Phylogenomic analysis of vertebrate thrombospondins reveals fish-specific paralogues, ancestral gene relationships and a tetrapod innovation

BACKGROUND: Thrombospondins (TSPs) are evolutionarily-conserved, extracellular, calcium-binding glycoproteins with important roles in cell-extracellular matrix interactions, angiogenesis, synaptogenesis and connective tissue organisation. Five TSPs, designated TSP-1 through TSP-5, are encoded in the human genome. All but one have known roles in acquired or inherited human diseases. To further understand the roles of TSPs in human physiology and pathology, it would be advantageous to extend the repertoire of relevant vertebrate models. In general the zebrafish is proving an excellent model organism for vertebrate biology, therefore we set out to evaluate the status of TSPs in zebrafish and two species of pufferfish. RESULTS: We identified by bioinformatics that three fish species encode larger numbers of TSPs than vertebrates, yet all these sequences group as homologues of TSP-1 to -4. By phylogenomic analysis of neighboring genes, we uncovered that, in fish, a TSP-4-like sequence is encoded from the gene corresponding to the tetrapod TSP-5 gene. Thus, all TSP genes show conservation of synteny between fish and tetrapods. In the human genome, the TSP-1, TSP-3, TSP-4 and TSP-5 genes lie within paralogous regions that provide insight into the ancestral genomic context of vertebrate TSPs. CONCLUSION: A new model for TSP evolution in vertebrates is presented. The TSP-5 protein sequence has evolved rapidly from a TSP-4-like sequence as an innovation in the tetrapod lineage. TSP biology in fish is complicated by the presence of additional lineage- and species-specific TSP paralogues. These novel results give deeper insight into the evolution of TSPs in vertebrates and open new directions for understanding the physiological and pathological roles of TSP-4 and TSP-5 in humans

A low speed two-dimensional study of flow separation on the GA(W)-1 airfoil with 30-percent chord Fowler flap

Measurements of flow fields with low speed turbulent boundary layers were made for the GA(W)-1 airfoil with a 0.30 c Fowler flap deflected 40 deg at angles of attack of 2.7 deg, 7.7 deg, and 12.8 deg, at a Reynolds number of 2.2 million, and a Mach number of 0.13. Details of velocity and pressure fields associated with the airfoil flap combination are presented for cases of narrow, optimum and wide slot gaps. Extensive flow field turbulence surveys were also conducted employing hot-film anemometry. For the optimum gap setting, the boundaries of the regions of flow reversal within the wake were determined by this technique for two angles of attack. Local skin friction distributions for the basic airfoil and the airfoil with flap (optimum gap) were obtained using the razor blade technique

Development of a Fowler flap system for a high performance general aviation airfoil

A two-dimensional wind-tunnel evaluation of two Fowler flap configurations on the new GA(W)-1 airfoil was conducted. One configuration used a computer-designed 29-percent chord Fowler flap. The second configuration was modified to have increased Fowler action with a 30-percent chord flap. Force, pressure, and flow-visualization data were obtained at Reynolds numbers of 2.2 million to 2.9 million. Optimum slot geometry and performance were found to be close to computer predictions. A C sub L max of 3.8 was achieved. Optimum flap deflection, slot gap, and flap overlap are presented as functions of C sub L. Tests were made with the lower surface cusp filled in to show the performance penalties that result. Some data on the effects of adding vortex generators and hinged-plate spoilers were obtained

Experimental studies of flow separation and stalling on a two-dimensional airfoil at low speeds

Detailed measurements of flow fields associated with low-speed turbulent boundary layers were made for the 17% thick GA(W)-1 airfoil section at nominal angles of attack of 10 deg, 14 deg, and 18 deg, Reynolds number 2.2 x 10, and Mach number 0.13. The data include pressure and velocity surveys of the pre- and post-separated regions on the airfoil and the associated wake. The boundary layer characteristics including regions of separation on the airfoil are also presented

Experimental studies of flow separation of three airfoils at low speeds

Wind tunnel tests were conducted on the NASA LS(1)-0421 Mod, NACA 2412 and NASA GA(W)-2 airfoil sections at a Reynolds number of 2.2 x 10(6) and a Mach number of 0.13. Detailed measurements of flow fields associated with turbulent boundary layers of these airfoils were obtained at pre-stall, near-stall, and post-stall angles of attack. Velocity and pressure survey results over the airfoil and in the associated wake, are presented for fully attached flow conditions through the stalled flow condition. Extensive force, pressure, tuft survey, hot-film survey, local skin friction and boundary layer data are also included

Experimental Studies of Flow Separation of the NACA 2412 Airfoil at Low Speeds

Wind tunnel tests have been conducted on an NACA 2412 airfoil section at Reynolds number of 2.2 x 10(exp 6) and Mach number of 0.13. Detailed measurements of flow fields associated with turbulent boundary layers have been obtained at angles of attack of 12.4 degrees, 14.4 degrees, and 16.4 degrees. Pre- and post-separated velocity and pressure survey results over the airfoil and in the associated wake are presented. Extensive force, pressure, tuft survey, hot-film survey, local skin friction, and boundary layer data are also included. Pressure distributions and separation point locations show good agreement with theory for the two layer angles of attack. Boundary layer displacement thickness, momentum thickness, and shape factor agree well with theory up to the point of separation. There is considerable disparity between extent of flow reversal in the wake as measured by pressure and hot-film probes. The difference is attributed to the intermittent nature of the flow reversal

Climate change impacts and potential benefits of heat-tolerant maize in South Asia

Article Purchased; Published online: 14 September 2016Maize is grown by millions of smallholder farmers in South Asia (SA) under diverse environments. The crop is grown in different seasons in a year with varying exposure to weather extremes, including high temperatures at critical growth stages which are expected to increase with climate change. This study assesses the impact of current and future heat stress on maize and the benefit of heat-tolerant varieties in SA. Annual mean maximum temperatures may increase by 1.4–1.8 °C in 2030 and 2.1–2.6 °C in 2050, with large monthly, seasonal, and spatial variations across SA. The extent of heat stressed areas in SA could increase by up to 12 % in 2030 and 21 % in 2050 relative to the baseline. The impact of heat stress and the benefit from heat-tolerant varieties vary with the level of temperature increase and planting season. At a regional scale, climate change would reduce rainfed maize yield by an average of 3.3–6.4 % in 2030 and 5.2–12.2 % in 2050 and irrigated yield by 3–8 % in 2030 and 5–14 % in 2050 if current varieties were grown under the future climate. Under projected climate, heat-tolerant varieties could minimize yield loss (relative to current maize varieties) by up to 36 and 93 % in 2030 and 33 and 86 % in 2050 under rainfed and irrigated conditions, respectively. Heat-tolerant maize varieties, therefore, have the potential to shield maize farmers from severe yield loss due to heat stress and help them adapt to climate change impacts

Trends in clinical and oncological outcomes of robot-assisted radical prostatectomy before and after the 2012 US Preventive Services Task Force recommendation against PSA screening: a decade of experience

Objective: To assess the influence of the 2012 US Preventive Services Task Force (USPSTF) recommendation against prostate-specific antigen (PSA)-based screening on oncological and functional outcomes following robot-assisted laparoscopic prostatectomy (RALP). Materials and Methods: We retrospectively analysed patients who underwent RALP between 2008 and 2018 with a minimum of 12-month follow-up from a prospectively collected institutional review board-approved database. The impact of the USPSTF recommendation against PSA screening on our surgical outcomes was assessed using a logistic regression model using two groups comprising patients treated before/after the USPSTF statement and indicating time trends for each successive year. Results: The mean preoperative PSA increased from 6.0 to 7.4 ng/mL after the USPSTF recommendation. We detected statistically significant time-trend changes after 2012, including an increase in the positive slope of Gleason ≥3 + 4 or ≥pT3 disease. We detected a fall in bilateral full nerve-sparing and an increase in partial nerve-sparing. The total positive surgical margin (PSM) rate increased after the USPSTF recommendation; however, PSM rates pertinent to each pathological stage did not change significantly after 2012. There was a significant negative trend change in the postoperative 12-month continence and potency rates, indicating a breakpoint in functional outcomes after 2012. We detected a 1.7-fold increase in 12-month biochemical recurrence (BCR) rates. The 12-month BCR, potency and continence rates were maintained in young (<55 years) patients with a Sexual Health Inventory for Men score >22 and low-volume disease. Conclusion: Since the USPSTF’s recommendation in 2012, we have seen a significant increase in the incidence of high-risk disease that has forced us to modify our approach to the procedure and the grade of nerve-sparing used, leading to a wider resection, in order to reduce PSMs. This has led to a decrease in postoperative functional recovery. Patients with favourable characteristics had good outcomes before and after the USPSTF’s recommendation, implying that the quality of surgery did not change over time

(2R*,3R*,4aS*,6aR*,11aS*,11bS*)-Methyl 2-acet­oxy-11b-hydr­oxy-3,7-dimethyl-1,2,3,4,4a,5,6,6a,7,11,11a,11b-dodeca­hydro­phenanthro[3,2-b]furan-3-carboxyl­ate

In the title compound, C22H30O6, the conformation of the mol­ecule is dictated by an intra­molecular C—H⋯O contact. The crystal structure is stabilized via inter­molecular C—H⋯O, O—H⋯O and C—H⋯π contacts

Human iPS cell-derived astrocyte transplants preserve respiratory function after spinal cord injury.

Transplantation-based replacement of lost and/or dysfunctional astrocytes is a promising therapy for spinal cord injury (SCI) that has not been extensively explored, despite the integral roles played by astrocytes in the central nervous system (CNS). Induced pluripotent stem (iPS) cells are a clinically-relevant source of pluripotent cells that both avoid ethical issues of embryonic stem cells and allow for homogeneous derivation of mature cell types in large quantities, potentially in an autologous fashion. Despite their promise, the iPS cell field is in its infancy with respect to evaluating in vivo graft integration and therapeutic efficacy in SCI models. Astrocytes express the major glutamate transporter, GLT1, which is responsible for the vast majority of glutamate uptake in spinal cord. Following SCI, compromised GLT1 expression/function can increase susceptibility to excitotoxicity. We therefore evaluated intraspinal transplantation of human iPS cell-derived astrocytes (hIPSAs) following cervical contusion SCI as a novel strategy for reconstituting GLT1 expression and for protecting diaphragmatic respiratory neural circuitry. Transplant-derived cells showed robust long-term survival post-injection and efficiently differentiated into astrocytes in injured spinal cord of both immunesuppressed mice and rats. However, the majority of transplant-derived astrocytes did not express high levels of GLT1, particularly at early times post-injection. To enhance their ability to modulate extracellular glutamate levels, we engineered hIPSAs with lentivirus to constitutively express GLT1. Overexpression significantly increased GLT1 protein and functional GLT1-mediated glutamate uptake levels in hIPSAs both in vitro and in vivo post-transplantation. Compared to human fibroblast control and unmodified hIPSA transplantation, GLT1-overexpressing hIPSAs reduced (1) lesion size within the injured cervical spinal cord, (2) morphological denervation by respiratory phrenic motor neurons at the diaphragm neuromuscular junction, and (3) functional diaphragm denervation as measured by recording of spontaneous EMGs and evoked compound muscle action potentials. Our findings demonstrate that hiPSA transplantation is a therapeutically-powerful approach for SCI