Images obtained by the Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) cameras onboard the Rosetta spacecraft reveal that asteroid 21 Lutetia has a complex geology and one of the highest asteroid densities measured so far, 3.4 ± 0.3 grams per cubic centimeter. The north pole region is covered by a thick layer of regolith, which is seen to flow in major landslides associated with albedo variation. Its geologically complex surface, ancient surface age, and high density suggest that Lutetia is most likely a primordial planetesimal. This contrasts with smaller asteroids visited by previous spacecraft, which are probably shattered bodies, fragments of larger parents, or reaccumulated rubble piles.

Understanding how comets work--what drives their activity--is crucial to the use of comets in studying the early solar system. EPOXI (Extrasolar Planet Observation and Deep Impact Extended Investigation) flew past comet 103P/Hartley 2, one with an unusually small but very active nucleus, taking both images and spectra. Unlike large, relatively inactive nuclei, this nucleus is outgassing primarily because of CO(2), which drags chunks of ice out of the nucleus. It also shows substantial differences in the relative abundance of volatiles from various parts of the nucleus.

Cartilage tumours present ongoing therapeutic challenges due to their chondrogenic extracellular matrix that potentially hampers drug delivery, their low percentage of dividing cells, and their poor vascularity. In this context, and based on the affinity of the quaternary ammonium moiety for proteoglycans (PG), we developed a strategy that uses the quaternary ammonium function to selectively deliver DNA alkylating agents to the cartilage tumour tissue. We engineered the quaternary ammonium derivative of melphalan (Mel-AQ) and assessed its antitumoural activity in vitro and in vivo. In vitro, micromolar concentrations of Mel-AQ inhibited the proliferation of human HEMC-SS chondrosarcoma and Saos-2 osteosarcoma cell lines. Moreover, 24-h incubation with 20 μM Mel-AQ induced a 2.5-fold increase in S population and a 1.5-fold increase in subG0G1 population compared to controls. In vivo, Mel-AQ demonstrated antitumour activity in the orthotopic model of primary Swarm rat chondrosarcoma. When given to chondrosarcoma-bearing rats (three doses of 16 μmol/kg at days 8, 12 and 16 post-implant), Mel-AQ demonstrated an optimal antitumour effect at day 43, when tumour cell growth inhibition peaked at 69%. Interestingly, the treatment protocol was proved well tolerated, since the animals showed no weight loss over the course of the study. This antitumoural effect was assessed in vivo by scintigraphic imaging using (99m)Tc-NTP 15-5 developed in our lab as a PG-targeting radiotracer, and tumour tissue was analyzed at study-end by biochemical PG assay with Alcian blue staining. Mel-AQ treatment led to a significant decrease in the PG content of tumoural tissue. These experimental results highlighted the promising antitumour potential of Mel-AQ as a PG-targeting strategy for therapeutic management of chondrosarcoma.

Our lab developed (99m)Tc-NTP 15-5 radiotracer as targeting proteoglycans (PGs) for the scintigraphic imaging of joint. This paper reports preclinical results of (99m)Tc-NTP 15-5 imaging of an orthotopic model of Swarm rat chondrosarcoma (SRC).(99m)Tc-NTP 15-5 imaging of SRC-bearing and sham-operated animals was performed and quantified at regular intervals after surgery and compared to bone scintigraphy and tumoural volume. Tumours were characterized by histology and PG assay. SRC exhibited a significant (99m)Tc-NTP 15-5 uptake at very early stage after implant (with tumour/muscle ratio of 1.61 ± 0.14), whereas no measurable tumour was evidenced. As tumour grew, mean tumour/muscle ratio was increased by 2.4, between the early and late stage of pathology. Bone scintigraphy failed to image chondrosarcoma, even at the later stage of study.(99m)Tc-NTP 15-5 imaging provided a suitable set of quantitative criteria for the in vivo characterization of chondrosarcoma behaviour in bone environment, useful for achieving a greater understanding of the pathology.

The European Space Agency's Rosetta mission encountered the main-belt asteroid (2867) Steins while on its way to rendezvous with comet 67P/Churyumov-Gerasimenko. Images taken with the OSIRIS (optical, spectroscopic, and infrared remote()imaging system) cameras on board Rosetta show that Steins is an oblate body with an effective spherical diameter of 5.3 kilometers. Its surface does not show color variations. The morphology of Steins is dominated by linear faults and a large 2.1-kilometer-diameter crater near its south pole. Crater counts reveal a distinct lack of small craters. Steins is not solid rock but a rubble pile and has a conical appearance that is probably the result of reshaping due to Yarkovsky-O'Keefe-Radzievskii-Paddack (YORP) spin-up. The OSIRIS images constitute direct evidence for the YORP effect on a main-belt asteroid.

The incidence of ischemic cardiac diseases increases with age and elderly subjects are more vulnerable to myocardial infarction. Endurance exercise (e.g. treadmill training) provides cardioprotection against an ischemia and reperfusion (IR) event in adult heart but such a potential beneficial effect of regular exercise has never been evaluated during aging. Therefore, this study investigated the effects of moderate running training on post-ischemic recovery of contractile function and coronary perfusion in senescent myocardium. Isolated hearts of sedentary (24 mo-sedentary; n=10) and trained senescent (24 mo-trained; n=11; moderate running: 1h/day, 5 days/week for 12 weeks) rats were submitted to 45min low-flow ischemia (15% of initial coronary flow (CF)) followed by 30min reperfusion. Active tension (AT) and CF were recorded at baseline and after 1, 3, 5, 10, 15, 20, 25 and 30min of reperfusion. Left ventricular protein carbonylation, and both heat-shock-protein 70 (HSP70) and endothelial nitric oxide synthase (eNOS) contents were determined by Oxyblotting and Western blotting, respectively. Regular physical exercise improves impairment of functional post-ischemic recovery (AT and CF) of aged hearts during reperfusion and this cardioprotection is associated to limited protein oxidation and increased HSP70 and eNOS myocardial contents.

Translationally controlled tumor protein (TCTP) is a potential target for cancer therapy. It functions as a growth regulating protein implicated in the TSC1-TSC2 -mTOR pathway or a guanine nucleotide dissociation inhibitor for the elongation factors EF1A and EF1Bbeta. Accumulating evidence indicates that TCTP also functions as an antiapoptotic protein, through a hitherto unknown mechanism. In keeping with this, we show here that loss of tctp expression in mice leads to increased spontaneous apoptosis during embryogenesis and causes lethality between E6.5 and E9.5. To gain further mechanistic insights into this apoptotic function, we solved and refined the crystal structure of human TCTP at 2.0 A resolution. We found a structural similarity between the H2-H3 helices of TCTP and the H5-H6 helices of Bax, which have been previously implicated in regulating the mitochondrial membrane permeability during apoptosis. By site-directed mutagenesis we establish the relevance of the H2-H3 helices in TCTP's antiapoptotic function. Finally, we show that TCTP antagonizes apoptosis by inserting into the mitochondrial membrane and inhibiting Bax dimerization. Together, these data therefore further confirm the antiapoptotic role of TCTP in vivo and provide new mechanistic insights into this key function of TCTP.Cell Death and Differentiation advance online publication, 15 February 2008; doi:10.1038/cdd.2008.18.

Cardiovascular ageing is associated with an increase in cardiac susceptibility to ischaemia and reperfusion and production of reactive oxygen species has been suspected to be responsible for this age-associated particular vulnerability. To determine whether administration of antioxidant treatment could afford some protection against ischaemia and reperfusion during aging, isolated perfused hearts from adult and senescent rats were submitted to normoxia (180 min), prolonged low-flow ischaemia (15% of initial coronary flow;180 min) or low-flow ischaemia/reperfusion (45 min/30 min), without or with antioxidant enzymes (superoxide dismutase+catalase; 50IU/ml). Contractile function and coronary perfusion were measured and protein oxidation was quantitated in left ventricle after normoxia, ischaemia and ischaemia/reperfusion. Protein oxidation was higher in senescent than in adult hearts after ischaemia-reperfusion, in contrast to prolonged ischaemia. During prolonged ischaemia, antioxidant treatment prevented coronary vasoconstriction at both ages and delayed contractile dysfunction in senescent hearts but did not limit protein oxidation. During reperfusion, antioxidant treatment prevented coronary vasoconstriction and protein oxidation at both ages and considerably improved recovery of contractile function in senescent hearts. In conclusion, antioxidant treatment fully protects the senescent heart against ischaemia/reperfusion but not against prolonged ischaemia injury, indicating that oxidative stress plays a central role in the age-associated vulnerability to ischaemia-reperfusion.

None of the many theories of senescence can account for the aging process in its entirety. These theories include the evolutionary theory of aging and its EvoDevo corollary, the replicative senescence and free radicals theory, theories based on large-scale analyses (proteomics, etc.), and systemic theories. Cardiovascular senescence is first and foremost due to vascular senescence. Aging is associated with enhanced aortic characteristic impedance, which is mainly due to glycation of vessel wall proteins. This increased impedance overloads the left ventricle and causes compensatory left ventricular hypertrophy, usually associated with fibrosis. Extreme aging (> 80 years in humans,> 30 months in rats) is associated with age-related heart failure. Senescence favors heart failure, atrial fibrillation and cardiac hypertrophy. It is also associated with increased systolic pressure and decreased diastolic pressure. The most characteristic features are enhanced pulse pressure and arterial compliance.

BACKGROUND:: The myocardial negative inotropic effects of desflurane are less pronounced than those of other halogenated anesthetics, partly because of intramyocardial catecholamine store release. However, the effects of desflurane on aging myocardium are unknown, whereas aging is known to be associated with an attenuation of catecholamine responsiveness. METHODS:: The effects of desflurane (1.9-9.3 vol%) were studied in left ventricular papillary muscle of adult and senescent rats (29 degrees C; 0.5 mm Ca; stimulation frequency 12 pulses/min). The inotropic effects were compared under low and high loads, using the maximum unloaded shortening velocity and maximum isometric active force, and without or with alpha- and beta-adrenoceptor blockade. RESULTS:: Desflurane induced a moderate positive inotropic effect in adult rats but a negative inotropic effect in senescent rats. After alpha- and beta-adrenoceptor blockade, desflurane induced a comparable negative inotropic effect in adult and senescent rats. No lusitropic effect under low load was observed, whereas desflurane induced a slight but significant positive lusitropic effect under high load similar between the two groups of rats. This positive effect was abolished by adrenoceptor blockade. CONCLUSION:: The authors' study suggests that desflurane does not induce significant intramyocardial catecholamine release in senescent myocardium, a result that should be integrated in the well-known alteration in the catecholamine response during aging.