1,613 research outputs found

    In Vivo Targeting of Organic Calcium Sensors via Genetically Selected Peptides

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    AbstractA library of constrained peptides that form stable folded structures was screened for aptamers that bind with high affinity to the fluorescent dye Texas red. Two selected clones had binding constants to Texas red of 25 and 80 pM as phage and binding had minimal effects on the fluorescence of Texas red. The peptides interact with distinct but overlapping regions of Texas red. One peptide bound to X-rhod calcium sensors, which share the same core fluorophore as Texas red. These dyes retained calcium sensitivity when bound to the peptide. This peptide was used to label a fusion protein with X-rhod-5F in vivo, and X-rhod sensed changes in calcium locally. Thus, minimal, constrained peptides can functionally bind to environmentally sensitive dyes or other organic agents in biological contexts, suggesting tools for in vivo imaging and analysis

    COP9 signalosome component JAB1/CSN5 is necessary for T cell signaling through LFA-1 and HIV-1 replication.

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    To determine critical host factors involved in HIV-1 replication, a dominant effector genetics approach was developed to reveal signaling pathways on which HIV-1 depends for replication. A large library of short peptide aptamers was expressed via retroviral delivery in T cells. Peptides that interfered with T cell activation-dependent processes that might support HIV-1 replication were identified. One of the selected peptides altered signaling, lead to a difference in T cell activation status, and inhibited HIV-1 replication. The target of the peptide was JAB1/CSN5, a component of the signalosome complex. JAB1 expression overcame the inhibition of HIV-1 replication in the presence of peptide and also promoted HIV-1 replication in activated primary CD4(+) T cells. This peptide blocked physiological release of JAB1 from the accessory T cell surface protein LFA-1, downstream AP-1 dependent events, NFAT activation, and HIV-1 replication. Thus, genetic selection for intracellular aptamer inhibitors of host cell processes proximal to signals at the immunological synapse of T cells can define unique mechanisms important to HIV-1 replication

    Does regular exercise reduce the pain and stiffness of osteoarthritis?

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    Exercise helps reduce the pain, but it's unclear whether it helps with stiffness. Exercise moderately reduces pain in elderly patients with osteoarthritis (strength of recommendation [SOR]: A, 3 systematic reviews, including high-quality studies) and has a small effect on reducing self-reported disability (SOR: B, 2 systematic reviews, including reviews of smaller studies). No studies have evaluated the effect of exercise on stiffness

    Next generation bone tissue engineering: non-viral miR-133a inhibition using collagen-nanohydroxyapatite scaffolds rapidly enhances osteogenesis.

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    Bone grafts are the second most transplanted materials worldwide at a global cost to healthcare systems valued over $30 billion every year. The influence of microRNAs in the regenerative capacity of stem cells offers vast therapeutic potential towards bone grafting; however their efficient delivery to the target site remains a major challenge. This study describes how the functionalisation of porous collagen-nanohydroxyapatite (nHA) scaffolds with miR-133a inhibiting complexes, delivered using non-viral nHA particles, enhanced human mesenchymal stem cell-mediated osteogenesis through the novel focus on a key activator of osteogenesis, Runx2. This study showed enhanced Runx2 and osteocalcin expression, as well as increased alkaline phosphatase activity and calcium deposition, thus demonstrating a further enhanced therapeutic potential of a biomaterial previously optimised for bone repair applications. The promising features of this platform offer potential for a myriad of applications beyond bone repair and tissue engineering, thus presenting a new paradigm for microRNA-based therapeutics

    On the aerodynamics of an enclosed-wheel racing car: an assessment and proposal of add-on devices for a fourth, high-performance configuration of the DrivAer model

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    A modern benchmark for passenger cars – DrivAer model – has provided significant contributions to aerodynamics-related topics in automotive engineering, where three categories of passenger cars have been successfully represented. However, a reference model for highperformance car configurations has not been considered appropriately yet. Technical knowledge in motorsport is also restricted due to competitiveness in performance, reputation and commercial gains. The consequence is a shortage of open-access material to be used as technical references for either motorsport community or academic research purposes. In this paper, a parametric assessment of race car aerodynamic devices are presented into four groups of studies. These are: (i) forebody strakes (dive planes), (ii) front bumper splitter, (iii) rear-end spoiler, and (iv) underbody diffuser. The simplified design of these add-ons focuses on the main parameters (such as length, position, or incidence), leading to easier manufacturing for experiments and implementation in computational studies. Consequently, a proposed model aims to address enclosed-wheel racing car categories, adapting a simplified, 35% scaled-model DrivAer Fastback shape (i.e. smooth underbody, no wheels, and with side mirrors). Experimental data were obtained at the 8ft x 6ft Cranfield Wind Tunnel using an internal balance for force and moment measurements. The aerodynamic performance of each group of add-on was assessed individually in a range of ride heights over a moving belt. All cases represent the vehicle at a zero-yaw condition, Reynolds number (car length-based) of 4.2 × 106 and Mach number equal to 0.12. The proposed high-performance configuration (DrivAer hp-F) was tested and a respective Reynolds number dependency study is also provided. In line with the open-access concept of the DrivAer model, the CAD geometry and experimental data will be made available online to the international community to support independent studies

    Seasonal variability of the warm Atlantic Water layer in the vicinity of the Greenland shelf break

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    The warmest water reaching the east and west coast of Greenland is found between 200?m and 600?m. Whilst important for melting Greenland's outlet glaciers, limited winter observations of this layer prohibit determination of its seasonality. To address this, temperature data from Argo profiling floats, a range of sources within the World Ocean Database and unprecedented coverage from marine-mammal borne sensors have been analysed for the period 2002-2011. A significant seasonal range in temperature (~1-2?°C) is found in the warm layer, in contrast to most of the surrounding ocean. The phase of the seasonal cycle exhibits considerable spatial variability, with the warmest water found near the eastern and southwestern shelf-break towards the end of the calendar year. High-resolution ocean model trajectory analysis suggest the timing of the arrival of the year's warmest water is a function of advection time from the subduction site in the Irminger Basin

    Finite temperature bosonization

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    Finite temperature properties of a non-Fermi liquid system is one of the most challenging probelms in current understanding of strongly correlated electron systems. The paradigmatic arena for studying non-Fermi liquids is in one dimension, where the concept of a Luttinger liquid has arisen. The existence of a critical point at zero temperature in one dimensional systems, and the fact that experiments are all undertaken at finite temperature, implies a need for these one dimensional systems to be examined at finite temperature. Accordingly, we extended the well-known bosonization method of one dimensional electron systems to finite temperatures. We have used this new bosonization method to calculate finite temperature asymptotic correlation functions for linear fermions, the Tomonaga-Luttinger model, and the Hubbard model.Comment: REVTex, 48 page

    Twenty-first century laparoscopic hysterectomy: should we not leave the vaginal step out?

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    The objective of this study was to compare surgical outcomes for laparoscopically assisted vaginal hysterectomy (LAVH) with total laparoscopic hysterectomy (TLH) in three teaching hospitals in the Netherlands. This study is a multicenter cohort retrospective analysis of consecutive cases (Canadian Task Force classification II-2). One hundred and four women underwent a laparoscopic hysterectomy between March 1995 and March 2005 at one of three teaching hospitals. This included 37 women who underwent LAVH and 67 who underwent TLH. Blood loss, operating time, and intraoperative complications such as bladder or ureteric injury as well as conversion to an open procedure were recorded. In the TLH group, average age was statistically significant lower, as well as the mean parity, whereas estimated uterus size was statistically significant larger, compared to the LAVH group. Main indication in both groups was dysfunctional uterine bleeding. In the TLH group, mean blood loss (173 mL) was significant lower compared to the LAVH group (457 mL), whereas length of surgery, uterus weight, and complication rates were comparable between the two groups. The method of choice at the start of the study period was LAVH, and by the end of the study period, it had been superceded by TLH. LAVH should not be regarded as the novice’s laparoscopic hysterectomy. Moreover, with regard blood loss, TLH shows advantages above LAVH. This might be due to the influence of the altered anatomy in the vaginal stage of the LAVH procedure. Therefore, when a vaginal hysterectomy is contraindicated, TLH is the procedure of choice. LAVH remains indicated in case of vaginal hysterectomy with accompanying adnexal surgery
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