Rapidly evolving protointrons in Saccharomyces genomes revealed by a hungry spliceosome.

Introns are a prevalent feature of eukaryotic genomes, yet their origins and contributions to genome function and evolution remain mysterious. In budding yeast, repression of the highly transcribed intron-containing ribosomal protein genes (RPGs) globally increases splicing of non-RPG transcripts through reduced competition for the spliceosome. We show that under these "hungry spliceosome" conditions, splicing occurs at more than 150 previously unannotated locations we call protointrons that do not overlap known introns. Protointrons use a less constrained set of splice sites and branchpoints than standard introns, including in one case AT-AC in place of GT-AG. Protointrons are not conserved in all closely related species, suggesting that most are not under positive selection and are fated to disappear. Some are found in non-coding RNAs (e. g. CUTs and SUTs), where they may contribute to the creation of new genes. Others are found across boundaries between noncoding and coding sequences, or within coding sequences, where they offer pathways to the creation of new protein variants, or new regulatory controls for existing genes. We define protointrons as (1) nonconserved intron-like sequences that are (2) infrequently spliced, and importantly (3) are not currently understood to contribute to gene expression or regulation in the way that standard introns function. A very few protointrons in S. cerevisiae challenge this classification by their increased splicing frequency and potential function, consistent with the proposed evolutionary process of "intronization", whereby new standard introns are created. This snapshot of intron evolution highlights the important role of the spliceosome in the expansion of transcribed genomic sequence space, providing a pathway for the rare events that may lead to the birth of new eukaryotic genes and the refinement of existing gene function

Rare Solid Tumors of the Pancreas as Differential Diagnosis of Pancreatic Adenocarcinoma

Context Rare solid tumors of the pancreas can be misinterpreted as primary pancreatic cancer. Objective The aim of this study was to report our experience in the treatment of patients with rare tumor lesions of the pancreas and to discuss clinical and pathological characteristics in the context of the role of surgery. Design Data from patients of our prospective data-base with rare benign and malignant tumors of the pancreas, treated in our division from January 2004 to August 2010, were analyzed retrospectively. Results One-thousand and ninety-eight patients with solid tumors of the pancreas underwent pancreatic surgery. In 19 patients (10 women, 9 men) with a mean age of 57 years (range: 20-74 years) rare pancreatic tumors (metastasis, solid pseudopapillary tumor, teratoma, hemangioma, accessory spleen, lymphoepithelial cyst, hamartoma, sarcoidosis, yolk sac tumor) were the reason for surgical intervention. Conclusion If rare benign and malignant pancreatic tumors, intrapancreatic metastasis, as well as pancreatic malformations or other abnormalities, present themselves as solid masses of the pancreas, they constitute an important differential diagnosis to primary pancreatic neoplasia, e.g. pancreatic ductal adenocarcinoma. Clinical imaging techniques cannot always rule out malignancy, thus operative exploration often remains the treatment of choice to provide the correct diagnosis and initiate adequate surgical therapy

Eine Test- und Ansteuerschaltung für eine neuartige 3D Verbindungstechnologie

In der vorliegenden Arbeit wird eine Built-In Self-Test Schaltung (BIST) vorgestellt, welche die vertikalen Inter-Chip-Verbindungen in einer neuartigen 3D Schaltungstechnologie auf ihre Funktionalität zur Datenübertragung überprüft. Die 3D Technologie beruht auf der Stapelung mehrerer aktiver Silizium-CMOS-ICs, welche durch das Siliziumsubstrat hindurch vertikal miteinander elektrisch verbunden sind. Bei diesen Vias sind die zu erwartenden Defekte hochohmige Verbindungen und Kurzschlüsse. </p><p style=&quot;line-height: 20px;&quot;> Die entwickelte Testschaltung ermöglicht es, beliebige Konstellationen von vertikalen Verbindungen auf Fehler zu untersuchen, und das Ergebnis entweder zur Analyse der 3D Technologie auszulesen oder innerhalb des Chipstapels zu verwenden, um defekte Vias zu umgehen. Die Schaltung wurde in einer 0,13μm Technologie entworfen und simuliert. Ein Testchip ist momentan in Produktion

Yield-improving test and routing circuits for a novel 3-D interconnect technology

This work presents a system to increase the yield of a novel 3-D chip integration technology. A built-in self-test and a routing system have been developed to identify and avoid faults on vertical connections between different stacked chips. The 3-D technology is based on stacking several active CMOS-ICs, which have through-substrate electrical contacts to communicate with each other. The expected defects of these vias are shorts and resistances that are too high. <P> The test and routing system is designed to analyze an arbitrary number of connections. The result ist used to gain information about the reliability of the new 3-D processing and to increase its yield. The circuits have been developed in 0.13 μm technology, one chip has been fabricated and tested, another one is in production

RNA Methylation by the MIS Complex Regulates a Cell Fate Decision in Yeast

For the yeast Saccharomyces cerevisiae, nutrient limitation is a key developmental signal causing diploid cells to switch from yeast-form budding to either foraging pseudohyphal (PH) growth or meiosis and sporulation. Prolonged starvation leads to lineage restriction, such that cells exiting meiotic prophase are committed to complete sporulation even if nutrients are restored. Here, we have identified an earlier commitment point in the starvation program. After this point, cells, returned to nutrient-rich medium, entered a form of synchronous PH development that was morphologically and genetically indistinguishable from starvation-induced PH growth. We show that lineage restriction during this time was, in part, dependent on the mRNA methyltransferase activity of Ime4, which played separable roles in meiotic induction and suppression of the PH program. Normal levels of meiotic mRNA methylation required the catalytic domain of Ime4, as well as two meiotic proteins, Mum2 and Slz1, which interacted and co-immunoprecipitated with Ime4. This MIS complex (Mum2, Ime4, and Slz1) functioned in both starvation pathways. Together, our results support the notion that the yeast starvation response is an extended process that progressively restricts cell fate and reveal a broad role of post-transcriptional RNA methylation in these decisions