Abstract The Chk1 protein kinase preserves genome integrity in normal proliferating cells and experiencing replicative genotoxic stress. is currently being targeted anticancer regimens. Here, we identify damaged DNA-binding 1 (DDB1) as a novel Chk1-interacting protein. DDB1 part of an E3 ligase complex that includes the cullin proteins Cul4A Cul4B. We report Cul4A/DDB1 negatively regulates stability vivo. associates with during unperturbed cell division cycle both phosphorylation replication...

Significance Toll-like receptors (TLRs) are key innate immune that sense pathogen- or danger-associated molecules. The members of the TLR family can be classified into two groups based on their subcellular localization patterns—cell surface vs. endolysosomes—but how individual is targeted to its destination largely unknown. UNC93B1 was regarded specifically bind endolysosomal TLRs in endoplasmic reticulum and deliver them endolysosomes with no role for surface-localized TLRs. In this study,...

CDT2 targets proteins involved in replication licensing (CDT1), cell cycle control (p21), and chromatin modification (SET8) for destruction by the CUL4-based E3 ligase (CRL4). CRL4CDT2 recruits these substrates through interactions with chromatin-bound PCNA ubiquitinates them exclusively on chromatin. Rereplication G2 arrest are observed CDT2-depleted cells. The rereplication phenotype has been attributed to an inability destroy CDT1, but molecular target important cells not identified. Here...

TLRs are divided into two groups based on their subcellular localization patterns. TLR1, 2, 4, 5, and 6 expressed the cell surface, whereas nucleotide-sensing TLRs, such as TLR3, 7, 8, 9 stay mainly inside cells. The polytopic membrane protein UNC93B1 physically interacts with delivers them from endoplasmic reticulum to endolysosomes, where recognize ligands initiate signaling. In cells nonfunctional UNC93B1, nucleic acid-sensing fail exit consequently do not signal. However, detailed...

In neuronal axons, the ratio of motile-to-stationary mitochondria is tightly regulated by activation, thereby meeting need for local calcium buffering and maintaining ATP supply. However, molecular players detailed regulatory mechanisms behind mitochondrial movement are not completely understood. Here, we found that activation-induced anchoring Disrupted-in-schizophrenia 1 (DISC1), which accomplished functional association with Syntaphilin (SNPH). DISC1 deficiency resulted in reduced axonal...

Abstract This study aimed to address the diversity issue in fashion design education by developing two prototypes for Inclusive Fashion Design (IFD) education. The were constructed based on 3C3R model of Project-Based Learning (PBL) and incorporated Persona/Scenario (P/S) toolkit IFD. Additionally, examined effectiveness FEA (Function, Expressive, Aesthetics) self-checklist P/S IFD process. experiments involved instructors, teaching assistants, 12 senior-level students divided into four...

The objective of this study was to develop an inclusive fashion design (IFD) process using digital tools for educational purposes. consisted three stages: development IFD prototypes 1 and 2 with different phases incorporating diverse users' information (before after the ideation phase), conducting experiment on ten undergraduate students two types prototypes, analysing through protocol analysis, statistical experts' assessment. found that timing user can have a significant impact design....

Flagellin, a major structural protein of the flagellum found in all motile bacteria, activates TLR5- or NLRC4 inflammasomedependent signaling pathway to induce innate immune responses. Flagellin can also serve as specific antigen for adaptive system and stimulate anti-flagellin antibody Failure recognize commensal-derived flagellin TLR5-deficient mice leads reduction antiflagellin IgA antibodies at steady state causes microbial dysbiosis mucosal barrier breach by flagellated bacteria promote...

Toll-like receptors (TLRs) play critical roles in the first line of host defense against pathogens through recognition pathogen-associated molecular patterns and initiation innate immune responses. The proper localization TLRs specific subcellular compartments is crucial for their ligand downstream signaling to ensure appropriate responses while avoiding erroneous or excessive activation. Several TLRs, including TLR7 TLR9 but not TLR4, depend on UNC93B1 intracellular signaling. Accumulating...

Abstract Background Gastrointestinal microbiome has a great impact on human health and diseases. Fusobacterium nucleatum , an oral resident gram-negative microorganism, been reported to differentially prevail in colorectal cancer (CRC). However, the effect of its enrichment was not clearly explored terms microbial homeostasis stability at early stage disease development. Result Our analysis longitudinal metagenomic data generated by Integrative Human Microbiome Project (iHMP) showed that F....

A localization algorithm for topological maps with dynamics is proposed in this paper. Especially, considers a when some nodes are deleted by door closing and has two main features. First, lots of edge information used efficient way. Second, the calculates probability node to be current location systematic general Experiments map conducted show performance algorithm.

This study aimed to create a Persona/Scenario (P/S) toolkit for promoting inclusive fashion design. The development of the P/S drew inspiration from Lamb and Kallal"s FEA model design planning, integrating various factors such as disabilities, body types, social contexts, diverse situations. Additionally, its concepts consider identities, roles, practicality, personal tastes, psychological needs user. Based on participant interviews, goes beyond conventional methods by encouraging designers...

Supplementary Figure 1 from DDB1 Targets Chk1 to the Cul4 E3 Ligase Complex in Normal Cycling Cells and Experiencing Replication Stress

Supplementary Figure 2 from DDB1 Targets Chk1 to the Cul4 E3 Ligase Complex in Normal Cycling Cells and Experiencing Replication Stress

Supplementary Figure 4 from DDB1 Targets Chk1 to the Cul4 E3 Ligase Complex in Normal Cycling Cells and Experiencing Replication Stress

Supplementary Figure 3 from DDB1 Targets Chk1 to the Cul4 E3 Ligase Complex in Normal Cycling Cells and Experiencing Replication Stress

<div>Abstract<p>The Chk1 protein kinase preserves genome integrity in normal proliferating cells and experiencing replicative genotoxic stress. is currently being targeted anticancer regimens. Here, we identify damaged DNA-binding 1 (DDB1) as a novel Chk1-interacting protein. DDB1 part of an E3 ligase complex that includes the cullin proteins Cul4A Cul4B. We report Cul4A/DDB1 negatively regulates stability <i>in vivo</i>. associates with during unperturbed cell...

<div>Abstract<p>The Chk1 protein kinase preserves genome integrity in normal proliferating cells and experiencing replicative genotoxic stress. is currently being targeted anticancer regimens. Here, we identify damaged DNA-binding 1 (DDB1) as a novel Chk1-interacting protein. DDB1 part of an E3 ligase complex that includes the cullin proteins Cul4A Cul4B. We report Cul4A/DDB1 negatively regulates stability <i>in vivo</i>. associates with during unperturbed cell...

Supplementary Figure 1 from DDB1 Targets Chk1 to the Cul4 E3 Ligase Complex in Normal Cycling Cells and Experiencing Replication Stress

Supplementary Figure 2 from DDB1 Targets Chk1 to the Cul4 E3 Ligase Complex in Normal Cycling Cells and Experiencing Replication Stress

Supplementary Figure 4 from DDB1 Targets Chk1 to the Cul4 E3 Ligase Complex in Normal Cycling Cells and Experiencing Replication Stress