The effects of synthesis conditions on the FAU/EMT content and the size of nanocrystals, formed from inorganic aluminosilicate sols, were investigated. High-resolution transmission electron ...microscopy imaging and comparison of experimental X-ray diffraction patterns with simulations demonstrated that all materials made starting from synthesis mixtures in the composition range (1.8–33) SiO2:1 Al2O3:(2.7–33) Na2O:(41–1000) H2O contain FAU/EMT intergrowths. Compositions with low water content increase the FAU fraction up to 0.8 but the crystal size exceeds 100 nm. Extension of the higher FAU purity to nanocrystals was achieved only by first mixing the sol at high water content compositions that favor nanocrystal formation and thenafter a certain timelowering by freeze-drying the water to levels favoring the formation of FAU. Cryogenic transmission electron microscopy and small-angle X-ray scattering from representative optically clear and colloidally stable precursor sols (aged and crystallized at ambient temperature) reveal the formation of amorphous aggregates before the detection of crystals, in agreement with earlier findings and an existing model for the aggregative growth of the zeolite MFI. The presence of these amorphous aggregates coincides with the aforementioned state of sol that preserves the original trajectory toward nanocrystals after the pronounced reduction of water content by freeze-drying. If water reduction by freeze-drying is applied earlier (before the detection of amorphous aggregates), the sol follows the low water content trajectory toward larger crystals. Despite this memory effect, the sol at this stage is still agnostic toward FAU or EMT formation, the relative content of which is dominantly determined by the final water content. These findings demonstrate that it is possible to combine the effects of pre- and post-nucleation sol composition to steer crystal size and crystal structure, respectively. They confirm precursor nanoparticle evolution, while they emphasize the importance of solution phase composition at both pre- and post-nucleation stages of aggregative crystal growth.
Self-Catalyzing Hydrogen-Storage Material Yang, Jun; Sudik, Andrea; Siegel, Donald J ...
Angewandte Chemie (International ed.),
01/2008, Letnik:
47, Številka:
5
Journal Article
Recenzirano
Greater than the sum of its parts: Hydrogen storage in complex hydrides is accelerated by using the ternary composite 2 LiNH2/LiBH4/MgH2, which exhibits a “self‐catalyzing” reaction pathway that ...results in faster H2 desorption, lower desorption temperatures, and suppression of NH3 release in comparison to the constituent binary composites (see diagram). The enhanced properties arise from the incorporation of an ionic liquid phase (Li4BH3H10) and from ancillary‐reaction seeding of a reversible H2 storage reaction.
Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic ...etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract Current approaches to dissect the molecular neurobiology of complex neuropsychiatric disorders such as schizophrenia and major depression have been rightly criticized for failing to provide ...benefits to patients. Improving the translational potential of our efforts will require the development and refinement of better disease models that consider a wide variety of contributing factors, such as genetic variation, gene-by-environment interactions, endophenotype or intermediate phenotype assessment, cross species analysis, sex differences, and developmental stages. During a targeted expert meeting of the European College of Neuropsychopharmacology (ECNP) in Istanbul, we addressed the opportunities and pitfalls of current translational animal models of psychiatric disorders and agreed on a series of core guidelines and recommendations that we believe will help guiding further research in this area.
We have investigated the ternary mixture of complex hydrides with stoichiometry 2LiNH2+LiBH4+MgH2, and have identified a set of novel hydrogen storage reactions. One of these reactions involves the ...known reversible reaction Mg(NH2)2+2LiH{left-right arrow}Li2Mg(NH)2+2H2. Previous studies have shown that initiating this reaction from the binary mixture 2LiNH2+MgH2 results in poor hydrogen desorption kinetics and a small amount of NH3 release. In contrast to this behavior, here we demonstrate that by starting from the ternary mixture 2LiNH2+LiBH4+MgH2, the above reaction can proceed at lower temperatures and with improved kinetics, while maintaining reversibility. The advantage of starting with the ternary mixture can be traced to the subsequent formation, melting, and reaction of Li4BH4(NH2)3 with MgH2 to form the mixed imide phase Li2Mg(NH)2, which acts as a seed for the reversible reaction, and is at least partly responsible for the improved kinetic response.
Background
There is considerable unexplained variability in alcohol abstinence rates (AR) in the placebo groups of randomized controlled trials (RCTs) for alcohol dependence (AD). This is of ...particular interest because placebo responses correlate negatively with treatment effect size. Recent evidence suggests that the placebo response is lower in very heavy drinkers who show no “spontaneous improvement” prior to treatment initiation (high‐severity population) than in a mild‐severity population and in studies with longer treatment duration. We systematically investigated the relationship between population severity, treatment duration, and the placebo response in AR to inform a strategy aimed at reducing the placebo response and thereby increasing assay sensitivity in RCTs for AD.
Methods
We conducted a systematic literature review on placebo‐controlled RCTs for AD.We assigned retained RCTs to high‐ or mild‐severity groups of studies based on baseline drinking risk levels and abstinence duration before treatment initiation. We tested the effects of population severity and treatment duration on the placebo response in AR using meta‐regression analysis.
Results
Among the 19 retained RCTs (comprising 1996 placebo‐treated patients), 11 trials were high‐severity and 8 were mild‐severity RCTs. The between‐study variability in AR was lower in the high‐severity than in the mild‐severity studies (interquartile range: 7.4% vs. 20.9%). The AR in placebo groups was dependent on population severity (p = 0.004) and treatment duration (p = 0.017) and was lower in the high‐severity studies (16.8% at 3 months) than the mild‐severity studies (36.7% at 3 months).
Conclusions
Pharmacological RCTs for AD should select high‐severity patients to decrease the magnitude and variability in the placebo effect and and improve the efficiency of drug development efforts for AD.
Fragile X syndrome, a common form of inherited intellectual disability, is caused by loss of the fragile X mental retardation protein FMRP. FMRP is present predominantly in the cytoplasm, where it ...regulates translation of proteins that are important for synaptic function. We identify FMRP as a chromatin-binding protein that functions in the DNA damage response (DDR). Specifically, we show that FMRP binds chromatin through its tandem Tudor (Agenet) domain in vitro and associates with chromatin in vivo. We also demonstrate that FMRP participates in the DDR in a chromatin-binding-dependent manner. The DDR machinery is known to play important roles in developmental processes such as gametogenesis. We show that FMRP occupies meiotic chromosomes and regulates the dynamics of the DDR machinery during mouse spermatogenesis. These findings suggest that nuclear FMRP regulates genomic stability at the chromatin interface and may impact gametogenesis and some developmental aspects of fragile X syndrome.
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•Fragile X mental retardation protein FMRP binds chromatin via its Agenet domain•FMRP participates in the DNA damage response in a chromatin-dependent manner•FMRP occupies chromosomes and regulates DNA damage machinery in male mouse meiosis•Lack of FMRP results in meiotic defects such as incomplete chromosome pairing
In addition to its classical role as a translational regulator at neuronal synapses, the fragile X mental retardation protein has a role in the nucleus, where it targets chromatin and regulates the DNA damage response and mammalian gametogenesis.
Poised (bivalent) chromatin is defined by the simultaneous presence of histone modifications associated with both gene activation and repression. This epigenetic feature was first observed at ...promoters of lineage-specific regulatory genes in embryonic stem cells in culture. More recent work has shown that, in vivo, mammalian germ cells maintain poised chromatin at promoters of many genes that regulate somatic development, and that they retain this state from fetal stages through meiosis and gametogenesis. We hypothesize that the poised chromatin state is essential for germ cell identity and function. We propose three roles for poised chromatin in the mammalian germ line: prevention of DNA methylation, maintenance of germ cell identity and preparation for totipotency. We discuss these roles in the context of recently proposed models for germline potency and epigenetic inheritance.
Objective
Adolescents with anorexia (AN) and bulimia nervosa (BN) often struggle with emotion regulation (ER). These difficulties have predominantly been assessed across emotions, without considering ...adaptive and maladaptive ER separately. We compared adolescents with AN or BN to healthy adolescents (HCs) regarding the adaptive and maladaptive ER of three emotions.
Method
A treatment‐seeking sample of 197 adolescents (atypical/full‐threshold AN: N = 118, atypical/full‐threshold BN: N = 32; HC: N = 47) reported emotion‐specific ER with the FEEL‐KJ questionnaire. Mixed models were calculated for adaptive and maladaptive ER to assess differences between emotions (anxiety, anger, and sadness) and groups (AN, BN, and HC).
Results
Main effects of emotion (p < .001) and group (p < .001) were found, but no interaction effects were found (p > .05). Post hoc tests showed lower maladaptive and higher adaptive ER for anxiety than anger or sadness (p < .001). AN and BN reported lower adaptive (p < .001) and higher maladaptive ER than HCs (p < .001). BN showed the highest levels of maladaptive ER (p = .009).
Discussion
The differences between AN and BN in adaptive and maladaptive ER should be considered. Furthermore, investigating differences in ER of other emotions in eating disorders might be promising.
Genotype-phenotype correlations for most monogenic neurological disorders are incompletely understood. Fu et al. draw upon data on 615 HPRT mutations, including 130 new cases, and their relationship ...to Lesch-Nyhan disease severity. The effect of mutations on hypoxanthine-guanine phosphoribosyltransferase activity accounts for much but not all of the phenotypic variability.
Establishing meaningful relationships between genetic variations and clinical disease is a fundamental goal for all human genetic disorders. However, these genotype–phenotype correlations remain incompletely characterized and sometimes conflicting for many diseases. Lesch-Nyhan disease is an X-linked recessive disorder that is caused by a wide variety of mutations in the HPRT1 gene. The gene encodes hypoxanthine-guanine phosphoribosyl transferase, an enzyme involved in purine metabolism. The fine structure of enzyme has been established by crystallography studies, and its function can be measured with very precise biochemical assays. This rich knowledge of genetic alterations in the gene and their functional effect on its protein product provides a powerful model for exploring factors that influence genotype–phenotype correlations. The present study summarizes 615 known genetic mutations, their influence on the gene product, and their relationship to the clinical phenotype. In general, the results are compatible with the concept that the overall severity of the disease depends on how mutations ultimately influence enzyme activity. However, careful evaluation of exceptions to this concept point to several additional genetic and non-genetic factors that influence genotype–phenotype correlations. These factors are not unique to Lesch-Nyhan disease, and are relevant to most other genetic diseases. The disease therefore serves as a valuable model for understanding the challenges associated with establishing genotype–phenotype correlations for other disorders.
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