Assessment of complementary white matter microstructural changes and grey matter atrophy in the 6-OHDA-induced model of Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by motor symptoms such as tremors, rigidity, and bradykinesia. Magnetic resonance imaging (MRI) offers a non-invasive means to study PD and its progression. This study utilized the unilateral 6-hydroxydopamine (6-OHDA) rat model of parkinsonism to assess whether white matter microstructural integrity measured using advanced free-water diffusion tensor imaging metrics (fw-DTI) and gray matter density using voxel-based morphometry (VBM) can serve as imaging biomarkers of pathological changes following nigrostriatal denervation.

The α-synuclein seed amplification assay: Interpreting a test of Parkinson's pathology.

The α-synuclein seed amplification assay (αSyn-SAA) sensitively detects Lewy pathology, the amyloid state of α-synuclein, in the cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD). The αSyn-SAA harnesses the physics of seeding, whereby a superconcentrated solution of recombinant α-synuclein lowers the thermodynamic threshold (nucleation barrier) for aggregated α-synuclein to act as a nucleation catalyst ("seed") to trigger the precipitation (nucleation) of monomeric α-synuclein into pathology. This laboratory setup increases the signal for identifying a catalyst if one is present in the tissue examined.

The effects of chemogenetic targeting of serotonin-projecting pathways on L-DOPA-induced dyskinesia and psychosis in a bilateral rat model of Parkinson's disease.

Introduction: Parkinson's disease (PD) is commonly characterized by severe dopamine (DA) depletion within the substantia nigra (SN) leading to a myriad of motor and non-motor symptoms. One underappreciated and prevalent non-motor symptom, Parkinson's disease-associated psychosis (PDAP), significantly erodes patient and caregiver quality of life yet remains vastly understudied. While the gold standard pharmacotherapy for motor symptoms Levodopa (LD) is initially highly effective, it can lead to motor fluctuations like LD-induced dyskinesia (LID) and non-motor fluctuations such as intermittent PDAP.

Slit regulates compartment-specific targeting of dendrites and axons in the brain.

Proper functioning of the nervous system requires precise neuronal connections at subcellular domains, which can be achieved by projection of axons or dendrites to subcellular domains of target neurons. Here we studied subcellular-specific targeting of dendrites and axons in the mushroom body (MB), where mushroom body output neurons (MBONs) and local dopaminergic neurons (DAN) project their dendrites and axons, respectively, to specific compartments of MB axons. Through genetic ablation, we demonstrate that compartment-specific targeting of MBON dendrites and DAN axons involves mutual repulsion of MBON dendrites and/or DAN axons between neighboring compartments.

Engineered AAV capsid transport mutants overcome transduction deficiencies in the aged CNS.

Adeno-associated virus (AAV)-based gene therapy has enjoyed great successes over the past decade, with Food and Drug Administration-approved therapeutics and a robust clinical pipeline. Nonetheless, barriers to successful translation remain. For example, advanced age is associated with impaired brain transduction, with the diminution of infectivity depending on anatomical region and capsid.

ENGINEERED NANOBODIES WITH PROGRAMMABLE TARGET ANTIGEN PROTEOLYSIS (PTAP) FUSIONS REGULATE INTRACELLULAR ALPHA-SYNUCLEIN IN VITRO AND IN VIVO.

Alpha-synuclein (αSyn) aggregation and the formation of Lewy pathology (LP) is a foundational pathophysiological phenomenon in synucleinopathies. Delivering therapeutic single-chain and single-domain antibodies that bind pathogenic targets can disrupt intracellular aggregation. The fusion of antibody fragments to a negatively-charged proteasomal targeting motif (PEST) creates bifunctional constructs that enhance both solubility and turnover.

Quinpirole inhibits levodopa-induced dyskinesias at structural and behavioral levels: Efficacy negated by co-administration of isradipine.

Dopamine depletion associated with parkinsonism induces plastic changes in striatal medium spiny neurons (MSN) that are maladaptive and associated with the emergence of the negative side-effect of standard treatment: the abnormal involuntary movements termed levodopa-induced dyskinesia (LID). Prevention of MSN dendritic spine loss is hypothesized to diminish liability for LID in Parkinson's disease. Blockade of striatal CaV1.

EEG coherence before and after giving birth.

During pregnancy and the postpartum period, changes in brain volume and in motivational, sensory, cognitive, and emotional processes have been described. However, to date, longitudinal modifications of brain function have been understudied. To explore regional cortical coupling, in pregnancy and at 3 months postpartum, we analyzed resting-state electroencephalographic (EEG) coherence in the delta, theta, alpha, alpha, beta, and beta frequency bands across frontal and parietal regions of the maternal brain (Fp1, Fp2, F3, F4, P3, and P4).

A comparison of machine learning approaches for the quantification of microglial cells in the brain of mice, rats and non-human primates.

Microglial cells are brain-specific macrophages that swiftly react to disruptive events in the brain. Microglial activation leads to specific modifications, including proliferation, morphological changes, migration to the site of insult, and changes in gene expression profiles. A change in inflammatory status has been linked to many neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease.

Downregulation of striatal Ca1.3 inhibits the escalation of levodopa-induced dyskinesia in male and female parkinsonian rats of advanced age.

In the past 25 years, the prevalence of Parkinson's disease (PD) has nearly doubled. Age remains the primary risk factor for PD and as the global aging population increases this trend is predicted to continue. Even when treated with levodopa, the gold standard dopamine (DA) replacement therapy, individuals with PD frequently develop therapeutic side effects.

Epidemiological Characteristics of Deaths from COVID-19 in Peru during the Initial Pandemic Response.

Background And Aim: Peru is the country with the highest mortality rate from COVID-19 globally, so the analysis of the characteristics of deaths is of national and international interest. The aim was to determine the epidemiological characteristics of deaths from COVID-19 in Peru from 28 March to 21 May 2020.

Methods: Deaths from various sources were investigated, including the COVID-19 Epidemiological Surveillance and the National System of Deaths (SINADEF).

Killer whale innovation: teaching animals to use their creativity upon request.

Thinking flexibly is a skill that enables animals to adapt to changing environments, which enhances survival. Killer whales, Orcinus orca, as the ocean apex predator display a number of complex cognitive abilities, especially flexible thinking or creativity when it comes to foraging. In human care, smaller dolphins and other marine mammals have been trained to think creatively while under stimulus control.

Circle Method for Robust Estimation of Local Conduction Velocity High-Density Maps From Optical Mapping Data: Characterization of Radiofrequency Ablation Sites.

Conduction velocity (CV) slowing is associated with atrial fibrillation (AF) and reentrant ventricular tachycardia (VT). Clinical electroanatomical mapping systems used to localize AF or VT sources as ablation targets remain limited by the number of measuring electrodes and signal processing methods to generate high-density local activation time (LAT) and CV maps of heterogeneous atrial or trabeculated ventricular endocardium. The morphology and amplitude of bipolar electrograms depend on the direction of propagating electrical wavefront, making identification of low-amplitude signal sources commonly associated with fibrotic area difficulty.

The E-Syt3 cleavage and traffic uncovers the primordial cisterna, a new organelle that mothers the lipid droplets in the adipocyte.

Extended synaptotagmins are endoplasmic reticulum proteins consisting of an SMP domain and multiple C2 domains that bind phospholipids and Ca . E-Syts create contact junctions between the ER and plasma membrane (PM) to facilitate the exchange of glycerophospholipids between the apposed membranes. We find in the differentiating adipocyte that the E-Syt3 carboxyl domain is cleaved by a multi-step mechanism that includes removing the C2C domain.

Seroprevalence of Brucella canis in canines from a dog shelter in Bogotá, Colombia.

Introduction: The risk of Brucella canis infection in humans and dogs has increased due to the permanent exposure to asymptomatic carrier dogs. In Colombia, there is evidence of B. canis infection in humans living with dogs.

Thresholds, Firing Rates, and Order of Recruitment of Anterior Temporalis Muscle Single-Motor Units During Experimental Masseter Muscle Pain.

Aims: To test the hypothesis that, in comparison with control, experimental noxious stimulation of the right masseter muscle would result in significant changes in the firing rates, thresholds, and recruitment orders of single-motor units (SMUs) of the nonpainful, synergistic right anterior temporalis muscle during goal-directed isometric biting task performance.

Methods: Twenty healthy volunteers received an infusion of hypertonic saline (HS; 5% sodium chloride) into the right masseter to produce pain intensity of 40 to 60 on a 100-mm visual analog scale (VAS). Isotonic saline (IS) infusion was a control.

Gene Therapy to Modulate Alpha-Synuclein in Synucleinopathies.

The protein alpha-Synuclein (α-Syn) is a key contributor to the etiology of Parkinson's disease (PD) with aggregation, trans-neuronal spread, and/or depletion of α-Syn being viewed as crucial events in the molecular processes that result in neurodegeneration. The exact succession of pathological occurrences that lead to neuronal death are still largely unknown and are likely to be multifactorial in nature. Despite this unknown, α-Syn dose and stability, autophagy-lysosomal dysfunction, and inflammation, amongst other cellular impairments, have all been described as participatory events in the neurodegenerative process.

Netrin-1 receptor UNC5C cleavage by active δ-secretase enhances neurodegeneration, promoting Alzheimer's disease pathologies.

Netrin-1, a family member of laminin-related secreted proteins, mediates axon guidance and cell migration during neural development. T835M mutation in netrin receptor UNC5C predisposes to the late-onset Alzheimer's disease (AD) and increases neuronal cell death. However, it remains unclear how this receptor is molecularly regulated in AD.

α-Synuclein antisense oligonucleotides as a disease-modifying therapy for Parkinson's disease.

Parkinson's disease (PD) is a prevalent neurodegenerative disease with no approved disease-modifying therapies. Multiplications, mutations, and single nucleotide polymorphisms in the SNCA gene, encoding α-synuclein (aSyn) protein, either cause or increase risk for PD. Intracellular accumulations of aSyn are pathological hallmarks of PD.

A silent public health threat: emergence of Mayaro virus and co-infection with Dengue in Peru.

Objective: To describe frequency and clinical characteristics of MAYV infection in Piura, as well as the association of this pathogen with DENV.

Results: A total of 86/496 (17.3%) cases of MAYV were detected, of which 54 were MAYV mono-infection and 32 were co-infection with DENV, accounting for 10.

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.

Striatal Nurr1 Facilitates the Dyskinetic State and Exacerbates Levodopa-Induced Dyskinesia in a Rat Model of Parkinson's Disease.

The transcription factor Nurr1 has been identified to be ectopically induced in the striatum of rodents expressing l-DOPA-induced dyskinesia (LID). In the present study, we sought to characterize Nurr1 as a causative factor in LID expression. We used rAAV2/5 to overexpress Nurr1 or GFP in the parkinsonian striatum of LID-resistant Lewis or LID-prone Fischer-344 (F344) male rats.

Oropouche infection a neglected arbovirus in patients with acute febrile illness from the Peruvian coast.

Objective: To evaluate the frequency of infection caused by the Oropouche virus (OROV) in 496 patients with acute febrile disease (AFI), whose samples were obtained for the analysis of endemic arboviruses in a previous investigation carried out in 2016.

Results: OROV was detected in 26.4% (131/496) of serum samples from patients with AFI.