Development modulates the serum induced effect on the incorporation of [2-3H]mannose into chick optic lobe protein: the possible role of glia.

Recently, we described that serum decreases tritiated mannose incorporation into protein in the chick optic lobe at 18 days of embryonic age (Rossi et al., 1990). In this paper, we found a strikingly different response of this serum effect according to age. The data obtained showed no serum induced decrease in 6-10-day-old embryo. In addition, our results demonstrate that the differential response of the tissue to the serum is independent of the rate of sugar entry into nerve cells. Furthermore, we also report that the variation of mannose or leucine incorporation into protein coincides very closely with the pattern of protein and glycoprotein accumulation during chick optic lobe development. Finally, data were obtained to define glial cells as the cellular target of the serum induced effect. This finding may contribute to elucidate the mechanism of cellular pathogenesis of cerebral lesions that occur after the breakdown of the blood brain barrier, such as in some diseases or during bleeding after injuries.     

TECPR2 Associated Neuroaxonal Dystrophy in Spanish Water Dogs

Clinical, pathological and genetic examination revealed an as yet uncharacterized juvenile-onset neuroaxonal dystrophy (NAD) in Spanish water dogs. Affected dogs presented with various neurological deficits including gait abnormalities and behavioral deficits. Histopathology demonstrated spheroid formation accentuated in the grey matter of the cerebral hemispheres, the cerebellum, the brain stem and in the sensory pathways of the spinal cord. Iron accumulation was absent. Ultrastructurally spheroids contained predominantly closely packed vesicles with a double-layered membrane, which were characterized as autophagosomes using immunohistochemistry. The family history of the four affected dogs suggested an autosomal recessive inheritance. SNP genotyping showed a single genomic region of extended homozygosity of 4.5 Mb in the four cases on CFA 8. Linkage analysis revealed a maximal parametric LOD score of 2.5 at this region. By whole genome re-sequencing of one affected dog, a perfectly associated, single, non-synonymous coding variant in the canine tectonin beta-propeller repeat-containing protein 2 (TECPR2) gene affecting a highly conserved region was detected (c.4009C>T or p.R1337W). This canine NAD form displays etiologic parallels to an inherited TECPR2 associated type of human hereditary spastic paraparesis (HSP). In contrast to the canine NAD, the spinal cord lesions in most types of human HSP involve the sensory and the motor pathways. Furthermore, the canine NAD form reveals similarities to cases of human NAD defined by widespread spheroid formation without iron accumulation in the basal ganglia. Thus TECPR2 should also be considered as candidate gene for human NAD. Immunohistochemistry and the ultrastructural findings further support the assumption, that TECPR2 regulates autophagosome accumulation in the autophagic pathways. Consequently, this report provides the first genetic characterization of juvenile canine NAD, describes the histopathological features associated with the TECPR2 mutation and provides evidence to emphasize the association between failure of autophagy and neurodegeneration.     

Photosynthetic responses to temperature of two tropical rainforest tree species from Costa Rica

Annual mean temperature increases will cause alterations in many ecosystem processes, which affect plants given their physiological sensitivity to temperature. That is closely related with plant growing conditions, genotype and plasticity. We studied the photosynthetic responses to instantaneous temperature changes and functional leaf traits in two tropical tree species associated with different successional positions, Zygia longifolia (early successional) and Dipteryx oleifera (late successional), in the northern lowlands of Costa Rica. We found that D. oleifera had thicker leaves and lower stomatal density, but similar specific leaf area to Z. longifolia. Maximum photosynthetic rate (A _max) and maximum RuBP saturate rate of carboxylation were higher in Z. longifolia than in D. oleifera. At 37 °C, only Z. longifolia reduced A _max and water use efficiency (WUE). But D. panamensis presented more severe effects on the quantum yield, respiration and light compensation points. The temperature response curves showed a similar optimum temperature near 27 °C for both species. On the other hand, the low and high temperature compensation points were different, with D. oleifera showing a narrower range than Z. longifolia. As a whole, we found two different strategies to avoid temperature stress: one reducing WUE (Z. longifolia), and the other one increasing metabolic rates (D. oleifera). However, the ability to withstand stressful situations may, in a larger context, negatively affect ecosystem water and carbon fluxes. Also, functional plasticity in response to temperature changes may relatively affect the ecosystem by causing long-term variations in their representation within the complex diversity mosaic of their forest habitats.     

Enabling Iron‐Based Highly Effective Electrochemical Water‐Splitting and Selective Oxygenation of Organic Substrates through In Situ Surface Modification of Intermetallic Iron Stannide Precatalyst

A strategy to overcome the unsatisfying catalytic performance and the durability of monometallic iron‐based materials for the electrochemical oxygen evolution reaction (OER) is provided by heterobimetallic iron–metal systems. Monometallic Fe catalysts show limited performance mostly due to poor conductivity and stability. Here, by taking advantage of the structurally ordered and highly conducting FeSn₂ nanostructure, for the first time, an intermetallic iron material is employed as an efficient anode for the alkaline OER, overall water‐splitting, and also for selective oxygenation of organic substrates. The electrophoretically deposited FeSn₂ on nickel foam (NF) and fluorine‐doped tin oxide (FTO) electrodes displays remarkable OER activity and durability with substantially low overpotentials of 197 and 273 mV at 10 mA cm^?2, respectively, which outperform most of the benchmarking NiFe‐based catalysts. The resulting superior activity is attributed to the in situ generation of α‐FeO(OH)@FeSn₂ where α‐FeO(OH) acts as the active site while FeSn₂ remains the conductive core. When the FeSn₂ anode is coupled with a Pt cathode for overall alkaline water‐splitting, a reduced cell potential (1.53 V) is attained outperforming that of noble metal‐based catalysts. FeSn₂ is further applied as an anode to produce value‐added products through selective oxygenation reactions of organic substrates.     

Medicinal ethnobotany in Huacareta (Chuquisaca, Bolivia)

ABSTRACT: BACKGROUND: The aim of this study was to document the types of diseases treated by the use of medicinal plants, their main applications and also to have a report of the major diseases treated at the Hospital of St. Paul of Huacareta (Chuquisaca Bolivia). METHODS: We conducted semi-structured interviews on the use medicinal plants with 10 local informants, and categorized the kinds of diseases treated by traditional medicine. We obtained reports of cases treated at the Hospital of Huacareta in order to compare the use frequency of traditional medicine and allopathic medicine for the treatment of recurrent diseases in the area. RESULTS: Our survey identified 258 traditional medicine uses, spanning a total of 13 diseases categories and including 91 native and exotic plant species and one unidentified sample plant type. Gastrointestinal disorders (55%) were most frequently treated with medicinal plants, followed by afflictions of the musculoskeletal system (25%) and dermatological disorders (24%). Hospital information indicates that the most common diseases are acute respiratory infections (47%) and acute diarrheal diseases (37%). The herbal remedies were mostly used in the form of teas and decoctions. The informants used mainly native plant species, although exotic species has been introduced to the pharmacopoeia. CONCLUSIONS: The treatment of gastrointestinal disorders is the primary objective of the medical ethnobotany of the inhabitants of Huacareta, while respiratory system diseases are mostly treated in the hospital. Looking at the data from the Hospital records we can infer that gastrointestinal disorders are among the most common diseases in the study area. For most respondents, traditional medicine is a reliable choice for the care of their illnesses. However, the preference of the population for either traditional medicine or allopathic medicine needs to be clarified in future comparative studies to obtain more convincing results. The results presented can be used as a base for subsequent work related to traditional medicine and its contribution to allopathic medicine in San Pablo de Huacareta. Introduccion El objetivo del presente estudio fue documentar los tipos de enfermedades tratadas mediante el uso de plantas medicinales, sus aplicaciones principales y tambien tener un reporte de las enfermedades mayormente atendidas en el Hospital de San Pablo de Huacareta (Chuquisaca, Bolivia). Metodos Se realizaron encuestas semiestructuradas a 10 informantes locales anotando los usos atribuidos a sus plantas medicinales, se agruparon las plantas por categorias de enfermedades tratadas en la medicina tradicional. Se obtuvieron reportes de casos tratados en el Hospital de Huacareta para poder relacionar el tratamiento de enfermedades recurrentes en la zona entre la medicina tradicional y la medicina occidental. Resultados Se reportaron 91 especies nativas y exoticas, ademas de un especimen indeterminado exotico que intervienen en un total de 258 aplicaciones medicinales, las cuales son empleadas en un total de 13 categorias de enfermedades. Los desordenes gastrointestinales (55%) son mayormente tratados mediante plantas medicinales, seguidas de las afecciones al sistema esqueleto-muscular (25%) y enfermedades dermatologicas (24%). La informacion del Hospital indica que las enfermedades mas frecuentes son Infecciones Respiratorias Agudas (47%) y Enfermedades Diarreicas Agudas (37%). Los remedios vegetales se emplean en forma de infusiones y cocciones principalmente. Se emplean mayormente plantas nativas, tambien se introdujo en la farmacopea medica el uso de plantas exoticas al lugar. Conclusiones El tratamiento de trastornos gastrointestinales constituye el objetivo primordial de la etnobotanica medica de los habitantes de Huacareta, las enfermedades del sistema respiratorio, son mayormente tratadas en el Hospital. Observando los datos del libro de consultas del Hospital, se puede inferir que los desordenes gastrointestinales estan entre las enfermedades mas frecuentes en el area estudiada. Para la mayoria de los entrevistados, la medicina tradicional es una opcion confiable para la atencion de sus enfermedades. Sin embargo, la preferencia de los habitantes entre la medicina tradicional y la medicina alopatica podria ser clarificada a partir de futuros estudios comparativos que permitan obtener resultados mas convincentes. Los resultados expuestos pueden ser usados como una base de datos para posteriores trabajos relacionados a la medicina tradicional y su contribucion con la medicina alopatica en San Pablo de Huacareta.     

The RANKL signaling axis is sufficient to elicit ductal side-branching and alveologenesis in the mammary gland of the virgin mouse

Receptor of Activated NF-κB Ligand (RANKL) is implicated as one of a number of effector molecules that mediate progesterone and prolactin signaling in the murine mammary epithelium. Using a mouse transgenic approach, we demonstrate that installation of the RANKL signaling axis into the mammary epithelium results in precocious ductal side-branching and alveologenesis in the virgin animal. These morphological changes occur due to RANKL-induced mammary epithelial proliferation, which is accompanied by increases in expression of activated NF-kB and cyclin D1. With age, prolonged RANKL exposure elicits limited mammary epithelial hyperplasia. While these transgenics exhibit RANKL-induced salivary gland adenocarcinomas, palpable mammary tumors are not observed due to RANKL-suppression of its own signaling receptor (RANK) in the mammary epithelium. Together, these studies reveal not only that the RANKL signaling axis can program many of the normal epithelial changes attributed to progesterone and prolactin action in the normal mammary gland during early pregnancy, but underscore the necessity for tight control of this signaling molecule to avoid unwarranted developmental changes that could lead to mammary hyperplasia in later life.     

Characterization of a tyrosine sulfotransferase in rat brain using cholecystokinin derivatives as acceptors

An apparently novel tyrosyl sulfotransferase activity was detected in a crude microsomal fraction from rat cerebral cortex by using 3'-phosphoadenosine 5'-phospho[35S]sulfate [( 35S]PAPS) as the sulfate donor and various cholecystokinin (CCK) fragments or derivatives as acceptors. Among the latter, the shortest substrate was tert-butoxycarbonylaspartyltyrosine (Boc-Asp-Tyr), but the reaction was optimized by increasing the length of the peptide sequence on the C-terminal side up to tert-butoxycarbonylcholecystokinin octapeptide (Boc-CCK-8) as well as by the presence of acidic amino acid residues at the N-terminal side. Peptides with an N-terminal Tyr residue (e.g., CCK-7 or enkephalins) were not sulfated. With Boc-CCK-8 the optimum pH was 5.8, and apparent KM values were 0.14 +/- 0.02 mM for the peptide (0.5 microM PAPS) and 0.12 +/- 0.01 microM for PAPS (0.25 mM Boc-CCK-8). In the presence of 0.2 mM MnCl2 the Vmax of the reaction was enhanced without change of apparent affinities of the two substrates. The possible role of this sulfotransferase activity in posttranslational modification of CCK and other secretory proteins is suggested.     

Characterization of 3''-Phosphoadenosine 5''-Phospho[35S]Sulfate Transport Carrier from Rat Brain Microsomes

3'-Phosphoadenosine 5'-phospho[35S]sulfate [( 35S]PAPS) specific binding properties of rat brain tissue were studied. [35S]PAPS specific binding was optimal at pH 5.8 in either Tris-maleate or potassium phosphate buffers. Association was maximal at low temperature, reaching equilibrium in 20 min. Dissociation was rapid, with a dissociation time of 80 s. Scatchard analysis of [35S]PAPS specific binding was consistent with a single site having a KD of 0.46 +/- 0.06 microM and a Bmax of 20.8 +/- 2.0 pmol/mg of protein. Low concentrations of Triton X-100 (0.025%) were effective in increasing the number of binding sites to a Bmax of 44.5 +/- 4.6 pmol/mg of protein without affecting the affinity. [35S]PAPS specific binding was enriched in crude synaptic membranes (P2) and microsomes (P3). Regional distribution of [35S]PAPS specific binding was quite homogeneous in all brain structures studied. The pharmacological profile of [35S]PAPS specific binding in rat brain microsomes was consistent with a membrane protein having a high selectivity for the 3'-O-phosphoryl group substitution on the ribose moiety. Thus, 3'-phosphoadenosine 5'-phosphate was more potent than 2'-phosphoadenosine 5'-phosphate in competing for [35S]PAPS specific binding. Adenosine 5'-phosphosulfate was a good inhibitor of [35S]PAPS specific binding. ATP and ADP were also good displacers. Dipyridamole, a highly selective marker for adenosine uptake sites, was ineffective. 4,4-Diisothiocyanostilbene-2,2-disulfonic acid, the chloride transporter inhibitor, showed an IC50 of 36 +/- 5.1 microM for inhibition of [35S]PAPS specific binding. 2,6-Dichloro-4-nitrophenol had a low selectivity in competing for the [35S]PAPS binding site.(ABSTRACT TRUNCATED AT 250 WORDS)