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Death domain (DD)-fold assemblies play a crucial role in regulating the signaling to cell survival or death. Here we report the crystal structure of the caspase recruitment domain (CARD)-CARD disk of the human apoptosome. The structure surprisingly reveals that three 1:1 Apaf-1:procaspase-9 CARD protomers form a novel helical DD-fold assembly on the heptameric wheel-like platform of the apoptosome. The small-angle X-ray scattering and multi-angle light scattering data also support that three protomers could form an oligomeric complex similar to the crystal structure. Interestingly, the quasi-equivalent environment of CARDs could generate different quaternary CARD assemblies. We also found that the type II interaction is conserved in all DD-fold complexes, whereas the type I interaction is found only in the helical DD-fold assemblies. This study provides crucial insights into the caspase activation mechanism, which is tightly controlled by a sophisticated and highly evolved CARD assembly on the apoptosome, and also enables better understanding of the intricate DD-fold assembly.

Recognition of linear polyubiquitin by specific ubiquitin-binding proteins plays an important role in mediating nuclear factor-κB (NF-κB) signaling. A20 binding proteins, ABINs, recognize linear polyubiquitin and A20 through UBAN and AHD1, respectively, for the inhibition of NF-κB activation. Here we report the crystal structure of the AHD1-UBAN fragment of ABIN2 in complex with linear tri-ubiquitin, which reveals a 2:1 stoichiometry of the complex. Structural analyses together with mutagenesis, pull-down, and isothermal titration calorimetry assays show that the hABIN2:tri-ubiquitin interaction is mainly through the primary ubiquitin-binding site, and also through the secondary ubiquitin-binding site under a high local protein concentration. Surprisingly, three ubiquitin units could form a right-handed helical trimer to bridge two ABIN2 dimers. The residues around the M1-linkage are crucial for ABIN2 to recognize tri-ubiquitin. The tri-ubiquitin bridging two ABIN2 dimers model suggests a possible higher-order signaling complex assembled between M1-linked polyubiquitinated proteins, ubiquitin-binding proteins, and effector signaling proteins in signal transduction.

Objective This study investigated the prevalence of depression and dementia in long-term institutionalized older leprosy patients in Taiwan. We then examined the effectiveness of reminiscence group therapy on depressive symptoms and cognitive function in this population. Methods We recruited 129 long-term institutionalized older leprosy patients in Taiwan and used the Geriatric Depression Scale—Short Form (GDS-SF), the mini mental state examination (MMSE), and the Clinical Dementia Rating (CDR) scale for outcome measurement. We then conducted a single-blind, randomized, longitudinal quasi-experimental analysis comparing the pre-test and post-test results of two equivalent groups at a 24-week intervention interval. The intervention in the experimental group was three sessions of reminiscence group therapy per week, whereas that in the control group was weekly individual supportive interviews. Results The prevalence of dementia was 45.7–50.4% according to a CDR score ≥ 0.5 and an MMSE score

CARD subfamily is the second largest subfamily in the DD superfamily that plays important roles in regulating various signaling pathways, including but not limited to NF-kB activation signaling, apoptosis signaling and inflammatory signaling. The CARD subfamily contains 33 human CARD-containing proteins, regulating the assembly of many signaling complexes, including apoptosome, inflammsome, nodosome, the CBM complex, PIDDosome, the TRAF2 complex, and the MAVS signalosome, by homotypic CARD-CARD interactions. The mechanism of how CARDs find the right binding partner to form a specific complex remains unclear. This review uses different classification schemes to update the classification of CARD-containing proteins. Combining the classification based on domain structures, functions, associated signaling complexes, and roles would help better understand the structural and function diversity of CARD-containing proteins. This review also summarizes recent structural studies on CARDs. Especially, the CARD-containing complexes can be divided into the homodimeric, heterodimeric, oligomeric, filamentous CARD complexes and the CARD-ubiquitin complex. This review will give an overview of the versatile roles of CARDs in regulating signaling transduction, as well as the therapeutic drugs targeting CARD-containing proteins.

Schizophrenia is a condition marked by a disrupted brain functional network. In schizophrenia, the brain network is characterized by reduced distributed information processing efficiency; however, the correlation between information processing efficiency and the symptomatology of schizophrenia remains unclear. Few studies have examined path length efficiencies in schizophrenia. In this study, we examined small-world network metrics computed from resting state functional magnetic resonance imaging data collected from 49 patients with schizophrenia and 28 healthy people. We calculated brain network efficiency using graph theoretical analysis of the networks of brain areas, as defined by the Automated Anatomical Labeling parcellation scheme, and investigated efficiency correlations by using the 5-factor model of psychopathology, which considers the various domains of schizophrenic symptoms and might also consider discrete pathogenetic processes. The global efficiency of the resting schizophrenic brains was lower than that of the healthy controls, but local efficiency did not differ between the groups. The severity of psychopathology, negative symptoms, and depression and anxiety symptoms were correlated with global efficiency in schizophrenic brains. The severity of psychopathology was correlated with increased network efficiency from short-range connections, but not networks from long-range connections. Our findings indicate that schizophrenic psychopathology is correlated with brain network information processing efficiency.

Executive dysfunction is one of the core symptoms of schizophrenia. Functional neuro-imaging studies have suggested an association between deficits in activating the dorsolateral prefrontal cortex (DLPFC) and executive dysfunction, but neuro-integration from the DLPFC to the whole brain remains unclear. Studies investigating the neuro-integration from the DLPFC to the whole brain in unaffected but genetically liable family members are scant. In this study, we report DLPFC neuro-integrative deficits correlated with executive dysfunction and family history of schizophrenia using resting-state functional magnetic resonance imaging (fMRI). Using seed regions in DLPFC, we examined resting-state functional connectivity in 25 patients with schizophrenia, 25 unaffected first-degree relatives (UR), and 25 healthy control (HC) persons. Schizophrenia patients and UR have impaired connectivity from DLPFC to its coordinated regions (ANOVA: F=7.316-10.974, p

This study investigated whetherTerminalia catappaL. hydrophilic extract (TCLW) prevents photoaging in human dermal fibroblasts after exposure to UVB radiation. TCLW exhibited DPPH free radical scavenging activity and protected erythrocytes against AAPH-induced hemolysis. In the gelatin digestion assay, the rates of collagenase inhibition by TCL methanol extract, TCLW, and its hydrolysates were greater than 100% at the concentration of 1 mg/mL. We found that serial dilutions of TCLW (10–500 μg/mL) inhibited collagenase activity in a dose-dependent manner (82.3% to 101.0%). However, TCLW did not significantly inhibit elastase activity. In addition, TCLW inhibited MMP-1 and MMP-9 protein expression at a concentration of 25 μg/mL and inhibited MMP-3 protein expression at a concentration of 50 μg/mL. TCLW also promoted the protein expression of type I procollagen. We also found that TCLW attenuated the expression of MMP-1, -3, and -9 by inhibiting the phosphorylation of ERK, JNK, and p38. These findings suggest that TCLW increases the production of type I procollagen by inhibiting the activity of MMP-1, -3 and -9, and, therefore, has potential use in anti-aging cosmetics.

This study investigated the prevalence of depression and dementia in long-term institutionalized older leprosy patients in Taiwan. We then examined the effectiveness of reminiscence group therapy on depressive symptoms and cognitive function in this population.We recruited 129 long-term institutionalized older leprosy patients in Taiwan and used the Geriatric Depression Scale-Short Form (GDS-SF), the mini mental state examination (MMSE), and the Clinical Dementia Rating (CDR) scale for outcome measurement. We then conducted a single-blind, randomized, longitudinal quasi-experimental analysis comparing the pre-test and post-test results of two equivalent groups at a 24-week intervention interval. The intervention in the experimental group was three sessions of reminiscence group therapy per week, whereas that in the control group was weekly individual supportive interviews.The prevalence of dementia was 45.7-50.4% according to a CDR score ≥ 0.5 and an MMSE score 25, and the prevalence of depression was 25% based on a GDS-SF score ≥ 7. According to the Wilcoxon signed-rank test, the GDS-SF scores in the experimental group decreased significantly (p = 0.02) after intervention as compared with that in the control group (p = 0.22), whereas the MMSE scores in both groups remained steady.The prevalence of dementia and depression in long-term institutionalized older leprosy patients in Taiwan is high. Reminiscence group therapy has been confirmed effective on depression in this population, but its effectiveness on cognitive function requires further verification.