Extending the socio-sexual brain: arginine-vasopressin immunoreactive circuits in the telencephalon of mice

Quantitative analysis of the immunoreactivity for arginine-vasopressin (AVP-ir) in the telencephalon of male (intact and castrated) and female CD1 mice allows us to precisely locate two sexually dimorphic (more abundant in intact than castrated males and females) AVP-ir cell groups in the posterior bed nucleus of the stria terminalis (BST) and the amygdala. Chemoarchitecture (NADPH diaphorase) reveals that the intraamygdaloid AVP-ir cells are located in the intra-amygdaloid BST (BSTIA) rather than the medial amygdala (Me), as previously thought. Then, we have used for the first time tract tracing (combined with AVP immunofluorescence) and fiber-sparing lesions of the BST to analyze the projections of the telencephalic AVP-ir cell groups. The results demonstrate that the posterior BST originates the sexually dimorphic innervation of the lateral septum, the posterodorsal Me and a substance P-negative area in the medioventral striato-pallidum (mvStP).The BSTIA may also contribute to some of these terminal fields. Our material also reveals non-dimorphic AVP-ir processes in two locations of the amygdala. First, the ventral Me shows dendrite-like AVP-ir processes apparently belonging supraoptic neurons, whose possible functions are discussed. Second, the Ce shows sparse, thick AVP-ir axons with high individual variability in density and distribution, whose possible influence on stress coping in relation to the affiliative or agonistic behaviors mediated by the Me are discussed. Finally, we propose that the region of the mvStP showing sexually dimorphic AVP-ir innervation is part of the brain network for socio-sexual behavior, in which it would mediate motivational aspects of chemosensory-guided social interactions.     

Avian mycobacteriosis in free-living raptors in Majorca Island,Spain

Avian mycobacteriosis is a chronic, infectious disease caused by different species of mycobacteria, usually belonging to the Mycobacterium avium complex. From 2004 to 2007, 589 raptors brought dead or sick to a wildlife rehabilitation centre in Majorca (Balearic Islands, Spain) were necropsied. The birds belonged to 12 different species, chiefly common kestrel (Falco tinnunculus) (n=297), scops owl (Otus scops) (n=109), barn owl (Tyto alba) (n=75), long-eared owl (Asio otus) (n=58), peregrine falcon (Falco peregrinus) (n=27), and booted eagle (Hieraaetus pennatus) (n=13). Gross lesions compatible with mycobacteriosis were observed in 14 birds (2.4%) found in several locations in Majorca. They were 12 kestrels (prevalence in this species, 4.0%), one long-eared owl (1.7%) and one scops owl (0.9%), all the birds presenting white–yellowish nodules from pinpoint size to 1 cm in diameter in diverse organs, mainly in the liver, spleen and intestine. Affected organs were subjected to bacteriology and molecular identification by polymerase chain reaction and, in all cases, infection with M. avium subspecies avium was confirmed. The observed prevalences are similar to those previously observed in Holland, although the actual prevalence detected in this study is likely to be higher than reported because only birds with gross lesions were subjected to culture. Further molecular characterization with a set of six mycobacterial interspersed repetitive unit–variable number tandem repeat loci was used to sub-type the isolates in order to show the existence of possible epidemiological links. Six different genotypes were found, which points to infection from multiple foci. No temporal or geographical aggregation of the cases was observed to be associated with the presence of positive birds or with the different variable number tandem repeat allelic profiles. The most feasible origin might be water or food sources, although the reservoir of mycobacteria remains unknown.     

FISH mapping of microsatellite loci from <Emphasis Type="Italic">Drosophila subobscura</Emphasis> and its comparison to related species

Microsatellites are highly polymorphic markers that are distributed through all the genome being more abundant in non-coding regions. Whether they are neutral or under selection, these markers if localized can be used as co-dominant molecular markers to explore the dynamics of the evolutionary processes. Their cytological localization can allow identifying genes under selection, inferring recombination from a genomic point of view, or screening for the genomic reorganizations occurring during the evolution of a lineage, among others. In this paper, we report for the first time the localization of microsatellite loci by fluorescent in situ hybridization on Drosophila polytene chromosomes. In Drosophila subobscura, 72 dinucleotide microsatellite loci were localized by fluorescent in situ hybridization yielding unique hybridization signals. In the sex chromosome, microsatellite distribution was not uniform and its density was higher than in autosomes. We identified homologous segments to the sequence flanking the microsatellite loci by browsing the genome sequence of Drosophila pseudoobscura and Drosophila melanogaster. Their localization supports the conservation of Muller’s chromosomal elements among Drosophila species and the existence of multiple intrachromosomal rearrangements within each evolutionary lineage. Finally, the lack of microsatellite repeats in the homologous D. melanogaster sequences suggests convergent evolution for high microsatellite density in the distal part of the X chromosome.     

Determinants of HIV progression and assessment of the optimal time to initiate highly active antiretroviral therapy: PISCIS Cohort (Spain)

OBJECTIVE: We analyze the factors related to progression to AIDS or death in HIV-infected patients from the Proyecto para la Informatización del Seguimiento Clínico epidemiológico de los pacientes con Infección por VIH/SIDA (PISCIS) Cohort and we assess the optimal time to initiate highly active antiretroviral therapy (HAART) taking lead time into account. METHODS: We selected naive patients who were AIDS-free and initiated HAART after January 1998. Statistical analyses were performed using Cox proportional hazards models. Lead time was defined as the time it took the deferred group with an early disease stage to reach the later stage. The analysis accounting for lead time was performed using multiple imputation methods based on estimates from the pre-HAART period as described elsewhere. RESULTS: Multivariate analysis on 2035 patients (median follow-up = 34.3 months) showed significantly higher hazard ratios (HRs) for a CD4 count <200 cells/microL (HR = 3.79, 95% confidence interval [CI]: 2.18 to 6.57), HIV-1 RNA level >100,000 copies/mL (HR = 1.84, 95% CI: 1.26 to 2.69), and hepatitis C virus (HCV) coinfection (HR = 2.40, 95% CI: 1.65 to 3.49), whereas a lower risk was found for those who started HAART between January 2001 and June 2004 (HR = 0.55, 95% CI: 0.30 to 0.90). When lead time and unseen events were included, we found a higher risk of progression to AIDS among patients who deferred treatment when the CD4 count reached <200 cells/microL (HR = 2.97, 95% CI: 1.91 to 4.63) and 200 to 350 cells/microL (HR = 1.85, 95% CI: 1.03 to 3.33) compared with those who started treatment with CD4 counts from 200 to 350 cells/microL and >350 cells/microL, respectively. CONCLUSIONS: Advanced HIV disease, HCV coinfection, and early HAART period were determinants of AIDS progression or death. Lead-time analysis in asymptomatic HIV-infected patients suggests that the best time to start HAART is before the CD4 count falls to lower than 350 cells/microL.     

Effect of the long-term regular intake of virgin olive oil on the phenolic metabolites in human fasting plasma

The effect of repeated consumption of virgin olive oil on endogenous phenolic metabolites of fasting plasma is unknown. For this reason, we hypothesized that regular long-term virgin olive oil intake could have an indirect protection effect on the endogenous phenols. Thus, the aim of the study was to determine the phenolic profile of human plasma in a fasting state of long-term regular virgin olive oil consumers, using the fasting plasma of non-consumers as a natural control. Forty participants living in the area of Reus (Catalonia, Spain) were selected, 20 life-long regular consumers of virgin olive oil and a natural control of 20 non-consumers, the latter being Rumanians who dislike the taste of olive oil. The diet was obtained from 3-day food records. The results showed similar phenolic composition of fasting plasmas of the two volunteer groups. Of special interest is that more of the compounds quantified showed higher concentration in fasting plasma from habitual virgin olive oil consumers. The compounds were semi-quantified using caffeic acid as the calibration standard. The quantification of fasting consumer's plasma showed higher concentration of a hydroxyflavanone type compound (2.90 ± 0.04 μM vs 1.5 ± 0.04 μM) and a catecholamine derivative (0.70 ± 0.03 μM vs 0.56 ± 0.03 μM) than the plasma of non-consumers (P < 0.05). The results suggest an indirect protective mechanism of long-term regular virgin olive oil consumption related to the protection of the endogenous antioxidant system.     

A noncognate aminoacyl-tRNA synthetase that may resolve a missing link in protein evolution

Efforts to delineate the advent of many enzymes essential to protein translation are often limited by the fact that the modern genetic code evolved before divergence of the tree of life. Glutaminyl-tRNA synthetase (GlnRS) is one noteworthy exception to the universality of the translation apparatus. In eukaryotes and some bacteria, this enzyme is essential for the biosynthesis of Gln-tRNAGln, an obligate intermediate in translation. GlnRS is absent, however, in archaea, and most bacteria, organelles, and chloroplasts. Phylogenetic analyses predict that GlnRS arose from glutamyl-tRNA synthetase (GluRS), via gene duplication with subsequent evolution of specificity. A pertinent question to ask is whether, in the advent of GlnRS, a transient GluRS-like intermediate could have been retained in an extant organism. Here, we report the discovery of an essential GluRS-like enzyme (GluRS2), which coexists with another GluRS (GluRS1) in Helicobacter pylori. We show that GluRS2's primary role is to generate Glu-tRNAGln, not Glu-tRNAGlu. Thus, GluRS2 appears to be a transient GluRS-like ancestor of GlnRS and can be defined as a GluGlnRS.     

Counteraction of type 1 diabetic alterations by engineering skeletal muscle to produce insulin: insights from transgenic mice

Insulin replacement therapy in type 1 diabetes is imperfect because proper glycemic control is not always achieved. Most patients develop microvascular, macrovascular, and neurological complications, which increase with the degree of hyperglycemia. Engineered muscle cells continuously secreting basal levels of insulin might be used to improve the efficacy of insulin treatment. Here we examined the control of glucose homeostasis in healthy and diabetic transgenic mice constitutively expressing mature human insulin in skeletal muscle. Fed transgenic mice were normoglycemic and normoinsulinemic and, after an intraperitoneal glucose tolerance test, showed increased glucose disposal. When treated with streptozotocin (STZ), transgenic mice showed increased insulinemia and reduced hyperglycemia when fed and normoglycemia and normoinsulinemia when fasted. Injection of low doses of soluble insulin restored normoglycemia in fed STZ-treated transgenic mice, while STZ-treated controls remained highly hyperglycemic, indicating that diabetic transgenic mice were more sensitive to the hypoglycemic effects of insulin. Furthermore, STZ-treated transgenic mice presented normalization of both skeletal muscle and liver glucose metabolism. These results indicate that skeletal muscle may be a key target tissue for insulin production and suggest that muscle cells secreting basal levels of insulin, in conjunction with insulin therapy, may permit tight regulation of glycemia.     

The N-ras proto-oncogene can suppress the malignant phenotype in the presence or absence of its oncogene

ras proto-oncogenes have traditionally been associated with the regulation and promotion of cell growth. We have induced thymic lymphomas in N-ras(-/-) mice and in transgenic mice that overexpress wild-type N-ras and found that the lack of wild-type N-ras alleles favors the development of thymic lymphomas,whereas overexpression of wild-type N-ras protects against thymic lymphomagenesis in the presence or absence of its oncogene. To investigate the inhibitory role of wild-type N-ras in in vitro transformation, we introduced wild-type N-ras in N-ras-deficient tumor cells that lack ras activating mutations and found decreased growth in both low serum and soft agar. Taken together, our results indicate that wild-type N-ras has "tumor suppressor" activity, even in the absence of its oncogenic allele.     

Fine-needle aspiration cytology of intraductal papillary mucinous tumors of the pancreas

BACKGROUND: Intraductal papillary mucinous tumors (IPMT) account for 5% of pancreatic neoplasms. Preoperative identification is important because of their frequent multifocal or diffuse involvement in pancreatic ducts, which makes extensive surgery necessary even in benign cases. To the authors' knowledge, the cytologic features of this entity in fine-needle aspiration biopsy (FNAB) specimens have seldom been described and are poorly standardized. METHODS: Eleven consecutive cases of surgically proven IPMT with previous endoscopic ultrasonography (EUS)-guided FNAB were collected for retrospective analysis. EUS-FNAB had been performed with on-site attendance of a cytopathologist in all cases. Macroscopic and microscopic appearance of mucin, cellular type and arrangement, presence of nuclear grooves, and degree of nuclear atypia were recorded. RESULTS: Final diagnosis was benign IPMT (B) in four cases, borderline IPMT (Bo) in two cases, malignant IPMT (M) in one case, and IPMT associated with invasive carcinoma (Ca) in four. Retrospective analysis found moderate to high levels of extracellular mucin in 10 of the 11 cases. The other case (one Ca) showed a small amount of thick mucin. In all cases, epithelial cells were identified, although cellularity was very low in four cases (three B and one Bo). Atypia was absent in two cases (two B) slight in two cases (two B), moderate in three cases (one Bo and two Ca), and severe in four cases (one Bo, one M, and two Ca). Mucinous epithelium was found in nine cases and nonmucinous epithelium in five cases (one Bo and four Ca). Papillary structures were observed in five cases (two Bo and three Ca), sheets in eight cases (four B, one Bo, one M, and two Ca), single atypical cells in five cases (one Bo and four Ca), irregular clusters in three cases (one Bo and two Ca), and nuclear grooves in two cases (one B and one Bo). CONCLUSIONS: The most common features of IPMT were extracellular mucin and sheets of mucinous epithelium. Papillae and nuclear grooves were not consistently found. Nonmucinous epithelium, severe atypia, single atypical cells, and irregular clusters indicated a high probability of malignant transformation. Even in the absence of atypia, a clinically significant diagnostic orientation can be established in most cases on the basis of the characteristic cytologic picture.