Agritourism Development Issues In Rural Places: Evidence From Armenia

The following paper summarizes the arguments and counterarguments within the scientific discussion on the issues of agritourism development issues in rural places. Agritourism development is a good source for rural development, as it will contribute to the investments in villages, increase rural income, emlpoyment, etc. The main purpose of the article is to analyze agritourism development opportunities and issues in Armenian rural place

Up-regulation of expression and lack of 5' CpG island hypermethylation of p16 INK4a in HPV-positive cervical carcinomas

BACKGROUND: High risk type human papilloma viruses (HR-HPV) induce carcinomas of the uterine cervix by expressing viral oncogenes E6 and E7. Oncogene E7 of HR-HPV disrupts the pRb/E2F interaction, which negatively regulates the S phase entry. Expression of tumor suppressor p16(ink4a )drastically increases in majority of HR-HPV associated carcinomas due to removal of pRb repression. The p16(ink4a )overexpression is an indicator of an aberrant expression of viral oncogenes and may serve as a marker for early diagnostic of cervical cancer. On the other hand, in 25–57% of cervical carcinomas hypermethylation of the p16 INK4a promoter has been demonstrated using a methylation-specific PCR, MSP. To evaluate a potential usage of the p16 INK4a 5' CpG island hypermethylation as an indicator of tumor cell along with p16(ink4a )overexpression, we analyzed the methylation status of p16 INK4a in cervical carcinomas METHODS: Methylation status of p16 INK4a was analyzed by MSP and by bisulfite-modified DNA sequencing. The expression of p16(ink4a )was analyzed by RT-PCR and by immunohistochemical technique. RESULTS: The extensive methylation within p16 INK4a 5' CpG island was not detected either in 13 primary cervical carcinomas or in 5 cancer cell lines by bisulfite-modified DNA sequencing (including those that were positive by MSP in our hands). The number and distribution of rare partially methylated CpG sites did not differ considerably in tumors and adjacent normal tissues. The levels of the p16 INK4a mRNA were increased in carcinomas compared to the normal tissues independently of the number of partially methylated CpGs within 5'CpG island. The transcriptional activation of p16 INK4a was accompanied by p16(ink4a )cytoplasmic immunoreactivity in the majority of tumor cells and presence of a varied number of the p16 positive nuclei in different tumors. CONCLUSION: Hypermethylaion of the p16INK4a 5' CpG island is not a frequent event in HR-HPV-positive cervical carcinomas and cannot be an effective marker of cancer cells with up-regulated expression of p16(ink4a). Our data confirm other previous studies claiming specific p16INK4a up-regulation in the majority of cervical carcinomas at both the protein and mRNA levels. Cytoplasmic accumulation of p16(ink4a )is a feature of cervical carcinomas

The Formin-Homology Protein SmDia Interacts with the Src Kinase SmTK and the GTPase SmRho1 in the Gonads of Schistosoma mansoni

BACKGROUND:Schistosomiasis (bilharzia) is a parasitic disease of worldwide significance affecting human and animals. As schistosome eggs are responsible for pathogenesis, the understanding of processes controlling gonad development might open new perspectives for intervention. The Src-like tyrosine-kinase SmTK3 of Schistosoma mansoni is expressed in the gonads, and its pharmacological inhibition reduces mitogenic activity and egg production in paired females in vitro. Since Src kinases are important signal transduction proteins it is of interest to unravel the signaling cascades SmTK3 is involved in to understand its cellular role in the gonads. METHODOLOGY AND RESULTS:Towards this end we established and screened a yeast two-hybrid (Y2H) cDNA library of adult S. mansoni with a bait construct encoding the SH3 (src homology) domain and unique site of SmTK3. Among the binding partners found was a diaphanous homolog (SmDia), which was characterized further. SmDia is a single-copy gene transcribed throughout development with a bias towards male transcription. Its deduced amino acid sequence reveals all diaphanous-characteristic functional domains. Binding studies with truncated SmDia clones identified SmTK3 interaction sites demonstrating that maximal binding efficiency depends on the N-terminal part of the FH1 (formin homology) domain and the inter-domain region of SmDia located upstream of FH1 in combination with the unique site and the SH3 domain of SmTK3, respectively. SmDia also directly interacted with the GTPase SmRho1 of S. mansoni. In situ hybridization experiments finally demonstrated that SmDia, SmRho1, and SmTK3 are transcribed in the gonads of both genders. CONCLUSION:These data provide first evidence for the existence of two cooperating pathways involving Rho and Src that bridge at SmDia probably organizing cytoskeletal events in the reproductive organs of a parasite, and beyond that in gonads of eukaryotes. Furthermore, the FH1 and inter domain region of SmDia have been discovered as binding sites for the SH3 and unique site domains of SmTK3, respectively

Inhibition of Src kinase activity attenuates amyloid associated microgliosis in a murine model of Alzheimer’s disease

<p>Abstract</p> <p>Background</p> <p>Microglial activation is an important histologic characteristic of the pathology of Alzheimer’s disease (AD). One hypothesis is that amyloid beta (Aβ) peptide serves as a specific stimulus for tyrosine kinase-based microglial activation leading to pro-inflammatory changes that contribute to disease. Therefore, inhibiting Aβ stimulation of microglia may prove to be an important therapeutic strategy for AD.</p> <p>Methods</p> <p>Primary murine microglia cultures and the murine microglia cell line, BV2, were used for stimulation with fibrillar Aβ1-42. The non-receptor tyrosine kinase inhibitor, dasatinib, was used to treat the cells to determine whether Src family kinase activity was required for the Aβ stimulated signaling response and subsequent increase in TNFα secretion using Western blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. A histologic longitudinal analysis was performed using an AD transgenic mouse model, APP/PS1, to determine an age at which microglial protein tyrosine kinase levels increased in order to administer dasatinib via mini osmotic pump diffusion. Effects of dasatinib administration on microglial and astroglial activation, protein phosphotyrosine levels, active Src kinase levels, Aβ plaque deposition, and spatial working memory were assessed via immunohistochemistry, Western blot, and T maze analysis.</p> <p>Results</p> <p>Aβ fibrils stimulated primary murine microglia via a tyrosine kinase pathway involving Src kinase that was attenuated by dasatinib. Dasatinib administration to APP/PS1 mice decreased protein phosphotyrosine, active Src, reactive microglia, and TNFα levels in the hippocampus and temporal cortex. The drug had no effect on GFAP levels, Aβ plaque load, or the related tyrosine kinase, Lyn. These anti-inflammatory changes correlated with improved performance on the T maze test in dasatinib infused animals compared to control animals.</p> <p>Conclusions</p> <p>These data suggest that amyloid dependent microgliosis may be Src kinase dependent <it>in vitro</it> and <it>in vivo.</it> This study defines a role for Src kinase in the microgliosis characteristic of diseased brains and suggests that particular tyrosine kinase inhibition may be a valid anti-inflammatory approach to disease. Dasatinib is an FDA-approved drug for treating chronic myeloid leukemia cancer with a reported ability to cross the blood-brain barrier. Therefore, this suggests a novel use for this drug as well as similar acting molecules.</p

Complementarity of end regions increases the lifetime of small RNAs in mammalian cells.

Two RNAs (4.5SH and 4.5SI) with unknown functions share a number of features: short length (about 100 nt), transcription by RNA polymerase III, predominately nuclear localization, the presence in various tissues, and relatively narrow taxonomic distribution (4 and 3 rodent families, respectively). It was reported that 4.5SH RNA turns over rapidly, whereas 4.5SI RNA is stable in the cell, but their lifetimes remained unknown. We showed that 4.5SH is indeed short-lived (t(1/2)~18 min) and 4.5SI is long-lived (t(1/2)~22 h) in Krebs ascites carcinoma cells. The RNA structures specifying rapid or slow decay of different small cellular RNAs remain unstudied. We searched for RNA structural features that determine the short lifetime of 4.5SH in comparison with the long lifetime of 4.5SI RNA. The sequences of genes of 4.5SH and 4.5SI RNAs were altered and human cells (HeLa) were transfected with these genes. The decay rate of the original and altered RNAs was measured. The complementarity of 16-nt end regions of 4.5SI RNA proved to contribute to its stability in cells, whereas the lack of such complementarity in 4.5SH RNA caused its rapid decay. Possible mechanisms of the phenomenon are discussed

Аналіз попиту на агротуристичні послуги серед туристів: на прикладі Вірменії

У рамках статті авторами систематизовано аргументи та контраргументи в рамках наукової дискусії щодо питань розвитку агротуризму у Вірменії. Головною метою дослідження є аналіз попиту на агротуристичні послуги та визначення потреб іноземних туристів. Авторами відмічено, що Вірменія має високий рівень туристичного потенціалу, який забезпечується низкою факторів, а саме: багатою історично-культурною спадщиною, красою природи, смачною кухнею, збереженою етнічною самобутністю в сільських місцевостях тощо. При цьому зазначені вище фактори сприяють стрімкому розвитку агротуризму в сільській місцевості. У статті наголошено, що агротуристичний пакет складається з наступних послуг: участь в сільськогосподарській діяльності, землеробство, догляд за тваринами, полювання, рибалка, верхова їзда, бджільництво, килимарство, ремесла, збір врожаю, виноробство, готування національних страв, випічка хліба, відвідування історичних і культурних місць, участь в різних фестивалях тощо. У рамках даного дослідження проаналізовано та систематизовано науковий доробок з метою узагальнення низки підходів до визначення сутності та значення агротуризму. Крім того, у ході дослідження авторами проведено опитування іноземних туристів для визначення їх потреб щодо агротуристичних послуг. Отримані результати емпіричного дослідження засвідчили, що іноземні туристи сприймають сільську місцевість Вірменія, як затишне та привабливе місце для відпочинку. За результатами тестування критерію Пірсона встановлено істотний зв’язок між факторами-впливу на рівень сприйняття агротуристичних послуг іноземними туристами. У статті авторами доведено, що, неодружені відпочивають в сільській місцевості поодинці або з друзями та готові платити більше, ніж одружені люди, у яких є діти. На основі отриманих даних було сформовано систему заходів щодо удосконалення агротуризму в Вірменія, а саме: удосконалити маркетингову діяльність щодо промоції агротуристичних послуг, організувати тренінги для місцевих жителів і фермерів тощо. Результати дослідження мають практичне значення і можуть бути прийняті до впровадження з метою розроблення ефективних стратегій та маркетингових планів щодо розвитку агротуризму в сільській місцевості.This paper summarises the arguments and counterarguments in the frame of the scientific discussion on the issue of agritourism development in Armenia. The research aims at analysing the demand of agritourism development for international tourists in Armenia, find out their needs. The analysis of the available literature sources and approaches shows the essence of agritourism, its activities, functions, needs of tourists. Armenia has a rich history and culture, beautiful nature, delicious cuisine, Armenian villages have a traditional way of life and ethnic diversity. All these factors are important for developing agritourism in rural places offering various activities for tourists: participation in agricultural activities, farming, animal care, hunting, fishing, horseback riding, beekeeping, carpet weaving, handicrafts, harvesting, winemaking, making national dishes, baking bread, also visiting historical and cultural places, participation in various festivals, etc. Investigation of the topic in the paper is carried out in the following rational arrangement. The essence and significance of agritourism in the literature are discussed, then a survey is done among international tourists to find out their needs. The results of the empirical analysis are presented in the paper, which shows that Armenia is considered as a quiet and beautiful place for tourists who wish to rest in Armenian rural places, participate in many activities. The Pearson Chi-square testing shows some significant relationship between some factors. Mainly unmarried people want to rest in rural places alone or with friends, and they are willing to pay more than married people who have children. The tourists have also made some suggestions for agritourism development in Armenia: making everything more natural and fresher, doing good marketing, organizing pieces of training for local people and farmers, etc. The research results may be useful for developing agritourism in rural areas by organizing good strategies and marketing plans

Agritourism Development Issues In Rural Places: Evidence From Armenia

The following paper summarizes the arguments and counterarguments within the scientific discussion on the issues of agritourism development issues in rural places. Agritourism development is a good source for rural development, as it will contribute to the investments in villages, increase rural income, emlpoyment, etc. The main purpose of the article is to analyze agritourism development opportunities and issues in Armenian rural place