Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations

Background: Cerebral dysfunction occurring in mental disorders can show metabolic disturbances which are limited to circumscribed brain areas. Auditory hallucinations have been shown to be related to defined cortical areas linked to specific language functions. Here, we investigated if the study of metabolic changes in auditory hallucinations requires a functional rather than an anatomical definition of their location and size to allow a reliable investigation by magnetic resonance spectroscopy (MRS). Methods: Schizophrenia patients with (AH; n = 12) and without hallucinations (NH; n = 8) and healthy controls (HC; n = 11) underwent a verbal fluency task in functional MRI (fMRI) to functionally define Broca's and Wernicke's areas. Left and right Heschl's gyri were defined anatomically. Results: The mean distances in native space between the fMRI-defined regions and a corresponding anatomically defined area were 12.4 ± 6.1 mm (range: 2.7–36.1 mm) for Broca's area and 16.8 ± 6.2 mm (range: 4.5–26.4 mm) for Wernicke's area, respectively. Hence, the spatial variance was of similar extent as the size of the investigated regions. Splitting the investigations into a single voxel examination in the frontal brain and a spectroscopic imaging part for the more homogeneous field areas led to good spectral quality for almost all spectra. In Broca's area, there was a significant group effect (p = 0.03) with lower levels of N-acetyl-aspartate (NAA) in NH compared to HC (p = 0.02). There were positive associations of NAA levels in the left Heschl's gyrus with total (p = 0.03) and negative (p = 0.006) PANSS scores. In Broca's area, there was a negative association of myo-inositol levels with total PANSS scores (p = 0.008). Conclusion: This study supports the neurodegenerative hypothesis of schizophrenia only in a frontal region whereas the results obtained from temporal regions are in contrast to the majority of previous studies. Future research should test the hypothesis raised by this study that a functional definition of language regions is needed if neurochemical imbalances are expected to be restricted to functional foci.

Tissue metabolomics of hepatocellular carcinoma: Tumor energy metabolism and the role of transcriptomic classification

Hepatocellular carcinoma (HCC) is one of the commonest causes of death from cancer. A plethora of metabolomic investigations of HCC have yielded molecules in biofluids that are both up- and down-regulated but no real consensus has emerged regarding exploitable biomarkers for early detection of HCC. We report here a different approach, a combined transcriptomics and metabolomics study of energy metabolism in HCC. A panel of 31 pairs of HCC tumors and corresponding nontumor liver tissues from the same patients was investigated by gas chromatography-mass spectrometry (GCMS)-based metabolomics. HCC was characterized by ∼2-fold depletion of glucose, glycerol 3- and 2-phosphate, malate, alanine, myo-inositol, and linoleic acid. Data are consistent with a metabolic remodeling involving a 4-fold increase in glycolysis over mitochondrial oxidative phosphorylation. A second panel of 59 HCC that had been typed by transcriptomics and classified in G1 to G6 subgroups was also subjected to GCMS tissue metabolomics. No differences in glucose, lactate, alanine, glycerol 3-phosphate, malate, myo-inositol, or stearic acid tissue concentrations were found, suggesting that the Wnt/β-catenin pathway activated by CTNNB1 mutation in subgroups G5 and G6 did not exhibit specific metabolic remodeling. However, subgroup G1 had markedly reduced tissue concentrations of 1-stearoylglycerol, 1-palmitoylglycerol, and palmitic acid, suggesting that the high serum α-fetoprotein phenotype of G1, associated with the known overexpression of lipid catabolic enzymes, could be detected through metabolomics as increased lipid catabolism. Conclusion: Tissue metabolomics yielded precise biochemical information regarding HCC tumor metabolic remodeling from mitochondrial oxidation to aerobic glycolysis and the impact of molecular subtypes on this process.

GENETIC PREDICTORS OF HYPERGLYCEMIA DUE TO HYDROCHLOROTHIAZIDE THERAPY

Response to pharmacological treatment is variable among individuals. Some patients respond favorably to a drug while others develop adverse reactions. Early investigations showed evidence of variation in genes that code for drug receptors, drug transporters, and drug metabolizing enzymes; and pharmacogenetics appeared as the science that studies the relationship between drug response and genetic variation. Thiazide diuretics are the recommended first-line monotherapy for hypertension (i.e. SBP>140 or DBP>90). Even so, diuretics are associated with adverse metabolic side effects, such as hyperglycemia, which increase the risk of developing type 2 diabetes. Published approaches testing variation in candidate genes (e.g. the renin-angiotensin-aldosteron system (RAAS) and salt–sensitivity genes) have met with only limited success. We conducted the first genome wide association study to identify genes influencing hyperglycemia as an adverse effect of thiazide diuretics in non-Hispanic White hypertensive patients participating in the Genetic Epidemiology of Responses to Antihypertensives (GERA) and Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) clinical trials. No SNP reached the a priori defined threshold of statistical significance (p<5x10-8). We detected 50 SNPs in 9 genomic regions with suggestive p-values (p<1x10-5). Two of them, rs6870564 (p-value=3.28 X 10-6) and rs7702121 (p-value=5.09 X 10-6), were located close to biologic candidate genes, MYO and MGAT1, and one SNP in a genomic region in chromosome 6, rs7762018 (p-value=4.59 X 10-6) has been previously related to Insulin-Dependent Diabetes Mellitus (IDDM8). I conclude that 1) there are unlikely to be common SNPs with large effects on the adverse metabolic effects to hydrochlorothiazide treatment and 2) larger sample sizes are needed for pharmacogenetic studies of inter-individual variation in response to commonly prescribed medication.

Pollen and macroremains from sediment core Aschenhütte

The Upper Pleistocene sediments of the Aschenhütte sink-hole (west of Herzberg am Harz, Lower Saxony) enable one to make interesting correlations between palynological and geological results. The sequence is composed of limnic-telmatic deposits (Eemain to Lower Weichselian) and loess with paleosoils (Weichselian). Sedimentation started during the hornbeam-dominated phase of the Eemian interglacial period and continued throughout the Eemian, the Weichselian Brörup interstadial (sensu Andersen) and parts of the preceding and the following stadial phases, the Herning and the Rederstall stadials. As opposed to most of the known Eemian sites spruce was a major tree species during the hornbeam-dominated phase of the Eemian. The vegetational development during the interstadial phase does not show a period of climatic deterioration as is the case for the Brörup interstadial when considering regions with a more demanding vegetation or regions close to the natural boundaries of the tree species concerned. Pollen or seeds of Bruckenthalia and Picea omoricoides have not been found in the Aschenhütte cores. The limnic-telmatic sediments interlock with loess-paleosoils (Eemian soil and Lower Weichselian bleaching soils) at the lake shore. They are overlaid by loess paleosoils of the Stillfried-B interstadial (Hattorf soil and Lohne soil). Lake level fluctuations were determined by means of the facies distribution and isochrones as defined by pollen analysis. A relatively high stand of the lake level existed after the end of the Eemian interglacial and during the Brörup interstadial periods. In the course of the Herning stadial period the water level dropped, whereas during the Rederstall stadial phase the lake basin was covered by sediments and therefore dried up.

Concentración de benciladenina, tipo y dosis de carbohidratos en el medio de cultivo para proliferación de brotes de Agave americana

Para evaluar la proliferación in vitro de brotes de Agave americana var. oaxacensis, piezas de callo con dos a tres brotes adventicios se establecieron en diversos medios de cultivo con pH 5,8 y consistencia de gel, con sales minerales MS, 100 mg L-1 myo-inositol, diversas concentraciones de benciladenina (BA) (0, 2, 4, 6, 8 y 10 mg L-1), tipo de carbohidrato (sacarosa o jarabe fructosado) y concentración de carbohidrato (20, 30, 40 g). Los cultivos se incubaron 60 días bajo luz fluorescente blanca en 16 h luz/8 h oscuridad, temperatura 20- 28°C. El experimento se estableció según un diseño completamente al azar con arreglo factorial 6x2x3. La sacarosa resultó mejor fuente de carbohidrato que el jarabe fructosado. Los explantos en el medio de cultivo sin BA y 20 g L-1 de sacarosa formaron cuatro brotes de 10,8 cm, con raíces adventicias. Al aumentar la concentración de BA y sacarosa los explantos formaron más brotes, pero en el medio con 6 mg L-1 BA y 40 g L-1 sacarosa los explantos formaron hasta 21 brotes de 6,5 cm de tamaño. La citocinina inhibió la formación de raíces.

Pollen record and lithology of a profile from Dumfriesshire, Scotland

Four samples, G5, G7, G8, and G10, collected by Dr W. W. Bishop from an exposed section in the bank of the River Annan, at Roberthill Farm, Dumfriesshire (S35, 110794) were submitted for pollen analysis (Table I.). The samples, with the exception of the uppermost, were from thin peat layers that lie in the middle of a series of water- laid sands, silts and clays several feet in thickness and now rather strongly arched. The lowermost sample, G5, was taken from an organic layer about | in. thick overlying fine sand and underlying some 2.5 in. of grey, silty fine sand. A narrow layer of sandy peat immediately above the silty, fine sand yielded sample G7, and G8 was collected from a similar peaty layer separated from G7 by more sandy- silty peat. The uppermost sample, G10, was taken from light grey clay 13 in. above sample G8.

Pollen record from Golkow, Poland

Janczyk-Kopikowa (1966): The series of the organic deposits, developed in the vicinity of Golkow near Warsaw as oil shales and peats, was laid down in a grough valley and now rests on the deposits of the Middle Polish Glaciation (Riss). The organic deposits are overlain by the fluviale deposits of the North Polish Glaciation (Würm). The locality Golkow occurs beyond the extent of the continental glacier of this glaciation. Polen analysis completed by microfloristic examinations allows to determine the age of the organic series that is thought to be Eemian. The pollen diagram from Golkow does not call in question the stratigraphical position of the deposits investigated mainly due to its characteristic features such as minimum content of coniferous trees in the climatic optimum - about 5%, high percentage of Corylus - 77.5% and well developed phase of hornbeam. It may be well compared with other Eemian diagrams from the area of Poland and reveals much similar features. The development of vegetation at Golkow has depended upon the prevailing climate. At first, the cool climate brings about the development of plants having small thermal requirements. Here belong thin, park-like forests with pine and birch (Pinus, Betula) accompanied by the heliophilic plants such as Hippohäe and Ephedra. Improvement of climate that becomes warm and humid provides for development of deciduous forests prevailing in the climatic optimum, of the interglacial. Decrease of temperature causes a repeated change in the type of forest. This latter changes into coniferous forest with prevailing spruce (Picea) and fir (Abies) at the beginning, and then with pine (Pinus) and birch (Betula). During the Eemian Interglacial, the development of plants at Golkow terminates with a new and long-lasting predominance of pine-birch forests. However, such a longevity may be apparent only. Apparent character of this phenomenon is proved by a fact that the pollen spectra of the warm climatic periods have found their reflex in the oil shale that increased considerably slower than the layers off feebly decomposed peat evidencing the existence of cool pine-birch forests from the decline of the Interglacial. The water basin, in which the polen grains were laid down from surrounding plants is characterized by a calm sedimentation as proved by the occurrence of the oil shale. An insignificant water flow left behind some thin sand laminae. The not too deep basin becomes shallower owing to the growing water vegetation, and marshy vegetation. The growing of the plants causes a complete shallowing of the basin and formation of peat bog in situ, as proved by the peat beds occurring in the section. ---- Gadomska (1966): In the vicinity of Golków a series of organic deposits occurs amounting to 6.5-9.3 m in thickness, and consisting of oil shales, lacustrine silts and sands, as well as peats and peaty silts. The organic deposits fill up an old, small, but fairly deep lake basin, probably of finger-lake origin. It may be seen to-day as a slight lowering of the relief, filled up with soaked ground, stretching from north to south. On the basis of palaeobotanical examinations the organic deposits considered are of Eemian Interglacial age (Z. Janczyk-Kopikowa, 1063). The lower part of the organic series consists of a compact oil shale horizon, the maximum thickness of which may attain up to 8 m. The oil shales contain particularly in their upper part, numerous intercalations of arenaceous silts, dark grey or black in colour, or of sands mainly of lacustrine provenance. At the top of the oil shales are found peats, up to 2.5 m in thickness, covered by black, humus silts with numerous plant remains. The Eemian Interglacial deposits are covered by a series of fluviatile sands belonging partly to the Baltic Glaciation (bottom part of the series), partly to the Holocene (top part of the series). The thickness of the sands is 0.5-3.7 m. Higher up, there are found the Holocene and present-day deposits developed as clayey alluvion, or arenaceous slide rocks, or arenaceous-silty soil.

Pollen profiles from 8 sediment cores from the Degersee, Southern Germany

The discovery of a neolithic pile field in the shallow water near the eastern shore of the Degersee confirmed earlier palynological and sedimentological studies stating that early man was active in the region since more than 6000 years. The already available off-site data were freshly assessed, completed by additional data from old and new cores and the interpretations revised. A common time scale for the off-site data and the on-site data was obtained by AMS dating of terrestrial macro remains of the neolithic section of off-site core De_I+De_H. The ages can thus be parallelled with AMS ages of construction timber on-site. Pollen analyses from all cores provide a further time scale. The continuously and densely sampled pollen profile of the profundal zone embracing the entire Late glacial and Holocene serves as a reference. From the Boreal onwards the relative ages are transformed by AMS ages and varve counts into calibrated and absolute. A transect cored close to the neolithic pile field across the lake marl-platform demonstrates its geological architecture in the shallow water since the Lateglacial. Studies of the microfabric of thin sections of drilled cores and of box cores from the excavations demonstrate that neolithic settlements now at 2-3,5 m water depth had been erected on lake marl freshly fallen dry, thus indicating earlier lake levels dropped by 1.5-2 m. The neolithic section of the highly resolved off-site profile in the lake=s profundal zone has laminated and calcareous zones alternating with massive ones. Assemblages of diatoms and concentrations of trace elements changing simultaneously characterise the calcareous sections as deposits of low lake levels that lasted between some 40 and more than 300 years. The ages of discovered lake shore dwellings fall into calcareous segments with low lake levels. From the end of the Upper Atlantic period (F VII) appear Secondary Forest Cycles in the beech forest, a man-made sequence of repeated vegetational development with an identical pattern: With a decrease of beech pollen appear pollen of grasses, herbs and cultural indicators. These are suppressed by the light demanding hazel and birch, those again by ash, and finally by the shade demanding beech forming a new pollen peak. Seven main Forest Cycles are identified In the upper Neolithic period each comprising some 250, 450 or 800 years. They are subdivided into subcycles that can be broken down by very dense sampling in even shorter cycles of decadal length. Farming settlers have caused minor patchy clearances of the beech-mixed-forest with the use of fire. The phases of clearance coincide with peaks of charcoal and low stands of the lake levels. The Secondary Forest Cycles and the continuous occurrence of charcoal prove a continued occupation of the region. Together with the repeated restoration of the beech climax forest they point to pulsating occupation probably associated with dynamic demography. The synchronism of the many palynological, sedimentological and archaeological data point to an external forcing as the climate that affects comprehensively all these proxies. The fluctuations of the activity of the sun as manifested in the residual d14C go largely along with the proxies. The initial clearances at the begin of the forest cycles are linked to low lake levels and negative values of d14C that point to dry and warm phases of a more continental climate type. The subcycles exist independent from climatic changes, indicating that early man acted largely independent from external forces.

Pollen records and age determination of site Bokanjacko Blato

In summary, one may conclude that human influence in the Bokanjac area started in the Eneolithic or Earlier Bronze Age - the third to second millennia Cal. BC. Traces of agriculture are weak or missing in the pollen diagram but grazing is indicated. Chestnut and walnut were introduced by humans to the area in classical times. These findings are in general agreement with the results of earlier studies at coastal sites north-west and south-east of Bokanjacko Blato.

High-resolution multi-proxy record of the last glacial period from Lake Van, eastern Anatolian high plateau, Turkey

Detailed analyses of the Lake Van pollen, Ca/K ratio and stable oxygen isotope record allow the identification of millennial-scale vegetation and environmental changes in eastern Anatolia throughout the last glacial (~75-15 ka BP). The climate within the last glacial was cold and dry, with low arboreal pollen (AP) levels. The driest and coldest period corresponds to Marine Isotope Stage (MIS) 2 (~28-14.5 ka BP) dominated by the highest values of xerophytic steppe vegetation. Our high-resolution multi proxy record shows rapid expansions and contractions of tree populations that reflects variability in temperature and moisture availability. This rapid vegetation and environmental changes can be linked to the stadial-interstadial pattern of the Dansgaard-Oeschger (DO) events as recorded in the Greenland ice cores. Periods of reduced moisture availability were characterized by enhanced xerophytic species and high terrigenous input from the Lake Van catchment area. Furthermore, comparison with the marine realm reveals that the complex atmosphere-ocean interaction can be explained by the strength and position of the westerlies, which is responsible for the supply of humidity in eastern Anatolia. Influenced by diverse topography of the Lake Van catchment, larger DO interstadials (e.g. DO 19, 17-16, 14, 12 and 8) show the highest expansion of temperate species within the last glacial. However, Heinrich events (HE), characterized by highest concentrations of ice-rafted debris (IRD) in marine sediments, are identified in eastern Anatolia by AP values not lower and high steppe components not more abundant than during DO stadials. In addition, this work is a first attempt to establish a continuous microscopic charcoal record over the last glacial in the Near East, which documents an initial immediate response to millennial-scale climate and environmental variability and enables us to shed light on the history of fire activity during the last glacial.

Abundance of plant macrofossils, mollusca and ostracoda in sediments obtained near Tessin, north Germany

A depression filled with Late Glacial and Holocene sediments was excavated during the geological exploration and recovery of a dump area near Tessin close to Rostock, and initiated the studies of the present paper. Pebble analysis of three exposed or respectively drilled till horizons as well as pollenanalytical, carpological and faunistical studies carried out allow the stratigraphical subdivision of the Quaternary sequence of the dump area. The basal till was probably the result of dead ice decay, and was lithostratigraphically assigned to the Pomerian Stage (qw2). The palynological results of boreholes RKS 19/93 and A/92 reveal pre-Allerod and other sediments instead of the expected interweichselian deposits. Based on the palynological and carpological findings, we correlated the beginning of the late glacial development in the locality with the end of the Meiendorf-lnterstadial sensu Menke in Bock et al. (1985, doi:10.3285/eg.35.1.18). The limnic-telmatic sedimentation could be observed pollen floristically probably starting with the Meiendorf-lnterstadial (Hippophae-Betula nana-phase) followed by the Bolling-(Betula nana-B. alba s.l.-Artemisia-Helianthemum-Poaceae-phase) and the Allerad-lnterstadial [Betula alba s.l.-(Pinus)-Cyperaceae-phase] lasting up to the Younger Dryas (Juniperus-Artemisia-Poaceae-phase). Sedimentation closed during the Younger Dryas with the accumulation of fine sands. It was reactivated later during the Holocene due to the anthropogene influence (Older and Younger Subatlantic, dampness of the depression by clearing).

Palynology and radiocarbon dating on sediment profile PG1756 from Lake Billyakh, NE Siberia, Russia

In this study a radiocarbon-dated pollen record from Lake Billyakh (65°17'N, 126°47'E; 340 m a.s.l.) in the Verkhoyansk Mountains was used to reconstruct vegetation and climate change since about 15 kyr BP (1 kyr=1000 cal. yr). The pollen record and pollen-based biome reconstruction suggest that open cool steppe and grass and sedge tundra communities with Poaceae, Cyperaceae, Artemisia, Chenopodiaceae, Caryophyllaceae and Selaginella rupestris dominated the area from 15 to 13.5 kyr BP. On the other hand, the constant presence of Larix pollen in quantities comparable to today's values points to the constant presence of boreal deciduous conifer trees in the regional vegetation during the last glaciation. A major spread of shrub tundra communities, including birch (Betula sect. Nanae), alder (Duschekia fruticosa) and willow (Salix) species, is dated to 13.5-12.7 kyr BP, indicating a noticeable increase in precipitation toward the end of the last glaciation, particularly during the Allerød Interstadial. Between 12.7 and 11.4 kyr BP pollen percentages of herbaceous taxa rapidly increased, whereas shrub taxa percentages decreased, suggesting strengthening of the steppe communities associated with the relatively cold and dry Younger Dryas Stadial. However, the pollen data in hand indicate that Younger Dryas climate was less severe than the climate during the earlier interval from 15 to 13.5 kyr BP. The onset of the Holocene is marked in the pollen record by the highest values of shrub and lowest values of herbaceous taxa, suggesting a return of warmer and wetter conditions after 11.4 kyr BP. Percentages of tree taxa increase gradually and reach maximum values after 7 kyr BP, reflecting the spread of boreal cold deciduous and taiga forests in the region. An interval between 7 and 2 kyr BP is noticeable for the highest percentages of Scots spine (Pinus subgen. Diploxylon), spruce (Picea) and fir (Abies) pollen, indicating mid-Holocene spread of boreal forest communities in response to climate amelioration and degradation of the permafrost layer.

High-resolution multi-proxy record of the last interglacial period from Lake Van, eastern Anatolian high plateau, Turkey

A high-resolution multi-proxy record from Lake Van, eastern Anatolia, derived from a lacustrine sequence cored at the 357 m deep Ahlat Ridge (AR), allows a comprehensive view of paleoclimate and environmental history in the continental Near East during the last interglacial (LI). We combined paleovegetation (pollen), stable oxygen isotope (d18Obulk) and XRF data from the same sedimentary sequence, showing distinct variations during the period from 135 to 110 ka ago leading into and out of full interglacial conditions. The last interglacial plateau, as defined by the presence of thermophilous steppe-forest communities, lasted ca. 13.5 ka, from ~129.1-115.6 ka BP. The detailed palynological sequence at Lake Van documents a vegetation succession with several climatic phases: (I) the Pistacia zone (ca. 131.2-129.1 ka BP) indicates summer dryness and mild winter conditions during the initial warming, (II) the Quercus-Ulmus zone (ca. 129.1-127.2 ka BP) occurred during warm and humid climate conditions with enhanced evaporation, (III) the Carpinus zone (ca. 127.2-124.1 ka BP) suggest increasingly cooler and wetter conditions, and (IV) the expansion of Pinus at ~124.1 ka BP marks the onset of a colder/drier environment that extended into the interval of global ice growth. Pollen data suggest migration of thermophilous trees from refugial areas at the beginning of the last interglacial. Analogous to the current interglacial, the migration documents a time lag between the onset of climatic amelioration and the establishment of an oak steppe-forest, spanning 2.1 ka. Hence, the major difference between the last interglacial compared to the current interglacial (Holocene) is the abundance of Pinus as well as the decrease of deciduous broad-leaved trees, indicating higher continentality during the last interglacial. Finally, our results demonstrate intra-interglacial variability in the low mid-latitudes and suggest a close connection with the high-frequency climate variability recorded in Greenland ice cores.

AMS radiocarbon dates and pollen analysis of ODP Hole 175-1078C

ODP Site 1078 situated under the coast of Angola provides the first record of the vegetation history for Angola. The upper 11 m of the core covers the past 30 thousand years, which has been analysed palynologically in decadal to centennial resolution. Alkenone sea surface temperature estimates were analysed in centennial resolution. We studied sea surface temperatures and vegetation development during full glacial, deglacial, and interglacial conditions. During the glacial the vegetation in Angola was very open consisting of grass and heath lands, deserts and semi-deserts, which suggests a cool and dry climate. A change to warmer and more humid conditions is indicated by forest expansion starting in step with the earliest temperature rise in Antarctica, 22 thousand years ago. We infer that around the period of Heinrich Event 1, a northward excursion of the Angola Benguela Front and the Congo Air Boundary resulted in cool sea surface temperatures but rain forest remained present in the northern lowlands of Angola. Rain forest and dry forest area increase 15 thousand years ago. During the Holocene, dry forests and Miombo woodlands expanded. Also in Angola globally recognised climate changes at 8 thousand and 4 thousand years ago had an impact on the vegetation. During the past 2 thousand years, savannah vegetation became dominant.

Pollen record and age determination of a sediment profile from Schmiechener See, Germany

Die untersuchten Schluffe und Kiese sind unter kaltzeitlichen Bedingungen in einem See mit Schwimmpflanzengesellschaften abgelagert worden. Zur Sedimentationszeit gab es in der Umgebung des Sees eine tundrenartige Vegetation, die auch Steppenarten enthielt.