Mid-Holocene marine faunas from the Bangkok Clay deposits in Nakhon Nayok, the Central Plain of Thailand.

Based on several field investigations, many molluscan shells and chondrichthyan teeth, together with other invertebrate and actinopterygian remains were found from the marine Bangkok Clay deposits in Ongkharak, Nakhon Nayok, at a depth of ~ 5-7 m below the topsoil surface. Animal macrofossils recovered from these Holocene marine deposits were identified and their chronological context was investigated in order to reconstruct the paleoenvironments of the area at that time. The majority of marine fossils recovered from the site consist of molluscs, with a total of 63 species identified. Other invertebrate species include a stony coral, a mud lobster, barnacles, and a sea urchin. The vertebrates are represented by fish remains, including carcharhinid shark teeth from at least nine species, stingray and trichiurid teeth, and one sciaenid otolith. The molluscan fauna indicates that the paleoenvironments of the area corresponded to intertidal to sublittoral zones, where some areas were mangrove forests and intertidal mudflats. The fish fauna is dominated by the river shark Glyphis, indicating freshwater influences and possibly occasional brackish conditions. The carbon-14 analysis of mollusc and charcoal remains shows that deposition of the marine sediment sequence began during the mid-Holocene, spanning approximately from 8,800 to 5,300 cal yr BP. This study provides in-depth insights into the diversity of fishes, marine molluscs, and other invertebrates from the Bangkok Clay deposits, supporting the existence of a marine transgression onto the Lower Central Plain of Thailand during the mid-Holocene.

First fossil-leaf floras from Brunei Darussalam show dipterocarp dominance in Borneo by the Pliocene.

The Malay Archipelago is one of the most biodiverse regions on Earth, but it suffers high extinction risks due to severe anthropogenic pressures. Paleobotanical knowledge provides baselines for the conservation of living analogs and improved understanding of vegetation, biogeography, and paleoenvironments through time. The Malesian bioregion is well studied palynologically, but there have been very few investigations of Cenozoic paleobotany (plant macrofossils) in a century or more. We report the first paleobotanical survey of Brunei Darussalam, a sultanate on the north coast of Borneo that still preserves the majority of its extraordinarily diverse, old-growth tropical rainforests. We discovered abundant compression floras dominated by angiosperm leaves at two sites of probable Pliocene age: Berakas Beach, in the Liang Formation, and Kampong Lugu, in an undescribed stratigraphic unit. Both sites also yielded rich palynofloral assemblages from the macrofossil-bearing beds, indicating lowland fern-dominated swamp (Berakas Beach) and mangrove swamp (Kampong Lugu) depositional environments. Fern spores from at least nine families dominate both palynological assemblages, along with abundant fungal and freshwater algal remains, rare marine microplankton, at least four mangrove genera, and a diverse rainforest tree and liana contribution (at least 19 families) with scarce pollen of Dipterocarpaceae, today's dominant regional life form. Compressed leaves and rare reproductive material represent influx to the depocenters from the adjacent coastal rainforests. Although only about 40% of specimens preserve informative details, we can distinguish 23 leaf and two reproductive morphotypes among the two sites. Dipterocarps are by far the most abundant group in both compression assemblages, providing rare, localized evidence for dipterocarp-dominated lowland rainforests in the Malay Archipelago before the Pleistocene. The dipterocarp fossils include winged Shorea fruits, at least two species of plicate Dipterocarpus leaves, and very common Dryobalanops leaves. We attribute additional leaf taxa to Rhamnaceae (Ziziphus), Melastomataceae, and Araceae (Rhaphidophora), all rare or new fossil records for the region. The dipterocarp leaf dominance contrasts sharply with the family's <1% representation in the palynofloras from the same strata. This result directly demonstrates that dipterocarp pollen is prone to strong taphonomic filtering and underscores the importance of macrofossils for quantifying the timing of the dipterocarps' rise to dominance in the region. Our work shows that complex coastal rainforests dominated by dipterocarps, adjacent to swamps and mangroves and otherwise similar to modern ecosystems, have existed in Borneo for at least 4-5 million years. Our findings add historical impetus for the conservation of these gravely imperiled and extremely biodiverse ecosystems.

Model-based evaluation of the microhemodynamic effects of PEGylated HBOC molecules in the rat brain cortex: a laser speckle imaging study.

Hemoglobin-based oxygen carriers (HBOCs) were developed with the aim of substituting transfusions in emergency events. However, they exhibit adverse events, such as nitric oxide (NO) scavenging, vasoactivity, enhanced platelet aggregation, presently hampering their clinical application. The impact of two prototypical PEGylated HBOCs, Euro-PEG-Hb and PEG-HbO2, endowed by different oxygen affinities and hydrodynamic volumes, was assessed on the cerebrocortical parenchymal microhemodynamics, and extravasation through the blood-brain-barrier (BBB) by laser speckle contrast imaging (LSCI) method and near-infrared (NIR) imaging, respectively. By evaluating voxel-wise cerebrocortical red blood cell velocity, non-invasively for its mean kernel-wise value ( v ¯ RBC ), and model-derived kernel-wise predictions for microregional tissue hematocrit, THt, and fractional change in hematocrit-corrected vascular resistance, R', as measures of potential adverse effects (enhanced platelet aggregation and vasoactivity, respectively) we found i) no significant difference between tested HBOCs in the systemic and microregional parameters, and in the relative spatial dispersion of THt, and R' as additional measures of HBOC-related adverse effects, and ii) no extravasation through BBB by Euro-PEG-Hb. We conclude that Euro-PEG-Hb does not exhibit adverse effects in the brain microcirculation that could be directly attributed to NO scavenging.

Genetic diversity and parentage analysis of grape rootstocks.

KEY MESSAGE: The maternal and paternal parentage of 36 rootstocks was determined and verified. The results of this study indicate that existing grape rootstocks are closely related to each other and have a narrow genetic background. Rootstocks are used to protect grapevines from biotic and abiotic stresses including phylloxera, nematodes, viruses, limestone-based soils, salinity and drought. The most important rootstocks were developed from three grape species between the 1890s and the 1930s in European breeding programs. In this report, we developed nuclear and chloroplast SSR fingerprint data from rootstock selections maintained in germplasm collections, compared them to develop a reference dataset, and carried out parentage analysis to resolve previously reported, and determine new, breeding records. We refined and updated the parentage of 26 rootstocks based on 21 nuclear and 14 chloroplast markers. Results indicate that 39% of the genetic background of analyzed rootstocks originated from only three accessions of three grape species: Vitis berlandieri cv. Rességuier 2, V. rupestris cv. du Lot and V. riparia cv. Gloire de Montpellier. Results determined that Rességuier 2 is the maternal parent for 14 commercial rootstocks, 9 of which are full-sibs with Gloire de Montpellier as the paternal parent. Similarly, du Lot is the paternal parent of nine rootstocks. The pedigree information for 28 rootstocks was determined or corrected in this study. The previously reported pedigree information for eight of the rootstocks was correct. The results found that the world's existing rootstocks have a narrow genetic base derived from only a few American grape species. Future rootstock breeding efforts should use a more diverse array of species to combat a changing climate and pest pressure.

Early African Fossils Elucidate the Origin of Embrithopod Mammals.

Modern mammals rapidly evolved in the early Cenozoic in all continental provinces, including in Africa, with one of the first placental branches, the Afrotheria [1, 2]. Afrotherian evolution is at the origin of the major radiation of African ungulate-like mammals, including extant hyrax, elephant, and sea cow orders, which all belong to the Paenungulata. The paenungulate radiation also includes the extinct order Embrithopoda of uncertain interordinal relationships, which is best known for the giant and strangely specialized Oligocene genus Arsinoitherium. The Ouled Abdoun basin, Morocco, yielded exceptional Paleocene-Eocene fossils documenting the early paenungulate evolution [3-8]. Here we report two new small Ypresian species, Stylolophus minor n.g., n.sp. and cf. Stylolophus sp., which are the earliest and most primitive embrithopods. The cladistic analysis relates the Embrithopoda to crown paenungulates as the stem-group of the Tethytheria, which makes crown tethytherians restricted to extant elephant and sea cow orders. The Embrithopoda is therefore an early tethytherian offshoot predating the elephant and sea cow divergence. The resulting phylogeny supports a strictly African early radiation of the paenungulates excluding the Phenacolophidae and Anthracobunia. It sustains an at least early Paleocene African origin of the Embrithopoda. The unique tooth pattern of the embrithopods (hyperdilambdodont and pseudolophodont molars) is resolved as evolving early and directly from the dilambdodont (W-shaped labial molar crests) ancestral paenungulate morphotype. The specialized upper molar morphology with two transverse crests is convergent and non-homologous in embrithopods and crown Tethytheria. These convergences for specialized folivorous diet were driven by free herbivorous African niches in the early Paleogene.

Environmental stress and vestibular inputs modulate cardiovascular responses to orthostasis in hypertensive rats.

The frequent accompaniment of hypertension by orthostatic circulatory disorders prompted us to investigate the effect of repeated and sustained head-up and head-down tilt positions on cardiovascular responses in spontaneously hypertensive rats vs. Wistar rats using radiotelemetric implants. Repeated orthostasis caused a transient elevation in blood pressure (7.3±1.7 mmHg) and heart rate (39.7±10.5 BPM), while repeated antiorthostasis led only to reversible tachycardia (85.6±11.7-54.3±16.8 BPM) in spontaneously hypertensive rats. In contrast to the Wistar rats, sustained tilt failed to affect the blood pressure or heart rate in spontaneously hypertensive rats because the environmental stress of being placed in horizontal tilt cages prior to the sustained tilt test induced marked changes in cardiovascular parameters. Non-specific stress responses were eliminated both by the anxiolytic diazepam and a sub-anesthetic dose of chloralose. Unlike diazepam, chloralose amplified the orthostatic pressor responses in the Wistar rats. In contrast to diazepam preventing the pressor response and associated tachycardia in spontaneously hypertensive rats, chloralose elicited this effect during both sustained orthostasis (36.0±7.3 mmHg, 63.7±21.8 BPM) and antiorthostasis (42.9±10.9 mmHg, 82.8±25.4 BPM), with a reduced baroreflex sensitivity. However, during sustained orthostasis, removal of the vestibular input led to a depressor response with bradycardia (12.5±3.2 mmHg, 59.3±17.3 BPM), whereas antiorthostasis only reduced blood pressure (20.5±7.1 mmHg) in the spontaneously hypertensive rats. We conclude that repeated tilts induce a transient pressor response and/or tachycardia in spontaneously hypertensive rats. Cardiovascular parameters are suppressed by diazepam, whereas chloralose evokes both blood pressure and heart rate responses during sustained tilts, which are primarily elicited by baroreflex suppression in hypertension. Vestibular inputs support cardiovascular tolerance to sustained postural changes in a rat model of human 'essential' hypertension.

Neogene sharks and rays from the Brazilian 'Blue Amazon'.

The lower Miocene Pirabas Formation in the North of Brazil was deposited under influence of the proto-Amazon River and is characterized by large changes in the ecological niches from the early Miocene onwards. To evaluate these ecological changes, the elasmobranch fauna of the fully marine, carbonate-rich beds was investigated. A diverse fauna with 24 taxa of sharks and rays was identified with the dominant groups being carcharhiniforms and myliobatiforms. This faunal composition is similar to other early Miocene assemblages from the proto-Carribbean bioprovince. However, the Pirabas Formation has unique features compared to the other localities; being the only Neogene fossil fish assemblage described from the Atlantic coast of Tropical Americas. Phosphate oxygen isotope composition of elasmobranch teeth served as proxies for paleotemperatures and paleoecology. The data are compatible with a predominantly tropical marine setting with recognized inshore and offshore habitats with some probable depth preferences (e.g., Aetomylaeus groups). Paleohabitat of taxa particularly found in the Neogene of the Americas (†Carcharhinus ackermannii, †Aetomylaeus cubensis) are estimated to have been principally coastal and shallow waters. Larger variation among the few analyzed modern selachians reflects a larger range for the isotopic composition of recent seawater compared to the early Miocene. This probably links to an increased influence of the Amazon River in the coastal regions during the Holocene.

Ferrocene-cinchona hybrids with triazolyl-chalcone linkers act as pro-oxidants and sensitize human cancer cell lines to paclitaxel.

Recently, we demonstrated that ferrocene-containing compounds with a cinchona moiety displayed marked anticancer activity. Here we report on the effects of the most promising isomers encompassing quinine- (compounds 4 and 5) and quinidine-epimers (compounds 6 and 7) - synthesized using improved methods providing controlled diastereoselectivity - in three different human multidrug resistant (MDR) cancer cell lines and their sensitive counterparts (non-small cell lung carcinoma NCI-H460/R/NCI-H460, colorectal carcinoma DLD1-TxR/DLD1 and glioblastoma U87-TxR/U87). We observed that the presence of the MDR phenotype did not diminish the activity of the compounds suggesting that ferrocene quinine- and quinidine-epimers are not substrates for P-glycoprotein, which has been indicated as a major mechanism of MDR in the cell lines used. Considering that metal-based anticancer agents mainly act by increasing ROS production, we investigated the potential of ferrocene-quinidine epimers to generate ROS. We found that 6 and 7 more readily increased ROS production and induced mitochondrial damage in MDR cancer cells. According to cell death analysis, 6 and 7 were more active against MDR cancer cells showing collateral sensitivity. In addition, our data suggest that these compounds could act as inhibitors of autophagy. Importantly, simultaneous treatments of 6 and 7 with paclitaxel (PTX) increased the sensitivity of MDR cancer cells to PTX. In conclusion, the ferrocene-quinidine epimers, besides being selective towards MDR cancer cells, could also possess potential to overcome PTX resistance.

Physical determinants of vesicle mobility and supply at a central synapse.

Encoding continuous sensory variables requires sustained synaptic signalling. At several sensory synapses, rapid vesicle supply is achieved via highly mobile vesicles and specialized ribbon structures, but how this is achieved at central synapses without ribbons is unclear. Here we examine vesicle mobility at excitatory cerebellar mossy fibre synapses which sustain transmission over a broad frequency bandwidth. Fluorescent recovery after photobleaching in slices from VGLUT1(Venus) knock-in mice reveal 75% of VGLUT1-containing vesicles have a high mobility, comparable to that at ribbon synapses. Experimentally constrained models establish hydrodynamic interactions and vesicle collisions are major determinants of vesicle mobility in crowded presynaptic terminals. Moreover, models incorporating 3D reconstructions of vesicle clouds near active zones (AZs) predict the measured releasable pool size and replenishment rate from the reserve pool. They also show that while vesicle reloading at AZs is not diffusion-limited at the onset of release, diffusion limits vesicle reloading during sustained high-frequency signalling.

Synthesis, structure and in vitro cytostatic activity of ferrocene-Cinchona hybrids.

Exploring copper(I)- and ruthenium(II)-catalyzed azide-alkyne cycloadditions and a Sonogashira protocol, novel cytostatic ferrocene-cinchona hybrids were synthetized displaying significant in vitro activity on HepG-2 and HT-29 cells. Preliminary SAR studies disclosed that compounds incorporating linkers with 1,2,3-triazole and chalchone residues can be considered as promising lead structures. According to the best of our knowledge this is the first letter on the incorporation of ferrocene nucleus in the reputed cinchona family via triazole and chalcone linkers with established pharmaceutical profile.

Geochemical compositions of marine fossils as proxies for reconstructing ancient environmental conditions.

A brief summary is given here about some of the geochemical methodologies that are often used to obtain information from fossils and sediments about the past environment. Such methods are frequently applied in our project in which the formation of Paleogene phosphate sequences in North Africa is investigated. These layers were deposited in shallow marine seas during a period of extreme warm climate with a high CO(2) concentration in the atmosphere. Some of the characteristics of this greenhouse interval are similar to the modern anthropogenic situation hence it is intensively investigated from several aspects by many scientists. Here the geochemical compositions of fossils deposited during this time are discussed, focusing on how the data are obtained and how they could be evaluated in terms of palaeo-environmental conditions.

Fractal characterization of complexity in dynamic signals: application to cerebral hemodynamics.

We introduce the concept of spatial and temporal complexity with emphasis on how its fractal characterization for 1D, 2D or 3D hemodynamic brain signals can be carried out. Using high-resolution experimental data sets acquired in animal and human brain by noninvasive methods - such as laser Doppler flowmetry, laser speckle, near infrared, or functional magnetic resonance imaging - the spatiotemporal complexity of cerebral hemodynamics is demonstrated. It is characterized by spontaneous, seemingly random (that is disorderly) fluctuation of the hemodynamic signals. Fractal analysis, however, proved that these fluctuations are correlated according to the special order of self-similarity. The degree of correlation can be assessed quantitatively either in the temporal or the frequency domain respectively by the Hurst exponent (H) and the spectral index (beta). The values of H for parenchymal regions of white and gray matter of the rat brain cortex are distinctly different. In human studies, the values of beta were instrumental in identifying age-related stiffening of cerebral vasculature and their potential vulnerability in watershed areas of the brain cortex such as in borderline regions between frontal and temporal lobes. Biological complexity seems to be present within a restricted range of H or beta values which may have medical significance because outlying values can indicate a state of pathology.

[Kinesiological examination in AIS]. / Kineziológiai vizsgálatok adolescens idiopathiás scoliosisban.

AIM: To define the shape of the scoliotic spine by the CMS-system, to analyze the changes of the scoliotic spine as compared to that of non-scoliotic patients and to study the effect of loading on the deformed spine in AIS. The aim of the authors was to find a connection between the progression of scoliosis and the changes of movements of the deformed spine. They also analyse the effect of loading on the deformed spine and reach conclusions with regard to the progression of the spine deformity. PATIENTS AND METHOD: In a prospective study 25 scoliotic patients with type King 1-2-3 scoliosis were examined. Mean Cobb grades were dorsal 27 degrees (min. 15, max. 42), lumbal 25 degrees (min. 14, max. 43). RESULTS: The significant increase of extension seems to be in connection with increased lordosis in scoliosis. The significant increase of right rotation in AIS emphasizes that very often the first sign is the increased rotation on the thoracic spine, which could be larger than the right curve on the spine itself. However, the significant decrease of left and right bending is not in correlation with the severity of the spine deformities. Up to 30 degrees Cobb grades the pp angle is in significant correlation with the Cobb grade, but over 30 Cobb grade this correlation is weak. CONCLUSION: During the clinical examination of the patient's spine only the "processus spinosus angle" may be observed, not the so-called Cobb angle, that is why we cannot leave out of consideration the X-ray analysis during the follow-up of the patients. The loading has a great influence on the degree of the gibbus and the severity of the thoracic curve.

Ultrasound based measuring-diagnostic and muscle activity measuring system for spinal analysis.

A modern motion analysis laboratory was installed by way of several scientific research instrumentation grants awarded to the Department of Applied Mechanics, BUTE. Motion and spine analysis is performed by a CMS-HS ultrasound-based system. System operation is based on ultrasound spread characteristics. In the area of spine analysis, it is possible to investigate the shape of the spine, its movement characteristics, mobility, and the movement characteristics of the cervical spine separately. The results of traditional spine tests are adequately supplemented by the results of the tests performed by this motion analysis system, considered to be a specialty throughout Europe. With the EMG (ElectroMyoGraph) sensors specify whether the muscles operate insufficiently or become active during the wrong motion, limiting the patient in motion.

Analysis of human walking and running parameters as a function of speed.

Recently, there has been great improvement in the field of movement analysis, which is a worldwide tendency. There is a continuous improvement of new methods, combined with traditional ones. In the last few years, we have managed to set up a modern, absolutely up-to-date motion analysis laboratory at the Budapest University of Technology and Economics (BUTE). The primary purpose of this study was to determine usual walking and running parameters as a function of speed and compare our results with the data of other studies. We tested the gait and running characteristics of people at different speeds, measuring the usual parameters of walking and running. On the basis of these measurements, we observed the interrelation of the three main parameters of gait and running (speed, cadence, stride length) and determined the dependence of cadence and stride length on speed as well. The determined energetically optimal walking speed (EOWS) and the usual walking speed (UWS) correlate well with the values in literature. Our measurements were performed on a running corridor, and at the facilities provided by the Biomechanical Laboratory, including an instrumented treadmill connected to the measurement system.

In vitro binding and functional studies of Ac-RYYRIK-ol and its derivatives, novel partial agonists of the nociceptin/orphanin F/Q receptor.

Following the discovery of nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) and its endogenous ligand, an extensive search has started to find selective agonists and antagonists targeting this novel receptor-ligand system due to their therapeutic potentials. By the help of the combinatorial chemistry a series of hexapeptides with a general formula of Ac-RYY-R/K-W/I-R/K-NH(2) having high NOP receptor affinity and selectivity were identified. On the basis of this information we developed a number of novel compounds. The detailed structure-activity studies on the partial agonist Ac-RYYRIK-NH(2) are reported in this communication. Besides the modifications on N- and C-terminal, Arg-Cit exchange was performed on the template structure. The novel hexapeptides were analyzed in radioligand binding, functional biochemical [(35)S]GTPgammaS binding assays by using membranes from rat brains and Chinese hamster ovary cells expressing human NOP receptor. The agonist/antagonist properties were also tested on in the mouse vas deferens bioassay. C-terminal modification yielded a high affinity, selective and potent NOP ligand (Ac-RYYRIK-ol) with a partial agonist property. Several analogs of this compound were synthesized. The presence of the positively charged arginine residue at the first position turned out to be crucial for the biological activity of the hexapeptide. The N-terminal modifications with various acyl groups (ClAc, pivaloyl, formyl, benzoyl, mesyl) decreased the affinity of the ligand towards the receptor and the intrinsic activity for stimulating the G-protein activation was also decreased. The structure-activity studies on the hexapeptide derivatives provided some basic information on the structural requirements for receptor binding and activation.

In vitro and in vivo pharmacological characterization of the nociceptin/orphanin FQ receptor ligand Ac-RYYRIK-ol.

It was recently reported that the hexapeptide Ac-RYYRIK-ol binds with high affinity nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptors and competitively antagonizes N/OFQ actions in the mouse vas deferens assay. Here we further describe the in vitro and in vivo pharmacological features of this NOP receptor ligand. In mouse brain homogenate the degradation half life of Ac-RYYRIK-ol (2.48 min) was significantly higher than that of the parent compound Ac-RYYRIK-NH2 (1.20 min). In the electrically stimulated mouse vas deferens, Ac-RYYRIK-ol (10-1000 nM) competitively antagonized the inhibitory effect of N/OFQ (pA2=8.46), while in the isolated mouse colon the hexapeptide mimicked N/OFQ contractile effects thus behaving as a NOP receptor agonist (pEC50=9.09). This latter effect was no longer evident in colon tissues taken from mice knock out for the NOP receptor gene (NOP-/-). In vivo in mice, similarly to N/OFQ, Ac-RYYRIK-ol (dose range 0.001-1 nmol) produced: i) pronociceptive effects after intracerebroventricular (i.c.v.) administration and antinociceptive actions when given intrathecally (i.t.) in the tail withdrawal assay; ii) inhibition of locomotor activity and iii) stimulation of food intake after supraspinal administration. Finally, in the forced swimming test, Ac-RYYRIK-ol was inactive per se, but reversed the antidepressant-like effects elicited by the NOP receptor selective antagonist UFP-101 ([Nphe(1),Arg(14),Lys(15)]N/OFQ-NH2). Thus, in all these in vivo assays Ac-RYYRIK-ol mimicked the actions of N/OFQ showing however higher potency. In conclusion, Ac-RYYRIK-ol displayed a complex pharmacological profile which is likely due to the low efficacy agonist nature of this novel ligand of the NOP receptor. The high potency, selectivity of action, and in vivo effectiveness make Ac-RYYRIK-ol a useful pharmacological tool for future studies in the field of N/OFQ and its NOP receptor.

Prediction of the main cortical areas and connections involved in the tactile function of the visual cortex by network analysis.

We explored the cortical pathways from the primary somatosensory cortex to the primary visual cortex (V1) by analysing connectional data in the macaque monkey using graph-theoretical tools. Cluster analysis revealed the close relationship of the dorsal visual stream and the sensorimotor cortex. It was shown that prefrontal area 46 and parietal areas VIP and 7a occupy a central position between the different clusters in the visuo-tactile network. Among these structures all the shortest paths from primary somatosensory cortex (3a, 1 and 2) to V1 pass through VIP and then reach V1 via MT, V3 and PO. Comparison of the input and output fields suggested a larger specificity for the 3a/1-VIP-MT/V3-V1 pathways among the alternative routes. A reinforcement learning algorithm was used to evaluate the importance of the aforementioned pathways. The results suggest a higher role for V3 in relaying more direct sensorimotor information to V1. Analysing cliques, which identify areas with the strongest coupling in the network, supported the role of VIP, MT and V3 in visuo-tactile integration. These findings indicate that areas 3a, 1, VIP, MT and V3 play a major role in shaping the tactile information reaching V1 in both sighted and blind subjects. Our observations greatly support the findings of the experimental studies and provide a deeper insight into the network architecture underlying visuo-tactile integration in the primate cerebral cortex.

Inverse-orthostasis may induce elevation of blood pressure due to sympathetic activation.

Microgravity and simulated microgravity may cause cardiovascular deconditioning, but mechanisms of instantaneous responses to inverse-orthostasis are not studied. Hence, we investigated transient and steady state cardiovascular changes by combining the tilt technique with cardiovascular telemetry. Normotensive and NO-deprived hypertensive Wistar rats were used to analyze responses of mean arterial blood pressure, heart rate, contractility, spontaneous baroreflex sensitivity (sBRS), and autonomic balance. Inverse-orthostasis tests were carried out by 45 degrees head-down tilting (repeated 3 x 5 mins "R", or sustained for 120 mins "S"). In normotensive rats, horizontal control blood pressure was R111.3 +/- 1.7/S110.4 +/- 2.3 mm Hg and heart rate was R385.2 +/- 5.9/S371.1 +/- 6.1 BPM. Head-down tilt induced an increase in blood pressure by R5.9/S10.6 mm Hg, while heart rate, contractility, sBRS, and autonomic balance did not change. The hypertensive response was sustained, could be prevented by prazosin (10 mg/kgbw), and augmented by subanesthetic doses of chloralose (26 and 43 mg/kgbw). In NO-suppressed hypertension, control blood pressure and heart rate were R132.4 +/- 2.9/S130.0 +/- 4.1 mm Hg and R339.2 +/- 7.9/S307.2 +/- 23.6 BPM, respectively. Head-down tilt further increased blood pressure by R5.1/S10.5 mm Hg. These data demonstrate that conscious rats respond to inverse-orthostasis by sustained elevation of blood pressure independent of NO synthesis. This response is neither due to increased contractility and altered sBRS, nor due to non-specific stress, but probably due to sympathetic activation elicited by gravity-related reflexes, which increase peripheral resistance.

Endomorphin synthesis in rat brain from intracerebroventricularly injected [3H]-Tyr-Pro: a possible biosynthetic route for endomorphins.

In spite of concentrated efforts, the biosynthetic route of mu-opioid receptor agonist brain tetrapeptide endomorphins (Tyr-Pro-Trp-Phe-NH2 and Tyr-Pro-Phe-Phe-NH2), discovered in 1997, is still obscure. We report presently that 30 min after intracerebroventricular injection of 20 or 200 microCi [3H]Tyr-Pro (49.9 Ci mmol(-1)) the incorporated radioactivity was found in endomorphin-related tetra- and tripeptides in rat brain extracts. As detected by the combination of HPLC with radiodetection, a peak corresponding to endomorphin-2-OH could be identified in two of four extracts of "20 microCi" series. Radioactive peaks in position of Tyr, Tyr-Pro, Tyr-Pro-Phe or Tyr-Pro-Trp appeared regularly in both series and also in the "tetrapeptide cluster" constituted by endomorphins and their free carboxylic forms. In one of the four extracts in the "200 microCi" series a robust active peak in the position of endomorphin 2 could be detected. Intracerebroventricularly injected 100 nmol, but not 10 or 1000 nmol cold Tyr-Pro (devoid of opioid activity in vitro), caused a naloxone-reversible prolongation of tail-flick latency in rats, peaking between 15 and 30 min. We suggest that Tyr-Pro may serve as a biosynthetic precursor to endomorphin synthesis.