XNP/ATRX, a causative gene of X-linked alpha-thalassemia/mental retardation syndrome, encodes an SNF2 family ATPase/helicase protein. To better understand the role of XNP/ATRX in development, we isolated and characterized a Drosophila XNP/ATRX homolog, dXNP, which contains highly conserved SNF2 and helicase domains. Ectopically expressed dXNP induced strong apoptosis in the developing eye and wing, but did not affect cell cycle progression or the expression of wingless and engrailed, essential regulators of development. The dXNP-induced apoptosis was strongly suppressed by DJNKK/hemipterous mutation, and dXNP increased JNK activity. Taken together, these results suggest that dXNP regulates apoptosis via JNK activation. 相似文献
The novel Ca2+-binding protein, Scarf (skin calmodulin-related factor) belongs to the calmodulin-like protein family and is expressed in the differentiated layers of the epidermis. To determine the roles of Scarf during stratification, we set out to identify the binding target proteins by affinity chromatography and subsequent analysis by mass spectrometry. Several binding factors, including 14-3-3s, annexins, calreticulin, ERp72 (endoplasmic reticulum protein 72), and nucleolin, were identified, and their interactions with Scarf were corroborated by co-immunoprecipitation and co-localization analyses. To further understand the functions of Scarf in epidermis in vivo, we altered the epidermal Ca2+ gradient by acute barrier disruption. The change in the expression levels of Scarf and its binding target proteins were determined by immunohistochemistry and Western blot analysis. The expression of Scarf, annexins, calreticulin, and ERp72 were up-regulated by Ca2+ gradient disruption, whereas the expression of 14-3-3s and nucleolin was reduced. Because annexins, calreticulin, and ERp72 have been implicated in Ca2+-induced cellular trafficking, including the secretion of lamellar bodies and Ca2+ homeostasis, we propose that the interaction of Scarf with these proteins might be crucial in the process of barrier restoration. On the other hand, down-regulation of 14-3-3s and nucleolin is potentially involved in the process of keratinocyte differentiation and growth inhibition. The calcium-dependent localization and up-regulation of Scarf and its binding target proteins were studied in mouse keratinocytes treated with ionomycin and during the wound-healing process. We found increased expression and nuclear presence of Scarf in the epidermis of the wound edge 4 and 7 days post-wounding, entailing the role of Scarf in barrier restoration. Our results suggest that Scarf plays a critical role as a Ca2+ sensor, potentially regulating the function of its binding target proteins in a Ca2+-dependent manner in the process of restoration of epidermal Ca2+ gradient as well as during epidermal barrier formation. 相似文献
Pyrolysis mass spectrometry (PyMS) is a rapid, simple, high-resolution analytical method based on thermal degradation of complex
material in a vacuum, and has been widely applied to the discrimination of closely related microbial strains. Minimally prepared
samples of embryogenic and non-embryogenic calluses derived from various higher plants (sweet potato, morning glory, Korean
ginseng, Siberian ginseng, and balloon flower) were subjected to PyMS for spectral fingerprinting. A dendrogram based on the
unweighted pair group method, with arithmetic mean of pyrolysis mass spectra, divided the calluses into Siberian ginseng embryogenic
callus and the others, which were subsequently divided into embryogenic and non-embryogenic callus groups, regardless of plant
species from which the calluses were derived. In the non-embryogenic callus group, the dendrogram was in agreement with the
known taxonomy of the plants. These results indicate that PyMS analysis could be applied for discriminating plant calluses
based on embryogenic capacity and taxonomic classification. 相似文献
Microsomal prostaglandin E2 synthase (mPGES-1) has been identified recently as a novel target for treating pain and inflammation. The aim of this study
is to understand the binding affinities of reported inhibitors for mPGES-1 and further to design potential new mPGES-1 inhibitors.
3D-QSAR-CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) - techniques
were employed on a series of indole derivatives that act as selective mPGES-1 inhibitors. The lowest energy conformer of the
most active compound obtained from systematic conformational search was used as a template for the alignment of 32 compounds.
The models obtained were used to predict the activities of the test set of eight compounds, and the predicted values were
in good agreement with the experimental results. The 3D-QSAR models derived from the training set of 24 compounds were all
statistically significant (CoMFA; q2 = 0.89, r2 = 0.95, , and CoMSIA; q2 = 0.84, r2 = 0.93, , ). Contour plots generated for the CoMFA and CoMSIA models reveal useful clues for improving the activity of mPGES-1 inhibitors.
In particular, substitutions of an electronegative fluorine atom or a bulky hydrophilic phenoxy group at the meta or para positions of the biphenyl rings might improve inhibitory activity. A plausible binding mode between the ligands and mPGES-1
is also proposed. 相似文献
High accumulation and selective delivery of boron into tumor tissues are the most important requirements to achieve efficient
neutron capture therapy of cancers. We focused on liposomal boron delivery system to achieve a large amount of boron delivery
to tumor. We succeeded in the synthesis of the double-tailed boron cluster lipids 4a–c and 5a–c, which has a B12H11S-moiety as a hydrophilic function, by S-alkylation of B12H11SH with bromoacetyl and chloroacetocarbamate derivatives of diacylglycerols. Size distribution of liposomes prepared from
the boron cluster lipid 4b, dimyristoylphosphatidylcholine, polyethyleneglycol-conjugated distearoylphosphatidylethanolamine, and cholesterol was determined
as 100 nm in diameter by an electrophoretic light scattering spectrophotometer. Calcein-encapsulation experiments revealed
that these boronated liposomes are stable at 37 °C in fetal bovine serum solution for 24 h. 相似文献
Catecholamines, including epinephrine (E), norepinephrine (NE), and dopamine (DA), are associated with the response to stressful conditions. However, the relationships of catecholamines with intelligence and their interactions with stress remain unclear. This study assessed stress, intelligence quotient (IQ), and catecholamine levels in 70 healthy subjects to elucidate associations between catecholamines and stress, and between catecholamines and IQ. Additionally, the associations of catecholamines with stress and IQ were analyzed according to hemispheric dominance using the Brain Preference Indicator (BPI). There were positive correlations between the NE/E ratio and the somatization of stress but negative correlations between the E/NE ratio and the somatization of stress among the total number of subjects. In the right-brain-dominant group, a high E/DA ratio was correlated with low levels of stress, somatization and depression, and high NE/E and DA/E ratios were associated with high levels of somatization. In the left-brain-dominant group, high E levels were correlated with low levels of depression. In the total subjects, there were positive correlations between the NE/E and DA/E ratios and the sum of the vocabulary, arithmetic, picture arrangement, and block design IQ subtests. Thus, these catecholamines were associated with stress and IQ, which suggests that the autonomic functional regulation of catecholamine levels in relation to stress may also affect cognitive functions related to intelligence in the brain. Furthermore, the relationships between catecholamines and stress or IQ differed depending on hemispheric dominance, which suggests that the present results could be used to inform the development of personalized therapies based on hemispheric asymmetry.
The Alzheimer's Disease Sequencing Project (ADSP) performed whole genome sequencing (WGS) of 584 subjects from 111 multiplex families at three sequencing centers. Genotype calling of single nucleotide variants (SNVs) and insertion-deletion variants (indels) was performed centrally using GATK-HaplotypeCaller and Atlas V2. The ADSP Quality Control (QC) Working Group applied QC protocols to project-level variant call format files (VCFs) from each pipeline, and developed and implemented a novel protocol, termed “consensus calling,” to combine genotype calls from both pipelines into a single high-quality set. QC was applied to autosomal bi-allelic SNVs and indels, and included pipeline-recommended QC filters, variant-level QC, and sample-level QC. Low-quality variants or genotypes were excluded, and sample outliers were noted. Quality was assessed by examining Mendelian inconsistencies (MIs) among 67 parent-offspring pairs, and MIs were used to establish additional genotype-specific filters for GATK calls. After QC, 578 subjects remained. Pipeline-specific QC excluded ~12.0% of GATK and 14.5% of Atlas SNVs. Between pipelines, ~91% of SNV genotypes across all QCed variants were concordant; 4.23% and 4.56% of genotypes were exclusive to Atlas or GATK, respectively; the remaining ~0.01% of discordant genotypes were excluded. For indels, variant-level QC excluded ~36.8% of GATK and 35.3% of Atlas indels. Between pipelines, ~55.6% of indel genotypes were concordant; while 10.3% and 28.3% were exclusive to Atlas or GATK, respectively; and ~0.29% of discordant genotypes were. The final WGS consensus dataset contains 27,896,774 SNVs and 3,133,926 indels and is publicly available. 相似文献