Microsatellite instability in colorectal cancer

Colorectal cancer (CRC) is a heterogeneous disease that is caused by the interaction of genetic and environmental factors. Although it is one of the most common cancers worldwide, CRC would be one of the most curable cancers if it is detected in the early stages. Molecular changes that occur in colorectal cancer may be categorized into three main groups: 1) Chromosomal Instability (CIN), 2) Microsatellite Instability (MSI), and 3) CpG Island Methylator phenotype (CIMP). Microsatellites, also known as Short Tandem Repeats (STRs) are small (1-6 base pairs) repeating stretches of DNA scattered throughout the entire genome and account for approximately 3 % of the human genome. Due to their repeated structure, microsatellites are prone to high mutation rate. Microsatellite instability (MSI) is a unique molecular alteration and hyper-mutable phenotype, which is the result of a defective DNA mismatch repair (MMR) system, and can be defined as the presence of alternate sized repetitive DNA sequences which are not present in the corresponding germ line DNA. The presence of MSI is found in sporadic colon, gastric, sporadic endometrial and the majority of other cancers. Approximately, 15-20 % of colorectal cancers display MSI. Determination of MSI status in CRC has prognostic and therapeutic implications. As well, detecting MSI is used diagnostically for tumor detection and classification. For these reasons, microsatellite instability analysis is becoming more and more important in colorectal cancer patients. The objective of this review is to provide the comprehensive summary of the update knowledge of colorectal cancer classification and diagnostic features of microsatellite instability

Freedom of Expression and Justiciability in Pakistan

This paper would discuss freedom of expression and restrictions on the freedom with particular reference to the provisions of International Covenant on Civil and Political Rights (ICCPR) and the „Justiciability Doctrine‟ as enshrined in the European Convention of Human Rights (ECHR). The question whether the freedom of expression claims are justiciable or not, in third world countries like Pakistan and how it helps in the advancement of rule of law and good governance would be explored. The focus would be on the cultural relativism narrative developed ever since the adoption of the Universal Declaration of Human Rights (UDHR). The claims of „Universalism‟ associated with human rights especially freedom of expression would be criticized with respect to the Margin of Appreciation Doctrine as reflected in the jurisprudence of the European Court of Human Rights (ECtHR) and adopted in other jurisdictions. Freedom of expression and the rights of minorities in Pakistan would be discussed with a special mention of proselytization and forced conversions. Lastly, the role of legislation and judiciary in Pakistan for the protection and advancement of the freedom of expression guarantee would be discussed

The Usability of classroom Technologies in English Language Teaching and Learning (ELT & ELL)

In language teaching and learning, we have a lot to choose from the world of technology: Radio, TV, CD Rom, Computers, C.A.L.L., the Internet, Electronic Dictionary, Email, Blogs and Audio Cassettes, PowerPoint, Videos, DVD‟s or VCD‟s. The last two decades have witnessed a revolution due to the onset of technology, and has changed the dynamics of various industries, and has also influenced the industries and the way people interact and work in the society. This rapid rising and development of information technology have offered a better pattern to explore the new teaching model. As a result, technology plays a very important role in English teaching. Using multimedia to create a context to teach English has its unique advantages.We examined the effect of teaching and learning with technology on student cognitive and affective outcomes using the available technique. Screening studies obtained from an electric search of databases resulted in 58 studies (2013-2014). Overall, effect sizes were small to moderate across the cognitive and affective outcome measures. Specific teaching/learning components such as context/making sense, challenging activity, instructional conversation, and joint productivity were associated with effect sizes. Instructional features such as objectives, the pattern of student computer use, and type of learning task also moderated effect sizes. Suggestions are made for teachers to include these instructional features and teaching strategies in teaching and learning with classroom technology.Keywords: Technology, Teaching and learning, Computer-assisted instruction, Good instructional practices, Student outcome

A Review of Important Indicators in Scientomerics (Co-Citation & Co-Word) and the Necessity of Using Them in Scientific Products Analysis

The main objective of this study is to introduce important indicators of scientometrics such as co-citation and co-word and their application in the analysis and visualization of scientific records indexed in citation databases. This research is conducted relying on scientometric approach; and the scientific products related to exegesis in Web of Science database are used as the statistical population in the second part of this research. Using scientometric techniques, experts in information science analyze scientific products and records indexed in different citation databases to find out top authors, countries, institutes, and organizations in every thematic field as well as main topics and core journals in order to visualize the scientific products in every given field for the purpose of scientific mapping using various scientometric techniques such as co-citation and co-word. Showing the frequency of words, co-word analysis displays the most significant research topics in every given field. Moreover, co-citation analysis which has high application in scientific product analysis is used to map the intellectual structure in a research domain

Hydroxonium hydrate tris­(2,4,6-tri­amino-1,3,5-triazin-1-ium) bis­[bis­(pyri­dine-2,6-dicarboxyl­ato)cuprate(II)] pyridine-2,6-dicarboxylic acid hexa­hydrate

The reaction of copper(II) nitrate hexa­hydrate with pyridine-2,6-dicarboxylic acid (pydcH2) and 2,4,6-triamino-1,3,5-triazine (melamine) in aqueous solution in a 1:2:2 molar ratio gave the title compound, (H5O2)(C3H7N6)3[Cu(C7H3NO4)2]2·C7H5NO4·6H2O. The hydroxonium hydrate (H5O2)+, also known as the Zundel cation, resides on a twofold rotation axis. The O—H distance is 1.274 (14) Å, the O⋯O distance is 2.518 (5) Å, and the O—H—O angle is 162 (8)°. One of the melamine H+ cations, the uncoordinated pydcH2, and two water mol­ecules also reside on crystallographic twofold axes. The CuII atom has a tetra­gonally distorted octa­hedral coordination environment. The structure features extensive hydrogen bonding, with 21 distinct inter­actions. There is also a centrosymmetric C=O⋯π inter­action with an O⋯centroid distance of 3.288 (3) Å. The structure is similar to a mixed-valence manganese(II/III) structure but shows inter­esting differences in the metal-atom coordination. One of the water molecules is equally disordered with respect to a twofold axis

Pax5が制御するヒストンの脱メチル化によるB細胞の分化促進機構の解析

指導教員: 多比良, 和

Creating the conditions for scaling up the integration of reproductive health services for men in health and family welfare centers in Bangladesh

An operations research study, supported by the Population Council’s Frontiers in Reproductive Health (FRONTIERS) program, showed that reproductive health services for men could be feasibly and acceptably integrated within the Health and Family Welfare Centres in Bangladesh, which have been primarily women-centered health facilities. Given these findings, a follow-up study was implemented to create the conditions for scaling up the model through identifying and piloting the operational details to consider when taking the intervention to scale. The findings presented in this report suggest that this model of service delivery and training can be scaled up countrywide, preferably in stages. To ensure compliance with systematic screening by all providers, the report recommends instituting supportive supervision, especially during the early stages of expansion, and holding clinical training in a facility where many RTI/STI cases are treated (such as a district hospital)

Evaluation of microsatellite instability in tumor and tumor marginal samples of sporadic colorectal cancer using mononucleotide markers

Microsatellite instability (MSI) is a unique molecular alteration that is due to a defective DNA mismatch repair (MMR) system. Approximately, 15-20 % of sporadic colorectal cancers (CRC) display MSI. Determination of MSI status in CRC has prognostic and predictive implications. Additionally, detecting MSI is used diagnostically for tumor detection and classification. The present study analyzed a panel of five mononucleotide markers, BAT- 25, BAT-26, NR-21, NR-22 and NR-27, amplified in a single multiplex PCR reaction to evaluate MSI status in CRC patients. Genomic DNA from 50 CRC and paired adjacent normal tissues was used for PCR-based MSI analysis. Our finding showed microsatellite instability in 36 % of specimens. Instability with differences in allele lengths was observed in the tumoral DNA compared to the tumor-free margin DNA sample. The frequency of instability in NR-21, BAT-26 and BAT-25 markers were more than others; their frequency were 35.48 %, 29.03 %, and 22.58 %, respectively. In conclusion, the NR-21, BAT-26, and BAT-25 were the most useful markers for discriminating cancer tissue from normal, therefore these markers have demonstrated promising potential for determining MSI status in patients with sporadic colorectal cancer

p38 MAPK as a gatekeeper of reprogramming in mouse migratory primordial germ cells

Mammalian germ cells are derived from primordial germ cells (PGCs) and ensure species continuity through generations. Unlike irreversible committed mature germ cells, migratory PGCs exhibit a latent pluripotency characterized by the ability to derive embryonic germ cells (EGCs) and form teratoma. Here, we show that inhibition of p38 mitogen-activated protein kinase (MAPK) by chemical compounds in mouse migratory PGCs enables derivation of chemically induced Embryonic Germ-like Cells (cEGLCs) that do not require conventional growth factors like LIF and FGF2/Activin-A, and possess unique naïve pluripotent-like characteristics with epiblast features and chimera formation potential. Furthermore, cEGLCs are regulated by a unique PI3K-Akt signaling pathway, distinct from conventional naïve pluripotent stem cells described previously. Consistent with this notion, we show by performing ex vivo analysis that inhibition of p38 MAPK in organ culture supports the survival and proliferation of PGCs and also potentially reprograms PGCs to acquire indefinite proliferative capabilities, marking these cells as putative teratoma-producing cells. These findings highlight the utility of our ex vivo model in mimicking in vivo teratoma formation, thereby providing valuable insights into the cellular mechanisms underlying tumorigenesis. Taken together, our research underscores a key role of p38 MAPK in germ cell development, maintaining proper cell fate by preventing unscheduled pluripotency and teratoma formation with a balance between proliferation and differentiation