Role of lipase in the regulation of upper gastrointestinal function in humans.

The role of lipase in the regulation of upper gastrointestinal function is poorly understood. We studied the effect of orlistat, a new, potent, and highly specific lipase inhibitor, on gastric emptying, cholecystokinin (CCK) release, and pancreaticobiliary secretion. Three groups of studies were performed in nine healthy volunteers, using the double-indicator technique with a triple-lumen duodenal tube, polyethylene glycol 4000 as a duodenal perfusion marker, and 99mTc-diethylenetriamine pentaacetic acid as a meal marker. Gastric emptying, pancreaticobiliary output, and postprandial plasma CCK levels were measured after ingestion of the following isocaloric 500-ml liquid meals with or without 200 mg orlistat: 1) a pure fat meal (10% Intralipid), 2) a meal containing free fatty acids, or 3) an albumin-glucose meal. All experiments were performed in a randomized, placebo-controlled, crossover design. Orlistat markedly inhibited lipase activity in all three experiments. Orlistat given with the fat meal reduced CCK release and output of lipase, trypsin, and bilirubin and accelerated the rate of gastric emptying (P < 0.05). After ingestion of the free fatty acid or albumin-glucose meal, orlistat had no significant effect on any of these parameters. We conclude that lipase plays an important, nutrient-specific role in the regulation of gastric emptying and pancreaticobiliary secretion after ingestion of fatty meals in humans.

Single Subject Finger Somatotopy Mapping at 7T.

Introduction: The primary somatosensory cortex (SI) contains Brodmann areas (BA) 1, 2, 3a, and 3b. Research in non-human primates showed that BAs 3b, 1, and 2 each contain one full representation of the hand with separate representations for each finger. This research also showed that the finger representation in BA3b has larger and clearer finger somatotopy than BA1 and 2. Although several efforts to map finger somatotopy in SI by fMRI have been made at 1.5 and 3T these studies have yielded variable results and were not able to detect single subject finger somatotopy, probably due to the limited spatial extent of the cortical areas representing a digit (close to the resolution in most fMRI experiments), complications due to acquisition of consistent maps for individual subjects (Schweizer et al 2008), or inter-individual variability in sulcal anatomy impeding group studies. Here, we used 7T fMRI to investigate finger somatotopy in SI, some of its functional characteristics, and its reproducibility. Methods: Eight right-handed male subjects were scanned on a 7T scanner (Siemens Medical, Germany) with an 8-channel Tx/Rx rf-coil (Rapid Biomedical, Germany). 1.3x1.3x1.3mm3 resolution fMRI data were acquired using a sinusoidal readout EPI sequence (Speck et al, 2008) and FOV=210mm, TE/TR=27ms/2.5s, GRAPPA=2. Each volume contained 28 transverse slices covering SI. A single EPI volume with 64 slices was acquired to aid coregistration. 1x1x1mm3 anatomical data were acquire using the MP2RAGE sequence (Marques et al, 2009; TE/TR/TI1,2/TRmprage=2.63ms/7.2ms/0.9,3.2s/5s). Subjects were positioned supine in the scanner with their right arm comfortably against the magnet bore. An experimenter was positioned at the entrance of the bore where he could easily reach and stroke successively the two distal phalanxes of each digit. The order of stroked digit was D1 (thumb)-D3-D5-D2-D4, with 20s ON, 10s OFF alternated. This sequence was repeated four times per run and two functional runs were acquired per subject. Realignment, smoothing (FWHM 2 mm), coregistration of the anatomical to the fMRI data and calculation of t-statistics were done using SPM8. An SI mask was obtained via an F-contrast (p<0.001) over all digits. Within the mask, voxels were labeled with the number of the digit demonstrating the highest t-value for that particular voxel. Results: For all subjects, areas corresponding to the five digits were identified in contralateral SI. BA3b showed the most consistent somatotopic finger representation (see an example in Fig.1). The five digits were localized in a consecutive order in the cortex, with D1 most anterior, inferior and distal and D5, most posterior, superior and medial (mean distance between centres of mass of digit representations ±stderr: 4.2±0.7mm; see Fig. 2). The analysis of average beta values within each finger representation region revealed the specificity of the somatotopic region to the tactile input for each tested finger (except digit 4 and 5). Five of these subjects also presented an orderly and consecutive representation of the five digits in BA1 and 2. Conclusions: Our data reveal that the increased BOLD sensitivity at 7T and the high spatial resolution used in this study allow consistent somatotopic mapping using human touch as a stimulus and that human SI contains at least three separate regions that contain five separate representations of all single contralateral fingers. Moreover, adjacent fingers were represented at adjacent cortical regions across the three SI regions. The spatial organization of SI as reflected in individual subject topography corresponds well with previous electrophysiological data in non-human primates. The small distance between digit representations highlights the need for the high spatial resolution available at 7T.

Some reflections on Geobotany and Vegetation mapping

uivalent Spanish and Catalan terms.

Mapping cell-matrix stresses during stretch reveals inelastic reorganization of the cytoskeleton.

The mechanical properties of the living cell are intimately related to cell signaling biology through cytoskeletal tension. The tension borne by the cytoskeleton (CSK) is in part generated internally by the actomyosin machinery and externally by stretch. Here we studied how cytoskeletal tension is modified during stretch and the tensional changes undergone by the sites of cell-matrix interaction. To this end we developed a novel technique to map cell-matrix stresses during application of stretch. We found that cell-matrix stresses increased with imposition of stretch but dropped below baseline levels on stretch release. Inhibition of the actomyosin machinery resulted in a larger relative increase in CSK tension with stretch and in a smaller drop in tension after stretch release. Cell-matrix stress maps showed that the loci of cell adhesion initially bearing greater stress also exhibited larger drops in traction forces after stretch removal. Our results suggest that stretch partially disrupts the actin-myosin apparatus and the cytoskeletal structures that support the largest CSK tension. These findings indicate that cells use the mechanical energy injected by stretch to rapidly reorganize their structure and redistribute tension.

Descriptive epidemiology of Cornelia de Lange syndrome in Europe.

Cornelia de Lange syndrome (CdLS) is a multiple congenital anomaly/mental retardation syndrome consisting of characteristic dysmorphic features, microcephaly, hypertrichosis, upper limb defects, growth retardation, developmental delay, and a variety of associated malformations. We present a population-based epidemiological study of the classical form of CdLS. The data were extracted from the database of European Surveillance of Congenital Anomalies (EUROCAT) database, a European network of birth defect registries which follow a standard methodology. Based on 23 years of epidemiologic monitoring (8,558,346 births in the 1980-2002 period), we found the prevalence of the classical form of CdLS to be 1.24/100,000 births or 1:81,000 births and estimated the overall CdLS prevalence at 1.6-2.2/100,000. Live born children accounted for 91.5% (97/106) of cases, fetal deaths 2.8% (3/106), and terminations of pregnancy following prenatal diagnosis 5.7% (6/106). The most frequent associated congenital malformations were limb defects (73.1%), congenital heart defects (45.6%), central nervous system malformations (40.2%), and cleft palate (21.7%). In the last 11 years, as much as 68% of cases with major malformations were not detected by routine prenatal US. Live born infants with CdLS have a high first week survival (91.4%). All patients were sporadic. Maternal and paternal age did not seem to be risk factors for CdLS. Almost 70% of patients, born after the 37th week of gestation, weighed <or=2,500 g. Low birth weight correlated with a more severe phenotype. Severe limb anomalies were significantly more often present in males.

Genesis and classification of Oxisols in a highland toposequence of the upper Jequitinhonha Valley (MG)

The Brazilian System of Soil Classification (SiBCS) is a taxonomic system, open and in permanent construction, as new knowledge on Brazilian soils is obtained. The objective of this study was to characterize the chemical, physical, morphological, micro-morphological and mineralogical properties of four pedons of Oxisols in a highland toposequence in the upper Jequitinhonha Valley, emphasizing aspects of their genesis, classification and landscape development. The pedons occupy the following slope positions: summit - Red Oxisol (LV), mid slope (upper third) - Yellow-Red Oxisol (LVA), lower slope (middle third)- Yellow Oxisol (LA) and bottom of the valley (lowest third) - "Gray Oxisol" ("LAC"). These pedons were described and sampled for characterization in chemical and physical routine analyses. The total Fe, Al and Mn contents were determined by sulfuric attack and the Fe, Al and Mn oxides in dithionite-citrate-bicarbonate and oxalate extraction. The mineralogy of silicate clays was identified by X ray diffraction and the Fe oxides were detected by differential X ray diffraction. Total Ti, Ga and Zr contents were determined by X ray fluorescence spectrometry. The "LAC" is gray-colored and contains significant fragments of structure units in the form of a dense paste, characteristic of a gleysoil, in the horizons A and BA. All pedons are very clayey, dystrophic and have low contents of available P and a pH of around 5. The soil color was related to the Fe oxide content, which decreased along the slope. The decrease of crystalline and low- crystalline Fe along the slope confirmed the loss of Fe from the "LAC". Total Si increased along the slope and total Al remained constant. The clay fraction in all pedons was dominated by kaolinite and gibbsite. Hematite and goethite were identified in LV, low-intensity hematite and goethite in LVA, goethite in LA. In the "LAC", no hematite peaks and goethite were detected by differential X ray diffraction. The micro-morphology indicated prevalence of granular microstructure and porosity with complex stacking patterns.. The soil properties in the toposequence converged to a single soil class, the Oxisols, derived from the same source material. The landscape evolution and genesis of Oxisols of the highlands in the upper Jequitinhonha Valley are related to the evolution of the drainage system and the activity of excavating fauna.

Interactome mapping of the phosphatidylinositol 3-kinase-mammalian target of rapamycin pathway identifies deformed epidermal autoregulatory factor-1 as a new glycogen synthase kinase-3 interactor.

The phosphatidylinositol 3-kinase-mammalian target of rapamycin (PI3K-mTOR) pathway plays pivotal roles in cell survival, growth, and proliferation downstream of growth factors. Its perturbations are associated with cancer progression, type 2 diabetes, and neurological disorders. To better understand the mechanisms of action and regulation of this pathway, we initiated a large scale yeast two-hybrid screen for 33 components of the PI3K-mTOR pathway. Identification of 67 new interactions was followed by validation by co-affinity purification and exhaustive literature curation of existing information. We provide a nearly complete, functionally annotated interactome of 802 interactions for the PI3K-mTOR pathway. Our screen revealed a predominant place for glycogen synthase kinase-3 (GSK3) A and B and the AMP-activated protein kinase. In particular, we identified the deformed epidermal autoregulatory factor-1 (DEAF1) transcription factor as an interactor and in vitro substrate of GSK3A and GSK3B. Moreover, GSK3 inhibitors increased DEAF1 transcriptional activity on the 5-HT1A serotonin receptor promoter. We propose that DEAF1 may represent a therapeutic target of lithium and other GSK3 inhibitors used in bipolar disease and depression.

An inventory of the marine and transitional Middle/Upper Eocene deposits of the Southeastern Pyrenean Foreland Basin (NE Spain)

In the southeastern Ebro Foreland Basin, the marine deposits of Lutetian and Bartonian age show excellent outcrop conditions, with a great lateral and horizontal continuity of lithostratigraphic units. In addition, the rich fossil record -mainly larger foraminifers-, provides biostratigraphic data of regional relevance for the whole Paleogene Pyrenean Basin, that can be used for the Middle Eocene biocorrelation of the western Tethys. This contribution is a sedimentary and biostratigraphic synthesis of the basic outcrops and sections of the Lutetian andBartonian marine and transitional deposits in the southeastern sector of the Ebro Foreland Basin.

Marine and transitional Middle/Upper Eocenen units of the Southeastern Pyrenean Foreland Basin (NE Spain)

The stratigraphic basis of this work has allowed the use of larger foraminifers in the biostratigraphic characterisation of the new Shallow Benthic Zones (SBZ). This part of the volume presents a description of the sedimentary cycles formed by the transgressive-regressive systems of the Lutetian and Bartonian in the southeastern sector of the Ebro Foreland Basin. Concerning the Lutetian deposits studied in the Amer-Vic and Empordà areas, four sedimentary cycles have been characterised. The first and second are found within the Tavertet/Girona Limestone Formation (Reguant, 1967; Pallí, 1972), while the third and fourth cycles cover the Coll de Malla Marl Formation (Clavell et al., 1970), the Bracons Formation (Gich, 1969, 1972), the Banyoles Marl Formation (Almela and Ríos, 1943), and the Bellmunt Formation (Gich, 1969, 1972). In the Bartonian deposits studied in the Igualada area, two transgressive-regressive sedimentary cycles have been characterised in the Collbàs Formation (Ferrer, 1971), the Igualada Formation (Ferrer, 1971), and the Tossa Formation (Ferrer, 1971). The Shallow Benthic Zones (SBZs) recognised within the Lutetian are the following: SBZ 13, from the Early Lutetian, in the transgressive system of the first cycle; SBZ 14, from the Middle Lutetian, in the second cycle and the lower part of the transgressive system of the third cycle; SBZ 15, from the Middle Lutetian, in the remaining parts of the third system; SBZ 16, from the Late Lutetian, throughout the fourth cycle. The association of larger foraminifers in the first and second cycles of the Bartonian in the Igualada area has been used as the basis for the definition of SBZs 17 and 18 recognised in the Bartonian of the western Tethys.

Upper Cretaceous (Santonian-Campanian) radiolarians from Voronesh Anticline, southwestern Russia

Core-samples from wells and an outcrop located on the Voronesh Anticline in the southeastern part of the Russian Platform contain Late Cretaceous radiolaria. 83 species are described and illustrated (SEM and transmitted light images) from Santonian-early Campanian deposits, and two assemblages are distinguished. The older assemblage with Alievium gallowayi, Archaeospongoprunum bipartitum, Archaeospongoprunum. cf. A. salumi as well as other less age-diagnostic taxa, is interpreted as Santonian correlative with the Euchitonia santonica-Alievium gallowayi Assemblage Zone of the Moscow Basin (Vishnevskaya 1993). The younger assemblage, of Santonian - early Campanian age, contains Patulibracchium cf. P. davisi, Crucella irwini, Cryptamphorella sphaerica, Praeconocaryomma californiensis, Dictyomitra lamellicostata among other species and is correlative with the Orbiculiforma quadrata-Lithostrobus rostovtsevi Assemblage Zone of the Moscow Basin. In terms of inter-regional faunal comparisons, both of the Voronesh Anticline radiolarian assemblages demonstrate relatively close affinities to coeval rocks from the Volga River region, but less similarity to the assemblages from the Moscow Basin. Only a few of the common endemic species of Siberian assemblages occur in our samples. On an inter-regional level, the radiolarian assemblages described herein have similarities with assemblages reported from Japan and California. Index-species characteristic for the Santonian-Campanian radiolarian biozonations of the Atlantic and Pacific Oceans are not found in our collection. However, the presence of many cosmopolitan species known from the European Platform, Japan and California suggests a marine connection between the Voronesh Anticline region, the western Atlantic and eastern Tethys during Santonian-Early Campanian time.

The contribution of rectangularization to the secular increase of life expectancy: an empirical study.

BACKGROUND: In low-mortality countries, life expectancy is increasing steadily. This increase can be disentangled into two separate components: the delayed incidence of death (i.e. the rectangularization of the survival curve) and the shift of maximal age at death to the right (i.e. the extension of longevity). METHODS: We studied the secular increase of life expectancy at age 50 in nine European countries between 1922 and 2006. The respective contributions of rectangularization and longevity to increasing life expectancy are quantified with a specific tool. RESULTS: For men, an acceleration of rectangularization was observed in the 1980s in all nine countries, whereas a deceleration occurred among women in six countries in the 1960s. These diverging trends are likely to reflect the gender-specific trends in smoking. As for longevity, the extension was steady from 1922 in both genders in almost all countries. The gain of years due to longevity extension exceeded the gain due to rectangularization. This predominance over rectangularization was still observed during the most recent decades. CONCLUSIONS: Disentangling life expectancy into components offers new insights into the underlying mechanisms and possible determinants. Rectangularization mainly reflects the secular changes of the known determinants of early mortality, including smoking. Explaining the increase of maximal age at death is a more complex challenge. It might be related to slow and lifelong changes in the socio-economic environment and lifestyles as well as population composition. The still increasing longevity does not suggest that we are approaching any upper limit of human longevity.

Highlands of the upper Jequitinhonha valley, Brazil: I - characterization and classification

In the upper Jequitinhonha valley, state of Minas Gerais, Brazi, there are large plane areas known as "chapadas", which are separated by areas dissected by tributaries of the Jequitinhonha and Araçuaí rivers. These dissected areas have a surface drainage system with tree, shrub, and grass vegetation, more commonly known as "veredas", i.e., palm swamps. The main purpose of this study was to characterize soil physical, chemical and morphological properties of a representative toposequence in the watershed of the Vereda Lagoa do Leandro, a swamp near Minas Novas, MG, on "chapadas", the highlands of the Alto Jequitinhonha region Different soil types are observed in the landscape: at the top - Typic Haplustox (LVA), in the middle slope - Xanthic Haplustox (LA), at the footslope - Xanthic Haplustox, gray color, here called "Gray Haplustox" ("LAC") and, at the bottom of the palm swamp - Typic Albaquult (GXbd). These soils were first morphologically described; samples of disturbed and undisturbed soils were collected from all horizons and subhorizons, to evaluate their essential physical and chemical properties, by means of standard determination of Fe, Al, Mn, Ti and Si oxides after sulfuric extraction. The contents of Fe, Al and Mn, extracted with dithionite-citrate-bicarbonate and oxalate treatments, were also determined. In the well-drained soils of the slope positions, the typical morphological, physical and chemical properties of Oxisols were found. The GXbd sample, from the bottom of the palm swamp, is grayish and has high texture gradient (B/A) and massive structure. The reduction of the proportion of crystalline iron compounds and the low crystallinity along the slope confirmed the loss of iron during pedogenesis, which is reflected in the current soil color. The Si and Al contents were lowest in the "LAC" soil. There was a decrease of the Fe2O3/TiO2 ratio downhill, indicating progressive drainage restriction along the toposequence. The genesis and all physical and chemical properties of the soils at the footslope and the bottom of the palm swamp of the "chapadas" of the Alto Jequitinhonha region are strongly influenced by the occurrence of ground water on the surface or near the surface all year long, at present and/or in the past. Total concentrations of iron oxides, Fe d and Fe o in soils of the toposequence studied are related to the past and/or present soil colors and drainage conditions.