SARS-CoV-2 and HSV-1 Induce Amyloid Aggregation in Human CSF Resulting in Drastic Soluble Protein Depletion.

The corona virus (SARS-CoV-2) pandemic and the resulting long-term neurological complications in patients, known as long COVID, have renewed interest in the correlation between viral infections and neurodegenerative brain disorders. While many viruses can reach the central nervous system (CNS) causing acute or chronic infections (such as herpes simplex virus 1, HSV-1), the lack of a clear mechanistic link between viruses and protein aggregation into amyloids, a characteristic of several neurodegenerative diseases, has rendered such a connection elusive. Recently, we showed that viruses can induce aggregation of purified amyloidogenic proteins via the direct physicochemical mechanism of heterogeneous nucleation (HEN).

Compartment-specific small non-coding RNA changes and nucleolar defects in human mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (mTLE) is a debilitating disease characterized by recurrent seizures originating from temporal lobe structures such as the hippocampus. The pathogenic mechanisms underlying mTLE are incompletely understood but include changes in the expression of non-coding RNAs in affected brain regions. Previous work indicates that some of these changes may be selective to specific sub-cellular compartments, but the full extent of these changes and how these sub-cellular compartments themselves are affected remains largely unknown.

Resting-state functional MRI of the nose as a novel investigational window into the nervous system.

Besides being responsible for olfaction and air intake, the nose contains abundant vasculature and autonomic nervous system innervations, and it is a cerebrospinal fluid clearance site. Therefore, the nose is an attractive target for functional MRI (fMRI). Yet, nose fMRI has not been possible so far due to signal losses originating from nasal air-tissue interfaces.

The link between amyloid β and ferroptosis pathway in Alzheimer's disease progression.

Alzheimer's disease (AD) affects millions of people worldwide and represents the most prevalent form of dementia. Treatment strategies aiming to interfere with the formation of amyloid β (Aβ) plaques and neurofibrillary tangles (NFTs), the two major AD hallmarks, have shown modest or no effect. Recent evidence suggests that ferroptosis, a type of programmed cell death caused by iron accumulation and lipid peroxidation, contributes to AD pathogenesis.

Regular Exercise Training Induces More Changes on Intestinal Glucose Uptake from Blood and Microbiota Composition in Leaner Compared to Heavier Individuals in Monozygotic Twins Discordant for BMI.

Background/objectives: Obesity impairs intestinal glucose uptake (GU) (intestinal uptake of circulating glucose from blood) and alters gut microbiome. Exercise improves intestinal insulin-stimulated GU and alters microbiome. Genetics influence the risk of obesity and gut microbiome.

Clinical development and proof of principle testing of new regenerative vascular endothelial growth factor-D therapy for refractory angina: rationale and design of the phase 2 ReGenHeart trial.

Background: Despite tremendous therapeutic advancements, a significant proportion of coronary artery disease patients suffer from refractory angina pectoris, that is, quality-of-life-compromising angina that is non-manageable with established pharmacological and interventional treatment options. Adenoviral vascular endothelial growth factor-D (AdVEGF-D)-encoding gene therapy (GT) holds promise for the treatment of refractory angina.

Methods: ReGenHeart is an investigator-initiated, multicentre, randomised, placebo-controlled and double-blinded phase 2 clinical trial that aims to study the safety and efficacy of intramyocardially administered angiogenic AdVEGF-D GT for refractory angina.

Circulating microRNAs and isomiRs as biomarkers for the initial insult and epileptogenesis in four experimental epilepsy models: The EPITARGET study.

Objective: Structural epilepsies can manifest months or years after the occurrence of an initial epileptogenic insult, making them amenable for secondary prevention. However, development of preventive treatments has been challenged by a lack of biomarkers for identifying the subset of individuals with the highest risk of epilepsy after the epileptogenic insult.

Methods: Four different rat models of epileptogenesis were investigated to identify differentially expressed circulating microRNA (miRNA) and isomiR profiles as biomarkers for epileptogenesis.

Novel Metabolites Associated with Decreased GFR in Finnish Men: A 12-Year Follow-Up of the METSIM Cohort.

Identification of the individuals having impaired kidney function is essential in preventing the complications of this disease. We measured 1009 metabolites at the baseline study in 10,159 Finnish men of the METSIM cohort and associated the metabolites with an estimated glomerular filtration rate (eGFR). A total of 7090 men participated in the 12-year follow-up study.

Effects of Obesity and Exercise on Hepatic and Pancreatic Lipid Content and Glucose Metabolism: PET Studies in Twins Discordant for BMI.

Obesity and sedentarism are associated with increased liver and pancreatic fat content (LFC and PFC, respectively) as well as impaired organ metabolism. Exercise training is known to decrease organ ectopic fat but its effects on organ metabolism are unclear. Genetic background affects susceptibility to obesity and the response to training.

Human iPSC-derived pericyte-like cells carrying APP Swedish mutation overproduce beta-amyloid and induce cerebral amyloid angiopathy-like changes.

Background: Patients with Alzheimer's disease (AD) frequently present with cerebral amyloid angiopathy (CAA), characterized by the accumulation of beta-amyloid (Aβ) within the cerebral blood vessels, leading to cerebrovascular dysfunction. Pericytes, which wrap around vascular capillaries, are crucial for regulating cerebral blood flow, angiogenesis, and vessel stability. Despite the known impact of vascular dysfunction on the progression of neurodegenerative diseases, the specific role of pericytes in AD pathology remains to be elucidated.

Lifestyle differences between co-twins are associated with decreased similarity in their internal and external exposome profiles.

Whether differences in lifestyle between co-twins are reflected in differences in their internal or external exposome profiles remains largely underexplored. We therefore investigated whether within-pair differences in lifestyle were associated with within-pair differences in exposome profiles across four domains: the external exposome, proteome, metabolome and epigenetic age acceleration (EAA). For each domain, we assessed the similarity of co-twin profiles using Gaussian similarities in up to 257 young adult same-sex twin pairs (54% monozygotic).

Making Multiplexed Imaging Flexible: Combining Essential Markers With Established Antibody Panels.

Multiplexed immunofluorescence (IF) can be achieved using different commercially available platforms, often making use of conjugated antibodies detected in iterative cycles. A growing portfolio of pre-conjugated antibodies is offered by the providers, as well as the possibility for conjugation. For many conjugation methods and kits, there are limitations in which antibodies can be used, and conjugation results are sometimes irreproducible.

Emerging Models to Study Human Microglia In vitro.

New in vitro models provide an exciting opportunity to study live human microglia. Previously, a major limitation in understanding human microglia in health and disease has been their limited availability. Here, we provide an overview of methods to obtain human stem cell or blood monocyte-derived microglia-like cells that provide a nearly unlimited source of live human microglia for research.

Review of Myocardial Ischemia, Scar, and Viability Estimation with Molecular Magnetic Resonance Imaging.

Background: Cardiovascular diseases, particularly myocardial ischemia from coronary artery obstruction, remain a leading cause of global morbidity. This review explores cardiac molecular magnetic resonance imaging (mMRI) and other molecular imaging techniques for the evaluation of myocardial ischemia, scarring, and viability.

Results And Findings: mMRI imaging methods provide detailed information on myocardial ischemia, edema, and scar tissue using techniques like cine imaging, T1 and T2 mapping, and gadolinium-based contrast agents.

Metabolic profiles associated with exposure to ambient particulate air pollution: findings from the Betula cohort.

Introduction: Air pollution is a significant contributor to morbidity and mortality globally and has been linked to an increased risk of dementia. Previous studies within the Betula cohort in Northern Sweden have demonstrated associations between air pollution and dementia, as well as distinctive metabolomic profiles in dementia patients compared to controls. This study aimed to investigate whether air pollution is associated with quantitative changes in metabolite levels within this cohort, and whether future dementia status would modify this association.

Nonparametric distributions of tensor-valued Lorentzian diffusion spectra for model-free data inversion in multidimensional diffusion MRI.

Magnetic resonance imaging (MRI) is the method of choice for noninvasive studies of micrometer-scale structures in biological tissues via their effects on the time- and frequency-dependent (restricted) and anisotropic self-diffusion of water. While new designs of time-dependent magnetic field gradient waveforms have enabled disambiguation between different aspects of translational motion that are convolved in traditional MRI methods relying on single pairs of field gradient pulses, data analysis for complex heterogeneous materials remains a challenge. Here, we propose and demonstrate nonparametric distributions of tensor-valued Lorentzian diffusion spectra, or "D(ω) distributions," as a general representation with sufficient flexibility to describe the MRI signal response from a wide range of model systems and biological tissues investigated with modulated gradient waveforms separating and correlating the effects of restricted and anisotropic diffusion.

A patient-derived amyotrophic lateral sclerosis blood-brain barrier model for focused ultrasound-mediated anti-TDP-43 antibody delivery.

Background: Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disorder with minimally effective treatment options. An important hurdle in ALS drug development is the non-invasive therapeutic access to the motor cortex currently limited by the presence of the blood-brain barrier (BBB). Focused ultrasound and microbubble (FUS) treatment is an emerging technology that was successfully used in ALS patients to temporarily open the cortical BBB.

Brain plasticity and neuroinflammatory protein biomarkers with circulating MicroRNAs as predictors of acute brain injury outcome - A prospective cohort study.

Background: Brain recovery mechanisms after injuries like aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS), and traumatic brain injury (TBI) involve brain plasticity, synaptic regeneration, and neuroinflammation. We hypothesized that serum levels of the p75 neurotrophic receptor (p75NTR) and associated signaling proteins, as well as differentially expressed (DE) microRNAs, could predict recovery outcomes irrespective of injury type.

Methods: A prospective patient cohort with ischemic stroke (IS, n = 30), aneurysmal subarachnoid hemorrhage (aSAH, n = 31), and traumatic brain injury (TBI, n = 13) were evaluated (total n = 74).