GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets.

Psoriasis is a common, debilitating immune-mediated skin disease. Genetic studies have identified biological mechanisms of psoriasis risk, including those targeted by effective therapies. However, the genetic liability to psoriasis is not fully explained by variation at robustly identified risk loci.

Tandem repeat expansions and copy number variations as risk factors and diagnostic tools for amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder leading to upper and lower motoneurons degeneration. Although several mechanisms potentially involved in disease development have been identified, its pathogenesis is not fully understood. From the patient side, ALS diagnosis, still based on clinical criteria, can be difficult and may take up to 1 year.

Sodium valproate, a potential repurposed treatment for the neurodegeneration in Wolfram syndrome (TREATWOLFRAM): trial protocol for a pivotal multicentre, randomised double-blind controlled trial.

Introduction: Wolfram syndrome (Spectrum Disorder) is an ultra-rare monogenic form of progressive neurodegeneration and diabetes mellitus. In common with most rare diseases, there are no therapies to slow or stop disease progression. Sodium valproate, an anticonvulsant with neuroprotective properties, is anticipated to mediate its effect via alteration of cell cycle kinetics, increases in p21 expression levels and reduction in apoptosis and increase in Wolframin protein expression.

AskBeacon-performing genomic data exchange and analytics with natural language.

Motivation: Enabling clinicians and researchers to directly interact with global genomic data resources by removing technological barriers is vital for medical genomics. AskBeacon enables large language models (LLMs) to be applied to securely shared cohorts via the Global Alliance for Genomics and Health Beacon protocol. By simply "asking" Beacon, actionable insights can be gained, analyzed, and made publication-ready.

Exploring the Potential Imaging Biomarkers for Parkinson's Disease Using Machine Learning Approach.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and neuropsychiatric symptoms resulting from the loss of dopamine-producing neurons in the substantia nigra pars compacta (SNc). Dopamine transporter scan (DATSCAN), based on single-photon emission computed tomography (SPECT), is commonly used to evaluate the loss of dopaminergic neurons in the striatum. This study aims to identify a biomarker from DATSCAN images and develop a machine learning (ML) algorithm for PD diagnosis.

Whole blood transcriptome profile identifies motor neurone disease RNA biomarker signatures.

Blood-based biomarkers for motor neuron disease are needed for better diagnosis, progression prediction, and clinical trial monitoring. We used whole blood-derived total RNA and performed whole transcriptome analysis to compare the gene expression profiles in (motor neurone disease) MND patients to the control subjects. We compared 42 MND patients to 42 aged and sex-matched healthy controls and described the whole transcriptome profile characteristic for MND.

Lipid-mediated resolution of inflammation and survival in amyotrophic lateral sclerosis.

Neuroinflammation impacts on the progression of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. Specialized pro-resolving mediators trigger the resolution of inflammation. We investigate the specialized pro-resolving mediator blood profile and their receptors' expression in peripheral blood mononuclear cells in relation to survival in ALS.

Enhancing Aseptic Inflammation Resolution with 1-(2-Ethoxyethyl)-4-(pent-1-yn-1-yl)piperidin-4-yl Propionate: A Novel β-Cyclodextrin Complex as a Therapeutic Agent.

The synthesized compound, 1-(2-ethoxyethyl)-4-(pent-1-yn-1-yl)piperidin-4-yl propionate (), and its 1:1 complex with β-cyclodextrin () have been characterized for the first time through a comprehensive suite of analytical methods. This study explores the therapeutic potential of in modulating immune responses and accelerating the resolution of septic inflammation induced by chromium and vanadium ions in outbred male rats. The research highlights the significant impact of on the dynamics of regulatory T lymphocytes (Tregs), notably causing a reduction in the CD4CD25 fractions at the onset of inflammation.

Gender-different effect of Src family kinases antagonism on photophobia and trigeminal ganglion activity.

Background: Src family kinases (SFKs) contribute to migraine pathogenesis, yet its role in regulating photophobia behaviour, one of the most common forms of migraine, remains unknown. Here, we addressed whether SFKs antagonism alleviates photophobia behavior and explored the underlying mechanism involving hypothalamus and trigeminal ganglion activity, as measured by the alteration of neuropeptide levels and transcriptome respectively.

Methods: A rapid-onset and injury-free mouse model of photophobia was developed following intranasal injection of the TRPA1 activator, umbellulone.

Corrigendum: Genome-wide association study identifying variants related to performance and injury in high-performance athletes.

[This corrects the article DOI: 10.1177/15353702231198068.].

SVA Regulation of Transposable Element Clustered Transcription within the Major Histocompatibility Complex Genomic Class II Region of the Parkinson's Progression Markers Initiative.

SINE-VNTR-Alu (SVA) retrotransposons can regulate expression quantitative trait loci (eQTL) of coding and noncoding genes including transposable elements (TEs) distributed throughout the human genome. Previously, we reported that expressed SVAs and human leucocyte antigen (HLA) class II genotypes on chromosome 6 were associated significantly with Parkinson's disease (PD). Here, our aim was to follow-up our previous study and evaluate the SVA associations and their regulatory effects on the transcription of TEs within the HLA class II genomic region.

Dopamine Pathway and Parkinson's Risk Variants Are Associated with Levodopa-Induced Dyskinesia.

Background: Levodopa-induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson's disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including GBA1 and LRRK2.

Objectives: Our goal was to investigate the effects of genetic variants on risk and time to LID.

The whole transcriptome analysis using FFPE and fresh tissue samples identifies the molecular fingerprint of osteosarcoma.

Osteosarcoma is a form of bone cancer that predominantly impacts osteoblasts, the cells responsible for creating fresh bone tissue. Typical indications include bone pain, inflammation, sensitivity, mobility constraints, and fractures. Utilising imaging techniques such as X-rays, MRI scans, and CT scans can provide insights into the size and location of the tumour.

Exploring the Complexity of the Human Respiratory Virome through an In Silico Analysis of Shotgun Metagenomic Data Retrieved from Public Repositories.

Background: Respiratory viruses significantly impact global morbidity and mortality, causing more disease in humans than any other infectious agent. Beyond pathogens, various viruses and bacteria colonize the respiratory tract without causing disease, potentially influencing respiratory diseases' pathogenesis. Nevertheless, our understanding of respiratory microbiota is limited by technical constraints, predominantly focusing on bacteria and neglecting crucial populations like viruses.

Deciphering the role of a SINE-VNTR-Alu retrotransposon polymorphism as a biomarker of Parkinson's disease progression.

SINE-VNTR-Alu (SVA) retrotransposons are transposable elements which represent a source of genetic variation. We previously demonstrated that the presence/absence of a human-specific SVA, termed SVA_67, correlated with the progression of Parkinson's disease (PD). In the present study, we demonstrate that SVA_67 acts as expression quantitative trait loci, thereby exhibiting a strong regulatory effect across the genome using whole genome and transcriptomic data from the Parkinson's progression markers initiative cohort.

Regulatory SVA retrotransposons and classical HLA genotyped-transcripts associated with Parkinson's disease.

Introduction: Parkinson's disease (PD) is a neurodegenerative and polygenic disorder characterised by the progressive loss of neural dopamine and onset of movement disorders. We previously described eight SINE-VNTR-Alu (SVA) retrotransposon-insertion-polymorphisms (RIPs) located and expressed within the Human Leucocyte Antigen (HLA) genomic region of chromosome 6 that modulate the differential co-expression of 71 different genes including the HLA classical class I and class II genes in a Parkinson's Progression Markers Initiative (PPMI) cohort.

Aims And Methods: In the present study, we (1) reanalysed the PPMI genomic and transcriptomic sequencing data obtained from whole blood of 1521 individuals (867 cases and 654 controls) to infer the genotypes of the transcripts expressed by eight classical HLA class I and class II genes as well as and the haplotypes, and (2) examined the statistical differences between three different PD subgroups (cases) and healthy controls (HC) for the HLA and SVA transcribed genotypes and inferred haplotypes.

Exploring SVA Insertion Polymorphisms in Shaping Differential Gene Expressions in the Central Nervous System.

Transposable elements (TEs) are repetitive elements which make up around 45% of the human genome. A class of TEs, known as SINE-VNTR-Alu (SVA), demonstrate the capacity to mobilise throughout the genome, resulting in SVA polymorphisms for their presence or absence within the population. Although studies have previously highlighted the involvement of TEs within neurodegenerative diseases, such as Parkinson's disease and amyotrophic lateral sclerosis (ALS), the exact mechanism has yet to be identified.

Transcriptional Landscape of Repetitive Elements in Psoriatic Skin from Large Cohort Studies: Relevance to Psoriasis Pathophysiology.

While studies demonstrating the expression of repetitive elements (REs) in psoriatic skin using RNA-seq have been published before, not many studies have focused on the genome-wide expression patterns using larger cohorts. This study investigated the transcriptional landscape of differentially expressed REs in lesional and non-lesional skin from two previously published large datasets. We observed significant differential expression of REs in lesional psoriatic skin as well as the skin of healthy controls.

Regulation of expression quantitative trait loci by SVA retrotransposons within the major histocompatibility complex.

Genomic and transcriptomic studies of expression quantitative trait loci (eQTL) revealed that SINE-VNTR-Alu (SVA) retrotransposon insertion polymorphisms (RIPs) within human genomes markedly affect the co-expression of many coding and noncoding genes by coordinated regulatory processes. This study examined the polymorphic SVA modulation of gene co-expression within the major histocompatibility complex (MHC) genomic region where more than 160 coding genes are involved in innate and adaptive immunity. We characterized the modulation of SVA RIPs utilizing the genomic and transcriptomic sequencing data obtained from whole blood of 1266 individuals in the Parkinson's Progression Markers Initiative (PPMI) cohort that included an analysis of human leukocyte antigen () regulation in a subpopulation of the cohort.

Genome-Wide Differential Transcription of Long Noncoding RNAs in Psoriatic Skin.

Long noncoding RNAs (lncRNAs) may contribute to the formation of psoriatic lesions. The present study's objective was to identify long lncRNA genes that are differentially expressed in patient samples of psoriasis through computational analysis techniques. By using previously published RNA sequencing data from psoriatic and healthy patients (n = 324), we analysed the differential expression of lncRNAs to determine transcripts of heightened expression.

Transcriptomic profiling of cerebrospinal fluid identifies ALS pathway enrichment and RNA biomarkers in MND individuals.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder and the most common form of motor neurone disease (MND) which is characterized by the damage and death of motor neurons in the brain and spinal cord of affected individuals. Due to the heterogeneity of the disease, a better understanding of the interaction between genetics and biochemistry with the identification of biomarkers is crucial for therapy development. In this study, we used cerebrospinal fluid (CSF) RNA-sequencing data from the New York Genome Center (NYGC) ALS Consortium and analyzed differential gene expression between 47 MND individuals and 29 healthy controls.