On November 2015, one of Brazil's most important watersheds was impacted by the mine waste from Fundão dam collapse in Mariana. The mine waste traveled over 600 km along the Doce River before ...reaching the sea, causing severe devastation along its way. Here we assessed trace element concentrations and cytogenotoxic effects of the released mine waste. Water samples were collected along the Doce River ten days after the disaster in two impacted sites and one non-impacted site. Sampling points were located hundreds of kilometers downstream of the collapsed dam. Water samples were used for trace element quantification and to run an experiment using Allium cepa to test cytogenotoxicity. We found extremely high concentrations of particulate Fe, Al, and Mn in the impacted sites. We observed cytogenotoxic effects such as alterations in mitotic and phase indexes, and enhanced frequency of chromosomal aberrations. Our results indicate interferences in the cell cycle in impacted sites located hundreds of kilometers downstream of the disaster. The environmental impacts of the dam collapse may not only be far-reaching but also very likely long-lasting, because the mine waste may persist in the Doce River sediment for decades.
•Higher concentrations of particulate metals were found in impacted sites.•Cytogenotoxic effects were found in the impacted sites.•Mining waste affected genetic aspects of Allium cepa.•Impacts of the tragedy are far-reaching and long-lasting.
The Americas were the last inhabitable continents to be occupied by humans, with a growing multidisciplinary consensus for entry 15–25 thousand years ago (kya) from northeast Asia via the former ...Beringia land bridge 1–4. Autosomal DNA analyses have dated the separation of Native American ancestors from the Asian gene pool to 23 kya or later 5, 6 and mtDNA analyses to ∼25 kya 7, followed by isolation (“Beringian Standstill” 8, 9) for 2.4–9 ky and then a rapid expansion throughout the Americas. Here, we present a calibrated sequence-based analysis of 222 Native American and relevant Eurasian Y chromosomes (24 new) from haplogroups Q and C 10, with four major conclusions. First, we identify three to four independent lineages as autochthonous and likely founders: the major Q-M3 and rarer Q-CTS1780 present throughout the Americas, the very rare C3-MPB373 in South America, and possibly the C3-P39/Z30536 in North America. Second, from the divergence times and Eurasian/American distribution of lineages, we estimate a Beringian Standstill duration of 2.7 ky or 4.6 ky, according to alternative models, and entry south of the ice sheet after 19.5 kya. Third, we describe the star-like expansion of Q-M848 (within Q-M3) starting at 15 kya 11 in the Americas, followed by establishment of substantial spatial structure in South America by 12 kya. Fourth, the deep branches of the Q-CTS1780 lineage present at low frequencies throughout the Americas today 12 may reflect a separate out-of-Beringia dispersal after the melting of the glaciers at the end of the Pleistocene.
•We sequenced 20 Native American Y chromosomes chosen for their genetic diversity•A Beringian Standstill of <4,600 years led to both Siberian and American Y-lineages•Y-lineage split times rule out occupation of the Americas before 19,500 years ago•Present-day male population structure in South America arose before 12,000 years ago
Pinotti et al. provide a genetic analysis of male history in the Americas that reveals three or four founding lineages, an occupation of Beringia for no longer than 4,600 years, entry south of the ice sheets after 19,500 years ago, and the establishment of the present-day male population structure in South America by 12,000 years ago.
The mummy of a seven-year-old child that was discovered in 1985 in Cerro Aconcagua (Mendoza, Argentina) was likely part of an Inka sacrificial religious practice known as capacocha. Previous ...uniparental DNA marker studies conducted by some scholars have suggested that the mummified child may be related to the southern Andean population of Peru. However, autosome genome-wide analysis performed by others has indicated that the child was more closely related to the population along the northern Peruvian coast than to that of the southern Andes. In this study, we aimed to determine possible genealogical connections in the male lineage of the mummified child. To achieve this, we compared the genetic profile of the mummy with an extensive database of contemporary individuals from the northern Peruvian coastal and southern Andean regions. We used single nucleotide polymorphisms and short tandem repeats from the nonrecombining region of the Y-chromosome for our analysis. Our results confirmed that the Inka child mummy was closely related to individuals from the north coast of Peru. This suggests that the child was likely descended from the Muchik–Chimor-speaking people.
Acute renal failure is a serious complication of human envenoming by Bothrops snakes. The ion pump Na+/K+-ATPase has an important role in renal tubule function, where it modulates sodium reabsorption ...and homeostasis of the extracellular compartment. Here, we investigated the morphological and functional renal alterations and changes in Na+/K+-ATPase expression and activity in rats injected with Bothrops alternatus snake venom.
Male Wistar rats were injected with venom (0.8mg/kg, i.v.) and renal function was assessed 6, 24, 48 and 72h and 7days post-venom. The rats were then killed and renal Na+/K+-ATPase activity was assayed based on phosphate release from ATP; gene and protein expressions were assessed by real time PCR and immunofluorescence microscopy, respectively.
Venom caused lobulation of the capillary tufts, dilation of Bowman's capsular space, F-actin disruption in Bowman's capsule and renal tubule brush border, and deposition of collagen around glomeruli and proximal tubules that persisted seven days after envenoming. Enhanced sodium and potassium excretion, reduced proximal sodium reabsorption, and proteinuria were observed 6h post-venom, followed by a transient decrease in the glomerular filtration rate. Gene and protein expressions of the Na+/K+-ATPase α1 subunit were increased 6h post-venom, whereas Na+/K+-ATPase activity increased 6h and 24h post-venom.
Bothrops alternatus venom caused marked morphological and functional renal alterations with enhanced Na+/K+-ATPase expression and activity in the early phase of renal damage.
Enhanced Na+/K+-ATPase activity in the early hours after envenoming may attenuate the renal dysfunction associated with venom-induced damage.
► Bothrops alternatus snake venom causes renal dysfunction in rats. ► This dysfunction is accompanied by marked renal structural alterations. ► Na+/K+-ATPase expression and activity are enhanced during early renal damage. ► Enhanced Na+/K+-ATPase activity may attenuate renal dysfunction after envenoming.
Water pollution is a global environmental issue, and aquatic sediments are important compartments that might act as sinks or sources of contaminants. Once in the environment, inorganic contaminants ...such as metals can cause cytogenotoxic effects that damage genetic material and harm the aquatic community. Biological assays such as the Allium test can be used to investigate potential cytogenotoxicity of contaminated sediments based on the alterations of cell cycle indexes and chromosomal aberration frequencies. Therefore, we aimed to assess the toxicity of sediments from four Brazilian reservoirs using the Allium test. Sediments were sampled and elutriates were prepared in a simulating sediment resuspension in the water column. The Allium test was applied to the elutriates, and the metals copper, chromium, cadmium, lead, zinc, and iron were quantified. The elutriates derived from reservoir sediments were able to reduce the mitotic and anaphase index, increase the prophase and metaphase index, and boost chromosomal aberrations compared to the negative control. The cytogenotoxic effects observed may be linked to the presence of copper, zinc, and iron. Therefore, our results showed that the Allium test was a sensitive tool for warning the occurrence of genotoxic contaminants in sediment elutriates from four Brazilian reservoirs.
Aim
The effects of past climatic shifts remain enigmatic for the Amazon region, especially for islands of savanna within the tropical forest known as “Amazonian savannas” (AS). These disjunct savanna ...areas share many plant and animal species with the Cerrado biome in central Brazil (the CC), fuelling debate over historical connections. We evaluate hypothesized corridors between the CC and the AS, and specifically investigate whether a history of isolation versus recent connections is supported by genetic tests.
Location
Cerrado and Amazon biomes.
Taxon
Two woody plant species: Byrsonima coccolobifolia and B. crassifolia (Malpighiaceae).
Methods
Analyses of genomic data (SNPs from more than 4,500 loci) in 28 populations, as well as chloroplast DNA (cpDNA), were used to test for parallel geographic structuring between the CC and AS—an expected structure if putative corridors provided regional connections between different areas of the CC and AS, and divergence times between the CC and AS were estimated using a composite‐likelihood method based on the site frequency spectrum.
Results
Genomic data, in contrast with cpDNA, generally show strong, concordant genetic structure between the CC and AS in both species, rather than regional grouping of CC with AS populations. In addition, divergence between the CC and AS predates the Last Glacial Maximum.
Main conclusions
Our results suggest the AS have remained relatively isolated from the CC even though the strong structure of genomic variation is not shared by cpDNA. We note that past evidence of putative corridors between the CC and AS based solely on cpDNA should be interpreted cautiously since the lack of structure may reflect limited genetic resolution rather than gene flow. As such, the uniqueness of AS may be more pronounced than previously thought, highlighting the importance of protecting these highly threatened areas.
Objective
Rehabilitation top‐down techniques based on brain stimulation present variable outcomes in unilateral spatial neglect (USN) after stroke. This study aimed to examine the effects of physical ...therapy after anodal and cathodal transcranial direct current stimulation (A‐tDCS and C‐tDCS, respectively) to improve visuospatial and functional impairments in individuals with USN after stroke.
Methods
This double‐blinded, pilot randomized clinical trial enrolled patients with USN after ischemic stroke. Randomization was stratified according to the Behavior Inattention Test–Conventional (BIT‐C) and Catherine Bergego Scale (CBS). Outpatient physical therapy was conducted for 7.5 weeks after 20 minutes of tDCS. The primary outcome was the USN degree evaluated by the BIT‐C. Secondary outcomes were the difference in CBS score, stroke severity (National Institutes of Health Stroke Scale NIHSS), disability (modified Rankin Scale), autonomy (Barthel Index, Functional Independence Measure), and quality of life (EuroQol Group 5‐Dimension Self‐Report Questionnaire). Outcomes were analyzed using an analysis of covariance model corrected by age, baseline NIHSS, and baseline BIT‐C. Pairwise post hoc comparisons were performed using Bonferroni correction.
Results
In the primary outcomes, A‐tDCS led to greater improvement in BIT‐C after intervention (mean difference MD = 18.4, 95% confidence interval CI = 3.9–32.8, p = 0.008) compared to sham. However, no significant differences were observed between A‐tDCS and C‐tDCS (MD = 13.9, 95% CI = −0.3 to 28.1, p = 0.057), or C‐tDCS and sham (MD = 4.5, 95% CI = −9.7 to 18.8, p = 0.99). There were no significant differences between groups in terms of secondary outcomes.
Interpretation
A‐tDCS associated with physical therapy can decrease the severity of USN after stroke. However, these preliminary findings must be confirmed by collecting additional evidence in a larger phase 3 trial. ANN NEUROL 2022;92:400–410
The present study tests the hypothesis that mitochondrial genes have retrograde signaling capacity that influences the expression of nuclear genes related to angiogenesis pathways. Cytoplasmic hybrid ...(cybrid) in vitro cell lines with patient specific mitochondria inserted into an immortalized retinal pigment epithelial cell line (ARPE-19) were used to test this hypothesis. This type of analysis can provide important information to identify the optimal regimen of anti-VEGF treatment, personalizing age-related macular degeneration (AMD) therapies.
Mitochondria deficient ARPE-19 cells (Rho0) were fused with AMD donor's platelets to create individual cybrid cell lines containing mitochondria from patients with phenotypic AMD disease and nuclear DNA from the immortalized RPE cell line. The cybrids were treated with Ranibizumab (Lucentis, Genentech, San Francisco, CA), at 4 different concentrations for 24 h, and subsequently the levels of reactive oxygen species (ROS), gene expression for VEGF-A, hypoxia-inducible factor 1-alpha (HIF1-a) and manganese superoxide dismutase (SOD2) were measured. The clinical evolution of the two AMD-donors were correlated with the molecular findings found in their 'personalized' cybrids.
Cybrids from Patient-01 showed down-regulation of gene expression of VEGF-A and HIF-1a at both 1X and 4X Ranibizumab concentrations. Patient-01 AMD cybrid cultures had an increase in the ROS levels at 1X (P = 0.0317), no changes at 2X (P = 0.8350) and a decrease at 4X (P = 0.0015) and 10X (P = 0.0011) of Ranibizumab. Clinically, Patient-01 responded to anti-VEGF therapy but eventually developed geographic atrophy. Patient-02 cybrids demonstrated up-regulation of gene expression of VEGF-A and HIF-1a at Ranibizumab 1X and 4X concentrations. There was decreased ROS levels with Ranibizumab 1X (P = 0.1606), 2X (P = 0.0388), 4X (P = 0.0010) and 10X (P = < 0.0001). Clinically, Patient-02 presented with a neovascular lesion associated with a prominent production of intraretinal fluid in clinical follow-up requiring regular and repeated intravitreal injections of Ranibizumab with recurrent subretinal fluid.
Our cybrid model has the potential to help personalize the treatment regimen with anti-VEGF drugs in patients with neovascular AMD. Further investigation is needed to better understand the role that the mitochondria play in the cellular response to anti-VEGF drugs. Future studies that focus on this model have the potential to help personalize anti-VEGF treatment.
•Low-cost polymer optical fiber sensor for human-robot interaction forces.•Analytical model and experimental validation of the POF strain gauge proposed.•Application of the sensor on a lower limb ...exoskeleton with impedance controller.•Comparison between the proposed POF sensor system and electronic strain gauge.
This paper presents the development of a polymer optical fiber (POF) strain gauge based on the light coupling principle, which the power attenuation is created by the misalignment between two POFs. The misalignment, in this case, is proportional to the strain on the structure that the fibers are attached. This principle has the advantages of low cost, ease of implementation, temperature insensitiveness, electromagnetic fields immunity and simplicity on the sensor interrogation and signal processing. Such advantages make the proposed solution an interesting alternative to the electronic strain gauges. For this reason, an analytical model for the POF strain gauge is proposed and validated. Furthermore, the proposed POF sensor is applied on an active orthosis for knee rehabilitation exercises through flexion/extension cycles. The controller of the orthosis provides 10 different levels of robotic assistance on the flexion/extension movement. The POF strain gauge is tested at each one of these levels. Results show good correlation between the optical and electronic strain gauges with root mean squared deviation (RMSD) of 1.87 Nm when all cycles are analyzed, which represents a deviation of less than 8%. For the application, the proposed sensor presented higher stability than the electronic one, which can provide advantages on the rehabilitation exercises and on the inner controller of the device.
PDF
