Cortical activity pattern computation

Neural computations are modelled in various ways, but still there is no clear understanding of how the brain performs its computational tasks. This paper presents new results about analysis of neural processes in terms of activity pattern computations. It is shown that it is possible to extract from high-resolution EEG data a first order Markov approximation of a neural communication system employing pattern computations, which is significantly different from similar purely random systems. In our view this result shows that it is likely that neural activity patterns measurable at the macro-level by EEG are correlated with underlying neural computations.     

Biotechnological approach to the synthesis of 9alpha-hydroxylated steroids

The steroid 9alpha-hydroxylase gene has been cloned from Mycobacterium smegmatis into Escherichia coli BL21. Progesterone added to bioreactors was subjected to in vivo transformation into 9alpha-hydroxyprogesterone. In 7 days, 43.6 mg 9alpha-hydroxyprogesterone was formed from 53.8 mg/L progesterone. The enzyme also has shown evidence of processing 4-androstene-3,17-dione in vivo. An extensive analytical method development, including LLE, HPLC-DAD, MS, and NMR was performed to verify the product and to enable a quantitative analysis. Protocols for analytical and preparative separation have been developed, using binaphtol as internal standard. Both the growth pattern and the bioconversion rate were unaffected by the presence of binaphtol in the bioreactor. The enzyme was purified by immobilised metal affinity and ion exchange chromatography, resulting in low in vitro activity.     

Nitric oxide, mitochondrial hyperpolarization, and T cell activation

T lymphocyte activation is associated with nitric oxide (NO) production, which plays an essential role in multiple T cell functions. NO acts as a messenger, activating soluble guanyl cyclase and participating in the transduction signaling pathways involving cyclic GMP. NO modulates mitochondrial events that are involved in apoptosis and regulates mitochondrial membrane potential and mitochondrial biogenesis in many cell types, including lymphocytes. Mitochondrial hyperpolarization (MHP), an early and reversible event during both activation and apoptosis of Tlymphocytes, is regulated by NO. Here, we discuss recent evidence that NO-induced MHP represents a molecular switch in multiple T cell signaling pathways. Overproduction of NO in systemic lupus erythematosus induces mitochondrial biogenesis and alters Ca(2+) signaling. Thus, whereas NO plays a physiological role in lymphocyte cell signaling, its overproduction may disturb normal T cell function, contributing to the pathogenesis of autoimmunity.     

Mitochondrial DNA heteroplasmy in ovine fetuses and sheep cloned by somatic cell nuclear transfer

Background  

The mitochondrial DNA (mtDNA) of the cloned sheep "Dolly" and nine other ovine clones produced by somatic cell nuclear transfer (SCNT) was reported to consist only of recipient oocyte mtDNA without any detectable mtDNA contribution from the nucleus donor cell. In cattle, mouse and pig several or most of the clones showed transmission of nuclear donor mtDNA resulting in mitochondrial heteroplasmy. To clarify the discrepant transmission pattern of donor mtDNA in sheep clones we analysed the mtDNA composition of seven fetuses and five lambs cloned from fetal fibroblasts.     

Life‐history traits and climatic responsiveness in noctuid moths

Emergence phenology has been shown to advance considerably in the past decades in many lepidopterans. Noctuid moths (Noctuidae) constitute a species‐rich family of lepidopterans with a large diversity of life history traits presumably driving climatic responsiveness. In our study we aim to assess the role of life‐history and ecological traits in climatic responsiveness of noctuid moths, whilst controlling for phylogenetic dependence. We used a long‐term dataset of European noctuid moths collected from a light‐trap in northeastern Hungary. As the study site is located at the intersection of several biogeographical zones harbouring a large number of noctuid moth species, our dataset provides a unique possibility to investigate the moths’ climatic sensitivity. To estimate the role of life‐history traits and ecological factors in driving lepidopterans’ response to climatic trends, we employed three proxies related to the species’ ecology (habitat affinity, food plant specialization and food type) and two robust types of life‐history traits (migration strategy and hibernation form). The degree of temporal shifts of various measures of emergence phenology was related to hibernation stage, food type and migration strategy. Large‐scale phylogenetic relatedness exerted little constraint in all models fitted on each measure of phenology. Our results imply that noctuid moths overwintering as adults exhibited greater degrees of phenological shifts than species hibernating as larvae or pupae. It implies that moths hibernating as adults are forced to suspend activity in our climate and the prolongation of autumn activity might be the result of increased plasticity in flight periods.     

MMP-13 selective alpha-sulfone hydroxamates: identification of selective P1' amides

Continuing our interest in designing compounds preferentially potent and selective for MMP-13, we report on a series of hydroxamic acids with a flexible amide P1′ substituents. We identify an amide which spares both MMP-1 and -14, and shows >500 fold selectivity for MMP-13 versus MMP-2 and -8.