345 research outputs found
Identification of two distinct intron elements involved in alternative splicing of beta-tropomyosin pre-mRNA
The rat beta-tropomyosin gene encodes two isoforms, termed skeletal muscle beta-tropomyosin and fibroblast last tropomyosim 1 (TM-1), via an alternative RNA processing mechanism. The gene contains 11 exons. Exons 1-5 and exons 8 and 9 are common to all mRNAs expressed from the gene. Exons 6 and 11 are used in fibroblasts, as well as smooth muscle, whereas exons 7 and 10 are used only in skeletal muscle. In the present studies we focused on the mutually exclusive internal alternative splice choice involving exon 6 (fibroblast-type splice) and exon 7 (skeletal muscle-type splice). We have identified two distinct elements in the intron, upstream of exon 7, involved in splice site selection. The first element is comprised of a polypyrimidine tract located 89-143 nucleotides upstream of the 3' splice site, which specifies the location of the lariat branchpoints used, 144-153 nucleotides upstream of exon 7. The 3' splice site AG dinucleotide has no role in selection of these branchpoints. The second element is comprised of intron sequences located between the polypyrimidine tract and the 3' splice site of exon 7. It contains an important determinant in alternative splice site selection, because deletion of these sequences results in the use of the skeletal muscle-specific exon in nonmuscle cells. We propose that the use of lariat branchpoints located far upstream from a 3' splice site may be a general feature of some alternatively excised introns, reflecting the presence of regulatory sequences located between the lariat branch site and the 3' splice site. The data also indicate that alternative splicing of the rat beta-tropomyosin gene is regulated by a somewhat different mechanism from that described for rat alpha-tropomyosin gene and the transformer-2 gene of Drosophila melanogaster
Імітація монаршної поведінки в “дивних” вчинках Богдана Хмельницького на початку 1649 р.
Увага до постаті Богдана Хмельницького як на фаховому, так і на дилетантському рівні не вщухає вже, навіть попри періодичні офіційні чи неофіційні заборони, протягом трьох з половиною століть. Політичні та ідеологічні чинники, як можна спостерігати останні півтора десятиліття в Україні та, частково, у Польщі, регулярно посилюють інтерес до біографії гетьмана, його вчинків, наслідків діяльності, супроводжуючись, як нерідко трапляється в аналогічних ситуаціях, створенням зі складної, протирічливой, трагічної постаті Б.Хмельницького національного ідола, усі дії якого набувають містичного, пророчого, апріорно історично-виправданого характреру. Концептуальні трагічні помилки, прорахунки, прояви некомпетентності, невиправданої навіть за поняттями тієї епохи жорстокості переважно «делікатно» замовчуються, у кращому разі – обмежуються легкими докорами, а здебільше - пояснюються «злочинною змовою» сучасників-поляків, які свідомо з метою дискредитації сфальсифікували вчинки гетьмана, перебільшивши закономірні для усіх війн трагічні складові україно-польської війни. Як не парадоксально, до сьогодні залишаються, на жаль, поодинокими спроби дати добре аргументоване, позбавлене соціологічних та психологічних штампів, пояснення тих чи інших вчинків Б.Хмельницького та його соратників (як, власне, і представників польського, татарського, російського та турецького таборів), яке б базувалося не на упередженому заздалегідь виправдальному чи звинувачувальному ставленні до подій середини XVII ст., а на підгрунті максимально повного врахування ментальних, поведінкових стереотипів доби. Ми маємо на увазі вишукано-резонансну рецензію Н.Яковенко на серію публікацій перш за все В.Смолія та В.Степанкова [17; див. також: 19], а також деяких інших авторів, зокрема О.Толочка [11] та автора цих рядків [2], присвячених політичній та духовній ситуації в Україні напередодні Хмельничини, українській національній революції та постаті Хмельницького. Для наших подальших роздумів немає особливої потреби здійснювати розлогий джерелознавчий та історіографічний аналіз, оскільки він, з одного боку, вимагає спеціальної концептуальної зосередженості, а з іншого - надалі ми будемо оперувати у необхідних випадках виключно загальновідомими, хрестоматійними аргументами, коли можна дозволити собі уникнути розлогих екскурсів щодо розгляду джерел та літератури. Зазначимо лише, що безпосередньо біографії Б.Хмельницького присвячена досить велика кількість робіт з різних наукових та ідеологічних таборів, серед яких в першу чергу слід назвати імена М.Грушевського, М.Кордуби, В.Липинського, І. Крип’якевича, В.Замлинського, Я.Дашкевича, В.Смолія, В.Степанкова, П.Гоя, Я.Федорука, В.Горобця, Т.Чухліба, В.Сергійчука, В.Серчика та багатьох інших. Події кінця 1648 – початку 1648 рр. з огляду на їх особливу роль в контексті подій українських визвольних змагань і які будуть нас цікавити в першу чергу
“Piggy-Backing” on Diagnostic Platforms Brings Hope to Neglected Diseases: The Case of Sleeping Sickness
Radical nephroureterectomy for pathologic T4 upper tract urothelial cancer: can oncologic outcomes be improved with multimodality therapy?
Purpose To report the outcomes of patients with pathologic T4 UTUC and investigate the potential impact of peri-operative chemotherapy combined with radical nephroureterectomy (RNU) and regional lymph node dissection (LND) on oncologic outcomes. Materials and Methods Patients with pathologic T4 UTUC were identified from the cohort of 1464 patients treated with RNU at 13 academic centers between 1987 and 2007. Oncologic outcomes were stratified according to utilization of perioperative systemic chemotherapy and regional LND as an adjunct to RNU. Results The study included 69 patients, 42 males (61%) with median age 73 (range 43-98). Median follow-up was 17 months (range: 6-88). Lymphovascular invasion was found in 47 (68%) and regional lymph node metastases were found in 31 (45%). Peri-operative chemotherapy was utilized in 29 (42%) patients. Patients treated with peri-operative chemotherapy and RNU with LND demonstrated superior oncologic outcomes compared to those not treated by chemotherapy and/or LND during RNU (3Y-DFS: 35% vs. 10%; P = 0.02 and 3Y-CSS: 28% vs. 14%; P = 0.08). In multivariate Cox regression analysis, administration of peri-operative chemotherapy and utilization of LND during RNU was associated with lower probability of recurrence (HR: 0.4, P = 0.01), and cancer specific mortality (HR: 0.5, P = 0.06). Conclusions Pathological T4 UTUC is associated with poor prognosis. Peri-operative chemotherapy combined with aggressive surgery, including lymph node dissection, may improve oncological outcomes. Our findings support the use of aggressive multimodal treatment in patients with advanced UTUC
Radical nephroureterectomy for pathologic T4 upper tract urothelial cancer: can oncologic outcomes be improved with multimodality therapy?
Purpose To report the outcomes of patients with pathologic T4 UTUC and investigate the potential impact of peri-operative chemotherapy combined with radical nephroureterectomy (RNU) and regional lymph node dissection (LND) on oncologic outcomes. Materials and Methods Patients with pathologic T4 UTUC were identified from the cohort of 1464 patients treated with RNU at 13 academic centers between 1987 and 2007. Oncologic outcomes were stratified according to utilization of perioperative systemic chemotherapy and regional LND as an adjunct to RNU. Results The study included 69 patients, 42 males (61%) with median age 73 (range 43-98). Median follow-up was 17 months (range: 6-88). Lymphovascular invasion was found in 47 (68%) and regional lymph node metastases were found in 31 (45%). Peri-operative chemotherapy was utilized in 29 (42%) patients. Patients treated with peri-operative chemotherapy and RNU with LND demonstrated superior oncologic outcomes compared to those not treated by chemotherapy and/or LND during RNU (3Y-DFS: 35% vs. 10%; P = 0.02 and 3Y-CSS: 28% vs. 14%; P = 0.08). In multivariate Cox regression analysis, administration of peri-operative chemotherapy and utilization of LND during RNU was associated with lower probability of recurrence (HR: 0.4, P = 0.01), and cancer specific mortality (HR: 0.5, P = 0.06). Conclusions Pathological T4 UTUC is associated with poor prognosis. Peri-operative chemotherapy combined with aggressive surgery, including lymph node dissection, may improve oncological outcomes. Our findings support the use of aggressive multimodal treatment in patients with advanced UTUC
The Impact of Previous Ureteroscopic Tumor Ablation on Oncologic Outcomes After Radical Nephrouretectomy for Upper Urinary Tract Urothelial Carcinoma
We investigated whether a history of endoscopic tumor ablation impacts oncologic outcomes after radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC). Using a multi-institutional database that contained patients who were treated with RNU, oncologic outcomes were assessed according to history of ureteroscopic tumor ablation. Disease-free survival (DFS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier survival analysis. Multivariate Cox regression analyses were performed to determine independent predictors of disease recurrence and cancer-specific mortality after RNU. The study included 1268 patients, 853 men and 415 women, with a mean age of 67.5 years (range 32-94 y) and 52.8 months median follow-up after RNU. A total of 175 (13%) patients underwent RNU after endoscopic tumor ablation and 1093 (87%) patients underwent RNU without a history of endoscopic ablation. The 5-year DFS and CSS rates were 72% and 77% in those with a history of tumor ablation vs 69% and 73% in those without a history of ablation (P = 0.171 and P = 0.365, respectively). In multivariate Cox regression analysis, history of ablation therapy was not associated with disease recurrence or cancer-specific mortality (hazard ratio [HR]: 0.79, P = 0.185 and HR: 0.7, P = 0.078, respectively). Our collaborative international efforts suggest that in selected patients, endoscopic tumor ablation does not adversely affect the recurrence and survival after subsequent RNU for UTUC. Our data support the continued role of ureteroscopic ablation of UTUC in appropriately selected patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90497/1/end-2E2010-2E0396.pd
Multiparametric magnetic resonance imaging and clinical variables: Which is the best combination to predict reclassification in active surveillance patients?
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Upper urinary tract urothelial carcinoma with loco‐regional nodal metastases: insights from the Upper Tract Urothelial Carcinoma Collaboration
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86906/1/j.1464-410X.2011.10075.x.pd
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Symbolic closure: Towards a renewed sociological perspective on the relationship between higher education, credentials and the graduate labour market
This article explores how our understanding of the graduate labour market can be improved by re-assessing some of the insights of the conflictual tradition within sociology. In particular, its theorising of ‘social closure’ and the use of educational credentials within the labour market remain highly relevant. Yet these ideas need to be modified to better deal with the current social, economic and educational contexts. This article extends the social closure literature to deal with some of the changes within the graduate labour market by turning to Pierre Bourdieu’s ideas on symbolic violence. I will argue that ‘symbolic closure’, the reliance on exclusion through categorisation and classification, becomes of greater importance in a graduate labour market that no longer offers any clarity about what graduate skills, jobs and rewards constitute and signify
Does an unexpected final pathology of pT3a renal tumour undermine cancer control in clinically T1N0M0 patients who were initially treated with nephron sparing surgery?
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