Calcitonin administration improves endometrial receptivity via regulation of LIF,Muc-1 and microRNA Let-7a in mice

Calcitonin (CT) is one of the factors affecting the embryo implantation, but its effects on the implantation window have not been fully investigated. The current study investigated the effects of CT on the endometrium receptivity by morphological study and evaluation of leukemia inhibitory factor (LIF), mucin 1 (Muc-1), and microRNA (miRNA) Let-7a in the ovarian stimulation and the normal ovarian cycle. Then the mechanism of the CT effects through the mammalian target of rapamycin (mTOR) signaling pathway was studied by using PP242. A total of 64 BALB/c mice were divided into the normal ovarian cycle and ovarian stimulation groups. Each group consisted of four subgroups: control, calcitonin, PP242, and calcitonin+PP242. CT and PP242 were injected on the fourth of pregnancy into the mice and 24 hr later all the mice were killed. The uterine tissue samples were used for morphological analysis, and endometrial cells were mechanically isolated for evaluation of gene and protein expression. The results showed that ovarian stimulation induced mTOR phosphorylation as well as increased expression of the Let-7a miRNA. In addition, CT injection increased the expression of LIF and miRNA Let-7a in ovarian stimulation similar to that in normal ovarian cycles. However, injection of PP242 reduced expression of miRNA Let-7a and increased Muc-1 expression in ovarian stimulation group. In conclusion, the administration of CT improved endometrial receptivity in mice. This phenomenon occurred by upregulation of LIF, miRNA Let-7a and downregulation of Muc-1 via mTOR signaling pathway.     

Development of α4 integrin DNA aptamer as a potential therapeutic tool for multiple sclerosis

One of the most important molecules for multiple sclerosis pathogenesis is α4 integrin, which is responsible for autoreactive leukocytes migration into the brain. The monoclonal antibody, natalizumab, was introduced to market for blocking the extravasation of autoreactive leukocytes via inhibition of α4 integrin. However, the disadvantages of antibodies provided a suitable background for other agents to be replaced with antibodies. Considering the profound advantages of aptamers over antibodies, aptamer isolation against α4 integrin was intended in the current study. The α4 integrin-specific aptamers were selected using cell-systematic evolution of ligands by exponential enrichment (SELEX) method with human embryonic kidney (HEK)-293T overexpressing α4 integrin and HEK-293T as target and control cells, respectively. Evaluation of selected aptamer was performed through flow cytometric analysis. The selected clones were then sequenced and analyzed for any possible secondary structure and affinity. The results of this study led to isolation of 13 different single-stranded DNA clones in 11 rounds of selection which were categorized to three clusters based on common structural motifs and the equilibrium dissociation constant (K _d) of the most stable structure was calculated. The evaluation of SELEX progress showed growth in aptamer affinity with increasing of the number of cycles. Taken together, the findings of this study demonstrated the isolation of α4-specific single-stranded DNA aptamers with suitable affinity for ligand, which can further be replaced with natalizumab.     

On the optimality of the genetic code, with the consideration of coevolution theory by comparison of prominent cost measure matrices

Statistical and biochemical studies have revealed non-random patterns in codon assignments. The canonical genetic code is known to be highly efficient in minimizing the effects of mistranslation errors and point mutations, since it is known that when an amino acid is converted to another due to error, the biochemical properties of the resulted amino acid are usually very similar to those of the original one. In this study, using altered forms of the fitness functions used in the prior studies, we have optimized the parameters involved in the calculation of the error minimizing property of the genetic code so that the genetic code outscores the random codes as much as possible. This work also compares two prominent matrices, the Mutation Matrix and Point Accepted Mutations 74-100 (PAM(74-100)). It has been resulted that the hypothetical properties of the coevolution theory of the genetic code are already considered in PAM(74-100), giving more evidence on the existence of bias towards the genetic code in this matrix. Furthermore, our results indicate that PAM(74-100) is biased towards the single base mistranslation occurrences in second codon position as well as the frequency of amino acids. Thus PAM(74-100) is not a suitable substitution matrix for the studies conducted on the evolution of the genetic code.     

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.     

Reaction of sunflower varieties to Sclerotinia sclerotiorum under various inoculation methods,time of field evaluation and phylogenic stages of host

Sunflower cultivation is affected seriously by Sclerotinia sclerotiorum (Lib.) de Bary in Iran, particularly north-western areas. Because of economic and environmental harms by chemical control, it is necessary to develop cultivars with adequate genetic resistance for reduction of yield losses. The purpose of this study was to find an effective method of inoculation with S. sclerotiorum under field evaluations. Three stem-inoculation techniques including: 1 – mycelium plug, 2 – oxalic acid solution (OAS) and 3 – infested wheat seeds with Sclerotinia mycelium were employed under field conditions. Four genotypes including Ghalami (local variety in market), Confeta, Allstar and Master were used in this study. The lesion length, lesion width and lesion as up and down leading on the stem from inoculation site were measured after 3, 7, 10 and 14 days of inoculation. The analysis of variance showed significant difference between all employed techniques and incubation days after inoculation. Mycelial plug (MP) inoculation technique produced significantly more developed lesions on the treated stems. In spite of this effect, Master variety demonstrated reasonable resistance reaction against the disease. The progress of disease in wounded treatments was also faster than the non-wounded ones. And, the shortest time to obtain significant differences between varieties was 10?days after inoculation. By comparison of results of lesion length at flowering and seed-filling stages, the more obvious effectiveness of the disease was observed at the second stage. Finally, there were negative correlations between mean temperature and mean lesion length in all three inoculation methods.     

Salt oversensitivity derived from mutation breeding improves salinity tolerance in barley <Emphasis Type="Italic">via</Emphasis> ion homeostasis

Salt stress imposes a major environmental threat to agriculture, therefore, understanding the basic physiology and genetics of cell under salt stress is crucial for developing any breeding strategy. In the present study, the expression profile of genes involved in ion homeostasis including salt overly sensitive (HvSOS1, HvSOS2, HvSOS3), vacuolar Na⁺/H⁺ antiporter (HvNHX1), and H⁺-ATPase (HVA) along with ion content measurement were investigated in two genotypes of Hordeum vulgare under 300 mM NaCl. The gene expressions were measured in the roots and shoots of a salt-tolerant mutant genotype M4-73-30 and in its wild-type cv. Zarjou by real-time qPCR technique. The critical differences between the salt-tolerant mutant and its wild-type were observed in the expressions of HvSOS1 (105-fold), HvSOS2 (24-fold), HvSOS3 (31-fold), and HVA (202-fold) genes in roots after 6-h exposure to NaCl. The parallel early up-regulation of these genes in root samples of the salt-tolerant mutant genotype indicated induction of Na⁺/H⁺ antiporters activity and Na+ exclusion into apoplast and vacuole. The earlier up-regulation of HvSOS1, HVA, and HvNHX1 genes in shoot of the wild-type genotype corresponded to the relative accumulation of Na⁺ which was not observed in salt-tolerant mutant genotype because of efficient inhibitory role of the root in Na+ transport to the shoot. In conclusion, the lack of similarity in gene expression patterns between the two genotypes with similar genetic background may confirm the hypothesis that mutation breeding could change the ability of salt-tolerant mutant genotype for efficient ion homeostasis via salinity oversensitivity response.     

Error minimization explains the codon usage of highly expressed genes in Escherichia coli

Different organisms use synonymous codons with different preferences. Several measures have been introduced to compute the extent of codon usage bias within a gene or genome, among which the codon adaptation index (CAI) has been shown to be well correlated with mRNA levels of Escherichia coli. In this work an error adaptation index (eAI) is introduced, which estimates the level at which a gene can tolerate the effects of mistranslations. It is shown that the eAI has a strong correlation with CAI, as well as with mRNA levels, which suggests that the codons of highly expressed genes are selected so that mistranslation would have the minimum possible effect on the structure and function of the related proteins.     

Degradation of dibutyl phthalate by Paenarthrobacter sp. Shss isolated from Saravan landfill,Hyrcanian Forests,Iran

Biodegradation - Phthalic acid esters are predominantly used as plasticizers and are industrially produced on the million ton scale per year. They exhibit endocrine-disrupting, carcinogenic,...