Mesenchymal stem cells (MSCs) not only possess extensive self-renewal potential and can modulate immune cell activation [1], but also they are easily expanded and stored ex vivo, and are considered to be "immune privileged". MSCs modulate the function of immune cells, including T and B lymphocytes, dendritic cells, and natural killer cells, inhibit their proliferation and alter their cytokine secretion. Previous data from our group and others [2-4] demonstrated the immunosuppressive and anti-inflammatory effects of MSCs in the treatment of several animal disease models including autoimmune diseases. As a result of these unique qualities, MSCs are attractive candidates in stem cell-based therapy.

Exploration of neural sources and their effective connectivity based on transient changes in electrophysiological activities to external stimuli is important for understanding brain mechanisms of sensory information processing. However, such cortical mechanisms have not yet been well characterized in electrophysiological studies since (1) it is difficult to estimate the stimulus-activated neural sources and their activities and (2) it is difficult to identify transient effective connectivity between neural sources in the order of millisecond. To address these issues, we developed a time-varying source connectivity approach to effectively capture fast-changing information flows between neural sources from high-density Electroencephalography (EEG) recordings. This time-varying source connectivity approach was applied to somatosensory evoked potentials (SEPs), which were elicited by electrical stimulation of right hand and recorded using 64 channels from 16 subjects, to reveal human somatosensory information processing. First, SEP sources and their activities were estimated, both at single-subject and group level, using equivalent current dipolar source modeling. Then, the functional integration among SEP sources was explored using a Kalman smoother based time-varying effective connectivity inference method. The results showed that SEPs were mainly generated from the contralateral primary somatosensory cortex (SI), bilateral secondary somatosensory cortex (SII), and cingulate cortex (CC). Importantly, we observed a serial processing of somatosensory information in human somatosensory cortices (from SI to SII) at earlier latencies (<150ms) and a reciprocal processing between SII and CC at later latencies (>200ms).

OBJECTIVE: It is widely believed that in most female mammalian neonates, all germ cells enter meiosis to form the primary oocyte at the end of foetal development, and as a result, the postnatal mammalian ovary harbours only a limited supply of oocytes that cannot be regenerated. However, this idea has been challenged by the discovery of the existence of female germline stem cells (FGSCs) in postnatal mammalian ovaries. MATERIALS AND METHODS: We have isolated ovarian GSCs from neonatal and adult mouse ovaries and expanded them in the same culture conditions as embryonic stem cells (ESCs). RESULTS: LIF and BIO were beneficial for formation of FGSC colonies. BIO promoted proliferation of FGSCs through activation of β-catenin and up-regulation of E-cadherin. The FGSCs formed compact round colonies with unclear borders, maintained ESC characteristics and alkaline phosphatase (AP) activity, expressing germ-cell markers-Vasa, and stem-cell markers: Oct4, Klf4, C-myc, Nanog, CD49f, Sox2, CD133, SSEA1 and SSEA4. These cells had the ability to form embryoid bodies (EBs), which expressed specific markers for all three germ layers. Then we induced EBs to differentiate into neurons, cardiomyocytes, pancreatic cells and germ cells, which showed the expression of specific markers, β-III-tubulin, cardiac a-actin, Pdx1 and Zps respectively. DISCUSSION AND CONCLUSION: This study reveals the existence of FGSCs in postnatal mouse ovary with multipotent characteristics. BIO played an important role in regulation of proliferation and maintenance of the FGSCs. This could help provide a better understanding of causes of ovarian infertility, prevention and potential treatment of infertility.

BACKGROUND: Her2 and β2-adrenergic receptor (β2-AR) can form a heterocomplex in cardiomyocytes and agonists can induce Her2 transactivation, which is important for cardiovascular homeostasis. The scaffolding molecules that mediate β2-AR/Her2 interaction are currently unknown. Erbin, a PDZ domain-containing protein is a binding partner of Her2. The C-terminus of β2-AR harbors a PDZ domain-binding motif. Hypothesis of this study is that Erbin may organize the assembly of β2-AR/Her2 complex. METHODS: The interaction among β2-AR, Her2 and Erbin was investigated in COS-7, HEK-293 and H9c2 cells and rat brain and heart tissues by coimmunoprecipitation. The β2-AR binding region of Erbin was identified by utilizing the Erbin deletion mutants. The functional significance of Erbin in cardiomyocytes was determined by Erbin silencing, contraction frequency measurement and cellular apoptosis assays. RESULTS: Erbin was able to form a complex with both exogenous and endogenous β2-AR and Her2 in the presence of isoproterenol (ISO). Deletion of the Erbin LRR domain did not affect its binding to β2-AR and Her2, whereas lacking of the PDZ domain lost the ability of Erbin. Silencing of Erbin greatly abrogated ISO-induced activation of ERK. The treatment of H9c2 cells transfected with the Erbin siRNA with ISO caused severe cell apoptosis. Knock-down of Erbin expression in primary neonatal rat cardiomyocytes led to a remarkable reduction of the beating frequency after ISO stimulation. CONCLUSIONS: Erbin mediates catecholamine-induced β2-AR/Her2 complexation and promotes catecholamine-induced activation of ERK signaling in cardiomyocytes, conferring protection of cardiomyocytes from apoptosis induced by chronic catecholamine stimulation.

OBJECTIVE: To investigate the function and mechanism of CYR61 on the migration and invasion of the trophoblast cell line, HTR-8/SVneo cells. STUDY DESIGN: The mRNA and protein levels of NUR77 in the placentas of normal and preeclampsia (PE) women were evaluated using real-time PCR and Western blot, respectively. Paraffin-embedded tissues were processed for localization of NUR77 protein in placental villus by immunohistochemistry. HTR-8/SVneo cells were cultured in the presence of CYR61, Ad-NUR77 or a small interfering RNA for NUR77 (Ad-sinur77). The expression of NUR77 in the HTR-8/SVneo cells was detected and the effects of CYR61 on the migration and invasion of HTR-8/SVneo cells were assessed in wound-healing and transwell experiments, respectively. Gelatin zymography was used to measure the MMP2 release in HTR-8/SVneo cells. RESULTS: NUR77 is significantly decreased in the placenta of women with PE compared with the levels during a normal pregnancy. CYR61 can significantly increase the expression of NUR77 in HTR-8/SVneo cells. CYR61, as well as NUR77, can promote HTR-8/SVneo cells migration and invasion, which can be blocked by Ad-sinur77. Both CYR61 and Ad-nur77 reduced the mRNA expression of TIMP2 in HTR-8/SVneo cells. CONCLUSIONS: CYR61 may promote HTR-8/SVneo cells migration and invasion through the upregulation of NUR77, leading to the increase of MMP2 release and the downregulation of TIMP2 expression.

Municipal solid waste used for landfill becomes stabilized, or aged, some years after placement, and can be safely excavated; the term 'mineralized refuse' is used in this study. The adsorptions of phosphorus, and the nitrification of the mineralized refuse and clay, were investigated by batch incubation. The variation of phosphorus adsorption in the mineralized refuse was fitted to the Freundlich adsorption isotherm equation, giving a maximum phosphorus adsorption capacity of 2310 mg kg(-1). Based on the Langmuir isotherm equation, maximum phosphorus adsorption capacity was calculated to be 1976 mg kg(-1), almost twice that of the clay. The equations for both the mineralized refuse and clay were fitted to zero-order kinetics (R2 > 0.98, P < 0.01, n = 11), giving concentrations of phosphorus as phosphates less than 250 mg L(-1). The K value for the mineralized refuse was about 3.5 times higher than for the clay. The production of nitrogen as nitrates in both the mineralized refuse and the clay after 120 h incubation yielded a first-order reaction kinetics value of 100 mg kg(-1) NH4(+)-N from the initial concentration. The calculated net nitrification as nitrates for the mineralized refuse was 6.3 times higher than for the clay. Domestic wastewater was then treated in a mineralized refuse-based bioreactor for 30 days. The removal rates of COD(cr), total nitrogen and total phosphorus were 73.77 +/- 8.10%, 61.01 +/- 6.75%, and 69.14 +/- 9.25%, respectively. Large accumulations of nitrates occurred in the mineralized refuse-based bioreactor. For the full-scale design, a high column of mineralized refuse is recommended for the denitrification.

Deformable image registration (DIR) is increasingly used in radiotherapy applications and provides the basis for a previously described model of patient-specific respiratory motion. We examine the accuracy of a DIR algorithm and a motion model with respiration-correlated CT (RCCT) images of software phantom with known displacement fields, physical deformable abdominal phantom with implanted fiducials in the liver and small liver structures in patient images. The motion model is derived from a principal component analysis that relates volumetric deformations with the motion of the diaphragm or fiducials in the RCCT. Patient data analysis compares DIR with rigid registration as ground truth: the mean ± standard deviation 3D discrepancy of liver structure centroid positions is 2.0 ± 2.2 mm. DIR discrepancy in the software phantom is 3.8 ± 2.0 mm in lung and 3.7 ± 1.8 mm in abdomen; discrepancies near the chest wall are larger than indicated by image feature matching. Marker's 3D discrepancy in the physical phantom is 3.6 ± 2.8 mm. The results indicate that visible features in the images are important for guiding the DIR algorithm. Motion model accuracy is comparable to DIR, indicating that two principal components are sufficient to describe DIR-derived deformation in these datasets.

CD14 is a monocytic differentiation antigen that regulates innate immune responses to pathogens. Here, we show that murine Cd14 SNPs regulate the length of Cd14 mRNA and CD14 protein translation efficiency, and consequently the basal level of soluble CD14 (sCD14) and type I IFN production by murine macrophages. This has substantial downstream consequences for the innate immune response; the level of expression of at least 40 IFN-responsive murine genes was altered by this mechanism. We also observed that there was substantial variation in the length of human CD14 mRNAs and in their translation efficiency. sCD14 increased cytokine production by human dendritic cells (DCs), and sCD14-primed DCs augmented human CD4T cell proliferation. These findings may provide a mechanism for exploring the complex relationship between CD14 SNPs, serum sCD14 levels, and susceptibility to human infectious and allergic diseases.

The development of drugs that attenuate neurodegeneration is important for the treatment of Alzheimer's disease (AD). We previously found that smilagenin (SMI), a steroidal sapogenin from traditional Chinese medicinal herbs improves memory in animal models, is neither a cholinesterase inhibitor nor a glutamate receptor antagonist, but can significantly elevate the declined muscarinic receptor (M receptor) density. In this article, to clarify whether SMI represents a new approach for treating neurodegeneration disease, we first demonstrate that SMI pretreatment significantly attenuates the neurodegenerative changes induced by beta amyloid 25-35 (Aβ(25-35)) in cultured rat cortical neurons, including decreased cholinergic neuron number, shortened neurite outgrowth length, and declined muscarinic receptor density. Brain-derived neurotrophic factor (BDNF) protein levels in the culture medium were also decreased by Aβ(25-35) and significantly elevated by SMI. Parallel experiments revealed that when the trk receptors were inhibited by K252a or the action of BDNF was inhibited by a neutralizing anti-BDNF antibody, the effects of SMI on the Aβ(25-35)-induced neurodegeneration in rat cortical neurons were almost completely abolished. In the all-trans retinoic acid-differentiated SH-SY5Y neuroblastoma cells, the BDNF transcription rate measured by a nuclear run-on assay was significantly suppressed by Aβ(25-35) and elevated by SMI, but the BDNF degradation rate measured by half-life determination was unchanged by Aβ(25-35) and SMI. Transcript analysis of the SH-SY5Y cells using quantitative RT-PCR showed that the IV and VI transcripts of BDNF mRNA were significantly decreased by Aβ(25-35) and elevated by SMI. Taken together, we conclude that SMI attenuates Aβ(25-35)-induced neurodegeneration in cultured rat cortical neurons and SH-SY5Y cells mainly through stimulating BDNF mRNA transcription implicating that SMI may represent a novel therapeutic strategy for AD.

Unilateral fracture of the condylar neck in immature subjects might lead to mandible asymmetry and condyle remodelling. A rat model was used to investigate mandibular deviation and condylar remodelling associated with condyle fracture. 72 4-week-old male rats were randomly divided into three groups: an experimental group (unilateral transverse condylar fracture induced surgically), a sham operation group (surgical exposure but no fracture), and a non-operative control group (no operation). The rats were killed at intervals up to 9weeks after surgery, and outcomes were assessed using various measures of mandible deviation, histological and X-ray observation, and immunohistochemical measures of expression levels of connective tissue growth factor (CTGF) and type II collagen (Col II). The fracture led to the degeneration of mandibular size, associated with atrophy of fractured condylar process. Progressive remodelling of cartilage and increasing expression levels of CTGF and Col II were found. The authors conclude that condylar fracture can lead to asymmetries in mandible and condyle remodelling and expression of CTGF and Col II in condylar cartilage on both the ipsilateral and the contralateral sides.