Evaluation of graphical models for multi-group metabolomics data.

Gaussian graphical model is a strong tool for identifying interactions from metabolomics data based on conditional correlation. However, data may be collected from different stages or subgroups of subjects with heterogeneity or hierarchical structure. There are different integrating strategies of graphical models for multi-group data proposed by data scientists.

Effect and mechanism of "Danggui-kushen" herb pair on ischemic heart disease.

Aims: The purpose of this study was to investigate the mechanism and effects of "Danggui-kushen" herb pair (DKHP) better than single drug in ischemic heart disease (IHD).

Methods: IHD model was established by left anterior descending branch of coronary artery in rats. Rats were randomized into six groups and oral administration for 7 days: control, model, Danshen dripping pills (DS) (5.

Effect of 17β-oestradiol on T-type calcium channels in the lateral habenula.

T-type calcium channels (T-channels) are critical for regulating neuronal excitability. Oestrogen alters neuronal excitability by modulating the expression of T-channels. The lateral habenula (LHb), as a link between the limbic system and midbrain structures, expresses T-channels and ERs.

Clinicopathological Significance of Mucin 2 Immuno-histochemical Expression in Colorectal Cancer: A Meta-Analysis.

Objective: To evaluate the association between mucin 2 (MUC2) expression and clinicopathological characters of colorectal cancer.

Methods: A literature search was performed on December 31, 2010 according to defined selection criteria. We evaluated the correlation between MUC2 (detected by immunohistochemistry) and clinicopathological characters of colorectal cancer.

Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans.

We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34(+) cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (months), low-level (< 0.

Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction.

Gene therapy (GT) for adenosine deaminase-deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada(-/-)). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months.

Altered expression of MUC2 and MUC5AC in progression of colorectal carcinoma.

Aim: To study the expression profiles of MUC2 and MUC5AC in tumorigenesis of colorectal carcinoma and in its different pathologic types.

Methods: Formalin-fixed, paraffin-embedded human colorectal tissue specimens were immunostained with antibodies against MUC2 and MUC5AC. Six samples of normal mucosa (NM), 12 samples of hyperplastic polyp (HP), 15 samples of tubular adenoma with low-grade dysplasia (LGD), 14 samples of tubular adenoma with high-grade dysplasia (HGD), 26 samples of conventional colorectal adenocarcinoma (CCA), 15 samples of mucinous carcinoma (MC), and 8 samples of signet-ring cell carcinoma (SRCC) were collected.

[Development and verification of Chinese dietary exposure evaluation model software].

Objective: To develop the dietary exposure evaluation model software accredited of Chinese intellectual property rights and to verify the rationality and accuracy of the results from the probabilistic model in Chinese dietary exposure evaluation model software according to international standards.

Methods: The software of SAS was used to build various evaluation model based on the data from Chinese dietary survey and the chemical compound in food surveillance and to design an operation interface. The results from probabilistic dietary exposure model for children 2 - 7 years old were compared with that from duplicate portion study of 2-7 years children dietary exposure in Jinhu, Jiangsu province in order to analyze the rationality of model.

[Establishment of non-parametric probabilistic model for evaluation of Chinese dietary exposure].

Objective: To establish a non-parametric probabilistic model for evaluation of Chinese dietary exposure and to improve the assessment accuracy while integrating into the global risk assessment on food safety.

Methods: Contamination data was from the national food contamination monitoring program during 2000 - 2006, including heavy metals, pesticides and mycotoxins, amounting to 135 contaminants with 499 commodities and 487 819 samples. Food consumption data was obtained from the national diet and nutrition survey conducted in 2002 with three consecutive days by 24-hour recall method, and 66 172 consumers were included.

Combining previously published studies with current data in Bayesian logistic regression model: an example for identifying susceptibility genes related to lung cancer in humans.

A general analysis method is proposed that utilizes meta-analysis to incorporate similar studies in addition to our current investigation in order to obtain informative prior effect parameters in a logistic regression model. It is common in epidemiological studies that data from similar previous studies are available. The case of gene susceptibility association with increased lung cancer frequency was used to demonstrate this methodology.

Neonatal bone marrow transplantation of ADA-deficient SCID mice results in immunologic reconstitution despite low levels of engraftment and an absence of selective donor T lymphoid expansion.

Adenosine deaminase (ADA)-deficient severe combined immune deficiency (SCID) may be treated by allogeneic hematopoietic stem cell transplantation without prior cytoreductive conditioning, although the mechanism of immune reconstitution is unclear. We studied this process in a murine gene knockout model of ADA-deficient SCID. Newborn ADA-deficient pups received transplants of intravenous infusion of normal congenic bone marrow, without prior cytoreductive conditioning, which resulted in long-term survival, multisystem correction, and nearly normal lymphocyte numbers and mitogenic proliferative responses.

Stable gene transfer to human CD34(+) hematopoietic cells using the Sleeping Beauty transposon.

Objective: Methods of gene transfer to hematopoietic stem cells that result in stable integration may provide treatments for many inherited and acquired blood diseases. It has been demonstrated previously that a gene delivery system based on the Sleeping Beauty (SB) transposon can be derived where a plasmid transiently expressing the SB transposase can mediate the stable chromosomal integration of a codelivered second plasmid containing a gene expression unit flanked by the inverted repeats derived from the transposon.

Methods: Plasmid DNA containing the elements required for SB transposition was delivered to hematopoietic cells via electroporation.

Transient gene expression by nonintegrating lentiviral vectors.

Nonintegrating lentiviral (NIL) vectors were produced from HIV-1-based lentiviral vectors by introducing combinations of mutations made to disable the integrase protein itself and to alter the integrase recognition sequences (att) in the viral LTR. NIL vectors with these novel combinations of mutations were used to transduce the human T lymphoid cell line Jurkat and primary human CD34(+) hematopoietic progenitor cells to assess their efficacy measured through transient expression of the enhanced green fluorescent protein (eGFP) reporter gene. The most disabled NIL vectors resulted in initial high levels of eGFP expression (approximately 90% of cells), but expression was transient, diminishing toward background (<0.

Specific and stable gene transfer to human embryonic stem cells using pseudotyped lentiviral vectors.

Genetic modification of human embryonic stem cells (hESCs) is an important tool for understanding and influencing their biologic properties. At the present time, lentiviral vectors pseudotyped with the vesicular stomatitis virus G protein (VSV-G) have been most effective for stable gene transfer to hESCs. However, they also efficiently transduce murine embryonic fibroblasts (MEF), used to support the undifferentiated state of many commonly used hESC lines.

The Moloney murine leukemia virus repressor binding site represses expression in murine and human hematopoietic stem cells.

The Moloney murine leukemia virus (MLV) repressor binding site (RBS) is a major determinant of restricted expression of MLV in undifferentiated mouse embryonic stem (ES) cells and mouse embryonal carcinoma (EC) lines. We show here that the RBS repressed expression when placed outside of its normal MLV genome context in a self-inactivating (SIN) lentiviral vector. In the lentiviral vector genome context, the RBS repressed expression of a modified MLV long terminal repeat (MNDU3) promoter, a simian virus 40 promoter, and three cellular promoters: ubiquitin C, mPGK, and hEF-1a.

Expression from second-generation feline immunodeficiency virus vectors is impaired in human hematopoietic cells.

Vectors based on the feline immunodeficiency virus (FIV) have been developed as an alternative to those based on another lentivirus, human immunodeficiency virus-1 (HIV-1), because of theoretical safety advantages. We compared the efficiency of gene transfer and expression in human and feline hematopoietic progenitors using second-generation HIV-1 and FIV-based vectors. Vector pairs were tested using either human cytomegalovirus or murine phospho-glycerate kinase (PGK) internal promoters and were pseudotyped with the vesicular stomatitis virus G protein (VSV-G).