Label free, capillary-scale blood flow mapping in vivo reveals that low-intensity focused ultrasound evokes persistent dilation in cortical microvasculature.

Non-invasive, low intensity focused ultrasound is an emerging neuromodulation technique that offers the potential for precision, personalized therapy. An increasing body of research has identified mechanosensitive ion channels that can be modulated by FUS and support acute electrical activity in neurons. However, neuromodulatory effects that persist from hours to days have also been reported.

Parkinson's families project: a UK-wide study of early onset and familial Parkinson's disease.

The Parkinson's Families Project is a UK-wide study aimed at identifying genetic variation associated with familial and early-onset Parkinson's disease (PD). We recruited individuals with a clinical diagnosis of PD and age at motor symptom onset ≤45 years and/or a family history of PD in up to third-degree relatives. Where possible, we also recruited affected and unaffected relatives.

Label free, capillary-scale blood flow mapping reveals that low intensity focused ultrasound evokes persistent dilation in cortical microvasculature.

Non-invasive, low intensity focused ultrasound (FUS) is an emerging neuromodulation technique that offers the potential for precision, personalized therapy. An increasing body of research has identified mechanosensitive ion channels that can be modulated by FUS and support acute electrical activity in neurons. However, neuromodulatory effects that persist from hours to days have also been reported.

CONSISTENT SPECTRAL CLUSTERING OF NETWORK BLOCK MODELS UNDER LOCAL DIFFERENTIAL PRIVACY.

The stochastic block model (SBM) and degree-corrected block model (DCBM) are network models often selected as the fundamental setting in which to analyze the theoretical properties of community detection methods. We consider the problem of spectral clustering of SBM and DCBM networks under a local form of edge differential privacy. Using a randomized response privacy mechanism called the edge-flip mechanism, we develop theoretical guarantees for differentially private community detection, demonstrating conditions under which this strong privacy guarantee can be upheld while achieving spectral clustering convergence rates that match the known rates without privacy.

Assessing the relationship between monoallelic PRKN mutations and Parkinson's risk.

Biallelic Parkin (PRKN) mutations cause autosomal recessive Parkinson's disease (PD); however, the role of monoallelic PRKN mutations as a risk factor for PD remains unclear. We investigated the role of single heterozygous PRKN mutations in three large independent case-control cohorts totalling 10 858 PD cases and 8328 controls. Overall, after exclusion of biallelic carriers, single PRKN mutations were more common in PD than controls conferring a >1.

The Effect of Frailty versus Initial Glasgow Coma Score in Predicting Outcomes Following Chronic Subdural Hemorrhage: A Preliminary Analysis.

Background Initial Glasgow Coma Score (iGCS) is a well-known predictor of adverse outcomes following chronic subdural hemorrhage (cSDH). Frailty, i.e.

Genetic Analysis Using a Multi-Parent Wheat Population Identifies Novel Sources of Septoria Tritici Blotch Resistance.

is the causative fungal pathogen of septoria tritici blotch (STB) disease of wheat ( L.) that continuously threatens wheat crops in Ireland and throughout Europe. Under favorable conditions, STB can cause up to 50% yield losses if left untreated.

The Effect of Frailty and Patient Comorbidities on Outcomes After Acute Subdural Hemorrhage: A Preliminary Analysis.

Background: Frailty is associated with worse outcomes across a variety of neurosurgical diseases. However, its effect on acute subdural hemorrhage (aSDH) outcomes is unclear. The goal of this study is to compare 3 measures of frailty with the gold standard (i.

Taxonomically Restricted Wheat Genes Interact With Small Secreted Fungal Proteins and Enhance Resistance to Septoria Tritici Blotch Disease.

Understanding the nuances of host/pathogen interactions are paramount if we wish to effectively control cereal diseases. In the case of the wheat/ interaction that leads to Septoria tritici blotch (STB) disease, a 10,000-year-old conflict has led to considerable armaments being developed on both sides which are not reflected in conventional model systems. Taxonomically restricted genes (TRGs) have evolved in wheat to better allow it to cope with stress caused by fungal pathogens, and has evolved specialized effectors which allow it to manipulate its' host.

Ambroxol for the Treatment of Patients With Parkinson Disease With and Without Glucocerebrosidase Gene Mutations: A Nonrandomized, Noncontrolled Trial.

Importance: Mutations of the glucocerebrosidase gene, GBA1 (OMIM 606463), are the most important risk factor for Parkinson disease (PD). In vitro and in vivo studies have reported that ambroxol increases β-glucocerebrosidase (GCase) enzyme activity and reduces α-synuclein levels. These observations support a potential role for ambroxol therapy in modifying a relevant pathogenetic pathway in PD.

Genetic analysis of Mendelian mutations in a large UK population-based Parkinson's disease study.

Our objective was to define the prevalence and clinical features of genetic Parkinson's disease in a large UK population-based cohort, the largest multicentre prospective clinico-genetic incident study in the world. We collected demographic data, Movement Disorder Society Unified Parkinson's Disease Rating Scale scores, and Montreal Cognitive Assessment scores. We analysed mutations in PRKN (parkin), PINK1, LRRK2 and SNCA in relation to age at symptom onset, family history and clinical features.

A Pathogen-Responsive Leucine Rich Receptor Like Kinase Contributes to Resistance in Cereals.

Receptor-like kinases form the largest family of receptors in plants and play an important role in recognizing pathogen-associated molecular patterns and modulating the plant immune responses to invasive fungi, including cereal defenses against fungal diseases. But hitherto, none have been shown to modulate the wheat response to the economically important Fusarium head blight (FHB) disease of small-grain cereals. Homologous genes were identified on barley chromosome 6H () and wheat chromosome 6DL (), which encode the characteristic domains of surface-localized receptor like kinases.

Analysis of the genetic variability in Parkinson's disease from Southern Spain.

To date, a large spectrum of genetic variants has been related to familial and sporadic Parkinson's disease (PD) in diverse populations worldwide. However, very little is known about the genetic landscape of PD in Southern Spain, despite its particular genetic landscape coming from multiple historical migrations. We included 134 PD patients in this study, of which 97 individuals were diagnosed with late-onset sporadic PD (LOPD), 28 with early-onset sporadic PD (EOPD), and 9 with familial PD (FPD).

A 6.4 Mb duplication of the α-synuclein locus causing frontotemporal dementia and Parkinsonism: phenotype-genotype correlations.

Importance: α-Synuclein (SNCA) locus duplications are associated with variable clinical features and reduced penetrance but the reasons underlying this variability are unknown.

Objectives: To report a novel family carrying a heterozygous 6.4 Mb duplication of the SNCA locus with an atypical clinical presentation strongly reminiscent of frontotemporal dementia and late-onset pallidopyramidal syndromes and study phenotype-genotype correlations in SNCA locus duplications.

C9orf72 expansions are the most common genetic cause of Huntington disease phenocopies.

Objective: In many cases where Huntington disease (HD) is suspected, the genetic test for HD is negative: these are known as HD phenocopies. A repeat expansion in the C9orf72 gene has recently been identified as a major cause of familial and sporadic frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Our objective was to determine whether this mutation causes HD phenocopies.

Amplification refractory mutation system linear extension: a novel, gel-free, enzyme-linked immunoassay method for DNA genotyping.

A single synthesis cycle of the amplification refractory mutation system (ARMS) was applied to the analysis of K-ras alleles amplified by polymerase chain reaction and immobilized in streptavidin-coated microtiter plates. The ARMS cycle provided the specificity and molecular switch characteristics of a conventional ARMS assay. This allowed linear extension from an allele-specific primer and the incorporation of digoxigenin-labeled deoxyuridine monophosphate from digoxigenin-11-deoxyuridine triphosphate in the presence of the appropriate K-ras allele.

The detection of K-ras mutations in colorectal cancer using the amplification-refractory mutation system.

A total of 301 colorectal carcinoma (CRC) archival samples were analysed using the amplification-refractory mutation system (ARMS). Each sample was examined to determine the mutation status of codons 12 and 13 of the K-ras oncogene. The results from direct DNA sequence analysis carried out on 30 of the samples differed from the ARMS result in almost 50% of the cases as a result of the relative excess of wild-type to mutated DNA sequences.

Bioethics and natural law: the relationship in Catholic teaching.

In the discipline of Catholic moral theology, bioethics (traditionally described as medical ethics) has held a major place. The systematic development of bioethics has drawn principally upon a natural law ethic, supported by broader religious arguments. The purpose of this essay is to examine the status and role of natural law in Catholic teaching as it bears upon bioethics.