Two asymmetric syntheses of AMG 221, an inhibitor of 11beta-hydroxysteroid dehydrogenase type 1.

Two asymmetric syntheses of AMG 221 (2), an inhibitor of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) discovered in our laboratories, are reported. One of the syntheses utilizes chiral trimethylsilyl cyanohydrin 12 as starting material and the other utilizes its enantiomer ent-12. The displacement approach involves the conversion of 12 to 2 via a six-step sequence, occurs with net inversion of configuration, and employs amine 6 as starting material.

Method for effectively utilizing tunable one-pump fiber parametric wavelength converters as an enabling device for WDM routers.

In this paper a method is proposed to maximize the bandwidth of the WDM router based on one-pump fiber parametric wavelength converters. It is proved that for such converters there exists an optimum signal (idler) frequency at which the output (input) tuning range can be maximized. Analytical expressions of the optimum frequency and the maximal tuning range are deduced.

Estradiol promotes pituitary cell proliferation and gonadotroph differentiation at different doses and with different mechanisms in chick embryo.

Estrogens are known to play a role in the feedback regulation of pituitary gonadotropin secretion in adults. However, it is still unknown whether estrogens are involved in promoting pituitary development. In this study, we selected chick embryo as the animal model and microinjected different doses of estradiol (E2) at stage E27-28, which was when endogenous E2 was not detected.

Cytosolic viral sensor RIG-I is a 5'-triphosphate-dependent translocase on double-stranded RNA.

Retinoic acid inducible-gene I (RIG-I) is a cytosolic multidomain protein that detects viral RNA and elicits an antiviral immune response. Two N-terminal caspase activation and recruitment domains (CARDs) transmit the signal, and the regulatory domain prevents signaling in the absence of viral RNA. 5'-triphosphate and double-stranded RNA (dsRNA) are two molecular patterns that enable RIG-I to discriminate pathogenic from self-RNA.

Roles of RIG-I N-terminal tandem CARD and splice variant in TRIM25-mediated antiviral signal transduction.

The caspase recruitment domain (CARD) of intracellular adaptors and sensors plays a critical role in the assembly of signaling complexes involved in innate host defense against pathogens and in the regulation of inflammatory responses. The cytosolic receptor retinoic acid-inducible gene-I (RIG-I) recognizes viral RNA in a 5'-triphosphate-dependent manner and initiates an antiviral signaling cascade. Upon viral infection, the N-terminal CARDs of RIG-I undergo the K(63)-linked ubiquitination induced by tripartite motif protein 25 (TRIM25), critical for the interaction of RIG-I with its downstream signaling partner MAVS/VISA/IPS-1/Cardif.

Ethanol attenuates the HFS-induced, ERK-mediated LTP in a dose-dependent manner in rat striatum.

Background: The striatum has been implicated to play a role in the control of voluntary behavior, and striatal synaptic plasticity is involved in instrumental learning. Ethanol is known to alter synaptic plasticity, in turn altering the behavior of human and animals. However, it remains unclear whether the striatum plays a role in the effects of ethanol on the central nervous system.

The expression changes of genes associated with protein metabolism, folding, transport, localizati on and assembly during rat liver regeneration.

To study the expression and function of protein metabolism, folding, transport, localization and assembly-associated genes in rat liver regeneration (LR) at transcriptional level, we obtained above genes from databases and scientific articles, detected their expression profiles in rat LR using Rat Genome 230 2.0 array, and determined liver regeneration-associated genes by comparing the partial hepatectomy (PH) group with sham operation (SO) group. Totally 1147 genes were preliminarily confirmed to be LR-associated.

Application of nanosized Fe3O4 in anticancer drug carriers with target-orientation and sustained-release properties.

The purpose of this study was to prepare human serum albumin (HSA) microspheres with Fe(3)O(4) magnetic nanoparticles for tumor target therapy. Fe(3)O(4) was obtained by liquid-phase coprecipitation; HSA-coated magnetic particles were attained by solidification at high temperature. The result was that nanosized Fe(3)O(4) is a cubic crystal by XRD and the average size is 18.

The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I.

The ATPase RIG-I senses viral RNAs that contain 5'-triphosphates in the cytoplasm. It initiates a signaling cascade that activates innate immune response by interferon and cytokine production, providing essential antiviral protection for the host. The mode of RNA 5'-triphosphate sensing by RIG-I remains elusive.

New methods for the synthesis of 2-aminothiazolones.

Two new methods for the synthesis of 2-aminothiazolones from 2-(4-methoxybenzylthio)acetic acids are described. A single reagent and simple experimental conditions are used in the key tandem deprotection-cyclization process. In the first approach 2-aminothiazolones are directly accessed via cyclization of the corresponding N-acylisothioureas.

Ontogeny of estrogen receptor alpha, estrogen receptor beta and androgen receptor, and their co-localization with Islet-1 in the dorsal root ganglia of sheep fetuses during gestation.

The aims of the present study were to detect the ontogeny of estrogen receptor (ERalpha and ERbeta) and androgen receptor (AR) expressions and their co-localization with Islet-1 in the developing dorsal root ganglia (DRG) of sheep fetuses by immunohistochemistry. From the single staining results, the ERalpha immunoreactivity (ERalpha-ir), ERbeta immunoreactivity (ERbeta-ir) and AR immunoreactivity (AR-ir) was first detected at days 90, 120 and 90 of gestation, respectively. From days 90 to 120, ERalpha and AR were consistently detected in the nuclei of DRG neurons and the relative percentage (approximately 60%) of ERalpha-ir or AR-ir cells did not change significantly.

Specificity protein 1 (Sp1) plays role in regulating LIM homeodomain transcription factor Lhx4 gene expression.

Both Sp-family factor Specificity protein 1 (Sp1) and LIM homeodomain transcription factor Lhx4 are involved in regulating the development of pituitary gland and nervous system in mammals. Sp1 gene mutation results in death of mouse embryo around day 11 of gestation, and mouse anterior pituitary development is severely hypoplastic after Lhx4 mutation. While Sp1 interacts with the related Lhx3 gene it is unclear whether Sp1 and Lhx4 also interact to regulate their physiological functions.

Toxic effects of zearalenone and its derivatives alpha-zearalenol on male reproductive system in mice.

The current study evaluated effects of zearalenone (ZEA) and its derivative alpha-zearalenol (alpha-ZOL) on male mouse semen quality, fertility and serum testosterone concentrations. Adult male mice were exposed to intraperitoneal (i.p.

Different quaternary structures of human RECQ1 are associated with its dual enzymatic activity.

RecQ helicases are essential for the maintenance of chromosome stability. In addition to DNA unwinding, some RecQ enzymes have an intrinsic DNA strand annealing activity. The function of this dual enzymatic activity and the mechanism that regulates it is, however, unknown.

Expression of androgen receptor and its co-localization with estrogen receptor-alpha in the developing pituitary gland of sheep fetus.

No information is known concerning the expression of androgen receptor (AR) and its co-localization with estrogen receptor alpha (ERalpha) in the developing pituitary of sheep fetus. In the present study, we detected AR expression and its co-localization with ERalpha in the anterior pituitary of sheep fetus from day 60 of gestation to the postnatal by dual immunochemistry. The results showed that both AR immunoreactivity (AR-ir) and ERalpha immunoreactivity (ERalpha-ir) were predominantly localized in the nuclei of LH positive gonadotropes.

Toxic effects of zearalenone and alpha-zearalenol on the regulation of steroidogenesis and testosterone production in mouse Leydig cells.

Zearalenone (ZEA) and its derivative alpha-zearalenol (alpha-ZOL) are produced by fungi of the genus Fusarium and, after ingestion via contaminated cereals, may lead to animal fertility disturbances and other reproductive pathologies. The previous study demonstrated the toxic effects of ZEA and alpha-ZOL through disturbances in male fertility and other reproductive pathologies in mice. In this study, we further examined the direct biological effects of ZEA and alpha-ZOL on steroidogenesis production, primarily in Leydig cells of mice.

LIM homeodomain proteins Islet-1 and Lim-3 expressions in the developing pineal gland of chick embryo by immunohistochemistry.

LIM homeodomain proteins Islet-1 and Lim-3 expression and their role in nervous tissue and endocrine glands have been reported; however, nothing is known concerning Islet-1 and Lim-3 expression in the developing pineal gland of the chick embryo. The aim of the present study was to determine the ontogeny of Islet-1 and Lim-3 expression in the developing pineal gland of chick embryo using immunohistochemistry. The results showed that Islet-1 and Lim-3 immunopositive cells were first detected in the pineal evagination of chick embryos at day 4 (E4) and E4.

Detection and estrogen regulation of leptin receptor expression in rat dorsal root ganglion.

Leptin receptor (OB-R) is a polypeptide consisting of a single transmembrane-spanning component. OB-R widely distributes in various tissues, including the peripheral nervous system (PNS). However, there is no data about the expression of OB-R in the dorsal root ganglion (DRG).

Surprisingly efficient catalytic Cr-mediated coupling reactions.

[reaction: see text] With use of 1 mol % of Cr catalyst 5, surprisingly efficient Cr-mediated couplings of aldehydes with various types of nucleophiles have been realized. The catalyst set of Cr catalyst 5 and Ni catalyst 4 is used for alkenylation, alkynylation, and arylation, whereas the catalyst set of Cr catalyst 5 and CoPc (cobalt phthalocyanine) is used for 2-haloallylation, alkylation, and propargylation. Only the Cr catalyst 5 is required for allylation.

A new method for translating the asymmetric Ni/Cr-mediated coupling reactions from stoichiometric to catalytic.

[reaction: see text] A new method has been developed for effectively translating the degree of asymmetric induction and the chemical yield achieved in the stoichiometric asymmetric Ni/Cr-mediated coupling to a catalytic asymmetric process via a chiral sulfonamide ligand. It has also been shown that the Ni catalyst plays a central role. Among a number of the Ni catalysts, the 2,9-dimethylphenanthroline/NiCl(2) complex (7) has been found to be the most effective.

Expression of cysteine sulfinate decarboxylase (CSD) in male reproductive organs of mice.

Cysteine sulfinate decarboxylase (CSD) is the rate-limiting biosynthetic enzyme of taurine, but it is still controversial whether the male reproductive organs have the function to synthesize taurine through CSD pathway. The present study was thus undertaken to detect CSD expression in male mouse reproductive organs by RT-PCR, Western blot and immunohistochemistry. The results show that CSD is expressed both at the mRNA and protein levels in the testis, epididymis and ductus deferens.

Developmental changes of Islet-1 and its co-localization with pituitary hormones in the pituitary gland of chick embryo by immunohistochemistry.

Although Islet-1 expression in the pituitary gland of early mouse embryo has been previously described, there are no reports concerning the correlation of Islet-1 expression with lineage restrictions in cell types at the later stages of pituitary development. The role of Islet-1 in chickens is also unknown. The purpose of this study was to follow, by using immunohistochemistry, the ontogeny of pituitary Islet-1 and the various cell types that contain Islet-1 throughout chick embryo development.

Biochemical analysis of the DNA unwinding and strand annealing activities catalyzed by human RECQ1.

RecQ helicases play an important role in preserving genomic integrity, and their cellular roles in DNA repair, recombination, and replication have been of considerable interest. Of the five human RecQ helicases identified, three are associated with genetic disorders characterized by an elevated incidence of cancer or premature aging: Werner syndrome, Bloom syndrome, and Rothmund-Thomson syndrome. Although the biochemical properties and protein interactions of the WRN and BLM helicases defective in Werner syndrome and Bloom syndrome, respectively, have been extensively investigated, less information is available concerning the functions of the other human RecQ helicases.