Large-scale stem cell production system by newly designed bioreactor

Large scale cell production system is required in drug discovery and cell based therapy. However there are technically challenges in maintaining high quality and low cost for practical biomanufacturing industry. 3D suspension culture is one of attractive process, especially static culture is ultimate free from shear force. Utilizing static 3D suspension culture, automated closed system is newly designed and demonstrated expansion culture over several subcultures. Cell growth curves of this system and conventional manual method have good accordance. The system is also compatible with good scalability for scale up and scale out use. Please click Additional Files below to see the full abstract

Isolation and Characterization of Renal Erythropoietin-Producing Cells from Genetically Produced Anemia Mice

Understanding the nature of renal erythropoietin-producing cells (REPs) remains a central challenge for elucidating the mechanisms involved in hypoxia and/or anemia-induced erythropoietin (Epo) production in adult mammals. Previous studies have shown that REPs are renal peritubular cells, but further details are lacking. Here, we describe an approach to isolate and characterize REPs. We bred mice bearing an Epo gene allele to which green fluorescent protein (GFP) reporter cDNA was knocked-in (EpoGFP) with mice bearing an Epo gene allele lacking the 3′ enhancer (EpoΔ3′E). Mice harboring the mutant EpoGFP/Δ3′E gene exhibited anemia (average Hematocrit 18% at 4 to 6 days after birth), and this perinatal anemia enabled us to identify and purify REPs based on GFP expression from the kidney. Light and confocal microscopy revealed that GFP immunostaining was confined to fibroblastic cells that reside in the peritubular interstitial space, confirming our previous observation in Epo-GFP transgenic reporter assays. Flow cytometry analyses revealed that the GFP fraction constitutes approximately 0.2% of the whole kidney cells and 63% of GFP-positive cells co-express CD73 (a marker for cortical fibroblasts and Epo-expressing cells in the kidney). Quantitative RT-PCR analyses confirmed that Epo expression was increased by approximately 100-fold in the purified population of REPs compared with that of the unsorted cells or CD73-positive fraction. Gene expression analyses showed enrichment of Hif2α and Hif3α mRNA in the purified population of REPs. The genetic approach described here provides a means to isolate a pure population of REPs, allowing the analysis of gene expression of a defined population of cells essential for Epo production in the kidney. This has provided evidence that positive regulation by HIF2α and negative regulation by HIF3α might be necessary for correct renal Epo induction. (282 words

Tabular Two-Dimensional Correlation Analysis for Multifaceted Characterization Data

We propose tabular two-dimensional correlation analysis for extracting features from multifaceted characterization data, essential for understanding material properties. This method visualizes similarities and phase lags in structural parameter changes through heatmaps, combining hierarchical clustering and asynchronous correlations. We applied the proposed method to datasets of carbon nanotube (CNTs) films annealed at various temperatures and revealed the complexity of their hierarchical structures, which include elements like voids, bundles, and amorphous carbon. Our analysis addresses the challenge of attempting to understand the sequence of structural changes, especially in multifaceted characterization data where 11 structural parameters derived from 8 characterization methods interact with complex behavior. The results show how phase lags (asynchronous changes from stimuli) and parameter similarities can illuminate the sequence of structural changes in materials, providing insights into phenomena like the removal of amorphous carbon and graphitization in annealed CNTs. This approach is beneficial even with limited data and holds promise for a wide range of material analyses, demonstrating its potential in elucidating complex material behaviors and properties.Comment: 15 pages, 4 figure

Association between hand-grip strength and depressive symptoms: Locomotive Syndrome and Health Outcomes in Aizu Cohort Study (LOHAS).

First published online: February 21, 2015no study has examined the longitudinal association between hand-grip strength and mental health, such as depressive symptoms

Development of finite strain in the convecting lower mantle and its implications for seismic anisotropy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94627/1/jgrb13518.pd

Development of anisotropic structure in the Earth's lower mantle by solid-state convection

Seismological observations reveal highly anisotropic patches at the bottom of the Earth's lower mantle, whereas the bulk of the mantle has been observed to be largely isotropic(1-4). These patches have been interpreted to correspond to areas where subduction has taken place in the past or to areas where mantle plumes are upwelling, but the underlying cause for the anisotropy is unknown-both shape-preferred orientation of elastically heterogenous materials(5) and lattice-preferred orientation of a homogeneous material(6-8) have been proposed. Both of these mechanisms imply that large-strain deformation occurs within the anisotropic regions, but the geodynamic implications of the mechanisms differ. Shape-preferred orientation would imply the presence of large elastic (and hence chemical) heterogeneity whereas lattice-preferred orientation requires deformation at high stresses. Here we show, on the basis of numerical modelling incorporating mineral physics of elasticity and development of lattice-preferred orientation, that slab deformation in the deep lower mantle can account for the presence of strong anisotropy in the circum-Pacific region. In this model-where development of the mineral fabric (the alignment of mineral grains) is caused solely by solid-state deformation of chemically homogeneous mantle material-anisotropy is caused by large-strain deformation at high stresses, due to the collision of subducted slabs with the core-mantle boundary.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62804/1/416310a.pd

Dietary flavonoid intake and risk of incident depression in midlife and older women

Background: The impact of dietary flavonoid intakes on risk of depression is unclear. Objective: We prospectively examined associations between estimated habitual intakes of dietary flavonoids and depression risk. Design: We followed 82,643 women without a previous history of depression at baseline from the Nurses’ Health Study [(NHS) aged 53–80 y] and the Nurses’ Health Study II [(NHSII) aged 36–55 y]. Intakes of total flavonoids and subclasses (flavonols, flavones, flavanones, anthocyanins, flavan-3-ols, polymeric flavonoids, and proanthocyanidins) were calculated from validated food-frequency questionnaires collected every 2–4 y. Depression was defined as physician- or clinician-diagnosed depression or antidepressant use and was self-reported in response to periodic questionnaires. Cox proportional hazards models were performed to examine associations. Results: A total of 10,752 incident depression cases occurred during a 10-y follow-up. Inverse associations between flavonol, flavone, and flavanone intakes and depression risk were observed. Pooled multivariable-adjusted HRs (95% CIs) were 0.93 (0.88, 0.99), 0.92 (0.86, 0.98), and 0.90 (0.85, 0.96) when comparing the highest (quintile 5) with the lowest (quintile 1) quintiles, respectively, with evidence of linear trends across quintiles (P-trend = 0.0004–0.08). In flavonoid-rich food-based analyses, the HR was 0.82 (95% CI: 0.74, 0.91) among participants who consumed ≥2 servings citrus fruit or juices/d compared with <1 serving/wk. In the NHS only, total flavonoids, polymers, and proanthocyanidin intakes showed significant (9–12%) lower depression risks. In analyses among late-life NHS participants (aged ≥65 y at baseline or during follow-up), for whom we were able to incorporate depressive symptoms into the outcome definition, higher intakes of all flavonoid subclasses except for flavan-3-ols were associated with significantly lower depression risk; flavones and proanthocyanidins showed the strongest associations (HR for both: 0.83; 95% CI: 0.77, 0.90). Conclusions: Higher flavonoid intakes may be associated with lower depression risk, particularly among older women. Further studies are needed to confirm these associations

Arp2/3 Complex Regulates Asymmetric Division and Cytokinesis in Mouse Oocytes

Mammalian oocyte meiotic maturation involves oocyte polarization and a unique asymmetric division, but until now, the underlying mechanisms have been poorly understood. Arp2/3 complex has been shown to regulate actin nucleation and is widely involved in a diverse range of processes such as cell locomotion, phagocytosis and the establishment of cell polarity. Whether Arp2/3 complex participates in oocyte polarization and asymmetric division is unknown. The present study investigated the expression and functions of Arp2/3 complex during mouse oocyte meiotic maturation. Immunofluorescent staining showed that the Arp2/3 complex was restricted to the cortex, with a thickened cap above the meiotic apparatus, and that this localization pattern was depended on actin. Disruption of Arp2/3 complex by a newly-found specific inhibitor CK666, as well as by Arpc2 and Arpc3 RNAi, resulted in a range of effects. These included the failure of asymmetric division, spindle migration, and the formation and completion of oocyte cytokinesis. The formation of the actin cap and cortical granule-free domain (CGFD) was also disrupted, which further confirmed the disruption of spindle migration. Our data suggest that the Arp2/3 complex probably regulates oocyte polarization through its effect on spindle migration, asymmetric division and cytokinesis during mouse oocyte meiotic maturation

Achieving LDL cholesterol target levels <1.81 mmol/L may provide extra cardiovascular protection in patients at high risk: Exploratory analysis of the Standard Versus Intensive Statin Therapy for Patients with Hypercholesterolaemia and Diabetic Retinopathy study

Aims To assess the benefits of intensive statin therapy on reducing cardiovascular (CV) events in patients with type 2 diabetes complicated with hyperlipidaemia and retinopathy in a primary prevention setting in Japan. In the intension-to-treat population, intensive therapy [targeting LDL cholesterol = 2.59 to = 100 to = 2.59 to <3.10 mmol/L in patients with hypercholesterolaemia and diabetic retinopathy