Integrating larval connectivity into the marine conservation decision-making process across spatial scales.

Larval dispersal connectivity is typically integrated into spatial conservation decisions at regional or national scales, but implementing agencies struggle with translating these methods to local scales. We used larval dispersal connectivity at regional (hundreds of kilometers) and local (tens of kilometers) scales to aid in design of networks of no-take reserves in Southeast Sulawesi, Indonesia. We used Marxan with Connectivity informed by biophysical larval dispersal models and remotely sensed coral reef habitat data to design marine reserve networks for 4 commercially important reef species across the region. We complemented regional spatial prioritization with decision trees that combined network-based connectivity metrics and habitat quality to design reserve boundaries locally. Decision trees were used in consensus-based workshops with stakeholders to qualitatively assess site desirability, and Marxan was used to identify areas for subsequent network expansion. Priority areas for protection and expected benefits differed among species, with little overlap in reserve network solutions. Because reef quality varied considerably across reefs, we suggest reef degradation must inform the interpretation of larval dispersal patterns and the conservation benefits achievable from protecting reefs. Our methods can be readily applied by conservation practitioners, in this region and elsewhere, to integrate connectivity data across multiple spatial scales.

Integración de la conectividad larval al proceso de toma de decisiones en la conservación marina en escalas espaciales Resumen Comúnmente se integra la conectividad de la dispersión larval a las decisiones de conservación espacial a escalas regionales o nacionales, pero las agencias de implementación luchan con la transferencia de estos métodos a las escalas locales. Usamos la conectividad de la dispersión larval a escalas regionales (cientos de kilómetros) y locales (decenas de kilómetros) para ayudar en el diseño de redes de reservas con protección total en Sulawesi Sudoriental, Indonesia. Usamos Marxan con la conectividad guiada por los modelos biofísicos de dispersión larval y detectamos a distancia los datos de hábitat de los arrecifes de coral para diseñar redes de reservas marinas para cuatro especies de importancia comercial en la región. Complementamos la priorización espacial regional con árboles de decisión que combinaron medidas de conectividad basadas en las redes y la calidad del hábitat para diseñar localmente los límites de la reserva. Usamos los árboles de decisión con los actores en talleres basados en el consenso para evaluar cualitativamente la conveniencia del sitio. También usamos Marxan para identificar áreas para la expansión subsecuente de la red. Las áreas prioritarias para la protección y los beneficios esperados difirieron entre especies, con un traslape reducido en las soluciones de la red de reservas. Ya que la calidad del arrecife varió considerablemente entre los arrecifes, sugerimos que la degradación de estos debe orientar la interpretación de los patrones de dispersión larval y los beneficios de conservación alcanzables con la protección de los arrecifes. Los practicantes de la conservación pueden aplicar nuestros métodos inmediatamente, en esta región o en cualquier otra, para integrar los datos de conectividad en varias escalas espaciales.

A Comparative Study of the Effects of Platinum (II) Complexes on ß-Amyloid Aggregation: Potential Neurodrug Applications.

Herein the effects of three platinum complexes, namely (SP-4-2)-(2,2'-bipyridine)dichloridoplatinum(II), Pt-bpy, (SP-4-2)-dichlorido(1,10-phenanthroline) platinum(II), Pt-phen, and (SP-4-2)-chlorido(2,2':6',2''-terpyridine)platinum(II) chloride, Pt-terpy, on the aggregation of an amyloid model system derived from the C-terminal domain of Aß peptide (Aß21-40) were investigated. Thioflavin T (ThT) binding assays revealed the ability of Pt(II) compounds to repress amyloid aggregation in a dose-dependent way, whereas the ability of Aß21-40 peptide to interfere with ligand field of metal complexes was analyzed through UV-Vis absorption spectroscopy and electrospray ionization mass spectrometry. Spectroscopic data provided micromolar EC50 values and allowed to assess that the observed inhibition of amyloid aggregation is due to the formation of adducts between Aß21-40 peptide and complexes upon the release of labile ligands as chloride and that they can explore different modes of coordination toward Aß21-40 with respect to the entire Aß1-40 polypeptide. In addition, conformational studies through circular dichroism (CD) spectroscopy suggested that Pt-terpy induces soluble ß-structures of monomeric Aß21-40, thus limiting self-recognition. Noticeably, Pt-terpy demonstrated the ability to reduce the cytotoxicity of amyloid peptide in human SH-SY5Y neuroblastoma cells. Presented data corroborate the hypothesis to enlarge the application field of already known metal-based agents to neurodegenerative diseases, as potential neurodrugs.

Multi-Year Monitoring of the Toxicological Risk of Heavy Metals Related to Fish Consumption by the Population of the Kendari Region (Southeast Sulawesi, Indonesia).

This study measured the concentrations of Hg, As, Ni, Cd, and Pb in six fish species commonly consumed in Kendari. Samples were bought within local markets from 2012 to 2017 at the end of the dry season. Results showed that mercury concentrations fluctuated between years and within species, except in the Caranx sexfasciatus, which showed no significant differences (Kruskall-Wallis, p-value > 0.05, df = 5) and an average concentration of 0.371 ± 0.162 µg g-1 DW. Arsenic was found in high concentrations across species and years and varied widely in C. sexfasciatus, the lowest value being 0.32 ± 0.01 µg g-1 DW in 2012 and the highest was 5.63 ± 1.89 µg g-1 DW in 2017. The highest nickel concentrations were found in 2016 across four of the six species. The fish samples displayed very low cadmium and lead concentrations throughout the study. In addition, the potential human health risk due to fish consumption was assessed. This showed that mercury is the only one of the five metals present in concentrations high enough to individually pose a potential hazard, the only metal likely to be accumulated beyond a safe concentration in Kendari. Chanos chanos never posed a toxicological risk based on the results of this research.

Characterization of a MLIC Detector for QA in Scanned Proton and Carbon Ion Beams.

PURPOSE: Beam energy validation is a fundamental aspect of the routine quality assurance (QA) protocol of a particle therapy facility. A multilayer ionization chamber (MLIC) detector provides the optimal tradeoff between achieving accuracy in particle range determination and saving operational time in measurements and analysis procedures. We propose the characterization of a commercial MLIC as a suitable QA tool for a clinical environment with proton and carbon-ion scanning beams. MATERIALS AND METHODS: Commercial MLIC Giraffe (IBA Dosimetry, Schwarzenbruck, Germany) was primarily evaluated in terms of short-term and long-term stability, linearity with dose, and dose-rate independence. Accuracy was tested by analyzing range of integrated depth-dose curves for a set of representative energies against reference acquisitions in water for proton and carbon ion beams; in addition, 2 modulated proton spread-out Bragg peaks were also measured. Possible methods to increase the native spatial resolution of the detector were also investigated. RESULTS: Measurements showed a high repeatability: mean relative standard deviation was within 0.5% for all channels and both particle types. The long-term stability of the gain calibration showed discrepancies less than 1% at different times. The detector response was linear with dose (R 2 > 0.99) and independent on the dose rate. Measurements of integrated depth-dose curve ranges revealed a mean deviation from reference measurements in water of 0.1 ± 0.3 mm for protons with a maximum difference of 0.4 mm and 0.2 ± 0.6 mm with maximum difference of 0.85 mm for carbon ion beams. For the 2 modulated proton spread-out Bragg peaks, measured differences in distal dose falloff were ≤0.5 mm against calculated values. CONCLUSIONS: The detector is stable, linearly responding with dose, precise, and easy to handle for QA beam energy checks of proton and carbon ion beams.

Molecular signaling involving intrinsically disordered proteins in prostate cancer.

Investigations on cellular protein interaction networks (PINs) reveal that proteins that constitute hubs in a PIN are notably enriched in Intrinsically Disordered Proteins (IDPs) compared to proteins that constitute edges, highlighting the role of IDPs in signaling pathways. Most IDPs rapidly undergo disorder-to-order transitions upon binding to their biological targets to perform their function. Conformational dynamics enables IDPs to be versatile and to interact with a broad range of interactors under normal physiological conditions where their expression is tightly modulated. IDPs are involved in many cellular processes such as cellular signaling, transcriptional regulation, and splicing; thus, their high-specificity/low-affinity interactions play crucial roles in many human diseases including cancer. Prostate cancer (PCa) is one of the leading causes of cancer-related mortality in men worldwide. Therefore, identifying molecular mechanisms of the oncogenic signaling pathways that are involved in prostate carcinogenesis is crucial. In this review, we focus on the aspects of cellular pathways leading to PCa in which IDPs exert a primary role.