Up-regulation of protein serine/threonine phosphatase type 2C during 1α,25-dihydroxyvitamin D3-induced monocytic differentiation of leukemic HL-60 cells

AbstractTreatment with 20 nM 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) caused a progressive increase in the activity of Mg2+-dependent protein serine/threonine phosphatase type 2C (PP2C) in subcellular fractions of HL-60 cells, whereas PP2C activity was relatively constant throughout all-trans retinoic acid-induced (1 μM) granulocytic differentiation. The increase in PP2C activity appeared to parallel the 1,25(OH)2D3-induced phenotypic and functional changes in HL-60 cells. Immunoblot and Northern blot analysis indicated that the increase in PP2C activity corresponded to the increased expression of PP2C protein, which was preceded by an increase in the level of mRNA for PP2Cβ. No mRNA for PP2Cα was detected in resting or 1,25(OH)2D3-stimulated HL-60 cells. These results suggest that the increased expression of PP2C is related with the 1,25(OH)2D3-induced monocytic differentiation of HL-60 cells

Economic Crisis and Investor Behaviour

This study investigates the effects of crises on domestic and foreign investors’ behaviours by utilizing a nonlinear approach. Considering the nonlinearity inherent in many financial variables, this study proposes an appropriate econometric modelling for analysing the investors’ behaviour, particularly during turbulent times. Specifically, STAR-STGARCH family models and generalized impulse response function analysis (GIRF) are employed to understand the different reactions of foreign and domestic investors at the Malaysian Stock Exchange market during the 1997 Asian crisis. The results of the model and the GIRF analysis have shown that foreign investors exhibited a herding behavior during the crisis and responded the shock more quickly than the domestic investors. When the same analysis is applied to understand the effects of the 2008 Subprime Mortgage Crisis in the Malaysian market, the behaviors of foreign and domestic investors are found to be very similar

Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas

RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations altering this enzyme have not previously been linked to any pathology in humans, which is a testament to its indispensable role in cell biology. On the basis of a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II (ref. 1), hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors show dysregulation of key meningeal identity genes including WNT6 and ZIC1/ZIC4. In addition to mutations in POLR2A, NF2, SMARCB1, TRAF7, KLF4, AKT1, PIK3CA, and SMO4 we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features

Glioma Through the Looking GLASS: Molecular Evolution of Diffuse Gliomas and the Glioma Longitudinal AnalySiS Consortium

Adult diffuse gliomas are a diverse group of brain neoplasms that inflict a high emotional toll on patients and their families. The Cancer Genome Atlas (TCGA) and similar projects have provided a comprehensive understanding of the somatic alterations and molecular subtypes of glioma at diagnosis. However, gliomas undergo significant cellular and molecular evolution during disease progression. We review the current knowledge on the genomic and epigenetic abnormalities in primary tumors and after disease recurrence, highlight the gaps in the literature, and elaborate on the need for a new multi-institutional effort to bridge these knowledge gaps and how the Glioma Longitudinal AnalySiS Consortium (GLASS) aims to systemically catalog the longitudinal changes in gliomas. The GLASS initiative will provide essential insights into the evolution of glioma toward a lethal phenotype, with the potential to reveal targetable vulnerabilities, and ultimately, improved outcomes for a patient population in need

Advances, gaps and way forward in provision of climate services over the Greater Horn of Africa

The Greater Horn of Africa is prone to extreme climatic conditions, thus, making climate services increasingly important in supporting decision-making processes across a range of climate sensitive sectors. This study aims to provide a comprehensive review of the recent advances, gaps and challenges in the provision of climate services over the region, for each of the components of the Global Framework for Climate Services. The study explores various milestones that have been achieved toward climate service delivery. The achievements include improvement of station network coverage, and enhancing the capacity of member states to utilize various tools in data analysis and generate routine climate products. The advancement in science, and availability of High-Performance Computing has made it possible for forecast information to be provided from nowcasting to seasonal timescales. Moreover, operationalizing of the objective forecasting method for monthly and seasonal forecasts has made it possible to translate tercile forecasts for applications models. Additionally, innovative approaches to user engagement through co-production, communication channels, user-friendly interfaces, and dissemination of climate information have also been developed. Despite the significant progress that has been made in the provision of climate services, there are still many challenges and gaps that need to be overcome in order to ensure that these services are effectively meeting the needs of users. The research of the science underpinning climate variability, capacity building and stakeholder engagement, as well as improved data management and quality control processes are some of the gaps that exist over the region. Additionally, communication and dissemination of climate information, including timely warnings and risk communication, require improvement to reach diverse user groups effectively. Addressing these challenges will require strengthened partnerships, increased investment in capacity building, enhanced collaboration between the climate information producers and stakeholders, and the development of user-friendly climate products. Bridging these gaps will foster greater resilience to climate-related hazards and disasters in the Greater Horn of Africa and support sustainable development in the region

Esansiyel hipertansiyonu olan stabil angina pektorisli olgularda adenozin difosfat ve epinefrinle uyarılmış in-vitro trombosit aggregasyon yanıtı

Hipertansiyon, koroner arter hastalığı (KAH) için cinsiyet farkı olmaksızın bağımsız bir risk faktörüdür. Hem hipertansiyonda hem de KAH'nın gelişimi sırasında trombositlerin aktivasyonu söz konusudur. Çalışmamızda stabil angina pektorisli (SAP) olgularda, kontrol altında bulunan sınıf 1-2 hipertansiyonun in vitro trombosit agregasyon yanıtı üzerine olan etkilerinin araştırılması amaçlandı. Çalışmaya klinik verileriyle SAP, koroner anjiyografi ile KAH tanısı almış toplam 103 hasta alındı. Kontrol edilmiş esansiyel hipertansiyonu olan 45 KAH olgusu Grup I'i oluşturdu. Grup II ise hipertansif olmayan 58 KAH olgusundan oluşuyordu. Olgulardan sabah aç karnına ve oda ısısında alınan venöz kan örnekleri santrifüje edilerek trombositten zengin plazma (TZP) örnekleri hazırlandı. TZP daha sonra in-vitro adenozin difosfat (ADP) ve epinefrinle muamele edildi. Bohr'un Turbidometrik yöntemi kullanılarak trombosit agregasyon eğrileri oluşturuldu ve özel milimetrik kağıtlara yazdırıldı. Eğrilerden primer ve sekonder dalgaların aktivite yüzdeleri (% amplitüd) ve süreleri (sn) hesaplandı. Gruplar arasındaki veriler t testi ile karşılaştırıldı. Grup I grup II ile kıyaslandığında, epinefrin ve ADP ile indüklenmiş in vitro trombosit agregasyon yanıt yüzdelerinin (A%) hem primer hem de sekonder dalga için anlamlı oranda arttığı gözlendi (p0.05), sekonder dalga sürelerinin grup I'de anlamlı oranda artış gösterdiği belirlendi (p0.05). Hipertansif SAP'li olgularda, tedavi edilmiş olsalar bile, hipertansif olmayan SAP olgularıyla karşılaştırıldığında, anlamlı derecede artmış trombosit agregasyon yanıtı oluşmaktadır. Sonuç olarak; bu olgularda antiagregan özelliği olan antihipertansif ajanlarla birlikte, daha etkili antiagregan sağaltımın uygulanması gerekliliği sonucuna varabilmek için, daha geniş sayıda ve homojen antihipertansif sağaltım verilen hasta gruplarında in vivo ve prospektif çalışmalara gereksinim bulunmaktadır

Surgical treatment of Cushing's disease: Analysis of an experience of 12 years

This study reports our experience with respect to diagnosis and surgical treatment of 41 consecutive patients with Cushing's disease. The series consisted of 33 (79%) female, 8 (21%) male patents with a mean age of 35.4 years. Out of 41 patients, 18 underwent selective adenomectomy, 19 had partial hypophysectomy and 2 had subtotal hypophysectomy along with tumor removal. There were no serious complications attributable to the surgical interventions. The rate of initial remission was 92%. Six patients were treated for recurrences. After a mean follow up period of 38 months (range of 6 to 144 months), 35 of 41 patients remain in remission. In this study the results partial hypophysectomy was not found to be superior to selective adenonectomy. We conclude that radical transsphenoidal surgery is a safe and effective treatment method for Cushing's disease

Evaluation of Manisa propolis effect on leukemia cell line by telomerase activity

WOS: 000232242800017PubMed ID: 16055186Propolis is a resinous substance which is used by bees to repair and maintain their hives. It has more than 180 compounds including flavonoids, phenolic acids and its esters which have anti-inflammatory, antibacterial, antiviral, immunomodulatory, antioxidant and antiproliferative effects. Propolis is shown to inhibit cell division and protein synthesis. However the exact mechanism underlying antitumor effect is not clearly described. On the other hand progressive telomere shortening to a critical level results with senescence of normal cells by inducing apoptosis and telomerase prevents erosion of telomeres. In this study we aimed to evaluate hTERT ratios in propolis-treated T-cell acute lymphoblastic leukemia (CCFR-CEM) cell line. Cell counts and cell viability of propolis-treated and propolis-free T-cell acute lymphoblastic leukemia (CCFR-CEM) cell line were assessed by trypan blue dye exclusion test and MTT assay. The LightCycler instrument was used (online real-time PCR) for the quantification of hTERT in CCFR-CEM cell line. The hTERT ratio significantly decreased 60 and 93% after 24 and 72 h respectively compared to the initial value of the cells incubated with propolis. It had almost no cytotoxic effect and caused 30, 30, 22 and 12% decrease in cell counts after 24, 48, 72 and 96 h respectively which is statistically significant. In conclusion propolis may show antitumor and apoptotic effect via inhibiting telomerase expression besides the mechanisins which have been described previously. (c) 2005 Elsevier Ltd. All rights reserved