TUNDA ISLAND AS A TOURIST ATTRACTION IN TIRTAYASA DISTRICT, SERANG REGENCY

 The lack of research related to the potential for tourist attraction of Tunda Island from natural, artificial, cultural, and various other aspects based on existing conditions, is the urgency of this research. Tourist visits that are still fluctuating require special attention from the Serang Regency Government to optimize development. Therefore, this study's purpose is to identify the existing conditions and tourism potential of Tunda Island. Thus it can become a guideline for decision-making related to the tourism development in Tunda Island in the future. This research used qualitative research methods with a case study design. By purposive sampling, informants who are the community and tourism managers of Tunda Island were selected for in-depth interviews. The proportion of the results of this study was also more inclined to the field observations to achieve the research objectives. Secondary data came from literature studies related to previous research and also document studies from data to Tunda Island. The results showed that the potential of Tunda Island as a tourist attraction has the opportunity or the potential for natural or marine tourism. However, the potential cultural tourism attractions, both tangible and intangible, also need to be packaged and raised as a tourist attraction based on local potential. Also found in the potential for an artificial tourist attraction that can support tourism on Tunda Island. In the end, the results of this study expected to become input for the Serang Regency Government and other stakeholders to develop tourism activities that are relevant and able to integrate cultural, natural, and artificial tourism attractions.   &nbsp

Performance of BOADICEA and BRCAPRO genetic models and of empirical criteria based on cancer family history for predicting BRCA mutation carrier probabilities: A retrospective study in a sample of Italian cancer genetics clinics

Abstract Purpose To evaluate in current practice the performance of BOADICEA and BRCAPRO risk models and empirical criteria based on cancer family history for the selection of individuals for BRCA genetic testing. Patients and methods The probability of BRCA mutation according to the three tools was retrospectively estimated in 918 index cases consecutively undergone BRCA testing at 15 Italian cancer genetics clinics between 2006 and 2008. Results 179 of 918 cases (19.5%) carried BRCA mutations. With the strict use of the criteria based on cancer family history 173 BRCA (21.9%) mutations would have been detected in 789 individuals. At the commonly used 10% threshold of BRCA mutation carrier probability, the genetic models showed a similar performance [PPV (38% and 37%), sensitivity (76% and 77%) and specificity (70% and 69%)]. Their strict use would have avoided around 60% of the tests but would have missed approximately 1 every 4 carriers. Conclusion Our data highlight the complexity of BRCA testing referral in routine practice and question the strict use of genetic models for BRCA risk assessment

Prognostic significance of germline BRCA mutations in patients with HER2-POSITIVE breast cancer.

Background: HER2-positive breast cancers are rare amongst BRCA mutation carriers. No data exist regarding clinicopathological characteristics and prognosis of this subgroup of patients. Materials and methods: Using a retrospective matched cohort design, we collected data from 700 women who were diagnosed with operable invasive breast cancer from January 2006 to December 2016 and were screened for germline BRCA mutations. Clinicopathological features and survival rates were analyzed by BRCA and HER2 status. Results: One hundred and fifteen HER2-positive/BRCA mutated cases were evaluated in comparison to the three control groups: HER2-positive/BRCA wild type (n = 129), HER2-negative/BRCA mutated (n = 222), HER2-negative/BRCA wild type (n = 234). HER2-positive breast cancers were more likely to have high histologic grade and high proliferation rate than HER2-negative neoplasms, regardless of BRCA mutation status. An interaction between BRCA mutations and HER2-positive status was found to correlate with worse survival after adjusting for prognostic variables (HR = 3.4; 95% CI: 1.3-16.7). Conclusions: Co-occurrence of BRCA mutations and HER2-positive status is a poor prognostic factor in patients with early or locally advanced breast cancer. This finding may be a proof of concept that a combined pharmacological intervention directed to these targets could be synergistic

Combining PARP Inhibition with Platinum, Ruthenium or Gold Complexes for Cancer Therapy

Platinum drugs are heavily used first-line chemotherapeutic agents for many solid tumours and have stimulated substantial interest in the biological activity of DNA-binding metal complexes. These complexes generate DNA lesions which trigger the activation of DNA damage response (DDR) pathways that are essential to maintain genomic integrity. Cancer cells exploit this intrinsic DNA repair network to counteract many types of chemotherapies. Now, advances in the molecular biology of cancer has paved the way for the combination of DDR inhibitors such as poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) and agents that induce high levels of DNA replication stress or single-strand break damage for synergistic cancer cell killing. In this review, we summarise early-stage, preclinical and clinical findings exploring platinum and emerging ruthenium anti-cancer complexes alongside PARPi in combination therapy for cancer and also describe emerging work on the ability of ruthenium and gold complexes to directly inhibit PARP activity

U-Pb zircon dating of ash fall deposits from the paleozoic paran? basin of Brazil and Uruguay: A reevaluation of the stratigraphic correlations

Ash fall layers and vitroclastic-carrying sediments distributed throughout the entire Permian stratigraphic range of the Paraná Basin (Brazil and Uruguay) occur in the Tubarão Supergroup (Rio Bonito Formation) and the Passa Dois Group (Irati, Estrada Nova/Teresina, Corumbataí, and Rio do Rasto Formations), which constitute the Gondwana 1 Supersequence. U-Pb zircon ages, acquired by SHRIMP and isotope-dissolution thermal ionization mass spectrometer (IDTIMS) from tuffs within the Mangrullo and Yaguari Formations of Uruguay, are compatible with a correlation with the Irati and parts of the Teresina and Rio do Rasto Formations, respectively, of Brazil. U-Pb zircon ages suggest maximum depositional ages for the samples: (1) Rio Bonito Formation: ages ranging from 295:8 5 3:1 to 304:0 5 5:6 Ma (Asselian, lowermost Permian), consistent with the age range of the Protohaploxypinus goraiensis subzone; (2) Irati Formation: ages ranging from 279:9 5 4:8 to 280:0 5 3:0 Ma (Artinskian, middle Permian), consistent with the occurrence of species of the Lueckisporites virkkiae zone; (3) Rio do Rasto Formation: ages ranging from 266:7 5 5:4 to 274:6 5 6:3Ma (Wordian to Roadian, middle Permian). All the SHRIMP U-Pb zircon ages are consistent with their superimposition order in the stratigraphy, the latest revisions to the Permian timescale (International Commission of Stratigraphy, 2018 version), and the most recent appraisals of biostratigraphic data. The ID-TIMS U-Pb zircon ages from the Corumbataí Formation suggest that U-Pb ages may be 110% younger than interpreted biostratigraphic ages

Ediacaran Corumbella has a cataphract calcareous skeleton with controlled biomineralization

Corumbella is a terminal Ediacaran tubular, benthic fossil of debated morphology, composition, and biological affinity. Here, we show that Corumbella had a biomineralized skeleton, with a bilayered construction of imbricated calcareous plates and rings (sclerites) yielding a cataphract organization, that enhanced flexibility. Each sclerite likely possessed a laminar microfabric with consistent crystallographic orientation, within an organic matrix. Original aragonitic mineralogy is supported by relict aragonite and elevated Sr (mean = ca. 11,800 ppm in central parts of sclerites). In sum, the presence of a polarisation axis, sclerites with a laminar microfabric, and a cataphract skeletal organization reminiscent of early Cambrian taxa, are all consistent with, but not necessarily indicative of, a bilaterian affinity. A cataphract skeleton with an inferred complex microstructure confirms the presence of controlled biomineralization in metazoans by the terminal Ediacaran, and offers insights into the evolution of development and ecology at the root of the ‘Cambrian radiation’

Molecular biomineralization of octocoral skeletons: calcite versus aragonite

Aragonite and calcite represent the two most common polymorphs of calcium carbonate (CaCO3) formed biogenically by organisms. The mechanisms that allow animals to selectively deposit aragonite and/or calcite has been extensively studied in molluscs, but information on corals (class Anthozoa, phylum Cnidaria) is lacking. Contrary to scleractinian corals, exclusively producing aragonite skeletons, members of the coral subclass Octocorallia exhibit both calcitic and aragonitic skeletal structures. They thus represent an interesting target to study biological and environmental control over CaCO3 polymorphs in corals. In this project we selected different octocoral species - characterized by aragonite or calcite skeletons - to investigate the evolution and mechanisms underlying aragonite and calcite biomineralization in corals. Main objectives of this study were 1) the characterization of the molecular machinery employed to deposit the two different CaCO3 polymorphs, and 2) study the effects of seawater chemistry on skeleton mineralogy and gene expression. In the introductory section (Chapter 1) relevant concepts, terminology and background information is provided. Chapter 2 and 3 aimed at filling the gap in terms of availability of -omic resources for octocorals compared to scleractinians. New resources generated as part of the project include reference transcriptomes and skeletal proteomes for four octocoral species with different biomineralization strategies. The transcriptomic analysis presented in Chapter 2 provides a taxonomically comprehensive presence map for homologs of coral calcification genes across early-branching metazoans. By sensibly increasing taxonomic sampling, we expanded the distribution for several genes and reported homologs presence in previously unsurveyed groups. Homologs datasets were used for phylogenetic inferences, which provided insight into the evolution of acidic proteins and allowed to propose an alternative evolutionary scenario for the scleractinian protein galaxin senso stricto. In Chapter 3 several new proteins with putative functions in octocoral biomineralization are described. A comparative characterization of skeleton proteomes in Octocorallia and Scleractinia is also provided. This analysis highlighted an extremely low overlap in terms of proteins presence between aragonite and calcite-forming species, while at the same time identifying a small set of proteins that constitute the core proteome of octocoral sclerites. Instances of similarity between scleractinians and octocorals are also listed, and include galaxin-related proteins, carbonic anhydrases and multicopper oxidases. Finally, as in scleractinians, some octocoral skeletogenic proteins appear to have acquired their role in calcification as the result of secondary co-option and following the enrichment - within the sequence - of acidic residues. Chapter 4 and 5 focused on the interaction between environmental conditions and calcification in octocorals and scleractinians. Chapter 4 revolves around the effect of the magnesium-calcium molar ratio (mMg:mCa) and its effects on the skeleton polymorph. Exposure to calcite-inducing mMg:mCa did not cause a polymorph switch in H. coerulea, while calcite was incorporated in the skeleton of M. digitata. We did not observe changes in expression for skeletogenic proteins, with the exception of one gene coding for the uncharacterized skeleton organic matrix protein 5 (in M. digitata) and endothelin converting enzyme 1 (in H. coerulea). However, carbonic anhydrases and different calcium transporters and channels were affected, suggesting a potential response to changes in mMg:mCa centered around ions transport, rather than a direct involvement of the organic matrix. In Chapter 5, we exposed the octocoral Pinnigrogia flava to sublethal seawater temperature and lower pH (~7.3). We showed how the calcification process in this octocoral is decoupled from the response to stress. Increasing water temperature triggered a stress response but did not affect calcification, while acidification downregulated the expression of several calcification-related genes without causing stress. This represents a mechanistic explanation for the higher tolerance to anthropic stressors exhibited by octocorals. Finally in Chapter 6, an optimized protocol for 16S sequencing in bacteria, using the Illumina MiniSeq available at the Chair for Geobiology & Paleontology of the Department of Earth- and Environmental Sciences at Ludwig-Maximilians-Universität München in Munich (Germany), is presented. This protocol allowed to characterize bacterial communities from different sources, including aquarium seawater, and could thus represent a valuable tool to perform microbiome characterizations from marine organisms in the future. This dissertation contributes to our understanding of the mechanisms underlying the formation of aragonite and calcite skeletons in corals. It includes the first characterizations of octocoral skeleton proteomes, and led to the identification of several - previously unknown - genes with putative calcification-related functions. These novel targets represent a valuable groundwork for further studies, including functional investigations aiming at elucidating the exact mechanisms behind coral biomineralization. It also shed new light on the calcification responses triggered by predicted past and future environmental conditions, providing a better understanding on how corals reacted to changes during their evolutionary history, and their ability to cope with future ones

Molecular biomineralization of octocoral skeletons: calcite versus aragonite

Aragonite and calcite represent the two most common polymorphs of calcium carbonate (CaCO3) formed biogenically by organisms. The mechanisms that allow animals to selectively deposit aragonite and/or calcite has been extensively studied in molluscs, but information on corals (class Anthozoa, phylum Cnidaria) is lacking. Contrary to scleractinian corals, exclusively producing aragonite skeletons, members of the coral subclass Octocorallia exhibit both calcitic and aragonitic skeletal structures. They thus represent an interesting target to study biological and environmental control over CaCO3 polymorphs in corals. In this project we selected different octocoral species - characterized by aragonite or calcite skeletons - to investigate the evolution and mechanisms underlying aragonite and calcite biomineralization in corals. Main objectives of this study were 1) the characterization of the molecular machinery employed to deposit the two different CaCO3 polymorphs, and 2) study the effects of seawater chemistry on skeleton mineralogy and gene expression. In the introductory section (Chapter 1) relevant concepts, terminology and background information is provided. Chapter 2 and 3 aimed at filling the gap in terms of availability of -omic resources for octocorals compared to scleractinians. New resources generated as part of the project include reference transcriptomes and skeletal proteomes for four octocoral species with different biomineralization strategies. The transcriptomic analysis presented in Chapter 2 provides a taxonomically comprehensive presence map for homologs of coral calcification genes across early-branching metazoans. By sensibly increasing taxonomic sampling, we expanded the distribution for several genes and reported homologs presence in previously unsurveyed groups. Homologs datasets were used for phylogenetic inferences, which provided insight into the evolution of acidic proteins and allowed to propose an alternative evolutionary scenario for the scleractinian protein galaxin senso stricto. In Chapter 3 several new proteins with putative functions in octocoral biomineralization are described. A comparative characterization of skeleton proteomes in Octocorallia and Scleractinia is also provided. This analysis highlighted an extremely low overlap in terms of proteins presence between aragonite and calcite-forming species, while at the same time identifying a small set of proteins that constitute the core proteome of octocoral sclerites. Instances of similarity between scleractinians and octocorals are also listed, and include galaxin-related proteins, carbonic anhydrases and multicopper oxidases. Finally, as in scleractinians, some octocoral skeletogenic proteins appear to have acquired their role in calcification as the result of secondary co-option and following the enrichment - within the sequence - of acidic residues. Chapter 4 and 5 focused on the interaction between environmental conditions and calcification in octocorals and scleractinians. Chapter 4 revolves around the effect of the magnesium-calcium molar ratio (mMg:mCa) and its effects on the skeleton polymorph. Exposure to calcite-inducing mMg:mCa did not cause a polymorph switch in H. coerulea, while calcite was incorporated in the skeleton of M. digitata. We did not observe changes in expression for skeletogenic proteins, with the exception of one gene coding for the uncharacterized skeleton organic matrix protein 5 (in M. digitata) and endothelin converting enzyme 1 (in H. coerulea). However, carbonic anhydrases and different calcium transporters and channels were affected, suggesting a potential response to changes in mMg:mCa centered around ions transport, rather than a direct involvement of the organic matrix. In Chapter 5, we exposed the octocoral Pinnigrogia flava to sublethal seawater temperature and lower pH (~7.3). We showed how the calcification process in this octocoral is decoupled from the response to stress. Increasing water temperature triggered a stress response but did not affect calcification, while acidification downregulated the expression of several calcification-related genes without causing stress. This represents a mechanistic explanation for the higher tolerance to anthropic stressors exhibited by octocorals. Finally in Chapter 6, an optimized protocol for 16S sequencing in bacteria, using the Illumina MiniSeq available at the Chair for Geobiology & Paleontology of the Department of Earth- and Environmental Sciences at Ludwig-Maximilians-Universität München in Munich (Germany), is presented. This protocol allowed to characterize bacterial communities from different sources, including aquarium seawater, and could thus represent a valuable tool to perform microbiome characterizations from marine organisms in the future. This dissertation contributes to our understanding of the mechanisms underlying the formation of aragonite and calcite skeletons in corals. It includes the first characterizations of octocoral skeleton proteomes, and led to the identification of several - previously unknown - genes with putative calcification-related functions. These novel targets represent a valuable groundwork for further studies, including functional investigations aiming at elucidating the exact mechanisms behind coral biomineralization. It also shed new light on the calcification responses triggered by predicted past and future environmental conditions, providing a better understanding on how corals reacted to changes during their evolutionary history, and their ability to cope with future ones

Celebrating 120 Years of Butantan Institute Contributions for Toxinology

This is collection of original and review articles selected in recognition of the contribution of Instituto Butantan to the field of toxinology and its continued and relevant role in this field in the 120 years since its foundation. Congratulations to the Butantan Institute, its house scientists, and collaborators on its 120th anniversary