Quantifying Drosophila melanogaster Eye Phenotypes: A Computational Approach Integrating ilastik and Flynotyper.

The Drosophila melanogaster compound eye is a well-structured and comprehensive array of around 800 ommatidia, exhibiting a symmetrical and hexagonal pattern. This regularity and ease of observation make the Drosophila eye system a powerful tool to model various human neurodegenerative diseases. However, ways of quantifying abnormal phenotypes, such as manual ranking of eye severity scores, have limitations, especially when ranking weak alterations in eye morphology.

FDA-approved PDE4 inhibitors alleviate the dominant toxicity of ALS-FTD-associated CHCHD10S59L by reducing the PINK1/Parkin pathway.

Background: Mutations in coiled-coil-helix-coiled-coil-helix domain containing 10 () have been identified as a genetic cause of amyotrophic lateral sclerosis and/or frontotemporal dementia(ALS-FTD). In our previous studies using in vivo model expressing CHCHD10, and human cell models expressing CHCHD10, we have identified that the PINK1/Parkin pathway is activated and causes cellular toxicity. Furthermore, we demonstrated that pseudo-substrate inhibitors for PINK1 and mitofusin2 agonists mitigated the cellular toxicity of CHCHD10.

Orange maker: a CRISPR/Cas9-mediated genome editing and screening project to generate orange-eyed DarkJedi GAL4 lines by undergraduate students.

One of the greatest strengths of Drosophila genetics is its easily observable and selectable phenotypic markers. The mini-white marker has been widely used as a transgenic marker for Drosophila transgenesis. Flies carrying a mini-white construct can exhibit various eye colors ranging from pale orange to intense red, depending on the insertion site and gene dosage.

FDA-approved PDE4 inhibitors reduce the dominant toxicity of ALS-FTD-associated .

Mutations in coiled-coil-helix-coiled-coil-helix domain containing 10( ) have been identified as a genetic cause of amyotrophic lateral sclerosis and/or frontotemporal dementia(ALS-FTD). In our previous studies using in vivo model expressing C2C10H , and human cell models expressing CHCHD10 , we have identified that the PINK1/Parkin pathway is activated and causes cellular toxicity. Furthermore, we demonstrated that pseudo-substrate inhibitors for PINK1 and mitofusin2 agonists mitigated the cellular toxicity of CHCHD10 .

Fabrication of WO Quantum Dots with Different Emitting Colors and Their Utilization in Luminescent Woods.

With a rising interest in smart windows and optical displays, the utilization of metal oxides (MOs) has garnered significant attention owing to their high active sites, flexibility, and tunable electronic and optical properties. Despite these advantages, achieving precise tuning of optical properties in MOs-based quantum dots and their mass production remains a challenge. In this study, we present an easily scalable approach to generate WO quantum dots with diverse sizes through sequential insertion/exfoliation processes in solvents with suitable surface tension.

Application of the extended parallel process model and risk perception attitude framework to obesity knowledge and obesity prevention behaviors among Korean adults.

Background: Perceiving oneself as obese has been associated with weight loss attempts. However, such a perception may not sufficiently drive significant weight reduction in many individuals. Hence, relying solely on the traditionally emphasized perceived risk of behavioral changes in obesity is challenging.

Eip74EF is a dominant modifier for ALS-FTD-linked VCP phenotypes in the Drosophila eye model.

Objectives: In 2012, Liu et al. reported that miR-34 is an age-related miRNA regulating age-associated events and long-term brain integrity in Drosophila. They demonstrated that modulating miR-34 and its downstream target, Eip74EF, showed beneficial effects on an age-related disease using a Drosophila model of Spinocerebellar ataxia type 3 expressing SCA3trQ78.

Metallic Phase Transition Metal Dichalcogenide Quantum Dots as Promising Bio-Imaging Materials.

Transition metal dichalcogenide-based quantum dots are promising materials for applications in diverse fields, such as sensors, electronics, catalysis, and biomedicine, because of their outstanding physicochemical properties. In this study, we propose bio-imaging characteristics through utilizing water-soluble MoS quantum dots (MoS-QDs) with two different sizes (i.e.

TDP-43 and PINK1 mediate CHCHD10 mutation-induced defects in Drosophila and in vitro.

Mutations in coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) can cause amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). However, the underlying mechanisms are unclear. Here, we generate CHCH10-mutant Drosophila melanogaster and HeLa cell lines to model CHCHD10-associated ALS-FTD.

Selective modulation of the androgen receptor AF2 domain rescues degeneration in spinal bulbar muscular atrophy.

Spinal bulbar muscular atrophy (SBMA) is a motor neuron disease caused by toxic gain of function of the androgen receptor (AR). Previously, we found that co-regulator binding through the activation function-2 (AF2) domain of AR is essential for pathogenesis, suggesting that AF2 may be a potential drug target for selective modulation of toxic AR activity. We screened previously identified AF2 modulators for their ability to rescue toxicity in a Drosophila model of SBMA.

C9orf72 Dipeptide Repeats Impair the Assembly, Dynamics, and Function of Membrane-Less Organelles.

Expansion of a hexanucleotide repeat GGGGCC (GC) in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Transcripts carrying (GC) expansions undergo unconventional, non-ATG-dependent translation, generating toxic dipeptide repeat (DPR) proteins thought to contribute to disease. Here, we identify the interactome of all DPRs and find that arginine-containing DPRs, polyGly-Arg (GR) and polyPro-Arg (PR), interact with RNA-binding proteins and proteins with low complexity sequence domains (LCDs) that often mediate the assembly of membrane-less organelles.

GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport.

The GGGGCC (G4C2) repeat expansion in a noncoding region of C9orf72 is the most common cause of sporadic and familial forms of amyotrophic lateral sclerosis and frontotemporal dementia. The basis for pathogenesis is unknown. To elucidate the consequences of G4C2 repeat expansion in a tractable genetic system, we generated transgenic fly lines expressing 8, 28 or 58 G4C2-repeat-containing transcripts that do not have a translation start site (AUG) but contain an open-reading frame for green fluorescent protein to detect repeat-associated non-AUG (RAN) translation.

Clinicopathologic correlation of autophagy-related Beclin-1 expression in gallbladder cancer.

Background/aims: Autophagy plays critical roles in both cell survival and cell death. Beclin-1, a key modulator of autophagy function, is considered a haploinsufficient tumor suppressor. The role of Beclin-1 expression in cancer is still controversial.

Comments on “SVD-based modeling for image texture classification using wavelet transform”.

This correspondence points out that in [1] there are some errors in two important formulas and the performance of the proposed singular value decomposition (SVD) feature is severely overestimated. It also presents a modified SVD feature which competes with the Gabor feature.

Expression of multidrug resistance-associated protein 2 in human gallbladder carcinoma.

Gallbladder carcinoma (GBCA) is one of the most aggressive malignancies. It is usually diagnosed at an advanced stage, and prognosis remains poor despite advances in imaging techniques and aggressive surgical treatment. Overexpression of multidrug resistance-associated proteins (MRPs) in tumor cells is a major cause of the intrinsic multidrug resistance phenotype.

VCP is essential for mitochondrial quality control by PINK1/Parkin and this function is impaired by VCP mutations.

Mutations in VCP cause multisystem degeneration impacting the nervous system, muscle, and/or bone. Patients may present with ALS, Parkinsonism, frontotemporal dementia, myopathy, Paget's disease, or a combination of these. The disease mechanism is unknown.

Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS.

Algorithms designed to identify canonical yeast prions predict that around 250 human proteins, including several RNA-binding proteins associated with neurodegenerative disease, harbour a distinctive prion-like domain (PrLD) enriched in uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins are essential for the assembly of ribonucleoprotein granules. However, the interplay between human PrLD function and disease is not understood.

Relay of retrograde synaptogenic signals through axonal transport of BMP receptors.

Neuronal function depends on the retrograde relay of growth and survival signals from the synaptic terminal, where the neuron interacts with its targets, to the nucleus, where gene transcription is regulated. Activation of the Bone Morphogenetic Protein (BMP) pathway at the Drosophila larval neuromuscular junction results in nuclear accumulation of the phosphorylated form of the transcription factor Mad in the motoneuron nucleus. This in turn regulates transcription of genes that control synaptic growth.

The Ly6 neurotoxin-like molecule target of wit regulates spontaneous neurotransmitter release at the developing neuromuscular junction in Drosophila.

Refinement of neural circuits during development requires formation and elimination of synaptic connections, a process governed by activity-dependent mechanisms and developmental genetic programs. Bone Morphogenetic Protein (BMP) retrograde signaling through the type II receptor Wishful thinking (Wit) is essential for synaptic growth and functional development of the Drosophila larval neuromuscular junction. However, little is known about the genes that are regulated by the pathway to effect synaptic growth and proper synaptic transmission.

Identification of downstream targets of the bone morphogenetic protein pathway in the Drosophila nervous system.

Bone Morphogenetic Protein (BMP) signaling mediated by the receptor Wishful thinking (Wit) is essential for nervous system development in Drosophila. Mutants lacking wit function show defects in neuromuscular junction development and function, specification of neurosecretory phenotypes, and eclosion behavior that result in lethality. The ligand is Glass bottom boat, the Drosophila ortholog of mammalian BMP-7, which acts as a retrograde signal through the Wit receptor.

Methods for nutrigenomics and longevity studies in Drosophila: effects of diets high in sucrose, palmitic acid, soy, or beef.

Nutrigenomics is the study of gene-nutrient interactions and how they affect the health and metabolism of an organism. Combining nutrigenomics with longevity studies is a natural extension and promises to help identify mechanisms whereby nutrients affect the aging process, life span, and, with the incorporation of age-dependent functional measures, health span. The topics we discuss in this chapter are genetic techniques, dietary manipulations, metabolic studies, and microarray analysis methods to investigate how nutrition affects gene expression, life span, triglyceride levels, total protein levels, and live weight in Drosophila.