[Cooperation of geriatrics and trauma surgery in certified geriatric trauma centers : Insights into different care models and the implementation of requirements resulting from certification]. / Zusammenarbeit von Geriatrie und Unfallchirurgie in zertifizierten alterstraumatologischen Zentren : Einblicke in unterschiedliche Versorgungsmodelle und in die Umsetzung von Anforderungen, die sich aus der Zertifizierung ergeben.

BACKGROUND: In Germany, different models of orthogeriatric co-management have been implemented in certified geriatric trauma centers. So far, it is not clear how the different models are implemented and what influence the certification has on the structures and processes within the centers. The present study examined the extent of cooperation between surgery and geriatrics and if the quality of care had changed since the certification of the centers. METHODS: In this study 4 guided focus group interviews (FGI) were conducted in different teams of certified geriatric trauma centers in 3 federal states with 16 participants. To specify the content of the FGI, two additional interviews were conducted with system auditors. Both types of interview were analyzed by content analysis. RESULTS: The certification supported the implementation of structures and processes in the different orthogeriatric models; however, the quality of care and cooperation between surgery and geriatrics depends on the spatial proximity and the orthogeriatric care model in the geriatric trauma centers. Simultaneously, challenges in the area of geriatric syndromes and the recruitment of skilled staff became relevant. DISCUSSION: The results can help to reflect processes in the certified geriatric trauma centers and to treat geriatric syndromes more effectively. In the future, the challenge will be to establish geriatric care under the existing shortage of skilled staff.

The Saccharomyces cerevisiae ubiquitin E3 ligase Asr1p targets calmodulin for ubiquitylation.

Yeast calmodulin known to be ubiquitylated in vivo in a Ca(2+) dependent manner has long remained an orphan substrate. Here we identify Saccharomyces cerevisiae Asr1p as an ubiquitin E3 ligase for yeast calmodulin, a protein involved in calcium signaling. A short region within Asr1p-C harboring two putative calmodulin-binding motifs is sufficient and necessary for interaction with calmodulin. The interaction is direct, occurs in vivo and depends on physiological concentrations of Ca(2+). A minimal set of purified proteins including Asr1p E3 ligase was sufficient for in vitro ubiquitylation of calmodulin, a reaction that required a functional Asr1p Ring domain. We propose a role of the Asr1p E3 ligase activity in coping with stress.

Rtr1 is the Saccharomyces cerevisiae homolog of a novel family of RNA polymerase II-binding proteins.

Cells must rapidly sense and respond to a wide variety of potentially cytotoxic external stressors to survive in a constantly changing environment. In a search for novel genes required for stress tolerance in Saccharomyces cerevisiae, we identified the uncharacterized open reading frame YER139C as a gene required for growth at 37 degrees C in the presence of the heat shock mimetic formamide. YER139C encodes the closest yeast homolog of the human RPAP2 protein, recently identified as a novel RNA polymerase II (RNAPII)-associated factor. Multiple lines of evidence support a role for this gene family in transcription, prompting us to rename YER139C RTR1 (regulator of transcription). The core RNAPII subunits RPB5, RPB7, and RPB9 were isolated as potent high-copy-number suppressors of the rtr1Delta temperature-sensitive growth phenotype, and deletion of the nonessential subunits RPB4 and RPB9 hypersensitized cells to RTR1 overexpression. Disruption of RTR1 resulted in mycophenolic acid sensitivity and synthetic genetic interactions with a number of genes involved in multiple phases of transcription. Consistently, rtr1Delta cells are defective in inducible transcription from the GAL1 promoter. Rtr1 constitutively shuttles between the cytoplasm and nucleus, where it physically associates with an active RNAPII transcriptional complex. Taken together, our data reveal a role for members of the RTR1/RPAP2 family as regulators of core RNAPII function.

A novel conserved nuclear localization signal is recognized by a group of yeast importins.

Nucleo-cytoplasmic transport of proteins is mostly mediated by specific interaction between transport receptors of the importin beta family and signal sequences present in their cargo. While several signal sequences, in particular the classical nuclear localization signal (NLS) recognized by the heterodimeric importin alpha/beta complex are well known, the signals recognized by other importin beta-like transport receptors remain to be characterized in detail. Here we present the systematic analysis of the nuclear import of Saccharomyces cerevisiae Asr1p, a nonessential alcohol-responsive Ring/PHD finger protein that shuttles between nucleus and cytoplasm but accumulates in the nucleus upon alcohol stress. Nuclear import of Asr1p is constitutive and mediated by its C-terminal domain. A short sequence comprising residues 243-280 is sufficient and necessary for active targeting to the nucleus. Moreover, the nuclear import signal is conserved from yeast to mammals. In vitro, the nuclear localization signal of Asr1p directly interacts with the importins Kap114p, Kap95p, Pse1p, Kap123p, or Kap104p, interactions that are sensitive to the presence of RanGTP. In vivo, these importins cooperate in nuclear import. Interestingly, the same importins mediate nuclear transport of histone H2A. Based on mutational analysis and sequence comparison with a region mediating nuclear import of histone H2A, we identified a novel type of NLS with the consensus sequence R/KxxL(x)(n)V/YxxV/IxK/RxxxK/R that is recognized by five yeast importins and connects them into a highly efficient network for nuclear import of proteins.