Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural killer T cells: lessons from obesity, diabetes and psoriasis

Aims/hypothesis The innate immune cells, invariant natural killer T cells (iNKT cells), are implicated in the pathogenesis of psoriasis, an inflammatory condition associated with obesity and other metabolic diseases, such as diabetes and dyslipidaemia. We observed an improvement in psoriasis severity in a patient within days of starting treatment with an incretin-mimetic, glucagon-like peptide-1 (GLP-1) receptor agonist. This was independent of change in glycaemic control. We proposed that this unexpected clinical outcome resulted from a direct effect of GLP-1 on iNKTcells. Methods We measured circulating and psoriatic plaque iNKT cell numbers in two patients with type 2 diabetes and psoriasis before and after commencing GLP-1 analogue therapy. In addition, we investigated the in vitro effects of GLP-1 on iNKT cells and looked for a functional GLP-1 receptor on these cells. Results The Psoriasis Area and Severity Index improved in both patients following 6 weeks of GLP-1 analogue therapy. This was associated with an alteration in iNKT cell number, with an increased number in the circulation and a decreased number in psoriatic plaques. The GLP-1 receptor was expressed on iNKT cells, and GLP-1 induced a dose-dependent inhibition of iNKT cell cytokine secretion, but not cytolytic degranulation in vitro. Conclusions/interpretation The clinical effect observed and the direct interaction between GLP-1 and the immune system raise the possibility of therapeutic applications for GLP-1 in inflammatory conditions such as psoriasis

Detection and impacts of leakage from sub-seafloor deep geological carbon dioxide storage

Fossil fuel power generation and other industrial emissions of carbon dioxide are a threat to global climate1, yet many economies will remain reliant on these technologies for several decades2. Carbon dioxide capture and storage (CCS) in deep geological formations provides an effective option to remove these emissions from the climate system3. In many regions storage reservoirs are located offshore4, 5, over a kilometre or more below societally important shelf seas6. Therefore, concerns about the possibility of leakage7, 8 and potential environmental impacts, along with economics, have contributed to delaying development of operational CCS. Here we investigate the detectability and environmental impact of leakage from a controlled sub-seabed release of CO2. We show that the biological impact and footprint of this small leak analogue (<1 tonne CO2 d?1) is confined to a few tens of metres. Migration of CO2 through the shallow seabed is influenced by near-surface sediment structure, and by dissolution and re-precipitation of calcium carbonate naturally present in sediments. Results reported here advance the understanding of environmental sensitivity to leakage and identify appropriate monitoring strategies for full-scale carbon storage operations

ESolvent-free, enzyme-catalyzed biodiesel production from mango, neem, and shea oils via response surface methodology

Mango, neem and shea kernels produce non-conventional oils whose potentials are not fully exploited. To give an added value to these oils, they were transesterified into biodiesel in a solvent-free system using immobilized enzyme lipozyme from Mucor miehei. The Doehlert experimental design was used to evaluate the methyl ester (ME) yields as influenced by enzyme concentration—EC, temperature—T, added water content—AWC, and reaction time—RT. Biodiesel yields were quantified by (1)H NMR spectroscopy and subsequently modeled by a second order polynomial equation with interactions. Lipozyme enzymes were more tolerant to high temperatures in neem and shea oils reaction media compared to that of mango oil. The optimum reaction conditions EC, T, AWC, and RT assuring near complete conversion were as follows: mango oil 7.25 %, 36.6 °C, 10.9 %, 36.4 h; neem oil EC = 7.19 %, T = 45.7 °C, AWC = 8.43 %, RT = 25.08 h; and shea oil EC = 4.43 %, T = 45.65 °C, AWC = 6.21 % and RT = 25.08 h. Validation experiments of these optimum conditions gave ME yields of 98.1 ± 1.0, 98.5 ± 1.6 and 99.3 ± 0.4 % for mango, neem and shea oils, respectively, which all met ASTM biodiesel standards

Seismic monitoring of hydraulic fracturing: techniques for determining fluid flow paths and state of stress away from a wellbore

Hydraulic fracturing has gained in popularity in recent years as a way to determine the orientations and magnitudes of tectonic stresses. By augmenting conventional hydraulic fracturing measurements with detection and mapping of the microearthquakes induced by fracturing, we can supplement and idependently confirm information obtained from conventional analysis. Important information obtained from seismic monitoring includes: the state of stress of the rock, orientation and spacing of the major joint sets, and measurements of rock elastic parameters at locations distant from the wellbore. While conventional well logging operations can provide information about several of these parameters, the zone of interrogation is usually limited to the immediate proximity of the borehole. The seismic waveforms of the microearthquakes contain a wealth of information about the rock in regions that are otherwise inaccessible for study. By reliably locating the hypocenters of many microearthquakes, we have inferred the joint patterns in the rock. We observed that microearthquake locations do not define a simple, thin, planar distribution, that the fault plane solutions are consistent with shear slippage, and that spectral analysis indicates that the source dimensions and slip along the faults are small. Hence we believe that the microearthquakes result from slip along preexisting joints, and not from tensile extension at the tip of the fracture. Orientations of the principal stresses can be estimated by using fault plane solutions of the larger microearthquakes. By using a joint earthquake location scheme, and/or calibrations with downhole detonators, rock velocities and heterogeneities thereof can be investigated in rock volumes that are far enough from the borehole to be representative of intrincis rock properties

Multicore Scheduling for Lightweight Communicating Processes

Process-oriented programming is a design methodology in which software applications are constructed from communicating concurrent processes. A process-oriented design is typically composed of a large number of small isolated concurrent components. These components allow for the scalable parallel execution of the resulting application on both shared-memory and distributed-memory architectures. In this paper we present a runtime designed to support process-oriented programming by providing lightweight processes and communication primitives. Our run-time scheduler, implemented using lock-free algorithms, automatically executes concurrent components in parallel on multicore systems. Run-time heuristics dynamically group processes into cache-affine work units based on communication patterns. Work units are then distributed via wait-free work-stealing. Initial performance analysis shows that, using the algorithms presented in this paper, process-oriented software can execute with an efficiency approaching that of optimised sequential and coarse-grain threaded designs

Perception, knowledge and attitudes of Brazilian orthodontists on the treatment of Class II malocclusions

The present study aimed to assess the perception and knowledge of Brazilian orthodontists on the ideal moment to treat Class II malocclusions. Questionnaires with open, semi-open and close questions were sent by e-mail to 1653 Brazilian orthodontists. These orthodontists were registered in the Brazilian Association of Orthodontics and Dentofacial Orthopedics (ABOR). One-hundred and three (9.86%) Orthodontists replied to the questionnaires. Most of them were males (60.5%) with specialization as the highest level of professional qualification (59.9%). Most of the orthodontists (51%) reported preference for treating Class II malocclusions in late mixed dentition, followed by the early mixed dentition (29%). The age range between 10 and 12 years old figured as the most prevalent in patients searching for treatment (42.7%). Most of the patients searching for treatment were females (69.7%). Preferences for functional orthopedic appliances were reported by 35% of the orthodontists. Brazilian orthodontists revealed a trend for treating patients with Class II malocclusions in the late mixed dentition. Female patients aged from 10 to 12 years old represented the majority of patients that search for orthodontic treatment. Functional orthopedic appliances were preferred by Brazilian orthodontists for treating Class II malocclusions.8942875288