Alteration of plasma glutamate and glutamine levels in children with high-functioning autism

Background

It has recently been hypothesized that hyperglutamatergia in the brain is involved in the pathophysiology of autism. However, there is no conclusive evidence of the validity of this hypothesis. As peripheral glutamate/glutamine levels have been reported to be correlated with those of the central nervous system, the authors examined whether the levels of 25 amino acids, including glutamate and glutamine, in the platelet-poor plasma of drug-naïve, male children with high-functioning autism (HFA) would be altered compared with those of normal controls.

Methodology/Principal Findings

Plasma levels of 25 amino acids in male children (N = 23) with HFA and normally developed healthy male controls (N = 22) were determined using high-performance liquid chromatography. Multiple testing was allowed for in the analyses. Compared with the normal control group, the HFA group had higher levels of plasma glutamate and lower levels of plasma glutamine. No significant group difference was found in the remaining 23 amino acids. The effect size (Cohen''s d) for glutamate and glutamine was large: 1.13 and 1.36, respectively. Using discriminant analysis with logistic regression, the two values of plasma glutamate and glutamine were shown to well-differentiate the HFA group from the control group; the rate of correct classification was 91%.

Conclusions/Significance

The present study suggests that plasma glutamate and glutamine levels can serve as a diagnostic tool for the early detection of autism, especially normal IQ autism. These findings indicate that glutamatergic abnormalities in the brain may be associated with the pathobiology of autism.     

A genome-wide survey of genes for enzymes involved in pigment synthesis in an ascidian, Ciona intestinalis

The draft genome sequence and a large quantity of EST and cDNA information are now available for the ascidian Ciona intestinalis. In the present study, genes involved in pigment synthesis pathways were identified in the decoded genome of Ciona, and information about these genes was obtained from available EST and cDNA sequences. It was found that the Ciona genome contains orthologous genes for each enzyme of the melanin, pteridine, ommochrome, papiliochrome, and heme synthesis pathways. Several appear as independent duplications in the Ciona genome. Because cDNA clones for all but two of these genes have already been isolated by the cDNA project, C. intestinalis will provide an experimental system to explore molecular mechanisms underlying color patterns, through future genome-wide studies.     

A hypothesis: radiation-related leukemia is mainly attributable to the small number of people who carry pre-existing clonally expanded preleukemic cells

Human leukemia frequently involves recurrent translocations. Since radiation is a well-known inducer of both leukemia and chromosomal translocations, it has long been suspected that radiation might cause leukemia by inducing specific translocations. However, recent studies clearly indicate that spontaneous translocations specific to acute lymphocytic leukemia (ALL) actually occur much more frequently than do leukemia cases with the same translocations. Moreover, the ALL-associated translocation-bearing cells are often found to have clonally expanded in individuals who do not develop ALL. Since radiation-induced DNA damage is generated essentially randomly in the genome, it does not seem likely that radiation could ever be responsible for the induction of identical translocations of relevance to ALL in multiple cells of an individual and hence be the primary cause of radiation-related leukemia. An alternative hypothesis described here is that the radiation-related ALL risk for a population is almost entirely attributable to a small number of predisposed individuals in whom relatively large numbers of translocation-carrying pre-ALL cells have accumulated. This preleukemic clone hypothesis explains various known characteristics of radiation-related ALL and implies that people who do not have substantial numbers of preleukemic cells (i.e. the great majority) are likely at low risk of developing leukemia. The hypothesis can also be applied to chronic myelogenous leukemia and to young-at-exposure cases of acute myelogenous leukemia.     

Polysaccharide-poly(ethylene glycol) star copolymer as a scaffold for the production of bioactive hydrogels

The production of polysaccharide-derivatized surfaces, polymers, and biomaterials has been shown to be a useful strategy for mediating the biological properties of materials, owing to the importance of polysaccharides for the sequestration and protection of bioactive proteins in vivo. We have therefore sought to combine the benefits of polysaccharide derivatization of polymers with unique opportunities to use these polymers for the production of bioactive, noncovalently assembled hydrogels. Accordingly, we report the synthesis of a heparin-modified poly(ethylene glycol) (PEG) star copolymer that can be used in the assembly of bioactive hydrogel networks via multiple strategies and that is also competent for the delivery of bioactive growth factors. A heparin-decorated polymer, synthesized by the reaction of thiol end-terminated four-arm star PEG (M(n) = 10 000) with maleimide functionalized low molecular weight heparin (LMWH, M(r) = 3000), has been characterized via (1)H NMR spectroscopy and size-exclusion chromatography; results indicate attachment of the LMWH with at least 73% efficiency. Both covalently and noncovalently assembled hydrogels can be produced from the PEG-LMWH conjugate. Viscoelastic noncovalently assembled hydrogels have been formed on the basis of the interaction of the PEG-LMWH with a PEG polymer bearing multiple heparin-binding peptide motifs. The binding and release of therapeutically important proteins from the assembled hydrogels have also been demonstrated via immunochemical assays, which demonstrate the slow release of basic fibroblast growth factor (bFGF) as a function of matrix erosion. The combination of these results suggests the opportunities for producing polymer-polysaccharide conjugates that can assemble into novel hydrogel networks on the basis of peptide-saccharide interactions and for employing these materials in delivery applications.     

Germline transgenesis of the ascidian Ciona intestinalis by electroporation

Microinjection of the Minos transposon is the only reported technique for generating stable transgenic lines in the cosmopolitan ascidian, Ciona intestinalis. To establish a more amenable method for generating stable transgenic Ciona, we examined the possibility of using electroporation of DNA into eggs. From 0-44.4% of electroporated individuals transmitted transgenes to the next generation. The transgene was integrated into one chromosome and multiple copies of the transgene were inserted into one site of the chromosome, indicating that electroporation is an easy and powerful technique for achieving stable transgenesis in C. intestinalis. Together with possible inland culture of this ascidian, this technique will be useful for generating stable lines which have reporter gene expression in a specific tissue or organ and the generation of transposase-expressing stable transgenic (jump-starter) lines and mutator lines which contain a lot of Minos transposons in an insertion position.     

Analysis of FMRFamide-like peptide (FLP) diversity in phylum Nematoda

This study reports a series of systematic BLAST searches of nematode ESTs on the Genbank database, using search strings derived from known nematode FLPs (those encoded by Caenorhabditis elegans flp genes as well as those isolated from other nematodes including Ascaris suum), as well as query sequences representative of theoretical FLPs. Over 1000 putative FLP-encoding ESTs were identified from multiple nematode species. A total of 969 ESTs representing sequelogs of the 23 known C. elegans flp genes were identified in 32 species, from clades I, III, IV and V. Numerical analysis of EST numbers suggests that flp-1, flp-11 and flp-14 are amongst the most highly expressed flp genes. Speculative BLAST searches were performed using theoretical FLP C-termini as queries, in an attempt to identify putative novel FLP sequences in the EST database. These searches yielded eight multi-species sequelogs encoding FLPs with novel signatures that are believed to identify distinct flp genes. These novel genes encode 25 distinct previously unidentified FLPs, and raise the current total of known nematode flp genes to 31. Additionally, software-based analyses of the presence of signal peptides were performed, with signal peptides being identified on at least one member of each group of flp ESTs, further confirming their status as secreted peptides. The data reveal that nematode FLPs encompass the most complex neuropeptide family known within the metazoa. Moreover, individual FLPs and FLP motifs are highly conserved across the nematodes with little evidence for inter-clade or inter-lifestyle variation, supporting their fundamental role in free-living and parasitic species.     

Effect of the melanocortin receptor stimulation or inhibition on ethanol intake in alcohol-preferring rats

It has been recently reported that acute intracerebroventricular injection of 1 nmol/rat of the non-selective melanocortin 3 and 4 receptor (MC3/4) agonist MTII reduces ethanol intake in female AA alcohol-preferring rats and alters opioid peptide levels in the ventral tegmental area of rats. To better understand the role of the MC system in the control of ethanol intake, we tested the acute and chronic effects of lateral ventricular (LV) injections of 0.01-1 nmol MTII, of 0.1-1 nmol of the MC3/4R receptor antagonist agouti related peptide (AgRP), and 0.1-0.5 nmol of the MC3/4R receptor antagonist SHU9119 on food, water, and 10% ethanol intake in Marchigian-Sardinian alcohol-preferring (msP) rats, which spontaneously ingest pharmacologically relevant quantities of ethanol both under short and long term access conditions. The data showed that with 2h/day ethanol access, LV MTII injections reduced intake of food and ethanol intakes. When food, water, and ethanol were available ad libitum and 0.01 nmol MTII was given by daily LV injection, however, ethanol intake was reduced for only the first 2 days, whereas food intake was reduced for all 5 days of treatment. Finally, acute LV injection of neither AgRP nor SHU9119 affected ethanol intake under ad libitum conditions, although both antagonists significantly increased food and water intake. In conclusion, these data fail to support a role for endogenous MC3/4R in the control of spontaneous ethanol intake in the msP rat. MC3/4R agonism, however, reduced ethanol intake in association with reduced food intake, suggesting that MTII might reduce nutrient-related controls of ethanol intake rather than, or in addition to, reward-related controls of ethanol intake.     

DSC study of sucrose melting

An early endothermic peak at approximately 150 degrees C was observed for crystalline sucrose by differential scanning calorimetry. The enthalpy at this temperature was found to vary with recrystallised sucrose from different sources. The addition of mineral salts to recrystallisation solutions decreased the enthalpy of the peak at around 150 degrees C, whereas the absence of salts increased it. The presence of organic solvents and polysaccharides in solution had a minor effect compared to the inorganic impurities. The peak was also depleted by increasing the amount of stirring and temperature at which recrystallisation was performed.