Evaluating the Relationship between Calendar Anomalies and Stock Return of TSE Listed Companies

To expand the financial literature and also in view of the necessity of updating in today's knowledge of the world, this research examines one of the most recent issues of financial management, means science of behavioural finance that is dedicated to the behavioral character of the capital market and the study of the behavioral and psychological aspects of the capital market. In this field, one of the interesting topics is the calendar effects that deal with the anomalies in behavior and performance of market in different times of day, week, month and year. The problem that follows in this study is to investigate the relationship between weekdays, including the categories of periodic or calendar effects, on stock returns, and claims that there are heterogeneous returns on different days of the week, at that time, it would be possible to generate extra returns by formulating strategies for these daily patterns. To achieve this goal, five hypotheses have been formulated and 160 companies were selected from listed companies in the Tehran Stock Exchange for a period of 5 years, 2012 to 2016. The method of this research is applied and descriptive-correlational. To test the hypotheses, linear regression model and panel data are used. The results of testing the hypotheses show that there is a significant relationship between calendar events and stock returns and the effect of Tuesday has been significant in estimations

Optimizing CRISPR/Cas9 Editing of Repetitive Single Nucleotide Variants

CRISPR/Cas9, base editors and prime editors comprise the contemporary genome editing toolbox. Many studies have optimized the use of CRISPR/Cas9, as the original CRISPR genome editing system, in substituting single nucleotides by homology directed repair (HDR), although this remains challenging. Studies describing modifications that improve editing efficiency fall short of isolating clonal cell lines or have not been validated for challenging loci or cell models. We present data from 95 transfections using a colony forming and an immortalized cell line comparing the effect on editing efficiency of donor template modifications, concentration of components, HDR enhancing agents and cold shock. We found that in silico predictions of guide RNA efficiency correlated poorly withactivity in cells. Using NGS and ddPCR we detected editing efficiencies of 5-12% in the transfected populations which fell to 1% on clonal cell line isolation. Our data demonstrate the variability of CRISPR efficiency by cell model, target locus and other factors. Successful genome editing requires a comparison of systems and modifications to develop the optimal protocol for the cell model and locus. We describe the steps in this process in a flowchart for those embarking on genome editing using any system and incorporate validated HDR-boosting modifications for those using CRISPR/Cas9

Use of the HPRT gene to study nuclease-induced DNA double-strand break repair

© The Authors 2015. Published by Oxford University Press. Understanding the mechanisms of chromosomal double-strand break repair (DSBR) provides insight into genome instability, oncogenesis and genome engineering, including disease gene correction. Research into DSBR exploits rare-cutting endonucleases to cleave exogenous reporter constructs integrated into the genome. Multiple reporter constructs have been developed to detect various DSBR pathways. Here, using a single endogenous reporter gene, the X-chromosomal disease gene encoding hypoxanthine phosphoribosyltransferase (HPRT), we monitor the relative utilization of three DSBR pathways following cleavage by I-SceI or CRISPR/Cas9 nucleases. For I-SceI, our estimated frequencies of accurate or mutagenic nonhomologous end-joining and gene correction by homologous recombination are 4.1, 1.5 and 0.16%, respectively. Unexpectedly, I-SceI and Cas9 induced markedly different DSBR profiles. Also, using an I-SceI-sensitive HPRT minigene, we show that gene correction is more efficient when using long double-stranded DNA than single- or double-stranded oligonucleotides. Finally, using both endogenous HPRT and exogenous reporters, we validate novel cell cycle phase-specific I-SceI derivatives for investigating cell cycle variations in DSBR. The results obtained using these novel approaches provide new insights into template design for gene correction and the relationships between multiple DSBR pathways at a single endogenous disease gene.This work was supported in part by the Biotechnology and Biological Research Council (BB/H003371/1 to A.C.G.P.), the Medical Research Council (MC_PC_12003 to T.C.H.), Cancer Research UK (C5255/A15935 to S.A.) and University of Oxford (Clarendon Scholarship to S.A.). Funding to pay the Open Access publication charges for this article was provided by the Research Councils UK open access fund

Genetic analysis of DNA double-strand break mis-repair mechanisms using the human endogenous HPRT gene

DNA double strand breaks (DSBs) are the most lethal radiation-induced lesions in response to which cells employ either the error free homologous recombination (HR) repair pathway or error prone mechanisms, such as non homologous end joining (NHEJ) and microhomology- mediated end joining (MMEJ). While MMEJ is suppressed by C-NHEJ, the relationship between HR and MMEJ is less clear. In this thesis, I have exploited the human endogenous HPRT gene to develop a novel genetic technology to detect mutation frequencies and signatures in response to DNA DSBs in different genetic backgrounds. Using a sensitive HPRT assay we describe a role for HR genes in suppressing MMEJ in human cells. By monitoring DSB mis-repair, we found that depletion of HR proteins, including RAD51, BRCA2, BRCA1 or SETD2, resulted in a distinct mutational signature associated with significant increases in break-induced mutation frequencies, deletion lengths and the annealing of short regions of microhomology (2â6 bp) across the break-site. This signature was dependent on CtIP, MRE11, POLQ and PARP, and thus indicative of MMEJ. In contrast to CtIP or MRE11, depletion of BRCA1 resulted in increased partial resection and MMEJ, thus revealing a functional distinction between these early acting HR factors. Together these findings indicate that HR factors suppress mutagenic MMEJ following DSB resection. Further, I have defined a role for the SETD2 histone methyltransferase in suppressing break-induced mutations, and have shown that CRISPR/Cas9 and ISceI- induced DSBs resulted in different repair profiles.</p

Genetic analysis of DNA double-strand break mis-repair mechanisms using the human endogenous HPRT gene

DNA double strand breaks (DSBs) are the most lethal radiation-induced lesions in response to which cells employ either the error free homologous recombination (HR) repair pathway or error prone mechanisms, such as non homologous end joining (NHEJ) and microhomology- mediated end joining (MMEJ). While MMEJ is suppressed by C-NHEJ, the relationship between HR and MMEJ is less clear. In this thesis, I have exploited the human endogenous HPRT gene to develop a novel genetic technology to detect mutation frequencies and signatures in response to DNA DSBs in different genetic backgrounds. Using a sensitive HPRT assay we describe a role for HR genes in suppressing MMEJ in human cells. By monitoring DSB mis-repair, we found that depletion of HR proteins, including RAD51, BRCA2, BRCA1 or SETD2, resulted in a distinct mutational signature associated with significant increases in break-induced mutation frequencies, deletion lengths and the annealing of short regions of microhomology (2–6 bp) across the break-site. This signature was dependent on CtIP, MRE11, POLQ and PARP, and thus indicative of MMEJ. In contrast to CtIP or MRE11, depletion of BRCA1 resulted in increased partial resection and MMEJ, thus revealing a functional distinction between these early acting HR factors. Together these findings indicate that HR factors suppress mutagenic MMEJ following DSB resection. Further, I have defined a role for the SETD2 histone methyltransferase in suppressing break-induced mutations, and have shown that CRISPR/Cas9 and ISceI- induced DSBs resulted in different repair profiles.</p

PKD1 haploinsufficiency causes a syndrome of inappropriate antidiuresis in mice.

Mutations in PKD1 are associated with autosomal dominant polycystic kidney disease. Studies in mouse models suggest that the vasopressin (AVP) V2 receptor (V2R) pathway is involved in renal cyst progression, but potential changes before cystogenesis are unknown. This study used a noncystic mouse model to investigate the effect of Pkd1 haploinsufficiency on water handling and AVP signaling in the collecting duct (CD). In comparison with wild-type littermates, Pkd1(+/-) mice showed inappropriate antidiuresis with higher urine osmolality and lower plasma osmolality at baseline, despite similar renal function and water intake. The Pkd1(+/-) mice had a decreased aquaretic response to both a water load and a selective V2R antagonist, despite similar V2R distribution and affinity. They showed an inappropriate expression of AVP in brain, irrespective of the hypo-osmolality. The cAMP levels in kidney and urine were unchanged, as were the mRNA levels of aquaporin-2 (AQP2), V2R, and cAMP-dependent mediators in kidney. However, the (Ser256) phosphorylated AQP2 was upregulated in Pkd1(+/-) kidneys, with AQP2 recruitment to the apical plasma membrane of CD principal cells. The basal intracellular Ca(2+) concentration was significantly lower in isolated Pkd1(+/-) CD, with downregulated phosphorylated extracellular signal-regulated kinase 1/2 and decreased RhoA activity. Thus, in absence of cystic changes, reduced Pkd1 gene dosage is associated with a syndrome of inappropriate antidiuresis (positive water balance) reflecting decreased intracellular Ca(2+) concentration, decreased activity of RhoA, recruitment of AQP2 in the CD, and inappropriate expression of AVP in the brain. These data give new insights in the potential roles of polycystin-1 in the AVP and Ca(2+) signaling and the trafficking of AQP2 in the CD