UV-protective compounds in marine organisms from the Southern Ocean

Solar radiation represents a key abiotic factor in the evolution of life in the oceans. In general, marine, biota particularly in euphotic and dysphotic zones depends directly or indirectly on light, but ultraviolet radiation (UV-R) can damage vital molecular machineries. UV-R induces the formation of reactive oxygen species (ROS) and impairs intracellular structures and enzymatic reactions. It can also affect organismal physiologies and eventually alter trophic chains at the ecosystem level. In Antarctica, physical drivers, such as sunlight, sea-ice, seasonality and low temperature are particularly influencing as compared to other regions. The springtime ozone depletion over the Southern Ocean makes organisms be more vulnerable to UV-R. Nonetheless, Antarctic species seem to possess analogous UV photoprotection and repair mechanisms as those found in organisms from other latitudes. The lack of data on species-specific responses towards increased UV-B still limits the understanding about the ecological impact and the tolerance levels related to ozone depletion in this region. The photobiology of Antarctic biota is largely unknown, in spite of representing a highly promising reservoir in the discovery of novel cosmeceutical products. This review compiles the most relevant information on photoprotection and UV-repair processes described in organisms from the Southern Ocean, in the context of this unique marine polar environment

Molecular adaptations in Antarctic fish and bacteria

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Leptin Enhances, via AP-1, Expression of Aromatase in the MCF-7 Cell Line *

Leptin, a product of adipocytes, is involved in the regulation of body weight and results strongly correlated to body fat content. An excess of fat mass represents a breast cancer risk factor particularly in postmenopausal women, where estrogen production by adipose tissue through its own aromatase activity stimulates tumor progression. Leptin stimulates estrogen production through the increase of aromatase expression and activity in human luteinized granulosa cells and adipose stromal cells. In the present study, we have examined the possible link that exists between leptin and breast cancer, focusing our attention on the direct effect of leptin on aromatase activity, which may enhance estrogen production and induce tumor cell growth stimulation. We have shown that leptin enhances aromatase mRNA expression, aromatase content, and its enzymatic activity in MCF-7. Aromatase expression appears to be regulated by tissue-specific promoter. It has been demonstrated that promoters II and 1.3 are the major promoters that drive aromatase expression in MCF-7. Transient transfection experiments using vector containing human aromatase promoters II and 1.3 sequence fused with luciferase reporter gene demonstrated that leptin is able to activate this promoter. In the presence of either mitogen-activated protein kinase inhibitor PD 98059 or ERK2 dominant negative as well as in the presence of STAT3 dominant negative, the stimulatory effects of leptin on aromatase promoter, enzymatic activity, and aromatase protein content were inhibited. Functional studies of mutagenesis and electrophoretic mobility shift assay revealed that the AP-1 motif is important in determining the up-regulatory effects induced by leptin on aromatase expression in MCF-7

Human Papilloma Virus (HPV) status, P16INK4a and p53 overexpression in epithelial malignant and borderline ovarian neoplasms

This investigation is the first to evaluate simultaneously human papilloma virus (HPV) status, p16(INK4a), and p53 immunoreactivity in epithelial ovarian neoplasms. The results were analyzed and correlated with histological type, histological grade, and survival of patients. Subtypes considered are papillary serous and mucinous. Polymerase chain reaction (PCR) analysis, performed in our previous study, had already demonstrated a small number of HPV-positive epithelial ovarian neoplasms. No significant correlation was found between the presence of HPV DNA and subtypes of ovarian neoplasms; thus, HPV cannot be considered responsible for epithelial ovarian neoplasm. Since p16 immunoreactivity was present in many other HPV-negative cases of epithelial ovarian neoplasms, this study suggests that p16 overexpression in some neoplasms of the female genital tract is not related to HPV carcinogenesis. A higher p53 expression rate observed between borderline and malignant serous tumors and between serous and mucinous neoplasms can confirm a recent dualistic model of ovarian carcinogenesis. According to this theory, low-grade serous carcinomas (serous intraepithelial carcinomas, serous borderline neoplasm, and ovarian mucinous neoplasms) (type I tumors) develop from mutations of KAS and BRAF, while high-grade serous carcinomas (type II tumors) develop from mutation of p53. In malignant neoplasms, for univariate analysis, patient survival seems to be related to p53, strong and diffuse p16 overexpression, and the stage of development of neoplasms at the diagnosis. In multinomial logistic regression, used to evaluate the role of staging, grading, p16 and p53 immunopositivity as predictor variables of unfavorable outcome of the disease, only p16 positivity was significantly related to the poor prognosis of the cancer

The Evolution of Nitric Oxide Function: From Reactivity in the Prebiotic Earth to Examples of Biological Roles and Therapeutic Applications

Nitric oxide was once considered to be of marginal interest to the biological sciences and medicine; however, there is now wide recognition, but not yet a comprehensive understanding, of its functions and effects. NO is a reactive, toxic free radical with numerous biological targets, especially metal ions. However, NO and its reaction products also play key roles as reductant and oxidant in biological redox processes, in signal transduction, immunity and infection, as well as other roles. Consequently, it can be sensed, metabolized and modified in biological systems. Here, we present a brief overview of the chemistry and biology of NO—in particular, its origins in geological time and in contemporary biology, its toxic consequences and its critical biological functions. Given that NO, with its intrinsic reactivity, appeared in the early Earth’s atmosphere before the evolution of complex lifeforms, we speculate that the potential for toxicity preceded biological function. To examine this hypothesis, we consider the nature of non-biological and biological targets of NO, the evolution of biological mechanisms for NO detoxification, and how living organisms generate this multifunctional gas

Conformational Flexibility Drives Cold Adaptation in Pseudoalteromonas haloplanktis TAC125 Globins

Significance: Temperature is one of the most important drivers in shaping protein adaptations. Many biochemical and physiological processes are influenced by temperature. Proteins and enzymes from organisms living at low temperature are less stable in comparison to high-temperature adapted proteins. The lower stability is generally due to greater conformational flexibility. Recent Advances: Adaptive changes in the structure of cold-adapted proteins may occur at subunit interfaces, distant from the active site, thus producing energy changes associated with conformational transitions transmitted to the active site by allosteric modulation, valid also for monomeric proteins in which tertiary structural changes may play an essential role. Critical Issues: Despite efforts, the current experimental and computational methods still fail to produce general principles on protein evolution, since many changes are protein and species dependent. Environmental constraints or other biological cellular signals may override the ancestral information included in the structure of the protein, thus introducing inaccuracy in estimates and predictions on the evolutionary adaptations of proteins in response to cold adaptation. Future Directions: In this review, we describe the studies and approaches used to investigate stability and flexibility in the cold-adapted globins of the Antarctic marine bacterium Pseudoalteromonas haloplanktis TAC125. In fact, future research directions will be prescient on more detailed investigation of cold-adapted proteins and the role of fluctuations between different conformational states.Fil: Giordano, Daniela. Institute Of Biosciences And Bioresources; ItaliaFil: Boubeta, Fernando Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: di Prisco, Guido. Institute Of Biosciences And Bioresources; ItaliaFil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Smulevich, Giulietta. Firenze University; ItaliaFil: Viappiani, Christiano. Università di Parma; ItaliaFil: Verde, Cinzia. Institute Of Biosciences And Bioresources; Itali

Adipocyte-derived extracellular vesicles promote breast cancer cell malignancy through HIF-1α activity.

Abstract Extracellular vesicles (EVs) are emerging key protagonists in intercellular communication between adipocytes and breast cancer (BC) cells. Here, we described a new mechanism by which EVs released by mature adipocytes promoted breast cancer cell malignancy "in vitro" and "in vivo". We found that adipocyte-derived EVs enhanced growth, motility and invasion, stem cell-like properties, as well as specific traits of epithelial-to-mesenchymal transition in both estrogen receptor positive and triple negative BC cells. Of note, adipocyte-derived EVs aid breast tumor cells in lung metastatic colonization after tail-vein injection in mice. These EV-mediated effects occur via the induction of HIF-1α activity, since they were abrogated by the use of the HIF-1α inhibitor KC7F2 or in cells silenced for HIF-1α expression. Moreover, using an "ex vivo" model of obese adipocytes we found that the depletion of EVs counteracted the ability of obese adipocytes to sustain pro-invasive phenotype in BC cells. Interestingly, EVs released by undifferentiated adipocytes failed to induce aggressiveness and HIF-1α expression. These findings shed new light on the role of adipocyte-derived EVs in breast cancer progression, suggesting the possibility to target HIF-1α activity to block the harmful adipocyte-tumor cell dialogue, especially in obese settings