Maimonides' Commentar zum Tractat Challah : zum 1. Male im arab. Urtext hrsg., mit verb. hebr. Uebers., deutscher Uebersetzung, Einl. u. Anm. vers.

von Selig Bamberger

Neurocognitive impairment in relation to glutathione S-transferase enzyme polymorphisms among medulloblastoma patients

Background. Medulloblastoma is a type of brain cancer that accounts for approximately 7-8% of all intracranial tumors and 20-30% of pediatric brain tumors. It is the most common type of malignant brain tumor in childhood. It was reported that majority of survivors with medulloblastoma have social problems, endocrine deficits, and neurological complications. Furthermore, all had significant deficits in neurocognitive functioning. Glutathione S-transferases belong to a family of isoenzymes that catalyze the glutathione conjugation of a variety of electrophilic compounds. ^ Objective. We aimed to determine whether the development of neurocognitive impairment is associated with GST polymorphisms among children and adolescents diagnosed with medulloblastoma (MB) after radiation therapy. ^ Methods. A pilot study composing of 16 children and adolescents diagnosed with MB at Texas Children's Cancer Center was conducted. The t-test was used to determine if the GST polymorphisms were related to neurocognitive impairment and logistic regression was performed to explore association between GST polymorphisms and gender, age at diagnosis, race/ethnicity, and risk group. ^ Results. An association was observed between GSTT1 polymorphism and cognitive impairment one year after radiation and GSTM1 polymorphism two years after radiation. It was observed that patients with GSTT1 null genotype have lower performance IQ (p=0.03) and full scale IQ (p=0.02) one year after radiation and patients with GSTM1 null genotype have lower verbal IQ (p=0.02) two years after radiation. Patients under age 8 have a statistically non-significant higher risk of having not null genotypes compared to those older than age 8 (OR= 7.5, 95%CI: 0.62-90.65 and OR= 2.63, 95%CI: 0.30-23.00 for GSTT1 and GSTM1 respectively). ^ Conclusion. There was a significant association between GSTT1 polymorphism and cognitive impairment one year after radiation and between GSTM1 polymorphism and cognitive impairment two years after radiation. Further large scale studies may be needed to confirm this finding and to examine the underlying mechanism of neurocognitive impairments after treatment of medulloblastoma patients.^

Role of the glutathione S -transferase P1 (GSTP1) electrophile binding site (H-site) in protection from doxorubicin -mediated cytotoxicity

The hypothesis addressed in this project was that novel variants of naturally occurring human glutathione S-transferase P1 (GSTP1) can be created by random mutagenesis of the GSTP1 active site to yield polypeptides with increased enzymatic activity against electrophilic substrates. Specifically, the mutant proteins would metabolize and inactivate selected electrophiles more efficiently than wild-type GSTP1 and confer significant cytoprotection, as measured by reduced apoptosis and increased clonogenic survival. Glutathione S-transferase P1, a major electrophile metabolizing and detoxifying enzyme, is encoded by a polymorphic genetic locus. This locus contains nucleotide transitions in the region encoding the active site of the peptide that yields proteins with significant structural and functional differences. The method of Degenerate Oligonucleotide Mediated Random Mutagenesis (DOMRM) was used to generate cDNAs encoding unique GSTP1 polypeptides with mutations within electrophile binding site (H-site) while leaving the glutathione binding site unaffected. A prokaryotic expression library of the mutant GSTP1 polypeptides was created and screened for increased resistance to cisplatin. This screen resulted in the isolation of 96 clones representing 22 distinct mutant cDNA sequences. To investigate the effects of the changes in the H-site on the biological activity of GSTP1, the cDNA of wild-type GSTP1c and two of the identified mutants were stably transfected into human LNCaP-Pro5 prostate cancer cells that do not endogenously express GSTP1. Wild-type transfectants were resistant to doxorubicin-induced apoptosis and displayed increased clonogenic survival compared to vector controls. However, contrary to the hypothesis, in both assays the mutant transfectants were no more resistant to doxorubicin than the wild-type transfectants. To elucidate the mechanisms underlying GSTP1-mediated survival, an in-vitro assay was developed to determine whether active GSTP1 protein directly metabolizes doxorubicin by conjugation to reduced glutathione (GSH). Although GSH did promote the appearance of a unique doxorubicin conjugate, conjugate formation was not substantially increased by the addition of GSTP1 in a variety of reaction conditions. ^

Characterizing Overall Response to Two-shot Vaccination for BVDV Type 2 in Angus Weanling Calves

Vaccination is a management strategy utilized to help reduce prevalence of bovine respiratory disease in feedlots. However, not all animals respond similarly to vaccinations. It is believed that an animal’s genetics control part of the ability to respond to a vaccination protocol. In order to evaluate the genetic control of a new trait such as response to vaccination, it is important to understand the non-genetic factors that affect an animal’s response to vaccination. The objective of this study was to characterize the non-genetic factors affecting overall response to a two-shot vaccination for bovine viral diarrhea virus type 2 (BVDV2) in Angus weanling calves.

(Table 2) Survivorship of transplanted seedlings of Picea glauca inside and outside three tree islands in 1994, 1995, 2009 and after 15 years

The northern boundary of boreal forest and the ranges of tree species are expected to shift northward in response to climate warming, which will result in a decrease in the albedo of areas currently covered by tundra vegetation, an increase in terrestrial carbon sequestration, and an alteration of biodiversity in the current Low Arctic. Central to the prediction of forest expansion is an increase in the reproductive capacity and establishment of individual trees. We assessed cone production, seed viability, and transplanted seedling success of Picea glauca (Moench.) Voss. (white spruce) in the early 1990s and again in the late 2000s at four forest stand sites and eight tree island sites (clonal populations beyond present treeline) in the Mackenzie Delta region of the Northwest Territories, Canada. Over the past 20 years, average temperatures in this region have increased by 0.9 °C. This area has the northernmost forest-tundra ecotone in North America and is one of the few circumpolar regions where the northern limit of conifer trees reaches the Arctic Ocean. We found that cone production and seed viability did not change between the two periods of examination and that both variables decreased northward across the forest-tundra ecotone. Nevertheless, white spruce individuals at the northern limit of the forest-tundra ecotone produced viable seeds. Furthermore, transplanted seedlings were able to survive in the northernmost sites for 15 years, but there were no signs of natural regeneration. These results indicate that if climatic conditions continue to ameliorate, reproductive output will likely increase, but seedling establishment and forest expansion within the forest-tundra of this region is unlikely to occur without the availability of suitable recruitment sites. Processes that affect the availability of recruitment sites are likely to be important elsewhere in the circumpolar ecotone, and should be incorporated into models and predictions of climate change and its effects on the northern forest-tundra ecotone.

Deep drilling of glaciers: Russian projects in the Arctic (1975-1995)

The data collection "Deep Drilling of Glaciers: Soviet-Russian projects in Arctic, 1975-1995" was collected by the following basic considerations: - compilation of deep (>100 m) drilling projects on Arctic glaciers, using data of (a) publications; (b) archives of IGRAN; (c) personal communication of project participants; - documentation of parameters, references. Accuracy of data and techniques applied to determine different parameters are not evaluated. The accuracy of some geochemical parameters (up to 1984 and heavy metalls) is uncertain. Most reconstructions of ice core age and of annual layer thickness are discussed; - digitizing of published diagrams (in case, when original numerical data were lost) and subsequent data conversion to equal range series and adjustment to the common units. Therefore, the equal-range series were calculated from original data or converted from digitized chart values as indicated in the metadata. For the methodological purpose, the equal-range series obtained from original and reconstructed data were compared repeatedly; the systematic difference was less then 5-7%. Special attention should be given to the fact, that the data for individual ice core parameters varies, because some parameters were originally measured or registered. Parameters were converted in equal-range series using 2 m steps; - two or more parameter values were determined, then the mean-weighted (i.e. accounting the sample length) value is assigned to the entire interval; - one parameter value was determined, measured or registered independently from the parameter values in depth intervals which over- and underlie it, then the value is assigned to the entire interval; - one parameter value was determined, measured or registered for two adjoining depth intervals, then the specific value is assigned to the depth interval, which represents >75% of sample length ; if each of adjoining depth intervals represents <75% of sample length, then the correspondent parameter value is assigned to both intervals of depth. This collection of ice core data (version 2000) was made available through the EU funded QUEEN project by S.M. Arkhipov, Moscow.

Physico-chemical parameters of sediment core PG1972-1 (09-Tik-03) from a Tundra Lake, Northeastern Siberia

Thermokarst lakes in the Siberian Arctic contain sediment archives that can be used for paleoenvironmental inference. Until now, however, there has been no study from the inner Lena River Delta with a focus on diatoms. The objective of this study was to investigate how the diatom community in a thermokarst lake responded to past limnogeological changes and what specific factors drove variations in the diatom assemblage. We analysed fossil diatom species, organic content, grain-size distribution and elemental composition in a sediment core retrieved in 2009 from a shallow thermokarst lake in the Arga Complex, western Lena River Delta. The core contains a 3,000-year record of sediment accumulation. Shifts in the predominantly benthic and epiphytic diatom species composition parallel changes in sediment characteristics. Paleoenvironmental and limnogeological development, inferred from multiple biological and sedimentological variables, are discussed in the context of four diatom zones, and indicate a strong relation between changes in the diatom assemblage and thermokarst processes. We conclude that limnogeological and thermokarst processes such as lake drainage, rather than direct climate forcing, were the main factors that altered the aquatic ecosystem by influencing, for example, habitat availability, hydrochemistry, and water level.

Wetland maps including open water extent dynamics based on ENVISAT ASAR WS for Siberia, 2007 and 2008, links to GeoTIFFs

Wetlands store large amounts of carbon, and depending on their status and type, they release specific amounts of methane gas to the atmosphere. The connection between wetland type and methane emission has been investigated in various studies and utilized in climate change monitoring and modelling. For improved estimation of methane emissions, land surface models require information such as the wetland fraction and its dynamics over large areas. Existing datasets of wetland dynamics present the total amount of wetland (fraction) for each model grid cell, but do not discriminate the different wetland types like permanent lakes, periodically inundated areas or peatlands. Wetland types differently influence methane fluxes and thus their contribution to the total wetland fraction should be quantified. Especially wetlands of permafrost regions are expected to have a strong impact on future climate due to soil thawing. In this study ENIVSAT ASAR Wide Swath data was tested for operational monitoring of the distribution of areas with a long-term SW near 1 (hSW) in northern Russia (SW = degree of saturation with water, 1 = saturated), which is a specific characteristic of peatlands. For the whole northern Russia, areas with hSW were delineated and discriminated from dynamic and open water bodies for the years 2007 and 2008. The area identified with this method amounts to approximately 300,000 km**2 in northern Siberia in 2007. It overlaps with zones of high carbon storage. Comparison with a range of related datasets (static and dynamic) showed that hSW represents not only peatlands but also temporary wetlands associated with post-forest fire conditions in permafrost regions. Annual long-term monitoring of change in boreal and tundra environments is possible with the presented approach. Sentinel-1, the successor of ENVISAT ASAR, will provide data that may allow continuous monitoring of these wetland dynamics in the future complementing global observations of wetland fraction.

Species and composition of tundra meadows

Observations of hummock and string-like microrelief features were made in High Arctic hydric meadows. Thermal shearing of thick bryophyte mats, and subsequent roll back during spring flooding appears to be one way in which this topography is formed. Hummocky and non-hummocky (flat) meadows show distinct floristic differences which may in part be due to observed differences in temperature, nutrient concentrations and moisture relations.

(Table 1) Effects of desiccation on photochemical processes and nitrogenase activity in Nostoc commune s.l. colonies

The effects of desiccation on photochemical processes and nitrogenase activity were evaluated in Nostoc commune s.l. colonies in situ from a wet thufur meadow at Petuniabukta, Billefjorden, Central Svalbard, during the 2009 arctic summer. The colonies were collected in the fully hydrated state, and were subjected to slow desiccation at ambient temperatures (5 - 8°C) and low light (30 - 80 µmol/m**2/s). For each colony the weight, area, photochemical performance, and nitrogenase activity were determined at the beginning, as well as on every day during the first four days of the experiment; thereafter, on every second day until desiccation was complete. The photochemical performance was evaluated from variable chlorophyll fluorescence parameters (FV/FM, Phi(PSII) , qP, and NPQ), and the nitrogenase activity was estimated by an acetylene-ethylene reduction assay. A significant decrease in the photochemically active area was recorded from the third day, when the colony had lost approximately 40% of its original weight indicating some changes in the extracellular matrix, and stopped on the 14th to 18th day. No effects of the desiccation on the main photochemical parameters (FV/FM, Phi(PSII), qP) were observed up to the sixth to eighth days of desiccation. Slightly lower values of FV/FM and Phi(PSII) recorded in fully-hydrated colonies could be caused by impaired diffusion of CO2 into cells. The steep reduction of photochemical activity occurred between the eighth and tenth day of the experiment, when the colony had lost approximately 80% of its fully-hydrated weight. The nitrogenase activity was highest on the first day, probably due to improved diffusion of N2 into cells, then declined, but was detectable until the sixth day of the experiment. Since Nostoc commune s.l. colonies were capable of photosynthesis and nitrogen fixation to the level of ca. 60% of its fully-hydrated weight, even partly-hydrated colonies contribute substantially to carbon and nitrogen cycling in the High Arctic wet meadow tundra ecosystem.

Environment and habitat characteristics of wintering lemmings in the Arctic

Snow cover has dramatic effects on the structure and functioning of Arctic ecosystems in winter. In the tundra, the subnivean space is the primary habitat of wintering small mammals and may be critical for their survival and reproduction. We have investigated the effects of snow cover and habitat features on the distributions of collared lemming (Dicrostonyx groenlandicus) and brown lemming (Lemmus trimucronatus) winter nests, as well as on their probabilities of reproduction and predation by stoats (Mustela erminea) and arctic foxes (Vulpes lagopus). We sampled 193 lemming winter nests and measured habitat features at all of these nests and at random sites at two spatial scales. We also monitored overwinter ground temperature at a subsample of nest and random sites. Our results demonstrate that nests were primarily located in areas with high micro-topography heterogeneity, steep slopes, deep snow cover providing thermal protection (reduced daily temperature fluctuations) and a high abundance of mosses. The probability of reproduction increased in collared lemming nests at low elevation and in brown lemming nests with high availability of some graminoid species. The probability of predation by stoats was density dependent and was higher in nests used by collared lemmings. Snow cover did not affect the probability of predation of lemming nests by stoats, but deep snow cover limited predation attempts by arctic foxes. We conclude that snow cover plays a key role in the spatial structure of wintering lemming populations and potentially in their population dynamics in the Arctic.

Distribution of diatoms in surface sediments and some limnological characteristics of studied lakes in the Siberian arctic

The investigation of the species composition and ecology of diatoms of modern bottom sediments in water bodies of arctic polygonal tundra in three subregions of North Yakutiya has been carried out. As a result, 161 taxons of diatoms were determined; the determinant role of the depth, conductivity, pH of the water, and geographic latitude in their distribution was confirmed, and two complexes of species with respect to the leading abiotic factors were distinguished. The diatoms of the first complex prefer shallow water bodies of high latitudes with neutral and slightly alkaline water and relatively high conductivity. The second complex is confined to the water bodies of lower latitudes with small conductivity, as well as neutral and slightly acidic water.