Factorial randomised controlled trial to examine the potential effect of a text message-based intervention on reducing adolescent susceptibility to e-cigarette use: a study protocol.

Introduction: Adolescent e-cigarette use, globally and within Australia, has increased in recent years. In response, public health agencies have called for the development of education and communication programmes targeting adolescents. Despite such recommendations, few rigorous evaluations of such interventions currently exist.

An ANXA11 P93S variant dysregulates TDP-43 and causes corticobasal syndrome.

Introduction: Variants of uncertain significance (VUS) surged with affordable genetic testing, posing challenges for determining pathogenicity. We examine the pathogenicity of a novel VUS P93S in Annexin A11 (ANXA11) - an amyotrophic lateral sclerosis/frontotemporal dementia-associated gene - in a corticobasal syndrome kindred. Established ANXA11 mutations cause ANXA11 aggregation, altered lysosomal-RNA granule co-trafficking, and transactive response DNA binding protein of 43 kDa (TDP-43) mis-localization.

Alpha-synuclein inclusion responsive microglia are resistant to CSF1R inhibition.

Background: Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by the presence of proteinaceous alpha-synuclein (α-syn) inclusions (Lewy bodies), markers of neuroinflammation and the progressive loss of nigrostriatal dopamine (DA) neurons. These pathological features can be recapitulated in vivo using the α-syn preformed fibril (PFF) model of synucleinopathy. We have previously determined that microglia proximal to PFF-induced nigral α-syn inclusions increase in soma size, upregulate major-histocompatibility complex-II (MHC-II) expression, and increase expression of a suite of inflammation-associated transcripts.

Factors associated with child and adolescent electronic nicotine and non-nicotine delivery systems use: A scoping review.

Objectives: To identify, characterise and broadly synthesise factors associated with child and adolescent electronic nicotine delivery systems (ENDS) and/or electronic non-nicotine delivery systems (ENNDS) ever-use and/or current use.

Methods: Four electronic databases were searched from inception to 3rd June 2022. Non-experimental studies that provided quantitative factors associated with adolescent and/or child ENDS or ENNDS ever-use and/or current use were included.

An P93S variant dysregulates TDP-43 and causes corticobasal syndrome.

As genetic testing has become more accessible and affordable, variants of uncertain significance (VUS) are increasingly identified, and determining whether these variants play causal roles in disease is a major challenge. The known disease-associated Annexin A11 (ANXA11) mutations result in ANXA11 aggregation, alterations in lysosomal-RNA granule co-trafficking, and TDP-43 mis-localization and present as amyotrophic lateral sclerosis or frontotemporal dementia. We identified a novel VUS in ANXA11 (P93S) in a kindred with corticobasal syndrome and unique radiographic features that segregated with disease.

Divergent patterns of healthy aging across human brain regions at single-cell resolution reveal links to neurodegenerative disease.

Age is a major common risk factor underlying neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Previous studies reported that chronological age correlates with differential gene expression across different brain regions. However, prior datasets have not disambiguated whether expression associations with age are due to changes in cell numbers and/or gene expression per cell.

Microglial depletion does not impact alpha-synuclein aggregation or nigrostriatal degeneration in the rat preformed fibril model.

Background: Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by the presence of proteinaceous alpha-synuclein (α-syn) inclusions (Lewy bodies), markers of neuroinflammation and the progressive loss of nigrostriatal dopamine (DA) neurons. These pathological features can be recapitulated in vivo using the α-syn preformed fibril (PFF) model of synucleinopathy. We have previously described the time course of microglial major-histocompatibility complex-II (MHC-II) expression and alterations in microglia morphology in the PFF model in rats.

Beta2-adrenoreceptor agonist clenbuterol produces transient decreases in alpha-synuclein mRNA but no long-term reduction in protein.

β2-adrenoreceptor (β2AR) agonists have been associated with a decreased risk of developing Parkinson's disease (PD) and are hypothesized to decrease expression of both alpha-synuclein mRNA (Snca) and protein (α-syn). Effects of β2AR agonist clenbuterol on the levels of Snca mRNA and α-syn protein were evaluated in vivo (rats and mice) and in rat primary cortical neurons by two independent laboratories. A modest decrease in Snca mRNA in the substantia nigra was observed after a single acute dose of clenbuterol in rats, however, this decrease was not maintained after multiple doses.

Preformed fibrils generated from mouse alpha-synuclein produce more inclusion pathology in rats than fibrils generated from rat alpha-synuclein.

Background: Alpha-synuclein (α-syn) preformed fibril (PFF)-induced pathology can be used to study the features and progression of synucleinopathies, such as Parkinson's disease. Intrastriatal injection of mouse α-syn PFFs produce accumulation of α-syn pathology in both mice and rats. Previous studies in mice have revealed that greater sequence homology between the α-syn amino acid sequence used to produce PFFs with that of the endogenous host α-syn increases α-syn pathology in vivo.

Stereotaxic Intracranial Delivery of Chemicals, Proteins or Viral Vectors to Study Parkinson's Disease.

Parkinson's disease (PD) is a progressive disorder traditionally defined by resting tremor and akinesia, primarily due to loss of dopaminergic neurons in the substantia nigra. Affected brain areas display intraneuronal fibrillar inclusions consisting mainly of alpha-synuclein (asyn) proteins. No animal model thus far has recapitulated all characteristics of this disease.

The BDNF Val66Met polymorphism (rs6265) enhances dopamine neuron graft efficacy and side-effect liability in rs6265 knock-in rats.

Prevalent in approximately 20% of the worldwide human population, the rs6265 (also called 'Val66Met') single nucleotide polymorphism (SNP) in the gene for brain-derived neurotrophic factor (BDNF) is a common genetic variant that can alter therapeutic responses in individuals with Parkinson's disease (PD). Possession of the variant Met allele results in decreased activity-dependent release of BDNF. Given the resurgent worldwide interest in neural transplantation for PD and the biological relevance of BDNF, the current studies examined the effects of the rs6265 SNP on therapeutic efficacy and side-effect development following primary dopamine (DA) neuron transplantation.

Extracellular clusterin limits the uptake of α-synuclein fibrils by murine and human astrocytes.

The progressive neuropathological damage seen in Parkinson's disease (PD) is thought to be related to the spreading of aggregated forms of α-synuclein. Clearance of extracellular α-synuclein released by degenerating neurons may be therefore a key mechanism to control the concentration of α-synuclein in the extracellular space. Several molecular chaperones control misfolded protein accumulation in the extracellular compartment.

4'-Phosphopantetheine corrects CoA, iron, and dopamine metabolic defects in mammalian models of PKAN.

Pantothenate kinase-associated neurodegeneration (PKAN) is an inborn error of CoA metabolism causing dystonia, parkinsonism, and brain iron accumulation. Lack of a good mammalian model has impeded studies of pathogenesis and development of rational therapeutics. We took a new approach to investigating an existing mouse mutant of Pank2 and found that isolating the disease-vulnerable brain revealed regional perturbations in CoA metabolism, iron homeostasis, and dopamine metabolism and functional defects in complex I and pyruvate dehydrogenase.

Cyanobacteria and cyanophage contributions to carbon and nitrogen cycling in an oligotrophic oxygen-deficient zone.

Up to half of marine N losses occur in oxygen-deficient zones (ODZs). Organic matter flux from productive surface waters is considered a primary control on N production. Here we investigate the offshore Eastern Tropical North Pacific (ETNP) where a secondary chlorophyll a maximum resides within the ODZ.

Generation of Alpha-Synuclein Preformed Fibrils from Monomers and Use In Vivo.

Use of the in vivo alpha-synuclein preformed fibril (α-syn PFF) model of synucleinopathy is gaining popularity among researchers aiming to model Parkinson's disease synucleinopathy and nigrostriatal degeneration. The standardization of α-syn PFF generation and in vivo application is critical in order to ensure consistent, robust α-syn pathology. Here, we present a detailed protocol for the generation of fibrils from monomeric α-syn, post-fibrilization quality control steps, and suggested parameters for successful neurosurgical injection of α-syn PFFs into rats or mice.

Progress and Challenges in Ocean Metaproteomics and Proposed Best Practices for Data Sharing.

Ocean metaproteomics is an emerging field enabling discoveries about marine microbial communities and their impact on global biogeochemical processes. Recent ocean metaproteomic studies have provided insight into microbial nutrient transport, colimitation of carbon fixation, the metabolism of microbial biofilms, and dynamics of carbon flux in marine ecosystems. Future methodological developments could provide new capabilities such as characterizing long-term ecosystem changes, biogeochemical reaction rates, and in situ stoichiometries.

Applying National Estimates of Adults With Indications for Pre-Exposure Prophylaxis to Populations of Men Who Have Sex With Men and People Who Inject Drugs in Colorado: Modeling Study.

Background: Oral pre-exposure prophylaxis (PrEP) is a highly effective option for HIV prevention. To realize the full benefit of PrEP at the population level, uptake must reach those at the greatest risk of HIV acquisition. Guidance published by Centers for Disease Control and Prevention (CDC) suggests that the number of individuals with indications for PrEP is 1.

Quality Over Quantity: Advantages of Using Alpha-Synuclein Preformed Fibril Triggered Synucleinopathy to Model Idiopathic Parkinson's Disease.

Animal models have significantly advanced our understanding of Parkinson's disease (PD). Alpha-synuclein (α-syn) has taken center stage due to its genetic connection to familial PD and localization to Lewy bodies, one pathological hallmark of PD. Animal models developed on the premise of elevated alpha-synuclein via germline manipulation or viral vector-mediated overexpression are used to investigate PD pathophysiology and vet novel therapeutics.

Correction to: Lewy body-like alpha-synuclein inclusions trigger reactive microgliosis prior to nigral degeneration.

After publication of the original article [1] it was noted that the name of author, D. Luke Fisher, was erroneously typeset in both the PDF and online formats of the manuscript as Luke D. Fisher.

Lewy body-like alpha-synuclein inclusions trigger reactive microgliosis prior to nigral degeneration.

Background: Converging evidence suggests a role for microglia-mediated neuroinflammation in Parkinson's disease (PD). Animal models of PD can serve as a platform to investigate the role of neuroinflammation in degeneration in PD. However, due to features of the previously available PD models, interpretations of the role of neuroinflammation as a contributor to or a consequence of neurodegeneration have remained elusive.

Best Practices for Generating and Using Alpha-Synuclein Pre-Formed Fibrils to Model Parkinson's Disease in Rodents.

Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting approximately one-percent of the population over the age of sixty. Although many animal models have been developed to study this disease, each model presents its own advantages and caveats. A unique model has arisen to study the role of alpha-synuclein (aSyn) in the pathogenesis of PD.

Metronomic administration of lomustine following palliative radiation therapy for appendicular osteosarcoma in dogs.

The purpose of this study was to determine if metronomic administration of lomustine following palliative radiation therapy (RT) improved length of palliation and therefore survival in dogs with appendicular osteosarcoma compared to treatment with palliative radiation alone. A search of medical records identified dogs with appendicular osteosarcoma, treated with palliative RT (2 fractions of 8 Gray in a 24 hour time frame, day 0 and day 1; or day 0, 6 hours apart). Data collected included signalment, history, clinical signs, physical examination findings, clinicopathologic abnormalities, extent of disease, response, toxicity, other therapy, survival time, and whether dogs received metronomic lomustine (ML) or not.