To tilt or not to tilt; the decision-making process.

PURPOSE: This study's aim was to explore the complexities of how power tilt use is integrated within the context of daily life. Other studies have used mobility-type metrics of frequency, duration, and amplitude as measures of power tilt use in the context of daily life but results lack depth in explaining the complex interplay of participating in daily activities and power tilt use. METHODS: This grounded theory study explored how power tilt was used in daily life from the perspectives of people experienced with using power tilt and therapists experienced with prescribing power tilt. Data collected from 22 in-depth interviews and five 3-day journals were analysed using a constant comparative approach. RESULTS: The resultant substantive theory offers an avenue for examining the complex, iterative relationships of person, environment, technology and occupation that comprise daily life, influencing how power tilt is used at any point during the course of the day. CONCLUSIONS: The knowledge generated from this research contributes to the advancement of understanding of how the decision to use tilt is integrated in daily life occupations. The theory can inform clinical practice related to individualizing power tilt use within the context of the person's own reality of daily life. IMPLICATIONS FOR REHABILITATION The decision to use tilt or not use tilt at any point during the day, is made contingent on the iterative transaction between environmental, functional and personal contexts at that point in time. Feedback from each experience where power tilt was used generates learning and knowledge about the context of power tilt use, informing subsequent occurrences where tilt use may be an option. The substantive theory generated in this study can provide an avenue to explore how and why context influences the decision-making process to foster an in-depth understanding of why tilt is chosen or not chosen to affect problems/issues/situations occurring in day-to-day life.

Reasons for using power tilt: perspectives from clients and therapists.

PURPOSE: A power tilt wheelchair allows independence in changing body position to address a variety of needs throughout the day; however, literature and clinical practice suggest that actual use varies greatly. This grounded theory study examined how power tilt was used in daily life from the perspectives of adults who used power tilt and therapists who prescribed this technology. METHODS: A constant comparative approach was used to collect and analyze interview data from five people who use power tilt and six therapists who prescribe this technology. RESULTS: This paper presents the findings specific to understanding the reasons why power tilt was used, focusing on the relationships between tilt use and (1) the reasons for use, (2) the reasons for prescribing power tilt and (3) the associated amplitudes of tilt. CONCLUSIONS: This study advances knowledge related to how power tilt is used in daily life by elucidating that how the reasons for use are conceptualized is complex. The three relationships related to the reason for power tilt use identified in this paper have the potential to influence the quality of communication about power tilt use in clinical practice between therapist and client and in research between researcher and participant. Implications for Rehabilitation: Understanding the inconsistencies and variations in how power tilt is used in daily life is dependent on exploring the reasons beyond the words or terms expressed to describe use. Reasons for tilt use are context dependent, particularly the activity occurring at the time of tilt use, the associated amplitude of tilt and the influence of other reasons occurring at the same time.

Nuclear positioning, higher-order folding, and gene expression of Mmu15 sequences are refractory to chromosomal translocation.

Nuclear localization influences the expression of certain genes. Chromosomal rearrangements can reposition genes in the nucleus and thus could impact the expression of genes far from chromosomal breakpoints. However, the extent to which chromosomal rearrangements influence nuclear organization and gene expression is poorly understood. We examined mouse progenitor B cell lymphomas with a common translocation, der(12)t(12;15), which fuses a gene-rich region of mouse chromosome 12 (Mmu 12) with a gene-poor region of mouse chromosome 15 (Mmu 15). We found that sequences 2.3 Mb proximal and 2.7 Mb distal to the der(12)t(12;15) breakpoint had different nuclear positions measured relative to the nuclear radius. However, their positions were similar on unrearranged chromosomes in the same tumor cells and normal progenitor B cells. In addition, higher-order chromatin folding marked by three-dimensional gene clustering was not significantly altered for the 7 Mb of Mmu 15 sequence distal to this translocation breakpoint. Translocation also did not correspond to significant changes in gene expression in this region. Thus, any changes to Mmu 15 structure and function imposed by the der(12)t(12;15) translocation are constrained to sequences near (<2.5 Mb) the translocation junction. These data contrast with those of certain other chromosomal rearrangements and suggest that significant changes to Mmu 15 sequence are structurally and functionally tolerated in the tumor cells examined.

Members of the RSC chromatin-remodeling complex are required for maintaining proper nuclear envelope structure and pore complex localization.

The assembly, distribution, and functional integrity of nuclear pore complexes (NPCs) in the nuclear envelope (NE) are key determinants in the nuclear periphery architecture. However, the mechanisms controlling proper NPC and NE structure are not fully defined. We used two different genetic screening approaches to identify Saccharomyces cerevisiae mutants with defects in NPC localization. The first approach examined green fluorescent protein (GFP)-Nic96 in 531 strains from the yeast Tet-promoters Hughes Collection with individual essential genes expressed from a doxycycline-regulated promoter (TetO(7)-orf). Under repressive conditions, depletion of the protein encoded by 44 TetO(7)-orf strains resulted in mislocalized GFP-Nic96. These included STH1, RSC4, RSC8, RSC9, RSC58, ARP7, and ARP9, each encoding components of the RSC chromatin remodeling complex. Second, a temperature-sensitive sth1-F793S (npa18-1) mutant was identified in an independent genetic screen for NPC assembly (npa) mutants. NPC mislocalization in the RSC mutants required new protein synthesis and ongoing transcription, confirming that lack of global transcription did not underlie the phenotypes. Electron microscopy studies showed significantly altered NEs and nuclear morphology, with coincident cytoplasmic membrane sheet accumulation. Strikingly, increasing membrane fluidity with benzyl alcohol treatment prevented the sth1-F793S NE structural defects and NPC mislocalization. We speculate that NE structure is functionally linked to proper chromatin architecture.

Functional genomic screens identify CINP as a genome maintenance protein.

The DNA damage response (DDR) has a critical role in maintaining genome integrity and serves as a barrier to tumorigenesis by promoting cell-cycle arrest, DNA repair, and apoptosis. The DDR is activated not only by genotoxic agents that induce DNA damage, but also during aberrant cell-division cycles caused by activated oncogenes and inactivated tumor suppressors. Here we use RNAi and cDNA overexpression screens in human cells to identify genes that, when deregulated, lead to activation of the DDR. The RNAi screen identified 73 genes that, when silenced in at least two cell types, cause DDR activation. Silencing several of these genes also caused an increased frequency of micronuclei, a marker of genetically unstable cells. The cDNA screen identified 97 genes that when overexpressed induce DDR activation in the absence of any exogenous genotoxic agent, with an overrepresentation of genes linked to cancer. Secondary RNAi screens identified CDK2-interacting protein (CINP) as a cell-cycle checkpoint protein. CINP interacts with ATR-interacting protein and regulates ATR-dependent signaling, resistance to replication stress, and G2 checkpoint integrity.