Mouse model of the human serotonin transporter-linked polymorphic region

Genetic factors play a significant role in risk for mood and anxiety disorders. Polymorphisms in genes that regulate the brain monoamine systems, such as catabolic enzymes and transporters, are attractive candidates for being risk factors for emotional disorders given the weight of evidence implicating monoamines involvement in these conditions. Several common genetic variants have been identified in the human serotonin transporter (5-HTT) gene, including a repetitive sequence located in the promoter region of the locus called the serotonin transporter-linked polymorphic region (5-HTT-LPR). This polymorphism has been associated with a number of mental traits in both humans and primates, including depression, neuroticism, and harm avoidance. Some, but not all, studies found a link between the polymorphism and 5-HTT levels, leaving open the question of whether the polymorphism affects risk for mental traits via changes in 5-HTT expression. To investigate the impact of the polymorphism on gene expression, serotonin homeostasis, and behavioral traits, we set out to develop a mouse model of the human 5-HTT-LPR. Here we describe the creation and characterization of a set of mouse lines with single-copy human transgenes carrying the short and long 5-HTT-LPR variants. Although we were not able to detect differences in expression between the short and long variants, we encountered several technical issues concerning the design of our humanized mice that are likely to have influenced our findings. Our study serves as a cautionary note for future studies aimed at studying human transgene regulation in the context of the living mouse.

     

Recognizing and interpreting vegetational belts: New wine in the old bottles of a von Humboldt's legacy

Since von Humboldt, recognizing and using elevational subdivisions is at the core of biogeographical and ecological studies in mountain ecosystems. However, despite the large use of vegetational belts, their conceptual definition and practical identification appear to be surprisingly loose and inconsistent. Many authors use variations in climatic conditions to identify elevational belts. These belts are useful to set a framework for ecological studies but cannot be considered a surrogate of vegetational belts, because factors different from climate play a major role in determining the distribution of plant assemblages. Vegetation physiognomy can be used to identify ‘biome‐type’ belts that are useful for comparisons across geographical areas with different floras. However, to properly reflect ecological conditions at local scale, vegetational belts should be based on species composition. One of the most effective statistical approaches for this purpose is the use spatially constrained cluster analysis. The use of indicator species analysis may be also recommended to identify the species that most characterize vegetational belts. This can help researchers to identify belts in the field. Since species identification can be difficult, some authors use plant functional types for belt delimitation. Plant functional types can be helpful to trace the adaptative responses of vegetation along elevational gradients, but cannot be recommended as a standard way to identify belts. In general, criteria to identify vegetational belts can be based on both vegetation structure (namely physiognomy and structural parameters) and/or species composition, depending on the scale and the aim of the analyses, and they should be clearly stated.     

Cone-shaped HIV-1 capsids are transported through intact nuclear pores

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Bartter's syndrome associated with indirect hyperbilirubinemia: a possible clinical variety

This report deals with three cases of Bartter's syndrome whose symptomatology was associated with indirect hyperbilirubinemia. The bilirubin disorder was suggestive of Gilbert's syndrome, with no pathological findings being detected as far as the liver function was concerned. Furthermore, the unconjugated fraction of bilirubin increased after fasting. The therapy with indomethacin exerted beneficial effects on both electrolytes and bilirubin disorders, and the patients recovered a good healthy state. These findings suggest the possibility that Bartter's syndrome may coexist in a variety associated with indirect hyperbilirubinemia.     

Pre-eclampsia onset and SPARC: A possible involvement in placenta development

Pre-eclampsia (PE) is a multisystem disorder commonly diagnosed in the latter half of pregnancy and it is a leading cause of intrauterine fetal growth retardation (IUGR). The aim of this study was to investigate the localization and the role of SPARC, secreted protein acidic, and rich in cysteine, in PE and PE–IUGR placentas in comparison with normal placentas. SPARC was mainly expressed in the villous and extravillous cytotrophoblastic cells in first trimester, whereas in PE, PE–IUGR and at term placentas, SPARC immunostaining was visible in both cytotrophoblastic cells and syncytiotrophoblast. SPARC expression significantly decreased in normal placenta from first to third trimester and a further significant reduction was demonstrated in PE and PE–IUGR. The latter downregulation of SPARC depends on hypoxic condition as shown by in vitro models. In conclusion, SPARC can play a pivotal role in PE and PE–IUGR onset and it should be considered as a key molecule for future investigations in such pathologies.