Trophic Relationships and Food Supply of Heterotrophic Animals in the Pelagic Ecosystem of the Black Sea

During recent decades, the Black Sea has been affected by many negative factors that strongly changed the condition of its ecosystem. Especially trophic relationships in the Black Sea pelagic system became very vulnerable influencing the food supply, productivity and abundance of many species and populations of this marine basin. Food is one of most important link between biota and its environment. In this monograph, the role and variability of trophodynamic processes that effect the well-being (health) of main heterotrophic components of ecosystem were analysed in detail for a few key species as indicators for estimation of ecosystem condition in whole. These are most significant mass species of the Black Sea pelagic ecosystem. Among copepods this is Calanus euxinus that dominates the mesozooplankton which makes up the fodder base of planktivorous fishes. Among gelatinous these are medusa Aurelia aurita and the alien ctenophores Mnemiopsis leidyi and Beroe ovata which affected strongly mesozooplankton composition. Lastly among fishes the anchovy Engraulis encrasicolus ponticus and sprat Sprattus sprattus phalericus that dominate small pelagic fishery. We considered in this monograph: • Diel feeding behaviour, in situ feeding rate of Calanus euxinus and impact of mesozooplankton on primary production and phytoplankton biomass. • The effect of vertical migrations on energy budget and its components in C. euxinus; metabolic substrates used in catabolic processes under both aerobic and hypoxic conditions, the role of reserve lipids and effect of abiotic factors on individual growth and population structure of this species. • The intensity and efficiency of ingestion and energy transformation in three gelatinous species ( jellyfish Aurelia aurita, ctenophores Mnemiopsis leidyi and Beroe ovata) and their predatory impact on zooplankton community. • Nutritional condition and food supply of anchovy and sprat in the close interaction with natural biotic and abiotic and anthropogenic factors. • Tendencies in this interaction during long time space: since 1960 s till present years. • Estimation of population condition of these species and its long-term change. This monograph is the collective work of Ukrainian and Turkish scientists studying complex hydrobiological problems of the Black Sea. Its aim is to reveal the significance of nutritional factors on the ecology of Black Sea biota, including changes which have already occurred, as well as offering some insight into changes that may happen in the future. Our joint investigations started in the first half of the 1990s, when conditions for the close cooperation of researchers from the two countries were suitable after the collapse of the Soviet era. This spirit continues to the present day. Professor Ümit Unluata, Director of Erdemli Institute of Marine Sciences (Middle East Technical University, Ankara) was of paramount importance in organising and fostering the work undertaken. We would like to devote this monograph to the memory of him, who died so prematurely. We are also grateful to Academician Professor V. N. Eremeev, Director of the Sevastopol Institute of Biology of the Southern Sea (National Academy of Sciences of Ukraine), and to the directors of Erdemli Institute of Marine Sciences (Professor Ilkay Salihoglu, Professor Sukru Besiktepe and Professor Ferit Bingel) who also made significant contributions to the Ukrainian–Turkish collaboration. We are grateful to Dr Bill Parr from the Black Sea Ecosystem Recovery Project for his valuable efforts in improving earlier drafts. All these investigations were carried out within the framework of the following five NATO linkage-grants: • Pelagic animal food supply in the unstable Black Sea environment, • Will the new alien ctenophore Beroe ovata control the plankton community in the Black Sea? • Grazing, growth and production of Calanus euxinus in the Black Sea, • Bioindicators for assessment of Black Sea ecosystem recovery, • Adaptability and vulnerability of marine species in changing environments. And four TUBITAK - NASU joint projects: • Quantification of the recent ctenophore invader Beroe ovata impact in the Black Sea • Monitoring of the Black Sea anchovy and sprat, • Salinity tolerance as a key factor of invasion success of the copepods of Calanus genus into the Sea of Marmara, • Salinity tolerance as a key factor of invasion success of the mesozooplankton species into the Sea of Marmara. We hope that this publication will make a substantial contribution to future studies of the Black Sea ecosystem and offers further understanding of those features regulating biological processes in this unique marine basin

Hyperpolarised 13C MRI: a new horizon for non-invasive diagnosis of aggressive breast cancer

Hyperpolarised 13C MRI (HP-MRI) is a novel imaging technique that allows real-time analysis of metabolic pathways in vivo. 1 The technology to conduct HP-MRI in humans has recently become available and is starting to be clinically applied. As knowledge of molecular biology advances, it is increasingly apparent that cancer cell metabolism is related to disease outcomes, with lactate attracting specific attention. 2 Recent reviews of breast cancer screening programs have raised concerns and increased public awareness of over treatment. The scientific community needs to shift focus from improving cancer detection alone to pursuing novel methods of distinguishing aggressive breast cancers from those which will remain indolent. HP-MRI offers the opportunity to identify aggressive tumour phenotypes and help monitor/predict therapeutic response. Here we report one of the first cases of breast cancer imaged using HP-MRI alongside correlative conventional imaging, including breast MRI

Point Mutations in c-Myc Uncouple Neoplastic Transformation from Multiple Other Phenotypes in Rat Fibroblasts

Deregulation of c-Myc (Myc) occurs in many cancers. In addition to transforming various cell types, Myc also influences additional transformation-associated cellular phenotypes including proliferation, survival, genomic instability, reactive oxygen species production, and metabolism. Although Myc is wild type in most cancers (wtMyc), it occasionally acquires point mutations in certain lymphomas. Some of these mutations confer a survival advantage despite partially attenuating proliferation and transformation. Here, we have evaluated four naturally-occurring or synthetic point mutations of Myc for their ability to affect these phenotypes, as well as to promote genomic instability, to generate reactive oxygen species and to up-regulate aerobic glycolysis and oxidative phosphorylation. Our findings indicate that many of these phenotypes are genetically and functionally independent of one another and are not necessary for transformation. Specifically, the higher rate of glucose metabolism known to be associated with wtMyc deregulation was found to be independent of transformation. One mutation (Q131R) was greatly impaired for nearly all of the studied Myc phenotypes, yet was able to retain some ability to transform. These findings indicate that, while the Myc phenotypes examined here make additive contributions to transformation, none, with the possible exception of increased reliance on extracellular glutamine for survival, are necessary for achieving this state

Cell-Type Independent MYC Target Genes Reveal a Primordial Signature Involved in Biomass Accumulation

The functions of key oncogenic transcription factors independent of context have not been fully delineated despite our richer understanding of the genetic alterations in human cancers. The MYC oncogene, which produces the Myc transcription factor, is frequently altered in human cancer and is a major regulatory hub for many cancers. In this regard, we sought to unravel the primordial signature of Myc function by using high-throughput genomic approaches to identify the cell-type independent core Myc target gene signature. Using a model of human B lymphoma cells bearing inducible MYC, we identified a stringent set of direct Myc target genes via chromatin immunoprecipitation (ChIP), global nuclear run-on assay, and changes in mRNA levels. We also identified direct Myc targets in human embryonic stem cells (ESCs). We further document that a Myc core signature (MCS) set of target genes is shared in mouse and human ESCs as well as in four other human cancer cell types. Remarkably, the expression of the MCS correlates with MYC expression in a cell-type independent manner across 8,129 microarray samples, which include 312 cell and tissue types. Furthermore, the expression of the MCS is elevated in vivo in Eμ-Myc transgenic murine lymphoma cells as compared with premalignant or normal B lymphocytes. Expression of the MCS in human B cell lymphomas, acute leukemia, lung cancers or Ewing sarcomas has the highest correlation with MYC expression. Annotation of this gene signature reveals Myc's primordial function in RNA processing, ribosome biogenesis and biomass accumulation as its key roles in cancer and stem cells

Low catalytic activity is insufficient to induce disease pathology in triosephosphate isomerase (TPI) deficiency

Triosephosphate isomerase (TPI) deficiency is a fatal genetic disorder characterized by hemolytic anemia and neurological dysfunction. Although the enzyme defect in TPI was discovered in the 1960s, the exact etiology of the disease is still debated. Some aspects indicate the disease could be caused by insufficient enzyme activity, whereas other observations indicate it could be a protein misfolding disease with tissue-specific differences in TPI activity. We generated a mouse model in which exchange of a conserved catalytic amino acid residue (isoleucine to valine, Ile170Val) reduces TPI specific activity without affecting the stability of the protein dimer. TPIIle170Val/Ile170Val mice exhibit an approximately 85% reduction in TPI activity consistently across all examined tissues, which is a stronger average, but more consistent, activity decline than observed in patients or symptomatic mouse models that carry structural defect mutant alleles. While monitoring protein expression levels revealed no evidence for protein instability, metabolite quantification indicated that glycolysis is affected by the active site mutation. TPIIle170Val/Ile170Val mice develop normally and show none of the disease symptoms associated with TPI deficiency. Therefore, without the stability defect that affects TPI activity in a tissue-specific manner, a strong decline in TPI catalytic activity is not sufficient to explain the pathological onset of TPI deficiency

Cancer metabolism: current perspectives and future directions

Cellular metabolism influences life and death decisions. An emerging theme in cancer biology is that metabolic regulation is intricately linked to cancer progression. In part, this is due to the fact that proliferation is tightly regulated by availability of nutrients. Mitogenic signals promote nutrient uptake and synthesis of DNA, RNA, proteins and lipids. Therefore, it seems straight-forward that oncogenes, that often promote proliferation, also promote metabolic changes. In this review we summarize our current understanding of how ‘metabolic transformation' is linked to oncogenic transformation, and why inhibition of metabolism may prove a cancer′s ‘Achilles' heel'. On one hand, mutation of metabolic enzymes and metabolic stress sensors confers synthetic lethality with inhibitors of metabolism. On the other hand, hyperactivation of oncogenic pathways makes tumors more susceptible to metabolic inhibition. Conversely, an adequate nutrient supply and active metabolism regulates Bcl-2 family proteins and inhibits susceptibility to apoptosis. Here, we provide an overview of the metabolic pathways that represent anti-cancer targets and the cell death pathways engaged by metabolic inhibitors. Additionally, we will detail the similarities between metabolism of cancer cells and metabolism of proliferating cells

Targeting cancer metabolism: a therapeutic window opens

Genetic events in cancer activate signalling pathways that alter cell metabolism. Clinical evidence has linked cell metabolism with cancer outcomes. Together, these observations have raised interest in targeting metabolic enzymes for cancer therapy, but they have also raised concerns that these therapies would have unacceptable effects on normal cells. However, some of the first cancer therapies that were developed target the specific metabolic needs of cancer cells and remain effective agents in the clinic today. Research into how changes in cell metabolism promote tumour growth has accelerated in recent years. This has refocused efforts to target metabolic dependencies of cancer cells as a selective anticancer strategy.Burroughs Wellcome FundSmith Family FoundationStarr Cancer ConsortiumDamon Runyon Cancer Research FoundationNational Institutes of Health (U.S.