This review focuses on the efficiency of different water treatment processes for the removal of cyanotoxins from potable water. Although several investigators have studied full-scale drinking water processes to determine the efficiency of cyanotoxin inactivation, many of the studies were based on ancillary practice. In this context, "ancillary practice" refers to the removal or inactivation of cyanotoxins by standard daily operational procedures and without a contingency operational plan utilizing specific treatment barriers. In this review, "auxiliary practice" refers to the implementation of inactivation/removal treatment barriers or operational changes explicitly designed to minimize risk from toxin-forming algae and their toxins to make potable water. Furthermore, the best drinking water treatment practices are based on extension of the multibarrier approach to remove cyanotoxins from water. Cyanotoxins are considered natural contaminants that occur worldwide and specific classes of cyanotoxins have shown regional prevalence. For example, freshwaters in the Americas often show high concentrations of microcystin, anatoxin-a, and cylindrospermopsin, whereas Australian water sources often show high concentrations of microcystin, cylindrospermopsin, and saxitoxins. Other less frequently reported cyanotoxins include lyngbyatoxin A, debromoaplysiatoxin, and beta-N-methylamino-L-alanine. This review focuses on the commonly used unit processes and treatment trains to reduce the toxicity of four classes of cyanotoxins: the microcystins, cylindrospermopsin, anatoxin-a, and saxitoxins. The goal of this review is to inform the reader of how each unit process participates in a treatment train and how an auxiliary multibarrier approach to water treatment can provide safer water for the consumer.

The colonization of the rodent gastrointestinal tract by enteric neuron precursors is controversial due to the lack of specific cellular markers at early stages. The transcription factor, Phox2b, is expressed by enteric neuron precursors (Pattyn et al. Development 124, 4065-4075, 1997). In this study, we have used an antiserum to Phox2b to characterize in detail the spatiotemporal expression of Phox2b in the gastrointestinal tract of adult mice and embryonic mice and rats. In adult mice, all enteric neurons (labeled with neuron-specific enolase antibodies), and a subpopulation of glial cells (labeled with GFAP antibodies), showed immunoreactivity to Phox2b. In embryonic mice, the appearance of Phox2b-immunoreactive cells was mapped during development of the gastrointestinal tract. At Embryonic Days 9.5-10 (E9.5-10), Phox2b-labeled cells were present only in the stomach, and during subsequent development, labeled cells appeared as a single rostrocaudal wave along the gastrointestinal tract; at E14 Phox2b-labeled cells were present along the entire length of the gastrointestinal tract. Ret and p75 have also been reported to label migratory-stage enteric neuron precursors. A unidirectional, rostral-to-caudal colonization of the gastrointestinal tract of embryonic mice by Ret- and p75-immunoreactive cells was also observed, and the locations of Ret- and p75-positive cells within the gut were very similar to that of Phox2b-positive cells. To verify the location of enteric neuron precursors within the gut, explants from spatiotemporally defined regions of embryonic intestine, 0.3-3 mm long, were grown in the kidney subcapsular space, or in catenary organ culture, and examined for the presence of neurons. The location and sequence of appearance of enteric neuron precursors deduced from the explants grown under the kidney capsule or in organ culture was very similar to that seen with the Phox2b, Ret, and p75 antisera. Previous studies have mapped the rostrocaudal colonization of the rat intestine by enteric neuron precursors using HNK-1 as a marker. In the current study, all HNK-1-labeled cells in the gastrointestinal tract of rat embryos showed immunoreactivity to Phox2b, but HNK-1 cells comprised only a small subpopulation of the Phox2b-labeled cells. In addition, in rats, Phox2b-labeled cells were present in advance of (more caudal to) the most caudal HNK-1-labeled cells by 600-700 microm in the hindgut at E15. We conclude that the neural crest cell population that arises from the vagal level of the neural axis and that populates the stomach, midgut, and hindgut expresses Phox2b, Ret, and p75. In contrast, the sacral-level neural crest cells that populate the hindgut either do not express, or show a delayed expression of, all of the known markers of vagal- and trunk-level neural crest cells.

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.

Binding of the peptide hormone angiotensin II (AngII) to the type 1 (AT 1A ) receptor and the subsequent activation of phospholipase C-mediated signaling, involves specific determinants within the AngII peptide sequence. In contrast, the contribution of such determinants to AT 1A receptor internalization, phosphorylation and activation of mitogen-activated protein kinase (MAPK) signaling is not known. In this study, the internalization of an enhanced green fluorescent protein-tagged AT 1A receptor (AT 1A -EGFP), in response to AngII and a series of substituted analogs, was visualized and quantified using confocal microscopy. AngII-stimulation resulted in a rapid, concentration-dependent internalization of the chimeric receptor, which was prevented by pretreatment with the nonpeptide AT 1 receptor antagonist EXP3174. Remarkably, AT 1A receptor internalization was unaffected by substitution of AngII side chains, including single and double substitutions of Tyr 4 and Phe 8 that abolish phospholipase C signaling through the receptor. AngII-induced receptor phosphorylation was significantly inhibited by several substitutions at Phe 8 as well as alanine replacement of Asp 1 . The activation of MAPK was only significantly inhibited by substitutions at position eight in the peptide and specific substitutions did not equally inhibit inositol phosphate production, receptor phosphorylation and MAPK activation. These results indicate that separate, yet overlapping, contacts made between the AngII peptide and the AT 1A receptor select/induce distinct receptor conformations that preferentially affect particular receptor outcomes. The requirements for AT 1A receptor internalization seem to be less stringent than receptor activation and signaling, suggesting an inherent bias toward receptor deactivation.