Kinetics and Inhibition Studies of the L205R Mutant of cAMP-Dependent Protein Kinase Involved in Cushing’s Syndrome

Overproduction of cortisol by the hypothalamus–pituitary–adrenal hormone system results in the clinical disorder known as Cushing\u27s syndrome. Genomics studies have identified a key mutation (L205R) in the α‐isoform of the catalytic subunit of cAMP‐dependent protein kinase (PKACα) in adrenal adenomas of patients with adrenocorticotropic hormone‐independent Cushing\u27s syndrome. Here, we conducted kinetics and inhibition studies on the L205R‐PKACα mutant. We have found that the L205R mutation affects the kinetics of both Kemptide and ATP as substrates, decreasing the catalytic efficiency (kcat/KM) for each substrate by 12‐fold and 4.5‐fold, respectively. We have also determined the IC50 and Ki for the peptide substrate‐competitive inhibitor PKI(5–24) and the ATP‐competitive inhibitor H89. The L205R mutation had no effect on the potency of H89, but causes a \u3e 250‐fold loss in potency for PKI(5–24). Collectively, these data provide insights for the development of L205R‐PKACα inhibitors as potential therapeutics

Fungal environment in different rabbit intensive farms

Many environmental factors (for example, temperature, relative humidity, ventilation, NH3 concentration) can influence the health and welfare of rabbits reared in intensive farms. Among these elements, microorganisms and, in particular, fungi play a pivotal role in the spreading of potential pathogenic and zoonotic diseases. Aim of our work was to evaluate the fungal contamination in two different rabbit rearing (A and B). SAS System® (PBI International, Italy) and opened plates, filled with cultural media for fungal growth (environmental and dermatophytes) have been used. The data collected in both the farms showed that, for environmental fungi, Aspergillus, Alternaria and Penicillium were the most spread. On the contrary, for dermatophytes, there was a difference between farm A and B. In fact, in the first one Microsporum canis (a known zoonotic agent) has been recovered in high concentration, while in the second rearing we have isolated Microsporum gypseum a geophilic fungus with a very low pathogenic potential

May the force be with you: why resistance training is essential for subjects with type 2 diabetes mellitus without complications

Physical activity, together with diet and pharmacological therapy, represents one of the three cornerstones in type 2 diabetes mellitus treatment and care. The therapeutic appeal of regular physical activity stems from: (i) its non-pharmacological nature; (ii) its beneficial effects on the metabolic risk factors associated with diabetes complications; (iii) its low costs. Evidence accumulated in the last years suggests that aerobic training\u2014endurance training\u2014constitutes a safe modality of intervention, achievable, and effective in diabetes treatment, whenever it is not limited by comorbidities. Aerobic training exerts insulin-mimetic effects and has been shown to lower mortality risk too. Anaerobic, intense physical activity, such as that of strength or power sports disciplines, is not univocally recognized as safe and simple to realize, however, it is important in stimulating energy and glucose metabolism. According to recent evidence, high-intensity training may be prescribed even in the face of cardiovascular diseases, peripheral vascular disease, or osteoarthritis. Some studies have shown resistance training to be more efficient than aerobic exercise in improving glycemic control. This review explores the most up-to-date indications emerging from literature in support of the beneficial effects of strength stimulation and resistance training in patients with type 2 diabetes without complications

Jesús en la tierra de los hombres

Gesù e la terra degli uomini pertenece al texto que el Papa Juan Pablo II encargó a Mario Luzi para el ejercicio del Via Crucis en el Coliseo romano, en la Pascua de 1999. La obra ha sido publicada posteriormente con el título de La Passione. En 2005, en un intervalo de poco más de un mes, tanto Juan Pablo II como Mario Luzi fallecieron, por lo que la estación adquiere un nuevo y hondo significado. La traducción es de Pedro Luis Ladrón de Guevara, quien también ha traducido y editado Ensayos críticos de Mario Luzi, de próxima aparición en la Colección Cátedra Félix Huarte

The Mw 6.3, 2009 L’Aquila earthquake: source, path and site effects from spectral analysis of strong motion data

The strong motion data of 2009 April 6 L’Aquila (Central Italy) earthquake (Mw = 6.3) and of 12 aftershocks (4.1 ≤ Mw ≤ 5.6) recorded by 56 stations of the Italian strong motion network are spectrally analysed to estimate the source parameters, the seismic attenuation, and the site amplification effects. The obtained source spectra for S wave have stress drop values ranging from 2.4 to 16.8 MPa, being the stress drop of the main shock equal to 9.2 MPa. The spectral curves describing the attenuation with distance show the presence of shoulders and bumps, mainly around 50 and 150 km, as consequence of significant reflected and refracted arrivals from crustal interfaces. The attenuation in the first 50 km is well described by a quality factor equal to Q( f ) = 59 f 0.56 obtained by fixing the geometrical spreading exponent to 1. Finally, the horizontal-to-vertical spectral ratio provides unreliable estimates of local site effects for those stations showing large amplifications over the vertical component of motion

Ultrasound for Non-invasive Fluid Droplet Detection inside a Sealed Container

Ultrasound has long been known to be capable of measuring water level. Zero-degree ultrasound transducers may be used to send an L-wave through the fluid and receive a reflected signal from the fluid/gas interface surface. The level of the fluid is proportional to the sound wave time of flight to traverse the water path. This approach may even be used from outside the fluid containment wall by sending the wave through the tank or pipe bottom. The approach, however, does not work well if there is only a thin layer of fluid consisting of one or two millimeters or even only a few droplets. Surface waves are also known to be sensitive to the presence or absence of fluid on a surface. A surface wave may be transmitted a significant distance by a transmitting transducer and then received by a similar transducer. If the surface along the wave path is wet with even a few droplets of fluid, the surface wave may be significantly attenuated. Generating and measuring such a surface wave from the opposite side of a tank or pipe containment wall and separating the near-wall surface wave from the far-wall surface wave, however, is more challenging. An approach for producing a surface wave on the opposite side of a steel plate to sense the presence or absence of fluid is discussed. This approach is supported by 2-D finite element modeling of the measurement configuration and by empirical demonstration of the technique’s sensitivity. This technique was developed for measurement of a very small amount of fluid that may condense within a spent nuclear fuel canister after it cools for several years. Such small amounts of fluid are of concern for initiating stress corrosion cracking over the decades that these nuclear waste containment structures are expected to remain leak-free. Early detection of fluid would provide advance warning of potential cracks in time for mitigation or management of the waste inside that container. Other potential applications include any non-intrusive liquid container fluid detection, detection of fluid within inaccessible plena of aircrafts or other complex welded skin structures

Evaluation of skin temperature change as stress indicator in rabbit through infrared thermography

AbstractStress-induced reactions in animals include behavioural and physiological modifications aiming at coping towards the stressor, such as manipulations. Thermography, that is the detection of ..