Karst processes are of primary importance for the generation of secondary porosity and permeability in carbonate reservoirs and aquifers. The topic investigated in this study are the effects of the ...facies and stratigraphy of different layers on the vertical distribution of solution cavities formed by hypogenic fluids in a carbonate sequence. This work uses the Toca da Boa Vista (TBV) and Toca da Barriguda (TBR) caves as analogues of carbonate reservoirs that are affected by karst processes. These are two different caves that are 400 m apart but exhibit the same geological characteristics and occur in the Neoproterozoic Salitre Formation (700-560 Ma), São Francisco Craton, Brazil. These caves form the longest cave system in South America, with conduits of lengths ∼107 km (TBV) and ∼34 km (TBR). Previous studies of these caves indicated their hypogene origins. These caves developed by an ascending fluid flow, mainly along fractures. The fluid then flowed laterally and was influenced by the following five stratigraphic units, from the bottom to the top: (1) cross-bedded oolitic grainstone, (2) fine grainstone with chert nodules, (3) microbial carbonate, (4) interbedded fine siliciclastics and marls, and (5) crystalline grainstone interfingered with chert layers. Units 4 and 5 formed a stratigraphic seal. Units 1, 2, and 3 below the seal supported the lateral redistribution of flow and respective conduit development. Therefore, these units exhibit a high degree of karstification. Veins related to the first fluid phases that compose a hydrothermal mineral assemblage cut across these units. We conclude that stratigraphic control is important for determining the architecture of the hypogenic cave system at the local scale.
•We study the lithostratigraphy and vein mineralogy of giant hypogenic caves.•Vein hypogene infillings include a hydrothermal assemblage of minerals.•The caves comprise a conduit-seal system in the carbonate-siliciclastic unit.•Lateral flow followed the dissolution of ascending fluids through vertical fractures.•Local stratigraphy controls the horizontal dissolution and karst development.
Angiogenesis is a dynamic morphogenetic process that refers to the growth of new blood vessels from the pre-existing vessels and is critical for tissue repair during wound healing. In adult normal ...tissues, quiescent endothelial cells and pericytes maintain vascular integrity, whereas angiogenesis is immediately induced upon tissue injury, thereby forming neovascular networks to maintain homeostasis. However, impaired angiogenesis results in development of chronic and non-healing wounds in various diseases such as diabetes and peripheral artery diseases. Zebrafish are a vertebrate model organism widely used for studying many medical and life science fields. Indeed, the molecular and cellular mechanisms underlying regulation of wound angiogenesis have recently been studied by performing fluorescence-based live-imaging of adult zebrafish. In this review, we describe how endothelial cells and pericytes establish neovascular networks during wound angiogenesis and also introduce a novel role of blood flow-driven intraluminal pressure in regulating angiogenesis during wound healing.
This paper focuses in the description, radiocarbon dating and isotopic analyses (δ13C, δ18O) of new fossils of Panthera onca from the late Pleistocene of the Brazilian Intertropical Region. This ...paper focuses on the paleoecology of this large cat and is of major importance to understand ecological niches in evolutionary time. Radiocarbon datings and stable isotope compositions (carbon and oxygen) were determined from the structural carbonate of enamel for two fossils of Panthera onca found in two caves in Bahia, Brazil. Isotopic data available of large faunivores and other extinct and extant herbivorous taxa from the late Pleistocene of the Brazilian Intertropical Region were used for paleoecological interpretations. Carbon and oxygen isotopic values from P. onca allow us to suggest that these individuals lived in arboreal savanna habitat between 26 and 33 kyr BP, could reach 209 kg and feed mainly on Nothrotherium maquinense, Tapirus terrestris and Alouatta sp., being a specialist. The isotopic niche overlap with Smilodon populator and Arctotherium wingei was high, while with Protocyon troglodytes was low. In the late Pleistocene P. onca probably suffer high ecological pressure by S. populator, while with A. wingei this could not occur, as this species could be mainly herbivorous.
•Two new records of Panthera onca fossils in caves of Bahia, Brazil.•Both remains are from the late Pleistocene (29 ka and 36 ka).•Body mass estimation varied between 89 kg and 209 kg.•The isotopic diet of P. onca was based mainly in ground sloths, tapirs and monkeys.•onca probably suffer high ecological pressure by S. populator.
NASA has been developing and testing a water recovery system for over two decades to minimize the amount of water required for long duration human space missions. A key system component is the total ...organic carbon analyzer (TOCA) that determines if the recovered water is below the toxicology-defined health limit of 5 mg/L TOC and is safe to drink. The TOCA is composed of a liquid phase loop and a gas phase loop. The TOCA employs an oxidizer to convert the organics in the liquid phase to carbon dioxide (CO2) and a liquid–gas separator to isolate the CO2 for measurement in the gas phase by infrared spectroscopy. In an effort to reduce the consumables, mass, volume, and power of the system, we investigated the ability of surface-enhanced Raman spectroscopy (SERS), and Raman spectroscopy to measure 5 mg/L carbon in water. The SERS measurement employed silver colloids to increase sensitivity, while the Raman measurements used multiple mirrors to increase sensitivity. Here, we present SERS measurements of carbonate (CO3=) at 3 mg/L carbon and Raman measurements of CO2 at 9 mg/L carbon in the effluent water of a new oxidizer being developed for a future TOCA. Both SERS and Raman techniques can determine TOC in the liquid phase, eliminating the need for the gas phase loop and associated supplies and replacement components, which could effectively decrease the size and weight of the current TOCA by as much as 50%.
Graphical Abstract
The abrupt climate event Younger Dryas (YD) has been extensively studied; however, its structure is still poorly understood. Climate in northeastern Brazil is very sensitive to the latitudinal ...position of the intertropical convergence zone (ITCZ) associated with abrupt climate change in the Atlantic. Here, we report changes in the ITCZ position within the YD by using precise speleothem multiproxy records from northeastern Brazil. We provide evidence for a gradual northward migration of the ITCZ preceding poleward shifts of the westerlies and the polar front in northern high latitudes within the YD. This can be attributed to gradual increase in atmospheric CO2 concentration as a consequence of the weakening Atlantic Meridional Overturning Circulation (AMOC). We suggest that a persistent increase in atmospheric CO2 might have triggered a resumption of the AMOC and reorganization of the atmosphere circulation in the Atlantic during the mid‐YD.
Plain Language Summary
The Younger Dryas (YD) is the most recent millennial‐scale abrupt climate event in Earth history. Although its origin has been extensively studied, its structure is still poorly understood. Climate in northeastern Brazil is very sensitive to the latitudinal position of the intertropical convergence zone (ITCZ) responds to abrupt climate change in the Atlantic (e.g., YD). By using stable isotope and trace element proxy records of speleothem from Toca da Boa Vista Cave, northeastern Brazil, together with other paleoclimatic records in the Atlantic realm, we provide evidence for a gradual northward migration of the ITCZ preceding poleward shifts of the westerlies and the polar front in northern high latitudes within the YD. This can be attributed to a gradual increase in atmospheric CO2 concentration under the situation of weakening Atlantic Meridional Overturning Circulation (AMOC). A persistent increase in atmospheric CO2 concentration might have triggered a resumption of the AMOC and reorganization of the atmosphere circulation in the Atlantic during the mid‐YD.
Key Points
Speleothem and other paleoclimate records confirm a wet climate in tropical South America within the Younger Dryas
Precise speleothem multiproxy records reflect a bipartition of the Younger Dryas precipitation in northeastern Brazil
Gradual South‐North climate transition in the Atlantic responded to a gradual increase in atmospheric CO2 within the YD
The objective of our study was to examine, in addition to using the TOCA Football System tool and training method, the effect of a 10-week intervention on elite youth athletes in terms of their ...sport-specific motor skills and anthropometric variables.
The study covered a group of 32 young players practicing football (U14) (13.45 ± 0.64 years). The junior U14 footballers were randomly assigned to an intervention or TOCA group (TG,
= 15, 13.25 ± 0.58 years) and a control group (CG,
= 17, 13.63 ± 0.66 years). Before starting the test, we performed full anthropometric measurements and assessed the sample's agility with and without the ball and their sport-specific endurance. The measurements were then repeated after the 10-week intervention.
Within-group analysis showed significant improvements in muscle mass (
< 0.001), sport-specific endurance (
< 0.001), (
< 0.004) and agility (in TG) both with and without the ball (
= 0.002), (
= 0.004) however, we did not find a significant change in body fat percentage in either group (
= 0.988,
= 0.288). In the CG, "agility with the ball" changed significantly only (
= 0.023). In the between-group analysis with a repeated-measures analysis of variance (mixed-design ANOVA), there was no significant interaction in any performance variables. The main findings of this study indicate that a TOCA Football training program in addition to normal training during the in-season period does not produce additional effects in anthropometric factors, sport-specific endurance and agility performance with the ball (dribbling) and without the ball in comparison with the control condition.
From a practical point of view, the presented anthropometric and physical profiles of players can be useful for football coaches in optimizing soccer training. Overall, it also can be concluded that the device can be safely used in the sensitive age group in terms of the development of motor skills since we did not find any negative effects during the use of the device in terms of the parameters we examined. In addition to the expansion of the number of elements and the inclusion of other age groups, it is advisable to carry out further complex tests, as the TOCA Football System offers many research opportunities.
When and how did the first human beings settle in the American continent? Numerous data, from archaeological researches as well as from palaeogenetics, anthropological and environmental studies, have ...led to partially contradictory interpretations in recent years, often because of the lack of a reliable chronological framework. The present study contributes to the establishment of such a framework using luminescence techniques to date a Brazilian archaeological site, the Toca da Tira Peia. It constitutes an exemplary case study: all our observations and measurements tend to prove the good integrity of the site and the anthropological nature of the artifacts and we are confident in the accuracy of the luminescence dating results. All these points underline the importance of the Toca da Tira Peia. The results bring new pieces of evidence of a human presence in the north-east of Brazil as early as 20,000 BC. The Toca da Tira Peia thus contributes to the rewriting of the history of the peopling of the American continent.
► The Toca da Tira Peia Rockshelter is a Brazilian archaeological site (Piauí). ► All observations and data lead us to conclude that the artifacts are truly cultural. ► OSL dating has been performed on the sediments. ► The results bring new evidence of a human presence in Brazil as early as 20,000 BC.
Prodrug-activator gene therapy with Toca 511, a tumor-selective retroviral replicating vector (RRV) encoding yeast cytosine deaminase, is being evaluated in recurrent high-grade glioma patients. ...Nonlytic retroviral infection leads to permanent integration of RRV into the cancer cell genome, converting infected cancer cell and progeny into stable vector producer cells, enabling ongoing transduction and viral persistence within tumors. Cytosine deaminase in infected tumor cells converts the antifungal prodrug 5-fluorocytosine into the anticancer drug 5-fluorouracil, mediating local tumor destruction without significant systemic adverse effects.
Here we investigated mechanisms underlying the therapeutic efficacy of this approach in orthotopic brain tumor models, employing both human glioma xenografts in immunodeficient hosts and syngeneic murine gliomas in immunocompetent hosts.
In both models, a single injection of replicating vector followed by prodrug administration achieved long-term survival benefit. In the immunodeficient model, tumors recurred repeatedly, but bioluminescence imaging of tumors enabled tailored scheduling of multicycle prodrug administration, continued control of disease burden, and long-term survival. In the immunocompetent model, complete loss of tumor signal was observed after only 1-2 cycles of prodrug, followed by long-term survival without recurrence for >300 days despite discontinuation of prodrug. Long-term survivors rejected challenge with uninfected glioma cells, indicating immunological responses against native tumor antigens, and immune cell depletion showed a critical role for CD4+ T cells.
These results support dual mechanisms of action contributing to the efficacy of RRV-mediated prodrug-activator gene therapy: long-term tumor control by prodrug conversion-mediated cytoreduction, and induction of antitumor immunity.
Endosome-to-Golgi transport is required for the function of many key membrane proteins and lipids, including signaling receptors, small-molecule transporters, and adhesion proteins. The retromer ...complex is well-known for its role in cargo sorting and vesicle budding from early endosomes, in most cases leading to cargo fusion with the trans-Golgi network (TGN). Transport from recycling endosomes to the TGN has also been reported, but much less is understood about the molecules that mediate this transport step. Here we provide evidence that the F-BAR domain proteins TOCA-1 and TOCA-2 (Transducer of Cdc42 dependent actin assembly), the small GTPase CDC-42 (Cell division control protein 42), associated polarity proteins PAR-6 (Partitioning defective 6) and PKC-3/atypical protein kinase C, and the WAVE actin nucleation complex mediate the transport of MIG-14/Wls and TGN-38/TGN38 cargo proteins from the recycling endosome to the TGN in Caenorhabditis elegans . Our results indicate that CDC-42, the TOCA proteins, and the WAVE component WVE-1 are enriched on RME-1–positive recycling endosomes in the intestine, unlike retromer components that act on early endosomes. Furthermore, we find that retrograde cargo TGN-38 is trapped in early endosomes after depletion of SNX-3 (a retromer component) but is mainly trapped in recycling endosomes after depletion of CDC-42, indicating that the CDC-42–associated complex functions after retromer in a distinct organelle. Thus, we identify a group of interacting proteins that mediate retrograde recycling, and link these proteins to a poorly understood trafficking step, recycling endosome-to-Golgi transport. We also provide evidence for the physiological importance of this pathway in WNT signaling.
Significance Endosomes are membrane-bound organelles that are required for the sorting of membrane-associated proteins and lipids. Once integral membrane proteins reach the endosomal system they can be sent to the lysosome for degradation, recycled to the plasma membrane, or recycled to the Golgi apparatus. Here we provide insight into the molecules that mediate a poorly understood route to the Golgi from recycling endosomes. The mediators of this transport step that we identified include the membrane-binding and -bending TOCA proteins, the small GTPase CDC-42, associated polarity proteins PAR-6 and PKC-3/atypical protein kinase C, and the WAVE actin nucleation complex. Many transmembrane proteins likely use this same transport mechanism.
Glioblastoma (GBM) is the most common primary brain tumor in adults. GBM treatment options have been the same for the past 30 years and have only modestly extended survival, despite aggressive ...multimodal treatments. The progressively better knowledge of GBM biology and a comprehensive analysis of its genomic profile have elucidated GBM heterogeneity, contributing to a more effective molecular classification and to the development of innovative targeted therapeutic approaches.
This article reports all the noteworthy innovations for immunotherapy and targeted therapy, providing insights into the current advances in trial designs, including combination therapies with immuno-oncology agents and target combinations.
GBM molecular heterogeneity and brain anatomical characteristics critically restrain drug effectiveness. Nevertheless, stimulating insights for future research and drug development come from innovative treatment strategies for GBM, such as multi-specific 'off-the-shelf' CAR-T therapy, oncolytic viral therapy and autologous dendritic cell vaccination. Disappointing results from targeted therapies-clinical trials are mainly due to complex interferences between signaling pathways and biological processes leading to drug resistance: hence, it is imperative in the future to develop combinatorial approaches and multimodal therapies.