Computational model of excitatory/inhibitory ratio imbalance role in attention deficit disorders

Impairments in attentional behaviors, including over-selectivity, under-selectivity, distractibility and difficulty in shift of attention, are widely reported in several developmental disorders, including autism. Uncharacteristic inhibitory to excitatory neuronal number ratio (IER) and abnormal synaptic strength levels in the brain are two broadly accepted neurobiological disorders observed in autistic individuals. These neurobiological findings are contrasting and their relation to the atypical attentional behaviors is not clear yet. In this paper, we take a computational approach to investigate the relation of imbalanced IER and abnormal synaptic strength to some well-documented spectrum of attentional impairments. The computational model is based on a modified version of a biologically plausible neural model of two competing minicolumns in IT cortex augmented with a simple model of top-down attention. Top-down attention is assumed to amplify (attenuates) attended (unattended) stimulus. The inhibitory synaptic strength parameter in the model is set such that typical attentional behavior is emerged. Then, according to related findings, the parameter is changed and the model's attentional behavior is considered. The simulation results show that, without any change in top-down attention, the abnormal inhibitory synaptic strength values - and IER imbalance- result in over-selectivity, under-selectivity, distractibility and difficulty in shift of attention in the model. It suggests that the modeled neurobiological abnormalities can be accounted for the attentional deficits. In addition, the atypical attentional behaviors do not necessarily point to impairments in top-down attention. Our simulations suggest that limited changes in the inhibitory synaptic strength and variations in top-down attention signal affect the model's attentional behaviors in the same way. So, limited deficits in the inhibitory strength may be alleviated by appropriate change in top-down attention biasing. Nevertheless, our model proposes that this compensation is not possible for very high and very low values of the inhibitory strength.     

Cysteine enhances activity and stability of immobilized papain

Immobilization of papain on Sepharose 6B in the presence of different concentrations of cysteine affected the enzyme activity depending on cysteine concentration. The maximum specific activity was observed when papain was immobilized with 200 mM cysteine. The immobilization process brought significant enhancement of stability to temperature and extreme pH values with respect to free papain. After immobilization, the optimum temperature of papain activity increased by 20°C (from 60 to 80°C) and its optimum pH activity shifted from 6.5 to 8.0. Catalytic efficiency (k_cat/K_m) and specific activity of the immobilized enzyme do not significantly change after immobilization. The temperature profile of this form of immobilized papain showed a broad range of activity compared with both free and immobilized form of papain in the absence of cysteine. This significant behavior in terms of activation energy is also discussed.     

Zinc-leuprolide complex: preparation, physicochemical characterization and release behaviour from in situ forming implant.

Leuprolide acetate (LA) has been accepted as treatment for prostatic cancer and is currently also being evaluated in phase II clinical trials for the treatment of Alzheimer's disease. In this study, the zinc complex of leuprolide was prepared and its structure determined by Fourier-transform infrared (FTIR), differential scanning calorimetry (DSC), UV, X-ray diffraction (XRD), atomic absorption spectroscopy, elemental analysis, and compared with these parameters for leuorolide acetate. Also, the in vitro release profile of leuprolide and its complex form in situ forming implant (ISFI) in comparison to a commercial formulation (Eligard) was investigated. These studies indicate that the zinc complex can be effectively synthesized and influenced on tri-phasic pattern after burst release of LA from the ISFI and shifts this trend to a continuous release profile. Non-linear regression test confirmed this transformation as a zero-order release profile as well.     

Effect of Fine-Grain Percent on Soil Strength Properties Improved By Biological Method

In many civil engineering projects, the foundation soils do not provide the required mechanical properties and therefore, there is a need to improve the soil. Compaction, soil reinforcement, soil mixing with natural, or chemical additives are common soil stabilization methods used to improve the soil mechanical properties. The incidence of some environmental problems in traditional improvement techniques has encouraged engineers to explore new methods. Recently in this category, a new technique in geotechnical engineering called biogeotechnology is introduced to improve the mechanical properties of the soil. It is an environmentally friendly approach that uses biological methods to solve geotechnical problems. This technique uses minerals producer microorganisms. This study investigates the possibility of improving soil strength properties with microbial calcite precipitation and the effect of fine-grained percentages in this regard. In order to determine the soil strength properties, consolidated drained direct shear tests have been carried on untreated and treated soil samples. The results showed that this method is applicable to improve all soil samples (from 100% coarse-grained (i.e., sand) to 100% fine-grained (i.e., clay)). However, increasing the strength in the sand is much more enhanced than that for finer soils. It was found that a considerable increase in cohesion of treated soil can be achieved for soil samples with maximum 10% fine content.     

Genetic diversity and population structure in four Cirsium (Asteraceae) species

The present study considers genetic diversity of 38 populations in 4 Cirsium species of the genus Cirsium Mill. (Asteraceae), occurring in different ecological regions and tries to compare degree of genetic variability among the species with wide geographical distribution versus endemic C. pyramidale showing confined geographical distribution. The results showed that the endemic species has similar value of genetic diversity parameters as the species with wider distribution. We also studied the possible admixture nature of these populations and tried to understand the relation between genetic changes, geographical distribution and polyploidy level and chromosome pairing in these species. ISSR analysis showed population difference in allele composition and frequency. Clustering and PcoA ordination produced different groupings in each species, while STRUCTURE and reticulation analyses revealed high degree of genetic admixture and gene exchange among populations as well as allelic rearrangement. No significant correlation was observed between geographical distance and genetic distance of the populations and AMOVA test revealed no significant difference among populations in each species studied. However, high amount of within population variation occurred in all 4 species indicating their cross-pollination nature and high genetic admixture. The populations also varied in chiasma frequency and chromosome pairing as well as the occurrence of heterozygote translocations all creating more variability to be used by plants for local adaptation.     

Immobilized papain on gold nanorods as heterogeneous biocatalysts

Papain, a thiol protease present in the latex of Carica papaya, is an enzyme which exhibits broad proteolytic activity, and, for this reason, it is utilized in a variety of industrial applications. Immobilization of papain on gold nanoparticles highly preserves its activity and enhances the stability, allowing the reuse of the linked enzyme many times without any significant loss of its catalytic performance. In particular, k _cat and K _M values remain substantially unchanged, while immobilized form shows a higher activity on a wider pH range retains 80 % residual activity also at 90 °C and shows higher functionality than the free form when incubated for long time (1 h) at 90 °C and at extreme pH values (3 and 12). A higher activity of immobilized papain with respect to the free form in the presence of various bivalent metal ions, known as strong inhibitors of papain, was also found. The reasons of this enhanced stability of gold nanorods immobilized papain are discussed.     

Ugi Bis-Amide Derivatives as Tyrosinase Inhibitor; Synthesis,Biology Assessment,and in Silico Analysis

Herein, a straightforward synthetic strategy mediated by Ugi reaction was developed to synthesize novel series of compounds as tyrosinase inhibitors. The structures of all compounds were confirmed by FT-IR, ¹H-NMR, ¹³C-NMR, and CHNOS techniques. The tyrosinase inhibitory activities of all synthesized derivatives 5a – m were determined against mushroom tyrosinase and it was found that derivative 5c possesses the best inhibition with an IC₅₀ value of 69.53±0.042 μM compared to the rest of the synthesized derivatives. Structure–activity relationships (SARs) showed that the presence of 4-MeO or 4-NO₂ at the R² position plays a key role in tyrosinase inhibitory activities. The enzyme kinetics studies showed that compound 5c is an noncompetitive inhibitor. For in silico study, the allosteric site detection was first applied to find the appropriate binding site and then molecular docking and molecular dynamic studies were performed to reveal the position and interactions of 5c as the most potent inhibitor within the tyrosinase active site. The results showed that 5c bind well with the proposed binding site and formed a stable complex with the target protein.