In vitro metabolism of C19 steroids in human endometrium

In order to quantitate the extent of intracellular metabolic conversions of C19 steroids in human endometrium, specimens of proliferative and secretory tissue were superfused at a constant rate with several pairs of labeled compounds at low concentrations. About 16% of dehydroepiandrosterone sulfate interacting with endometrial cells was converted to dehydroepiandrosterone and about 3% of this compound was converted to androstenedione. Androstenedione was reversibly reduced to testosterone and the extent of this conversion was shown to be several-fold higher in secretory than in proliferative tissue. About 1% of testosterone entering the cells was reduced to 5 alpha-dihydrotestosterone. These results demonstrate that the conversion of the main circulating C19 steroids in women, i.e. dehydroepiandrosterone sulfate and androstenedione, to 5 alpha-dihydrotestosterone, the compound considered to be the true intracellular androgen, is very small. In contrast, formation of testosterone from androstenedione is extensive and increases during the luteal phase under the influence of progesterone, a hormone known to stimulate the activity of 17 beta-hydroxysteroid dehydrogenase in human endometrium.     

Eight decades of invasion by Chromolaena odorata (Asteraceae) and its biological control in West Africa: the story so far

ABSTRACT

Chromolaena odorata (L.) R.M. King and H. Robinson (Asteraceae) is a perennial weedy shrub of neotropical origin and a serious biotic threat in its invasive range. The Asian-West Africa (AWA) biotype of C. odorata present in West Africa is both morphologically and genetically different from the southern African (SA) biotype. The AWA biotype was first introduced into Nigeria in the late 1930s and rapidly spread across West Africa. Currently, 12 of the 16 countries in West Africa have been invaded, with significant negative effects on indigenous flora and fauna. However, locals in West Africa have found several uses for the weed. As chemical, physical and other conventional methods were unsustainable, costly and largely ineffective, three biological control agents, Apion brunneonigrum (Coleoptera: Brentidae), Pareuchaetes pseudoinsulata (Lepidoptera: Erebidae) and Cecidochares connexa (Diptera: Tephritidae), have been released in West Africa between the 1970s and the early 2000s. However, only C. connexa and P. pseudoinsulata established, contributing to the control of the weed, in six and four countries in West Africa respectively. Limited research funding, the absence of post-release evaluations of the established agents, and the ‘conflict of interest’ status of C. odorata (i.e. being beneficial for local use but damaging to ecosystem services and agriculture), are serious factors deterring the overall biological control effort. Here, using historical records and field surveys, we examine the invasion history, spread, impacts, and management of C. odorata in West Africa and make recommendations for the sustainable management of C. odorata in the region.     

Light activates H2 15O flow in rice: Detailed monitoring using a positron-emitting tracer imaging system (PETIS)

Water (H₂ ¹⁵O) translocation from the roots to the top of rice plants ( Oryza saliva L. cv. Nipponbare) was visualized over time by a positron-emitting tracer imaging system (PETIS). H₂ ¹⁵O flow was activated 8 min after plants were exposed to bright light (1 500 μmol m⁻² s⁻¹). When the light was subsequently removed, the flow gradually slowed and completely stopped after 12 min. In plants exposed to low light (500 μmol m⁻² s⁻¹), H₂ ¹⁵O flow was activated more slowly, and a higher translocation rate of H₂ ¹⁵O was observed in the same low light at the end of the next dark period. NaCl (80 m M ) and methylmercury (1 m M ) directly suppressed absorption of H₂ ¹⁵O by the roots, while methionine sulfoximine (1 m M ), abscisic acid (10 μ M ) and carbonyl cyanide m -chlorophenylhydrazone (10 m M ) were transported to the leaves and enhanced stomatal closure, reducing H₂ ¹⁵O translocation.     

Clinical Characteristics of Preschool Children with Oppositional Defiant Disorder and Callous-Unemotional Traits

There is a need to know whether callous-unemotional (CU) traits identify a more severe group of oppositional defiant children (ODD). The aim of this study is to ascertain cross-sectionally and longitudinally the specific contribution of CU levels and the presence of ODD in the psychological state of preschool children from the general population. A total of 622 children were assessed longitudinally at ages 3 and 5 with a semi-structured diagnostic interview and questionnaires filled out by parents and teachers. In multivariate models simultaneously including ODD diagnosis and CU levels, controlling by socioeconomic status, ethnicity, sex, severity of conduct disorder symptoms and other comorbidity, high CU scores were related to higher levels of aggression, withdrawn, externalizing and global symptomatology, functional impairment and higher probability of comorbid disorders and use of services. The contribution of CU traits on children’s psychological state was not moderated by the presence/absence of ODD. Stability for CU traits and number of ODD-symptoms between ages 3 and 5 was statistically significant but moderate-low (intra-class correlation under .40). Assessment and identification of CU traits from preschool might help to identify a subset of children who could have socialization problems, not only among those with ODD but also among those without a diagnosis of conduct problems.     

Visual pigments in a living fossil,the Australian lungfish <Emphasis Type="Italic">Neoceratodus forsteri</Emphasis>

Background  

One of the greatest challenges facing the early land vertebrates was the need to effectively interpret a terrestrial environment. Interpretation was based on ocular adaptations evolved for an aquatic environment millions of years earlier. The Australian lungfish Neoceratodus forsteri is thought to be the closest living relative to the first terrestrial vertebrate, and yet nothing is known about the visual pigments present in lungfish or the early tetrapods.     

Effect of carbon and nitrogen sources, pH and temperature on in vitro culture of several isolates of Amanita caesarea (Scop.:Fr.) Pers.

Several isolates were obtained from sporocarps of Amanita caesarea (Scop.: Fr.) Pers. associated with Quercus suber and Castanea sativa coming from the southwest of Spain. Culture conditions were optimized for these isolates. The largest radial growth was obtained at pH 6–7, and optimal growth temperature was 24–28°C depending on the isolate. Albumin bovine and nitrate produced the largest patch size diameters, but the greatest mycelium dry weight yields were obtained with ammonium. Mannitol produced the largest radial growth, and mannitol and glucose yielded the biggest mycelium dry weights. Although variations in growth behaviour between isolates were observed, only one internal spacer sequence–restriction fragment length polymorphism type was obtained.     

Selective side-chain modification of cysteine and arginine residues blocks pathogenic activity of HIV-1-Tat functional peptides

Extracellular Tat protein of HIV-1 activates virus replication in HIV-infected cells and induces a variety of host factors in the uninfected cells, some of which play a critical role in the progression of HIV infection. The cysteine-rich and arginine-rich basic domains represent key components of the HIV-Tat protein for pathogenic effects of the full-length Tat protein and, therefore, could be ideal candidates for the development of a therapeutic AIDS vaccine. The present study describes selective modifications of the side-chain functional groups of cysteine and arginine amino acids of these HIV-Tat peptides to minimize the pathogenic effects of these peptides while maintaining natural peptide linkages. Modification of cysteine by introducing either a methyl or t-butyl group in the free sulfhydryl group and replacing the guanidine group with a urea linkage in the side chain of arginine in the cysteine-rich and arginine-rich Tat peptide sequences completely blocked the ability of these peptides to induce HIV replication, chemokine receptor CCR-5 expression, and NF-kappaB activity in monocytes. Such modifications also inhibited angiogenesis and migration of Kaposi's sarcoma cells normally induced by Tat peptides. Such chemical modifications of the cysteine-rich and arginine-rich peptides did not affect their reactivity with antibodies against the full-length Tat protein. With an estimated 40 million HIV-positive individuals worldwide and approximately 4 million new infections emerging every year, a synthetic subunit HIV-Tat vaccine comprised of functionally inactive Tat domains could provide a safe, effective, and economical therapeutic vaccine to reduce the progression of HIV disease.     

Molecular phylogenetic analysis shows that <Emphasis Type="Italic">Amanita ponderosa</Emphasis> and <Emphasis Type="Italic">A. curtipes</Emphasis> are distinct species

Amanita curtipes and A. ponderosa are two Mediterranean taxa sharing a number of morphological features as well as their habitat. Their synonymy or variety status has been proposed by several authors. To clarify this taxonomic issue we have sequenced the D1-D2 domains of the 28S rRNA gene as well as the complete ITS1-5.8S-ITS2 region of several specimens of the two species collected in Spain, and aligned these sequences with those from other Amanita species. Molecular phylogenetic analysis based on the two regions revealed that A. ponderosa and A. curtipes are clearly distinct species. The distribution of Amanita species in the phylogenetic trees was consistent with the division of the genus in subgenera and sections as proposed by previous authors. Sequences of A. ponderosa and A. curtipes were grouped in a monophyletic cluster together with other species of the section Amidella. However, A. ponderosa was closer to other species in the section, such as A. peckiana and A. volvata, than to A. curtipes. We also indicate the macromorphological characters that are most useful to reliably distinguish A. ponderosa and A. curtipes.     

Synthesis of N-isobutylnoroxymorphone from naltrexone by a selective cyclopropane ring opening reaction

Selective ring opening reaction of the N-cyclopropylmethyl group in naltrexone (1d) was effected in the presence of platinum (IV) oxide and hydrobromic acid under a hydrogen atmosphere at rt to selectively afford N-isobutyl derivative 10. The binding affinity of N-i-Bu derivative 10 for opioid receptors was 11-17 times less than that of the corresponding N-CPM compound, naltrexone (1d). However, compound 10 showed dose-dependent analgesic effects. Contrary to expectations based on previous structure-activity relationship studies for a series of N-substituted naltrexone derivatives that compound 10 would be an opioid antagonist, 10 showed dose-dependent analgesia in the mouse acetic acid writhing test (ED(50): 5.05 mg/kg, sc), indicating it was an opioid agonist. This finding may have a great influence on the drug design of opioid agonists.