size likely allows BRCA2 to sample a broad range of conformational space. We expect that the resulting dynamic arrangements of BRCA2 domains are a functionally important aspect of its role in homologous recombination DNA repair.

Polymorph-specific distribution of binding sites determines thioflavin-T fluorescence intensity in α-synuclein fibrils.

Thioflavin-T (ThT) is the most commonly used fluorescent dye for following amyloid formation semi-quantitatively in vitro, specifically probing the fibrillar cross-β-sheet content. In recent years, structural polymorphism of amyloid fibrils has been shown to be an important aspect of amyloid formation, both in vitro and in neurodegenerative diseases. Therefore, understanding ThT-amyloid interactions in the context of structural polymorphism of amyloids is necessary for correct interpretation of ThT fluorescence data.

The Recombination Mediator BRCA2: Architectural Plasticity of Recombination Intermediates Revealed by Single-Molecule Imaging (SFM/TIRF).

Cellular functions are defined by dynamic assembly, rearrangement, and disassembly of biomolecules to achieve control and specificity. As an example, effective DNA repair is brought about by the concerted action of several DNA processing proteins. Both changes in the structure of individual proteins and in the arrangement of multiple proteins together (referred to here as architecture) are inherent to biological function.

Distinct Mechanisms Determine α-Synuclein Fibril Morphology during Growth and Maturation.

Amyloid polymorphs have become one of the focal points of molecular studies of neurodegenerative diseases like Parkinson's disease. Due to their distinct biochemical properties and prion-like characteristics, insights into the molecular origin and stability of amyloid polymorphs over time are crucial for understanding the potential role of amyloid polymorphism in these diseases. Here, we systematically study the fibrillization of recombinantly produced human α-synuclein (αSyn) over an extended period of time to unravel the origin and temporal evolution of polymorphism.

Does Technical Success of Angioplasty in Dysfunctional Hemodialysis Accesses Correlate with Access Patency?

Purpose: To study if <30 % residual stenosis post angioplasty (PTA) correlates with primary access circuit patency, and if any variables predict technical success.

Materials And Methods: A prospective observational study was performed between January 2009 and December 2012, wherein 76 patients underwent 154 PTA events in 56 prosthetic grafts (AVG) and 98 autogenous fistulas (AVF). Data collected included patient age, gender, lesion location and laterality, access type and location, number of prior interventions, and transonic flow rates pre- and postintervention.

Conformational Compatibility Is Essential for Heterologous Aggregation of α-Synuclein.

Under aggregation-prone conditions, soluble amyloidogenic protein monomers can self-assemble into fibrils or they can fibrillize on preformed fibrillar seeds (seeded aggregation). Seeded aggregations are known to propagate the morphology of the seeds in the event of cross-seeding. However, not all proteins are known to cross-seed aggregation.

Functionally different α-synuclein inclusions yield insight into Parkinson's disease pathology.

The formation of α-synuclein (α-S) amyloid aggregates, called Lewy bodies (LBs), is a hallmark of Parkinson's disease (PD). The function of LBs in the disease process is however still unclear; they have been associated with both neuroprotection and toxicity. To obtain insight into this contradiction, we induced the formation of α-S inclusions, using three different induction methods in SH-SY5Y cells and rat-derived primary neuronal cells.

Elastic Recoil after Balloon Angioplasty in Hemodialysis Accesses: Does It Actually Occur and Is It Clinically Relevant?

Purpose To qualify and quantify elastic recoil and determine its effect on access patency. Materials and Methods Research ethics board approval was obtained and all patients signed an informed consent form. This was a prospective, nonrandomized study of mature accesses that underwent balloon percutaneous transluminal angioplasty (PTA) between January 2009 and December 2012.

Solution conditions define morphological homogeneity of α-synuclein fibrils.

The intrinsically disordered human α-synuclein (αSyn) protein exhibits considerable heterogeneity in in vitro fibrillization reactions. Using atomic force microscopy (AFM) we show that depending on the solvent conditions, A140C mutant and wild-type αSyn can be directed to reproducibly form homogeneous populations of fibrils exhibiting regular periodicity. Results from Thioflavin-T fluorescence assays, determination of residual monomer concentrations and native polyacrylamide gel electrophoresis reveal that solvent conditions including EDTA facilitate incorporation of a larger fraction of monomers into fibrils.

Improving pediatric radiology in India.

Background: India had a population of 1,259,271,000 in 2012, with 31% of its population composed of children younger than 15 years. In comparison, children younger than 15 compose 20% of the population in the United States and 16% in Canada. Despite the differences in this demographic, little emphasis is placed on pediatric radiology in India.

A hydrogen bond regulates slow motions in ubiquitin by modulating a β-turn flip.

Proteins exist as conformational ensembles composed of multiple interchanging substates separated by kinetic barriers. Interconverting conformations are often difficult to probe, owing to their sparse population and transient nature. Here, we report the identification and characterization of a subset of conformations in ubiquitin that participate in microsecond-to-millisecond motions in the amides of Ile23, Asn25, and Thr55.