Stoichiometry of aerobic mineralization (O/C) of aquatic macrophytes leachate from a tropical lagoon (São Paulo –Brazil)

The temporal variation of stoichiometry between consumed oxygen and oxidized carbon was investigated for the aerobic mineralization of leachates from aquatic macrophytes. Seven species of aquatic plants, viz. Cabomba piauhyensis, Cyperus giganteus, Egeria najas, Eichhornia azurea, Salvinia auriculata, Scirpus cubensisand Utricularia breviscapa, were collected from Òleo lagoon located in the floodplain of Mogi-Guacu river (São Paulo State, Brazil). After being collected, the plants were washed, oven-dried and triturated. In order to obtain the leachate, the fragments were submitted to an aqueous extraction (cold). Mineralization chambers were incubated at 20 °C containing leachates dissolved in water samples from Òleo lagoon to a final concentration of ca. 200 mg l^–1on carbon basis. The chambers were maintained under aerobic conditions; the concentrations of the organic carbon (particulate and dissolved) and the dissolved oxygen were measured during approximately 80 days. Elemental analysis of the detritus and the concentrations of the remaining material (DOC and POC) were used to determine the amounts of mineralized organic carbon. The data were analyzed with first-order kinetics models, from which the daily rates of consumption (carbon and oxygen) and the stoichiometry (O/C) were determined. In the early phase of mineralization the O/C rates increased before reaching a maximum, after which they tended to decrease. For the mineralization of leachates from C. giganteus, S. auriculata and U. breviscapa, the decrease was relatively slow. For all substrata the initial values were smaller than 1, and ranged from 0.42 (S. cubensis) to 0.81 (C. piauhyensis). The maximum values were within the range from 0.58 (U. breviscapa) to 23.1 (E. najas) and at their highest 26th (C. piauhyensis) and 106th (C. giganteus) days. These variations are believed to be associated with the chemical composition of the leachates, with their transformations and alterations of metabolic pathways involved in the mineralization.     

Incidence,prevalence, mortality,disability-adjusted life years and risk factors of cancer in Australia and comparison with OECD countries, 1990–2015: findings from the Global Burden of Disease Study 2015

BackgroundComparative evidence on the burden, trend, and risk factors of cancer is limited. Using data from the Global Burden of Disease (GBD) study, we aimed to assess cancer burden – incidence, prevalence, mortality, disability-adjusted life years (DALYs) – and attributable risk factors for Australia between 1990 and 2015, and to compare them with those of 34 members of the Organisation for Economic Co-operation and Development (OECD).MethodsThe general GBD cancer estimation methods were used with data input from vital registration systems and cancer registries. A comparative risk assessment approach was used to estimate the population-attributable fractions due to risk factors.ResultsIn 2015 there were 198,880 (95% uncertainty interval [UI]: 183,908–217,365) estimated incident cancer cases and 47,562 (95% UI: 46,061–49,004) cancer deaths in Australia. Twenty-nine percent (95% UI: 28.2–29.8) of total deaths and 17.0% (95% UI: 15.0–19.1) of DALYs were caused by cancer in Australia in 2015. Cancers of the trachea, bronchus and lung, colon and rectum, and prostate were the most common causes of cancer deaths. Thirty-six percent (95% UI: 33.1–37.9) of all cancer deaths were attributable to behavioral risks. The age-standardized cancer incidence rate (ASIR) increased between 1990 and 2015, while the age-standardized cancer death rate (ASDR) decreased over the same period. In 2015, compared to 34 other OECD countries Australia ranked first (highest) and 24^th based on ASIR and ASDR, respectively.ConclusionThe incidence of cancer has increased over 25 years, and behavioral risks are responsible for a large proportion of cancer deaths. Scaling up of prevention (using strategies targeting cancer risk factors), early detection, and treatment of cancer is required to effectively address this growing health challenge.     

Natural product pectolinarigenin exhibits potent anti-metastatic activity in colorectal carcinoma cells in vitro and in vivo

Colorectal carcinoma (CRC) is one of the most common cancers with high metastatic potential, explaining why identifying new drug candidates that inhibit tumour metastasis is an urgent need. The aim of this study was to evaluate the biological activities of pectolinarigenin (PEC, a natural flavonoid present in Cirsium chanroenicum) in CRC in vitro and in vivo and to determine its underlying mechanism of action. Here, we observed that treatment with PEC could inhibit cell viability and induce apoptosis in cancer cells in a concentration- and time-dependent manner. The occurrence of apoptosis was associated with activation of caspase-3 and Bax and decreased expression of Bcl-2. In addition, PEC markedly impaired CRC cell migration and invasion by downregulating the expression of matrix metalloproteinase (MMP-9) and phosphorylated-Stat3^Tyr705. Moreover, our studies showed that PEC inhibited abdominal metastasis models of murine colorectal cancer. In addition, histological and immunohistochemical analyses revealed a decrease in Ki67-positive cells, MMP9-positive cells and p-Stat3^Tyr705 cells upon treatment with PEC compared to control samples. Furthermore, PEC reduced the number of myeloid-derived suppressor cells (MDSCs) in the blood and tumours, which was accompanied by the increased infiltration of CD8⁺T cells in the blood. Taken together, our findings suggested that PEC could be used as a natural drug to inhibit CRC metastasis.     

The application of strand invasion phenomenon,directed by peptide nucleic acid (PNA) and single‐stranded DNA binding protein (SSB) for the recognition of specific sequences of human endogenous retroviral HERV‐W family

The HERV‐W family of human endogenous retroviruses represents a group of numerous sequences that show close similarity in genetic composition. It has been documented that some members of HERV‐W–derived expression products are supposed to play significant role in humans' pathology, such as multiple sclerosis or schizophrenia. Other members of the family are necessary to orchestrate physiological processes (eg, ERVWE1 coding syncytin‐1 that is engaged in syncytiotrophoblast formation). Therefore, an assay that would allow the recognition of particular form of HERV‐W members is highly desirable. A peptide nucleic acid (PNA)–mediated technique for the discrimination between multiple sclerosis‐associated retrovirus and ERVWE1 sequence has been developed. The assay uses a PNA probe that, being fully complementary to the ERVWE1 but not to multiple sclerosis‐associated retrovirus (MSRV) template, shows high selective potential. Single‐stranded DNA binding protein facilitates the PNA‐mediated, sequence‐specific formation of strand invasion complex and, consequently, local DNA unwinding. The target DNA may be then excluded from further analysis in any downstream process such as single‐stranded DNA‐specific exonuclease action. Finally, the reaction conditions have been optimized, and several PNA probes that are targeted toward distinct loci along whole HERV‐W env sequences have been evaluated. We believe that PNA/single‐stranded DNA binding protein–based application has the potential to selectively discriminate particular HERV‐W molecules as they are at least suspected to play pathogenic role in a broad range of medical conditions, from psycho‐neurologic disorders (multiple sclerosis and schizophrenia) and cancers (breast cancer) to that of an auto‐immunologic background (psoriasis and lupus erythematosus).     

Focus: A Multifaceted Battle Against Cancer: Extracting Knowledge from Chemical Imaging Data Using Computational Algorithms for Digital Cancer Diagnosis

Fourier transform infrared (FTIR) spectroscopic imaging is an emerging microscopy modality for clinical histopathologic diagnoses as well as for biomedical research. Spectral data recorded in this modality are indicative of the underlying, spatially resolved biochemical composition but need computerized algorithms to digitally recognize and transform this information to a diagnostic tool to identify cancer or other physiologic conditions. Statistical pattern recognition forms the backbone of these recognition protocols and can be used for highly accurate results. Aided by biochemical correlations with normal and diseased states and the power of modern computer-aided pattern recognition, this approach is capable of combating many standing questions of traditional histology-based diagnosis models. For example, a simple diagnostic test can be developed to determine cell types in tissue. As a more advanced application, IR spectral data can be integrated with patient information to predict risk of cancer, providing a potential road to precision medicine and personalized care in cancer treatment. The IR imaging approach can be implemented to complement conventional diagnoses, as the samples remain unperturbed and are not destroyed. Despite high potential and utility of this approach, clinical implementation has not yet been achieved due to practical hurdles like speed of data acquisition and lack of optimized computational procedures for extracting clinically actionable information rapidly. The latter problem has been addressed by developing highly efficient ways to process IR imaging data but remains one that has considerable scope for progress. Here, we summarize the major issues and provide practical considerations in implementing a modified Bayesian classification protocol for digital molecular pathology. We hope to familiarize readers with analysis methods in IR imaging data and enable researchers to develop methods that can lead to the use of this promising technique for digital diagnosis of cancer.     

The Functional Repertoire of Survivin's Tails

Survivin is a multitasking protein that can inhibit cell death and that is essential for mitosis. Due to these prosurvival activities and the correlation of its expression with tumor resistance to conventional cancer treatments, survivin has received much attention as a potential oncotherapeutic target. Nevertheless, many questions regarding its exact role at the molecular level remain to be elucidated. In this study we ask whether the extreme C- and NH₂ termini of survivin are required for it to carry out its cytoprotective and mitotic duties. When assayed for their ability to act as a cytoprotectant, both survivin_1–120 and survivin_11–142 were able to protect cells against TRAIL-mediated apoptosis, but when challenged with irradiation cells expressing survivin_11–142 had no survival advantage. During mitosis, however, removing the NH₂ terminal 10 amino acids (survivin_11–142) had no apparent effect but truncating 22 amino acids from the C-terminus (survivin_1–120) prevented survivin from transferring to the midzone microtubules during anaphase. Collectively the data herein presented suggest that the C-terminus is required for cell division, and that the NH₂ terminus is dispensable for apoptosis and mitosis but required for protection from irradiation.     

Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer

The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular FAs and their de novo synthesis. Given that oxidation of de novo synthesized FAs for energy would result in net-energy loss, there is an implication that FAs from these two sources must have distinct metabolic fates; however, hitherto, all FAs have been considered part of a common pool. To probe potential metabolic partitioning of cellular FAs, cancer cells were supplemented with stable isotope-labeled FAs. Structural analysis of the resulting glycerophospholipids revealed that labeled FAs from uptake were largely incorporated to canonical (sn-) positions on the glycerol backbone. Surprisingly, labeled FA uptake also disrupted canonical isomer patterns of the unlabeled lipidome and induced repartitioning of n-3 and n-6 PUFAs into glycerophospholipid classes. These structural changes support the existence of differences in the metabolic fates of FAs derived from uptake or de novo sources and demonstrate unique signaling and remodeling behaviors usually hidden from conventional lipidomics.