Geochemistry of acid mine drainage from a coal mining area and processes controlling metal attenuation in stream waters, southern Brazil

Acid drainage influence on the water and sediment quality was investigated in a coal mining area (southern Brazil). Mine drainage showed pH between 3.2 and 4.6 and elevated concentrations of sulfate, As and metals, of which, Fe, Mn and Zn exceeded the limits for the emission of effluents stated in the Brazilian legislation. Arsenic also exceeded the limit, but only slightly. Groundwater monitoring wells from active mines and tailings piles showed pH interval and chemical concentrations similar to those of mine drainage. However, the river and ground water samples of municipal public water supplies revealed a pH range from 7.2 to 7.5 and low chemical concentrations, although Cd concentration slightly exceeded the limit adopted by Brazilian legislation for groundwater. In general, surface waters showed large pH range (6 to 10.8), and changes caused by acid drainage in the chemical composition of these waters were not very significant. Locally, acid drainage seemed to have dissolved carbonate rocks present in the local stratigraphic sequence, attenuating the dispersion of metals and As. Stream sediments presented anomalies of these elements, which were strongly dependent on the proximity of tailings piles and abandoned mines. We found that precipitation processes in sediments and the dilution of dissolved phases were responsible for the attenuation of the concentrations of the metals and As in the acid drainage and river water mixing zone. In general, a larger influence of mining activities on the chemical composition of the surface waters and sediments was observed when enrichment factors in relation to regional background levels were used.Influência de drenagem ácida sobre a qualidade de água e sedimento foi investigada em uma área de mineração de carvão (sul do Brasil). A drenagem ácida mostrou pH entre 3,2 e 4,6 e elevadas concentrações de sulfato, As e metais, dos quais, Fe, Mn e Zn excederam os limites para emissão de efluentes da legislação brasileira. Arsênio também excedeu levemente o limite. Poços de monitoramento de água subterrânea situados em áreas de mina ativa e pilhas de rejeitos revelaram intervalo de pH e concentrações químicas semelhantes aqueles da drenagem ácida. Entretanto, amostras de águas subterrânea e de rio utilizadas para o abastecimento público municipal revelaram pH entre 7,2 e 7,5 e baixas concentrações químicas, embora a concentração de Cd tenha superado um pouco o limite adotado pela legislação brasileira para águas subterrâneas. Em geral, as águas de superfície mostraram grande intervalo de pH (6 a 10,8), e a influência da drenagem ácida em sua composição química não foi muito significativa. Localmente, drenagem ácida parece ter dissolvido rochas carbonáticas presentes na sequência estratigráfica local, atenuando a dispersão de metais e As. Anomalias destes elementos foram encontradas em sedimentos de corrente, e elas foram fortemente dependentes da proximidade de depósitos de rejeitos e minas abandonadas. Neste trabalho, processos de precipitação em sedimentos e diluição de fases dissolvidas foram considerados como os principais mecanismos responsáveis pela atenuação das concentrações de metais e As nas zonas de mistura entre drenagem ácida e água fluvial. Em geral, observou-se uma maior influência das atividades de mineração sobre a composição química de águas superficiais e sedimentos quando fatores de enriquecimento em relação aos níveis de background regionais foram utilizados.53955

Loading stress distribution in posterior teeth restored by different core materials under fixed zirconia partial denture: A 3d-fea study

Purpose: To evaluate the effect of different substrate stiffness [sound dentin (SD), resin composite core (RC) or metal core (MC)] on the stress distribution of a zirconia posterior three-unit fixed partial denture (FPD). Methods: The abutment teeth (first molar and first premolar) were modeled, containing 1.5 mm of axial reduction, and converging axial walls. A static structural analysis was performed using a finite element method and the maximum principal stress criterion to analyze the fixed partial denture (FPD) and the cement layers of both abutment teeth. The materials were considered isotropic, linear, elastic, homogeneous and with bonded contacts. An axial load (300 N) was applied to the occlusal surface of the second premolar. Results: The region of the prosthetic connectors showed the highest tensile stress magnitude in the FPD structure depending on the substrate stiffness with different core materials. The highest stress peak was observed with the use of MC (116.4 MPa) compared to RC and SD. For the cement layer, RC showed the highest values in the molar abutment (14.7 MPa) and the highest values for the premolar abutment (14.4 MPa) compared to SD (14.1 and 13.4 MPa) and MC (13.8 and 13.3 MPa). Both metal core and resin composite core produced adequate stress concentration in the zirconia fixed partial denture during the load incidence. However, more flexible substrates, such as composite cores, can increase the tensile stress magnitude on the cement

BMP‐2 signaling and mechanotransduction synergize to drive osteogenic differentiation via YAP/TAZ

Growth factors and mechanical cues synergistically affect cellular functions, triggering a variety of signaling pathways. The molecular levels of such cooperative interactions are not fully understood. Due to its role in osteogenesis, the growth factor bone morphogenetic protein 2 (BMP‐2) is of tremendous interest for bone regenerative medicine, osteoporosis therapeutics, and beyond. Here, contribution of BMP‐2 signaling and extracellular mechanical cues to the osteogenic commitment of C2C12 cells is investigated. It is revealed that these two distinct pathways are integrated at the transcriptional level to provide multifactorial control of cell differentiation. The activation of osteogenic genes requires the cooperation of BMP‐2 pathway‐associated Smad1/5/8 heteromeric complexes and mechanosensitive YAP/TAZ translocation. It is further demonstrated that the Smad complexes remain bound onto and active on target genes, even after BMP‐2 removal, suggesting that they act as a “molecular memory unit.” Thus, synergistic stimulation with BMP‐2 and mechanical cues drives osteogenic differentiation in a programmable fashion

GZMKhigh CD8+ T effector memory cells are associated with CD15high neutrophil abundance in non-metastatic colorectal tumors and predict poor clinical outcome.

CD8(+) T cells are a major prognostic determinant in solid tumors, including colorectal cancer (CRC). However, understanding how the interplay between different immune cells impacts on clinical outcome is still in its infancy. Here, we describe that the interaction of tumor infiltrating neutrophils expressing high levels of CD15 with CD8(+) T effector memory cells (T(EM)) correlates with tumor progression. Mechanistically, stromal cell-derived factor-1 (CXCL12/SDF-1) promotes the retention of neutrophils within tumors, increasing the crosstalk with CD8(+) T cells. As a consequence of the contact-mediated interaction with neutrophils, CD8(+) T cells are skewed to produce high levels of GZMK, which in turn decreases E-cadherin on the intestinal epithelium and favors tumor progression. Overall, our results highlight the emergence of GZMK(high) CD8(+) T(EM) in non-metastatic CRC tumors as a hallmark driven by the interaction with neutrophils, which could implement current patient stratification and be targeted by novel therapeutics

Extrapolating from model organisms in pharmacology

In this chapter we explore the process of extrapolating causal claims from model organisms to humans in pharmacology. We describe and compare four strategies of extrapolation: enumerative induction, comparative process tracing, phylogenetic reasoning, and robustness reasoning. We argue that evidence of mechanisms plays a crucial role in several strategies for extrapolation and in the underlying logic of extrapolation: the more directly a strategy establishes mechanistic similarities between a model and humans, the more reliable the extrapolation. We present case studies from the research on atherosclerosis and the development of statins, that illustrate these strategies and the role of mechanistic evidence in extrapolation

Genetic diversity and phylogenetic relationships of coevolving symbiont-harboring insect trypanosomatids, and their neotropical dispersal by invader African blowflies (Calliphoridae)

This study is about the inter- and intra-specific genetic diversity of trypanosomatids of the genus Angomonas, and their association with Calliphoridae (blowflies) in Neotropical and Afrotropical regions. Microscopic examination of 3,900 flies of various families, mostly Calliphoridae, revealed that 31% of them harbored trypanosomatids. Small subunit rRNA (SSU rRNA) barcoding showed that Angomonas predominated (46%) over the other common trypanosomatids of blowflies of genera Herpetomonas and Wallacemonas. Among Angomonas spp., A. deanei was much more common than the two-other species, A. desouzai and A. ambiguus. Phylogenetic analyses based on SSU rRNA, glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) and internal transcribed spacer rDNA (ITS rDNA) sequences revealed a marked genetic diversity within A. deanei, which comprised four infraspecific genotypes (Dea1– Dea4), and four corresponding symbiont genotypes (Kcr1–Kcr4). Host and symbiont phylogenies were highly congruent corroborating their co-divergence, consistent with host-symbiont interdependent metabolism and symbiont reduced genomes shaped by a long coevolutionary history. We compared the diversity of Angomonas/symbionts from three genera of blowflies, Lucilia, Chrysomya and Cochliomyia. A. deanei, A. desouzai, and A. ambiguus were found in the three genera of blowflies in South America. In Africa, A. deanei and A. ambiguus were identified in Chrysomya. The absence of A. desouzai in Africa and its presence in Neotropical Cochliomyia and Lucilia suggests parasite spillback of A. desouzai into Chrysomya, which was most likely introduced four decades ago from Africa into the Neotropic. The absence of correlation between parasite diversity and geographic and genetic distances, with identical genotypes of A. deanei found in the Neotropic and Afrotropic, is consistent with disjunct distribution due to the recent human-mediated transoceanic dispersal of Angomonas by Chrysomya. This study provides the most comprehensive data gathered so far on the genetic repertoires of a genus of trypanosomatids found in flies from a wide geographical range.The PROAFRICA, INCT-EPIAMO, and PROSUL programs of CNPq, PNIPB of Capes, and FAPESP (Process 2016/07487-0). CAPEs (PNPD) granted a postdoctoral scholarship to TB.http://www.frontiersin.org/Microbiologyam2018Veterinary Tropical Disease

The phylogeography of trypanosomes from South American alligatorids and African crocodilids is consistent with the geological history of South American river basins and the transoceanic dispersal of Crocodylus at the Miocene

Background: Little is known about the diversity, phylogenetic relationships, and biogeography of trypanosomes infecting non-mammalian hosts. In this study, we investigated the influence of host species and biogeography on shaping the genetic diversity, phylogenetic relationship, and distribution of trypanosomes from South American alligatorids and African crocodilids. Methods: Small Subunit rRNA (SSU rRNA) and glycosomal Glyceraldehyde Phosphate Dehydrogenase (gGAPDH) genes were employed for phylogenetic inferences. Trypanosomes from crocodilians were obtained by haemoculturing. Growth behaviour, morphology, and ultrastructural features complement the molecular description of two new species strongly supported by phylogenetic analyses. Results: The inferred phylogenies disclosed a strongly supported crocodilian-restricted clade comprising three subclades. The subclade T. grayi comprised the African Trypanosoma grayi from Crocodylus niloticus and tsetse flies. The subclade T. ralphi comprised alligatorid trypanosomes represented by Trypanosoma ralphi n. sp. From Melanosuchus niger, Caiman crocodilus and Caiman yacare from Brazilian river basins. T. grayi and T. ralphi were sister subclades. The basal subclade T. terena comprised alligatorid trypanosomes represented by Trypanosoma terena n. sp. from Ca. yacare sharing hosts and basins with the distantly genetic related T. ralphi. This subclade also included the trypanosome from Ca. crocodilus from the Orinoco basin in Venezuela and, unexpectedly, a trypanosome from the African crocodilian Osteolaemus tetraspis. Conclusion: The close relationship between South American and African trypanosomes is consistent with paleontological evidence of recent transoceanic dispersal of Crocodylus at the Miocene/Pliocene boundaries (4–5 mya), and host-switching of trypanosomes throughout the geological configuration of South American hydrographical basins shaping the evolutionary histories of the crocodilians and their trypanosomes.We are grateful to many people who kindly helped us in crocodilian capture\ud and sample collection in Brazil, Venezuela, and Guinea Bissau. We would like\ud to thank Dr. Miguel U. Trefault Rodrigues for the animal identifications. We\ud acknowledge the Brazilian Ministry of Science, Technology and Innovation\ud (MCTI) for support through the Mamirauá Institute for Sustainable\ud Development (IDSM). We thank Cristina Schwartz for the coordination of the\ud work in Guinea Bissau. We also thank Marcio C. Valentin from the Laboratory\ud of Electron Microscopy, Institute of Biosciences, USP, and Carlos E. Jared and\ud Marta M. Antoniazzi from the Institute Butantan, São Paulo, SP, Brazil, for\ud their kindly permission to use their electron microscopic facilities. This work\ud was supported by CNPq (PROAFRICA and PROSUL) and CAPES (Programa\ud Nacional de Incentivo à Pesquisa em Parasitologia Básica). LBV was\ud postdoctoral fellow sponsored by CNPq-MCTI (PROTAX – National Program\ud of Taxonomy) and CAPES (PNPD). BRF is recipient of a scholarship from\ud CNPq (PROTAX)

Exploring Health Science Students’ Notions on Organ Donation and Transplantation: A Multicenter Study

The knowledge acquired during university education about organ donation and transplantation (ODT) decisively influences the information future health professionals transmit. This is important in ODT where the participation of the general public is essential to obtain organs. Objective: To determine notions of Spanish medicine and nursing students on ODT and its relationship with attitude toward ODT. Methods and Design: and design. We conducted a sociologic, multicenter, and observational study. The population for our study consisted of medical and nursing students in Spanish universities. Our database was the Collaborative International Donor Project, stratified by geographic area and academic course. A validated questionnaire (PCID-DTO-RIOS) was self-administered and completed anonymously. Our sample consisted of 9598 medical and 10, 566 nursing students (99% confidence interval; precision of ±1%), stratified by geographic area and year of study. Results: The completion rate for our study was 90%. Only 20% (n=3640) of students thought their notions on ODT were good; 41% (n=7531) thought their notions were normal; 36% (n=6550) thought their notions were scarce. Comparing groups, there were differences between those who believed that their notions on ODT were good (44% nursing vs 56% medical students; P < .000), and those who believed it scarce (54% nursing vs 46% medical students; P < .000). Notions on ODT were related with attitude toward the donation of one''s own organs: those who considered their notions were good were more in favor then those who considered it scarce (88% vs 72%; P < .000). Conclusion: Only 20% of Spanish medical and nursing students thought their notions on ODT were good. Having good knowledge is related to a favorable attitude towards ODT. Receiving specific information on the subject could improve their knowledge about ODT during their training