High-confidence glycosome proteome for procyclic form <em>Trypanosoma brucei</em> by epitope-tag organelle enrichment and SILAC proteomics

The glycosome of the pathogenic African trypanosome Trypanosoma brucei is a specialized peroxisome that contains most of the enzymes of glycolysis and several other metabolic and catabolic pathways. The contents and transporters of this membrane-bounded organelle are of considerable interest as potential drug targets. Here we use epitope tagging, magnetic bead enrichment, and SILAC quantitative proteomics to determine a high-confidence glycosome proteome for the procyclic life cycle stage of the parasite using isotope ratios to discriminate glycosomal from mitochondrial and other contaminating proteins. The data confirm the presence of several previously demonstrated and suggested pathways in the organelle and identify previously unanticipated activities, such as protein phosphatases. The implications of the findings are discussed

Rescue of deficits by Brwd1 copy number restoration in the Ts65Dn mouse model of Down syndrome

With an incidence of ~1 in 800 births, Down syndrome (DS) is the most com- mon chromosomal condition linked to intellectual disability worldwide. While the genetic basis of DS has been identified as a triplication of chromosome 21 (HSA21), the genes encoded from HSA 21 that directly contribute to cognitive de fi cits remain incompletely understood. Here, we found that the HSA21- encoded chromatin effector, BRWD1, was upregulated in neurons derived from iPS cells from an individual with Down syndrome and brain of trisomic mice. We showed that selective copy number restoration of Brwd1 in trisomic animals rescued de fi cits in hippocampal LTP, cognition and gene expression. We demonstrated that Brwd1 tightly binds the BAF chromatin remodeling complex, and that increased Brwd1 expression promotes BAF genomic mistargeting. Importantly, Brwd1 renormalization rescued aberrant BAF localization, along with associated changes in chromatin accessibility and gene expression. These findings establish BRWD1 as a key epigenomic mediator of normal neurodevelopment and an important contributor to DS-related phenotypes

Computed tomography coronary angiography as initial work-up for unstable angina pectoris : [Unstable anjina pektoris için başlangıç work-up olarak bilgisayarlı tomografi koroner anjiyografi]

Computed Tomography Coronary Angiography (CTCA) is a rapid, non-invasive diagnostic tool for coronary artery disease (CAD). Rapid Access Chest Pain Clinics (RACPC) were introduced in UK in 2000, in order to assess rapidly patients with chest pain. To evaluate the use of CTCA as initial work-up for unstable angina pectoris in a primary care-based RACPC. Eighty-eight (n=88) patients were examined by a consultant cardiologist and referred for CTCA if indicated. CTCA was performed with a 640 slices, 320-row CT scanner. Thirty-five (n=35) patients were discharged without further investigations; 50 (mean age 59.8 years; 24 male) were referred for CTCA and 3 were referred directly for an invasive angiography (IA). Following CTCA, 17 patients were discharged. Seventeen (n=17) patients with no history of CAD, but with positive CTCA findings and eleven (n=11) patients with known CAD but without new lesions on CTCA were discharged after optimisation of medical treatment. Five (n=5) of the 50 patients eventually underwent IA; 2 were referred for CABG; 3 continued with medical treatment. No major adverse cardiac events were recorded in a 6-months' follow up period. The cost for each patient who underwent CTCA was £1,087; 94% of patients rated their experience as good or excellent. The time interval from RACPC visit-to-definitive diagnosis was &lt;3 weeks in 50% of patients, &lt;6 weeks in 90%. Use of CTCA as initial investigation in Primary Care, is both clinically and cost-effective. CTCA should be considered in the initial diagnostic work-up of unstable angina pectoris patients, with or without prior history of CAD.Bilgisayarlı tomografi koroner anjiyografi (BTKA) koroner arter hastalığı (KAH) için non invazif hızlı bir araştırma aracıdır. 2000 yılında Birleşik Krallıkta (UK) göğüs ağrısı olan hastalara hızlı bir şekilde yardımcı olmak için hızlı ulaşılan göğüs ağrısı klinikleri (RACPC) kurulmuştur. Çalışmanın amacı birinci basamak tabanlı RACPC de unstable anjina pektoris için başlangıç work-up olarak BTKA kullanımını araştırmaktı. Seksen sekiz (n=88) hasta bir konsultan kardiyolog tarafından muayene edildi ve eğer endikasyon varsa BTKA çekildi. BTKA bir 640 slices, 320 –row BT skaner ile uygulandı. Otuz beş (n=35) daha ileri araştırma yapılmadan taburcu edildi. 50 (ortalama yaş 59.8 yıl;24 erkek) hastaya BTKA çekildi ve 3 hasta doğrudan invazif anjiyografiye (IA) gönderildi. BTKA sonrası 17 hasta taburcu edildi. KAH öyküsü olmayan, fakat pozitif BTKA ‘si olan 17 hasta ve bilinen KAH öyküsü olan fakat BTKA’sinde yeni lezyon saptanmayan 11 hasta medikal tedavisi düzenlenerek taburcu edildi. Elli hastanın 5’ine IA yapıldı, 2’si CABG’ya yönlendirildi, 3’ünde medikal tedavi ile devam edildi. 6 aylık takip periyodu sonrası herhangi bir majör yan etki kaydedilmedi. BTKA yapılan her hastanın maliyeti £1,087idi; hastaların %94’ü deneyimlerini iyi veya mükemmel olarak derecelendirdiler. RACPC başvurusu ile kesin tanı arasındaki zaman aralığı hastaların %50’sinde &lt;3 hafta, %90’ında &lt;6 hafta idi. Birinci basamakta başlangıç araştırma yöntemi olarak BTKA kullanımı hem maliyet hem de klinik olarak etkindi. BTKA hem KAH olan hem de olmayan unstable anjina pektoris hastalarında başlangıç teşhis work-up olarak değerlendirilmelidir

Does angina vary with the menstrual cycle in women with premenopausal coronary artery disease?

OBJECTIVE—To determine whether angina in women with established coronary heart disease varies with changes in hormone concentrations during the menstrual cycle.
DESIGN—Subjects were prospectively studied once a week for four weeks.
SETTING—Cardiology outpatient department of tertiary referral centre.
SUBJECTS—Nine premenopausal women, mean (SEM) age 38.89 (2.18) years, with established coronary heart disease, symptomatic angina, and a positive exercise test.
MAIN OUTCOME MEASURE—Myocardial ischaemia as determined by time to 1 mm ST depression during symptom limited exercise testing. Position in the menstrual cycle was established from hormone concentrations.
RESULTS—The early follicular phase, when oestradiol and progesterone concentrations were both low, was associated with the worst exercise performance in terms of time to onset of myocardial ischaemia, at 290 (79) seconds; the best performance (418 (71) seconds) was when oestrogen concentrations were highest in the mid-cycle (p < 0.05). Similar trends were observed in other measured variables. Progesterone concentrations did not influence exercise performance.
CONCLUSIONS—During the menstrual cycle myocardial ischaemia was more easily induced when oestrogen concentrations were low. This may be important for timing the assessment and evaluating treatment in women with coronary heart disease.


Keywords: myocardial ischaemia; exercise testing; oestradiol; progesteron