Lung Cancer: Are we up to the Challenge?

Lung cancer is the leading cause of cancer deaths worldwide among both men and women, with more than 1 million deaths annually. Non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancers.Although recent advances have been made in diagnosis and treatment strategies, the prognosis of NSCLC patients is poor and it is basically due to a lack of early diagnostic tools.However, in the last years genetic and biochemical studies have provided more information about the protein and gene's mutations involved in lung tumors. Additionally, recent proteomic and microRNA's approaches have been introduced to help biomarker discovery.Here we would like to discuss the most recent discoveries in lung cancer pathways, focusing on the genetic and epigenetic factors that play a crucial role in malignant cell proliferation, and how they could be helpful in diagnosis and targeted therapy.     

Mitochondrial non-syndromic sensorineural hearing loss: a clinical, audiological and pathological study from Italy, and revision of the literature

Over the last decade, a number of distinct mutations in the mtDNA (mitochondrial DNA) have been found to be associated with both syndromic and non-syndromic forms of hearing impairment. Their real incidence as a cause of deafness is poorly understood and generally underestimated. Among the known mtDNA mutations, the A1555G mutation in the 12S gene has been identified to be one of the most common genetic cause of deafness, and it has been described to be both associated to non-syndromic progressive SNHL (sensorineural hearing loss) and to aminoglycoside-induced SNHL. In the present study, we have investigated the presence of mtDNA alterations in patients affected by idiopathic non-syndromic SNHL, both familiar and sporadic, in order to evaluate the frequency of mtDNA alterations as a cause of deafness and to describe the audiological manifestations of mitochondrial non-syndromic SNHL. In agreement with previous studies, we found the A1555G mutation to be responsible for a relevant percentage (5.4%) of cases affected with isolated idiopathic sensorineural hearing impairment.     

Design,synthesis, and biological screening of a series of 4′-fluoro-benzotriazole-acrylonitrile derivatives as microtubule-destabilising agents (MDAs)

Introduction: Colchicine-binding site inhibitors are some of the most interesting ligands belonging to the wider family of microtubule-destabilising agents.Results: A novel series of 4′-fluoro-substituted ligands (5–13) was synthesised. The antiproliferative activity assays resulted in nM values for the new benzotriazole-acrylonitrile derivatives. Compound 5, the hit compound, showed an evident blockade of HeLa cell cycle in the G2-M phase, but also a pro-apoptotic potential, and an increase of early and late apoptotic cells in HeLa and MCF-7 cell cycle analysis. Confocal microscopy analysis showed a segmented shape and a collapse of the cytoskeleton, as well as a consistent cell shrinkage after administration of 5 at 100 nM. Derivative 5 was also proved to compete with colchicine at colchicine-binding site, lowering its activity against tubulin polymerisation. In addition, co-administration of 5 and doxorubicin in drug-resistant A375 melanoma cell line highlighted a synergic potential in terms of inhibition of cell viability.Discussion: The 4′-fluoro substitution of benzotriazole-acrylonitrile scaffold brought us a step forward in the optimisation process to obtain compound 5 as promising MDA antiproliferative agent at nanomolar concentration.     

The influence of stochasticity,landscape structure and species traits on abundant–centre relationships

Species have been commonly hypothesized to have high population densities in geographic areas which correspond to either the centre of the species geographic range or climatic niche (abundant–centre hypothesis). However, there is mixed empirical support for this relationship, and little theoretical underpinning. We simulate a species spreading across a set of replicated artificial landscapes to examine the expected level of support for abundant–centre relationships in geographic and niche space. Species niche constraints were modeled as a single axis which was related directly to population growth rates. We found strong evidence for abundant–centre relationships when populations follow deterministic growth, dispersal is high, environmental noise is absent and intraspecific competition is low. However, the incorporation of ecological realism reduced the detectability of abundant–centre relationships considerably. Our results suggest that even in carefully constructed artificial landscapes designed to demonstrate abundant–centre dynamics, the incorporation of small amounts of demographic stochasticity, environmental heterogeneity or landscape structure can strongly influence the relationship between species population density and distance to species geographic range or niche centre. While some simulated relationships were of comparable strength to common empirical support for abundant–centre relationships, our results suggest that these relationships are expected to be fairly variable and weak.     

Exploring co-extinction correlates: the effects of habitat,biogeography and anthropogenic factors on ground squirrels–dung beetles associations

Co-extinction is a recurring topic in conservation biology. Quantification of co-extinction has been generally restricted to parasite–host, predator–prey and herbivore–host plant interactions. The loss of detritivorous insects upon the depletion of herbivore mammals has been poorly explored. Here, we used rarefaction curves to predict co-decline involving the decrease in scarab dung beetles diversity due to a reduction in the number of dens of the Asia minor ground squirrel in the Turkish steppe biome. We also evaluated the potential benefits provided by livestock in mitigating the decline of scarab beetle communities. Rarefaction curves estimated that a 50% reduction in the number of sample units where squirrel faecal pellets are the only available food resource accounts for a reduction of 28% of all the scarab species, and of 24% of the squirrel-linked species. The current decline of ground squirrels, mainly due to intensification of agriculture, may represent a threat for biodiversity in steppic environments because it may affect the specialized insects, and may produce a cascade effect also on their predators, i.e., saker falcon, buzzards, eagles and mustelids. We also showed that the conservation of ground squirrels and their affiliate scarab species may be ensured by a moderate livestock grazing, owing to the higher ecological success of these rodents in the presence of large herbivores keeping low the grass cover.     

Assessment of environmental quality by the diversity of epiphytic lichens in a semi-arid mediterranean area (Val Basento, South Italy)

The results of a bioindication study based on the diversity of epiphytic lichens in a semi-arid area of South Italy are presented. The area features the presence of an industrial zone located in a rural context. The survey was performed in 20 sampling sites. The lichen diversity values (LDV) were determined by the frequencies of all lichen species within a sampling grid placed on tree trunks. Lichens demonstrated a condition of environmental alteration extending to the industrial zone, and tending towards a recovery in the rural surroundings. The survey also showed evidence of eutrophication all over the study area.     

Climate Dynamics: A Network-Based Approach for the Analysis of Global Precipitation

Precipitation is one of the most important meteorological variables for defining the climate dynamics, but the spatial patterns of precipitation have not been fully investigated yet. The complex network theory, which provides a robust tool to investigate the statistical interdependence of many interacting elements, is used here to analyze the spatial dynamics of annual precipitation over seventy years (1941–2010). The precipitation network is built associating a node to a geographical region, which has a temporal distribution of precipitation, and identifying possible links among nodes through the correlation function.The precipitation network reveals significant spatial variability with barely connected regions, as Eastern China and Japan, and highly connected regions, such as the African Sahel, Eastern Australia and, to a lesser extent, Northern Europe. Sahel and Eastern Australia are remarkably dry regions, where low amounts of rainfall are uniformly distributed on continental scales and small-scale extreme events are rare. As a consequence, the precipitation gradient is low, making these regions well connected on a large spatial scale. On the contrary, the Asiatic South-East is often reached by extreme events such as monsoons, tropical cyclones and heat waves, which can all contribute to reduce the correlation to the short-range scale only.Some patterns emerging between mid-latitude and tropical regions suggest a possible impact of the propagation of planetary waves on precipitation at a global scale. Other links can be qualitatively associated to the atmospheric and oceanic circulation. To analyze the sensitivity of the network to the physical closeness of the nodes, short-term connections are broken. The African Sahel, Eastern Australia and Northern Europe regions again appear as the supernodes of the network, confirming furthermore their long-range connection structure. Almost all North-American and Asian nodes vanish, revealing that extreme events can enhance high precipitation gradients, leading to a systematic absence of long-range patterns.