Improved Estimation and Interpretation of Correlations in Neural Circuits

Ambitious projects aim to record the activity of ever larger and denser neuronal populations in vivo. Correlations in neural activity measured in such recordings can reveal important aspects of neural circuit organization. However, estimating and interpreting large correlation matrices is statistically challenging. Estimation can be improved by regularization, i.e. by imposing a structure on the estimate. The amount of improvement depends on how closely the assumed structure represents dependencies in the data. Therefore, the selection of the most efficient correlation matrix estimator for a given neural circuit must be determined empirically. Importantly, the identity and structure of the most efficient estimator informs about the types of dominant dependencies governing the system. We sought statistically efficient estimators of neural correlation matrices in recordings from large, dense groups of cortical neurons. Using fast 3D random-access laser scanning microscopy of calcium signals, we recorded the activity of nearly every neuron in volumes 200 μm wide and 100 μm deep (150–350 cells) in mouse visual cortex. We hypothesized that in these densely sampled recordings, the correlation matrix should be best modeled as the combination of a sparse graph of pairwise partial correlations representing local interactions and a low-rank component representing common fluctuations and external inputs. Indeed, in cross-validation tests, the covariance matrix estimator with this structure consistently outperformed other regularized estimators. The sparse component of the estimate defined a graph of interactions. These interactions reflected the physical distances and orientation tuning properties of cells: The density of positive ‘excitatory’ interactions decreased rapidly with geometric distances and with differences in orientation preference whereas negative ‘inhibitory’ interactions were less selective. Because of its superior performance, this ‘sparse+latent’ estimator likely provides a more physiologically relevant representation of the functional connectivity in densely sampled recordings than the sample correlation matrix.     

The river before damming: distribution and ecological notes on the endemic species <Emphasis Type="Italic">Echinogammarus cari</Emphasis> (Amphipoda: Gammaridae) in the Dobra River and its tributaries,Croatia

The endemic species Echinogammarus cari (Karaman 1931) is the only species of this genus present in the Black Sea drainage basin of Croatia. The species is known only from its type locality, the Bistrac spring. Since little is known about the distribution and ecology of this amphipod species, research was conducted to determine the extent of its distribution in the Dobra River and its tributaries, part of which will be flooded on the completion of a 52.5 m high dam in 2009. Sampling was conducted at 10 study sites in the drainage area of the sinking Gornja Dobra and at 19 study sites in the Gojačka Dobra, including measurement of physicochemical parameters. To examine microdistribution of this species, samples were collected on moss and on stony substrate. The species is confined to first 15 km of the Gojačka Dobra, its tributary streams Bistrica and Ribnjak, while it is absent in the drainage area of the Gornja Dobra. At all sites where it was recorded, it coexists with Gammarus fossarum, and its relative abundance was significantly higher on moss microhabitats, while G. fossarum was more abundant on a stony substrate. The downstream decrease in the relative abundance of E. cari could be related to the longitudinal decrease in conductivity and the increase of water temperature fluctuations. After the completion of the dam, 60% of the presently known distribution area of E. cari will be flooded. Consequently, the species is likely to become endangered.     

Withanolide A series steroidal lactones from Eucalyptus globulus bark

A new steroidal lactone of the Withanolide A series has been isolated from the supercritical fluid extract of Eucalyptus globulus L. (bark) as a major component (I) along with a known structurally similar steroidal lactone as minor component (II). The structural identification of the new lactone was accomplished by different spectroscopic techniques viz. ¹H and ¹³C NMR, etc. The relative stereochemistry was unequivocally determined from the X-ray crystallography.     

Detection of single base polymorphism in p53 gene by ligase detection reaction and rolling circle amplification on microarrays

We combined three modern technologies of single base polymorphism detection in human genome: ligase detection reaction, rolling circle amplification and IMAGE hydro-gel microarrays. Polymorphism in target DNA was tested by selective ligation on microarray. Product of the ligase reaction was determined in microarray gel pads by rolling circle amplification. Two different methods were compared. In first, selective ligation of short oligonucleotides immobilized on microarray was used with subsequent amplification on preformed circle probe ("common circle"). The circle probe was designed especially for human genome research. In second variant, allele-specific padlock probes that may be circularized by selective ligation were immobilized on microarray. Polymorphism of codon 72 in human p53 gene was used as a biological model. It was shown that LDR/RCA on microarray is a quantitative reaction and gives high discrimination of alleles. Principles and perspectives of selective ligation and rolling circle amplification are being discussed.     

Palladium(II) complexes of quinolinylaminophosphonates: synthesis, structural characterization, antitumor and antimicrobial activity

Three types of palladium(II) halide complexes of quinolinylaminophosphonates have been synthesized and studied. Diethyl and dibutyl [α-anilino-(quinolin-2-ylmethyl)]phosphonates (L1, L2) act as N,N-chelate ligands through the quinoline and aniline nitrogens giving complexes cis-[Pd(L1/L2)X₂] (X═Cl, Br) (1-4). Their 3-substituted analogues [α-anilino-(quinolin-3-ylmethyl)]phosphonates (L3, L4) form dihalidopalladium complexes trans-[Pd(L3/L4)₂X₂] (5-8), with trans N-bonded ligand molecules only through the quinoline nitrogen. Dialkyl [α-(quinolin-3-ylamino)-N-benzyl]phosphonates (L5, L6) give tetrahalidodipalladium complexes [Pd₂(L5/L6)₃X₄] (9-12), containing one bridging and two terminal ligand molecules. The bridging molecule is bonded to the both palladium atoms, one through the quinoline and the other through the aminoquinoline nitrogen, whereas terminal ligand molecules are coordinated each only to one palladium via the quinoline nitrogen. Each palladium ion is also bonded to two halide ions in a trans square-planar fashion. The new complexes were identified and characterized by elemental analyses and by IR, UV-visible, ¹H, ¹³C and ³¹P nuclear magnetic resonance and ESI-mass spectroscopic studies. The crystal structures of complexes 1-4 and 6 were determined by X-ray structure analysis. The antitumor activity of complexes in vitro was investigated on several human tumor cell lines and the highest activity with cell growth inhibitory effects in the low micromolar range was observed for dipalladium complexes 11 and 12 derived from dibutyl ester L6. The antimicrobial properties in vitro of ligands and their complexes were studied using a wide spectrum of bacterial and fungal strains. No specific activity was noted. Only ligands L3 and L4 and tetrahalidodipalladium complexes 9 and 11 show poor activities against some Gram positive bacteria.     

Suppression of PKR promotes network excitability and enhanced cognition by interferon-γ-mediated disinhibition

The double-stranded RNA-activated protein kinase (PKR) was originally identified as a sensor of virus infection, but its function in the brain remains unknown. Here, we report that the lack of PKR enhances learning and memory in several behavioral tasks while increasing network excitability. In addition, loss of PKR increases the late phase of long-lasting synaptic potentiation (L-LTP) in hippocampal slices. These effects are caused by an interferon-γ (IFN-γ)-mediated selective reduction in GABAergic synaptic action. Together, our results reveal that PKR finely tunes the network activity that must be maintained while storing a given episode during learning. Because PKR activity is altered in several neurological disorders, this kinase presents a promising new target for the treatment of cognitive dysfunction. As a first step in this direction, we show that a selective PKR inhibitor replicates the Pkr(-/-) phenotype in WT mice, enhancing long-term memory storage and L-LTP.     

Concentration on Diapak C 16 capsules of lovastatin, mevinolinic acid and other inhibitors of biosynthesis of sterins produced by Penicillium citrinum 89]

The method of lovastatine and mevinolinic acid known as competitive inhibitors of HMG-CoA-reductase and produced by micromycetes was elaborated. The inhibitors from diluted water solutions were fully absorbed on Diapak C16 patrons. The rate of inhibitors elution from the patrones was more than 95 per cent. Patrons may be used for concentration of lovastatine group inhibitors from the culture media. Inhibitors synthesis by the Penicillium citrinum 89 was investigated in dynamics with the use of Diapak C16 patrones. It was shown that UV-spectrum of inhibitor produced by P. citrinum 89 was identical with compactin spectrum and had absorbance maximum at 230, 237 and 247 nm.