Regulation of GABAergic neuron identity and diversity in the developing midbrain

Gamma-aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in the vertebrate brain. In the midbrain, GABAergic neurons contribute to the regulation of locomotion, nociception, defensive behaviours, fear and anxiety, as well as sensing reward and addiction. Despite the clinical relevance of this group of neurons, the mechanisms regulating their development are largely unknown. In addition, their migration and connectivity patterns are poorly characterized. This study focuses on the molecular mechanisms specifying the GABAergic fate, and the developmental origins of midbrain GABAergic neurons. First, we have characterized the function of a zink-finger transcription factor Gata2. Using a tissue-specific mutagenesis in mouse midbrain and anteror hindbrain, we showed that Gata2 is a crucial determinant of the GABAergic fate in midbrain. In the absence of Gata2, no GABAergic neurons are produced from the otherwise competent midbrain neuroepithelium. Instead, the Gata2-mutant cells acquire a glutamatergic neuron phenotype. Ectopic expression of Gata2 was also sufficient to induce GABAergic in chicken midbrain. Second, we have analyzed the midbrain phenotype of mice mutant for a proneural gene Ascl1, and described the variable and region-dependent requirements for Ascl1 in the midbrain GABAergic neurogenesis. These studies also have implications on the origin of distinct anatomical and functional GABAergic subpopulations in midbrain. Third, we have identified unique developmental properties of GABAergic neurons that are associated with the midbrain dopaminergic nuclei, the substantia nigra pars reticulata (SNpr) and ventral tegmental area (VTA). Namely, the genetic regulation of GABAergic fate in these cells is distinct from the rest of midbrain. In accordance to this phenomenon, our detailed fate-mapping analyses indicated that the SNpr-VTA GABAergic neurons are generated outside midbrain, in the neuroepithelium of anterior hindbrain.

Associations of serum perfluoroalkyl acid levels with T-helper cell-specific cytokines in children: By gender and asthma status

Perfluoroalkyl acids (PFAAs) are a group of common chemicals that ubiquitously exist in wildlife and humans. Experimental data suggest that they may alter T-lymphocyte functioning in situ by preferentially enhancing the development of T-helper 2 (TH2)- and inhibiting TH1-lymphocyte development and might increase allergic inflammation, but few human studies have been conducted. To evaluate the association between serum PFAAs concentrations and T-lymphocyte-related immunological markers of asthma in children, and further to assess whether gender modified this association, 231 asthmatic children and 225 non-asthmatic control children from Northern Taiwan were recruited into the Genetic and Biomarker study for Childhood Asthma. Serum concentrations of ten PFAAs and levels of TH1 [interferon (IFN)-γ, interleukin (IL)-2] and TH2 (IL-4 and IL-5) cytokines were measured. The results showed that asthmatics had significantly higher serum PFAAs concentrations compared with the healthy controls. When stratified by gender, a greater number of significant associations between PFAAs and asthma outcomeswere found in males than in females. Among males, adjusted odds ratios for asthma among those with the highest versus lowest quartile of PFAAs exposure ranged from 2.59 (95% CI: 1.14, 5.87) for the perfluorobutanesulfonate (PFBS) to 4.38 (95% CI: 2.02, 9.50) for perfluorooctanesulfonate (PFOS); and serum PFAAs were associated positively with TH2 cytokines and inversely with TH1 cytokines among male asthmatics. Among females, no significant associations between PFAAs and TH2 cytokines could be detected. In conclusion, increased serum PFAAs levels may promote TH cell dysregulation and alter the availability of key TH1 and TH2 cytokines, ultimately contributing to the development of asthma that may differentially impact males to a greater degree than females. These results have potential relevance in asthma prevention.

Gender and National Identity Constructions in the Cross-Border Merger Context

In this article we explore ways in which vertical gender inequality is accomplished in discourse in the context of a recent chain of cross-border mergers and acquisitions that resulted in the formation of a multinational Nordic company. We analyse social interactions of ‘doing’ gender in interviews with male senior executives from Denmark, Finland and Sweden. We argue that their explanations for the absence of women in the top echelons of the company serve to distance vertical gender inequality. The main contribution of the article is an analysis of how national identities are discursively (re)constructed in such distancing. New insights are offered to studying gender in multinationals with a cross-cultural team of researchers. Our study sheds light on how gender intersects with nationality in shaping the multinational organization and the identities of male executives in globalizing business.

Gender and female entrepreneurship in a pro-entrepreneurship magazine

In this working paper I discuss gendered entrepreneurship by exploring how the media writes about female entrepreneurship. The starting point is that the media when talking and writing about female entrepreneurs and female entrepreneurship, mould meanings of gender in entrepreneurship. I view entrepreneurship and gender as socially constructed, discursive phenomena. To uncover the processes of constructing gender in female entrepreneurship this paper applies a discursive framework, which treats language as a representational system producing and circulating meaning. The focus on language use as action implies that practises of writing and talking about female entrepreneurship ‘make’ gender as much as the women entrepreneurs) themselves: both involve working on culturally shared meanings to make reality intelligible. The data consists of articles published in Yrittäjä, a pro-SME magazine, in 1990-1997. In the analysis I show how gender is constructed in media talk. as a women’s issue Women entrepreneurs are constantly compared with men and with an implicitly masculine ideal of entrepreneurship and with strengths and weaknesses of women are displayed pointing out that the meaning making of gender taking place in the data refers to equality discourse. Finally I discuss possible consequences of the hegemonic equality discourse and suggest lines of further research.

Sukupuoli ja organisaatiot liikkeessä? Gender and Organisations in Flux?

Viimeaikainen sukupuolta ja organisaatiota käsittelevä tutkimus ja kirjallisuus on saanut paljon (toisinaan epäsuoria) vaikutteita feminismiä ympäröivistä keskusteluista. Lisäksi naisten aseman ja kokemuksien tunnistaminen organisaatioissa ja johtamisessa on vaikuttanut tutkimukseen. Erilaisten kansainvälisesti tutkittujen aiheiden kirjo on laaja: sukupuolisuhteet organisaatioiden ja johtoryhmien kulttuureissa ja kommunikaatiossa; sukupuolittunut työnjako; sukupuolittuneet hierarkiat, valta, auktoriteetti ja johtajuus organisaatioissa ja johtamisessa; sukupuolittuneet markkinat; sukupuolittuneet kuvat, symbolit ja mainokset; sukupuoli ja IT teknologia; seksuaalisuus, häirintä, kiusaaminen ja väkivalta organisaatioissa; työn ja kodin yhteensovittaminen; ja niin edelleen. Myös akateemiset organisaatiot sekä niiden sukupuolittuneet valtasuhteet ja johtaminen kaipaavat kipeästi huomiota. Useimpia mainituista alueista on tutkittu ainakin jonkin verran mutta paljon työtä on vielä myös jäljellä. Tämä kokoelma esittelee ajankohtaista suomalaista tutkimusta seuraavista teemoista: tasa-arvo organisaatioissa, naisjohtajuus, yrittäjyyden sukupuoli, verkostot, sukupuolen representaatio sekä sukupuoli ja uusi teknologia. Kokoelma on työryhmän yhdessä koostama joten se on ennen kaikkea yhteistyön tulos. Recent research and literature on the gendering of organisations has been strongly influenced, though sometimes indirectly, by debates in and around feminism, and on recognising women and women’s situations, experiences and voices in organisations and management. The range of topics and issues that have been studied internationally is vast: gender relations in organizational and management groups, cultures and communication; gender divisions of labour; gender divisions of hierarchy, power, authority and leadership in organizations and management; gendered markets; gender imagery, symbols and advertising; gender and information technology; sexuality, harassment, bullying and violence in organisations; home-work relations; and so on. There are also key issues of gender power relations in academic organizations and management themselves, which need urgent attention. Though most of these areas have been researched to some extent, much remains to be done. This collection brings together current Finnish research on: Equality in Organisations, Women in Management, Gender and Entrepreneurship, Networks, Representation of Gender, Gender and ICTs. The book has been put together by an editorial team and is thus first and foremost a collective effort.

Plant communities of field margins : the effects of management and environmental factors on species composition and diversity

Agri-environmental schemes have so far resulted in only minor positive implications for the biodiversity of agricultural environments, in contrast to what has been expected. Land-use intensification has decreased landscape heterogeneity and the amount of semi-natural habitats. Field margins are uncultivated areas of permanent vegetation located adjacent to fields. Since the number of these habitats is high, investing in their quality may result in more diverse agricultural landscapes. Field margins can be considered as multifunctional habitats providing agronomic, environmental and wildlife services. This thesis aimed at examining the plant communities of different types of field margin habitats and the factors affecting their species diversity and composition. The importance of edaphic, spatial and management factors was studied on regional, landscape and habitat scales. Vegetation surveys were conducted on regional and landscape scales and a field experiment on cutting management was conducted on a habitat scale. In field margin plant communities, species appeared to be indicators of high or intermediate soil fertility and moist soil conditions. The plant species diversity found was rather low, compared with most species-rich agricultural habitats in Finland, such as dry meadows. Among regions, land-use history, main production line, natural species and human induced distribution, climate and edaphic factors were elements inducing differences in species composition. The lowest regional species diversity of field margins was related to intensive and long-term cereal production. Management by cutting and removal or grazing had a positive effect on plant species diversity. The positive effect of cutting and removal on species richness was also dependent on the adjacent source of colonizing species. Therefore, in species-poor habitats and landscapes, establishment of margins with diverse seed mixtures can be recommended for enhancing the development of species richness. However, seed mixtures should include only native species preferably local origin. Management by cutting once a year for 5 years did not result in a decline in dominance of a harmful weed species, Elymus repens, showing that E. repens probably needs cutting more frequently than once per year. Agri-environmental schemes should include long-term contracts with farmers for the establishment, and management by cutting and removal or grazing, of field margins that are several metres wide. In such schemes, the timing and frequency of management should be planned so as not to harm other taxa, such as the insects and birds that are dependent on these habitats. All accidental herbicide drifts to field margins should be avoided when spraying the cultivated area to minimize the negative effects of sprayings on vegetation. The harmful effects of herbicides can be avoided by organic farming methods.

Effects of gender, and SLCO1B1 and CYP7A1 polymorphisms on plasma bile acids in humans and the pharmacokinetics of therapeutic ursodeoxycholic acid

Bile acids are important steroid-derived molecules essential for fat absorption in the small intestine. They are produced in the liver and secreted into the bile. Bile acids are transported by bile flow to the small intestine, where they aid the digestion of lipids. Most bile acids are reabsorbed in the small intestine and return to the liver through the portal vein. The whole recycling process is referred to as the enterohepatic circulation, during which only a small amount of bile acids are removed from the body via faeces. The enterohepatic circulation of bile acids involves the delicate coordination of a number of bile acid transporters expressed in the liver and the small intestine. Organic anion transporting polypeptide 1B1 (OATP1B1), encoded by the solute carrier organic anion transporter family, member 1B1 (SLCO1B1) gene, mediates the sodium independent hepatocellular uptake of bile acids. Two common SNPs in the SLCO1B1 gene are well known to affect the transport activity of OATP1B1. Moreover, bile acid synthesis is an important elimination route for cholesterol. Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme of bile acid production. The aim of this thesis was to investigate the effects of SLCO1B1 polymorphism on the fasting plasma levels of individual endogenous bile acids and a bile acid synthesis marker, and the pharmacokinetics of exogenously administered ursodeoxycholic acid (UDCA). Furthermore, the effects of CYP7A1 genetic polymorphism and gender on the fasting plasma concentrations of individual endogenous bile acids and the bile acid synthesis marker were evaluated. Firstly, a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of bile acids was developed (Study I). A retrospective study examined the effects of SLCO1B1 genetic polymorphism on the fasting plasma concentrations of individual bile acids and a bile acid synthesis marker in 65 healthy subjects (Study II). In another retrospective study with 143 healthy individuals, the effects of CYP7A1 genetic polymorphism and gender as well as SLCO1B1 polymorphism on the fasting plasma levels of individual bile acids and the bile acid synthesis marker were investigated (Study III). The effects of SLCO1B1 polymorphism on the pharmacokinetics of exogenously administered UDCA were evaluated in a prospective genotype panel study including 27 healthy volunteers (Study IV). A robust, sensitive and simple HPLC-MS/MS method was developed for the simultaneous determination of 16 individual bile acids in human plasma. The method validation parameters for all the analytes met the requirements of the FDA (Food and Drug Administration) bioanalytical guidelines. This HPLC-MS/MS method was applied in Studies II-IV. In Study II, the fasting plasma concentrations of several bile acids and the bile acid synthesis marker seemed to be affected by SLCO1B1 genetic polymorphism, but these findings were not replicated in Study III with a larger sample size. Moreover, SLCO1B1 polymorphism had no effect on the pharmacokinetic parameters of exogenously administered UDCA. Furthermore, no consistent association was observed between CYP7A1 genetic polymorphism and the fasting plasma concentrations of individual bile acids or the bile acid synthesis marker. In contrast, gender had a major effect on the fasting plasma concentrations of several bile acids and also total bile acids. In conclusion, gender, but not SLCO1B1 or CYP7A1 polymorphisms, has a major effect on the fasting plasma concentrations of individual bile acids. Moreover, the common genetic polymorphism of CYP7A1 is unlikely to influence the activity of CYP7A1 under normal physiological conditions. OATP1B1 does not play an important role in the in vivo disposition of exogenously administered UDCA.

Parasite abundance and diversity in mammals: correlates with host ecology

Fecally dispersed parasites of 12 wild mammal species in Mudumalai Sanctuary, southern India, were studied, Fecal propagule densities and parasite diversity measures were correlated with host ecological variables. Host species with higher predatory pressure had lower parasite loads and parasite diversity. Host body weight, home range, population density, gregariousness, and diet did not show predicted effects on parasite loads. Measures of a! diversity were positively correlated with parasite abundance and were negatively correlated with beta diversity, Based on these data, hypotheses regarding determinants of parasite community are discussed.

Does Long-Term Macrophyte Management in Lakes Affect Biotic Richness and Diversity?

We hypothesize that the richness and diversity of the biota in Lake Moraine (42°50’47”N, 75°31’39”W) in New York have been negatively impacted by 60 years of macrophyte and algae management to control Eurasian watermilfoil ( Myriophyllum spicatum L.) and associated noxious plants. To test this hypothesis we compare water quality characteristics, richness and selected indicators of plant diversity, zooplankton, benthic macroinvertebrates and fish in Lake Moraine with those in nearby Hatch Lake (42°50’06”N, 75°40’67”W). The latter is of similar size and would be expected to have similar biota, but has not been subjected to management. Measurements of temperature, pH, oxygen, conductivity, Secchi transparency, calcium, total phosphorus and nitrites + nitrates are comparable. Taxa richness and the diversity indices applied to the aquatic macrophytes are similar in both lakes. (PDF has 8 pages.)

Structure and diversity in Mytilus californianus (Mollusca: Bivalvia) communities

Mytilus californianus (Mollusca: Bivalvia), the California marine mussel, occurs in intertidal populations so derise that they are referred to as "Mussel beds." The mussel beds range in physical complexity from structurally simple, essentially mono-layered assemblages, to structurally complex, multi-layered assemblages. The internal environment within the bed varies accordingly. The mussel bed provides either directly or indirectly, habitat, food and shelter for a large community of associated invertebrates. This study examines the relationship between physical complexity of the mussel bed habitat and composition of the associated community.

Effects of trawling for ocean shrimp (Pandalus jordani) on macroinvertebrate abundance and diversity at four sites near Nehalem Bank, Oregon

Surveys with a remotely operated vehicle (ROV) at four mudhabitat sites with different histories of ocean shrimp (Pandalus jordani) trawling showed measurable effects of trawling on macroinvertebrate abundance and diversity. Densities of the sea whip (Halipteris spp., P<0.01), the flat mud star (Luidia foliolata, P< 0.001), unidentified Asteroidea (P<0.05), and squat lobsters (unidentified Galathoidea, P<0.001) were lower at heavily trawled (HT) sites, as was invertebrate diversity based on the Shannon-Wiener index. Sea cucumbers (unidentified Holothuroidea) and unidentified corals (Hydrocoralia) were observed at lightly trawled (LT) sites but not at HT sites. Hagfish (Eptatretus spp.) burrows were the dominant structural feature of the sediment surface at all sites and were more abundant at the HT sites (P<0.05), a result potentially related to effects from fishery discards. Substantial heterogeneity was found between the northern and southern site pairs, indicating high site-to-site variability in macroinvertebrate densities in these deep (146–156 m) mud habitats. Two of the study sites were closed to trawling in June 2006. The data from this study can be used in combination with future surveys to measure recovery rates of deep, mud, seaf loor habitats from the effects of trawling, thus providing a critical piece of information for ecosystem-based management.