ACE2 gene expression is up-regulated in the human failing heart

BACKGROUND: ACE2 is a novel homologue of angiotensin converting enzyme (ACE). ACE2 is highly expressed in human heart and animal data suggest that ACE2 is an essential regulator of cardiac function in vivo. Since overactivity of the renin-angiotensin system contributes to the progression of heart failure, this investigation assessed changes in gene expression of ACE2, ACE, AT(1 )receptor and renin in the human failing heart. METHODS: The sensitive technique of quantitative reverse transcriptase polymerase chain reaction was used to determine the level of mRNA expression of ACE and ACE2 in human ventricular myocardium from donors with non-diseased hearts (n = 9), idiopathic dilated cardiomyopathy (IDC, n = 11) and ischemic cardiomyopathy (ICM, n = 12). Following logarithmic transformation of the data, a one-way analysis of variance was performed for each target gene followed by a Dunnett's test to compare the two disease groups IDC and ICM versus control. RESULTS: As anticipated, ACE mRNA was found to be significantly increased in the failing heart with a 3.1 and 2.4-fold up-regulation found in IDC and ICM relative to non-diseased myocardium. Expression of ACE2 mRNA was also significantly up-regulated in IDC (2.4-fold increase) and ICM (1.8-fold increase) versus non-diseased myocardium. No change in angiotensin AT(1 )receptor mRNA expression was found in failing myocardium and renin mRNA was not detected. CONCLUSIONS: These data suggest that ACE2 is up-regulated in human IDC and ICM and are consistent with the hypothesis that differential regulation of this enzyme may have important functional consequences in heart failure. This strengthens the hypothesis that ACE2 may be a relevant target for the treatment of heart failure and will hopefully spur further studies to clarify the functional effects in human myocardium of ACE2 derived peptides

Crystallographic textures

In material science, crystallographic texture is an important microstructural parameter which directly determines the anisotropy degree of most physical properties of a polycrystalline material at the macro scale. Its characterization is thus of fundamental and applied importance, and should ideally be performed prior to any physical property measurement or modeling. Neutron diffraction is a tool of choice for characterizing crystallographic textures: its main advantages over other existing techniques, and especially over the X-ray diffraction techniques, are due to the low neutron absorption by most elements. The obtained information is representative of a large number of grains, leading to a better accuracy of the statistical description of texture

Lymphocyte Subsets Show Different Response Patterns to In Vivo Bound Natalizumab—A Flow Cytometric Study on Patients with Multiple Sclerosis

Natalizumab is an effective monoclonal antibody therapy for the treatment of relapsing- remitting multiple sclerosis (RRMS) and interferes with immune cell migration into the central nervous system by blocking the α4 subunit of very-late activation antigen-4 (VLA-4). Although well tolerated and very effective, some patients still suffer from relapses in spite of natalizumab therapy or from unwanted side effects like progressive multifocal leukoencephalopathy (PML). In search of a routine-qualified biomarker on the effectiveness of natalizumab therapy we applied flow cytometry and analyzed natalizumab binding to α4 and α4 integrin surface levels on T-cells, B-cells, natural killer (NK) cells, and NKT cells from 26 RRMS patients under up to 72 weeks of therapy. Four-weekly infusions of natalizumab resulted in a significant and sustained increase of lymphocyte-bound natalizumab (p<0.001) which was paralleled by a significant decrease in detectability of the α4 integrin subunit on all lymphocyte subsets (p<0.001). We observed pronounced natalizumab accumulations on T and B cells at single measurements in all patients who reported clinical disease activity (n = 4). The natalizumab binding capacity of in vitro saturated lymphocytes collected during therapy was strongly diminished compared to treatment-naive cells indicating a therapy-induced reduction of α4. Summing up, this pilot study shows that flow cytometry is a useful method to monitor natalizumab binding to lymphocytes from RRMS patients under therapy. Investigating natalizumab binding provides an opportunity to evaluate the molecular level of effectiveness of natalizumab therapy in individual patients. In combination with natalizumab saturation experiments, it possibly even provides a means of studying the feasability of patient-tailored infusion intervals. A routine-qualified biomarker on the basis of individual natalizumab saturation on lymphocyte subsets might be an effective tool to improve treatment safety

Über eine Klasse polynomialer Scharen selbstadjungierter Operatoren im Hilbertraum

HEK293A cells expressing either mouse MOG (mMOG) or rat MOG (rMOG) C terminally tagged with EGFP. (DOCX 2792 kb

Microwave assisted sintering of Na-β’’-Al2O3 in single mode cavities: Insights in the use of 2450 MHz frequency and preliminary experiments at 5800 MHz

Microwave assisted sintering of Na-beta’’-Al2O3 in single mode cavities was accurately investigated. The use of single mode cavity allowed monitoring the parameters affecting the sintering process, like the forward power, together with the temperature evolution, making possible to perform energy efficiency and specific energy consumption evaluations. Experiments have been performed at the frequency of 2450 MHz, but preliminary results are also reported using the higher frequency of 5800 MHz, in order to investigate its effect on important parameters like the power density distribution as well as the penetration depth, which are responsible of the resulting heating rate and sintering outcome. Dielectric properties of the powders were measured as a function of temperature in order to partially predict and support the understanding of their experimental heating behaviour. Furthermore, dielectric properties provide the fundamental information needed for the multiphysics numerical simulation, performed with the aim to reach insights into the power density evolution in the specimen as sintering proceeds

Textures of eclogites and blueschists from Syros island, Greece: inferences for elastic anisotropy of subducted oceanic crust

Many blueschists and eclogites are inferred to have formed from oceanic basalts in subducted slabs. Knowledge of their elastic behaviour is essential for reconstructing the internal structure of subduction zones. The Cycladic Blueschist Unit, exposed on Syros Island (Greece), contains rocks belonging to an exhumed Tertiary subduction complex. They were possibly part of a subduction channel, a shear zone above the subducting slab in which exhumation is possible during subduction. Intense plastic deformation, forming crystallographic preferred orientations (CPO), accompanied blueschist and eclogite metamorphism. CPO of the constituent minerals in the collected samples was determined by time-of-flight neutron diffraction. Two samples are foliated fine-grained blueschists with strong CPO, rich in glaucophane, zoisite and phengite. Two coarser-grained eclogite samples rich in omphacite and clinozoisite, or glaucophane, have weaker CPO. Vp and Vs anisotropies were computed from the orientation distribution function and single-crystal elastic constants. All samples show velocity maxima parallel to the mineral lineation, and minima normal to the foliation, providing important constraints on orientations of seismic anisotropy in subduction channels. Vp anisotropies are up to three times higher (6.5-12%) in the blueschists than in the eclogites (3-4%), pointing to a potentially important lithological control of elastic anisotropy in subducted oceanic crust