Evidence for a Transport-Trap Mode of Drosophila melanogaster gurken mRNA Localization

The Drosophila melanogaster gurken gene encodes a TGF alpha-like signaling molecule that is secreted from the oocyte during two distinct stages of oogenesis to define the coordinate axes of the follicle cell epithelium that surrounds the oocyte and its 15 anterior nurse cells. Because the gurken receptor is expressed throughout the epithelium, axial patterning requires region-specific secretion of Gurken protein, which in turn requires subcellular localization of gurken transcripts. The first stage of Gurken signaling induces anteroposterior pattern in the epithelium and requires the transport of gurken transcripts from nurse cells into the oocyte. The second stage of Gurken signaling induces dorsovental polarity in the epithelium and requires localization of gurken transcripts to the oocyte's anterodorsal corner. Previous studies, relying predominantly on real-time imaging of injected transcripts, indicated that anterodorsal localization involves transport of gurken transcripts to the oocyte's anterior cortex followed by transport to the anterodorsal corner, and anchoring. Such studies further indicated that a single RNA sequence element, the GLS, mediates both transport steps by facilitating association of gurken transcripts with a cytoplasmic dynein motor complex. Finally, it was proposed that the GLS somehow steers the motor complex toward that subset of microtubules that are nucleated around the oocyte nucleus, permitting directed transport to the anterodorsal corner. Here, we re-investigate the role of the GLS using a transgenic fly assay system that includes use of the endogenous gurken promoter and biological rescue as well as RNA localization assays. In contrast to previous reports, our studies indicate that the GLS is sufficient for anterior localization only. Our data support a model in which anterodorsal localization is brought about by repeated rounds of anterior transport, accompanied by specific trapping at the anterodorsal cortex. Our data further indicate that trapping at the anterodorsal corner requires at least one as-yet-unidentified gurken RLE

Secondary Endoleak Management Following TEVAR and EVAR.

Endovascular abdominal and thoracic aortic aneurysm repair and are widely used to treat increasingly complex aneurysms. Secondary endoleaks, defined as those detected more than 30 days after the procedure and after previous negative imaging, remain a challenge for aortic specialists, conferring a need for long-term surveillance and reintervention. Endoleaks are classified on the basis of their anatomic site and aetiology. Type 1 and type 2 endoleaks (EL1 and EL2) are the most common endoleaks necessitating intervention. The management of these requires an understanding of their mechanics, and the risk of sac enlargement and rupture due to increased sac pressure. Endovascular techniques are the main treatment approach to manage secondary endoleaks. However, surgery should be considered where endovascular treatments fail to arrest aneurysm growth. This chapter reviews the aetiology, significance, management strategy and techniques for different endoleak types

Transcriptional Profiling in Pathogenic and Non-Pathogenic SIV Infections Reveals Significant Distinctions in Kinetics and Tissue Compartmentalization

Simian immunodeficiency virus (SIV) infection leads to AIDS in experimentally infected macaques, whereas natural reservoir hosts exhibit limited disease and pathology. It is, however, unclear how natural hosts can sustain high viral loads, comparable to those observed in the pathogenic model, without developing severe disease. We performed transcriptional profiling on lymph node, blood, and colon samples from African green monkeys (natural host model) and Asian pigtailed macaques (pathogenic model) to directly compare gene expression patterns during acute pathogenic versus non-pathogenic SIV infection. The majority of gene expression changes that were unique to either model were detected in the lymph nodes at the time of peak viral load. Results suggest a shift toward cellular stress pathways and Th1 profiles during pathogenic infection, with strong and sustained type I and II interferon responses. In contrast, a strong type I interferon response was initially induced during non-pathogenic infection but resolved after peak viral load. The natural host also exhibited controlled Th1 profiles and better preservation of overall cell homeostasis. This study identified gene expression patterns that are specific to disease susceptibility, tissue compartmentalization, and infection duration. These patterns provide a unique view of how host responses differ depending upon lentiviral infection outcome

Another View on U.S. Treasury Term Premiums

The consensus suggests that subdued nominal U.S. Treasury yields on balance since the onset of the global financial crisis primarily reflect exceptionally low, if not occasionally negative, term premiums as opposed to low anticipated short rates. Depressed term premiums plausibly owe to unconventional Federal Reserve policy as well as to net flight-to-quality flows after 2007. However, two strands of evidence raise questions about this story. First, a purely survey-based expected forward term premium measure, as opposed to an approximate spot estimate, has increased rather than decreased in recent years. Second, with respect to the time-series dynamics of factors underlying affine term structure models, simple econometrics of recent data produce not only a more persistent level of the term structure but also a depressed long-run mean, which in turn implies an implausibly low expected short rate path. Strong caveats aside, an implication for central bankers is that unconventional monetary policy measures may have worked in more conventional ways, and an inference for investors is that longer-dated yields embed meaningful compensation for bearing duration risk

Technical and Early Outcomes Using Ultrasound-Guided Reentry for Chronic Total Occlusions

BackgroundSubintimal angioplasty is a common treatment for chronic total occlusions (CTOs) in the iliac and infrainguinal arteries. Although technical success has been described using intravascular ultrasound-guided reentry devices (IVUS-RED), outcomes are still not well defined. This report describes the technical aspects and longitudinal follow-up after intravascular ultrasound-guided reentry of iliac and infrainguinal CTOs.MethodsA retrospective review was performed of 20 patients with lower extremity CTO treated with IVUS-RED from 2011 to 2013. A matched cohort of patients who underwent lower extremity interventions without the use of IVUS-RED was also identified. Procedural success, patency estimates, ankle-brachial indices (ABIs), complications, and limb salvage were analyzed.ResultsTwenty patients (mean age, 69 ± 13 years), including 11 men and 9 women, underwent attempted IVUS-RED-guided recanalization. Median follow-up was 4.3 months (range, 0.4-24). Eleven patients presented with critical limb ischemia (CLI), and 9 presented with claudication. Technical success was achieved in 18 (90%) patients. Ten common iliac arteries, 3 external iliac arteries, and 5 superficial femoral arteries (SFA) were treated. No intraoperative complications resulted from device use. After procedure, ABIs significantly increased (0.5-0.9; P < 0.01) in the 13 patients with follow-up. Primary patency for the entire cohort was 62% at 12 months. No patient treated for claudication required reintervention, whereas 3 (27%) of those treated for CLI required repeat interventions. During follow-up, 2 patients died unrelated to the procedure, 1 patient required an amputation, and 1 patient eventually required open revascularization. When the IVUS-RED group was compared with a cohort matched on Trans-Atlantic Inter-Society Consensus and age, no difference was found in runoff scores and patency between the 2 groups during follow-up (P > 0.05).ConclusionsRecanalization of CTO using IVUS-RED is safe and effective. Use of IVUS-RED does not adversely impact outcomes in conjunction with other endovascular techniques. Early follow-up demonstrates acceptable patency, especially in patients with claudication, and freedom from reintervention