Whole-brain network transitions within the framework of ignition and transfer entropy following VIM-MRgFUS in essential tremor patients.

Magnetic resonance-guided focused ultrasound (MRgFUS) lesioning of the ventralis intermedius nucleus (VIM) has shown promise in treating drug-refractory essential tremor (ET). It remains unknown whether focal VIM lesions by MRgFUS have broader restorative effects on information flow within the whole-brain network of ET patients. We applied an information-theoretical approach based on intrinsic ignition and the concept of transfer entropy (TE) to assess the spatiotemporal dynamics after VIM-MRgFUS.

IBC's 23rd Annual Antibody Engineering, 10th Annual Antibody Therapeutics international conferences and the 2012 Annual Meeting of The Antibody Society: December 3-6, 2012, San Diego, CA.

The 23rd Annual Antibody Engineering, 10th Annual Antibody Therapeutics international conferences, and the 2012 Annual Meeting of The Antibody Society, organized by IBC Life Sciences with contributions from The Antibody Society and two Scientific Advisory Boards, were held December 3-6, 2012 in San Diego, CA. The meeting drew over 800 participants who attended sessions on a wide variety of topics relevant to antibody research and development. As a prelude to the main events, a pre-conference workshop held on December 2, 2012 focused on intellectual property issues that impact antibody engineering.

FOXO4-dependent upregulation of superoxide dismutase-2 in response to oxidative stress is impaired in spinocerebellar ataxia type 3.

Ataxin-3 (ATXN3), the disease protein in spinocerebellar ataxia type 3 (SCA3), binds to target gene promoters and modulates transcription by interaction with transcriptional regulators. Here, we show that ATXN3 interacts with the forkhead box O (FOXO) transcription factor FOXO4 and activates the FOXO4-dependent transcription of the manganese superoxide dismutase (SOD2) gene. Upon oxidative stress, ATXN3 and FOXO4 translocate to the nucleus, concomitantly bind to the SOD2 gene promoter and increase the expression of the antioxidant enzyme SOD2.

Expanding the concept of chemically programmable antibodies to RNA aptamers: chemically programmed biotherapeutics.

Chemically programmed antibodies represent a new class of biologic drugs that acquire their specificity through chemistry rather than through biology. To date, this approach has used small molecules and peptides to direct targeting and to extend the pharmacokinetics and otherwise enhance the biological function of the small molecule or peptide through Fc-based mechanisms of the antibody. However, other classes of therapeutically active molecules, such as aptamers, should benefit from antibody conjugation and the chemically programmed antibody approach.

[Inadequate reimbursement for surgical patients with Parkinson's disease according to diagnosis-related grouping].

Background: Parkinson's disease (PD) is a progressive degenerative disease of the human central nervous system with a demographical increase in surgical patients. Comorbidities are known to increase the perioperative risk profile and therefore amplify treatment expenses.

Aim: The aim of this study was to analyse whether the reimbursement of additional costs due to PD in surgical patients was sufficiently considered by diagnosis-related grouping (DRG).

An efficient chemical approach to bispecific antibodies and antibodies of high valency.

Irreversible chemical programming of monoclonal aldolase antibody (mAb) 38C2 has been accomplished with beta-lactam equipped mono- and bifunctional targeting modules, including a cyclic-RGD peptide linked to either the peptide (D-Lys(6))-LHRH or another cyclic RGD unit and a small-molecule integrin inhibitor SCS-873 conjugated to (D-Lys(6))LHRH. We also prepared monofunctional targeting modules containing either cyclic RGD or (D-Lys(6))-LHRH peptides. Binding of the chemically programmed antibodies to integrin receptors alpha(v)beta(3) and alpha(v)beta(5) and to the luteinizing hormone releasing hormone receptor were evaluated.

Beta-lactam-based approach for the chemical programming of aldolase antibody 38C2.

Irreversible chemical programming of monoclonal aldolase antibody (mAb) 38C2 has been accomplished with beta-lactam-equipped targeting modules. A model study was first performed with beta-lactam conjugated to biotin. This conjugate efficiently and selectively modified the catalytic site lysine (LysH93) of mAb 38C2.

Parkinson's disease influences the perioperative risk profile in surgery.

Background And Aims: Aim of this study was to define the perioperative risk profile in surgery of patients suffering from Parkinson's disease (PD) in order to improve treatment options in these patients.

Materials And Methods: Over a period of 13 years, 51 patients suffering from Parkinson's disease treated in the departments of general, visceral, thoracic, vascular, and trauma surgery were retrospectively compared using matched-pair analysis with 51 controls not affected by PD. Both groups of patients were assessed regarding morbidity and mortality, length of treatment, and rehabilitation.

Inactivation of the mouse Atxn3 (ataxin-3) gene increases protein ubiquitination.

Spinocerebellar ataxia type 3 is a neurodegenerative disease caused by expansion of a polyglutamine domain in the protein ataxin-3 (ATXN3). Physiological functions of ATXN3 presumably include ubiquitin protease and transcriptional corepressor activity. To gain insight into the function of ATXN3 and to test the hypothesis that loss of ATXN3 contributes to the pathology in SCA3 we generated Atxn3 knockout (ko) mice by targeted mutagenesis.

Potassium channel dysfunction and depolarized resting membrane potential in a cell model of SCA3.

Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant inherited neurodegenerative disease caused by the expansion of a polyglutamine repeat within the disease protein, ataxin-3. There is growing evidence that neuronal electrophysiological properties are altered in a variety of polyglutamine diseases such as Huntington's disease and SCA1 and that these alterations may contribute to disturbances of neuronal function prior to neurodegeneration. To elucidate possible electrophysiological changes in SCA3, we generated a stable PC12 cell model with inducible expression of normal and mutant human full-length ataxin-3 and analyzed the electrophysiological properties after induction of the recombinant ataxin-3 expression.

Alpha-synuclein and Parkinson's disease: implications from the screening of more than 1,900 patients.

Data on the frequency of alpha-synuclein mutations in Parkinson's disease (PD) are limited. Screening the entire coding region in 1,921 PD patients with denaturing high performance liquid chromatography and subsequent sequencing we only detected silent mutations (g.2654A>G, g.

The human MJD gene: genomic structure and functional characterization of the promoter region.

Machado-Joseph disease (MJD) is a progressive neurodegenerative disorder caused by expansion of a CAG motif within the translated region of the human MJD (hMJD) gene which has been mapped to chromosome 14q. In this study, the hMJD gene was identified in two overlapping bacterial artificial chromosome (BAC) clones and contained 11 exons resulting in a 6.14 kb transcript.