TDP-43 (43-kDa TAR DNA-binding protein) is a major constituent of ubiquitin-positive cytosolic aggregates present in neurons patients with amyotrophic lateral sclerosis (ALS) and fronto-temporal lobar degeneration (FTLD-U). Inherited mutations have been linked to familial forms ALS, indicating key role for disease pathogenesis. Here, we describe Drosophila melanogaster model proteinopathy. Expression wild-type human protein motor led dysfunction dramatic reduction life span. Interestingly,...

TDP-43 (43-kDa TAR DNA-binding domain protein) is a major constituent of ubiquitin-positive cytoplasmic aggregates present in neurons patients with fronto-temporal lobular dementia and amyotrophic lateral sclerosis (ALS). The pathologic significance aggregation not known; however, dominant mutations cause subset ALS cases, suggesting that misfolding and/or altered trafficking relevant to the disease process. Here, we show presenilin-binding protein ubiquilin 1 (UBQLN) plays role aggregation....

The mammalian circadian clock component PERIOD2 (PER2) plays a critical role in rhythm entrainment. Recently, missense mutation at putative phosphorylation site hPER2, Ser-662, was identified patients that suffer from familial advanced sleep phase syndrome (FASPS). Patients with FASPS display abnormal sleep-wake patterns characterized by lifelong pattern of onset the early evening and offset morning. Although PER2 is strongly implied functional studies, it has not been possible to study...

Abstract With intrinsic optical and dynamic properties of polysulfide chains, inverse vulcanized copolymers have demonstrated immense potential for infrared (IR) applications. However, preparing highly IR‐transparent sulfur‐rich without sacrificing their thermomechanical remains challenging. To overcome the trade‐off relationship between IR properties, an in situ microphase separation strategy vulcanization elemental sulfur utilizing self‐crosslinkable 1,3,5‐trivinylbenzene (TVB) is...

Abstract Vitrimers have shown advantages over conventional thermosets via capabilities of dynamic network rearrangement to endow repairability as well recyclability. Based on such characteristics, vitrimers been studied and promises a 3D printing ink material that can be recycled with the purpose waste reduction. However, despite brilliant approaches, there still remain limitations regarding requirement new reagents for recycling materials or reprintability issues. Here, class 4D printable...

Cytosolic aggregation of the nuclear RNA-binding protein TDP-43 is a histopathologic signature degenerating neurons in amyotrophic lateral sclerosis (ALS), and mutations TARDBP gene encoding cause dominantly inherited forms this condition. To understand relationship between misregulation neurotoxicity, we others have used Drosophila as model system, which overexpression either wild-type or its ALS-associated mutants sufficient to induce paralysis, early death. Using microarrays, examined...

Members of the conserved ubiquilin (UBQLN) family ubiquitin (Ub) chaperones harbor an antipodal UBL (Ub-like)-UBA (Ub-associated) domain arrangement and participate in proteasome autophagosome-mediated protein degradation. Mutations a proline-rich-repeat region (PRR) UBQLN2 cause amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD); however, neither normal functions PRR nor impacts ALS-associated mutations within it are well understood. In this study, we show that ALS perturb...

We have developed a method for stabilization of the uniform lying helix (ULH) texture short pitch cholesterics in an electro-optical device, based on flexoelectro-optic effect such texture. By using small concentration photoreactive liquid crystal monomer (less than 5wt.%) and selecting illumination conditions, we were able to create nonuniform polymeric network bulk (localized essentially at both substrate surfaces) which stabilized efficiently amplitude phase modulation modes device. Most...

Cytosolic aggregation of the nuclear RNA-binding protein (RBP) TDP-43 (43 kDa TAR DNA-binding domain protein) is a suspected direct or indirect cause motor neuron deterioration in amyotrophic lateral sclerosis (ALS). In this study, we implemented high-content, genome-wide RNAi screen to identify pathways controlling nucleocytoplasmic shuttling. We identified ∼60 genes whose silencing increased cytosolic localization TDP-43, including pore complex components and regulators G2/M cell cycle...

Mutations in the ubiquitin (Ub) chaperone Ubiquilin 2 (UBQLN2 ) cause X-linked forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) through unknown mechanisms. Here, we show that aggregation-prone, ALS-associated mutants UBQLN2 ALS trigger heat stress-dependent neurodegeneration Drosophila . A genetic modifier screen implicated endolysosomal axon guidance genes, including netrin receptor, Unc-5, as key modulators toxicity. Reduced gene dosage Unc-5 or its coreceptor...

We demonstrated a fast-switching liquid crystal display with bent polymer fibrils templated from nematic host bend structure. The morphology of the fibrils, formed by photopolymerizing small amount reactive monomer in host, depends on concentration, condition photopolymerization, and applied electric field during UV exposure. At low concentration curing voltage, can be oriented into twist or splay state at zero field. In contrast, high conveys dominance network damps electro-optical...

We developed an electro-optical device based on the flexoelectric effect of a polymer-stabilized cholesteric liquid crystal with uniform lying helix. Using dual-frequency switchable nematic, small amount chiral dopant and phase-separated polymer localized at substrate surfaces, we were able to create that operates in both amplitude (flexoelectric) phase (dielectric) modes. high-frequency voltage suppress mode preserve mode.

Activating transcription factor 1 (ATF1) and the closely related proteins CREB (cyclic AMP resonse element binding protein) CREM response modulator) constitute a subfamily of bZIP factors that play critical roles in regulation cellular growth, metabolism, survival. Previous studies demonstrated is phosphorylated on cluster conserved Ser residues, including Ser-111 Ser-121, to DNA damage through coordinated actions ataxia-telangiectasia-mutated (ATM) protein kinase casein kinases 2 (CK1/2)....

cAMP response element binding protein (CREB) is a key regulator of glucose metabolism and synaptic plasticity that canonically regulated through recruitment transcriptional coactivators. Here we show phosphorylation CREB on conserved cluster Ser residues (the ATM/CK cluster) by the DNA damage-activated kinase ataxia-telangiectasia-mutated (ATM) casein kinase1 (CK1) kinase2 (CK2) positively negatively regulates CREB-mediated transcription in signal dependent manner. In to genotoxic stress,...

Fused in sarcoma (FUS) encodes an RNA-binding protein with diverse roles transcriptional activation and RNA splicing. While oncogenic fusions of FUS transcription factor DNA-binding domains are associated soft tissue sarcomas, dominant mutations can cause amyotrophic lateral sclerosis. has also been implicated genome maintenance. However, the underlying mechanisms its actions stability unknown. Here, we applied gene editing, functional reconstitution, integrated proteomics transcriptomics to...

As the obese population increases in Korea, number of patients who are trying to lose weight has been increasing steadily. In these patients, skin laxity and deformation body contour occurs, which could possibly be corrected by various contouring surgeries. Here, we introduce brachioplasty method our experience surgeries performed center.From November 2009 August 2011, five cases were performed. When patient presented with sagging lateral inframammary crease bat wing deformity axilla,...

The human ribosomal protein S3 (rpS3) functions as a component of the 40S subunit and UV DNA repair endonuclease. This enzyme has an endonuclease activity for UV-irradiated oxidatively damaged DNAs. endonucleases recognize variety oxidative base damages in from E. coli to cells. III is especially known have iron-sulfur cluster co-factor. Here, we tried electron paramagnetic resonance (EPR) method first time observe signal that was previously reported. We compared it rpS3 order find out...

The cAMP response element-binding protein (CREB) is an important regulator of cell growth, metabolism, and synaptic plasticity. CREB activated through phosphorylation evolutionarily conserved Ser residue (S133) within its intrinsically disordered kinase-inducible domain (KID). Phosphorylation S133 in to cAMP, Ca2+, other stimuli triggers association the KID with KID-interacting (KIX) CREB-binding (CBP), a histone acetyl transferase (HAT) that promotes transcriptional activation. Here we...

ABSTRACT RIF1 (RAP1 interacting factor) fulfills diverse roles in DNA double-strand break repair, replication, and nuclear organization. is expressed as two splice variants, RIF1-Long (RIF1-L) RIF1-Short (RIF1-S), from the alternative splicing (AS) of Exon 32 (Ex32) which encodes a 26 aa Ser/Lys-rich cassette peptide C-terminal domain (CTD). Here we demonstrate that Ex32 inclusion was repressed by damage oncogenesis but peaked at G 2 /M phase cell cycle. splice-in catalyzed positive...