Casein Kinase 1δ Phosphorylates TDP-43 and Suppresses Its Function in Tau mRNA Processing.

Background: Neurofibrillary tangle aggregated from anomalous hyperphosphorylated tau is a hallmark of Alzheimer's disease (AD). Trans-active response DNA-binding protein of 43 kDa (TDP-43) enhances the instability and exon (E) 10 inclusion of tau mRNA. Cytoplasmic inclusion of hyperphosphorylated TDP-43 in the neurons constitutes the third most prevalent proteinopathy of AD.

Reduced expression in preterm birth of sFLT-1 and PlGF with a high sFLT-1/PlGF ratio in extracellular vesicles suggests a potential biomarker.

Preterm birth may have a pathological impact on intrauterine development of the fetal brain, resulting in developmental disabilities. In this study, we examine the expression of soluble Fms-like tyrosine kinase 1 (sFLT-1) and placental growth factor (PlGF), which is one of the vascular endothelial growth factors (VEGFs), as these play a key role in angiogenesis; in particular, we examine their effect on the sFLT-1/PlGF ratio in cases of preterm birth as compared to typical pregnancies. Enzyme-linked immunosorbent assay was performed on samples of maternal-derived plasma and extracellular vesicles-exosomes (EVs-EXs) isolated at the third trimester, consisting of 17 samples from cases of preterm birth and 38 control cases.

HIF-1α Causes LCMT1/PP2A Deficiency and Mediates Tau Hyperphosphorylation and Cognitive Dysfunction during Chronic Hypoxia.

Chronic hypoxia is a risk factor for Alzheimer's disease (AD), and the neurofibrillary tangle (NFT) formed by hyperphosphorylated tau is one of the two major pathological changes in AD. However, the effect of chronic hypoxia on tau phosphorylation and its mechanism remains unclear. In this study, we investigated the role of HIF-1α (the functional subunit of hypoxia-inducible factor 1) in tau pathology.

Gut Microbiota and Immunotherapy for Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that eventually leads to dementia and death of the patient. Currently, no effective treatment is available that can slow or halt the progression of the disease. The gut microbiota can modulate the host immune system in the peripheral and central nervous system through the microbiota-gut-brain axis.

Zfra Inhibits the TRAPPC6AΔ-Initiated Pathway of Neurodegeneration.

When WWOX is downregulated in middle age, aggregation of a protein cascade, including TRAPPC6AΔ (TPC6AΔ), TIAF1, and SH3GLB2, may start to occur, and the event lasts more than 30 years, which results in amyloid precursor protein (APP) degradation, amyloid beta (Aβ) generation, and neurodegeneration, as shown in Alzheimer's disease (AD). Here, by treating neuroblastoma SK-N-SH cells with neurotoxin MPP+, upregulation and aggregation of TPC6AΔ, along with aggregation of TIAF1, SH3GLB2, Aβ, and tau, occurred. MPP+ is an inducer of Parkinson's disease (PD), suggesting that TPC6AΔ is a common initiator for AD and PD pathogenesis.

The Global Jukebox: A public database of performing arts and culture.

Standardized cross-cultural databases of the arts are critical to a balanced scientific understanding of the performing arts, and their role in other domains of human society. This paper introduces the Global Jukebox as a resource for comparative and cross-cultural study of the performing arts and culture. The Global Jukebox adds an extensive and detailed global database of the performing arts that enlarges our understanding of human cultural diversity.

Alzheimer's Disease: Challenges and a Therapeutic Opportunity to Treat It with a Neurotrophic Compound.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with an insidious onset and multifactorial nature. A deficit in neurogenesis and synaptic plasticity are considered the early pathological features associated with neurofibrillary tau and amyloid β pathologies and neuroinflammation. The imbalance of neurotrophic factors with an increase in FGF-2 level and a decrease in brain derived neurotrophic factor (BDNF) and neurotrophin 4 (NT-4) in the hippocampus, frontal cortex and parietal cortex and disruption of the brain micro-environment are other characteristics of AD.

A modified Cued Recall Test for detecting prodromal AD in adults with Down syndrome.

Introduction: The development of valid methods to diagnose prodromal Alzheimer's disease (AD) in adults with Down syndrome (DS) is one of the many goals of the Alzheimer's Biomarkers Consortium-Down Syndrome (ABC-DS).

Methods: The diagnostic utility of a modified Cued Recall Test (mCRT) was evaluated in 332 adults with DS ranging from 25 to 81 years of age. Total recall was selected a priori, as the primary indicator of performance.

Acute and chronic maternal exposure to fine particulate matter and prelabor rupture of the fetal membranes: A nation-wide survey in China.

Background: Prelabor rupture of the fetal membranes (PROM) is a major contributor to adverse perinatal outcomes. Some epidemiologic studies explored the association between maternal PM exposure and PROM but failed to treat the labor induction and prelabor cesarean section as censored observations.

Objective: We aimed to evaluated whether acute and chronic maternal ambient PM exposure may increase the risk of PROM in China.

Characterization of placental and decidual cell development in early pregnancy loss by single-cell RNA sequencing.

Background: Early pregnancy loss (EPL) presents as sporadic or recurrent miscarriage during the first trimester. In addition to chromosomal defects, EPL may result from impairment of the placental-decidual interface at early gestational age due to gene-environmental interactions.

Methods: To better understand the pathogenesis associated with this impairment, cell development in chorionic villi and decidua of different forms of EPL (sporadic or recurrent) was investigated with single-cell RNA sequencing and compared to that of normal first-trimester tissue.

Tau seeding activity in various regions of down syndrome brain assessed by two novel assays.

Propagation of tau pathology via the seeding of naive tau aggregation underlies the progression of Alzheimer's disease (AD) and related tauopathies. Individuals with Down syndrome (DS) develop tau pathology at the fourth decade of life, but tau seeding activity in DS brain has not yet been determined. To measure tau seeding activity, we developed capture assay and seeded-tau aggregation assay with truncated tau.

Preterm birth update in Australasia: A report of the international symposium of Preterm Birth International Collaborative-Australasia branch.

Preterm birth (PTB) is one of the most important problems that pose dilemmas for both the obstetrician and neonatologist, placing a heavy burden psychologically and financially on the families involved, and triggering high socio-economic costs to the public healthcare. The rate of PTB in Asian countries has been ranked at top globally. To reduce the PTB rate, to promote the prevention and intervention for PTB, and to better understand the pathophysiology underlying PTB, the Preterm Birth International Collaborative Australia branch (PREBIC-AA) was launched in 2017.

Correction: Hom et al. Cognitive Function during the Prodromal Stage of Alzheimer's Disease in Down Syndrome: Comparing Models. 2021, , 1220.

We would like to submit the following correction to our recently published paper [...

WWOX Controls Cell Survival, Immune Response and Disease Progression by pY33 to pS14 Transition to Alternate Signaling Partners.

Tumor suppressor WWOX inhibits cancer growth and retards Alzheimer's disease (AD) progression. Supporting evidence shows that the more strongly WWOX binds intracellular protein partners, the weaker is cancer cell growth in vivo. Whether this correlates with retardation of AD progression is unknown.

SIRT1 deficiency increases O-GlcNAcylation of tau, mediating synaptic tauopathy.

Hyperphosphorylation of the microtubule associated protein tau is associated with several neurodegenerative diseases including Alzheimer's Disease (AD), collectively referred to as tauopathies. However, the mechanisms by which tau is linked to synaptic dysfunction and memory impairment remain unclear. To address this question, we constructed a mouse model with brain-specific deficiency of SIRT1 (SIRT1 flox/Cre + ).

Heightened Tameness and Accelerated Handling-Habituation in 3×Tg-AD Mice on a B6;129 Genetic Background.

Background: The triple transgenic mouse model of Alzheimer's disease (3×Tg-AD) has gained popularity in Alzheimer's research owing to the progressive development of both amyloid- and tau pathologies in its brain. Prior handling-habituation, a necessary preparation procedure that reduces anxiety and stress in rodents, was seldom described in the literature involving these mice and needs to be addressed.

Objective: We sought to determine whether 3×Tg-AD mice differ from B6;129 genetic control mice in terms of tameness and prior habituation to handling.

Joint-label fusion brain atlases for dementia research in Down syndrome.

Unlabelled: Research suggests a link between Alzheimer's Disease in Down Syndrome (DS) and the overproduction of amyloid plaques. Using Positron Emission Tomography (PET) we can assess the in-vivo regional amyloid load using several available ligands. To measure amyloid distributions in specific brain regions, a brain atlas is used.

COVID-19 and Neurodegenerative Diseases: Prion-Like Spread and Long-Term Consequences.

COVID-19 emerged as a global pandemic starting from Wuhan in China and spread at a lightning speed to the rest of the world. One of the potential long-term outcomes that we speculate is the development of neurodegenerative diseases as a long-term consequence of SARS-CoV-2 especially in people that have developed severe neurological symptoms. Severe inflammatory reactions and aging are two very strong common links between neurodegenerative diseases and COVID-19.

SvAnna: efficient and accurate pathogenicity prediction of coding and regulatory structural variants in long-read genome sequencing.

Structural variants (SVs) are implicated in the etiology of Mendelian diseases but have been systematically underascertained owing to sequencing technology limitations. Long-read sequencing enables comprehensive detection of SVs, but approaches for prioritization of candidate SVs are needed. Structural variant Annotation and analysis (SvAnna) assesses all classes of SVs and their intersection with transcripts and regulatory sequences, relating predicted effects on gene function with clinical phenotype data.

Optimization, validation and initial clinical implications of a Luminex-based immunoassay for the quantification of Fragile X Protein from dried blood spots.

Fragile X Syndrome (FXS) is caused by a trinucleotide expansion leading to silencing of the FMR1 gene and lack of expression of Fragile X Protein (FXP, formerly known as Fragile X Mental Retardation Protein, FMRP). Phenotypic presentation of FXS is highly variable, and the lack of reproducible, sensitive assays to detect FXP makes evaluation of peripheral FXP as a source of clinical variability challenging. We optimized a Luminex-based assay to detect FXP in dried blot spots for increased reproducibility and sensitivity by improving reagent concentrations and buffer conditions.

Design, synthesis, and biological evaluation of polyphenol derivatives as DYRK1A inhibitors. The discovery of a potentially promising treatment for Multiple Sclerosis.

Green tea and its natural components are known for their usefulness against a variety of diseases. In particular, the activity of main catechin Epigallocatechin gallate (EGCG) against Dual-specificity tyrosine-(Y)-phosphorylation Regulated Kinase-1A (DYRK1A) has been reported; here we are showing a structure-activity relationship (SAR) for EGCG against this molecular target. We have studied the influence of all four rings on the activity and the nature of its absolute geometry.

AKT/GSK-3β signaling is altered through downregulation of mTOR during cerebral Ischemia/Reperfusion injury.

Purpose: Cellular responses following cerebral ischemia/reperfusion injury are critical to recovery and survival after ischemic stroke. Understanding of these cellular responses can help the design of therapies to protect brain tissue and promote recovery after stroke. One of these cellular responses may be mediated by the AKT (protein kinase B) signal transduction pathway.