Steroidogenesis of the testis - new genes and pathways

Defects of androgen biosynthesis cause 46,XY disorder of sexual development (DSD). All steroids are produced from cholesterol and the early steps of steroidogenesis are common to mineralocorticoid, glucocorticoid and sex steroid production. Genetic mutations in enzymes and proteins supporting the early biosynthesis pathways cause adrenal insufficiency (AI), DSD and gonadal insufficiency. The classic androgen biosynthesis defects with AI are lipoid CAH, CYP11A1 and HSD3B2 deficiencies. Deficiency of CYP17A1 rarely causes AI, and HSD17B3 or SRD5A2 deficiencies only cause 46,XY DSD and gonadal insufficiency. All androgen biosynthesis depends on 17,20 lyase activity of CYP17A1 which is supported by P450 oxidoreductase (POR) and cytochrome b5 (CYB5). Therefore 46,XY DSD with apparent 17,20 lyase deficiency may be due to mutations in CYP17A1, POR or CYB5. Illustrated by patients harboring mutations in SRD5A2, normal development of the male external genitalia depends largely on dihydrotestosterone (DHT) which is converted from circulating testicular testosterone (T) through SRD5A2 in the genital skin. In the classic androgen biosynthetic pathway, T is produced from DHEA and androstenedione/-diol in the testis. However, recently found mutations in AKR1C2/4 genes in undervirilized 46,XY individuals have established a role for a novel, alternative, backdoor pathway for fetal testicular DHT synthesis. In this pathway, which has been first elucidated for the tammar wallaby pouch young, 17-hydroxyprogesterone is converted directly to DHT by 5α-3α reductive steps without going through the androgens of the classic pathway. Enzymes AKR1C2/4 catalyse the critical 3αHSD reductive reaction which feeds 17OH-DHP into the backdoor pathway. In conclusion, androgen production in the fetal testis seems to utilize two pathways but their exact interplay remains to be elucidated.

Update chronische Hepatitis B und C

Der natürliche Verlauf einer HepatitisB-Virus(HBV)-Infektion ist komplex und wird einerseits durch das Alter zum Zeitpunkt der Infektion, anderseits durch Komorbiditäten bzw. Koinfektionen und zum Teil noch nicht identifizierte Faktoren bestimmt. Das HBV wird nie komplett eliminiert. Das Erreichen des inaktiven Trägerstatus ist aber ein realistisches Therapieziel. Zur Therapie stehen Nukleosid/NukleotidAnaloga sowie pegyliertes Interferonalpha zur Verfügung. Screening von bestimmten Patientengruppen und eine generelle Impfung sind wichtige prophylaktische Massnahmen. Die chronische Hepatitis-C-Virus(HCV) -Infektion führt in circa einem Drittel der Fälle zur Leberzirrhose. Eine Therapie ist generell ab Fibrosestadium Metavir 2 indiziert. Neue DAA (directly acting antivirals) erlauben kurzfristige, hochpotente und nebenwirkungsarme Therapieschemata.

[Smoking and digestive tract: a complex relationship. Part 2: Intestinal microblota and cigarette smoking]

The digestive tract is colonized from birth by a bacterial population called the microbiota which influences the development of the immune system. Modifications in its composition are associated with problems such as obesity or inflammatory bowel diseases. Antibiotics are known to influence the intestinal microbiota but other environmental factors such as cigarette smoking also seem to have an impact on its composition. This influence might partly explain weight gain which is observed after smoking cessation. Indeed there is a modification of the gut microbiota which becomes similar to that of obese people with a microbiotical profile which is more efficient to extract calories from ingested food. These new findings open new fields of diagnostic and therapeutic approaches through the regulation of the microbiota.

[Smoking and digestive tract: a complex relationship. Part 1: Inflammatory bowel disease and cigarette smoking]

Little is known about the effects of smoking on inflammatory bowel diseases (IBD). However the co-occurrence of smoking and IBD often happens in ambulatory care. Smokers have a doubled risk of developing a Crohn's disease with a more active disease course. After quitting, a decrease in risk can be observed after only one year. An inverse relationship is found between smoking and ulcerative colitis. Smoking seems protective for the development of the disease and its course is less active among smokers. Smoking cessation transitorily increases the risk of developing ulcerative colitis. Nevertheless, continuing smoking cannot be justified among those patients given the risks of long-term extra-digestive effects. It is thus important to counsel all smokers with an IBD to quit smoking.

The Differential Requirement of Albumin and Sodium Citrate on the Development of In Vitro Produced Bovine Embryos

In vitro culture for bovine embryos is largely not optimal. Our study was to determine the components necessary for early embryo development. In experiment 1, IVF embryos were cultured for two days in CR1aa medium containing sodium citrate and BSA from two sources (Sigma vs. ICPbio), subsequently for additional five days with cumulus monolayer in 10% FBS CR1aa. We found that supplementation with both Sigma-BSA and sodium citrate significantly increased total blastocyst (BL) development compared with the ICPbio-BSA groups (37% vs. 19-21%), and enhanced the total number of high quality (C1 BL, IETS standard) blastocysts (26% vs. 11-17%) (P < 0.05). In experiment 2 with serum free and/or somatic free culture, we found that CR1aa culture can support a comparable embryo development with a supplement of Sigma BSA. The addition of sodium citrate did not increase blastocyst development in either the Sigma-BSA or the ICPbio-BSA groups. An inferior blastocyst development occurring in ICPbio-BSA culture (1-3%) could be rescued by culture in CRlaa supplemented with 10% FBS (29%), more importantly, by culture in CR1aa with a replacement of Sigma BSA (24%) (P <0.05). C1 blastocysts rescued by FBS and Sigma BSA in ICPbio-BSA culture possessed indistinguishable morphology to embryos developed in a Sigma-BSA, FBS and somatic co-culture system, showing similar cell number/blastocyst (129-180, P > 0.05). Our study found a beneficial effect of sodium citrate and BSA on the in vitro development of bovine IVF embryos during co-culture. We also determined that differential embryotrophic factor(s) contained in BSA and serum, probably not sodium citrate, is necessary for promoting competent morula and blastocyst development in cattle.

The Cell Agglutination Agent, Phytohemagglutinin-L, Improves the Efficiency of Somatic Nuclear Transfer Cloning in Cattle (Bos taurus)

One of the several factors that contribute to the low efficiency of mammalian somatic cloning is poor fusion between the small somatic donor cell and the large recipient oocyte. This study was designed to test phytohemagglutinin (PHA) agglutination activity on fusion rate, and subsequent developmental potential of cloned bovine embryos. The toxicity of PHA was established by examining its effects on the development of parthenogenetic bovine oocytes treated with different doses (Experiment 1), and for different durations (Experiment 2). The effective dose and duration of PHA treatment (150 microg/mL, 20 min incubation) was selected and used to compare membrane fusion efficiency and embryo development following somatic cell nuclear transfer (Experiment 3). Cloning with somatic donor fibroblasts versus cumulus cells was also compared, both with and without PHA treatment (150 microg/mL, 20 min). Fusion rate of nuclear donor fibroblasts, after phytohemagglutinin treatment, was increased from 33 to 61% (P < 0.05), and from 59 to 88% (P < 0.05) with cumulus cell nuclear donors. The nuclear transfer (NT) efficiency per oocyte used was improved following PHA treatment, for both fibroblast (13% versus 22%) as well as cumulus cells (17% versus 34%; P < 0.05). The cloned embryos, both with and without PHA treatment, were subjected to vitrification and embryo transfer testing, and resulted in similar survival (approximately 90% hatching) and pregnancy rates (17-25%). Three calves were born following vitrification and embryo transfer of these embryos; two from the PHA-treated group, and one from non-PHA control group. We concluded that PHA treatment significantly improved the fusion efficiency of somatic NT in cattle, and therefore, increased the development of cloned blastocysts. Furthermore, within a determined range of dose and duration, PHA had no detrimental effect on embryo survival post-vitrification, nor on pregnancy or calving rates following embryo transfer.

Entrando a la música de cuerpo entero : un enfoque cognitivista para la enseñanza inicial de los instrumentos

La ejecución de un instrumento musical es un procedimiento complejo que, con un fin de expresión artística, conjuga habilidades provenientes de una diversidad de campos que exceden lo estrictamente musical. El individuo que se inicia en el estudio de un instrumento puede reducir la complejidad de la situación aprovechando su experiencia personal en los diferentes dominios involucrados. Tomando como marco teórico estudios cognitivistas que analizan los mecanismos de apropiación de conocimiento nuevo a partir de la reposición de conocimiento previo, las autoras trabajan sobre su adaptación al campo de la enseñanza inicial de los instrumentos musicales.

Cómplices y coautores del hecho : Delitos sexuales "en grupo" en la Provincia de Buenos Aires (1863-1903)

Los crímenes sexuales en general, y la violación en particular, suelen concebirse como una situación que involucra únicamente a dos personas: la víctima y su atacante. Sin embargo, los expedientes judiciales vinculados a estos delitos muestran un universo complejo de actores, que no ;se agota en aquel binomio. El presente trabajo se enfoca en algunas de esas ocasiones donde aquella lógica se demuestra incorrecta, mostrando cómo la justicia lidia con aquel desafío desde el discurso jurídico, analizando imágenes y concepciones que abogados y médicos expresan, afirman ;o discuten en relación al comportamiento esperado de hombres y mujeres, así como la situación de la justicia frente a crímenes que se alejan de la "normalidad" reconocida

Mineral composition and major element oxides of gabbros from ODP Hole 179-1105A, southwest Indian Ridge

Hole 1105A penetrated 158 m of gabbros at a site offset 1.3 km east-northeast from Hole 735B on the Atlantis Bank near the Atlantis II Fracture Zone. A total of 118 m of dominantly medium- to coarse-grained intercalated Fe-Ti oxide gabbro and olivine gabbro was recovered from Hole 1105A that shows many petrographic features similar to those recovered from the upper part of Hole 735B. The main rock types are distinguished based on the constituent cumulus phases, with the most primitive gabbros consisting of olivine, plagioclase, and clinopyroxene. The inferred crystallization order is subsequently Fe-Ti oxides (ilmenite and titanomagnetite), followed by orthopyroxene, then apatite, and finally biotite. Orthopyroxene appears to replace olivine in a narrow middle interval. The magmatic evolution is likewise reflected in the mineral compositions. Plagioclase varies from An66 to An28. Olivine varies from Fo78 to Fo35. The gap in olivine crystallization occurs between Fo46 and Fo40 and coincides approximately with the appearance of orthopyroxene (~En50). The clinopyroxenes show large compositional variation in Mg/(Mg + Fe total) from 0.84 to 0.51. The nonquadrilateral cations of clinopyroxene similarly show large variations with Ti increasing for the olivine gabbros and decreasing for the Fe-Ti oxide gabbros with the decrease in Mg/(Mg + Fe total). The apatites are mainly flourapatites. The compositional variation in the gabbros is interpreted as a comagmatic suite resulting from fractional crystallization. Pyroxene geothermometry suggests equilibration temperatures from 1100°C and below. The coexisting Fe-Ti oxide minerals indicate subsolidus equilibration temperatures from 900°C for olivine gabbros to 700°C for the most evolved apatite-bearing gabbros. The cryptic variation in the olivine gabbros defines two or three lenses, 40 to 60 m thick, each characterized by a distinct convex zoning with a lower segment indicating upward reverse fractionation, a central maximum, and an upper segment showing normal fractionation. The Fe-Ti oxide gabbros show cryptic variations independent of the host olivine gabbros and reveal a systematic upward normal fractionation trend transgressing host olivine gabbro boundaries. Forward fractional crystallization modeling, using a likely parental magma composition from the Atlantis II Fracture Zone (MgO = 7.2 wt%; Mg/[Mg + Fe2+] = 0.62), closely matches the compositions of coexisting olivine, plagioclase, and clinopyroxene. This modeling suggests cosaturation of olivine, plagioclase, and clinopyroxene from 1155°C and the addition of Fe-Ti oxides from 1100°C. The liquid line of descent initially shows increasing FeO with moderately increasing SiO2. After saturation of Fe-Ti oxides, the liquid strongly decreases in FeO and TiO2 and increases in SiO2, reaching dacitic compositions at ~10% liquid remaining. The calculations indicate that formation of olivine gabbros can be accounted for by <65% fractionation and that only the residual 35% liquid was saturated in Fe-Ti oxides. The modeling of the solid fractionation products shows that both the olivine gabbro and the Fe-Ti oxide gabbros contain very small amounts of trapped liquid (<5%). The implications are that the gabbros represent crystal mush that originated in a recharging and tapping subaxial chamber. Compaction and upward melt migration in the crystal mush appear to have been terminated with relatively large amounts of interstitial liquid remaining in the upper parts of the cumulate mush. This termination may have been caused by tectonic disturbances, uplift, and associated withdrawal of magma into the subaxial dike and sill system. Prolonged compaction and cooling of the trapped melt in the mush formed small differentiated bodies and lenses by pressure release migration and crystallization along syntectonic channels. This resulted in differentiation products along lateral and vertical channelways in the host gabbro that vary from olivine gabbro, to Fe-Ti oxide gabbro, gabbronorite, and apatite gabbros and show large compositional variations independent of the host olivine gabbros.

Cómplices y coautores del hecho : Delitos sexuales "en grupo" en la Provincia de Buenos Aires (1863-1903)

Los crímenes sexuales en general, y la violación en particular, suelen concebirse como una situación que involucra únicamente a dos personas: la víctima y su atacante. Sin embargo, los expedientes judiciales vinculados a estos delitos muestran un universo complejo de actores, que no ;se agota en aquel binomio. El presente trabajo se enfoca en algunas de esas ocasiones donde aquella lógica se demuestra incorrecta, mostrando cómo la justicia lidia con aquel desafío desde el discurso jurídico, analizando imágenes y concepciones que abogados y médicos expresan, afirman ;o discuten en relación al comportamiento esperado de hombres y mujeres, así como la situación de la justicia frente a crímenes que se alejan de la "normalidad" reconocida

Cómplices y coautores del hecho : Delitos sexuales "en grupo" en la Provincia de Buenos Aires (1863-1903)

Los crímenes sexuales en general, y la violación en particular, suelen concebirse como una situación que involucra únicamente a dos personas: la víctima y su atacante. Sin embargo, los expedientes judiciales vinculados a estos delitos muestran un universo complejo de actores, que no ;se agota en aquel binomio. El presente trabajo se enfoca en algunas de esas ocasiones donde aquella lógica se demuestra incorrecta, mostrando cómo la justicia lidia con aquel desafío desde el discurso jurídico, analizando imágenes y concepciones que abogados y médicos expresan, afirman ;o discuten en relación al comportamiento esperado de hombres y mujeres, así como la situación de la justicia frente a crímenes que se alejan de la "normalidad" reconocida

Major element and mineral composition of gabbroic xenoliths and megacrysts from Jeju Island, South Korea

Gabbroic xenoliths and diverse megacrysts (e.g., clinopyroxenes, amphiboles and plagioclases), which correspond to the lithology ranging from gabbro-norite to gabbro, occur in the Pleisto-Holocene alkali basalts from Jeju Island, South Korea. The gabbroic xenoliths consist primarily of moderate-K2O plagioclase, Ti-Al-rich clinopyroxene and CaO-rich orthopyroxene; additionally, TiO2-rich amphibole (kaersutite) and Ti-Fe oxides might or might not be present. The plagioclase is the most dominant phase (approx. 60-70 vol.%). The xenoliths and megacrysts provide evidence for the modal metasomatism of the lower continental crust by the mafic magmas during the Pleistocene. The coarse grain size (up to 5 mm), moderate Mg# [=100xMg/(Mg+Fe(total)) atomic ratio] of pyroxenes (70-77) and textural features (e.g., poikilitic) indicate that the gabbroic xenoliths are consistent with a cumulus origin. The clinopyroxenes from these xenoliths are enriched in REE with smooth convex-upward MREE patterns, which are expected for cumulus minerals formed from a melt enriched in incompatible trace elements. The strikingly similar major and trace element variations and the patterns of constituent minerals clearly indicate a genetic link between the gabbroic xenoliths (plus megacrysts) and the host basalt, indicating that the xenoliths belong to the Jeju Pleisto-Holocene magma system. On the basis of the textural features, the mineral equilibria and the major and trace element variations, the xenoliths appear to have crystallized from basaltic melts at the reservoir-roof environment within the lower crust (4-7 kbars) above the present Moho estimates beneath Jeju Island, where the xenoliths represent wall rocks. Following the consolidation of the xenolith lithologies, volatile- and incompatible element-enriched melt/fluid, as metasomatic agents, infiltrated through the grain boundaries and/or cracks and reacted with the preexisting anhydrous phases, which produced the metasomatic amphiboles. This volatile-enriched melt/fluid could have evolved from the initially anhydrous compositions to the volatile-saturated compositions by the active fractional crystallization in the Jeju Pleisto-Holocene magma system. This process was significant in that it was a relatively young event and played an important role in the formation of the hydrous minerals and the metasomatization of the lower continental crust, which is a plume-impacted area along the Asian continental margin. The major and trace element analyses of the mineral phases from the xenoliths were performed to define the principal geochemical characteristics of the crustal lithosphere segment represented by the studied xenoliths.

Petrography and mineral compositions of gabbros at DSDP Leg 60 Holes

The compositions, mineralogies, and textures of gabbros recovered in polymict breccias in Hole 453 indicate that they are the cumulus assemblages of calc-alkalic crystal fractional on that occurred beneath the West Mariana Ridge. They are among a class of gabbros known only from other calc-alkalic associations (e.g., the Lesser Antilles and the Peninsular Ranges batholith of Southern California) and differ from gabbros of stratiform complexes, ophiolites, and the ocean crust. Particularly abundant in the Hole 453 breccias are olivine-bearing gabbros with extremely calcic Plagioclase (An94-97) but with fairly iron-rich olivines (Fo76-77). Other gabbros contain biotite and amphibole and occur in breccias with fairly high-grade greenschist facies (amphibole-chlorite-stilpnomelane) metabasalts. One unusual gabbro has experienced almost complete subsolidus recrystallization to an assemblage of aluminous magnesio-hornblende, anorthite, and green hercynitic spinel. This reaction, the extremely calcic Plagioclase, the occurrence of biotite and amphibole, and the association with greenschist facies metamorphic rocks suggest that crystallization of the gabbros occurred at elevated P(H2O). Comparisons with other calc-alkalic gabbro suites suggest pressures in excess of 4 kbar (about 12 km depth). The gabbros were exposed by the early stages of opening of the Mariana Trough and imply that considerable uplift may have attended rifting. They were also subjected to hydrothermal alteration after breccia formation, resulting in formation of chlorite, epidote, actinolite, and prehnite. Temperatures of at least 200°C - and probably 350°C - were reached, and most likely could not have been attained without extrusion or intrusion of magmas nearby, even though no such rocks were cored.

Geochemistry of the gabbroic lithosphere in IODP Holes 304-U1309D and 305-U1309D

IODP Hole U1309D (Atlantis Massif, Mid-Atlantic Ridge 30°N) is the second deepest hole drilled into slow spread gabbroic lithosphere. It comprises 5.4% of olivine-rich troctolites (~ > 70% olivine), possibly the most primitive gabbroic rocks ever drilled at mid-ocean ridges. We present the result of an in situ trace element study carried out on a series of olivine-rich troctolites, and neighbouring troctolites and gabbros, from olivine-rich intervals in Hole U1309D. Olivine-rich troctolites display poikilitic textures; coarse-grained subhedral to medium-grained rounded olivine crystals are included into large undeformed clinopyroxene and plagioclase poikiloblasts. In contrast, gabbros and troctolites have irregularly seriate textures, with highly variable grain sizes, and locally poikilitic clinopyroxene oikocrysts in troctolites. Clinopyroxene is high Mg# augite (Mg# 87 in olivine-rich troctolites to 82 in gabbros), and plagioclase has anorthite contents ranging from 77 in olivine-rich troctolites to 68 in gabbros. Olivine has high forsterite contents (82-88 in olivine-rich troctolites, to 78-83 in gabbros) and is in Mg-Fe equilibrium with clinopyroxene. Clinopyroxene cores and plagioclase are depleted in trace elements (e.g., Ybcpx ~ 5-11 * Chondrite), they are in equilibrium with the same MORB-type melt in all studied rock-types. These compositions are not consistent with the progressively more trace element enriched (evolved) compositions expected from olivine rich primitive products to gabbros in a MORB cumulate sequence. They indicate that clinopyroxene and plagioclase crystallized concurrently, after melts having the same trace element composition, consistent with crystallization in an open system with a buffered magma composition. The slight trace element enrichments and lower Cr contents observed in clinopyroxene rims and interstitial grains results from crystallization of late-stage differentiated melts, probably indicating the closure of the magmatic system. In contrast to clinopyroxene and plagioclase, olivine is not in equilibrium with MORB, but with a highly fractionated depleted melt, similar to that in equilibrium with refractory oceanic peridotites, thus possibly indicating a mantle origin. In addition, textural relationships suggest that olivine was in part assimilated by the basaltic melts after which clinopyroxene and plagioclase crystallized (impregnation). These observations suggest a complex crystallization history in an open system involving impregnation by MORB-type melt(s) of an olivine-rich rock or mush. The documented magmatic processes suggest that olivine-rich troctolites were formed in a zone with large magmatic transfer and accumulation, similar to the mantle-crust transition zone documented in ophiolites and at fast spreading ridges.

Mineraly of oceanic crust from the Kane Transform, Mid-Atlantic Ridge

Gabbroic cumulates drilled south of the Kane Transform Fault on the slow-spread Mid-Atlantic Ridge preserve up to three discrete magnetization components. Here we use absolute age constraints derived from the paleomagnetic data to develop a model for the magmatic construction of this section of the lower oceanic crust. By comparing the paleomagnetic data with mineral compositions, and based on thermal models of local reheating, we infer that magmas that began crystallizing in the upper mantle intruded into the lower oceanic crust and formed meter-scale sills. Some of these magmas were crystal-laden and the subsequent expulsion of interstitial liquid from them produced '"cumulus" sills. These small-scale magmatic injections took place over at least 210 000 years and at distances of ~3 km from the ridge axis and may have formed much of the lower crust. This model explains many of the complexities described in this area and can be used to help understand the general formation of oceanic crust at slow-spread ridges.