Hydrolyzed collagen intake increases bone mass of growing rats trained with running exercise

BackgroundSome studies have shown that dietary hydrolyzed collagen peptides (HC) effectively prevent age-related bone loss. However, it is not known whether the intake of HC also has positive effect on bone mass or strength when combined with exercise during growth phase.MethodsWe examined the effects of 11 weeks of HC intake and running exercise on bone mass and strength in growing rats. Rats were randomized into four groups, the 20% casein group (Casein20), the 40% casein group (Casein40), the 20% HC group (HC20), and the 40% HC group (HC40). Each group was further divided into exercise groups (Casein20 + Ex, Casein40 + Ex, HC20 + Ex, HC40 + Ex) and non-exercise group (Casein20, Casein40, HC20, HC40). In the HC intake groups, 30% of casein protein was replaced with HC. Exercise group rats were trained 6 days per week on a treadmill (25–30 m/min, 60 min) for 60 days. After being sacrificed, their bone mineral content (BMC) and bone strength were evaluated.ResultsExercise and dietary HC effects were observed in the adjusted BMC of lumbar spine and tibia among the 20% protein groups (p < 0.001 for exercise; p < 0.05 for dietary HC, respectively). These effects were also noted in the adjusted wet weight and dry weight of femur among the 20% protein groups (p < 0.001, p < 0.01 for exercise; p < 0.01, p < 0.001 for dietary HC, respectively). On the other hand, in adjusted bone breaking force and energy, dietary HC effect was not significant. Among the 40% protein groups, similar results were obtained in the adjusted BMC, femoral weight, bone breaking force, and energy. There were no differences between the 20% protein groups and the 40% protein groups.ConclusionsThe present study demonstrated that moderate HC intake (where the diet contains 20% protein, of which 30% is HC) increased bone mass during growth period and further promoted the effect of running exercise. On the other hand, a higher HC intake (where the diet contains 40% protein, of which 30% is HC) had no more beneficial effect on bone mass than the moderate HC intake

Lack of impact of the ALDH2 rs671 variant on breast cancer development in Japanese BRCA1/2‐mutation carriers

The aldehyde degrading function of the ALDH2 enzyme is impaired by Glu504Lys polymorphisms (rs671, termed A allele), which causes alcohol flushing in east Asians, and elevates the risk of esophageal cancer among habitual drinkers. Recent studies suggested that the ALDH2 variant may lead to higher levels of DNA damage caused by endogenously generated aldehydes. This can be a threat to genome stability and/or cell viability in a synthetic manner in DNA repair-defective settings such as Fanconi anemia (FA). FA is an inherited bone marrow failure syndrome caused by defects in any one of so far identified 22 FANC genes including hereditary breast and ovarian cancer (HBOC) genes BRCA1 and BRCA2. We have previously reported that the progression of FA phenotypes is accelerated with the ALDH2 rs671 genotype. Individuals with HBOC are heterozygously mutated in either BRCA1 or BRCA2, and the cancer-initiating cells in these patients usually undergo loss of the wild-type BRCA1/2 allele, leading to homologous recombination defects. Therefore, we hypothesized that the ALDH2 genotypes may impact breast cancer development in BRCA1/2 mutant carriers. We genotyped ALDH2 in 103 HBOC patients recruited from multiple cancer centers in Japan. However, we were not able to detect any significant differences in clinical stages, histopathological classification, or age at clinical diagnosis across the ALDH2 genotypes. Unlike the effects in hematopoietic cells of FA, our current data suggest that there is no impact of the loss of ALDH2 function in cancer initiation and development in breast epithelium of HBOC patients

Differentiation of murine B cells induced by chondroitin sulfate B

A two-step culture system was used to investigate the role of chondroitin sulfate (CS) B, which is mitogenic to B cells, in differentiation of B cells. Mouse spleen B cells were incubated for 3 days with CSB in the presence of interleukin (IL)-4 and IL-5. After washing, the cells were replated at 10(5) viable cells/well and recultured without CSB in the presence of IL-4 and IL-5. CSB dose-dependently increased IgM production, the greatest enhancement being 450%. Dextran sulfate had a similar effect, whereas other glycosaminoglycans, CSA, CSC, heparin and hyaluronic acid, were marginally effective. Treatment of B cells with CSB resulted in increases in the number of IgM-secreting cells and numbers of CD138-positive cells and CD45R/B220-negative cells. CSB-induced IgM production was inhibited by the protein kinase C (PKC) inhibitor GF109203X but not by the phosphatidylinositol 3-kinase (P13K) inhibitor wortmannin. These results demonstrated that CSB promoted differentiation of B cells in the presence of IL-4 and IL-5 and suggested that PKC but not P13K is crucial for CSB-induced IgM production.</p

フレアイ ドウブツエン 二 オケル オオガタ ドウブツ ノ コウドウ

千葉市動物公園子ども動物園のふれあい施設において,ヤギとヒツジの行動を観察した。両種の単独行動における行動内容は類似しており,時間の 6割は採食や移動など動きを伴う行動に費やされた。ヤギは放飼場全体に広がっていたのに対し,ヒツジはヤギよりも劣位であり,あまり動き回らずに特定の場所にかたまる傾向があった。ヤギは入場者に対して友好的で,入場者数が増えると友好的行動の頻度も増えた。他方,ヤギの他個体に対する敵対的行動の頻度は入場者数と関連していなかった。気温はヤギのすべての社会行動に影響する大きな要因であり,行動頻度は高温時に低下した。ヤギは他個体に対して激しい攻撃的行動を示したが,入場者に危害を及ぼすような行動はまったく見られなかった。ヒツジの動きが少ないことは幼児が触りやすいという利点にもなることから,異なる動物種を混合飼育することは,展示上の長短所を補完できる点で有効といえる。全国のふれあい施設における大型動物としてはヤギ,ヒツジ,ウマが多く飼育されていたので,この3種を用いることの長短所を論じた。Comparative behavioral observation was made for 17 goats (males castrated) and 7 sheep at a children\u27s zoo area in the Chiba City Zoo for 18 days from July 28 to November 25, 2012. Observed behavior items were affiliative (approach to human and stand still near human) and refusal (escape and threat) behaviors of the animal towards human, as well as intra- and inter-specific aggressive behaviors among the goat and the sheep. Spatial use patterns of both species in the area were also compared. Behaviors were recorded every 10 minutes. Friendly actions of the goat towards human were significantly higher than refusal actions. With the increase of visitors, both the amicable actions and the refusal actions increased. But the correlation between the frequency of amicable actions and the number of visitors was stronger than that between the refusal actions and the visitors. It seemed that the existence of the visitors is not a burden for the goat. In other words the congested situation caused by visitors may not lead to a dangerous situation. On the other hand, frequency of inter- and intra-specific antagonistic actions of the goat showed neither correlation with the ambient temperature nor the number of visitors. The space use pattern of the goats was greatly different from that of sheep. The goats tended to spread all over the area, while the sheep tended to gather together. The goats were meritorious in that all visitors could touch them, and the sheep was suitable for contact with children. In this display, goats and sheep had both advantage and defect. The mixed breeding of both species is meritorious in compensating for the weak points of each. Merits and demerits of keeping goat, sheep and horse at children\u27s zoos were comparatively discussed

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target