Phosphomimetic substitutions in TDP-43's transiently α-helical region suppress phase separation.

Phosphorylated TAR DNA-binding protein of 43 kDa (TDP-43) is present within the aggregates of several age-related neurodegenerative disorders, such as amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Alzheimer's disease, to the point that the presence of phosphorylated TDP-43 is considered a hallmark of some of these diseases. The majority of known TDP-43 phosphorylation sites detected in amyotrophic lateral sclerosis and frontotemporal lobar degeneration patients is located in the low-complexity domain (LCD), the same domain that has been shown to be critical for TDP-43 liquid-liquid phase separation (LLPS). However, the effect of these LCD phosphorylation sites on TDP-43 LLPS has been largely unexplored, and any work that has been done has mainly focused on sites near the C-terminal end of the LCD.

Domain-specific modulatory effects of phosphomimetic substitutions on liquid-liquid phase separation of tau protein.

Aggregation of tau is one of the major pathogenic events in Alzheimer's disease and several other neurodegenerative disorders. Recent reports demonstrated that tau can condense into liquid droplets that undergo time-dependent transition to a solid-like state, suggesting that liquid condensates may be on the pathway to pathological aggregation of tau. While hyperphosphorylation is a key feature of tau isolated from brains of patients with Alzheimer's disease and other tauopathies, the mechanistic role of phosphorylation in tau liquid-liquid phase separation (LLPS) remains largely unexplored.

Study of Tau Liquid-Liquid Phase Separation In Vitro.

Aggregation of the microtubule-associated protein tau is one of the major pathogenic events in Alzheimer's disease and several other neurodegenerative disorders. Recent reports have demonstrated that purified tau can undergo liquid-liquid phase separation in vitro, forming liquid droplets. The protein within these droplets was also found to undergo accelerated transition to fibrillar aggregates, suggesting that LLPS may play an important role in pathological aggregation of tau in neurodegenerative disorders.

Tau liquid-liquid phase separation in neurodegenerative diseases.

Aggregation of the microtubule-associated protein tau plays a major role in Alzheimer's disease and several other neurodegenerative disorders. An exciting recent development is the finding that, akin to some other proteins associated with neurodegenerative disease, tau has a high propensity to condensate via the mechanism of liquid-liquid phase separation (LLPS). Here, we discuss the evidence for tau LLPS in vitro, the molecular mechanisms of this reaction, and the role of post-translational modifications and pathogenic mutations in tau phase separation.

[ANATOMICAL AND CLINICAL EXAMINATION OF THE INFERIOR VENA CAVA AND VENOUS RETURN IN CONDITIONS OF TUMOR VENOUS THROMBOSIS].

The aim of the study was to conduct an anatomical and clinical study of IVC and its tributaries, and to determine the pathways of collateral venous blood flow to improve the results of surgical treatment of patients with kidney cancer complicated by venous tumor thrombosis. The anatomical examination of the IVC and its tributaries included the results of autopsy of 27 corpses. The clinical part of the study is based on the results of examination and surgical treatment of 147 patients with renal cell carcinoma complicated by venous tumor thrombosis.

Neurotoxicity of oligomers of phosphorylated Tau protein carrying tauopathy-associated mutation is inhibited by prion protein.

Tauopathies, including Alzheimer's disease (AD), are manifested by the deposition of well-characterized amyloid aggregates of Tau protein in the brain. However, it is rather unlikely that these aggregates constitute the major form of Tau responsible for neurodegenerative changes. Currently, it is postulated that the intermediates termed as soluble oligomers, assembled on the amyloidogenic pathway, are the most neurotoxic form of Tau.

Deprescribing Medications Among Older People to Reduce Polypharmacy at a Comprehensive Academic Medical Center.

Objective: To evaluate deprescribing of select high-risk medications (HRMs) in an Acute Care for the Elderly (ACE) unit with pharmacist involvement compared with usual care in older people.

Design: Retrospective, single-center case-control study.

Setting: Medical-surgical units at an urban academic medical center.

Regulatory mechanisms of tau protein fibrillation under the conditions of liquid-liquid phase separation.

One of the hallmarks of Alzheimer's disease and several other neurodegenerative disorders is the aggregation of tau protein into fibrillar structures. Building on recent reports that tau readily undergoes liquid-liquid phase separation (LLPS), here we explored the relationship between disease-related mutations, LLPS, and tau fibrillation. Our data demonstrate that, in contrast to previous suggestions, pathogenic mutations within the pseudorepeat region do not affect tau441's propensity to form liquid droplets.

Small molecules as potent biphasic modulators of protein liquid-liquid phase separation.

Liquid-liquid phase separation (LLPS) of proteins that leads to formation of membrane-less organelles is critical to many biochemical processes in the cell. However, dysregulated LLPS can also facilitate aberrant phase transitions and lead to protein aggregation and disease. Accordingly, there is great interest in identifying small molecules that modulate LLPS.

Zinc promotes liquid-liquid phase separation of tau protein.

Tau is a microtubule-associated protein that plays a major role in Alzheimer's disease (AD) and other tauopathies. Recent reports indicate that, in the presence of crowding agents, tau can undergo liquid-liquid phase separation (LLPS), forming highly dynamic liquid droplets. Here, using recombinantly expressed proteins, turbidimetry, fluorescence microscopy imaging, and fluorescence recovery after photobleaching (FRAP) assays, we show that the divalent transition metal zinc strongly promotes this process, shifting the equilibrium phase boundary to lower protein or crowding agent concentrations.

Liquid-liquid phase separation of tau protein: The crucial role of electrostatic interactions.

Recent studies have indicated that tau, a protein involved in Alzheimer's disease and other neurodegenerative disorders, has a propensity to undergo liquid-liquid phase separation (LLPS). However, the mechanism of this process remains unknown. Here, we demonstrate that tau LLPS is largely driven by intermolecular electrostatic interactions between the negatively charged N-terminal and positively charged middle/C-terminal regions, whereas hydrophobic interactions play a surprisingly small role.

[Pharmacokinetics of noopept and its active metabolite cycloprolyl glycine in rats].

The study of the pharmacokinetics of new drugs and the identification of active metabolites is a necessary step for effective and safe use in the clinical practice. It is especially important for peptide drugs due to their enzymatic instability, low bioavailability and poor permeability through the blood-brain barrier (BBB). The role of endogenous neuropeptides containing cyclic amino acids, proline, pyroglutamic acid, and glycine, in the regulation of memory processes is known as terminal peptide fragments.

Amyloidogenic cross-seeding of Tau protein: Transient emergence of structural variants of fibrils.

Amyloid aggregates of Tau protein have been implicated in etiology of many neurodegenerative disorders including Alzheimer's disease (AD). When amyloid growth is induced by seeding with preformed fibrils assembled from the same protein, structural characteristics of the seed are usually imprinted in daughter generations of fibrils. This so-called conformational memory effect may be compromised when the seeding involves proteins with non-identical sequences leading to the emergence of distinct structural variants of fibrils (amyloid 'strains').

Development of a Professional Certification in Cancer Patient Education.

Patient educators come into the field from diverse professional backgrounds and often lack training in how to teach and develop patient education resources since no formal patient education professional certification program exists. A professional certification program for patient educators would further define the professional scope of practice and reduce variability in performance. The purpose of this study was to (1) determine the level of interest among Canadian cancer patient educators in a patient education professional certification program and (2) determine the competencies to be included in the professional certification program.

Self-management education interventions for patients with cancer: a systematic review.

Purpose: This systematic review was intended to identify the effectiveness and inclusion of essential components of self-management education interventions to support patients with cancer in developing the skills needed for effective self-management of their disease and the acute or immediate, long-term, and late harmful effects of treatments.

Methods: Self-management education interventions were included if they were randomized controlled trials (RCTs) containing at least one of the eight core elements outlined by the research team. A systematic search was conducted in Ovid MEDLINE (2005 through April 2015), Embase (2005 to 2015, week 15), the Cochrane Database of Systematic Reviews (Issue 4, April 2015), CINAHL (2005 to 2015) and PsychINFO (2005 to 2015).

What is Person-Centred Care? A Qualitative Inquiry into Oncology Staff and Patient and Family Experience of Person-Centred Care.

Introduction: To investigate the understanding and practice of person-centred care by health care professionals and support staff at a cancer centre and to learn how patients and family members understand and experience person-centred care.

Methods: The study was conducted in two phases. Phase 1 used large wall mounted posters and marking pens in public areas of the cancer centre to gather comments from staff, volunteers, students, patients, family members, and visitors to answer the question, "What does person-centred care mean to you?" Phase 2 used a six-question, open-ended, paper-based questionnaire for staff and patients.

[SURGICAL ANATOMY OF THE TRIBUTARIES OF INFERIOR VENA CAVA].

The results of the anatomical study of the inferior vena cava (IVC) and its tributaries on 27 fresh cadavers were analysed. It was established that in past hepatic part of IVC fall from 7 to 23 veins. The diameter of the main hepatic veins on average 12.

[THE CHOICE OF SURGICAL TREATMENT METHOD FOR THE DEEP VEINS THROMBOSIS IN SYSTEM OF VENA CAVA INFERIOR].

There were analyzed the results of examination and treatment of 455 patients, suffering deep veins thrombosis in a system of vena cava inferior, of whom 175 (38.5%) were operated on. Inclusion of ultrasound duplex scanning, roentgencontrast phlebography, multispiral computer tomography with intravenous contrasting, radionuclide phleboscintigraphy into complex of clinic-instrumental examination of the patients gives possibility to estimate the disorders of the main trunk and collateral venous blood flow in the deep veins thrombosis, as well as to substantiate indications and choice of the operative treatment method.

Improving the efficiency of plasmid transformation in Shewanella oneidensis MR-1 by removing ClaI restriction site.

Here we demonstrate that elimination of ClaI restriction site from the sequence of a plasmid DNA increases the efficiency of transformation of Shewanella oneidensis MR-1 significantly. To achieve reliable transformation of S. oneidensis MR-1 plasmids either lacking ClaI site or isolated from primary transformants of S.

Permeability of the blood-brain barrier for dilept and its active metabolite.

Experiments on rats with measurements by HPLC-MS/MS showed that antipsychotic preparation dilept (N-caproyl-L-prolyl-L-tyrosine methyl ester) administered per os in doses of 40 and 200 mg/kg crossed the blood-brain barrier and was detected in rat brain (unchanged drug and its active metabolite N-caproyl-L-prolyl-L-tyrosine). The brain/plasma distribution coefficient for dilept was 2.0, for metabolite 0.

Effective teaching strategies and methods of delivery for patient education: a systematic review and practice guideline recommendations.

The objective of this study was to determine effective teaching strategies and methods of delivery for patient education (PE). A systematic review was conducted and reviews with or without meta-analyses, which examined teaching strategies and methods of delivery for PE, were included. Teaching strategies identified are traditional lectures, discussions, simulated games, computer technology, written material, audiovisual sources, verbal recall, demonstration, and role playing.

Evaluation of cancer patient education and services.

On their first visit to the Regional Cancer Program, all patients are provided with the "Information for Patients and Families" binder that was designed by an interdisciplinary cancer patient education team. Patients were asked to complete a survey to evaluate the usefulness of this binder. Timely delivery of the "Information for Patients and Families" binder validates a higher level of satisfaction with oncology services because patients are better informed and this translates into a reduction of psychosocial problems.

Experimental study of the pharmacokinetics of a tryptophan-containing dipeptide GB-115.

Pharmacokinetics of an original compound GB-115 (N-phenylhexanoylglycyltryptophan) synthesized on the basis of the structure of endogenous tetrapeptide cholecystokinin-4 was studied by means of high-performance liquid chromatography. Pharmacokinetic parameters were calculated after intravenous and peroral administration of GB-115. Our results indicate that this dipeptide is resistant to peptidases.