Sea ice changes during the early 20th century Arctic warming in an Earth System Model

The Tenth Symposium on Polar Science/Ordinary sessions: [OM] Polar Meteorology and Glaciology, Thu. 5 Dec. / 2F Auditorium , National Institute of Polar Researc

In Vitro Chemosensitivity Assay for Soft Tissue Sarcoma Using Tumor Xenografts

The authors have investigated the clinical usefulness of an in vitro chemo-sensitivity assay for soft tissue sarcoma using tumor xenografts. Biopsy or surgical specimens from 47 patients with soft tissue sarcoma were trans-planted into nude mice. In vitro chemosensitivity of each patient was deter-mined using these early-generation xenografts by means of in vitro scintilla-tion assay. Thirty-three of 47 clinical samples (70.2 %) obtained from patients were successfully transplanted into nude mice. Of these 33 xeno-grafts, 25 met the criterion for in vitro growth. Overall, 25 of 47 (53 %) samples gave a successful assay. Twenty-four of the 47 patients died of metastatic disease at a median of 26.3 months (range, 2 to 86 months) . Five patients were excluded from this study: one patient died of chemotherapy side effects, one died of lung cancer and the other three were dropped out. The average follow-up period of 18 surviving patients was 85 months (range, 60 to 116 months) . A significant difference in the five-year survival rate was noted between the patients with a successful assay (36.6 %) and those with a failed assay (56.1 %) . Retrospectively, the in vitro results were compared with the clinical responses of 16 patients who received systemic chemotherapy and operation. The true positive rate, true negative rate, and predictive accuracy were 33 %, 100 %, and 75 %, respectively. The authors suggest that this in vitro chemosensitivity assay system provides a valid tool for prognosis and facilitates the exclusion of ineffective drugs for treating cases of soft tissuesarcoma. As a result, a more efficient therapy for this disease may be obtained

TNP-470 Suppresses the Tumorigenicity of HT1080 Fibrosarcoma Tumor Through the Inhibition of VEGF Secretion From the Tumor Cells

Angiogenesis inhibitors are a novel class of promising therapeutic agents for treating cancer. TNP-470, a systemic analogue of fumagillin, is an angiogenesis inhibitor capable of suppressing the tumorigenicity in several animal models even though the mechanisms of action have not been completely clarified. In the current study, we investigated the effects of TNP-470 on human fibrosarcoma cells in vivo and in vitro. The administration of TNP-470 could suppress the tumorigenicity of HT1080 fibrosarcoma tumor. The conditioned medium from HT1080 fibrosarcoma cells treated with TNP-470 inhibited the proliferation and migration of human endothelial cell line, HUVEC and ECV304. The concentration of VEGF in the conditioned medium from HT1080 cells treated with TNP-470 was lower than that of the cells without TNP-470 treatment, indicating that TNP-470 downregulates the secretion of VEGF from HT1080 cells. These findings strongly suggest that the direct action of TNP-470 on sarcoma cells inhibits angiogenesis through the downregulation of VEGF secretion and this angiogenesis suppression resulted in the inhibition of tumorigenicity of HT1080 fibrosarcoma tumo

Genomic regions involved in yield potential detected by genome-wide association analysis in Japanese high-yielding rice cultivars

BACKGROUND: High-yielding cultivars of rice (Oryza sativa L.) have been developed in Japan from crosses between overseas indica and domestic japonica cultivars. Recently, next-generation sequencing technology and high-throughput genotyping systems have shown many single-nucleotide polymorphisms (SNPs) that are proving useful for detailed analysis of genome composition. These SNPs can be used in genome-wide association studies to detect candidate genome regions associated with economically important traits. In this study, we used a custom SNP set to identify introgressed chromosomal regions in a set of high-yielding Japanese rice cultivars, and we performed an association study to identify genome regions associated with yield. RESULTS: An informative set of 1152 SNPs was established by screening 14 high-yielding or primary ancestral cultivars for 5760 validated SNPs. Analysis of the population structure of high-yielding cultivars showed three genome types: japonica-type, indica-type and a mixture of the two. SNP allele frequencies showed several regions derived predominantly from one of the two parental genome types. Distinct regions skewed for the presence of parental alleles were observed on chromosomes 1, 2, 7, 8, 11 and 12 (indica) and on chromosomes 1, 2 and 6 (japonica). A possible relationship between these introgressed regions and six yield traits (blast susceptibility, heading date, length of unhusked seeds, number of panicles, surface area of unhusked seeds and 1000-grain weight) was detected in eight genome regions dominated by alleles of one parental origin. Two of these regions were near Ghd7, a heading date locus, and Pi-ta, a blast resistance locus. The allele types (i.e., japonica or indica) of significant SNPs coincided with those previously reported for candidate genes Ghd7 and Pi-ta. CONCLUSIONS: Introgression breeding is an established strategy for the accumulation of QTLs and genes controlling high yield. Our custom SNP set is an effective tool for the identification of introgressed genome regions from a particular genetic background. This study demonstrates that changes in genome structure occurred during artificial selection for high yield, and provides information on several genomic regions associated with yield performance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-346) contains supplementary material, which is available to authorized users

Ultrasound flow phantom for transcranial Doppler: An assessment of angular mismatch effect on blood velocity measurement in comparison to optical particle image velocimetry

Detecting abnormal blood flow is possible through transcranial Doppler (TCD) ultrasound by measuring blood velocity in cerebral arteries. Velocity measurements are at the highest precision when the direction of blood flow coincides with the ultrasound beam. However, because TCD is typically performed blindly (i.e., without a B-mode), a 0° interrogation angle is usually assumed. This leads to a common issue of angular mismatch. This study quantitatively shows the angular mismatch effects on the measured velocities using a TCD ultrasound flow phantom compared with the velocities measured by optical particle image velocimetry (PIV) as control. Resulting errors with and without ultrasound machine angular correction were also considered. An ultrasound phantom developed by combining polyvinyl alcohol hydrogel (PVA-H), quartz glass as a scatterer, and a gypsum plate as a skull bone was utilized to approximate the middle cerebral artery TCD measurement from the temporal window. The PVA-H and quartz glass compositions were controlled to achieve transparency and enable PIV velocity measurement. Then, TCD velocity measurement was conducted on several interrogation and mismatch angles. Comparison results revealed that without an ultrasound machine angle correction, all measurements yielded underestimation with 73.9% at the highest in the 80° interrogation window at the 130 mL/min flow. On the other hand, with the correction, the errors in almost all angles were comparatively lower; however, at 80° at the 124 mL/min flow, a maximum overestimation rate of 113.7% was found, showing a larger error magnitude. Therefore, we find that angular mismatch, especially in larger angles, leads to inaccurate velocity measurements in TCD. Our results suggest that despite angle correction, velocity errors may still occur when the interrogation angle changes

Increased In Vitro Intercellular Barrier Function of Lung Epithelial Cells Using Adipose-Derived Mesenchymal Stem/Stromal Cells

With the emergence of coronavirus disease-2019, researchers have gained interest in the therapeutic efficacy of mesenchymal stem/stromal cells (MSCs) in acute respiratory distress syndrome; however, the mechanisms of the therapeutic effects of MSCs are unclear. We have previously reported that adipose-derived MSCs (AD-MSCs) strengthen the barrier function of the pulmonary vessels in scaffold-based bioengineered rat lungs. In this study, we evaluated whether AD-MSCs could enhance the intercellular barrier function of lung epithelial cells in vitro using a transwell coculture system. Transepithelial electrical resistance (TEER) measurements revealed that the peak TEER value was significantly higher in the AD-MSC coculture group than in the AD-MSC non-coculture group. Similarly, the permeability coefficient was significantly decreased in the AD-MSC coculture group compared to that in the AD-MSC non-coculture group. Immunostaining of insert membranes showed that zonula occuldens-1 expression was significantly high at cell junctions in the AD-MSC coculture group. Moreover, cell junction-related gene profiling showed that the expression of some claudin genes, including claudin-4, was upregulated in the AD-MSC coculture group. Taken together, these results showed that AD-MSCs enhanced the barrier function between lung epithelial cells, suggesting that both direct adhesion and indirect paracrine effects strengthened the barrier function of lung alveolar epithelium in vitro

Prediction of heading date, culm length, and biomass from canopy-height-related parameters derived from time-series UAV observations of rice

Unmanned aerial vehicles (UAVs) are powerful tools for monitoring crops for high-throughput phenotyping. Time-series aerial photography of fields can record the whole process of crop growth. Canopy height (CH), which is vertical plant growth, has been used as an indicator for the evaluation of lodging tolerance and the prediction of biomass and yield. However, there have been few attempts to use UAV-derived time-series CH data for field testing of crop lines. Here we provide a novel framework for trait prediction using CH data in rice. We generated UAV-based digital surface models of crops to extract CH data of 30 Japanese rice cultivars in 2019, 2020, and 2021. CH-related parameters were calculated in a non-linear time-series model as an S-shaped plant growth curve. The maximum saturation CH value was the most important predictor for culm length. The time point at the maximum CH contributed to the prediction of days to heading, and was able to predict stem and leaf weight and aboveground weight, possibly reflecting the association of biomass with duration of vegetative growth. These results indicate that the CH-related parameters acquired by UAV can be useful as predictors of traits typically measured by hand

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