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The paragenesis and composition of bavenite-bohseite were investigated in fifteen granitic pegmatites from the Bohemian Massif, Czech Republic. Three types distinct in their relation to primary Be precursors, mineral assemblages, morphology and origin were recognised: (1) primary hydrothermal bavenite-bohseite crystallised in miarolitic pockets from residual pegmatite fluids; and secondary bavenite-bohseite in two distinct types: (2) a proximal type restricted spatially to pseudomorphs after a primary Be mineral (beryl > phenakite, helvine-danalite); and (3) a distal type on brittle fractures and fissures of host pegmatite. The mineral assemblages are highly variable: (1) axinite-(Mn), smectite, calcite and pyrite; (2) bertrandite, milarite, secondary beryl, bazzite, K-feldspar, muscovite-illite, scolecite, gismondine-Ca, analcime, chlorite; and (3) muscovite, albite, quartz, epidote, pumpellyite-(Mg), pumpellyite-(Fe3+), titanite and chlorite. Electron microprobe analyses showed, in addition to major constituents (Si, Ca and Al), minor concentrations (in apfu) of Na (≤0.24), Fe (≤0.10), Mn (≤0.10) and F (≤0.36). The type 1 hydrothermal miarolitic bavenite-bohseite is mostly Al-rich (2.00-0.67 apfu) relative to type 2 proximal bavenite-bohseite and bohseite after beryl, phenakite and helvine-danalite (1.56-0.46, 0.70-0.05, 1.02-0.35 apfu, respectively); and type 3 distal bavenite-bohseite typically after beryl (1.63-0.09 apfu). Raman spectroscopy revealed that the distance between the OH- vibrational modes decreases with increasing bohseite component. The Al content of secondary type 2 proximal bavenite-bohseite is controlled by the composition of the Be precursor whereas type 3 distal bavenite-bohseite with beryl as the Be precursor is more variable and the composition is governed mainly by the composition of fluids. Calcium, a crucial component for bavenite-bohseite origins, was derived from residual pegmatite fluids (Vlastějovice, Vepice IV or Trebíc Plutons) or external sources (e.g. Drahonín IV, Věžná I or Marsíkov). Primary type 1 hydrothermal bavenite-bohseite from miarolitic pockets might have crystallised at T ≈ 300-400°C and P ≈ 200 MPa, whereas the secondary type 2 and 3 bavenite-bohseite formed at T ≈ 300-100°C and P ≈ 200-20 MPa.

Mineral assemblages of primary and secondary Be-minerals were examined in intraplutonic euxenite-type NYF pegmatites of the Třebíč Pluton, Moldanubian Zone occurring between Třebíč and Vladislav south of the Třebíč fault. Primary magmatic Be-minerals crystallized mainly in massive pegmatite (paragenetic type I) including common beryl I, helvite-danalite I, and a rare phenakite I. Rare primary hydrothermal beryl II and phenakite II occur in miarolitic pockets (paragenetic type II). Secondary hydrothermal Be-minerals replaced primary precursors or filled fractures and secondary cavities, or they are associated with \"adularía\" and quartz (paragenetic type III). They include minerals of bohseite-bavenite series, less abundant beryl III, bazzite III, helvite-danalite III, milarite-agakhanovite-(Y) III, phenakite III, and datolite-hmggamte-(Y) III. Chemical composition of the individual minerals is characterized by elevated contents of Na, Cs, Mg, Fe, Sc in beryl I and II; Na, Ca, Mg, Fe, Al in bazzite III; REE in milarite-agakhanovite-(Y) III; variations in Fe/Mn in helvite-danalite and high variation of Al in bohseite-bavenite series. Replacement reactions of primary Be-minerals are commonly complex and the sequence of crystallization of secondary Be-minerals is not defined; minerals of bohseite-bavenite series are mostly the latest. Beryl usually occurs in pegmatites with rare tourmaline, whereas helvite-danalite bearing pegmatites are tourmaline-rich. Abundant tourmaline in pegmatites with helvite-danalite and its scarcity in beryl-bearing pegmatites indicate that early tourmaline crystallization affected activity of Al in the parental medium and thus may have controlled formation of primary Be-minerals (beryl - higher Al, helvite-danalite - lower Al) which crystallized later. Secondary Be-minerals with dominant minerals of bohseite-bavenite series and milarite suggest high activity of Ca in fluids. Variations in chemical composition (Al contents) of bohseite-bavenite series were controlled by the chemical composition of the precursor. High variability of primary magmatic Be-minerals within a single pegmatite district is exceptional and it is constrained by variable activities of Si and mainly Al, divalent cations - Ca, Mn, Fe, Zn and Mg, trivalent cations - REEs, Sc, and B, S, and fO2 in the individual pegmatites.

Background/Objectives: The neuromorphological effects of prenatal administration of valproic acid (VPA) on the dopaminergic system has been studied by our groups for some time. Previously, we found a marked defasciculation of the mesotelencephalic pathway, and a reduction of dopaminergic ventrotegmental output, with diminished dopamine in the nucleus accumbens (NAc) but not in the caudatoputamen (CPu), in VPA exposed P7 mice. Further, we reported a marked decrease in the juxtapositions between tyrosine hydroxylase positive (TH+) axon terminals and calretinin or calbindin containing neurons in the NAc and tuberculum olfactorium (OT). Our aim was to test the existing findings, indicating diminished input of TH+ structures to dopamine recipient forebrain, by another robust and unbiased quantitative approach. Methods: Here, the intensity of TH immunolabel was quantified by 3D image analysis of whole-mount, tissue-cleared (by the iDISCO method) brain specimens of P7 mice born to VPA-exposed or control mothers. Results: We observed a robust reduction in TH+ immunostaining (expressed as mean voxel intensity within the ROI) in the OT, and a less prominent but significant reduction of this parameter in the NAc, in VPA exposed vs control mice. No such effect was observed in the CPu, indicating that the decrease of DA input affected predominantly the limbic component of dopamine recipient forebrain regions. Conclusions: Together with previous observations, the current results seem to converge upon a consistent interpretation, i.e., reduced DAergic fiber input to ventral forebrain regions, following VPA exposure of neonatal mice. Weaker supply of DA at a critical time of embryonic development may result in impaired pattern formation of ventrobasal forebrain regions involved in reward and sociability.

As of today, the most credible scientific paradigm pertaining to the origin of life on Earth is undoubtedly the RNA World scenario. It is built on the assumption that catalytically active replicators (most probably RNA-like macromolecules) may have been responsible for booting up life almost four billion years ago. The many different incarnations of nucleotide sequence (string) replicator models proposed recently are all attempts to explain on this basis how the genetic information transfer and the functional diversity of prebiotic replicator systems may have emerged, persisted and evolved into the first living cell. We have postulated three necessary conditions for an RNA World model system to be a dynamically feasible representation of prebiotic chemical evolution: (1) it must maintain and transfer a sufficient diversity of information reliably and indefinitely, (2) it must be ecologically stable and (3) it must be evolutionarily stable. In this review, we discuss the best-known prebiotic scenarios and the corresponding models of string-replicator dynamics and assess them against these criteria. We suggest that the most popular of prebiotic replicator systems, the hypercycle, is probably the worst performer in almost all of these respects, whereas a few other model concepts (parabolic replicator, open chaotic flows, stochastic corrector, metabolically coupled replicator system) are promising candidates for development into coherent models that may become experimentally accessible in the future.

Gestational exposure to valproic acid (VPA) is a valid rodent model of human autism spectrum disorder (ASD). VPA treatment is known to bring about specific behavioral deficits of sociability, matching similar alterations in human autism. Previous quantitative morphometric studies from our laboratory showed a marked reduction and defasciculation of the mesotelencephalic dopaminergic pathway of VPA treated mice, along with a decrease in tissue dopamine in the nucleus accumbens (NAc), but not in the caudatoputamen (CPu). In the present study, the correlative distribution of tyrosine hydroxylase positive (TH+) putative axon terminals, presynaptic to the target neurons containing calretinin (CR) or calbindin (CB), was assessed using double fluorescent immunocytochemistry and confocal laser microscopy in two dopamine recipient forebrain regions, NAc and olfactory tubercle (OT) of neonatal mice (mothers injected with VPA on ED13.5, pups investigated on PD7). Representative image stacks were volumetrically analyzed for spatial proximity and abundance of presynaptic (TH+) and postsynaptic (CR+, CB+) structures with the help of an Imaris (Bitplane) software. In VPA mice, TH/CR juxtapositions were reduced in the NAc, whereas the TH/CB juxtapositions were impoverished in OT. Volume ratios of CR+ and CB+ elements remained unchanged in NAc, whereas that of CB+ was markedly reduced in OT; here the abundance of TH+ axons was also diminished. CR and CB were found to partially colocalize with TH in the VTA and SN. In VPA exposed mice, the abundance of CR+ (but not CB+) perikarya increased both in VTA and SN, however, this upregulation was not mirrored by an increase of the number of CR+/TH+ double labeled cells. The observed reduction of total CB (but not of CB+ perikarya) in the OT of VPA exposed animals signifies a diminished probability of synaptic contacts with afferent TH+ axons, presumably by reducing the available synaptic surface. Altered dopaminergic input to ventrobasal forebrain targets during late embryonic development will likely perturb the development and consolidation of neural and synaptic architecture, resulting in lasting changes of the neuronal patterning (detected here as reduced synaptic input to dopaminoceptive interneurons) in ventrobasal forebrain regions specifically involved in motivation and reward.

Gestational exposure of mice to valproic acid (VPA) is one currently used experimental model for the investigation of typical failure symptoms associated with autism spectrum disorder (ASD). In the present study we hypothesized that the reduction of dopaminergic source neurons of the VTA, followed by perturbed growth of the mesotelencephalic dopamine pathway (MT), should also modify pattern formation in the dopaminoceptive target regions (particularly its mesoaccumbens/mesolimbic portion). Here, we investigated VPA-evoked cellular morphological (apoptosis-frequency detected by Caspase-3, abundance of Ca-binding proteins, CaBP), as well as synaptic proteomic (western blotting) changes, in selected dopaminoceptive subpallial, as compared to pallial, regions of mice, born to mothers treated with 500 mg/kg VPA on day 13.5 of pregnancy. We observed a surge of apoptosis on VPA treatment in nearly all investigated subpallial and pallial regions; with a non-significant trend of similar increase the nucleus accumbens (NAc) at P7, the age at which the MT pathway reduction has been reported (also supplemented by current findings). Of the CaBPs, calretinin (CR) expression was decreased in pallial regions, most prominently in retrosplenial cortex, but not in the subpallium of P7 mice. Calbindin-D 28K (CB) was selectively reduced in the caudate-putamen (CPu) of VPA exposed animals at P7 but no longer at P60, pointing to a potency of repairment. The VPA-associated overall increase in apoptosis at P7 did not correlate with the abundance and distribution of CaBPs, except in CPu, in which the marked drop of CB was negatively correlated with increased apoptosis. Abundance of parvalbumin (PV) at P60 showed no significant response to VPA treatment in any of the observed regions we did not find colocalization of apoptotic (Casp3+) cells with CaBP-immunoreactive neurons. The proteomic findings suggest reduction of tyrosine hydroxylase in the crude synaptosome fraction of NAc, but not in the CPu, without simultaneous decrease of the synaptic protein, synaptophysin, indicating selective impairment of dopaminergic synapses. The morpho-functional changes found in forebrain regions of VPA-exposed mice may signify dendritic and synaptic reorganization in dopaminergic target regions, with potential translational value to similar impairments in the pathogenesis of human ASD.

Gestational exposure to valproic acid (VPA) is known to cause behavioral deficits of sociability, matching similar alterations in human autism spectrum disorder (ASD). Available data are scarce on the neuromorphological changes in VPA-exposed animals. Here, we aimed to focus on alterations of the dopaminergic system, implicated in motivation and reward, with relevance to social cohesion. Whole brains from 7-day-old mice born to mothers injected with VPA (400 mg/kg b.wt.) on E13.5 were immunostained against tyrosine hydroxilase (TH) using the iDISCO method, scanned with a laser light-sheet microscope, and the reconstructed images analysed in 3D for quantitative morphometry. A marked reduction of mesotelencephalic (MT) axonal fascicles together with a widening of the MT tract were observed in VPA treated mice, while other major brain tracts appeared anatomically intact. We also found a reduction in the abundance of dopaminergic ventral tegmental (VTA) neurons, accompanied by diminished tissue level of DA in ventrobasal telencephalic regions (including the nucleus accumbens, olfactory tubercle, BST, substantia innominata). Such reduction of DA was not observed in the non-limbic caudatoputamen. Conversely, the abundance of TH+ cells in the substantia nigra (SN) was increased, presumably due to a compensatory mechanism or to an altered distribution of TH+ neurons occupying the SN and the VTA. The findings suggest that defasciculation of the MT tract and neuronal loss in VTA, followed by diminished dopaminergic input to the ventrobasal telencephalon at a critical time point of embryonic development (E13-E14) may hinder the patterning of certain brain centers underlying decision making and sociability.

The member of synthetic cathinone family, methylenedioxypyrovalerone (MDPV), is a frequently used psychoactive drug of abuse. The objective of our study was to determine the effect of MDPV (administered from the 8th to the 14th day of gestation) on the behavior of neonatal and adolescent mice, as well as its effect on maternal care. We measured maternal care (pup retrieval test, nest building), locomotor activity (open field test), and motor coordination (grip strength test) of dams, whereas on pups we examined locomotor activity at postnatal day 7 and day 21 (open field test) and motor coordination on day 21 (grip strength test). On fresh-frozen brain samples of the dams we examined the expression of two important peptides implicated in the regulation of maternal behavior and lactation: tuberoinfundibular peptide 39 (TIP39) mRNA in the thalamic posterior intralaminar complex, and amylin mRNA in the medial preoptic nucleus. We detected decreased birth rate and survival of offspring, and reduced maternal care in the drug-treated animals, whereas there was no difference between the motility of treated and control mothers. Locomotor activity of the pups was increased in the MDPV treated group both at 7 and 21 days of age, while motor coordination was unaffected by MDPV treatment. TIP39 and amylin were detected in their typical location but failed to show a significant difference of expression between the drug-treated and control groups. The results suggest that chronic systemic administration of the cathinone agent MDPV to pregnant mice can reduce birth rate and maternal care, and it also enhances motility (without impairment of motor coordination) of the offspring.

Several studies have shown that L-aspartate (Asp) is present in synaptic vesicles and released exocytotically from presynaptic terminals, possibly by Ca 2+ -dependent corelease of Asp and L-glutamate (Glu). It has been demonstrated that both excitatory amino acids (EAAs) are released from the rat striatum as part of corticostriatal neurotransmission. The single or colocalized occurrence of Asp and Glu in specific synaptic boutons of the chicken medial striatum/nucl. accumbens has been demonstrated by our group using ultrastructural immunocytochemistry. However, evidence for the presence of EAAs in any specific striatal pathway was only circumstantial. Here, we report on the distribution of Asp and Glu in specific synaptic terminals of the amygdalostriatal pathway, both in rat and chicken brains, combining anterograde tracing with postembedding immunogold labeling of Asp or Glu. Immunoreactivity for Asp and Glu was observed in amygdalofugal terminals with asymmetrical synaptic junctions (morphologically representing excitatory synapses) in both species. The postsynaptic targets were either dendritic spines or small dendrites, whereas axosomatic or axo-axonic connections were not observed. Ultrastructurally, the synaptic terminals immunoreactive for Asp were indistinguishable from those immunoreactive for Glu. The findigs are consistent with an Asp–Glu corelease mechanism, with a distinct synaptic contingent, evolutionarily conserved in the amygdalostriatal pathway.

Microbial symbiosis is extremely common among metabolically coupled cells, and, presumably, gave rise to mitochondria. How such symbioses emerge, evolve and stabilize are unknown, especially in the prokaryotic domain, where endosymbioses are virtually nonexistent. Yet there is growing evidence suggesting that the eukaryotic cell emerged from such a prokaryotic partnership, where integration was not the result of phagocytotic inclusion (as in case of plastids) but of metabolic cooperation. While prokaryotes almost ubiquitously engage in metabolic syntrophy, it is unknown if such cooperation alone can enable stable, dependent ectosymbioses that could pave the road toward physical integration of parties. Here, we tested the hypothesis that free-living syntrophy can lead to stable ectosymbiosis between microbial partners, using an ecological mathematical model. Assuming an already syntrophic and asymmetric partnership of free-living hosts and symbionts, we investigated under what conditions obligate ectosymbiosis evolve. Our results show that reduced inhibition (of self-inhibiting metabolic products) over the contact surface of partners can stabilize the ectosymbiotic consortia against free-living forms. Furthermore, strong metabolic activity between the host and their ectosymbionts could facilitate obligacy in their physical association. The model points to the significance of the contact surface in the evolution of crucial endosymbiotic features. Our results support the hypothesis that cooperative, syntrophic microbes (especially prokaryotes) are capable of coevolving to form species-specific ectosymbiosis by means of reducing the inhibition of accumulating products, a necessary first step towards endosymbiotic integration. The model provides a plausible explanation on how common metabolic syntrophy can lead to physical integration of parties through gradual ectosymbiosis. Moreover, our work fills a gap between microbial cooperation models (assuming free-living species) and those that are concerned only with already concluded physical integration under a multilevel selection paradigm.