大剂量~(60)Co照射后造血干细胞潜在的残留损伤

本文对受到临界全致死剂量——8.5Gy~(60)Co照射后的小鼠造血干细胞(HSC)的自我更新力进行了测试,并对照射后4个月,造血功能业已恢复的小鼠HSC的造血重建功能进行了研究。结果表明:应用骨髓连续移植实验所测得的照后3个月中骨髓CFU_s的自我更新潜能明显衰退了。用照射后造血恢复小鼠的CFU_s给全致死剂量照射的受体进行移植治疗,发现其移植效力比正常的显著减弱。在受体存活30天时,CFU_s的再生速率只有正常的1/17。通过对性染色体追踪观察的资料分析,此种小鼠的??造血细胞在受体中难以形成长期稳定的嵌合体。以上事实反映出,照射后小鼠的HSC的造血重建功能大大削弱了,揭示出残存干细胞质量上的缺陷。对于这种潜在的残留损伤的机制,从“干细胞增殖力耗竭学说”和“基因自我修整假说”的角度进行了讨论。     

Comparative toxicity,growth inhibitory and biochemical effects of terpenes and phenylpropenes on Spodoptera littoralis (Boisd.)

Eleven monoterpenes, phenylpropenes and sesquiterpenes were evaluated for their insecticidal and growth inhibitory activities against the second and fourth larval instars of Spodoptera littoralis. Among the tested compounds, 1,8-cineole revealed the highest fumigant toxicity against the 2nd and 4th larval instars with LC₅₀ values of 2.32 and 3.13 mg/L air, respectively. The monoterpenes, p-cymene, α-terpinene, (−)α-pinene and (−)-carvone were highly toxic to both larval stages as their LC₅₀ values ranged between 7.35 and 13.79 mg/L air against 2nd larval instar and between 14.66 and 32.02 mg/L air against 4th larval instar. In topical application assay against the 4th larval instar, (−)-carvone (LD₅₀ = 0.15 mg/larva) and cuminaldehyde (LD₅₀ = 0.27 mg/larva) were the most potent contact toxicants. In residual film assay, trans-cinnamaldehyde, (−)-citronellal and p-cymene showed the highest insecticidal activity against the 2nd larval instar, while α-terpinene and (−)-carvone were most effective compounds against the 4th larval instar. Moreover, the tested compounds caused strong growth reduction of both larval stages with growth inhibition higher than 80% in the 2nd larval instar and higher than 70% in the 4th larval instar. On the other hand, (−)-carvone, cuminaldehyde and (Z,E)-nerolidol showed pronounced inhibitory effects on acetylcholinesterase (AChE) and adenosine triphosphatases (ATPases) activity of S. littoralis larvae. Cuminaldehyde (IC₅₀ = 1.04 mM) and (Z,E)-nerolidol (IC₅₀ = 0.02 mM) caused the highest inhibition of AChE and ATPases, respectively. Taken together, the results indicate that monoterpenes, phenylpropenes and phenylpropenes could be used to develop new botanical insecticides for S. littoralis management.     

Effects of growth on residual stress distribution along the radial depth of cortical cylinders from bovine femurs

Residual stress is defined as the stress that remains in bone tissue without any external forces. This study investigated the effects of growth on residual stress distributions from the surface to deeper regions of cortical cylinders obtained from less-than-one-month-old (Group Y) and two-year-old (Group M) bovine femurs. In these experiments, five diaphysis specimens from each group were used. Residual stress was measured using a high-energy synchrotron white X-ray beam to penetrate X-rays into the deeper region of the bone specimens. The measurements in the cortical cylinders from Groups Y and M were performed at 0.5- and 1-mm intervals, respectively, from the outer surface to the deeper region of the diaphysis specimens at four positions: anterior, posterior, lateral, and medial. The residual stress was calculated on the basis of variation in the interplanar spacing of hydroxyapatite crystals in the bone tissue. According to the results, the diaphysis specimens from Group Y were not subjected to large residual stresses (average −1.2 MPa and 2.4 MPa at the surface region and 1.5 mm depth, respectively). In Group M, the surface region of the diaphysis specimens was subjected to tensile residual stresses (average 6.7 MPa) and the deeper region was subjected to compressive stresses (average −8.2 MPa at 3 mm depth). There was a strong significant difference between both these regions. The value of residual stresses at the surface region of the diaphysis specimens in both the groups had a positive statistical correlation with the cortical thickness at the measured locations.     

Pre-storage centrifugation conditions have significant impact on measured microRNA levels in biobanked EDTA plasma samples

BackgroundIn the past few years, an increasing number of studies have reported the potential use of microRNAs (miRNA) as circulating biomarkers for diagnosis or prognosis of a wide variety of diseases. There is, however, a lack of reproducibility between studies. Due to the high miRNA content in platelets this may partly be explained by residual platelets in the plasma samples used. When collecting fresh plasma samples, it is possible to produce cell-free/platelet-poor plasma by centrifugation. In this study, we systematically investigated whether biobanked EDTA plasma samples could be processed to be suitable for miRNA analysis.Materials and methodsBlood samples were collected from ten healthy volunteers and centrifuged to produce platelet-poor-plasma (PPP) and standard biobank plasma. After one week at ?80 °C the biobanked EDTA plasma was re-centrifuged by different steps to remove residual platelets. Using RT-qPCR the levels of 14 miRNAs in the different plasma preparations were compared to that of PPP.ResultsWe were able to remove residual platelets from biobanked EDTA plasma by re-centrifugation of the thawed samples. Nevertheless, for most of the investigated miRNAs, the miRNA level was significantly higher in the re-centrifuged biobanked plasma compared to PPP, even when the platelet count was reduced to 0–1×10⁹/L.ConclusionWe found, that pre-storage centrifugation conditions have a significant impact on the measured EDTA plasma level of miRNAs known to be present in platelets. Even for the miRNAs found to be less effected, we showed that a 1.5–3 fold change in plasma levels may possible be caused by or easily overseen due to sample preparation and/or storage.     

Residuals for proportional hazards models with interval-censored survival data

We develop diagnostic tools for use with proportional hazards models for interval-censored survival data. We propose counterparts to the Cox-Snell, Lagakos (or martingale), deviance, and Schoenfeld residuals. Many of the properties of these residuals carry over to the interval-censored case. In particular, the interval-censored versions of the Lagakos and Schoenfeld residuals may be derived as components of suitable score statistics. The Lagakos residuals may be used to check regression relationships, while the Schoenfeld residuals can help to detect nonproportional hazards in semiparametric models. The methods apply to parametric models and to the semiparametric model with discrete observation times.