Lateral Gene Expression in Drosophila Early Embryos Is Supported by Grainyhead-Mediated Activation and Tiers of Dorsally-Localized Repression

The general consensus in the field is that limiting amounts of the transcription factor Dorsal establish dorsal boundaries of genes expressed along the dorsal-ventral (DV) axis of early Drosophila embryos, while repressors establish ventral boundaries. Yet recent studies have provided evidence that repressors act to specify the dorsal boundary of intermediate neuroblasts defective (ind), a gene expressed in a stripe along the DV axis in lateral regions of the embryo. Here we show that a short 12 base pair sequence (“the A-box”) present twice within the ind CRM is both necessary and sufficient to support transcriptional repression in dorsal regions of embryos. To identify binding factors, we conducted affinity chromatography using the A-box element and found a number of DNA-binding proteins and chromatin-associated factors using mass spectroscopy. Only Grainyhead (Grh), a CP2 transcription factor with a unique DNA-binding domain, was found to bind the A-box sequence. Our results suggest that Grh acts as an activator to support expression of ind, which was surprising as we identified this factor using an element that mediates dorsally-localized repression. Grh and Dorsal both contribute to ind transcriptional activation. However, another recent study found that the repressor Capicua (Cic) also binds to the A-box sequence. While Cic was not identified through our A-box affinity chromatography, utilization of the same site, the A-box, by both factors Grh (activator) and Cic (repressor) may also support a “switch-like” response that helps to sharpen the ind dorsal boundary. Furthermore, our results also demonstrate that TGF-β signaling acts to refine ind CRM expression in an A-box independent manner in dorsal-most regions, suggesting that tiers of repression act in dorsal regions of the embryo

Submicron Structures Technology and Research

Contains reports on fifteen research projects.Joint Services Electronics Program (Contract DAALO3-86-K-0002)National Science Foundation (Grant ECS 87-09806)Semiconductor Research Corporation (Contract 87-SP-080)National Science Foundation (Grant ECS 85-03443)U.S. Air Force - Office of Scientific Research (Grant AFOSR 85-0376)National Science Foundation (Grant ECS 85-06565)U.S. Air Force - Office of Scientific Research (Grant AFOSR 85-0154)Lawrence Livermore National Laboratory (Subcontract 2069209)National Aeronautics and Space Adminstration (Grant NGL22-009-683)Collaboration with KMS Fusion, Inc

Submicron Structures Technology and Research

Contains table of contents for Part I, table of contents for Section 1 and reports on fourteen research projects.Joint Services Electronics Program (Contract DAAL03-86-K-0002)Joint Services Electronics Program (Contract DAAL03-89-C-0001)National Science Foundation (Grant ECS-87-09806)Semiconductor Research Corporation (Contract 87-SP-080)Hampshire Instruments CorporationNational Science Foundation (Grant ECS-85-03443)U.S. Air Force - Office of Scientific Research (Grant AFOSR-88-0304)National Science Foundation (Grant ECS-85-06565)X-Opt., IncorporatedU.S. Air Force - Office of Scientific Research (Grant AFOSR-85-0154)National Aeronautics and Space Administration (Grant NGL22-009-683)KMS Fusion, Incorporate

Postoperative Complications in the Ahmed Baerveldt Comparison Study During Five Years of Follow-up

To compare the late complications in the Ahmed Baerveldt Comparison Study during 5 years of follow-up

Double Immune Checkpoint Blockade in Renal Cell Carcinoma

 Long considered an immunogenic tumour, immunotherapy has been the cornerstone of systemic treatment in renal cell carcinoma (RCC) for decades, since the introduction of interleukin 2 and interferon-alfa in the 1980s to the more recently approved immune checkpoint inhibitors. Moreover, on the basis that anti-CTLA-4 and anti-PD-1/PD-L1 intrinsic mechanisms are different, double checkpoint inhibition was proposed to further improve anti-tumor immune response. The first trial to assess double checkpoint inhibition was Checkmate 016 (nivolumab and ipilimumab). It showed acceptable safety and promising antitumor activity that led to the first phase III trial with combination immunotherapy in RCC, Checkmate 214. This trial showed superior overall survival and response rate of the combination immunotherapy (nivolumab and ipilimumab) versus sunitinib in intermediate- and poor-risk advanced RCC, leading to its approval in this setting. Despite these advances, there is still room for improvement. In this context, cytokines and T-cell costimulatory molecules are currently under investigation. This review summarizes the principles of immunotherapy and its role in RCC, provides an update on double checkpoint blockade and discusses the major challenges with double checkpoint blockade.</jats:p

Is It Safe to Have an Ophthalmic Emergency in July?

To deter-mine whether house staff experience affects the quality of acute ophthalmic care delivered in an emergency room at one teaching hospital. The medical records of 360 patients who were seen by first-year ophthalmology residents in the Bascom Palmer Eye Institute emergency department were retrospectively reviewed. Records reviewed included 180 patients seen between July 15, 2002, and August 14, 2002 (the beginning of the training year), and 180 patients seen between June 1, 2003, and June 30, 2003 (the end of the training year). The rate of unscheduled return visits to the emergency department at the beginning and end of the training year was 6.1% (11 of 180) and 5.0% (9 of 180), respectively (P = .82). Agreement between initial and final diagnoses occurred in 96% of patients (108 of 113) at the beginning of the training year and 98% of patients (84 of 86) at the end of the training year (P = .70). There was no difference in the quality of medical care delivered by first-year ophthalmology residents at the beginning and end of the training year