Inhibiting Substance Research Articles

Abstract 3462: Comparative RNA-Seq analysis of MIS signaling: Potential relevance as therapeutic strategy in ovarian cancer treatment

Abstract Ovarian cancer (OC) is the fifth leading cause of cancer death in women in the US. Müllerian inhibiting substance (MIS) is a glycoprotein hormone that causes Müllerian duct regression through a complex of TGF- β family homologous receptors: a type II ligand-binding receptor (T2R) and a tissue-specific type I receptor (T1R) that initiates downstream signaling. MIS has been proposed as potential therapeutic agent in OC. We have previously shown that specific combination of T2R/T1R receptors are expressed on OC cells, however data is lacking on the MIS-dependent pathways activated in OC cells in a T1R-specific manner. These limitations hinder further development of MIS as a therapy. We sought to determine the downstream signaling pathways activated by MIS in a T1R specific manner. We designed a chimeric OC cell model system in which GM-CSF can function as the ligand to specifically activate candidate T2R/T1R combinations (MISRII with either ALK2, ALK3, or ALK6). RNA-Seq technology was used to identify differentially expressed early and late response genes. Over 15,032 genes were analyzed, restricted to genes in which there were > 32 counts for duplicate samples. Pathway analysis was performed using Ingenuity's Integrative Pathway Analysis Tool (IPA) for genes which were expressed over 2 fold, with an False Discovery Rate (FDR)<0.1 and log (Counts per Million, CPM)>-0.001. We observed 56, 37, and 51 early response (1hr) genes which were up- or down-regulated after stimulation in OC cells engineered to express either ALK2, ALK3, and ALK6, respectively. We identified a subset of 18 of genes (e.g., ID1, SMAD7, FOSB) which were upregulated after treatment in all MISRII/T1R combinations, suggesting redundancy amongst the three T1R partner receptors. These observations will be confirmed by RT-qPCR and immunoblotting. A majority of these redundant genes are known to play roles in TGF-β signaling and cell proliferation pathways. Importantly, as we have previously shown that not all T1R candidates are expressed in OC, we report subsets of genes (e.g., RASSF6, C/EBPBβ, CSMD3) which were uniquely altered after stimulation only in the presence of a specific T1R. This indicates specific pathway activation is dependent upon T1R expression pattern in OC and likely determines response. In addition to previously known TGF- β signaling pathway, we found gene signatures (e.g. FOSB, RASSF6, LRP1B, ID1) suggesting pathways which affect cell proliferation, apoptosis, chemotherapy resistance, and DNA repair in response to MIS. This is the first study to begin to define the specific roles candidate T1R's play in signaling in response to MIS in an OC model. An understanding of these pathways is a necessary prerequisite to examining MIS as a therapy. These preliminary data suggest a role for MIS in apoptosis, cytotoxic drug resistance and DNA repair. This can be used to test combination therapy with currently available drugs and MIS in OC treatment. Citation Format: Qing Zhang, Eati Basal, Jaime I. Davila, Xueqian Yin, Edward B. Leof, William A. Cliby. Comparative RNA-Seq analysis of MIS signaling: Potential relevance as therapeutic strategy in ovarian cancer treatment. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3462. doi:10.1158/1538-7445.AM2014-3462

Anti-Müllerian hormone - A hormone with narrow spectrum of action and broad spectrum of clinical significance

AMH (Anti-Müllerian Hormone, Müllerian Inhibiting Substance or Factor) is a member of the transforming growth factor - " family, secreted by the fetal and prepubertal testicular Sertoli cells, and to a lesser amount by the granulosa cells of the small ovarian follicles. It plays an important role in the shaping of the male reproductive tract and is one of the baseline hormones in the diagnostics of the disorders of the sex development in the male. In the female, in the recent years AMH has become an important clinical tool for evaluation of the ovarian follicular reserve, for predicting ovarian response to gonadotropin stimulation in IVF treatment and for the diagnosis of hyperandrogenism. Recombinant AMH is a promising medication for the treatment of gynecological cancers and endometriosis.

Application of barley straw to dammed river for algal control

In 1970s, barley straw has been known to be capable of controlling algal growth. In vitro and in situ experiments were performed to investigate the effects of barley straw on algal growth inhibition substances. In addition, its ecotoxicity and the algal growth inhibition substances extracted from barley straw were examined. In the in vitro experiment, barley straw and retinaspora leaf treatment groups caused significant decreases (p value < 0.05) in the number of cells in Anabaena affinis, Microcystis aeruginosa, and Scenedesmus quadricauda compared with the control group. However, the treatment group, which applied 0.2g of barley straw, showed a tendency of increasing the number of cells in S. quadricauda compared with the control group. It reveals that types of algae and proper applications of barley straw are important to inhibit algal growth. In addition, the barley straw showed almost no ecotoxicities in ecotoxicity experiments while the retinaspora leaf showed a certain degree of ecotoxicity (Toxicity unit >36). In the in situ experiment, algal growth was inhibited by barley straw. In particular, diatoms exhibited a tendency of decreasing the number of algal cells compared with blue-green algae. It shows that the barley straw does not inhibit the growth of all algae and shows different effects according to types of algae. The algal growth inhibition substances were extracted from the barley straw and tested. It was found that a ferulic acid in various phenol compounds affected the algal growth most.

Mullerian inhibiting substance suppresses proliferation and induces apoptosis and autophagy in endometriosis cells in vitro.

Objective. To determine the effects of Mullerian inhibiting substance (MIS) treatment on endometriosis cells through study of apoptosis and autophagy. Design. Experimental in vitro study. Setting. University research laboratory. Cell Line. CRL-7566 endometriosis cell line. This line was established from a benign ovarian cyst taken from a patient with endometriosis. Interventions. In vitro treatment with MIS. Main Outcome Measures. The main outcome measures were cellular viability, proliferation, cell-cycle arrest, and induction of apoptosis and autophagy in endometriotic cells. Results. MIS treatment inhibited proliferation of endometriosis cells and induced apoptosis, as indicated by Annexin V staining, and induced caspase-9 cleavage and cell-cycle arrest, as evidenced by increased expression of p27 CDK-inhibitor. MIS treatment also induced autophagy in endometriosis cells as demonstrated by a significant increase in LC3-II induction, a hallmark of autophagy. Conclusions. MIS inhibits cell growth and induces autophagy, as well as apoptosis, in ectopic endometrial cell lines. Our results suggest that MIS may have a potential as a novel approach for medical treatment of endometriosis. Further studies may be needed to test the efficacy of MIS treatment in animal models and to develop MIS treatment specifically targeted to the endometriosis.

Mullerian inhibiting substance expression in papillary thyroid cancer

To examine the expression of Mullerian inhibiting substance (MIS) in papillary thyroid cancer. The MIS expression was examined by studying the immunohistochemistry in deparafinized sections prepared from tissue blocks of patients who were diagnosed with papillary thyroid cancer, as given in the pathology archive records (n = 23). In all the cases studied, 50% (n = 10) showed strong staining and 50% showed moderate staining. The percentage of staining was found to be 94.2 ± 3.1% in strongly stained cases and 92.2 ± 2.1% in moderately stained cases. Normal thyroid tissues neighboring the tumor did not display any staining. The MIS expression can be used as a significant tool in differential diagnosis of papillary thyroid cancer and also to shed light on its etiopathogenesis.

Paracrine Mechanisms Involved in the Control of Early Stages of Mammalian Spermatogenesis

Within the testis, Sertoli-cell is the primary target of pituitary FSH. Several growth factors have been described to be produced specifically by Sertoli cells and modulate male germ cell development through paracrine mechanisms. Some have been shown to act directly on spermatogonia such as GDNF, which acts on self-renewal of spermatogonial stem cells (SSCs) while inhibiting their differentiation; BMP4, which has both a proliferative and differentiative effect on these cells, and KIT ligand (KL), which stimulates the KIT tyrosine-kinase receptor expressed by differentiating spermatogonia (but not by SSCs). KL not only controls the proliferative cycles of KIT-positive spermatogonia, but it also stimulates the expression of genes that are specific of the early phases of meiosis, whereas the expression of typical spermatogonial markers is down-regulated. On the contrary, FGF9 acts as a meiotic inhibiting substance both in fetal gonocytes and in post-natal spermatogonia through the induction of the RNA-binding protein NANOS2. Vitamin A, which is metabolized to Retinoic Acid in Sertoli cells, controls both SSCs differentiation through KIT induction and NANOS2 inhibition, and meiotic entry of differentiating spermatogonia through STRA8 upregulation.

Effect of Inhibition Substances on Monod Equation of Yeast Growth

Effect of Inhibition Substances on Monod Equation of Yeast Growth

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Ovarian cancer is the fifth most lethal malignancy in women. The standard treatment of this disease is chemotherapy which is, however, often inefficient. The failure of chemotherapy is due to the developing multidrug resistance and the presence of cancer stem cells. This article describes research on new drugs, which can overcome these limitations. Some of the substances which are effective in cancer cells resistant to the standard approach are bisintercalating anthracyclines and epothilones. One of the bisanthracyclines is WP 631, which is more effective than commonly used first-generation anthracyclines, even on cells resistant to cisplatin or doxorubicin. In turn, epothilones have a similar mechanism of action as taxanes. They stabilize microtubules and consequently perturb mitosis. Both WP 631 and epothilones appear to be hopeful candidates to break multidrug resistance because of their low affinity for P-glycoprotein – the efflux pump for drugs. Substances, which effectively eliminate cancer stem cells include metformin, Mullerian inhibiting substance, and salinomycin. Metformin has a proapoptotic activity and exhibits synergism with cisplatin – a chemotherapeutic agent used in ovarian cancer treatment. Mullerian inhibiting substance perturbs the cell cycle, while salinomycin inhibits proliferation and induces apoptosis in the ovarian cancer cells. The search for new drugs effective in the ovarian cancer treatment, especially in cases resistant to current forms of therapy, remains a challenging priority.

The Müllerian inhibiting substance type 2 receptor suppresses tumorigenesis in testes with sustained β-catenin signaling

Dysregulated WNT/β-catenin signaling in murine testes results in a phenotype with complete germ cell loss that resembles human Sertoli cell-only syndrome. In other systems, including the ovary, dysregulated WNT/β-catenin induces tumorigenesis but no tumors are observed in the mutant testes without deletion of a tumor suppressor, such as phosphatase and tensin homolog (PTEN). Müllerian inhibiting substance (MIS, also known as AMH), a member of the transforming growth factor-β family of growth factors responsible for Müllerian duct regression in fetal males, has been shown to inhibit tumor growth in vitro and in vivo but its role as an endogenous tumor suppressor has never been reported. We have deleted the MIS type 2 receptor (MISR2), and thus MIS signaling, in mice with dysregulated WNT/β-catenin and show that these mice develop testicular stromal tumors with 100% penetrance within a few months postnatal. The tumors are highly proliferative and have characteristics of either Sertoli cell tumors or progenitor Leydig cell tumors based on their marker profiles and histology. Phosphorylated Sma and mothers against decapentaplegic-related homolog 1/5/8 is absent in the tumors and β-catenin target genes are induced. The tumor suppressor TP53 is also highly expressed in the tumors, as is phosphorylated γH2AX, which is indicative of DNA damage. The phenotype of these tumors closely resembles those observed when PTEN is also deleted in mice with dysregulated WNT/β-catenin. Tumorigenesis in these mice provides conclusive evidence that physiological MIS signaling is a tumor suppressor mechanism and suggests that targeted treatment of MISR2-expressing cancers with therapeutic MIS should have a beneficial effect on tumor progression.

Green liquor pretreatment for improving enzymatic hydrolysis of corn stover

Green liquor consists of sodium carbonate and sodium sulfide and is readily available in any kraft mills. The green liquor pretreatment process for bioethanol production was developed for wood chips. This process uses only proven technology and equipment currently used in a kraft pulp mill and has several additional advantages such as high sugar recovery and concentration, no inhibitive substances produced, as compared to acid-based pretreatment methods. The liquor was used to pretreat corn stover for enhancing enzymatic hydrolysis in bioethanol production. Pulp yield of 70% with 45% lignin removal was achieved under optimized conditions (8% total titratable alkali, 40% sulfidity and 140°C). About 70% of the original polysaccharides were converted into fermentable sugars, using 20 FPU/g-pulp of enzyme in the subsequent enzymatic hydrolysis. The result indicates that green liquor is a feasible pretreatment to improve the enzymatic saccharification of corn stover for bioethanol production.

Spatial Restriction of Bone Morphogenetic Protein Signaling in Mouse Gastrula through the mVam2-Dependent Endocytic Pathway

The embryonic body plan is established through positive and negative control of various signaling cascades. Late endosomes and lysosomes are thought to terminate signal transduction by compartmentalizing the signaling molecules; however, their roles in embryogenesis remain poorly understood. We showed here that the endocytic pathway participates in the developmental program by regulating the signaling activity. We modified the mouse Vam2 (mVam2) locus encoding a regulator of membrane trafficking. mVam2-deficient cells exhibited abnormally fragmented late endosomal compartments. The mutant cells could terminate signaling after theremoval of the growth factors including TGF-β and EGF, except BMP-Smad1/Smad5 signaling. mVam2-deficient embryos exhibited ectopic activation of BMP signaling and disorganization of embryo patterning. We found that mVam2, which interacts with BMP type I receptor, is required for the spatiotemporal modulation of BMP signaling, via sequestration of the receptor complex in the late stages of the endocytic pathway.

Mullerian inhibiting substance (MIS) pathway as a therapeutic target in ovarian cancer: Deciphering the necessary components

Objective: Activation of mullerian inhibiting substance type II receptor (T2R) leads to dimerization with one of three candidate type I receptors (T1R) and growth inhibition of mullerian tissues. While T2R is commonly expressed in epithelial ovarian cancer (EOC), the prevalence of T1R is unknown; this data is critical because our in vitro studies suggest that biologic response is dependent upon which candidate T1R is involved in signaling. The aims of this research were to characterize the frequency of candidate T1R expression in EOC and determine if clinical outcomes are dependent on receptor expression.

On the properties of calcium-induced permeability transition in neonatal heart mitochondria

Permeability transition was examined in heart mitochondria isolated from neonate rats. We found that these mitochondria were more susceptible to Ca(2+)-induced membrane leakiness than mitochondria from adult rats. In K(+) containing medium, at 25°C, mitochondria were unable to accumulate Ca(2+). Conversely, in Na(+) containing medium, mitochondria accumulated effectively Ca(2+). At 15°C mitochondria accumulated Ca(2+) regardless of the presence of K(+). Kinetics of Ca(2+) accumulation showed a similar Vmax as that of adult mitochondria. Lipid milieu of inner membrane contained more unsaturated fatty acids than adult mitochondria. Aconitase inhibition and high thiobarbituric acid-reactive substances (TBARS) indicate that oxidative stress caused mitochondrial damage. In addition, proteomics analysis showed that there is a considerable diminution of succinate dehydrogenase C and subunit 4 of cytochrome oxidase in neonate mitochondria. Our proposal is that dysfunction of the respiratory chain makes neonate mitochondria more susceptible to damage by oxidative stress.

Effect of Ozone and Potassium Lactate on Lipid Oxidation and Survival of Salmonella typhimurium on Fresh Pork

The objective of this research was to evaluate the effect of ozone gas and potassium lactate on lipid oxidation and survival of Salmonella typhimurium on fresh pork. A total of 144 samples of fresh pork samples were cut into pieces approximately (8x5x0.6) cm in size, then (0, 2 and 4%) potassium lactate (KL), inoculated with S. typhimurium was applied by spreading a 0.5 mL cell suspension over each sample. The pork samples were then packed in (6"x8") airtight polyethylene bags with a thickness of 87.5 microm and a volume of 3.5 L with and without ozone. Ozone gas was injected into the plastic bags at a rate of 0, 200, 500 and 1,000 mg h(-1) and the samples later stored at 8 degrees C. Thio-barbituric Acid Reactive Substance (TBARS) and microbial loads were determined on days 0, 5, 10 and 15. Data was statistically analyzed using SPSS software and differences among means detected at the 0.5% confident level using the Scheffe's test. Samples treated with 2 and 4% KL had significantly (p<0.01) lower TBARS value than non-treated samples. Combination of ozone and KL showed inhibitory effects on S. typhimurium in samples. S. typhimurium was sensitive to 4% KL with and without ozone. At 1,000 mg h(-1), ozone improved KL inhibitory effect on S. typhimurium. Ozone and KL are potential substances for inhibition of S. typhimurium.

Study of enzymatic properties of phenol oxidase from nitrogen-fixing azotobacter chroococcum

Azotobacter chroococcum is a widespread free-living soil bacterium within the genus of Azotobacter known for assimilation of atmospheric nitrogen and subsequent conversion into nitrogenous compounds, which henceforth enrich the nitrogen content of soils. A. chroococcum SBUG 1484, isolated from composted earth, exhibits phenol oxidase (PO) activity when growing under nitrogen-fixing conditions. In the present study we provide incipient analysis of the crude PO activity expressed by A. chroococcum SBUG 1484 within comparative analysis to fungal crude PO from the white-rot fungus Pycnoporus cinnabarinus SBUG-M 1044 and tyrosinase (PPO) from the mushroom Agaricus bisporus in an attempt to reveal desirable properties for exploitation with future recombinant expression of this enzyme. Catalytic activity increased with pre-incubation at 35°C; however 70% of activity remained after pre-treatment at 50°C. Native A. chroococcum crude PO exhibited not only strong preference for 2,6-dimethoxyphenol, but also towards related methoxy-activated substrates as well as substituted ortho-benzenediols from over 40 substrates tested. Presence of CuSO4 enhanced crude phenol oxidase activity up to 30%, whereas NaN3 (0.1 mM) was identified as the most inhibiting substance of all inhibitors tested. Lowest inhibition of crude PO activity occurred after 60 minutes of incubation in presence of 15% methanol and ethanol with 63% and 77% remaining activities respectively, and presence of DMSO even led to increasing oxidizing activities. Substrate scope and inhibitor spectrum strongly differentiated A. chroococcum PO activity comprised in crude extracts from those of PPO and confirmed distinct similarities to fungal PO.

Müllerian inhibiting substance is anterogradely transported and does not attenuate avulsion-induced death of hypoglossal motor neurons

Müllerian Inhibiting Substance (MIS, Anti-Müllerian hormone) is a gonadal hormone that contributes to the subtle sex-biases in the nervous system. Mature neurons of both sexes also produce MIS, suggesting that MIS may be a paracrine regulator of adult neural networks. We report here that murine hypoglossal motor neurons produce MIS and its receptors, MISRII and bone morphogenetic protein receptor 1A (BMPR1A, ALK3), but differentially transport them, with only MIS being detectable in axons. The production of MIS and its receptors were rapidly down regulated after axonal damage, which is a characteristic of genes involved in mature neuronal function. MIS is a survival factor for embryonic spinal motor neurons, but the rate of cell loss after hypoglossal nerve avulsion was normal in Mis −/− mice and was not attenuated by intraventricular administration of MIS. These observations suggest that MIS may be involved in anterograde rather than autocrine or retrograde regulation of neurons.

Müllerian inhibiting substance preferentially inhibits stem/progenitors in human ovarian cancer cell lines compared with chemotherapeutics

Cancer stem cells are proposed to be tumor-initiating cells capable of tumorigenesis, recurrence, metastasis, and drug resistance, and, like somatic stem cells, are thought to be capable of unlimited self-renewal and, when stimulated, proliferation and differentiation. Here we select cells by expression of a panel of markers to enrich for a population with stem cell-like characteristics. A panel of eight was initially selected from 95 human cell surface antigens as each was shared among human ovarian primary cancers, ovarian cancer cell lines, and normal fimbria. A total of 150 combinations of markers were reduced to a panel of three--CD44, CD24, and Epcam--which selected, in three ovarian cancer cell lines, those cells which best formed colonies. Cells expressing CD44, CD24, and Epcam exhibited stem cell characteristics of shorter tumor-free intervals in vivo after limiting dilution, and enhanced migration in invasion assays in vitro. Also, doxorubicin, cisplatin, and paclitaxel increased this enriched population which, conversely, was significantly inhibited by Müllerian inhibiting substance (MIS) or the MIS mimetic SP600125. These findings demonstrate that flow cytometry can be used to detect a population which shows differential drug sensitivity, and imply that treatment of patients can be individualized to target both stem/progenitor cell enriched and nonenriched subpopulations. The findings also suggest that this population, amenable to isolation by flow cytometry, can be used to screen for novel treatment paradigms, including biologic agents such as MIS, which will improve outcomes for patients with ovarian cancer.

Association of WT1 and induction of apoptosis in endometriotic cell lines treated with MIS

OBJECTIVE: Products of steroidogenic factor-1 (SF-1) and Wilms' tumor-1(WT1) genes are essential for mammalian gonadogenesis prior to sexual differentiation. Prior studies demonstrated WT1 inhibits cAMP SF-1 pathway dependent p450arom expression in cultured endometriotic and endometrial stromal cells. Mullerian inhibiting substance is first identified as a factor that causes regression of Mullerian ducts in developing male embryos. Recent research has revealed MIS causes cell-cycle arrest in ovarian, cervical and endometrial cancer cell lines in vitro. In our unpublished data, we showed MIS induces apoptosis and inhibits basal autophagy in ectopic endometrial cells. We hypothesized that WT1 and cAMP SF-1 dependent p450arom plays a role in the effect of MIS on endometriotic cell lines. In this study we aimed to explain the association of WT1 and induction of apoptosis with MIS treatment in endometriosis cell lines.DESIGN: We studied WT1 protein expression in endometriotic cell lines treated with MIS compared to no treatment.MATERIALS AND METHODS: Cultured CRL-7566 endometriosis cell lines from ovarian cyst (ATCC) were harvested at 80% confluency and placed in wells. Each well was treated with 5mcg/ml human recombinant MIS twice 4 days apart or with PBS as control. WT1 protein expression was determined using Western analysis and normalized to β-actin.RESULTS: MIS treatment significantly induced WT1 expression on endometriotic stromal cells(p<0.05) compared to the sample treated with control.CONCLUSION: MIS induces apoptosis, inhibits cellular growth and basal autophagy in endometriosis cell lines. MIS treatment induces WT1 expression which may partially explain the pathway that leads to apoptosis. OBJECTIVE: Products of steroidogenic factor-1 (SF-1) and Wilms' tumor-1(WT1) genes are essential for mammalian gonadogenesis prior to sexual differentiation. Prior studies demonstrated WT1 inhibits cAMP SF-1 pathway dependent p450arom expression in cultured endometriotic and endometrial stromal cells. Mullerian inhibiting substance is first identified as a factor that causes regression of Mullerian ducts in developing male embryos. Recent research has revealed MIS causes cell-cycle arrest in ovarian, cervical and endometrial cancer cell lines in vitro. In our unpublished data, we showed MIS induces apoptosis and inhibits basal autophagy in ectopic endometrial cells. We hypothesized that WT1 and cAMP SF-1 dependent p450arom plays a role in the effect of MIS on endometriotic cell lines. In this study we aimed to explain the association of WT1 and induction of apoptosis with MIS treatment in endometriosis cell lines. DESIGN: We studied WT1 protein expression in endometriotic cell lines treated with MIS compared to no treatment. MATERIALS AND METHODS: Cultured CRL-7566 endometriosis cell lines from ovarian cyst (ATCC) were harvested at 80% confluency and placed in wells. Each well was treated with 5mcg/ml human recombinant MIS twice 4 days apart or with PBS as control. WT1 protein expression was determined using Western analysis and normalized to β-actin. RESULTS: MIS treatment significantly induced WT1 expression on endometriotic stromal cells(p<0.05) compared to the sample treated with control. CONCLUSION: MIS induces apoptosis, inhibits cellular growth and basal autophagy in endometriosis cell lines. MIS treatment induces WT1 expression which may partially explain the pathway that leads to apoptosis.

Cryptorchidism

Cryptorchidism is a very common anomaly of the male genitalia, affecting 2%-4% of male infants and is more common in premature infants. There are two separate stages of testicular descent. The first stage occurs at 8-15 weeks' gestation in the human fetus and is characterized by enlargement of the genito-inguinal ligament, or gubernaculum, and regression of the cranial suspensory ligament. The testis remains close to the future inguinal region as the fetal abdomen grows. Leydig cells in the testis produce insulin-like hormone 3, which stimulates the caudal gubernaculum to grow and become thicker. Mullerian inhibiting substance may have a role in the first phase of descent by stimulating the swelling reaction in the gubernaculum. The second phase of testicular descent requires migration of the gubernaculum and testis from the inguinal region to the scrotum, between 25 and 35 weeks' gestation. The genitofemoral nerve releases calcitonin gene-related peptide, a neurotransmitter that provides a chemotactic gradient to guide migration. The exact cause of cyrptorchidism remains elusive. Information is mainly derived from animal studies (especially in rodents), which may not extrapolate to the human setting. These findings, however, do have some similarities among mammalian species. The current recommended timing for orchidopexy is between 6 and 12 months of life in an effort to preserve the spermatogonia--the stem cells for subsequent spermatogenesis. Despite surgical treatment by orchidopexy, the long-term outcome still remains problematic and controversial. Impaired fertility (33% in unilateral cases and 66% in bilateral undescended testes) and a cancer risk 5-10 times greater than normal is observed over time. Further research into the cause and management of undescended testes is necessary.

Surface-retained organic matter of Microcystis aeruginosa inhibiting coagulation with polyaluminum chloride in drinking water treatment

Algogenic organic matter produced by the excess growth of cyanobacteria in semi-closed water areas causes coagulation inhibition in drinking water production. In this study, hydrophilic substances of Microcystis aeruginosa, which were mainly composed of lipopolysaccharide (LPS) and RNA, were prepared, and the involvement of these cyanobacterial hydrophilic substances in coagulation inhibition was investigated. As a result, it was found that the negatively charged hydrophilic substances with a molecular weight higher than 10 kDa have a significant role in coagulation inhibition. Further fractionation of cyanobacterial hydrophilic substances revealed that surface-retained organic matter (SOM), including LPS, could exhibit a potent inhibitory effect on the coagulation using polyaluminum chloride (PACl), presumably because of the direct interaction of hydrophilic SOM with cations originated from PACl, which could impede the hydrolysis of the coagulant.