Neuronal firing rates account for distractor effects on mnemonic accuracy in a visuo-spatial working memory task

Persistent neural activity constitutes one neuronal correlate of working memory, the ability to hold and manipulate information across time, a prerequisite for cognition. Yet, the underlying neuronal mechanisms are still elusive. Here, we design a visuo- spatial delayed-response task to identify the relationship between the cue-distractor spatial distance and mnemonic accuracy. Using a shared experimental and computational test protocol, we probe human subjects in computer experiments, and subsequently we evaluate different neural mechanisms underlying persistent activity using an in silico prefrontal network model. Five modes of action of the network were tested: weak or strong synaptic interactions, wide synaptic arborization, cellular bistability and reduced synaptic NMDA component. The five neural mechanisms and the human behavioral data, all exhibited a significant deterioration of the mnemonic accuracy with decreased spatial distance between the distractor and the cue. A subsequent computational analysis revealed that the firing rate and not the neural mechanism per se, accounted for the positive correlation between mnemonic accuracy and spatial distance. Moreover, the computational modeling predicts an inverse correlation between accuracy and distractibility. In conclusion, any pharmacological modulation, pathological condition or memory training paradigm targeting the underlying neural circuitry and altering the net population firing rate during the delay is predicted to determine the amount of influence of a visual distraction.     

Expression Profiling of Primary and Metastatic Ovarian Tumors Reveals Differences Indicative of Aggressive Disease

The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs) that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development.     

Cell suspension cultures of Populus tremula × P. tremuloides exhibit a high level of cellulose synthase gene expression that coincides with increased in vitro cellulose synthase activity

Summary. Compared to wood, cell suspension cultures provide convenient model systems to study many different cellular processes in plants. Here we have established cell suspension cultures of Populus tremula L. × P. tremuloides Michx. and characterized them by determining the enzymatic activities and/or mRNA expression levels of selected cell wall-specific proteins at the different stages of growth. While enzymes and proteins typically associated with primary cell wall synthesis and expansion were detected in the exponential growth phase of the cultures, the late stationary phase showed high expression of the secondary-cell-wall-associated cellulose synthase genes. Interestingly, detergent extracts of membranes from aging cell suspension cultures exhibited high levels of in vitro cellulose synthesis. The estimated ratio of cellulose to callose was as high as 50 : 50, as opposed to the ratio of 30 : 70 so far achieved with membrane preparations extracted from other systems. The increased cellulose synthase activity was also evidenced by higher levels of Calcofluor white binding in the cell material from the stationary-phase cultures. The ease of handling cell suspension cultures and the improved capacity for in vitro cellulose synthesis suggest that these cultures offer a new basis for studying the mechanism of cellulose biosynthesis. Correspondence and reprints: School of Biotechnology, Royal Institute of Technology, AlbaNova University Centre, 106 91 Stockholm, Sweden. Present address: Department of Biotechnology, Beijing Forestry University, Beijing, People’s Republic of China     

The ACADS gene variation spectrum in 114 patients with short-chain acyl-CoA dehydrogenase (SCAD) deficiency is dominated by missense variations leading to protein misfolding at the cellular level

Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is an inherited disorder of mitochondrial fatty acid oxidation associated with variations in the ACADS gene and variable clinical symptoms. In addition to rare ACADS inactivating variations, two common variations, c.511C > T (p.Arg171Trp) and c.625G > A (p.Gly209Ser), have been identified in patients, but these are also present in up to 14% of normal populations leading to questions of their clinical relevance. The common variant alleles encode proteins with nearly normal enzymatic activity at physiological conditions in vitro. SCAD enzyme function, however, is impaired at increased temperature and the tendency to misfold increases under conditions of cellular stress. The present study examines misfolding of variant SCAD proteins identified in patients with SCAD deficiency. Analysis of the ACADS gene in 114 patients revealed 29 variations, 26 missense, one start codon, and two stop codon variations. In vitro import studies of variant SCAD proteins in isolated mitochondria from SCAD deficient (SCAD−/−) mice demonstrated an increased tendency of the abnormal proteins to misfold and aggregate compared to the wild-type, a phenomenon that often leads to gain-of-function cellular phenotypes. However, no correlation was found between the clinical phenotype and the degree of SCAD dysfunction. We propose that SCAD deficiency should be considered as a disorder of protein folding that can lead to clinical disease in combination with other genetic and environmental factors. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Antigenic polysaccharides of bacteria: 40. The structures of O-specific polysaccharides from Shigella dysenteriae types 3 and 9 and S. boydii type 4 revised by NMR spectroscopy

The reported structures of O-specific polysaccharides from three standard strains of Shigella bacteria were corrected by modern NMR techniques. The revisions concerned the configuration of the O-glycoside linkage (S. dysenteriae type 3, structure 1), the positions of monosaccharide residue glycosylation and acetylation by pyruvic acid (S. dysenteriae type 9, structure 2), and the attachment position of the side monosaccharide chain (S. boydii type 4, structure 3) [struxture in text].     

Plankton composition and cycling of carbon during the rainy season in a tropical coastal ecosystem, Zanzibar, Tanzania

Biomass, species composition and production of the planktoniccommunity were investigated during the rainy season in May andJune 1999 outside Zanzibar Island, Tanzania. In general, theplankton biomass of different organisms was uniform betweendepths as well as over time. The integrated water column primaryproduction ranged from 204 to 4142 mg C m^–2 day^–1.Bacterial production varied between 10 and 72 mg C m^–2day^–1, comprising ~5% of the total bacterial standingstock. The data obtained from these experiments are summarizedin a carbon budget. At the most 77% of the total primary productionchannelled through the heterotrophic flagellates, ciliates andheterotrophic dinoflagellates to higher trophic levels. Of theestimated carbon demand for mesozooplankton, 28% could potentiallybe met by ciliates and heterotrophic dinoflagellates.     

Synthetic promoter libraries for Corynebacterium glutamicum

The ability to modulate gene expression is an important genetic tool in systems biology and biotechnology. Here, we demonstrate that a previously published easy and fast PCR-based method for modulating gene expression in lactic acid bacteria is also applicable to Corynebacterium glutamicum. We constructed constitutive promoter libraries based on various combinations of a previously reported C. glutamicum -10 consensus sequence (gngnTA(c/t)aaTgg) and the Escherichia coli -35 consensus, either with or without an AT-rich region upstream. A promoter library based on consensus sequences frequently found in low-GC Gram-positive microorganisms was also included. The strongest promoters were found in the library with a -35 region and a C. glutamicum -10 consensus, and this library also represents the largest activity span. Using the alternative -10 consensus TATAAT, which can be found in many other prokaryotes, resulted in a weaker but still useful promoter library. The upstream AT-rich region did not appear to affect promoter strength in C. glutamicum. In addition to the constitutive promoters, a synthetic inducible promoter library, based on the E. coli lac-promoter, was constructed by randomizing the 17-bp spacer between -35 and -10 consensus sequences and the sequences surrounding these. The inducible promoter library was shown to result in β-galactosidase activities ranging from 284 to 1,665 Miller units when induced by IPTG, and the induction fold ranged from 7–59. We find that the synthetic promoter library (SPL) technology is convenient for modulating gene expression in C. glutamicum and should have many future applications, within basic research as well as for optimizing industrial production organisms.     

High-affinity binding of the basement membrane protein collagen type IV to the crystalline virulence surface protein array of Aeromonas salmonicida

The surface of the fish pathogen Aeromonas salmonicida is covered by a paracrystalline array (the A-layer) which is a virulence factor for the organism. Quantification of the ability of A. salmonicida cells to bind collagen types I and IV in a ¹²⁵I-radiolabelled liquid-phase assay showed that A-layer-positive cells bound high levels of collagen type IV, but significantly lower levels of collagen type I. Collagen type IV binding was confirmed using non-radiolabelled enzyme-linked immunosorbent assays. ¹²⁵I-Collagen type IV binding was rapid, specific, saturable, high affinity, and essentially irreversible by unlabelled collagen type IV. The A-layer was responsible for collagen type IV binding because binding was inactivated by selective removal of the A-layer at pH 2.2, and neither isogenic A-layer-deficient A. salmonicida mutants nor strains of Aeromonas hydrophila possessing a morphologically similar paracrystalline array bound this basement membrane protein.     

Association of Helicobacter pylori and gastric autoimmunity: A population-based study

Abstract Based on clinical studies, a negative association between Helicobacter pylori and autoimmune corpus gastritis is described. In the present investigation of an unselected population of 1461 adults we can state, however, that there exists a relationship between H. pylori infection and the development of gastric corpus autoimmunity. As confirmation for the gastric autoantibody development through molecular mimicry, a high homology (72% in 25 amino acid overlap) between the beta subunit of H. pylori urease and that of H + K + ATPase, the gastric parietal cell autoantigen, was revealed.     

Growth Conditions Influence Expression of Cell Surface Hydrophobicity of Staphylococci and Other Wound Infection Pathogens

The initial adhesion of microbes to tissue and solid surfaces can be mediated by hydrophobic interaction. Expression of microbial cell surface hydrophobicity (CSH) is influenced by growth conditions, and often best expressed after growth under nutrient-poor conditions, or “starvation.” In the present study, the CSH of 133 strains of Enterobacteriaceae, Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus faecalis, group A streptococcus, Pseudomonas aeruginosa, Clostridium perfringens, Bacteroides fragilis, Peptococcus magnus, and of 8 Candida albicans strains was measured by the salt aggregation test after growth on hematin agar in a 5% CO₂ atmosphere, or under anaerobiosis. Cells of all but 8 strains expressed pronounced or moderate CSH, i.e., they aggregated in 0.01-2 M ammonium sulfate. When the agar surface was covered by human serum (diluted 1:5) to mimic growth conditions in a wound, 94 strains expressed higher CSH, and 44 strains the same CSH as after growth without serum. The CSH of 12 strains of different species was measured after growth on blood, hematin and PDM agar, with or without serum, and in an aerobic or a 5% CO₂ atmosphere. The highest CSH was expressed after growth in 5% CO₂ with serum, and the lowest growth after on blood agar in aerobic atmosphere. Identical results were obtained with native and heat-inactivated (56 C, 20 min) serum. The reduced surface tension obtained in 5% CO₂, as well as yet unidentified serum factors, promotes expression of CSH.