A multi-stage model for fundamental functional properties in primary visual cortex

Many neurons in mammalian primary visual cortex have properties such as sharp tuning for contour orientation, strong selectivity for motion direction, and insensitivity to stimulus polarity, that are not shared with their sub-cortical counterparts. Successful models have been developed for a number of these properties but in one case, direction selectivity, there is no consensus about underlying mechanisms. We here define a model that accounts for many of the empirical observations concerning direction selectivity. The model describes a single column of cat primary visual cortex and comprises a series of processing stages. Each neuron in the first cortical stage receives input from a small number of on-centre and off-centre relay cells in the lateral geniculate nucleus. Consistent with recent physiological evidence, the off-centre inputs to cortex precede the on-centre inputs by a small (～4 ms) interval, and it is this difference that confers direction selectivity on model neurons. We show that the resulting model successfully matches the following empirical data: the proportion of cells that are direction selective; tilted spatiotemporal receptive fields; phase advance in the response to a stationary contrast-reversing grating stepped across the receptive field. The model also accounts for several other fundamental properties. Receptive fields have elongated subregions, orientation selectivity is strong, and the distribution of orientation tuning bandwidth across neurons is similar to that seen in the laboratory. Finally, neurons in the first stage have properties corresponding to simple cells, and more complex-like cells emerge in later stages. The results therefore show that a simple feed-forward model can account for a number of the fundamental properties of primary visual cortex.     

Reduced frequency of circulating regulatory T cells and their related immunosuppressive mediators in treated celiac patients

Background

Regulatory T cells (Tregs) have an important role in the control of the immune responses. This study aimed to compare the frequency of peripheral blood (PB) CD4+?CD25+?FoxP3+?Treg cells and PB and duodenal expression levels of pro- and anti-inflammatory mediators in treated celiac disease (CD) patients and healthy controls.

Methods and results

Duodenal biopsy specimens and PB samples were collected from 60 treated CD patients and 60 controls. Flow cytometry analysis was conducted on peripheral blood mononuclear cell (PBMC) specimens and relative PB and duodenal mRNA expression levels of CD25, forkhead box P3 (Foxp3), interleukin (IL)-10 and granzyme B (GrzB) were evaluated using quantitative real-time PCR. The levels of serum IL-10 and IL-6 were tested with sandwich enzyme-linked immunosorbent assay kits. p values?<?0.05 were considered significant. Flow cytometry analysis showed a significant decrease in the number of Tregs in CD patients’ PBMC specimens (p?=?0.012). CD25 and Foxp3 PB mRNA expressions were also lower in CD patients without reaching the significance level (p?>?0.05). IL-10 PB mRNA and protein expression did not differ between the groups (p?>?0.05), and GrzB PB expression was significantly reduced in CD patients (p?=?0.001). In duodenal specimens of CD patients, while significantly increased CD25, Foxp3 mRNA expression (p?=?0.01 and 0.001, respectively) and decreased IL-10 mRNA expression (p?=?0.02) were observed, GrzB mRNA expression did not differ between groups (p?>?0.05). Moreover, a high serum level of IL-6 was observed in CD patients (p?=?0.001).

Conclusions

Despite following the gluten free diet, there may still be residual inflammation in the intestine of CD patients. Accordingly, finding a therapeutic approach based on strengthening the function of Treg cells in CD might be helpful.

     

Autoradiographic method to screen for soil microorganisms which accumulate zinc

An autoradiographic method was developed to screen for and isolate soil microorganisms which accumulate zinc (Zn). Diluted soil samples (Rubicon fine sand, Entic Haplorthods [pH 5.9]) were plated on soil extract-glucose agar containing radioactive 65Zn. After 7 days of incubation, individual colonies which accumulated sufficient 65Zn could be detected by autoradiography. These colonies were isolated and confirmed as Zn accumulators in pure culture by using the autoradiographic plate technique. Most Zn accumulators were filamentous fungi, identified as Penicillium janthinellum, Aspergillus fumigatus, and Paecilomyces sp. Isolates of Penicillium janthinellum were the most common Zn accumulators. The most abundant Zn-accumulating bacteria were Bacillus spp. The validity of the autoradiographic plate technique to differentiate soil microbes which accumulate Zn was examined independently by energy dispersive X-ray analysis in a scanning electron microscope. This method confirmed that fungal isolates which gave positive autoradiographic responses in the plate assay bioaccumulated more Zn in their biomass than fungal isolates from the same soil sample which gave negative autoradiographic responses. Thus, this technique can be applied to specifically screen for and isolate microbes from the environment which bioaccumulate Zn.     

Experimentation on Degradation of Petroleum in Contaminated Soils in the Root Zone of Maize (Zea Mays L.) Inoculated with Piriformospora Indica

Plant-based methods such as rhizodegradation are very promising for the remediation of petroleum-contaminated soils. Associations of plants with endophytes can further enhance their phytoremediation potential. In this study, a rhizobox experiment was conducted to investigate whether inoculation with the root-colonizing fungus Piriformospora indica could further enhance the degradation of petroleum hydrocarbons in the root zone of maize (Zea mays L.). The rhizoboxes were subdivided into compartments in accordance with distance from the plants. After filling the boxes with soil from a petroleum-contaminated site, seedlings that had either been inoculated with P. indica or not were grown in the middle compartments of the rhizoboxes and grown for 64 days. A plant-free treatment was included for control. The presence of roots strongly increased the counts of total and petroleum-degrading soil bacteria, respiration, dehydrogenase activity, water-soluble phenols and petroleum degradation. All these effects were also found in the soil adjacent to the middle compartments of the rhizoboxes, but strongly decreased further away from it. Inoculation with P. indica further enhanced all the recorded parameters without changing the spatial pattern of the effects. Inoculated plants also produced around 40% more root and shoot biomass than noninoculated plants and had greener leaves. Together, the results indicate that the treatment effects on the recorded soil microbial and biochemical parameters including petroleum hydrocarbon degradation were primarily due to increased root exudation. Irrespectively of this, they show that maize can be used to accelerate the rhizodegradation of petroleum hydrocarbons in soil and that inoculation with P. indica can substantially enhance the phytoremediation performance of maize.     

Extent of cell differentiation and capacity for cartilage synthesis in human adult adipose‐derived stem cells: Comparison with fetal chondrocytes

This study evaluated the extent of differentiation and cartilage biosynthetic capacity of human adult adipose‐derived stem cells relative to human fetal chondrocytes. Both types of cell were seeded into nonwoven‐mesh polyglycolic acid (PGA) scaffolds and cultured under dynamic conditions with and without addition of TGF‐β1 and insulin. Gene expression for aggrecan and collagen type II was upregulated in the stem cells in the presence of growth factors, and key components of articular cartilage such as glycosaminoglycan (GAG) and collagen type II were synthesized in cultured tissue constructs. However, on a per cell basis and in the presence of growth factors, accumulation of GAG and collagen type II were, respectively, 3.4‐ and 6.1‐fold lower in the stem cell cultures than in the chondrocyte cultures. Although the stem cells synthesized significantly higher levels of total collagen than the chondrocytes, only about 2.4% of this collagen was collagen type II. Relative to cultures without added growth factors, treatment of the stem cells with TGF‐β1 and insulin resulted in a 59% increase in GAG synthesis, but there was no significant change in collagen production even though collagen type II gene expression was upregulated 530‐fold. In contrast, in the chondrocyte cultures, synthesis of collagen type II and levels of collagen type II as a percentage of total collagen more than doubled after growth factors were applied. Although considerable progress has been achieved to develop differentiation strategies and scaffold‐based culture techniques for adult mesenchymal stem cells, the extent of differentiation of human adipose‐derived stem cells in this study and their capacity for cartilage synthesis fell considerably short of those of fetal chondrocytes. Biotechnol. Bioeng. 2010;107: 393–401. © 2010 Wiley Periodicals, Inc.     

How the Nucleus and Mitochondria Communicate in Energy Production During Stress: Nuclear MtATP6, an Early-Stress Responsive Gene, Regulates the Mitochondrial F1F0-ATP Synthase Complex

A small number of stress-responsive genes, such as those of the mitochondrial F₁F₀-ATP synthase complex, are encoded by both the nucleus and mitochondria. The regulatory mechanism of these joint products is mysterious. The expression of 6-kDa subunit (MtATP6), a relatively uncharacterized nucleus-encoded subunit of F₀ part, was measured during salinity stress in salt-tolerant and salt-sensitive cultivated wheat genotypes, as well as in the wild wheat genotypes, Triticum and Aegilops using qRT-PCR. The MtATP6 expression was suddenly induced 3 h after NaCl treatment in all genotypes, indicating an early inducible stress-responsive behavior. Promoter analysis showed that the MtATP6 promoter includes cis-acting elements such as ABRE, MYC, MYB, GTLs, and W-boxes, suggesting a role for this gene in abscisic acid-mediated signaling, energy metabolism, and stress response. It seems that 6-kDa subunit, as an early response gene and nuclear regulatory factor, translocates to mitochondria and completes the F₁F₀-ATP synthase complex to enhance ATP production and maintain ion homeostasis under stress conditions. These communications between nucleus and mitochondria are required for inducing mitochondrial responses to stress pathways. Dual targeting of 6-kDa subunit may comprise as a mean of inter-organelle communication and save energy for the cell. Interestingly, MtATP6 showed higher and longer expression in the salt-tolerant wheat and the wild genotypes compared to the salt-sensitive genotype. Apparently, salt-sensitive genotypes have lower ATP production efficiency and weaker energy management than wild genotypes; a stress tolerance mechanism that has not been transferred to cultivated genotypes.     

Assessment of Heavy Metal Pollution in Water and Sediments from the Ghalechay River,Baychebagh Copper Mine Area,Iran

The concentrations of selected heavy metals in sediments and waters in Baychebagh copper mine were determined using ICP-OES. Except for Co, the average concentrations of Cd, Cu, Pb, and Zn in sediments from the Ghalechay River in the district exceed the world-average shale and continental upper crust value. Enrichment factors for Pb, Cu, and Cd were significantly enriched in sediments, indicating environmental contamination. Geoaccumulation index calculated for different sampling stations indicates that the sediments are unpolluted with respect to Co and Zn while unpolluted to moderately polluted with Cu and highly polluted with Pb and Cd. The Sediment Quality Guidelines (SQGs) suggest that Cd and Pb may pose the highest risk for the environment. Sequential extraction analyses of sediments revealed that Cu, Co, Pb, and Zn bound to extractable, carbonate, reducible and oxidizable fractions are lower than residual fraction. About 10% of the total Pb was associated with the exchangeable fraction, indicating remobilization, while Cd (89%), Pb (73%) Co (58%), Cu (76%), and Zn (68%) closely associated with the residual and oxidizable fractions, resulting in their environmental immobility. The residual forms are not expected to be released under normal conditions in the river and could be considered an inert phase.     

Neotyphodium Endophyte Changes Phytoextraction of Zinc in Festuca arundinacea and Lolium perenne

The effect of Neotyphodium endophytes on growth parameters and zinc (Zn) tolerance and uptake was studied in two grass species of Festuca arundinacea and Lolium perenne. Plants were grown under different Zn concentrations (control, 200, 400, 800, and 1800 mg kg^?1) in potted soil for 5 months. The results showed that the number of plant tillers was 85 and 51% greater in endophyte infected Festuca (FaEI) and Lolium (LpEI), respectively, compared to their endophyte free (EF) plants. Roots and shoots dry weights in infected Festuca were 87 and 9% greater than non-infected counterparts but in opposite, EF Lolium had 47 and 8% greater root and shoot dry weights than LpEI. Endophyte infected Festuca and Lolium improved chlorophyll fluorescence as Fv/Fm at high concentrations of Zn, showing their better chlorophyll functions and significant reduction of Zn stress in endophyte infected plants. Shoots of endophyte infectedFestuca had 82% greater concentration of Zn than EF Festuca when grown in soil containing 1800 mg kg^?1 Zn. Festuca and Lolium may tolerate high Zn concentration in soil without reduction in shoot and root growth. Endophyte infection in Festuca may help the grass accumulate and transport more Zn in aboveground parts under Zn-stress, thereby aiding phytoremediation of contaminated soils.     

Aspergillus fumigatus AR04 obeys Arrhenius' rule in cultivation temperature shifts from 30 to 40°C

To set a benchmark in fungal growth rate, a differential analysis of prototrophic Aspergillus fumigatus AR04 with three ascomycetes applied in > 10³ t year^-1 scale was performed, i.e. Ashbya gosspyii (riboflavin), Aspergillus niger (citric acid) and Aspergillus oryzae (food-processing). While radial colony growth decreased 0.5-fold when A. gossypii was cultivated at 40°C instead of 28°C, A. fumigatus AR04 responded with 1.7-fold faster hyphal growth. A. niger and A. oryzae formed colonies at 40°C, but not at 43°C. Moreover, all A. fumigatus strains tested grew even at 49°C. In chemostat experiments, A. fumigatus AR04 reached steady state at a dilution rate of 0.7 h^-1 at 40°C, 120% more than reported for A. gossypii at 28°C. To study mycelial growth rates under unlimited conditions, carbon dioxide increase rates were calculated from concentrations detected online in the exhaust of batch fermentations for 3 h only. All rates calculated suggest that A. fumigatus AR04 approximates Arrhenius’ rule when comparing short cultivations at 30°C with those at 40°C. Linearization of the exponential phase and comparison of the slopes revealed an increase to 192% by the 10°C up-shift.     

Serotonin activates angiogenic phosphorylation signaling in human endothelial cells

Serotonin, a known neurotransmitter, also functions as an angiokine to promote angiogenesis. The majority of serotonin in the human body is stored in platelets, and platelet aggregation leads to significant release of serotonin in thrombotic tumor environment. We have investigated serotonin signaling in human endothelial cells. Through G-protein-coupled receptors, serotonin at physiologically relevant concentrations activated Src/PI3K/AKT/mTOR/p70S6K phosphorylation signaling, and this activation was similar to that seen with VEGF. This finding provides insight into the overlapping angiogenic signaling pathways stimulated by serotonin in tumor environment, and suggests one of the mechanisms underlying resistance to current VEGF-targeting antiangiogenic therapy against cancer.