Role of Human Interleukin-9 As a Megakaryocyte Potentiator in Culture

Experimental Hematology. Dec, 2002  |  Pubmed ID: 12482498

This study investigated the effect of interleukin-9 (IL-9) on the proliferation and differentiation of human colony-forming unit megakaryocytic progenitor cells (CFU-Meg).

Brefeldin A, a Cytotoxin Produced by Paecilomyces Sp. and Aspergillus Clavatus Isolated from Taxus Mairei and Torreya Grandis

FEMS Immunology and Medical Microbiology. Sep, 2002  |  Pubmed ID: 12208606

Paecilomyces sp. and Aspergillus clavatus, which were isolated from Taxus mairei and Torreya grandis from southeast China, produced toxic metabolites when grown in liquid culture. Nuclear magnetic resonance techniques, infrared spectrometry, electrospray ionization mass spectroscopy and X-ray analysis identified brefeldin A, a bioactive metabolite produced by a number of fungal species belonging to the genera Alternaria, Ascochyta, Penicillium, Curvularia, Cercospora and Phyllosticta. This is the first report of the isolation of the cytotoxin from Paecilomyces sp. and A. clavatus. The relevance of brefeldin A to the association between these fungi and their host plants is discussed.

SCID-repopulating Cell Activity of Human Cord Blood-derived CD34- Cells Assured by Intra-bone Marrow Injection

Blood. Apr, 2003  |  Pubmed ID: 12480697

Precise analysis of human CD34-negative (CD34(-)) hematopoietic stem cells (HSCs) has been hindered by the lack of a simple and reliable assay system of these rare cells. Here, we successfully identify human cord blood-derived CD34(-) severe combined immunodeficiency (SCID)- repopulating cells (SRCs) with extensive lymphoid and myeloid repopulating ability using the intra-bone marrow injection (IBMI) technique. Lineage-negative (Lin(-)) CD34(-) cells did not show SRC activity by conventional tail-vein injection, possibly due to their low levels of homing receptor expression and poor SDF-1/CXCR4- mediated homing abilities, while they clearly showed a high SRC activity by IBMI. They generated CD34(+) progenies not only in the injected left tibia but also in other bones following migration. Moreover, they showed slower differentiating and reconstituting kinetics than CD34(+) cells in vivo. These in vivo-generated CD34(+) cells showed a distinct SRC activity after secondary transplantation, clearly indicating the long-term human cell repopulating capacity of our identified CD34(-) SRCs in nonobese diabetic (NOD)/SCID mice. The unveiling of this novel class of primitive human CD34(-) SRCs by IBMI will provide a new concept of the hierarchy in the human HSC compartment and has important implications for clinical HSC transplantation as well as for basic research of HSC.

Human Body Surface Area: a Theoretical Approach

European Journal of Applied Physiology. Apr, 2004  |  Pubmed ID: 14634827

Knowledge of the human body surface area has important applications in medical practice, garment design, and other engineering sizing. Therefore, it is not surprising that several expressions correlating body surface area with direct measurements of body mass and length have been reported in the literature. In the present study, based on the assumption that the exterior shape of the human body is the result of convex and concave deformations from a basic cylinder, we derive a theoretical equation minimizing body surface area (BSA) at a fixed volume (V): BSA=(9pi VL)(0.5), where L is the reference length of the body. Assuming a body density value of 1,000 kg.m(-3), the equation becomes BSA=(BM.BH/35.37)(0.5), where BSA is in square meters, BM is the body mass in kilograms, and BH is the body height in meters. BSA values calculated by means of this equation fall within +/-7% of the values obtained by means of the equations available in the literature, in the range of BSA from children to adults. It is also suggested that the above equation, which is obtained by minimizing the outer body surface at a fixed volume, implies a fundamental relation set by the geometrical constraints governing the growth and the development of the human body.

A Unified Formula for Calculating Body Surface Area of Humans and Animals

European Journal of Applied Physiology. Jun, 2004  |  Pubmed ID: 15015002

We previously derived a formula for calculating human body surface area (BSA) from V (body volume) and L (reference body length): BSA=(9 pi VL)(0.5). In this paper, we analyse first the effects of body density variation on BSA during growth and the scaling relation of BSA to body mass. Then we utilise the derived formula to calculate BSA of animals and compare the obtained data with the direct measurements on the same animals, including rat, chicken, dog, and cattle, from the literature. It is shown that two problems remain to be solved for applying the derived formula to all mammals and other animals: one is to find out the L for each species of animal by means of direct measurements, and the other is to obtain the variation of body density during growth.

Proliferative and Migratory Potentials of Human Cord Blood-derived CD34- Severe Combined Immunodeficiency Repopulating Cells That Retain Secondary Reconstituting Capacity

International Journal of Hematology. May, 2004  |  Pubmed ID: 15218959

Using the intra-bone marrow injection (IBMI) technique, we recently identified human cord blood-derived CD34- severe combined immunodeficiency (SCID)-repopulating cells (SRCs) with extensive lymphomyeloid reconstituting ability. In this study, we further investigated the hematopoietic stem cell (HSC) characteristics of these cells in terms of proliferative and migratory potentials. The absolute numbers of CD45+ and CD34+ cells generated by 1 CD34- SRC are significantly higher than those generated by 1 CD34+ SRC. It is interesting that CD34- SRCs have significantly higher migratory and proliferative abilities than CD34+ SRCs. Moreover, only 2 CD34- SRCs transplanted to primary recipients consistently showed secondary reconstituting capacity. This finding suggested the more homogenous nature of CD34- SRCs than that of the population of CD34+ SRCs. These results provided further evidence that CD34- SRCs are functionally different from CD34+ SRCs and that they are a distinct class of primitive HSCs.

Simultaneous Injection of Bone Marrow Cells and Stromal Cells into Bone Marrow Accelerates Hematopoiesis in Vivo

Stem Cells (Dayton, Ohio). 2004  |  Pubmed ID: 15579644

We have previously demonstrated that stromal cells can support the proliferation and differentiation of hematopoietic cells in vitro and in vivo and that a major histocompatibility complex restriction exists between hematopoietic stem cells and stromal cells. We have also found that intra-bone marrow (IBM) injection of allogeneic bone marrow cells (BMCs) leads to more rapid reconstitution of hematopoietic cells than intravenous injection. In the present study, we examine the effect of simultaneous injection of stromal cells and BMCs into the same bone marrow on the recovery of donor hematopoietic cells and demonstrate that simultaneous IBM injection of BMCs plus stromal cells is more effective in reconstituting recipients with donor hematopoietic cells than intravenous injection of BMCs plus stromal cells or IBM injection of BMCs alone.

Mobilization of Bone Marrow Cells by G-CSF Rescues Mice from Cisplatin-induced Renal Failure, and M-CSF Enhances the Effects of G-CSF

Journal of the American Society of Nephrology : JASN. Mar, 2005  |  Pubmed ID: 15689404

Cisplatin, which is a broadly used anticancer drug, is widely known to induce acute renal failure as a result of renal tubular injury. This article examines whether G-CSF and/or M-CSF rescues mice from renal failure induced by cisplatin. BALB/c mice received intraperitoneal injections with or without G-CSF and/or M-CSF for 5 d (from day -5 to day -1). The day after the last injection of G-CSF and/or M-CSF (day 0), the mice received an intraperitoneal injection of cisplatin. When pretreated with G-CSF or G-CSF + M-CSF, the mice showed longer survival and lower serum creatinine and blood urea nitrogen levels than mice that had been received injections of M-CSF or saline. Histologically, pretreatment with G-CSF or G-CSF + M-CSF attenuated the damage to renal tubules induced by cisplatin. BALB/c mice that had received a transplant of bone marrow cells of enhanced green fluorescent protein (EGFP)-transgenic mice ([EGFP-->BALB/c] mice) were treated with or without G-CSF and/or M-CSF, followed by injection of cisplatin as well as above. [EGFP-->BALB/c] mice that were treated with G-CSF or G-CSF + M-CSF showed a significantly higher number of EGFP(+) tubular epithelial cells in the kidney than mice that were treated with only M-CSF or saline. These results suggest that bone marrow cells mobilized by G-CSF accelerate the improvement in renal functions and prevent the renal tubular injury induced by cisplatin and that M-CSF enhances the effects of G-CSF.

Autopsy Case of Primary Choriocarcinoma of the Urinary Bladder

Pathology International. Apr, 2005  |  Pubmed ID: 15826249

Choriocarcinomas usually develop in the uterus and ovaries in the female, being extremely rare in the extragenital organs in the male. Extragenital choriocarcinomas in the male usually develop in the mediastinum or retroperitoneum. The frequency of choriocarcinoma in the urinary bladder is extremely low. The purpose of the present paper was to report an autopsy case of choriocarcinoma in the urinary bladder in the male. An 81-year-old male patient with macrohematuria was first diagnosed with transitional cell carcinoma (TCC). At autopsy a hemorrhagic necrotic tumor, which was found in the urinary bladder with metastatic lesions in the lungs, was diagnosed as choriocarcinoma microscopically. There was no evidence for choriocarcinoma derived from any other organs than the urinary bladder, although there were metastatic lesions in both lungs and the direct invasion into the prostate. From these findings it is concluded that the tumor was a primary choriocarcinoma in the urinary bladder in a male patient. Choriocarcinoma of the urinary bladder is very rare, but the prognosis is extremely poor in comparison with TCC even in the urinary bladder. Therefore, it is essential to clearly discriminate between choriocarcinomas and TCC.

Cytotoxic and Antimicrobial Metabolites from Marine Lignicolous Fungi, Diaporthe Sp

FEMS Microbiology Letters. Oct, 2005  |  Pubmed ID: 16102912

A new compound (1), named diaporthelactone, together with two known compounds (2 and 3) were isolated from the culture of Diaporthe sp., a marine fungus growing in the submerged rotten leaves of Kandelia candel in the mangrove nature conservation areas of Fugong, Fujian Province of China. The new compound was elucidated to be 1,3-dihydro-4-methoxy-7-methyl-3-oxo-5-isobenzofuran-carboxyaldehyde (1), which showed cytotoxic activity against KB and Raji cell lines (IC50 6.25 and 5.51 microg mL(-1), respectively). Two known compounds, 7-methoxy-4,6-dimethyl-3H-isobenzofuran-1-one (2) and mycoepoxydiene (3), were also demonstrated to exhibit cytotoxic activities for the first time. All three compounds were assessed for antimicrobial activity.

Hepatocyte Growth Factor Delivered by Ultrasound-mediated Destruction of Microbubbles Induces Proliferation of Cardiomyocytes and Amelioration of Left Ventricular Contractile Function in Doxorubicin-induced Cardiomyopathy

Stem Cells (Dayton, Ohio). Nov-Dec, 2005  |  Pubmed ID: 16109756

At present, there is no curative strategy for advanced cardiomyopathy except for cardiac transplantation, which is not easily performed, mainly due to a shortage of donors. It has been reported that myocardial progenitor cells exist even in the postnatal heart, suggesting that myocardial progenitor cells could proliferate under some situations and might improve cardiac function in cardiomyopathy-induced hearts. In this study, recombinant human hepatocyte growth factor (rhHGF) was delivered using ultrasound-mediated destruction of microbubbles (UMDM) into the cardiomyopathy-induced heart by doxorubicin (20 mg/kg). Intravenous injection of rhHGF (IV-rhHGF) alone or UMDM alone failed to improve the morphology or the function of the cardiomyopathy-induced heart, but (IV-rhHGF + UMDM) treatment significantly improved the heart morphologically and functionally, and repetitive treatments of (IV-rhHGF + UMDM) enhanced the effects. The number of bromodeoxy-uridine-positive cardiomyocytes significantly increased in the (IV-rhHGF + UMDM)-treated hearts compared with the untreated hearts. Moreover, Sca-1+ myocardial progenitor cells express c-Met, a receptor for HGF. These results suggest that (IV-rhHGF + UMDM) treatment could morphologically and functionally improve the heart in the case of doxorubicin-induced cardiomyopathy through the proliferation of the myocardial progenitor cells.

Long-term Observation After Simultaneous Lung and Intra-bone Marrow-bone Marrow Transplantation

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. Sep, 2005  |  Pubmed ID: 16143265

Although lung transplantation is now an established treatment for end-stage lung diseases, allogeneic transplantation of parenchymal organs requires immunosuppressive therapy to prevent rejection. It has been reported that bone marrow transplantation (BMT) induces specific tolerance to donor organs. We have recently discovered a new method for BMT, which is called intra-bone marrow (IBM) BMT, in which bone marrow cells (BMCs) are injected directly into the bone marrow cavity. We demonstrate that IBM-BMT can be used to induce tolerance even in simultaneous lung transplantations in rats without administering any immunosuppressants.

Enhanced Susceptibility to Kainate-induced Seizures, Neuronal Apoptosis, and Death in Mice Lacking Gangliotetraose Gangliosides: Protection with LIGA 20, a Membrane-permeant Analog of GM1

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Nov, 2005  |  Pubmed ID: 16306414

Knock-out (KO) mice lacking gangliotetraose gangliosides attributable to disruption of the gene for GM2/GD2 synthase [GalNAcT (UDP-N-acetylgalactosamine:GM3/GD3 beta-1,4-N-acetylgalactosaminyltransferase; EC 2.4.1.92 [EC])] are revealing key neural functions for the complex gangliosides of brain. This study has found such animals to be highly susceptible to kainic acid (KA)-induced seizures in terms of both seizure severity and duration. Intraperitoneal injection of 25 mg/kg KA produced status epilepticus for approximately 200 min in normal mice or heterozygotes and more than four times longer in the KO mice. The latter group suffered approximately 30% mortality, which increased to approximately 75% at dosage of 30 mg/kg KA, compared with 10-14% for the other two genotypes at the latter dosage. Nissl staining and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling assay revealed substantial deterioration of pyramidal neurons attributable to apoptosis in the KO hippocampus, especially the CA3 region. Seizure activity in the KO mouse was only moderately diminished by intraperitoneal injection of GM1 ganglioside, whereas LIGA 20, a semisynthetic analog of GM1, substantially reduced both seizure severity and cell damage. The potency of LIGA 20 was correlated with its enhanced membrane permeability (compared with GM1), as seen in the increased uptake of [3H]LIGA 20 into the subcellular fractions of brain including cell nuclei. The latter finding is consonant with LIGA 20-induced restoration of the Na+/Ca2+ exchanger located at the inner membrane of the nuclear envelope in KO mice, an exchanger dependent on tight association with GM1 or its analog for optimal activity. These results point to a neuroprotective role for GM1 and its associated exchanger in the nucleus, based on regulation of Ca2+ flux between nucleoplasm and nuclear envelope.

Physiological Role of N-acetylaspartate: Contribution to Myelinogenesis

Advances in Experimental Medicine and Biology. 2006  |  Pubmed ID: 16802709

Characterization of Mesenchymal Stem Cells Isolated from Mouse Fetal Bone Marrow

Stem Cells (Dayton, Ohio). Mar, 2006  |  Pubmed ID: 16179426

Mesenchymal stem cells (MSCs) are defined as cells that can differentiate into multiple mesenchymal lineage cells. MSCs have some features (surface molecules and cytokine production, etc.) common to so-called traditional bone marrow (BM) stromal cells, which have the capacity to support hemopoiesis. In the present study, we isolated murine MSCs (mMSCs) from the fetal BM using an anti-PA6 monoclonal antibody (mAb) that is specific for bone marrow stromal cells. The mMSCs, called FMS/PA6-P cells, are adherent, fibroblastic, and extensively expanded and have the ability to differentiate not only into osteoblasts and adipocytes but also into vascular endothelial cells. The FMS/PA6-P cells produce a broad spectrum of cytokines and growth factors closely related to hemopoiesis and show good hemopoiesis-supporting capacity both in vivo and in vitro, suggesting that they are a component of the hemopoietic stem cell niche in vivo. Interestingly, although the FMS/PA6-P cells express a high level of the PA6 molecule, which is reactive with anti-PA6 mAb, they gradually lose their ability to express this molecule during the course of differentiation into osteoblasts and adipocytes, indicating that the PA6 molecule might serve as a novel marker of mMSCs.

Bimodal Occurrence of Aspartoacylase in Myelin and Cytosol of Brain

Journal of Neurochemistry. Apr, 2007  |  Pubmed ID: 17254025

The growing use of N-acetylaspartate as an indicator of neuronal viability has fostered interest in the biological function(s) of this unusual amino acid derivative. In considering the various physiological roles that have been proposed for this relatively abundant molecule one is obliged to take into account its unusual metabolic compartmentalization, according to which synthesis and storage occur in the neuron and hydrolytic cleavage in the oligodendrocyte. The latter reaction, catalyzed by aspartoacylase (ASPA), produces acetyl groups plus aspartate and has been proposed to occur in both soluble and membranous subfractions of white matter. Our study supports such bimodal occurrence and we now present immunoblot, proteomic, and biochemical evidence that the membrane-bound form of ASPA is intrinsic to purified myelin membranes. This was supported by a novel TLC-based method for the assay of ASPA. That observation, together with previous demonstrations of numerous lipid-synthesizing enzymes in myelin, suggests utilization of acetyl groups liberated by myelin-localized ASPA for lipid synthesis within the myelin sheath. Such synthesis might be selective and could explain the deficit of myelin lipids in animals lacking ASPA.

Identification of Long-term Repopulating Potential of Human Cord Blood-derived CD34-flt3- Severe Combined Immunodeficiency-repopulating Cells by Intra-bone Marrow Injection

Stem Cells (Dayton, Ohio). Jun, 2007  |  Pubmed ID: 17303816

Recently, we have identified human cord blood (CB)-derived CD34-negative (CD34(-)) severe combined immunodeficiency (SCID)-repopulating cells (SRCs) using the intra-bone marrow injection (IBMI) method (Blood 2003;101:2924). In contrast to murine CD34(-) Kit(+)Sca-1(+)Lineage(-) (KSL) cells, human CB-derived Lin(-)CD34(-) cells did not express detectable levels of c-kit by flow cytometry. In this study, we have investigated the function of flt3 in our identified human CB-derived CD34(-) SRCs. Both CD34(+)flt3(+/-) cells showed SRC activity. In the CD34(-) cell fraction, only CD34(-)flt3(-) cells showed distinct SRC activity by IBMI. Although CD34(+)flt3(+) cells showed a rather weak secondary repopulating activity, CD34(+)flt3(-) cells repopulated many more secondary recipient mice. However, CD34(-)flt3(-) cells repopulated all of the secondary recipients, and the repopulating rate was much higher. Next, we cocultured CD34(-)flt3(-) cells with the murine stromal cell line HESS-5. After 1 week, significant numbers of CD34(+)flt3(+/-) cells were generated, and they showed distinct SRC activity. These results indicated that CB-derived CD34(-)flt3(-) cells produced CD34(+)flt3(-) as well as CD34(+)flt3(+) SRCs in vitro. The present study has demonstrated for the first time that CB-derived CD34(-) SRCs, like murine CD34(-) KSL cells, do not express flt3. On the basis of these data, we propose that the immunophenotype of very primitive long-term repopulating human hematopoietic stem cells is Lin(-)CD34(-)c-kit(-)flt3(-). Disclosure of potential conflicts of interest is found at the end of this article.

Nitricoxide Synthase-induced Oxidative Stress in Prolonged Alcoholic Myopathies of Rats

Molecular and Cellular Biochemistry. Oct, 2007  |  Pubmed ID: 17607508

Previous studies showed that nitricoxide synthase (NOS) and oxidative stress can induce skeletal muscle atrophy in the muscular dystrophy and inclusion-body myopathy. There is a correlation between NOS and oxidative stress. However, it is not clear, whether there are some changes of the NOS activity in prolonged alcoholic myopathy (PAM), and whether NOS activity has relation to amyotrophy of PAM. We established experimental alcoholic myopathy model of rats by prolonged alcohol intake. We found that there is a reduction in GSH-px (P < 0.05) and an increase of SOD (P < 0.05), MDA (P < 0.05) and iNOS (P < 0.05) in the plantaris of the experimental group by spectrophotometer. In the soleus of the experimental group, except for MDA showed an increase (P < 0.05), the other enzymes showed no obvious difference (P > 0.05). The immunohistochemistry results showed that there was obvious expression of iNOS in the cytoplasm of plantaris in the experimental group and there was no expression of iNOS in the control group. There was a decrease of nNOS expression on the membranes of the plantaris cells in the experimental group by immunofluorescence. Meanwhile, we found the expression of nNOS in some cytoplasm. Our results suggested that NOS might be an important factor during the development of PAM. We could infer that there are some disturbances with regard to output and scavenging of free radical in PAM. Alcohol can induce the oxidative stress reaction and further result in imbalance of the oxidant-antioxidant status in the organism.

Long-term Donor-specific Tolerance in Rat Cardiac Allografts by Intrabone Marrow Injection of Donor Bone Marrow Cells

Transplantation. Jan, 2008  |  Pubmed ID: 18192918

Donor-specific central tolerance in cardiac allograft can be induced by hematopoietic chimerism via conventional intravenous bone marrow transplantation (IV-BMT). However, there are problems with IV-BMT, such as the risk of graft failure and of the toxicity from conditioning regimens.

Loss of TLE1 and TLE4 from the Del(9q) Commonly Deleted Region in AML Cooperates with AML1-ETO to Affect Myeloid Cell Proliferation and Survival

Blood. Apr, 2008  |  Pubmed ID: 18258796

Deletions on chromosome 9q are seen in a subset of acute myeloid leukemia (AML) cases and are specifically associated with t(8;21) AML. We previously defined the commonly deleted region in del(9q) AML and characterized the genes in this interval. To determine the critical lost gene(s) that might cooperate with the AML1-ETO fusion gene produced by t(8;21), we developed a set of shRNAs directed against each gene in this region. Within this library, shRNAs to TLE1 and TLE4 were the only shRNAs capable of rescuing AML1-ETO expressing U937T-A/E cells from AML1-ETO-induced cell-cycle arrest and apoptosis. Knockdown of TLE1 or TLE4 levels increased the rate of cell division of the AML1-ETO-expressing Kasumi-1 cell line, whereas forced expression of either TLE1 or TLE4 caused apoptosis and cell death. Knockdown of Gro3, a TLE homolog in zebrafish, cooperated with AML1-ETO to cause an accumulation of noncirculating hematopoietic blast cells. Our data are consistent with a model in which haploinsufficiency of these TLEs overcomes the negative survival and antiproliferative effects of AML1-ETO on myeloid progenitors, allowing preleukemic stem cells to expand into AML. This study is the first to implicate the TLEs as potential tumor suppressor genes in myeloid leukemia.

Preparation of N,N'-bisethoxyethane[12]amideferrocenophane and Its Application in Anion Recognition

The Journal of Physical Chemistry. B. May, 2008  |  Pubmed ID: 18402486

Novel N,N'-bisethoxyethane[12]amideferrocenophane has been synthesized by a condensation reaction and characterized by (1)H NMR and mass spectrum. The anion recognition properties of the compound are evaluated via (1)H NMR, FT-IR, and electrochemical measurement. It is found that N,N'-bisethoxyethane[12]amideferrocenophane exhibits remarkable electrochemical response to H(2)PO(4-) anion in CH(2)C(l2) or CH(3)CN solution, and response to anions can also be observed in CH(3)CN solution containing up to 15% water. Binding constants between the compound and HSO(4-) in different solutions have been determined by UV-vis spectrum titration experiments. The results indicate that the compound shows a selective recognition trend of H(2)PO(4-) > HSO(4-) (F(-)) > Br(-).

Administration of Granulocyte Colony-stimulating Factor to Recipients Followed by Intra-bone Marrow-bone Marrow Transplantation Accelerates Acceptance of Allogeneic Bone Marrow Cells in Mice

Immunobiology. 2008  |  Pubmed ID: 18472051

We have recently established a novel method for bone marrow transplantation: intra-bone marrow-bone marrow transplantation (IBM-BMT), by which the rapid recovery of donor-derived hematopoiesis can be expected even when reduced radiation doses are used. In this paper, we examine, using mice, whether the combination of pretreatment of recipients with granulocyte-colony-stimulating factor (G-CSF) and IBM-BMT can induce a more rapid recovery of donor-derived hematopoiesis than IBM-BMT alone. We first pretreated recipients with recombinant human (rh) G-CSF (250 microg/kg/day) for 5 consecutive days (days -6 to -2). On day -1, the recipients were irradiated, and IBM-BMT was carried out on day 0. On day 12, we performed colony-forming units of spleen (CFU-S) assays. The combination of G-CSF pretreatment and IBM-BMT augmented the CFU-S counts, the weight of spleens, and the numbers of donor-derived hematopoietic cells. We next analyzed the mechanisms underlying these effects of G-CSF and found that (i) G-CSF induces Th2 polarization, which can prevent graft rejection, and (ii) G-CSF augments natural suppressor activity, which suppresses graft rejection. The combination of G-CSF pretreatment and IBM-BMT can produce the rapid recovery of donor-derived hematopoiesis and suppress graft rejection. This method would lighten the burden on patients in allogeneic BMT.

Myelin Lipid Abnormalities in the Aspartoacylase-deficient Tremor Rat

Neurochemical Research. Jan, 2009  |  Pubmed ID: 18478328

The high concentration of N-acetylaspartate (NAA) in neurons of the central nervous system and its growing clinical use as an indicator of neuronal viability has intensified interest in the biological function of this amino acid derivative. The biomedical relevance of such inquiries is highlighted by the myelin-associated pathology of Canavan disease, an inherited childhood disorder resulting from mutation of aspartoacylase (ASPA), the NAA-hydrolyzing enzyme. This enzyme is known to be localized in oligodendrocytes with bimodal distribution in cytosol and the myelin sheath, and to produce acetyl groups utilized in myelin lipid synthesis. Loss of this acetyl source in Canavan disease and rodent models such as the tremor rat are thought to account for the observed myelin deficit. This study was undertaken to further define and quantify the specific lipid abnormalities that occur as a result of ASPA deficit in the tremor rat. Employing mass spectrometry together with high performance thin-layer chromatography, we found that myelin from 28-day-old animals showed major reduction in cerebrosides (CB) and sulfatides (Sulf) with unsubstituted fatty acids, and equal if not greater changes in myelin from 7-month-old tremors. Cerebrosides with 2-hydroxyfatty acids showed little if any change at either age; Sulf with 2-hydroxyfatty acids showed no significant change at 28 days, but surprisingly a major increase at 7 months. Two species of phosphatidylcholine, 32:0 and 34:1, also showed significant increase, but only at 28 days. One form of phosphatidylethanolamine, PE36:1, was reduced a modest amount at both ages, whereas the plasmalogen form did not change. The dysmyelination that results from inactivation of ASPA is thus characterized by selective decreases as well as some increases in specific lipids.

Cross-linking of GM1 Ganglioside by Galectin-1 Mediates Regulatory T Cell Activity Involving TRPC5 Channel Activation: Possible Role in Suppressing Experimental Autoimmune Encephalomyelitis

Journal of Immunology (Baltimore, Md. : 1950). Apr, 2009  |  Pubmed ID: 19299701

Several animal autoimmune disorders are suppressed by treatment with the GM1 cross-linking units of certain toxins such as B subunit of cholera toxin (CtxB). Due to the recent observation of GM1 being a binding partner for the endogenous lectin galectin-1 (Gal-1), which is known to ameliorate symptoms in certain animal models of autoimmune disorders, we tested the hypothesis that an operative Gal-1/GM1 interplay induces immunosuppression in a manner evidenced by both in vivo and in vitro systems. Our study of murine experimental autoimmune encephalomyelitis (EAE) indicated suppressive effects by both CtxB and Gal-1 and further highlighted the role of GM1 in demonstrating enhanced susceptibility to EAE in mice lacking this ganglioside. At the in vitro level, polyclonal activation of murine regulatory T (Treg) cells caused up-regulation of Gal-1 that was both cell bound and released to the medium. Similar activation of murine CD4(+) and CD8(+) effector T (Teff) cells resulted in significant elevation of GM1 and GD1a, the neuraminidase-reactive precursor to GM1. Activation of Teff cells also up-regulated TRPC5 channels which mediated Ca(2+) influx upon GM1 cross-linking by Gal-1 or CtxB. This involved co-cross-linking of heterodimeric integrin due to close association of these alpha(4)beta(1) and alpha(5)beta(1) glycoproteins with GM1. Short hairpin RNA (shRNA) knockdown of TRPC5 in Teff cells blocked contact-dependent proliferation inhibition by Treg cells as well as Gal-1/CtxB-triggered Ca(2+) influx. Our results thus indicate GM1 in Teff cells to be the primary target of Gal-1 expressed by Treg cells, the resulting co-cross-linking and TRPC5 channel activation contributing importantly to the mechanism of autoimmune suppression.

Through the Looking Glass, Mechanistic Insights from Enantiomeric Human Defensins

The Journal of Biological Chemistry. Oct, 2009  |  Pubmed ID: 19640840

Despite the small size and conserved tertiary structure of defensins, little is known at a molecular level about the basis of their functional versatility. For insight into the mechanism(s) of defensin function, we prepared enantiomeric pairs of four human defensins, HNP1, HNP4, HD5, and HBD2, and studied their killing of bacteria, inhibition of anthrax lethal factor, and binding to HIV-1 gp120. Unstructured HNP1, HD5, and HBD3 and several other human alpha- and beta-defensins were also examined. Crystallographic analysis showed a plane of symmetry that related (L)HNP1 and (D)HNP1 to each other. Either d-enantiomerization or linearization significantly impaired the ability of HNP1 and HD5 to kill Staphylococcus aureus but not Escherichia coli. In contrast, (L)HNP4 and (D)HNP4 were equally bactericidal against both bacteria. d-Enantiomers were generally weaker inhibitors or binders of lethal factor and gp120 than their respective native, all-l forms, although activity differences were modest, particularly for HNP4. A strong correlation existed among these different functions. Our data indicate: (a) that HNP1 and HD5 kill E. coli by a process that is mechanistically distinct from their actions that kill S. aureus and (b) that chiral molecular recognition is not a stringent prerequisite for other functions of these defensins, including their ability to inhibit lethal factor and bind gp120 of HIV-1.

Sialidase Occurs in Both Membranes of the Nuclear Envelope and Hydrolyzes Endogenous GD1a

Journal of Neurochemistry. Oct, 2009  |  Pubmed ID: 19686243

Previous reports indicated the presence of both gangliosides and sialidase in the nuclear envelope (NE) of primary neurons and the NG108-15 neural cell line. GM1, one of the major gangliosides of this membrane, was shown to be tightly associated with a sodium-calcium exchanger in the inner membrane of the NE and to potentiate exchanger activity. GD1a was the other major ganglioside detected in the NE and, like GM1, occurs in both inner and outer membranes. A subsequent report indicated the presence of sialidase activity in the NE without specification as to which of the two membranes express it. The present study was undertaken to determine the nature and locus of this activity within the NE of two cell lines: NG108-15 and SH-SY5Y. Western blot analysis of the separated membranes revealed occurrence of Neu3 in the inner membrane and Neu1 in the outer membrane of the NE. Moreover, sialidase activity at both sites was shown capable of catalyzing conversion of endogenous GD1a to GM1.

3,3'-Difluoro-4,4'-(p-phenyl-enedi-oxy)dibenzonitrile

Acta Crystallographica. Section E, Structure Reports Online. 2009  |  Pubmed ID: 21577811

The title compound, C(20)H(10)F(2)N(2)O(2), was synthesized from hydro-quinone and 3,4-difluoro-benzonitrile. The centroid of the central aromatic ring is on a crystallographic center of inversion. The dihedral angle between the central and terminal rings is 77.8 (3)°. In the crystal, chains linked by C-H⋯N bond occur.

4-(4-Cyano-2-fluoro-phen-oxy)phenyl 4-methyl-benzene-sulfonate

Acta Crystallographica. Section E, Structure Reports Online. 2009  |  Pubmed ID: 21583682

The title compound, C(20)H(14)FNO(4)S, was synthesized from hydro-quinone, p-toluene-sulfonyl chloride and 3,4-difluoro-benzonitrile. A folded conformation is adopted by the crystal structure. Inter-molecular C-H⋯N hydrogen bonds form dimers arranged around inversion centers.

3-Fluoro-4-(4-hy-droxy-phen-oxy)benzonitrile

Acta Crystallographica. Section E, Structure Reports Online. 2010  |  Pubmed ID: 21588053

The title compound, C(13)H(8)FNO(2), was synthesized from 3,4-difluoro-benzonitrile and hydro-quinone. The dihedral angle between the two aromatic rings is 70.9 (2)°. In the crystal structure, mol-ecules are linked by O-H⋯N hydrogen bonds, forming zigzag chains.

(1R,2R)-N,N'-Bis(ferrocenylmeth-yl)-1,2-diphenyl-ethane-1,2-diamine

Acta Crystallographica. Section E, Structure Reports Online. 2010  |  Pubmed ID: 21588210

The title compound, [Fe(2)(C(5)H(5))(2)(C(26)H(26)N(2))], was synthesized from a chiral diamine and ferrocenecarboxaldehyde and subsequent reduction with NaBH(4). It has two chiral centers which both exhibit an R configuration. Two ferrocene groups are present in the mol-ecular structure, with their cyclo-penta-dienyl ring planes showing an almost perpen-dicular arrangement [dihedral angle 88.6 (1)°].

Rectifying Switching Characteristics of Pt/ZnO/Pt Structure Based Resistive Memory

Journal of Nanoscience and Nanotechnology. Nov, 2010  |  Pubmed ID: 21137871

40 nm thick amorphous ZnO thin films were deposited by radio frequency magnetron sputtering at room temperature and asymmetric electrical switching characteristics are observed in the macroscopic symmetric Pt/ZnO/Pt structure. The crystal structure was examined by X-ray diffraction (XRD). The chemical bonding states of ZnO resistive switching layer was investigated by X-ray photoelectron spectroscopy (XPS). Keithley 4200 semiconductor characterization system was used to measure the current-voltage (I-V) characteristics of the fabricated devices. The results reveal that a reversible resistive switching behavior between the high resistance state and the low resistance state with rectifying effects can be repeated for more than 100 dc cycles. This asymmetric electrical behavior is thought to be related to the naturally self-formed PtOx between ZnO film and the Pt bottom electrode, which introduces an energy barrier when electrons flow from top electrode towards the bottom electrode. The model of Pt/ZnO/Pt memory cell is expected to be able to alleviate the misreading error in cross-point array for high density integrations.

Modelling Young's Modulus for Porous Bones with Microstructural Variation and Anisotropy

Journal of Materials Science. Materials in Medicine. Feb, 2010  |  Pubmed ID: 19882305

A structural model with three compositional phases and two levels of hierarchical organization is proposed for predicting Young's modulus of porous bones with microstructural variations and anisotropy based on their geometric similarity to metal foams. It has been shown that the proposed single model provides predictions of Young's modulus with high accuracy up to +/-30% for cortical and cancellous bones compared with measured data from the literature. In addition, the conversion of the solid bone shape from "Plate-like" to "Rod-like" at a porosity of 70% or higher (BV/TV 30% or lower)-verified by observations-can be predicted using the proposed model.

A Controllable Molecular Sieve for Na+ and K+ Ions

Journal of the American Chemical Society. Feb, 2010  |  Pubmed ID: 20102186

The selective rate of specific ion transport across nanoporous material is critical to biological and nanofluidic systems. Molecular sieves for ions can be achieved by steric and electrical effects. However, the radii of Na(+) and K(+) are quite similar; they both carry a positive charge, making them difficult to separate. Biological ionic channels contain precisely arranged arrays of amino acids that can efficiently recognize and guide the passage of K(+) or Na(+) across the cell membrane. However, the design of inorganic channels with novel recognition mechanisms that control the ionic selectivity remains a challenge. We present here a design for a controllable ion-selective nanopore (molecular sieve) based on a single-walled carbon nanotube with specially arranged carbonyl oxygen atoms modified inside the nanopore, which was inspired by the structure of potassium channels in membrane spanning proteins (e.g., KcsA). Our molecular dynamics simulations show that the remarkable selectivity is attributed to the hydration structure of Na(+) or K(+) confined in the nanochannels, which can be precisely tuned by different patterns of the carbonyl oxygen atoms. The results also suggest that a confined environment plays a dominant role in the selectivity process. These studies provide a better understanding of the mechanism of ionic selectivity in the KcsA channel and possible technical applications in nanotechnology and biotechnology, including serving as a laboratory-in-nanotube for special chemical interactions and as a high-efficiency nanodevice for purification or desalination of sea and brackish water.

Polarized GaN-based LED with an Integrated Multi-layer Subwavelength Structure

Optics Express. Mar, 2010  |  Pubmed ID: 20389722

A novel type of GaN-based LED with a highly polarized output using an integrated multi-layer subwavelength grating structure is proposed. Characteristics of both optical transmission and polarization extinction ratio of the polarized GaN-based LED with three different multi-layer subwavelength structures are investigated. It is found that both TM transmission (T(TM)) and the extinction ratio(ER) of the LED output can be effectively enhanced by incorporating a dielectric transition layer between the metal grating and GaN substrate with a lower refractive index than that of the GaN substrate. Flat sensitivity of the T(TM) on the period, duty cycle of the metallic grating, and the wide range of operating wavelength have been achieved in contrast to the conventional sensitive behavior in single-layer metallic grating. Up to 0.75 high duty cycle of the metallic grating can be employed to achieve >60dB ER while T(TM) maintains higher than ~90%, which breaks the conventional limit of T(TM) and ER being always a pair of trade-off parameters. Typical optimized multilayer structures in terms of material, thickness, grating periods and duty cycle using MgF(2) and ZnS, respectively, as the transition layers are obtained. The results provide guidance in designing, optimizing and fabricating the novel integrated GaN-based and polarized photonic devices.

Inactivation of Microorganisms in Apple Juice Using an Ultraviolet Silica-fiber Optical Device

Journal of Photochemistry and Photobiology. B, Biology. Sep, 2010  |  Pubmed ID: 20598561

Most juices are opaque to ultraviolet (UV) due to the high-suspended solids in them and therefore the conventional UV treatment, generally used for water treatment, cannot be used for treating juices. In order to achieve a high germicidal efficiency of UV processing, an optical device with silica optical fibers for UV light delivery was designed. Its suitability for application could be shown in experiments with Escherichia coli, Lactobacillus brevis, Saccharomyces cerevisiae and naturally contaminating microorganisms as test microorganisms. The thin-film thickness for treating apple juice was optimized. At 2.0-mm film thickness, E. coli and L. brevis were reduced by up to 6 log orders with the UV dose of 23.7 m J/cm(2) and the optical-fiber distribution density of 15 fibers/cm(2), while only about 4-log reduction of S. cerevisiae was achieved under the same condition. Naturally contaminating lactic acid bacteria, Enterobacteriaceae and yeasts and moulds in freshly extracted apple juice were reduced to below 10 CFU/ml. These results indicate that this optical device could be used to improve microbial safety and extend shelf-life of apple juice.

Eugenol Reduces the Expression of Virulence-related Exoproteins in Staphylococcus Aureus

Applied and Environmental Microbiology. Sep, 2010  |  Pubmed ID: 20639367

Eugenol, an essential oil component in plants, has been demonstrated to possess activity against both gram-positive and gram-negative bacteria. This study examined the influence that subinhibitory concentrations of eugenol may have on the expression of the major exotoxins produced by Staphylococcus aureus. The results from a tumor necrosis factor (TNF) release assay and a hemolysin assay indicated that S. aureus cultured with graded subinhibitory concentrations of eugenol (16 to 128 microg/ml) dose dependently decreased the TNF-inducing and hemolytic activities of culture supernatants. Western blot analysis showed that eugenol significantly reduced the production of staphylococcal enterotoxin A (SEA), SEB, and toxic shock syndrome toxin 1 (the key exotoxins to induce TNF release), as well as the expression of alpha-hemolysin (the major hemolysin to cause hemolysis). In addition, this suppression was also evaluated at the transcriptional level via real-time reverse transcription (RT)-PCR analysis. The transcriptional analysis indicated that 128 microg/ml of eugenol remarkably repressed the transcription of the S. aureus sea, seb, tst, and hla genes. According to these results, eugenol has the potential to be rationally applied on food products as a novel food antimicrobial agent both to inhibit the growth of bacteria and to suppress the production of exotoxins by S. aureus.

MCF-7/ADR Cells (re-designated NCI/ADR-RES) Are Not Derived from MCF-7 Breast Cancer Cells: a Loss for Breast Cancer Multidrug-resistant Research

Medical Oncology (Northwood, London, England). Dec, 2011  |  Pubmed ID: 21116879

MCF-7/ADR cells have been widely used as a multidrug-resistant breast cancer cell model in cancer research. The origin of MCF-7/ADR has been a matter of debate since MCF-7/ADR cells were re-designated NCI/ADR-RES in 1998. Many recent studies still describe MCF-7/ADR cells as originating from the breast cancer cell line MCF-7. Thus, the real origin of MCF-7/ADR cells remains more unclear. In this study, a new adriamycin (ADR)-resistant cell line MCF-7/ADR' was reproduced using the same procedure employed during the initial establishment of MCF-7/ADR. Since the MCF-7/ADR' cell line was definitely derived from parental MCF-7 cells, we were able to directly compare these cell lines together with MCF-7/ADR using immunocytochemical, morphological, and consecutive DNA fingerprinting analyses to determine the true origin of MCF-7/ADR. Both ADR-resistant cell lines displayed some similar phenotypic characteristics, such as high levels of P-glycoprotein (P-gp) expression, increased vacuolation, abundant filamentous material, and irregular pseudopodia. With increasing concentrations of ADR, the DNA fingerprints of MCF-7/ADR' cells were always identical to the parental MCF-7 cells. However, the DNA fingerprints of MCF-7/ADR cells did not relate to MCF-7 or MCF-7/ADR'. MCF-7/ADR and the breast cancer cell line MCF-7 are not of the same origin. Long-time culture in the presence of ADR does not cause significant changes in DNA fingerprint patterns.

Subinhibitory Concentrations of Farrerol Reduce α-toxin Expression in Staphylococcus Aureus

FEMS Microbiology Letters. Feb, 2011  |  Pubmed ID: 21175745

In this study, the antibacterial activity of farrerol against Staphylococcus aureus was determined. The minimum inhibitory concentrations capable of inhibiting 35 S. aureus strains ranged from 4 to 16 μg mL(-1) . A haemolysis assay, Western blot and real-time reverse transcriptase-PCR assay were performed to identify the influence of subinhibitory concentrations of farrerol on the secretion of α-toxin by S. aureus. The results show that farrerol significantly decreased, in a dose-dependent manner, the production of α-toxin by both methicillin-sensitive S. aureus and methicillin-resistant S. aureus.

Subinhibitory Concentrations of Perilla Oil Affect the Expression of Secreted Virulence Factor Genes in Staphylococcus Aureus

PloS One. 2011  |  Pubmed ID: 21283822

The pathogenicity of staphylococcus aureus is dependent largely upon its ability to secrete a number of virulence factors, therefore, anti-virulence strategy to combat S. aureus-mediated infections is now gaining great interest. It is widely recognized that some plant essential oils could affect the production of staphylococcal exotoxins when used at subinhibitory concentrations. Perilla [Perilla frutescens (L.) Britton], a natural medicine found in eastern Asia, is primarily used as both a medicinal and culinary herb. Its essential oil (perilla oil) has been previously demonstrated to be active against S. aureus. However, there are no data on the influence of perilla oil on the production of S. aureus exotoxins.

Menthol Diminishes Staphylococcus Aureus Virulence-associated Extracellular Proteins Expression

Applied Microbiology and Biotechnology. Apr, 2011  |  Pubmed ID: 21287163

Staphylococcus aureus is a significant human pathogen that is the major cause of a broad spectrum of illnesses, ranging from minor skin infections to life-threatening deep tissue infections and toxinosis. The ability of the organism to cause such a broad range of infections is, to a great extent, attributed to the secretion of a myriad of virulence-related extracellular proteins. Therefore, virulence as a target for antimicrobial chemotherapy has gained great interest. Menthol is a monocyclic terpene alcohol that occurs naturally in plants of the Mentha species lacking anti-S. aureus activity. In this paper, we demonstrate via hemolytic activity assays, tumor necrosis factor release assays, Western blot assays, and real-time reverse transcription-PCR assays that low concentrations of menthol can markedly inhibit the expression of α-hemolysin, enterotoxins A and B, and toxic shock syndrome toxin 1 in S. aureus. Our results indicate that menthol may be useful in managing S. aureus infections when used in combination with β-lactam antibiotics, which can often increase S. aureus toxin secretion when used at subinhibitory concentrations. In addition, the menthol basic structure has potential applications in the development of new anti-virulence drugs.

Urolithiasis in Pregnancy: Survey in Clinical Epidemiology

Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban. Apr, 2011  |  Pubmed ID: 21505990

This study examined the association of pregnancy with urolithiasis and provided new insights into urolithiasis in pregnancy. A total of 462 subjects were studied from January 2004 to December 2009 in Foshan Maternal and Child Health Hospital, China. Among the 462 subjects, 162 cases of urolithiasis during pregnancy (UPG) were selected as the observation group, 150 cases of no urolithiasis during pregnancy (NUPG) served as pregnancy control group, and 150 cases of no pregnancy (NPG) at reproductive age who took part in physical examination were randomly assigned into non-pregnant control group. At the same time, the patients in observation group were divided into the following sub-groups: no symptomatic urinary calculus (NSUC) and symptomatic urinary calculus (SUC) groups; SUC group was further divided into surgical intervention (SI) and conservative management (CM) groups. The general information and the data of blood and urine were collected and compared among the groups. The results showed that the incidence of urinary calculi in pregnant women was lower than that in non-pregnant women, the formation of urinary stone was associated with the change of metabolism of protein and sugar in pregnant women, and the surgical intervention was a practicable alternative to treat the clinical intractable symptomatic urinary calculi in pregnancy.

Isoalantolactone Protects Against Staphylococcus Aureus Pneumonia

FEMS Microbiology Letters. Nov, 2011  |  Pubmed ID: 22092816

Staphylococcus aureus is a versatile pathogen that can cause life-threatening infections. The growing emergence of methicillin-resistant S. aureus strains and a decrease in the discovery of new antibiotics warrant the search for new therapeutic targets to combat infections. Staphylococcus aureus produces many extracellular virulence factors that contribute to its pathogenicity. Therefore, targeting bacterial virulence as an alternative strategy to the development of new antimicrobials has gained great interest. α-Toxin is a 33.2-kDa, water-soluble, pore-forming toxin that is secreted by most S. aureus strains. α-Toxin is essential for the pathogenesis of pneumonia, as strains lacking α-toxin display a profound defect in virulence. In this report, we demonstrate that isoalantolactone (IAL), a naturally occurring compound found in Inula helenium (Compositae), has no anti-S. aureus activity as per MIC evaluation in vitro. However, IAL can markedly inhibit the expression of α-toxin in S. aureus at very low concentrations. Furthermore, the in vivo data indicate that treatment with IAL protects mice from S. aureus pneumonia.

Effects of Increased Matrix Metalloproteinase-9 Expression on Skeletal Muscle Fibrosis in Prolonged Alcoholic Myopathies of Rats

Molecular Medicine Reports. Jan, 2012  |  Pubmed ID: 21935573

This study evaluated the effects of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) on injured gastrocnemius, soleus and plantaris muscles, induced by alcohol in rats. A total of 60 male Sprague-Dawley rats (2.5 months old, 200 ± 20 g) were divided into 6 groups: i) untreated skeletal muscle and analyzed 2 weeks later (A1 group, 5 rats); ii) untreated skeletal muscle and analyzed 6 weeks later (A2 group, 5 rats); iii) untreated skeletal muscle and analyzed 12 weeks later (A3 group, 5 rats); iv) injured skeletal muscle and analyzed 2 weeks later (B1 group, 15 rats); v) injured skeletal muscle and analyzed 6 weeks later (B2 group, 15 rats); and vi) injured skeletal muscle and analyzed 12 weeks later (B3 group, 15 rats). The injured and uninjured muscles were observed by light microscopy and polarization microscopy. The MMP activity was evaluated through zymography, and messenger RNA (mRNA) of MMP-9 and of MMP-2 were assessed by RT-PCR. The expression of MMP-9 was assessed by Western blot analysis. The plantaris and gastrocnemius muscles in the rats subjected to alcohol ingestion were found to have a high expression of MMP-9, but not of MMP-2. Picrosirius red staining was used to assess whether increased fibrosis in the skeletal muscle was associated with alcohol exposure in rats. The study indicated that alcohol may be involved in the skeletal muscle interstitial fibrosis in our model of alcohol-exposed rats through increased MMP-9 expression, and that this increased expression may aggravate the development of prolonged alcohol muscle injury.

Layered Nanocomposites Inspired by the Structure and Mechanical Properties of Nacre

Chemical Society Reviews. Jan, 2012  |  Pubmed ID: 21959863

Nacre (mother-of-pearl), made of inorganic and organic constituents (95 vol% aragonite calcium carbonate (CaCO(3)) platelets and 5 vol% elastic biopolymers), possesses a unique combination of remarkable strength and toughness, which is compatible for conventional high performance materials. The excellent mechanical properties are related to its hierarchical structure and precisely designed organic-inorganic interface. The rational design of aragonite platelet strength, aspect ratio of aragonite platelets, and interface strength ensures that the strength of nacre is maximized under platelet pull-out failure mode. At the same time, the synergy of strain hardening mechanisms acting over multiple scales results in platelets sliding on one another, and thus maximizes the energy dissipation of viscoplastic biopolymers. The excellent integrated mechanical properties with hierarchical structure have inspired chemists and materials scientists to develop biomimetic strategies for artificial nacre materials. This critical review presents a broad overview of the state-of-the-art work on the preparation of layered organic-inorganic nanocomposites inspired by nacre, in particular, the advantages and disadvantages of various biomimetic strategies. Discussion is focused on the effect of the layered structure, interface, and component loading on strength and toughness of nacre-mimic layered nanocomposites (148 references).

Family-based Analysis of Susceptibility Loci for Polycystic Ovary Syndrome on Chromosome 2p16.3, 2p21 and 9q33.3

Human Reproduction (Oxford, England). Jan, 2012  |  Pubmed ID: 22081247

Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder. A previous genome-wide association study (GWAS) identified five single nucleotide polymorphisms (SNPs) which were independently associated with PCOS in Han Chinese. To overcome population stratification, a family-based analysis was conducted to validate whether these five SNPs are associated with PCOS.