Angiotensin II-induced cardiac hypertrophy is associated with different mitogen-activated protein kinase activation in normotensive and hypertensive mice.

OBJECTIVE: In addition to its haemodynamic effects, angiotensin II (AngII) is thought to contribute to the development of cardiac hypertrophy via its growth factor properties. The activation of mitogen-activated protein kinases (MAPK) is crucial for stimulating cardiac growth. Therefore, the present study aimed to determine whether the trophic effects of AngII and the AngII-induced haemodynamic load were associated with specific cardiac MAPK pathways during the development of hypertrophy. Methods The activation of the extracellular-signal-regulated kinase (ERK), the c-jun N-terminal kinase (JNK) and the p38 kinase was followed in the heart of normotensive and hypertensive transgenic mice with AngII-mediated cardiac hypertrophy. Secondly, we used physiological models of AngII-dependent and AngII-independent renovascular hypertension to study the activation of cardiac MAPK pathways during the development of hypertrophy. RESULTS: In normotensive transgenic animals with AngII-induced cardiac hypertrophy, p38 activation is associated with the development of hypertrophy while ERK and JNK are modestly stimulated. In hypertensive transgenic mice, further activation of ERK and JNK is observed. Moreover, in the AngII-independent model of renovascular hypertension and cardiac hypertrophy, p38 is not activated while ERK and JNK are strongly stimulated. In contrast, in the AngII-dependent model, all three kinases are stimulated. CONCLUSIONS: These data suggest that p38 activation is preferentially associated with the direct effects of AngII on cardiac cells, whereas stimulation of ERK and JNK occurs in association with AngII-induced mechanical stress.

Mycobacterium tuberculosis-specific CD8+ T cells are functionally and phenotypically different between latent infection and active disease.

Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8(+) T cells is controversial. Here we performed a broad phenotypic and functional characterization of Mtb-specific CD8(+) T cells in 326 subjects with latent Mtb infection (LTBI) or active TB disease (TB). Mtb-specific CD8(+) T cells were detected in most (60%) TB patients and few (15%) LTBI subjects but were of similar magnitude. Mtb-specific CD8(+) T cells in LTBI subjects were mostly T EMRA cells (CD45RA(+) CCR7(-)), coexpressing 2B4 and CD160, and in TB patients were mostly TEM cells (CD45RA(-) CCR7(-)), expressing 2B4 but lacking PD-1 and CD160. The cytokine profile was not significantly different in both groups. Furthermore, Mtb-specific CD8(+) T cells expressed low levels of perforin and granulysin but contained granzymes A and B. However, in vitro-expanded Mtb-specific CD8(+) T cells expressed perforin and granulysin. Finally, Mtb-specific CD8(+) T-cell responses were less frequently detected in extrapulmonary TB compared with pulmonary TB patients. Mtb-specific CD8(+) T-cell proliferation was also greater in patients with extrapulmonary compared with pulmonary TB. Thus, the activity of Mtb infection and clinical presentation are associated with distinct profiles of Mtb-specific CD8(+) T-cell responses. These results provide new insights in the interaction between Mtb and the host immune response.

Under- and over-water halves of Gyrinidae beetle eyes harbor different corneal nanocoatings providing adaptation to the water and air environments.

Whirligig beetles (Gyrinidae) inhabit water surfaces and possess unique eyes which are split into the overwater and underwater parts. In this study we analyze the micro- and nanostructure of the split eyes of two Gyrinidae beetles genera, Gyrinus and Orectochilus. We find that corneae of the overwater ommatidia are covered with maze-like nanostructures, while the corneal surface of the underwater eyes is smooth. We further show that the overwater nanostructures possess no anti-wetting, but the anti-reflective properties with the spectral preference in the range of 450-600 nm. These findings illustrate the adaptation of the corneal nanocoating of the two halves of an insect's eye to two different environments. The novel natural anti-reflective nanocoating we describe may find future technological applications.