Experience-dependent Tip60 nucleocytoplasmic transport is regulated by its NLS/NES sequences for neuroplasticity gene control.

Nucleocytoplasmic transport (NCT) in neurons is critical for enabling proteins to enter the nucleus and regulate plasticity genes in response to environmental cues. Such experience-dependent (ED) neural plasticity is central for establishing memory formation and cognitive function and can influence the severity of neurodegenerative disorders like Alzheimer's disease (AD). ED neural plasticity is driven by histone acetylation (HA) mediated epigenetic mechanisms that regulate dynamic activity-dependent gene transcription profiles in response to neuronal stimulation.

Novel EAAT2 activators improve motor and cognitive impairment in a transgenic model of Huntington's disease.

Introduction: Glutamate excitotoxicity is causal in striatal neurodegeneration underlying motor dysfunction and cognitive deficits in Huntington's disease (HD). Excitatory amino acid transporter 2 (EAAT2), the predominant glutamate transporter accounting for >90% of glutamate transport, plays a key role in preventing excitotoxicity by clearing excess glutamate from the intrasynaptic cleft. Accordingly, EAAT2 has emerged as a promising therapeutic target for prevention of neuronal excitotoxicity underlying HD and other neurodegenerative diseases.

Two splice forms of OsbZIP1, a homolog of AtHY5, function to regulate skotomorphogenesis and photomorphogenesis in rice.

Plants possess well-developed light sensing mechanisms and signal transduction systems for regulating photomorphogenesis. ELONGATED HYPOCOTYL5 (HY5), a basic leucine zipper (bZIP) transcription factor, has been extensively characterized in dicots. In this study, we show that OsbZIP1 is a functional homolog of Arabidopsis (Arabidopsis thaliana) HY5 (AtHY5) and is important for light-mediated regulation of seedling and mature plant development in rice (Oryza sativa).

Tip60's Novel RNA-Binding Function Modulates Alternative Splicing of Pre-mRNA Targets Implicated in Alzheimer's Disease.

The severity of Alzheimer's disease (AD) progression involves a complex interplay of genetics, age, and environmental factors orchestrated by histone acetyltransferase (HAT)-mediated neuroepigenetic mechanisms. While disruption of Tip60 HAT action in neural gene control is implicated in AD, alternative mechanisms underlying Tip60 function remain unexplored. Here, we report a novel RNA binding function for Tip60 in addition to its HAT function.

Stress-induced F-Box protein-coding gene OsFBX257 modulates drought stress adaptations and ABA responses in rice.

F-box (FB) proteins that form part of SKP1-CUL1-F-box (SCF) type of E3 ubiquitin ligases are important components of plant growth and development. Here we characterized OsFBX257, a rice FB protein-coding gene that is differentially expressed under drought conditions and other abiotic stresses. Population genomics analysis suggest that OsFBX257 shows high allelic diversity in aus accessions and has been under positive selection in some japonica, aromatic and indica cultivars.

Chromatin and transcriptomic profiling uncover dysregulation of the Tip60 HAT/HDAC2 epigenomic landscape in the neurodegenerative brain.

Disruption of histone acetylation-mediated gene control is a critical step in Alzheimer's Disease (AD), yet chromatin analysis of antagonistic histone acetyltransferases (HATs) and histone deacetylases (HDACs) causing these alterations remains uncharacterized. We report the first Tip60 HAT versus HDAC2 chromatin (ChIP-seq) and transcriptional (RNA-seq) profiling study in brains that model early human AD. We find Tip60 and HDAC2 predominantly recruited to identical neuronal genes.

A comprehensive transcriptome analysis of contrasting rice cultivars highlights the role of auxin and ABA responsive genes in heat stress response.

Sensing a change in ambient temperature is key to survival among all living organisms. Temperature fluctuations due to climate change are a matter of grave concern since it adversely affects growth and eventually the yield of crop plants, including two of the major cereals, i.e.

Amyloid-β Peptide Impact on Synaptic Function and Neuroepigenetic Gene Control Reveal New Therapeutic Strategies for Alzheimer's Disease.

Amyloid-β (Aβ) peptides can form protease-resistant aggregates within and outside of neurons. Accumulation of these aggregates is a hallmark of Alzheimer's disease (AD) neuropathology and contributes to devastating cognitive deficits associated with this disorder. The primary etiological factor for Aβ aggregation is either an increase in Aβ production or a decrease in its clearance.

Tip60 protects against amyloid-β-induced transcriptomic alterations via different modes of action in early versus late stages of neurodegeneration.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder hallmarked by amyloid-β (Aβ) plaque accumulation, neuronal cell death, and cognitive deficits that worsen during disease progression. Histone acetylation dysregulation, caused by an imbalance between reduced histone acetyltransferases (HAT) Tip60 and increased histone deacetylase 2 (HDAC2) levels, can directly contribute to AD pathology. However, whether such AD-associated neuroepigenetic alterations occur in response to Aβ peptide production and can be protected against by increasing Tip60 levels over the course of neurodegenerative progression remains unknown.

Disruption of Tip60 HAT mediated neural histone acetylation homeostasis is an early common event in neurodegenerative diseases.

Epigenetic dysregulation is a common mechanism shared by molecularly and clinically heterogenous neurodegenerative diseases (NDs). Histone acetylation homeostasis, maintained by the antagonistic activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs), is necessary for appropriate gene expression and neuronal function. Disruption of neural acetylation homeostasis has been implicated in multiple types of NDs including Alzheimer's disease (AD), yet mechanisms underlying alterations remain unclear.

Influence of SPRINT Study Type Automated Office Blood Pressure Measurements on Hypertension Diagnosis in Kidney Transplant Patients.

Background/aims: We compare conventional office blood pressure measurements with automated SPRINT-study type readings in kidney transplant recipients in order to determine the impact of the white coat effect in a prospective observational study.

Methods: Adult patients with a functional renal transplant not dependent on dialysis were eligible. Readings were taken in the office in presence of the physician with an oscillometric method.

OsbZIP48, a HY5 Transcription Factor Ortholog, Exerts Pleiotropic Effects in Light-Regulated Development.

Plants have evolved an intricate network of sensory photoreceptors and signaling components to regulate their development. Among the light signaling components identified to date, HY5, a basic leucine zipper (bZIP) transcription factor, has been investigated extensively. However, most of the work on HY5 has been carried out in Arabidopsis (), a dicot.

Prevalence and coexistence of KRAS, BRAF, PIK3CA, NRAS, TP53, and APC mutations in Indian colorectal cancer patients: Next-generation sequencing-based cohort study.

Colorectal cancer incidences are on a rise in India. In this study, we have analyzed the mutation frequencies of six potential biomarkers, their coexistence, association with clinicopathological characteristics, and tumor location in Indian colorectal cancer patients. Next-generation sequencing was performed to identify mutations in the six potential biomarker genes using formalin-fixed paraffin-embedded tissue blocks of 112 colorectal cancer patients.

Targeted molecular profiling of rare genetic alterations in colorectal cancer using next-generation sequencing.

Mutation frequencies of common genetic alterations in colorectal cancer have been in the spotlight for many years. This study highlights few rare somatic mutations, which possess the attributes of a potential CRC biomarker yet are often neglected. Next-generation sequencing was performed over 112 tumor samples to detect genetic alterations in 31 rare genes in colorectal cancer.