Frequent Seizures Are Associated with a Network of Gray Matter Atrophy in Temporal Lobe Epilepsy with or without Hippocampal Sclerosis

Objective

Patients with temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) have diffuse subtle gray matter (GM) atrophy detectable by MRI quantification analyses. However, it is not clear whether the etiology and seizure frequency are associated with this atrophy. We aimed to evaluate the occurrence of GM atrophy and the influence of seizure frequency in patients with TLE and either normal MRI (TLE-NL) or MRI signs of HS (TLE-HS).

Methods

We evaluated a group of 172 consecutive patients with unilateral TLE-HS or TLE-NL as defined by hippocampal volumetry and signal quantification (122 TLE-HS and 50 TLE-NL) plus a group of 82 healthy individuals. Voxel-based morphometry was performed with VBM8/SPM8 in 3T MRIs. Patients with up to three complex partial seizures and no generalized tonic-clonic seizures in the previous year were considered to have infrequent seizures. Those who did not fulfill these criteria were considered to have frequent seizures.

Results

Patients with TLE-HS had more pronounced GM atrophy, including the ipsilateral mesial temporal structures, temporal lobe, bilateral thalami and pre/post-central gyri. Patients with TLE-NL had more subtle GM atrophy, including the ipsilateral orbitofrontal cortex, bilateral thalami and pre/post-central gyri. Both TLE-HS and TLE-NL showed increased GM volume in the contralateral pons. TLE-HS patients with frequent seizures had more pronounced GM atrophy in extra-temporal regions than TLE-HS with infrequent seizures. Patients with TLE-NL and infrequent seizures had no detectable GM atrophy. In both TLE-HS and TLE-NL, the duration of epilepsy correlated with GM atrophy in extra-hippocampal regions.

Conclusion

Although a diffuse network GM atrophy occurs in both TLE-HS and TLE-NL, this is strikingly more evident in TLE-HS and in patients with frequent seizures. These findings suggest that neocortical atrophy in TLE is related to the ongoing seizures and epilepsy duration, while thalamic atrophy is more probably related to the original epileptogenic process.     

Conformational analysis of the dinucleotides 5'-methylphospho-N6-dimethyladenylyl-uridine (mpm62A-U) and 5'methylphospho-uridylyl-N6-dimethyladenosine (mpU-m62A) and of the trinucleotide U-m62A-U. A nuclear magnetic resonance and circular dichroic study

NMR and CD studies were carried out on the dinucleotides 5'-methylphospho-N6-dimethyladenylyl-uridine (mpm62-U) and 5'-methylphospho-uridylyl-N6-dimethyladenosine (mpU-m62A) and on the trinucleotide U-m62A-U. A detailed comparison is given of the conformational features of mpm62A-U and mpU-m62A with the corresponding 5'-nonphosphorylated dinucleotides m62A-U and U-m62A, respectively. The behaviour of the trinucleotide U-m62A-U is compared with the properties of the constituent dinucleotides U-m62A and mpm62A-U. Chemical-shift and CD data were used to determine the amount of stacking interactions. For each compound NMR spectra were recorded at two or three sample concentrations in order to separate intermolecular and intramolecular base-base interactions. The coupling constants of the ribose ring are interpreted in terms of the N/S equilibrium, and population distributions along the backbone angles beta, gamma and epsilon are presented. The combined data indicate a strong similarity between mpm62A-U and m62A-U both in degree and in mode of stacking. In contrast, the existence of different types of stacking interactions in mpU-m62A and U-m62A is suggested in order to explain the NMR and CD data. It is concluded that dinucleoside bisphosphates serve better as a model for the behaviour of trinucleotides than dinucleoside monophosphates. The trinucleotide U-m62A-U adopts a regular single-stranded stacked RNA structure with preference for N-type ribose and gamma+ and beta t backbone torsion angles. The difference in behaviour between the U-m62A- part of U-m62A-U and the dimer U-m62A is seen as a typical example of conformational transmission.     

caCORE: a common infrastructure for cancer informatics

MOTIVATION:Sites with substantive bioinformatics operations are challenged to build data processing and delivery infrastructure that provides reliable access and enables data integration. Locally generated data must be processed and stored such that relationships to external data sources can be presented. Consistency and comparability across data sets requires annotation with controlled vocabularies and, further, metadata standards for data representation. Programmatic access to the processed data should be supported to ensure the maximum possible value is extracted. Confronted with these challenges at the National Cancer Institute Center for Bioinformatics, we decided to develop a robust infrastructure for data management and integration that supports advanced biomedical applications. RESULTS: We have developed an interconnected set of software and services called caCORE. Enterprise Vocabulary Services (EVS) provide controlled vocabulary, dictionary and thesaurus services. The Cancer Data Standards Repository (caDSR) provides a metadata registry for common data elements. Cancer Bioinformatics Infrastructure Objects (caBIO) implements an object-oriented model of the biomedical domain and provides Java, Simple Object Access Protocol and HTTP-XML application programming interfaces. caCORE has been used to develop scientific applications that bring together data from distinct genomic and clinical science sources. AVAILABILITY: caCORE downloads and web interfaces can be accessed from links on the caCORE web site (http://ncicb.nci.nih.gov/core). caBIO software is distributed under an open source license that permits unrestricted academic and commercial use. Vocabulary and metadata content in the EVS and caDSR, respectively, is similarly unrestricted, and is available through web applications and FTP downloads. SUPPLEMENTARY INFORMATION: http://ncicb.nci.nih.gov/core/publications contains links to the caBIO 1.0 class diagram and the caCORE 1.0 Technical Guide, which provide detailed information on the present caCORE architecture, data sources and APIs. Updated information appears on a regular basis on the caCORE web site (http://ncicb.nci.nih.gov/core).     

Evolution of oestrogen functions in vertebrates

Steroidal oestrogens have been isolated from marine and terrestrial animals representative of all major classes of vertebrates including fish, amphibians, reptiles, birds and mammals. In general, oestrogens are responsible for most features characteristic of the female sex of a species, such as metabolic, behavioural and morphological changes during the stages of reproduction; they also support several processes in males. The evolution of the hormonal system always involves both the ligand and its sites of interaction. In the case of oestrogens, the steroid producing enzymes, mainly the aromatase complex, and the oestrogen receptor belong together within their co-evolution. The finding of oestrogenic steroids, the more recent identification of aromatase and receptor genes and their expression fit together, thereby confirming the importance for all vertebrates. Within the present paper, the evolution of the physiological functions of oestrogens from oviparous vertebrates to Eutherian mammals, oestrogen biosynthesis, metabolization and signalling pathways will be reviewed in detail.     

Presence of a Vanadium Nitrogenase in Azotobacter paspali

There have been no previous studies on the genetics of Azotobacter paspali, an aerobic bacterium which forms a highly specific diazotrophic association with Bahia grass (Paspalum notatum). We constructed A. paspali strains defective in the molybdenum nitrogenase so that alternative N₂ases could be studied. The cosmid vector pTBE and genomic DNA fragments (~50 kb) of A. paspali ATCC 23367 were used to construct a gene library in Escherichia coli. Recombinant cosmids containing sequences homologous to molybdenum nitrogenase nifDK structural genes were identified by hybridization. A 2.9-kb fragment bearing the putative nifDK genes of A. paspali was subcloned and mutagenized in vitro by the insertion of a kanamycin resistance gene cassette. The mutation was recombined into the chromosome of A. paspali with the suicide vector pCU101. One resultant mutant strain, AP2, was incapable of diazotrophic growth in a molybdenum-containing medium (Nif^-) without vanadium but grew well in a molybdenum-deficient medium with vanadium. The nitrogenase system in AP2 reduced acetylene to ethylene and produced ethane as 2.4% of the total products. Molybdenum levels as low as 10 nM prevented the diazotrophic growth of AP2, even in the presence of vanadium at levels up to 10 μM. These results are consistent with the existence of a vanadium nitrogenase system in A. paspali.     

Effects of drought and root injury on plant-generated CS2 emissions in soil

Conditions under which some plants emit carbon disulfide (CS₂) in the soil are unknown. A pot assembly was constructed to measure soil CS₂ emissions by Mimosa pudica under conditions of undisturbed growth, root injury, and drought stress. When M. pudica was grown without disturbance, soil CS₂ emissions were below the limit of detection (0.1 ng CS₂ mL^–1) for the entire 8-wk sampling period. However, when the roots of 6-wk-old M. pudica plants were cut to a depth of 10 cm, a maximum of 0.5 and 0.4 ng CS₂ mL^–1 was emitted within minutes at the 5- and 10-cm depths, respectively. These emissions declined slowly to undetectable levels after 50 min. No detectable CS₂ emissions were observed at the 0- and 15-cm depths. No CS₂ was emitted when 6-wk-old M. pudica plants were subjected to drought stress, however, when the same plants were watered, a maximum of 0.3, 0.4, and 0.5 ng CS₂ mL^–1 was emitted within minutes at the 5-, 10- and 15-cm depths, respectively. These emissions were detectable for at least 2 hr at the 10- and 15-cm depths. No detectable CS₂ emissions were observed at the 0-cm depth after watering. No detectable CS₂ emissions were observed at any depth under any conditions of undisturbed growth, root injury, or drought stress followed by watering for assemblies containing either no plants or Albizia julibrissin, a plant that is closely related to M. pudica but does not emit CS₂. Mimosa pudica emitted detectable CS₂ under conditions of root injury and rewetting of dry soil but not under conditions of undisturbed growth. Release of such a biocidal sulfide only during conditions of root injury or rewetting of dry soil would be advantageous to M. pudica.     

Conformational analysis of a modified ribotetranucleoside triphosphate: m6(2)A-U-m6(2)A-U studied in aqueous solution by nuclear magnetic resonance at 500 MHz

The complete and unequivocal assignment of the 24 ribose proton signals of m6(2)A(1)-U(2)-m6(2)(3)-U(4) by means of 500 MHz NMR spectroscopy at 17 degrees C is given. this assignment is based on scrupulous decoupling experiments carries out at various temperatures. Analysis of the observed chemical shifts and coupling constants of the tetramer shows that the two fragments -m6(2)A(3)-U(4) comprising the 3'-end occur mainly in the classical right-handed stack conformation, whereas the 5'-end the -U(2)- residue appears bulged out in favour of a less well-defined stacking interaction between the bases m6(2)A(1)-and -m6(2)A(3)-. Conformational populations about each of the torsional degrees of freedom along the backbone are discussed. A modernized version of pseudorotation analysis is used to delineate the conformational behaviour of the four ribose rings.