Vitamin D Affects Neuronal Peptides in Neurodegenerative Disease: Differences of V-D2 and V-D3 for Affinity to Amyloid-β and Scrapie Prion Protein In Vitro

The misfolding of neuronal peptides such as Aβ40/42 in Alzheimer’s disease and cellular prion protein in scrapie induce abnormal aggregation of the peptides in the brain. The seeding of peptides’ oligomers from monomers is the initial step to form molten-globule states before abnormal aggregation. Therefore, compounds targeting the step are useful to clarify the mechanisms underlying aggregation of the proteins and Vitamin D derivatives, which can interact with both Aβ40 and cellular prion protein; however they show different effects in the oligomerization step of the proteins. We discuss the different effects of Vitamin D2 and Vitamin D3 in the interaction with these peptides in brain

Crystal Structure of the Complex between Calyculin A and the Catalytic Subunit of Protein Phosphatase 1

AbstractThe crystal structure of the catalytic subunit of the protein phosphatase 1 (PP1), PP1γ, in complex with a marine toxin, calyculin A, was determined at 2.0 Å resolution. The metal binding site contains the phosphate group of calyculin A and forms a tight network via the hydrophilic interactions between PP1 and calyculin A. Calyculin A is located in two of the three grooves, namely, in the hydrophobic groove and the acidic groove on the molecular surface. This is the first observation to note that the inhibitor adopts not a pseudocyclic conformation but an extended conformation in order to form a complex with the protein. The amino acid terminus of calyculin A contributes, in a limited manner, to the binding to PP1γ, which is consistent with findings from the studies of dose-inhibition analysis

Psychosocial functioning in patients with treatment-resistant depression after group cognitive behavioral therapy

<p>Abstract</p> <p>Background</p> <p>Although patients with Treatment Resistant Depression (TRD) often have impaired social functioning, few studies have investigated the effectiveness of psychosocial treatment for these patients. We examined whether adding group cognitive behavioral therapy (group-CBT) to medication would improve both the depressive symptoms and the social functioning of patient with mild TRD, and whether any improvements would be maintained over one year.</p> <p>Methods</p> <p>Forty-three patients with TRD were treated with 12 weekly sessions of group-CBT. Patients were assessed with the Global Assessment of Functioning scale (GAF), the 36-item Short-Form Health Survey (SF-36), the Hamilton Rating Scale for Depression (HRSD), the Dysfunctional Attitudes Scale (DAS), and the Automatic Thought Questionnaire-Revised (ATQ-R) at baseline, at the termination of treatment, and at the 12-month follow-up.</p> <p>Results</p> <p>Thirty-eight patients completed treatment; five dropped out. For the patients who completed treatment, post-treatment scores on the GAF and SF-36 were significantly higher than baseline scores. Scores on the HRSD, DAS, and ATQ-R were significantly lower after the treatment. Thus patients improved on all measurements of psychosocial functioning and mood symptoms. Twenty patients participated in the 12-month follow-up. Their improvements for psychosocial functioning, depressive symptoms, and dysfunctional cognitions were sustained at 12 months following the completion of group-CBT.</p> <p>Conclusions</p> <p>These findings suggest a positive effect that the addition of cognitive behavioural group therapy to medication on depressive symptoms and social functioning of mildly depressed patients, showing treatment resistance.</p

市販茶系飲料の示すフリーラジカル消去活性

Tea drinks, prepared from the tea plant classified as Camellia sinensis, contain antioxidative phenolic compounds, like catechins and flavonols. We evaluated the free radical scavenging activities of tea drinks on the market by measuring luminol-amplified chemiluminescence stimulated by the free radical initiator 2,2'-azobis (2-amidinopropane9 dihydrochloride, and the absorption of 2,2'-azinobis (3-ethylbenzothiazoline-6-sulphonic acid) radica cation at 734 nm. Black tea drinks and green tea drinks mostly showed high free radical scavenging activities in either assay, followed in order by oolong tea drinks and blend tea drinks that contain extracts from plants other than the tea plant. Total phenol contents in tea drinks highly correlated with their free radical scavenging activities, indicating polyphenols in tea drinks are the major components contributing to the free radical scavenging activities of tea drinks

Radioligand Assay-Based Detection of Antibodies against SARS-CoV-2 in Hospital Workers Treating Patients with Severe COVID-19 in Japan.

This study aimed to clarify whether infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is prevalent among the staff of a hospital providing treatment to patients with severe coronavirus disease 2019 (COVID-19) using radioligand assay (RLA). One thousand samples from the staff of a general hospital providing treatment to patients with severe COVID-19 were assayed for SARS-CoV-2 nucleocapsid protein (N) IgG using RLA. Nine patients with COVID-19 who had been treated in inpatient settings and had already recovered were used as control subjects, and 186 blood donor samples obtained more than 10 years ago were used as negative controls. Four of the 1000 samples showed apparently positive results, and approximately 10 or more samples showed slightly high counts. Interestingly, a few among the blood donor samples also showed slightly high values. To validate the results, antibody examinations using ELISA and neutralizing antibody tests were performed on 21 samples, and chemiluminescence immunoassay (CLIA) was performed on 201 samples, both resulting in a very high correlation. One blood donor sample showed slightly positive results in both RLA and CLIA, suggesting a cross-reaction. This study showed that five months after the pandemic began in Japan, the staff of a general hospital with a tertiary emergency medical facility had an extremely low seroprevalence of the antibodies against SARS-CoV-2. Further investigation will be needed to determine whether the slightly high results were due to cross-reactions or a low titer of anti-SARS-CoV-2 antibodies. The quantitative RLA was considered sensitive enough to detect low titers of antibodies

Binding of 14-3-3β but not 14-3-3σ controls the cytoplasmic localization of CDC25B: Binding site preferences of 14-3-3 subtypes and the subcellular localization of CDC25B

The dual specificity phosphatase CDC25B positively controls the G2-M transition by activating CDK1/cyclin B. The binding of 14-3-3 to CDC25B has been shown to regulate the subcellular redistribution of CDC25B from the nucleus to the cytoplasm and may be correlated with the G2 checkpoint. We used a FLAG-tagged version of CDC25B to study the differences among the binding sites for the 14-3-3 subtypes, 14-3-3β, 14-3-3ε and 14-3-3σ, and the relationship between subtype binding and the subcellular localization of CDC25B. All three subtypes were found to bind to CDC25B. Site-directed mutagenesis studies revealed that 14-3-3β bound exclusively near serine-309 of CDC25B1, which is within a potential consensus motif for 14-3-3 binding. By contrast, 14-3-3σ bound preferentially to a site around serine-216, and the presence of serine-137 and -309 enhanced the binding. In addition to these binding-site differences, we found that the binding of 14-3-3β drove CDC25B to the cytoplasm and that mutation of serine-309 to alanine completely abolished the cytoplasmic localization of CDC25B. However, co-expression of 14-3-3σ and CDC25B did not affect the subeellular localization of CDC25B. Furthermore, serine-309 of CDC25B was sufficient to produce its cytoplasmic distribution with co-expression of 14-3-3β, even when other putative 14-3-3 binding sites were mutated. 14-3-3ε resembled 14-3-3β with regard to its binding to CDC25B and the control of CDC25B subcellujar localization. The results of the present study indicite that two 14-3-3 subtypes can control the subcellular localization of CDC25B by binding to a specific site and that 14-3-3σ has effects on CDC25B other than the control of its subcellular localization

マウス胸腺における脂肪化および脂肪細胞分化

The mouse thymus locates on a position close to the pericardial cavity and consists of two lobes. The lobes surrouded by a capsule are subdivided into many lobules by connective tissue trabeculae. Each lobule consists of lymphocytes-accumulated regions, cortex and medulla. In the previous study, since only lymphocytes in many kinds of thymus-constructing cell expressed the long type leptin receptor (OBRL), it was suggested that thymocytes were regulated with leptin produced by adipocytes differenciated and proliferated through thymic age involution. Then it is naturally interested in studying when lipogenesis and adipogenesis begin in the thymus either in embryogenesis or in postnatal growth. We extracted and measured the quantity of total lipid of the thymus and found that that began to increase at the period of 5 to 8 week-old after birth. The quantity of DNA of the thymus was little changed for this period. Then we directly observed histologically HE-stained sections under light microscope. The small number of adipocytes was observed at surrouding connective tissue, but never found in trabeculae of thymus of neonatal. In 5 week-old thymus adipocytes were first observed in small groups in the trabeculae. Secondly, we detected FGF10,PPARγ and leptin mENA expressions by the RTPCR method as the indication of adipogenesis in the thymus from embryo just before birth to 6 month-old. Both FGF10 and PPARγmRNA were detected in all specimens. The expression of PPARγ is slightly less than that of FGF10 in the embryonic thymus, but with incresing age it incresed and apparently more than that of FGF10 in the 6 moth-old thymus. These results suggest that adipogenesis in the thymus begins just before birth at the latest and that lipogenesis in the thymus does at 5 week-old after birth