The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues

Friedreich ataxia (FRDA) is caused by a homozygous GAA repeat expansion mutation within intron 1 of the FXN gene, leading to reduced expression of frataxin protein. Evidence suggests that the mutation may induce epigenetic changes and heterochromatin formation, thereby impeding gene transcription. In particular, studies using FRDA patient blood and lymphoblastoid cell lines have detected increased DNA methylation of specific CpG sites upstream of the GAA repeat and histone modifications in regions flanking the GAA repeat. In this report we show that such epigenetic changes are also present in FRDA patient brain, cerebellum and heart tissues, the primary affected systems of the disorder. Bisulfite sequence analysis of the FXN flanking GAA regions reveals a shift in the FRDA DNA methylation profile, with upstream CpG sites becoming consistently hypermethylated and downstream CpG sites becoming consistently hypomethylated. We also identify differential DNA methylation at three specific CpG sites within the FXN promoter and one CpG site within exon 1. Furthermore, we show by chromatin immunoprecipitation (ChIP) analysis that there is overall decreased histone H3K9 acetylation together with increased H3K9 methylation of FRDA brain tissue. Further studies of brain, cerebellum and heart tissues from our GAA repeat expansion-containing FRDA YAC transgenic mice reveal comparable epigenetic changes to those detected in FRDA patient tissue. We have thus developed a mouse model that will be a valuable resource for future therapeutic studies targeting epigenetic modifications of the FXN gene to increase frataxin expression

Klasifikasi Fasies pada Reservoir Menggunakan Crossplot Data Log P-Wave dan Data Log Density

Klasifikasi fasies merupakan salah satu cara untuk menentukan jenis batuan dari data well log. Telah dilakukan klasifikasi fasies pada reservoir untuk mengetahui persebaran properti dan fasiesnya. Metode yang digunakan ialah crossplot antara data log p-wave dengan data log density. Kontrol dilakukan dengan menggunakan data log gamma ray, log neutron, log porositas dan data core. Data fasies diklasifikasikan menjadi 4, yaitu Super Sandy Globigerina sebagai limestone berpori tinggi sebagai reservoir, Sandy Globigerina sebagai limestone yang didominasi oleh sand, Shaly Globigerina sebagai limestone yang didominasi oleh shale serta Compact Globigerina merupakan limestone kompak tanpa pori

Propofol and Kearns-Sayre Syndrome: An idiographic approach

With the focus on an idiographic approach whereby the observations incorporated the various dimensions of individual functioning ‘top-down’ to ‘bottom-up’, this case report describes the successful management of a 14-year-old girl with Kearns-Sayre syndrome and Dyggve-Melchior-Clausen disease requiring a transvenous permanent pacemaker implantation for complete heart block. The patient presented to a tertiary care centre in Muscat, Oman, in 2023 seeking consultation. The current idiographic approach appears to have a heuristic value for 2 interrelated reasons. Firstly, it is unlikely that even tertiary care units can accrue such rare presentations and scrutinise them under nomothetic approach. Secondly, by employing the idiographic approach that is capable of examining each case in-depth, the aspiration for good health and well-being may come to the forefront. To the best of the authors’ knowledge this is the first published idiographic report in anaesthesia care. Keywords: Intravenous Anaesthetics; Artificial Pacemaker; Kearns-Sayre Syndrome; Propofol; Idiographic Approach; Case Report; Oman

DICHLOROMETHANE EXTRACT OF THE LEAVES OF ARBUTUS PAVARII PAMP. EXHIBITS CYTOTOXICITY AGAINST THE PROSTATE CANCER CELL LINE PC3: A BIOASSAY-GUIDED ISOLATION AND IDENTIFICATION OF ARBUTIN AND BETULINIC ACID METHYL ESTER

Background: Arbutus pavarii Pamp. (fam. Ericaceae), commonly known as “Shmeri”, “Shmar” and “Libyan Strawberry”, is an endemic Libyan medicinal plant, growing almost exclusively in the Al-Jabel Al-Akhdar mountainous region in Libya. Aims: To assess the cytotoxicity of A. pavarii against human cancer cell lines and to carry out bioassay-guided isolation and identification of compounds. Materials and Methods: Shed-dried and ground leaves of A. pavarii were Soxhlet-extracted, successively, with n-hexane, dichloromethane (DCM) and methanol (MeOH), and assessed for cytotoxicity against several human cancer cell lines using the MTT assay. The cytotoxicity of the DCM extract against the normal human prostate cell line PNT2 was also assessed to determine the selectivity index (SI). The DCM extract was subjected to vacuum liquid chromatography (VLC) to produce eight fractions. A reversed-phase preparative HPLC analysis of the active VLC fraction was carried out to purify the major compounds present in the active fraction, and the structures of the compounds were elucidated by spectroscopic means. Results: The DCM extract was more cytotoxic against the PC3 cell line (IC50= 26 mg/mL) but less to the normal human prostate cell line PNT2 (IC50 = 90 mg/mL) with a selectivity index of 3.5. VLC analysis produced 8 fractions, with fraction VLC-5 most active against PC3 cells. Prep-HPLC-based purification of VLC-5 afforded the isolation of arbutin (1) and betulinic acid methyl ester (2), the structures of which were elucidated by spectroscopic means. Conclusion: The DCM extract of the leaves of A. pavarii exhibited significant cytotoxicity to PC3 cells, but much less cytotoxicity against normal human prostate cell line. The isolated compounds from the active fraction, arbutin (1) and betulinic acid methyl ester (2), which were previously shown to possess cytotoxic properties, could be responsible for the cytotoxicity of the DCM extract

S100A4 Elevation Empowers Expression of Metastasis Effector Molecules in Human Breast Cancer.

Many human glandular cancers metastasize along nerve tracts, but the mechanisms involved are generally poorly understood. The calcium-binding protein S100A4 is expressed at elevated levels in human cancers, where it has been linked to increased invasion and metastasis. Here we report genetic studies in a Drosophila model to define S100A4 effector functions that mediate metastatic dissemination of mutant Ras-induced tumors in the developing nervous system. In flies overexpressing mutant RasVal12 and S100A4, there was a significant increase in activation of the stress kinase JNK and production of the matrix metalloproteinase MMP1. Genetic or chemical blockades of JNK and MMP1 suppressed metastatic dissemination associated with S100A4 elevation, defining required signaling pathway(s) for S100A4 in this setting. In clinical specimens of human breast cancer, elevated levels of the mammalian paralogs MMP2, MMP9, and MMP13 are associated with a 4- to 9-fold relative decrease in patient survival. In individual tumors, levels of MMP2 and MMP13 correlated more closely with levels of S100A4, whereas MMP9 levels correlated more closely with the S100 family member S100P. Overall, our results suggest the existence of evolutionarily conserved pathways used by S100A4 to promote metastatic dissemination, with potential prognostic and therapeutic implications for metastasis by cancers that preferentially exploit nerve tract migration routes. Cancer Res; 77(3); 1-10. ©2016 AACR

Using Knowledge Management To Gain Competitve Advantage In Jordanian Pharmaceutical Industrial Organization

The ability to store, capture, and disseminate knowledge within and across pharmaceutical organizational boundaries has challenged manager for many years. However, as product lifecycles have decreased and environmental complexity and volatility have increase, the need tom manage knowledge is intensifying, particularly across the value chain. Firm view knowledge and knowledge management as part of their strategic orientation. The difficulties of managing knowledge of are faced by pharmaceutical firms of all size. Low – cost strategies may emphasize knowledge that can be used to cut costs, lower prices, and short cycle times whereas differentiation strategies may emphasize, knowledge that adds value to a product giving it unique characteristics that serve to differentiate it from the competition. This research examines the process of acquisition, retention, maintenance, and retrieval of knowledge both within the firm through organizational memory and across the value chain through knowledge management and compares these practices for small and large firms(Chang, Ching-Hsun,2011) This study focused on the relationship between knowledge management and competitive advantages in pharmaceutical firm, it also reviewed in the research  objectives, and its problems to find out solutions and to write down recommendations and suggestion that may be helpful for others. The study has reviewed some of the assumptions associated with this matter and the theories that worked out for the collection of information is a questionnaire which was adopted in the analysis the final, after collecting the information analyzed used SPSS program and reviewed and discussed the results and explaining them in tables and figures, at the end, results and recommendations reached. Key words: knowledge management, competitive advantage, pharmaceutical organizationa

The Bivariate Rogers-Szeg\"{o} Polynomials

We present an operator approach to deriving Mehler's formula and the Rogers formula for the bivariate Rogers-Szeg\"{o} polynomials $h_n(x,y|q)$. The proof of Mehler's formula can be considered as a new approach to the nonsymmetric Poisson kernel formula for the continuous big $q$-Hermite polynomials $H_n(x;a|q)$ due to Askey, Rahman and Suslov. Mehler's formula for $h_n(x,y|q)$ involves a ${}_3\phi_2$ sum and the Rogers formula involves a ${}_2\phi_1$ sum. The proofs of these results are based on parameter augmentation with respect to the $q$-exponential operator and the homogeneous $q$-shift operator in two variables. By extending recent results on the Rogers-Szeg\"{o} polynomials $h_n(x|q)$ due to Hou, Lascoux and Mu, we obtain another Rogers-type formula for $h_n(x,y|q)$. Finally, we give a change of base formula for $H_n(x;a|q)$ which can be used to evaluate some integrals by using the Askey-Wilson integral.Comment: 16 pages, revised version, to appear in J. Phys. A: Math. Theo

Facebook use and its predictive factors among students: Evidence from a lower- and middle-income country, Bangladesh

Background:Facebook is a popular social networking site in the modern world. It has an adverse effect such as impairing daily health and psychological health and also interpersonal relationships when the use becomes problematic.AimsTo examine problematic Facebook use (PFU) and its predictors among Bangladeshi students during the COVID-19 pandemic.MethodA cross-sectional online survey was conducted among 601 Bangladeshi students and collected data related to socio-demographic information, behavioral health, internet use behavior, depression, anxiety and problematic Facebook use [assessed using the Bergen Facebook Addiction Scale (BFAS)]. The data were analyzed using descriptive (frequencies and percentages) and inferential statistics (independent sample t-tests, one-way ANOVAs, correlations, and multivariable linear regression).ResultsThe results indicated that 29.1% of participants were problematic Facebook users (using cutoff ≥18 out of 30). Medical college students had higher mean score on PFU than other students (p < 0.001). In addition, the mean score of PFU was significantly higher among the students who were in a relationship (p = 0.001), did not engage in physical activity (p < 0.001), used the internet more than 5 h per day (p < 0.001), used social media (p < 0.001), and had depression or anxiety symptoms (p < 0.001). PFU was significantly associated with depression and anxiety among the whole sample. Predictive factors for PFU included relationship status, daily internet use time, gaming, social media use, depression, and anxiety. The model predicted almost 33.2% variance for PFU.ConclusionsFindings suggest interventions should be implemented for students with a special focus on medical students who had higher score of PFU than other types of students