ALBERT

Description: During the Noachian period, 4.1-3.7 Gys ago, the Martian environment was moderately similar to the one on present Earth. Liquid water was widespread in a neutral environment, volcanic activity and heat flow more vigorous, and atmospheric pressure and temperature were higher than today. These conditions may have favoured the spread of life on the surface of Mars. The recognition that different planets and moons share rocky material cast in space by meteoroid impact entails that life creation is not necessary for each single planetary body, but could travel through the Solar system on board of rock fragments. Studies conducted on the past forms of Martian life have already highlighted possible positive matches with microbialite-like structures, referable to the geo-environmental conditions in the Noachian and Hesperian. However, by necessity, these studies are on predominantly micro and meso-scopic scale structures and doubts arise as to their attribution to the biogenic world. We suggest that in the identification of Martian life, we are currently in a position similar to the one of Kalkowsky who in 1908, based solely on morphological and sedimentological arguments, hypothesized the (now accepted) view of the biotic origin of stromatolites. Our analysis of thousands of images from Spirit, Opportunity and Curiosity has provided a selection of images of ring-shaped, domal and coniform macrostructures that resemble terrestrial microbialites such as the ring-shaped stromatolites of Lake Thetis, and stacked cones reminiscent of the group of terrestrial Conophyton. Notably, the latter were detected by Curiosity in the mudstone known as ‘Sheepbed’, the same outcrop where past organic molecules have been detected and where the occurrence of microbial-induced sedimentary structures (MISS) and of many more microbialitic micro, meso and macrostructures has already been hypothesized. Some of the structures discussed in this work are so complex that alternative biological hypotheses can be formulated as possible algae. Alternate, non-abiotic explanations are examined but we find difficult to explain some of such structures in the context of normal sedimentary processes, both syngenetic or epigenetic.

Description: Multiple myeloma (MM) remains an incurable tumor due to the high rate of relapse that still occurs. Acquired drug resistance represents the most challenging obstacle to the extension of survival and several studies have been conducted to understand the mechanisms of this phenomenon. Mitochondrial pathways have been extensively investigated, demonstrating that cancer cells become resistant to drugs by reprogramming their metabolic assessment. MM cells acquire resistance to proteasome inhibitors (PIs), activating protection programs, such as a reduction in oxidative stress, down-regulating pro-apoptotic, and up-regulating anti-apoptotic signals. Knowledge of the mechanisms through which tumor cells escape control of the immune system and acquire resistance to drugs has led to the creation of new compounds that can restore the response by leading to cell death. In this scenario, based on all literature data available, our review represents the first collection of anti-mitochondrial compounds able to overcome drug resistance in MM. Caspase-independent mechanisms, mainly based on increased oxidative stress, result from 2-methoxyestradiol, Artesunate, ascorbic acid, Dihydroartemisinin, Evodiamine, b-AP15, VLX1570, Erw-ASNase, and TAK-242. Other agents restore PIs’ efficacy through caspase-dependent tools, such as CDDO-Im, NOXA-inhibitors, FTY720, GCS-100, LBH589, a derivative of ellipticine, AT-101, KD5170, SMAC-mimetics, glutaminase-1 (GLS1)-inhibitors, and thenoyltrifluoroacetone. Each of these substances improved the efficacy rates when employed in combination with the most frequently used antimyeloma drugs.