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Efficient repair of DNA double-strand breaks (DSBs) requires a coordinated DNA Damage Response (DDR), which includes phosphorylation of histone H2Ax, forming γH2Ax. This histone modification spreads beyond the DSB into neighboring chromatin, generating a DDR platform that protects against end disassociation and degradation, minimizing chromosomal rearrangements. However, mechanisms that determine the breadth and intensity of γH2Ax domains remain unclear. Here, we show that chromosomal contacts of a DSB site are the primary determinants for γH2Ax landscapes. DSBs that disrupt a topological border permit extension of γH2Ax domains into both adjacent compartments. In contrast, DSBs near a border produce highly asymmetric DDR platforms, with γH2Ax nearly absent from one broken end. Collectively, our findings lend insights into a basic DNA repair mechanism and how the precise location of a DSB may influence genome integrity., Formation of γH2Ax serves as a checkpoint for double-strand break (DSB) repair pathways. Here the authors reveal via integrated chromatin analysis that γH2Ax domains are established by chromosomal contacts with the DSB site.

This essay will consider new copyright models in libraries, and how libraries can and should modify their own systems to promote and provide access to open content. It focuses on the reasoning behind supporting new models and methods of distribution, especially with regards to open licenses like Creative Commons, and the resources and systems libraries have developed to provide access to open licensed work. The paper examines the current roles libraries take in promoting Creative Commons and Open Access, and possible future roles, as well as how libraries organize and share open access works and develop relationships with others producing or developing content.

Summary Natural killer (NK) cells develop from common progenitors but diverge into distinct subsets, which differ in cytokine production, cytotoxicity, homing, and memory traits. Given their promise in adoptive cell therapies for cancer, a deeper understanding of regulatory modules controlling clinically beneficial NK phenotypes is of high priority. We report integrated "-omics" analysis of human NK subsets, which revealed super-enhancers associated with gene cohorts that may coordinate NK functions and localization. A transcription factor-based regulatory scheme also emerged, which is evolutionarily conserved and shared by innate and adaptive lymphocytes. For both NK and T lineages, a TCF1-LEF1-MYC axis dominated the regulatory landscape of long-lived, proliferative subsets that traffic to lymph nodes. In contrast, effector populations circulating between blood and peripheral tissues shared a PRDM1-dominant landscape. This resource defines transcriptional modules, regulated by feedback loops, which may be leveraged to enhance phenotypes for NK cell-based therapies.

Rationale, aims, and objectives: All patients scheduled for elective orthopaedic surgery are seen by an anaesthesiologist routinely in the pre-anesthesia clinic as part of their standard pre-operative evaluation. This study aimed to assess the potential to reduce the number of elective orthopaedic surgery patients seen in the pre-anesthesia clinic, using a registered nurse (RN)-led pre-operative process to identify low-risk patients as part of a sensitive, individualized and caring approach.Method: This quality improvement study was performed across the orthopaedic services outpatient population, in a tertiary healthcare centre in Saudi Arabia. A simple ‘yes/no’ questionnaire was developed and utilized over a 3-month period to identify the low-risk adult patient population and determine if a pre-anesthesia clinic visit was necessary.Results: Among a sample of 193 patients, 36 (18.7%) were assessed as healthy and did not require an anaesthesiologist evaluation in the pre-anesthesia clinic.Conclusions: All elective orthopaedic surgery patients do not require a routine pre-anesthesia visit prior to their surgery. Pre-operative care should be tailored to the needs of each individual patient. This study demonstrates how an RN can improve the utilization of the pre-anesthesia clinic by using a validated screening tool and reduce the number of pre-anesthesia visits in the interests of individual patients and health services efficiency.

Research Note, VITIS - Journal of Grapevine Research, Vol. 44 No. 3 (2005): Vitis

Detached Vitis vinifera 'Cabernet Sauvignon' berries (12.5° Bé) were inoculated either singularly or in combination with spore suspensions of Botrytis cinerea, Colletotrichum acutatum and Greeneria uvicola and the degree of disease expression examined at either 20 or 27 °C. Berries were more susceptible to B. cinerea at 20 °C and to G. uvicola at 27 °C but were highly susceptible to C. acutatum at either temperature. In experiments involving inoculation of berries with mixtures of fungal organisms, B. cinerea infection was diminished at 27 °C by either C. acutatum or G. uvicola but only by C. acutatum at 20 °C. G. uvicola infection was diminished by C. acutatum at both temperatures investigated. B. cinerea reduced the level of infection of both C. acutatum and G. uvicola at 20 °C. The findings have implications for seasonal bunch rot management of grapes in relation to predicted changes in global temperature., VITIS - Journal of Grapevine Research, Vol. 50 No. 2 (2011): Vitis

Purpose: To study the histopathology of a stage III macular hole that had been treated by vitrectomy with cortical vitreous and epicortical vitreous membrane peeling and gas tamponade. Methods: The light and electron microscopic features of a treated macular hole were studied. Results: A 16-μm-wide break was present in the external limiting membrane. This was sealed by Muller cell processes. Photoreceptors adjacent to the healed defect appeared normal. No cystoid macular edema was present. Conclusion: Cortical vitreous peeling and gas tamponade can allow the macular hole to settle and the edges to re-approximate. The residual defect can be sealed by Muller cells.

Past research has left unanswered the question of how to reduce the negative effects of relationship conflict in work groups. This study investigates whether relational closeness in work groups buffers the negative association between relationship conflict and two important group behaviors that are often overlooked in conflict research: group-level helping behavior and counterproductive work behavior. The results of this field study show that the degree of relational closeness in work groups indeed buffers the negative affiliation between relationship conflict and group-level helping behavior and the positive association between relationship conflict and group-level counterproductive work behavior. Specifically, the results suggest that relationship conflicts are only harmful in relationally distant work groups in which members do not know each other well personally and do not feel close to each other. Theoretical implications and suggestions for organizational practice are discussed.

Editor,—Sarcoidosis, a multisystem granulomatous disease, involves the eye in approximately 25% to 50% of patients1 2 and produces numerous ocular findings.3 Definitive diagnosis requires a non-caseating granuloma in the absence of mycobacterial infection on biopsy. Although most patients have abnormal chest x rays, ocular sarcoidosis can precede pulmonary involvement, making diagnosis difficult. The following patient with ocular sarcoidosis—unresponsive to corticosteroids and cyclosporine—was diagnosed only after chorioretinal biopsy; she responded to azathioprine therapy. ### CASE REPORT A 32 year old white woman had a 12 year history of granulomatous uveitis in both eyes, resistant to treatment with topical, periocular, and systemic corticosteroids, as well as systemic cyclosporine. The patient presented …