Distinct regulation of Tau Monomer and aggregate uptake and intracellular accumulation in human neurons.

Background: The prion-like spreading of Tau pathology is the leading cause of disease progression in various tauopathies. A critical step in propagating pathologic Tau in the brain is the transport from the extracellular environment and accumulation inside naïve neurons. Current research indicates that human neurons internalize both the physiological extracellular Tau (eTau) monomers and the pathological eTau aggregates.

The type-I interferon response potentiates seeded tau aggregation and exacerbates tau pathology.

Introduction: Signatures of a type-I interferon (IFN-I) response are observed in the post mortem brain in Alzheimer's disease (AD) and other tauopathies. However, the effect of the IFN-I response on pathological tau accumulation remains unclear.

Methods: We examined the effects of IFN-I signaling in primary neural culture models of seeded tau aggregation and P301S-tau transgenic mouse models in the context of genetic deletion of the IFN-I receptor (IFNAR).

Use of Dexmedetomidine During an Emergent Exploratory Laparotomy in a High-Risk Cardiac Patient With an Intra-aortic Balloon Pump.

An intra-aortic balloon pump (IABP) may be placed preoperatively for high-risk patients with reduced ejection fraction or multivessel coronary disease undergoing non-cardiac surgery. Dexmedetomidine (DEX) has both anesthetic and cardioprotective effects, and little evidence is present on its effect on minimum alveolar concentration (MAC) and bispectral index (BIS). We present the case of a high-risk cardiac patient who was admitted and required fluid optimization prior to coronary artery bypass grafting (CABG).

Super-resolution imaging unveils the self-replication of tau aggregates upon seeding.

Tau is a soluble protein interacting with tubulin to stabilize microtubules. However, under pathological conditions, it becomes hyperphosphorylated and aggregates, a process that can be induced by treating cells with exogenously added tau fibrils. Here, we employ single-molecule localization microscopy to resolve the aggregate species formed in early stages of seeded tau aggregation.

Perforin-2 is a pore-forming effector of endocytic escape in cross-presenting dendritic cells.

During initiation of antiviral and antitumor T cell-mediated immune responses, dendritic cells (DCs) cross-present exogenous antigens on major histocompatibility complex (MHC) class I molecules. Cross-presentation relies on the unusual "leakiness" of endocytic compartments in DCs, whereby internalized proteins escape into the cytosol for proteasome-mediated generation of MHC I-binding peptides. Given that type 1 conventional DCs excel at cross-presentation, we searched for cell type-specific effectors of endocytic escape.

Effect of cetrimonium carrier micelles on bacterial membranes and extracellular DNA, an in silico study.

Microorganisms do not live as dispersed single cells but rather they form aggregates with extracellular polymeric substances at interfaces. Biofilms are considered efficient life forms because they shield bacteria from biocides and collect dilute nutrients. This is a big concern in industry since the microorganisms can colonize a wide range of surfaces, accelerating material deterioration, colonizing medical devices, contaminating ultrapure drinking water, increasing energy costs and creating focus of infection.

Cytosolic antibody receptor TRIM21 is required for effective tau immunotherapy in mouse models.

Aggregates of the protein tau are proposed to drive pathogenesis in neurodegenerative diseases. Tau can be targeted by using passively transferred antibodies (Abs), but the mechanisms of Ab protection are incompletely understood. In this work, we used a variety of cell and animal model systems and showed that the cytosolic Ab receptor and E3 ligase TRIM21 (T21) could play a role in Ab protection against tau pathology.

Extracellular DNA: A Critical Aspect of Marine Biofilms.

Multispecies biofilms represent a pervasive threat to marine-based industry, resulting in USD billions in annual losses through biofouling and microbiologically influenced corrosion (MIC). Biocides, the primary line of defence against marine biofilms, now face efficacy and toxicity challenges as chemical tolerance by microorganisms increases. A lack of fundamental understanding of species and EPS composition in marine biofilms remains a bottleneck for the development of effective, target-specific biocides with lower environmental impact.

Enhancing Biocide Efficacy: Targeting Extracellular DNA for Marine Biofilm Disruption.

Biofilm formation is a global health, safety and economic concern. The extracellular composition of deleterious multispecies biofilms remains uncanvassed, leading to an absence of targeted biofilm mitigation strategies. Besides economic incentives, drive also exists from industry and research to develop and apply environmentally sustainable chemical treatments (biocides); especially in engineered systems associated with the marine environment.

Cholesterol determines the cytosolic entry and seeded aggregation of tau.

Assemblies of tau can transit between neurons, seeding aggregation in a prion-like manner. To accomplish this, tau must cross cell-limiting membranes, a process that is poorly understood. Here, we establish assays for the study of tau entry into the cytosol as a phenomenon distinct from uptake, in real time, and at physiological concentrations.

Conditioning of metal surfaces enhances adhesion.

Microbiologically influenced corrosion and biofouling of steels depend on the adsorption of a conditioning film and subsequent attachment of bacteria. Extracellular deoxyribonucleic acid (eDNA) and amino acids are biologically critical nutrient sources and are ubiquitous in marine environments. However, little is known about their role as conditioning film molecules in early biofilm formation on metallic surfaces.

Efficiency of a Novel Multifunctional Corrosion Inhibitor Against Biofilms Developed on Carbon Steel.

In natural environments, populations of microorganisms rapidly colonise surfaces forming biofilms. These sessile communities comprise a variety of species which contribute to biofouling and microbiologically influenced corrosion (MIC), especially on metals. Species heterogeneity in natural systems confers higher tolerance to adverse conditions such as biocide treatment compared with single species laboratory simulations.

Evaluation of a novel, multi-functional inhibitor compound for prevention of biofilm formation on carbon steel in marine environments.

Chemical biocides remain the most effective mitigation strategy against microbiologically influenced corrosion (MIC), one of the costliest and most pervasive forms of corrosion in industry. However, toxicity and environmental concerns associated with these compounds are encouraging the development of more environmentally friendly MIC inhibitors. In this study, we evaluated the antimicrobial effect of a novel, multi-functional organic corrosion inhibitor (OCI) compound, cetrimonium trans-4-hydroxy-cinnamate (CTA-4OHcinn).

Tau assemblies do not behave like independently acting prion-like particles in mouse neural tissue.

A fundamental property of infectious agents is their particulate nature: infectivity arises from independently-acting particles rather than as a result of collective action. Assemblies of the protein tau can exhibit seeding behaviour, potentially underlying the apparent spread of tau aggregation in many neurodegenerative diseases. Here we ask whether tau assemblies share with classical pathogens the characteristic of particulate behaviour.

The Role of Antibodies and Their Receptors in Protection Against Ordered Protein Assembly in Neurodegeneration.

Ordered assemblies of proteins are found in the postmortem brains of sufferers of several neurodegenerative diseases. The cytoplasmic microtubule associated protein tau and alpha-synuclein (αS) are found in an assembled state in Alzheimer's disease and Parkinson's disease, respectively. An accumulating body of evidence suggests a "prion-like" mechanism of spread of these assemblies through the diseased brain.

The role of transesophageal echocardiography in the management of renal cell carcinoma with venous tumor thrombus.

We reviewed the role of transesophageal echocardiography (TEE) in the management of renal cell carcinoma (RCC) with associated tumor thrombus. Many consider intraoperative TEE as imperative in cases of Level 4 thrombi with atrial involvement, as well as in cases that require the use of cardiopulmonary bypass (CPB). However, the role of TEE in the surgical management of RCC with associated inferior vena cava (IVC) thrombus may expand beyond this subset.

Clinical Update in Pericardial Diseases.

Patients with pericardial disease often require interventional therapies or surgery, making it essential for anesthesiologists to understand the altered physiology of these disease states and the resultant impact on perioperative management. The broad spectrum of syndromes involving the pericardium present with varying degrees of clinical significance, from asymptomatic presentations to life-threatening emergencies. Impaired diastolic filling of the heart represents a common theme of pericardial disease, with the rate of onset of pericardial pathology largely determining the extent of this impairment and subsequent severity of presentation.

Incremental Value of Three-Dimensional Transesophageal Echocardiography over the Two-Dimensional Technique in the Assessment of a Thrombus in Transit through a Patent Foramen Ovale.

We report a case of a right atrial thrombus traversing a patent foramen ovale into the left atrium, where three-dimensional transesophageal echocardiography provided considerable incremental value over two-dimensional transesophageal echocardiography in its assessment. As well as allowing us to better spatially characterize the thrombus, three-dimensional transesophageal echocardiography provided a more quantitative assessment through estimation of total thrombus burden.

Live/real time three-dimensional transesophageal echocardiographic assessment of the spinal cord.

We present an adult patient in whom live/real time three-dimensional transesophageal echocardiography (3DTEE) provided incremental value in the assessment of the spinal cord as compared to two-dimensional transesophageal echocardiographic (2DTEE) findings published in the literature. It improved accurate identification and assessment of the anterior radiculomedullary spinal arteries which may have an important clinical application in monitoring for spinal cord ischemia during thoracic aortic surgery. Because the spinal cord and spinal canal could be examined using not only transverse but also coronal (frontal), sagittal, and oblique planes, 3DTEE further allowed for three-dimensional measurements of the dimensions and volumetric analysis of the visualized spinal cord and spinal canal.