Stroke Rehabilitation.

Despite contemporary rehabilitation strategies, stroke remains a leading cause of loss of function, limited mobility, psycho-social complications, and decreased quality of life. Stroke rehabilitation is a process that aims to prevent deterioration of function, increase function, and assist the patient in achieving the highest possible level of independence physically, socially, spiritually, psychologically, vocationally, and economically. The process begins with relearning activities of daily living such as grooming, bathing, toileting, eating, and dressing.

Natural cycles in South Pacific Gyre strength and the Southern Annular Mode.

The South Pacific Gyre (SPG) plays a vital role in regulating Southern Hemisphere climate and ecosystems. The SPG has been intensifying since the twentieth century due to changes in large scale wind forcing. These changes result from variability in the Southern Annular Mode (SAM), causing warming along the eastern SPG which affects local ecosystems.

Rapid proteomic analysis for solid tumors reveals LSD1 as a drug target in an end-stage cancer patient.

Recent advances in mass spectrometry (MS)-based technologies are now set to transform translational cancer proteomics from an idea to a practice. Here, we present a robust proteomic workflow for the analysis of clinically relevant human cancer tissues that allows quantitation of thousands of tumor proteins in several hours of measuring time and a total turnaround of a few days. We applied it to a chemorefractory metastatic case of the extremely rare urachal carcinoma.

Molecular genetics of the transcription factor GLIS3 identifies its dual function in beta cells and neurons.

The GLIS family zinc finger 3 isoform (GLIS3) is a risk gene for Type 1 and Type 2 diabetes, glaucoma and Alzheimer's disease endophenotype. We identified GLIS3 binding sites in insulin secreting cells (INS1) (FDR q<0.05; enrichment range 1.

Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo.

Mediator is a large multiprotein complex conserved in all eukaryotes, which has a crucial coregulator function in transcription by RNA polymerase II (Pol II). However, the molecular mechanisms of its action in vivo remain to be understood. Med17 is an essential and central component of the Mediator head module.

Natural variation of histone modification and its impact on gene expression in the rat genome.

Histone modifications are epigenetic marks that play fundamental roles in many biological processes including the control of chromatin-mediated regulation of gene expression. Little is known about interindividual variability of histone modification levels across the genome and to what extent they are influenced by genetic variation. We annotated the rat genome with histone modification maps, identified differences in histone trimethyl-lysine levels among strains, and described their underlying genetic basis at the genome-wide scale using ChIP-seq in heart and liver tissues in a panel of rat recombinant inbred and their progenitor strains.

Mediator links transcription and DNA repair by facilitating Rad2/XPG recruitment.

Mediator is a large multiprotein complex conserved in all eukaryotes. The crucial function of Mediator in transcription is now largely established. However, we found that this complex also plays an important role by connecting transcription with DNA repair.

The yeast RPL9B gene is regulated by modulation between two modes of transcription termination.

RNA Pol II transcription termination can occur by at least two alternative pathways. Cleavage and polyadenylation by the CPF/CF complex precedes mRNA transcription termination, while the Nrd1 complex is involved in transcription termination of non-coding RNAs such as sno/snRNAs or cryptic unstable transcripts. Here we show that transcription of RPL9B, one of the two genes coding for the ribosomal protein Rpl9p, terminates by either of these two pathways.

Enrichment of unstable non-coding RNAs and their genome-wide identification.

Cryptic unstable transcripts (CUTs) have been recently described as a major class of non-coding RNAs. These transcripts are, however, extremely unstable in normal cells and their analyzes pose specific technical problems. In this chapter, after a brief introduction discussing general aspects associated with the analysis of non-coding RNAs, we provide details of methods to enrich, map, and quantify this unconventional class of transcripts.

Widespread bidirectional promoters are the major source of cryptic transcripts in yeast.

Pervasive and hidden transcription is widespread in eukaryotes, but its global level, the mechanisms from which it originates and its functional significance are unclear. Cryptic unstable transcripts (CUTs) were recently described as a principal class of RNA polymerase II transcripts in Saccharomyces cerevisiae. These transcripts are targeted for degradation immediately after synthesis by the action of the Nrd1-exosome-TRAMP complexes.

Futile cycle of transcription initiation and termination modulates the response to nucleotide shortage in S. cerevisiae.

Hidden transcription in eukaryotes carries a large potential of regulatory functions that are only recently beginning to emerge. Cryptic unstable transcripts (CUTs) are generated by RNA polymerase II (Pol II) and rapidly degraded after transcription in wild-type yeast cells. Whether CUTs or the act of transcription without RNA production have a function is presently unclear.

Mutations of the RAG3 gene encoding a regulator of fermentation in Kluyveromyces lactis are suppressed by a mutation of the transcription factor gene KlGCR1.

In Kluyveromyces lactis, Rag3 regulates both fermentative metabolism and thiamine biosynthesis. Regulation of fermentation is exerted at the level of transcription of KlPDC1. We have isolated and identified a mutation of the transcription factor KlGCR1, Klgcr1-1, which suppressed the fermentative-deficient phenotype associated with the RAG3 deletion.

Sck1 activator coordinates glucose transport and glycolysis and is controlled by Rag8 casein kinase I in Kluyveromyces lactis.

Casein kinases I (CKI) are ubiquitous in eukaryotic cells and are crucial factors for nutrient-signalling pathways in yeasts. In Kluyveromyces lactis, the KlRgt1 repressor represses the expression of the glucose transporter RAG1 gene in absence of glucose, but in response to glucose availability, Rag8 CKI cooperates with the Rag4 glucose sensor to inactivate KlRgt1. The SCK1 gene, a rag8 mutation suppressor, encodes a bHLH activator required for maximal expression of the RAG1 and glycolytic genes in the presence of glucose.