Optimization of human mesenchymal stem cell manufacturing: the effects of animal/xeno-free media.

Due to their immunosuppressive properties, mesenchymal stem cells (MSC) have been evaluated for the treatment of immunological diseases. However, the animal-derived growth supplements utilized for MSC manufacturing may lead to clinical complications. Characterization of alternative media formulations is imperative for MSC therapeutic application. Human BMMSC and AdMSC were expanded in media supplemented with either human platelet lysates (HPL), serum-free media/xeno-free FDA-approved culture medium (SFM/XF), or fetal bovine serum (FBS) and the effects on their properties were investigated. The immunophenotype of resting and IFN-γ primed BMMSC and AdMSC remained unaltered in all media. Both HPL and SFM/XF increased the proliferation of BMMSC and AdMSC. Expansion of BMMSC and AdMSC in HPL increased their differentiation, compared to SFM/XF and FBS. Resting BMMSC and AdMSC, expanded in FBS or SFM/XF, demonstrated potent immunosuppressive properties in both non-primed and IFN-γ primed conditions, whereas HPL-expanded MSC exhibited diminished immunosuppressive properties. Finally, IFN-γ primed BMMSC and AdMSC expanded in SFM/XF and HPL expressed attenuated levels of IDO-1 compared to FBS. Herein, we provide strong evidence supporting the use of the FDA-approved SFM/XF medium, in contrast to the HPL medium, for the expansion of MSC towards therapeutic applications

Development of GCP ontology for sharing crop information.

Poster presented at 3rd international Biocuration Conference. Berlin (Germany). 17 Apr 2009

Immune Modulatory Effects of Vitamin D on Viral Infections.

Viral infections have been a cause of mortality for several centuries and continue to endanger the lives of many, specifically of the younger population. Vitamin D has long been recognized as a crucial element to the skeletal system in the human body. Recent evidence has indicated that vitamin D also plays an essential role in the immune response against viral infections and suggested that vitamin D deficiency increases susceptibility to viral infections as well as the risk of recurrent infections. For instance, low serum vitamin D levels were linked to increased occurrence of high burdens viral diseases such as hepatitis, influenza, Covid-19, and AIDS. As immune cells in infected patients are responsive to the ameliorative effects of vitamin D, the beneficial effects of supplementing vitamin D-deficient individuals with an infectious disease may extend beyond the impact on bone and calcium homeostasis. Even though numerous studies have highlighted the effect of vitamin D on the immune cells, vitamin D's antiviral mechanism has not been fully established. This paper reviews the recent mechanisms by which vitamin D regulates the immune system, both innate and adaptive systems, and reflects on the link between serum vitamin D levels and viral infections

The generation challenge programme platform: semantic standards and workbench for crop science.

doi:10.1155/2008/369601

The Polygenic and Monogenic Basis of Blood Traits and Diseases

Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation. Analysis of blood cell traits in the UK Biobank and other cohorts illuminates the full genetic architecture of hematopoietic phenotypes, with evidence supporting the omnigenic model for complex traits and linking polygenic burden with monogenic blood diseases

The Polygenic and Monogenic Basis of Blood Traits and Diseases

Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.</p

Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations

Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p &lt; 5 × 10−9, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies. Delineation of the genetic architecture of hematological traits in a multi-ethnic dataset allows identification of rare variants with strong effects specific to non-European populations and improved fine mapping of GWAS variants using the trans-ethnic approach

Flow Synthesis of 2-Methylpyridines via α-Methylation

A series of simple 2-methylpyridines were synthesized in an expedited and convenient manner using a simplified bench-top continuous flow setup. The reactions proceeded with a high degree of selectivity, producing α-methylated pyridines in a much greener fashion than is possible using conventional batch reaction protocols. Eight 2-methylated pyridines were produced by progressing starting material through a column packed with Raney® nickel using a low boiling point alcohol (1-propanol) at high temperature. Simple collection and removal of the solvent gave products in very good yields that were suitable for further use without additional work-up or purification. Overall, this continuous flow method represents a synthetically useful protocol that is superior to batch processes in terms of shorter reaction times, increased safety, avoidance of work-up procedures, and reduced waste. A brief discussion of the possible mechanism(s) of the reaction is also presented which involves heterogeneous catalysis and/or a Ladenberg rearrangement, with the proposed methyl source as C1 of the primary alcohol

Improved survival after treatments of patients with nonalcoholic fatty liver disease associated hepatocellular carcinoma

Worldwide, nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions and in parallel, hepatocellular carcinoma (HCC) has become one of the fastest growing cancers. Despite the rise in these disease entities, detailed long-term outcomes of large NAFLD-associated HCC cohorts are lacking. In this report, we compared the overall and recurrence-free survival rates of NAFLD HCC cases to patients with HBV and HCV-associated HCC cases. Distinguishing features of NAFLD-associated HCC patients in the cirrhosis and non-cirrhosis setting were also identified. We conducted a retrospective study of 125 NAFLD, 170 HBV and 159 HCV HCC patients, utilizing clinical, pathological and radiographic data. Multivariate regression models were used to study the overall and recurrence-free survival. The overall survival rates were significantly higher in the NAFLD-HCC cases compared to HBV-HCC (HR = 0.35, 95% CI 0.15-0.80) and HCV-HCC (HR = 0.37, 95% CI 0.17-0.77) cases. The NAFLD-HCC patients had a trend for higher recurrence-free survival rates compared to HBV and HCV-HCC cases. Within the NAFLD group, 18% did not have cirrhosis or advanced fibrosis; Hispanic ethnicity (OR = 12.34, 95% CI 2.59-58.82) and high BMI (OR = 1.19, 95% CI 1.07-1.33) were significantly associated with having cirrhosis. NAFLD-HCC cases were less likely to exhibit elevated serum AFP (p &lt; 0.0001). After treatments, NAFLD-related HCC patients had longer overall but not recurrence-free survival rates compared to patients with viral-associated HCC. Non-Hispanic ethnicity and normal BMI differentiated non-cirrhosis versus cirrhosis NAFLD HCC. Further studies are warranted to identify additional biomarkers to stratify NAFLD patients without cirrhosis who are at risk for HCC