Studies of the metabolism and the toxicity of N-Methylformamide and related amides

The hepatotoxicity of the industrial solvent and investigational anti-tumour agent N-methylformamide (NMF, HOCNHCH3) and several structural analogues was assessed in mice. NMF and its ethyl analogue (NEF) were equipotent hepatotoxins causing extensive centrilobular necrosis and damage to the gall bladder. Pretreatment of mice with SKF525A did not influence the toxicity of these N-alkylformamides. Replacement of the formyl hydrogen of NMF with deuterium or methyl significantly reduced its hepatotoxicity. An in vitro model for the study of the toxicity and metabolism of N-alkylformamides was developed using isolated mouse hepatocytes. The cytotoxicity of NMF in vitro was concentration-dependent with maximal toxicity being achieved at concentrations of 5mM or above. The cytotoxic potential of related amides correlated well with their in vivo hepatotoxic potential. Pretreatment of mice with buthionine sulphoximine (BSO), which depleted hepatocytic levels of glutathione to 15% of control values, exacerbated the cytotoxicity of NMF towards the hepatocytes. NMF (1mM or above), incubated with isolated mouse hepatocytes, depleted intracellular glutathione levels to 26% of control values within 4h. Depletion of glutathione was quantitatively matched by the formation of a carbamoylating metabolite. Metabolism was dependent on the concentration of NMF and was drastically reduced in incubations of hepatocytes isolated from mice pretreated with BSO. The carbamoylating metabolite, S-(N-methylcarbamoyl)-glutathione (SMG), was identified in vitro using FAB-MS. The generation of SMG was subject to a large primary H/D kinetic isotope effect when the formyl hydrogen was replaced with deuterium. Likewise, glutathione depletion and metabolite formation were reduced or abolished by the deuteration or methylation of the formyl moiety of NMF. NEF, like NMF, depleted hepatocytic glutathione levels and was metabolised to a carbamoylating metabolite. Radioactivity derived from 14C-NMF and 14C-NEF, labelled in the alkyl moieties, was found to be irreversibly associated with microsomal protein on incubation in vitro. Binding was dependent on the presence of NADPH and was mostly abolished in the presence of reduced glutathione. SKF525A failed to influence the binding.

Sensing and control of adipocyte function

Obesity has become a global epidemic. Approximately 15% of the world population is either overweight or obese. This figure rises to 75% in many westernised countries including the United Kingdom. Health costs in the UK to treat obesity and associated disease are conservatively estimated at 6% of the National Health Service (NHS) budget equating to 3.33 billion Euros. Excess adiposity, especially in visceral depots, increases the risk of type 2 diabetes, cardiovascular disease, gall stones, hypertension and cancer. Type 2 diabetes mellitus accounts for >90% of all cases of diabetes of which the majority can be attributed to increased adiposity, and approximately 70% of cardiovascular disease has been attributed to obesity in the US. Weight loss reduces risk of these complications and in some cases can eliminate the condition. However, weight loss by conventional non-medicated methods is often unsuccessful or promptly followed by weight regain. This thesis has investigated adipocytes development and adipokine signalling with a view to enhance the understanding of tissue functionality and to identify possible targets or pathways for therapeutic intervention. Adipocyte isolation from human tissue samples was undertaken for these investigative studies, and the methodology was optimised. The resulting isolates of pre-adipocytes and mature adipocytes were characterised and evaluated. Major findings from these studies indicate that mature adipocytes undergo cell division post terminal differentiation. Gene studies indicated that subcutaneous adipose tissue exuded greater concentrations and fluctuations of adipokine levels than visceral adipose tissue, indicating an important adiposensing role of subcutaneous adipose tissue. It was subsequently postulated that the subcutaneous depot may provide the major focus for control of overall energy balance and by extension weight control. One potential therapeutic target, 11ß-hydrosteroid dehydrogenase (11ß-HSD1) was investigated, and prospective inhibitors of its action were considered (BVT1, BVT2 and AZ121). Selective reduction of adiposity of the visceral depot was desired due to its correlation with the detrimental effects of obesity. However, studies indicated that although the visceral depot tissue was not unaffected, the subcutaneous depot was more susceptible to therapeutic inhibition by these compounds. This was determined to be a potentially valuable therapeutic intervention in light of previous postulations regarding long-term energy control via the subcutaneous tissue depot.

A jelzálogpiaci válság és a Közép-Kelet-Európában aktív nagybankok részvényárfolyama (The impact of the subprime crisis on the banks being active in Central and Eastern Europe)

Tanulmányunkban azt vizsgáljuk, hogy a jelzálogpiaci válsághoz köthető hírek milyen hatással vannak a Közép-Kelet-Európában aktív nagybankokra. A vizsgálathoz tíz Közép-Kelet-Európában aktív, tőzsdei nagybankot választottunk ki, amelyek közül hat nyugat-európai, míg négy közép-kelet-európai székhelyű bank volt. A tíz pénzintézettel kapcsolatosan 128 hírt gyűjtöttünk össze a 2007. június 1. és 2009. december 31. közötti időszakból. A híreket öt kategóriába csoportosítottuk, és az egyes kategóriáknak a részvényárfolyamokra gyakorolt, rövid távú hatását külön vizsgáltuk. Számításaink alapján a jelzálogpiaci válság során a befektetők pozitívan fogadták az állami feltőkésítéssel kapcsolatos bejelentéseket és a kielégítő védelmet nyújtó, átfogó kormányzati bankmentő csomagokat. A veszteségekkel, a leminősítéssel és az ECB intézkedéseivel kapcsolatos hírek esetén rövid távon nem tudtunk szignifikáns hatást kimutatni. A kutatás során a hírek számosságában igen, de a hírek által kiváltott hatás nagyságrendjében nem észleltünk jelentős különbséget a nyugat-európai és a középkelet- európai bankok között. ______ The research measures the impact of the subprime crisis on the shareholders of the banks being active in Central and Eastern Europe. The analysis focuses on the ten largest banks of the region measured by the asset size. The authors address the question whether the crisis affected more signifi cantly the large banks headquartered in Western Europe or the banks domiciled in Central and Eastern Europe. With the aim of capturing the short-term impact of various news on the shareholders of the banks, the popular event-study methodology with a one-day event window is employed. Within the period of 1 June 2007 and 31 December 2009, altogether 128 news were collected and grouped into fi ve categories (downgrades, loss, capital strengthening, governmental rescue packages, interventions of the ECB). Among others, the authors found empirical evidence that the shareholders appreciated the interventions of the governments: their capital injections resulted in signifi cant positive abnormal returns. Governmental rescue packages also resulted in signifi cant abnormal returns in the share price, however, the sign of the returns was unambiguous. No empirical evidence was found that in the short run the news in connection with loss announcements, downgrades and ECB interventions resulted in signifi cant abnormal returns. We concluded that although Western European banks and banks domiciled in Central and Eastern Europe differed in the number of news announced, the crisis affected the banks in both regions in a similar manner.

Diversity of Hymenoptera, cultivated plants and management practices in home garden agroecosystems, Kyrgyz Republic

Pollination-dependent fruit trees grown in home gardens play an important role in the agricultural based economy of Central Asian countries, yet little is known about the status of pollinator communities, the cultivated plant composition or the factors that influence management practices in Kyrgyz home garden agroecosystems. As agricultural systems are human created and managed, a logical approach to their study blends anthropological and ecological methods, an ethnoecological approach. Over three years, I investigated how species richness and abundance of Hymenoptera, cultivated plants, and home garden management were related using quantitative and qualitative methods in the Issyk-kul Man and Biosphere reserve. Structured surveys were undertaken with heads of households using a random sample stratified by village. Gardens were then mapped with participation of household members to inventory edible species in gardens, most of which are pollinator-dependent, and to compare home garden diversity as reported by respondents during interviews. Apple diversity was studied to the variety level to understand respondents’ classification system in the context of in situ agrobiodiversity conservation. Household members identified 52 edible plant species when mapping the garden, compared with 32 reported when interviewed. The proportion of plant species received from others through exchange and the number of plots cultivated significantly explained the variation in edible plant diversity among gardens. Insects were sampled in gardens and orchards to determine potential pollinator community composition and the effect of different management practices on Hymenoptera richness and abundance. I collected 756 Hymenoptera individuals (56 bee; 12 wasp species); 12 species were new records for Kyrgyzstan or within Kyrgyzstan. Economic pressures to intensify cultivation could impact management practices that currently promote diversity. A home garden development initiative was undertaken to study management practice improvement. Participants in the initiative had higher adoption rates than controls of management practices that improve long-term yield, ecological sustainability and stability of home gardens. Home gardens, as currently managed, support abundant and diverse pollinator communities and have high cultivated plant diversity with few differences in community composition between garden management types.

An investigation of the effects of mothers' participation in adult literacy classes on interactive literacy activities (ILAs) at home

The National Center for Family Literacy (2003a) and the National Even Start Association (2005) have stated that the single most effective and influential factor in increasing student academic achievement is parental involvement. The purpose of this qualitative study was to determine how participation in adult literacy courses influences parent-child interaction in various educationally related activities known as Interactive Literacy Activities (ILAs). This study investigated ILAs from the mothers? perspective, and examines the changes that occur in parental involvement or ILAs when immigrant parents of a limited educational background participate in an adult education program. The principal method of data collection was key informant interviews (Gall, Borg, & Gall, 1996). Other methods of data collection included observations of parent-child interactions and field observations. Data analysis methods included Memo-ing (Miles & Huberman, 1994), within case analysis and cross-case analysis. ^ Findings demonstrate that changes occurred in the parent-child relationship when mothers of a limited educational background participated in an adult literacy course. When participating in ILAs or English literacy activities related to second language acquisition (including reading and speaking for comprehension and pronunciation), the children of these mothers took on the role of the adult. Participation in literacy activities was often initiated by the child and the children were frequently concerned with their mother's literacy acquisition. Mothers reported that their children were more confident, worked harder on school related activities and were more open to communication. ^ It can be concluded from this study that, in the case of these immigrant families, a mother's participation in adult literacy classes is influential in the relationship between mother and child. These children participated in ILAs for the benefit of their mothers and initiated literacy activities more frequently. The children responded better to their parents during literacy activities because there was a positive change in the relationship between mother and child. The relationship between mother and child appeared to be strengthened by greater trust, a sense of pride and more communication. ^

Anti-diarrheal plants of central Anatolia: Do they inhibit diarrhea-causing bacteria?

Infectious diarrhea results in 2 to 5 million deaths worldwide per year, and treatments that are safe, effective, and readily available are under investigation. The field of medicinal ethnobotany focuses on plants that are used by different cultural groups for treating various diseases and evaluates these plants for efficacy and cytotoxicity. In the present study, ethnobotanical research was conducted with Central Anatolian villagers in Turkey. Folk concepts and etiologies surrounding diarrhea were analyzed, as were salient plant-based remedies for diarrhea. Reviewing the literature, 91 plant species were described as anti-diarrheal in all of Turkey. In Central Anatolia, villagers described 35 species. For continued research via bactericidal and bacteriostatic bioassays, 15 plants were selected. Methanolic and aqueous extracts of medicinally used plant parts were evaluated for inhibitory properties against 10 diarrhea-causing bacteria in the first bioassay, and later 21 bacteria in a second assay utilizing spectrophotometry. The cytotoxic properties were also evaluated in an Alamar Blue Assay using HepG-2, PC-3, and SkMEL-5 human cell lines. While several extracts showed bactericidal and bacteriostatic properties, the methanolic extract of R. canina galls inhibited the most bacteria at the lowest concentrations. They were not cytotoxic. Thus, R. canina methanolic gall extracts were selected for bio-assay guided fractionation. Antibacterial activity was maintained in the third fraction which was composed of almost pure ellagic acid. The bioassay was repeated with standard ellagic acid, and the polyphenol retained potency in inhibiting multiple bacterial strains. Several other extracts showed promise for safe, effective anti-bacterial remedies for diarrhea.

Diversity of Hymenoptera, Cultivated Plants and Management Practices in Home Garden Agroecosystems, Kyrgyz Republic

Pollination-dependent fruit trees grown in home gardens play an important role in the agricultural based economy of Central Asian countries, yet little is known about the status of pollinator communities, the cultivated plant composition or the factors that influence management practices in Kyrgyz home garden agroecosystems. As agricultural systems are human created and managed, a logical approach to their study blends anthropological and ecological methods, an ethnoecological approach. Over three years, I investigated how species richness and abundance of Hymenoptera, cultivated plants, and home garden management were related using quantitative and qualitative methods in the Issyk-kul Man and Biosphere reserve. Structured surveys were undertaken with heads of households using a random sample stratified by village. Gardens were then mapped with participation of household members to inventory edible species in gardens, most of which are pollinator-dependent, and to compare home garden diversity as reported by respondents during interviews. Apple diversity was studied to the variety level to understand respondents’ classification system in the context of in situ agrobiodiversity conservation. Household members identified 52 edible plant species when mapping the garden, compared with 32 reported when interviewed. The proportion of plant species received from others through exchange and the number of plots cultivated significantly explained the variation in edible plant diversity among gardens. Insects were sampled in gardens and orchards to determine potential pollinator community composition and the effect of different management practices on Hymenoptera richness and abundance. I collected 756 Hymenoptera individuals (56 bee; 12 wasp species); 12 species were new records for Kyrgyzstan or within Kyrgyzstan. Economic pressures to intensify cultivation could impact management practices that currently promote diversity. A home garden development initiative was undertaken to study management practice improvement. Participants in the initiative had higher adoption rates than controls of management practices that improve long-term yield, ecological sustainability and stability of home gardens. Home gardens, as currently managed, support abundant and diverse pollinator communities and have high cultivated plant diversity with few differences in community composition between garden management types.

Die Herrlichkeit Gottes : eine biblisch-theologische Untersuchung ausgedehnt über das alte Testament, die Targume, Apokryphen, Apokalypsen und das Neue Testament

von Lic.Dr. Freiherr von Gall, Lehrer am Realgymnasium und an der Realschule zu Mainz

Die Papyrusurkunden der jüdischen Gemeinde in Elephantine in ihrer Bedeutung für jüdische Religion und Geschichte

von August Freiherr von Gall, Lic.theol., Dr.phil., Professor am Gymn. und Privatdozent a.d. Univ. in Gießen

Um estudo sobre a variabilidade do vento no nordeste do Brasil através de métodos estatísticos e via modelos dinâmicos de meso e micro escala

The objective of this study was to determine the seasonal and interannual variability and calculate the trends of wind speed in NEB and then validate the mesoscale numerical model for after engage with the microscale numerical model in order to get the wind resource at some locations in the NEB. For this we use two data sets of wind speed (weather stations and anemometric towers) and two dynamic models; one of mesoscale and another of microscale. We use statistical tools to evaluate and validate the data obtained. The simulations of the dynamic mesoscale model were made using data assimilation methods (Newtonian Relaxation and Kalman filter). The main results show: (i) Five homogeneous groups of wind speed in the NEB with higher values in winter and spring and with lower in summer and fall; (ii) The interannual variability of the wind speed in some groups stood out with higher values; (iii) The large-scale circulation modified by the El Niño and La Niña intensified wind speed for the groups with higher values; (iv) The trend analysis showed more significant negative values for G3, G4 and G5 in all seasons and in the annual average; (v) The performance of dynamic mesoscale model showed smaller errors in the locations Paracuru and São João and major errors were observed in Triunfo; (vi) Application of the Kalman filter significantly reduce the systematic errors shown in the simulations of the dynamic mesoscale model; (vii) The wind resource indicate that Paracuru and Triunfo are favorable areas for the generation of energy, and the coupling technique after validation showed better results for Paracuru. We conclude that the objective was achieved, making it possible to identify trends in homogeneous groups of wind behavior, and to evaluate the quality of both simulations with the dynamic model of mesoscale and microscale to answer questions as necessary before planning research projects in Wind-Energy area in the NEB

Ora et labora : Los jardines monacales en el Alto Medioevo

El huerto-jardín en el Alto Medioevo manifiesta la capacidad humana para domesticar una naturaleza salvaje y hostil y para transformarla en un lugar apacible, acogedor. Tanto en el ámbito citadino en las casas privadas, como en el ámbito rural en los monasterios, en estos recintos se cultivaban variados vegetales, legumbres, árboles frutales y también flores, ya sea para el consumo como para la delectación. Ahora bien, nuestra propuesta se centrará en los huertos-jardines que integraban la estructura monástica en cuanto espacios privilegiados en donde se pone en acto la consigna que sustenta la Regla de san Benito, el ora et labora. Para ello analizaremos un plano realizado en el período carolingio, conservado en la abadía benedictina de Saint-Gall. Este documento icónico nos permitirá acercarnos virtualmente a los espacios abaciales ya que el paso del tiempo y los sucesivos actos de vandalismo y de pillaje destruyeron total o parcialmente la arquitectura monacal alto medieval. Plano "ideal" que da cuenta de los conocimientos teórico-prácticos sobre la agricultura y la horticultura pero que además nos acerca la concepción filosófica-teológica de la época

Geochemical composition of minerals obtained from ODP Sites 180-1109, 180-1117 and 180-1118

During the last 8 m.y. the Papuan Peninsula region of Papua New Guinea has been affected by extension which opened the Woodlark Basin. The present-day spreading tip is located at the foot of the Moresby Seamount, a crustal block whose northern flank is an active low-angle normal fault related to this extension. During Ocean Drilling Program Leg 180 (7 June-11 August 1998), 11 sites (1108-1118) were drilled along a north-south-trending transect across the Woodlark Basin just ahead of the spreading tip. Four of these sites (1118, 1109, 1114, and 1117) reached the crystalline basement, which is composed of diabase and gabbro. Sites 1118 and 1109, located on the Woodlark Rise, belong to the hanging wall block, and Sites 1114 and 1117, located on the crest of the Moresby Seamount, belong to the footwall block and the fault zone itself. Most of the basalt, diabase, and gabbro that were recovered show a well-preserved magmatic texture. The diabase, which is the most abundant rock type, has a coarse-grained ophitic texture composed of poikilitic clinopyroxene including radiating, locally skeletal plagioclase laths with interstitial iron oxide grains. Secondary mineralogy consists of chlorite, zeolite, calcite, albite, and quartz. The gabbro shows a medium-grained granular texture. The magmatic mineralogy consists of euhedral laths of plagioclase and anhedral interstitial clinopyroxene. Secondary mineralogy consists of a magnesio to actinolitic hornblende, chlorite, clinozoisite, zeolite, quartz, and calcite. The retrograde metamorphic evolution of both gabbro and diabase occurred under low amphibolite to subgreenschist facies conditions associated mainly with brittle deformation and the development of a local low-temperature shear zone. This shows no evidence for high thermal gradient in the crust during the continental rifting.

Exploring several nonconventional interactions of ice-binding proteins

Traditionally, ice-binding proteins (IBPs), also known as antifreeze proteins (AFPs), have been defined by two universal activities: ice recrystallization inhibition and thermal hysteresis. However, there remains the possibility IBPs have other complementary functions given the diversity found within this protein group. This thesis explores some of these in both natural and applied settings, in the hopes of furthering our understanding of this remarkable group of proteins. Plant IBPs could function as part of a defensive strategy against ice nucleators produced by certain pathogens. To assess this hypothesis, recombinant IBPs from perennial ryegrass and purple false brome were combined with the ice nucleation protein (INP) from the plant pathogen, Pseudomonas syringae. Strikingly, the plant proteins depressed the freezing point of the bacterial INP, while a fish AFP could not, nor did the INPs have any effect on IBP activity. Thus, the interaction between these two different proteins suggests a role in plant defensive strategies against pathogenic bacteria as another IBP function. In addition, the potential use of hyperactive insect IBPs in organ preservation was investigated. Current kidney preservation techniques involve storing the organ at 4 °C for a maximum of 24 h prior to transplantation. Extending this “safe” time would have profound effects on renal transplants, however, ischemic injury is prevalent when storage periods are prolonged. Experiments described here allowed subzero preservation for 72 h with the addition of a beetle IBP to CryoStasis® solution. Kidneys stored using the traditional technique for 24 h and the method developed here for 72 h showed similar levels of biomarker enzymes, underscoring the potential utility of insect IBPs for future transplant purposes. Finally, IBP function in the freeze-tolerant gall fly, Eurosta solidaginis, was examined. Larvae representing the mid-autumn stage displayed ice-binding activity, suggesting an IBP is being expressed, possibly as a protective measure against freezing damage when fall temperatures can unpredictably drop. IBP activity was also observed in the larvae’s host plant, Solidago spp. Mass spectrometry analysis of ice-affinity purified plant extracts provided three candidate pathogenesis-related proteins that could be responsible for the detected activity, further demonstrating additional functions of IBPs.

Perspectives on gender, migration and transnational work: joint work of social reproduction and care in Southern Europe

This paper presents the "state of the art" and some of the main issues discussed in relation to the topic of transnational migration and reproductive work in southern Europe. We start doing a genealogy of the complex theoretical development leading to the consolidation of the research program, linking consideration of gender with transnational migration and transformation of work and ways of survival, thus making the production aspects as reproductive, in a context of globalization. The analysis of the process of multiscale reconfiguration of social reproduction and care, with particular attention to its present global dimension is presented, pointing to the turning point of this line of research that would have taken place with the beginning of this century, with the rise notions such as "global care chains" (Hochschild, 2001), or "care drain" (Ehrenreich and Hochschild, 2013). Also, the role of this new agency, now composed in many cases women who migrate to other countries or continents, precisely to address these reproductive activities, is recognized. Finally, reference is made to some of the new conceptual and theoretical developments in this area.

PhytoREF: a reference database of the plastidial 16S rRNA gene of photosynthetic eukaryotes with curated taxonomy

Photosynthetic eukaryotes have a critical role as the main producers in most ecosystems of the biosphere. The ongoing environmental metabarcoding revolution opens the perspective for holistic ecosystems biological studies of these organisms, in particular the unicellular microalgae that often lack distinctive morphological characters and have complex life cycles. To interpret environmental sequences, metabarcoding necessarily relies on taxonomically curated databases containing reference sequences of the targeted gene (or barcode) from identified organisms. To date, no such reference framework exists for photosynthetic eukaryotes. In this study, we built the PhytoREF database that contains 6490 plastidial 16S rDNA reference sequences that originate from a large diversity of eukaryotes representing all known major photosynthetic lineages. We compiled 3333 amplicon sequences available from public databases and 879 sequences extracted from plastidial genomes, and generated 411 novel sequences from cultured marine microalgal strains belonging to different eukaryotic lineages. A total of 1867 environmental Sanger 16S rDNA sequences were also included in the database. Stringent quality filtering and a phylogeny-based taxonomic classification were applied for each 16S rDNA sequence. The database mainly focuses on marine microalgae, but sequences from land plants (representing half of the PhytoREF sequences) and freshwater taxa were also included to broaden the applicability of PhytoREF to different aquatic and terrestrial habitats. PhytoREF, accessible via a web interface (http://phytoref.fr), is a new resource in molecular ecology to foster the discovery, assessment and monitoring of the diversity of photosynthetic eukaryotes using high-throughput sequencing.