Genomic analyses correspond with deep persistence of peoples of Blackfoot Confederacy from glacial times.

Mutually beneficial partnerships between genomics researchers and North American Indigenous Nations are rare yet becoming more common. Here, we present one such partnership that provides insight into the peopling of the Americas and furnishes another line of evidence that can be used to further treaty and Indigenous rights. We show that the genomics of sampled individuals from the Blackfoot Confederacy belong to a previously undescribed ancient lineage that diverged from other genomic lineages in the Americas in Late Pleistocene times. Using multiple complementary forms of knowledge, we provide a scenario for Blackfoot population history that fits with oral tradition and provides a plausible model for the evolutionary process of the peopling of the Americas.

Predicting evolutionary targets and parameters of gene deletion from expression data.

Motivation: Gene deletion is traditionally thought of as a nonadaptive process that removes functional redundancy from genomes, such that it generally receives less attention than duplication in evolutionary turnover studies. Yet, mounting evidence suggests that deletion may promote adaptation via the "less-is-more" evolutionary hypothesis, as it often targets genes harboring unique sequences, expression profiles, and molecular functions. Hence, predicting the relative prevalence of redundant and unique functions among genes targeted by deletion, as well as the parameters underlying their evolution, can shed light on the role of gene deletion in adaptation. Results: Here, we present CLOUDe, a suite of machine learning methods for predicting evolutionary targets of gene deletion events from expression data. Specifically, CLOUDe models expression evolution as an Ornstein-Uhlenbeck process, and uses multi-layer neural network, extreme gradient boosting, random forest, and support vector machine architectures to predict whether deleted genes are "redundant" or "unique", as well as several parameters underlying their evolution. We show that CLOUDe boasts high power and accuracy in differentiating between classes, and high accuracy and precision in estimating evolutionary parameters, with optimal performance achieved by its neural network architecture. Application of CLOUDe to empirical data from Drosophila suggests that deletion primarily targets genes with unique functions, with further analysis showing these functions to be enriched for protein deubiquitination. Thus, CLOUDe represents a key advance in learning about the role of gene deletion in functional evolution and adaptation. Availability and implementation: CLOUDe is freely available on GitHub (https://github.com/anddssan/CLOUDe).

Genomic evidence for ancient human migration routes along South America's Atlantic coast.

An increasing body of archaeological and genomic evidence has hinted at a complex settlement process of the Americas by humans. This is especially true for South America, where unexpected ancestral signals have raised perplexing scenarios for the early migrations into different regions of the continent. Here, we present ancient human genomes from the archaeologically rich Northeast Brazil and compare them to ancient and present-day genomic data. We find a distinct relationship between ancient genomes from Northeast Brazil, Lagoa Santa, Uruguay and Panama, representing evidence for ancient migration routes along South America's Atlantic coast. To further add to the existing complexity, we also detect greater Denisovan than Neanderthal ancestry in ancient Uruguay and Panama individuals. Moreover, we find a strong Australasian signal in an ancient genome from Panama. This work sheds light on the deep demographic history of eastern South America and presents a starting point for future fine-scale investigations on the regional level.

Orthodontic bracket bonding techniques and adhesion failures: A systematic review and meta-analysis.

Background: This systematic review compared the bonding failures of orthodontic brackets bonded by indirect or direct techniques. Data sources: The searched databases were Cochrane Library, LILACS, BBO, PubMed, Scopus, Web of Science. Material and Methods: A search for randomized clinical trials comparing the two techniques was carried out to answer the research question: When considering orthodontic bracket bonding on permanent teeth, does the indirect technique reduce the number of bonding failures compared to the direct one over time? The quality of the included papers was assessed with Cochrane risk of bias tool and the quality of evidence with GRADE. Results: From 3096 articles identified, seven were included in the systematic review (five at unclear; two at low risk of bias). Meta-analysis was carried out according to the follow-up periods (0-6 months and 12-15 months). Results: In the first period, bonding techniques were similar with regard to adhesion failures (RR = 0.59; 95% CI 0.10-3.62; p = 0.00001; I2 = 92%); in the 12-to-15-month period, the direct bonding technique proved to be superior (RR = 1.44; 95% CI 1.05 - 1.99; p = 0.41; I2 = 0%). The quality of evidence was classified as low for the 0-6 months follow-up and high for the 12 months. Conclusions: Based on the absence of heterogeneity and the high quality of evidence, it is concluded that the direct bracket bonding technique has a lower failure rate than the indirect technique in the long term (12-15 months). Key words:Orthodontic brackets, fixed orthodontics, systematic review.

Threads in tubing: an innovative approach towards improved electrochemical thread-based microfluidic devices.

Thread-based microfluidic analytical devices have received growing attention since threads have some advantages over other materials. Compared to paper, threads are also capable of spontaneously transporting fluid due to capillary action, but they have superior mechanical strength and do not require hydrophobic barriers. Therefore, thread-based microfluidic devices can be inexpensively fabricated with no need for external pumps or sophisticated microfabrication apparatus. Despite these outstanding features, achieving a controlled and continuous flow rate is still a challenging task, mainly due to fluid evaporation. Here, we overcome this challenge by inserting a cotton thread into a polyethylene tube aiming to minimize fluid evaporation. Also, a cotton piece was inserted into the outlet reservoir to improve the wicking ability of the device. This strategy enabled the fabrication of an innovative electrochemical thread in a tubing microfluidic device that was capable to hold a consistent flow rate (0.38 µL s-1) for prolonged periods, allowing up to 100 injections in a single device by simply replacing the cotton piece in the outlet reservoir. The proposed device displayed satisfactory analytical performance for selected model analytes (dopamine, hydrogen peroxide, and tert-butylhydroquinone), in addition to being successfully used for quantification of nitrite in spiked artificial saliva samples. Beyond the flow rate improvement, this "thread-in-tube" strategy ensured the protection of the fluid from external contamination while making it easier to connect the electrode array to the microchannels. Thus, we envision that the thread in a tube strategy could bring interesting improvements to thread-based microfluidic analytical devices.

Fully independent validation and updating of a clinical pharmacy prioritizing risk score in an infectious disease hospital ward.

AIMS: The aim of this study was to validate and update the risk score originally developed at Hospital de Clínicas de Porto Alegre, verifying its performance in an infectious disease population. METHODS: This is an observational study with consecutive selection of admission in a ward of participants with infectious diseases. Predictors were age, number of medications, intravenous drugs, potentially dangerous drugs, renal dysfunction, liver dysfunction, use of nasoenteral tube, nasogastric tube, gastrostomy feeding, jejunostomy feeding, oral enteral tube, total parenteral nutrition, cardiac or pulmonary dysfunction and immunosuppression. Outcome was defined as preventable prescription incidents by a clinical pharmacist. A GEE model was fit to make predictions each week. RESULTS: A total of 219 patients participated in the study, 79.25% of whom had prescription incidents in the first week of admission. Predictors of the updated model were number of drugs prescribed, number of intravenous drugs, use of tubes, truncated age at 36 years and week of hospitalization. The performance of the original model was poor. The updated model's discrimination and calibration were moderate (overall AUC 0.74). A calculator to apply the model is available at https://pedrobrasil.shinyapps.io/INDWELL/. CONCLUSION: The updated risk score enabled the user to make predictions at admission and throughout the weeks, allowing for a prioritized weekly update for clinical pharmacy intervention. The updated model has a moderate and satisfactory performance for infectious disease patients.

Genetic divergence for adaptability and stability in sugarcane: Proposal for a more accurate evaluation.

The best agro-industrial performance presented by a crop genotype in one environment may not be reproduced in another owing to complex edaphoclimatic variations. Therefore, breeding programs are constantly attempting to obtain, through artificial hybridization, novel genotypes with high adaptability and stability potential. The objective of this study was to analyze genetic divergence in sugarcane based on the genotypic values of adaptability and stability. A total of 11 sugarcane genotypes were analyzed for eight agro-industrial traits. The genotypic values of the traits were determined using mixed model methodology, and the genetic divergence based on phenotypic and genotypic values was measured using the Mahalanobis distance. The distance matrices were correlated using the Mantel test, and the genotypes were grouped using the Tocher method. Genetic divergence is more accurate when based on genotypic values free of genotype-environment interactions and will differ from genetic divergence based on phenotypic data, changing the genotype allocations in the groups. The above methodology can be applied to assess genetic divergence to obtain novel sugarcane genotypes with higher productivity that are adapted to intensive agricultural systems using diverse technologies. This methodology can also be tested in other crops to increase accuracy in selecting the parents to be crossed.

Involvement of Leishmania Phosphatases in Parasite Biology and Pathogeny.

In the Leishmania lifecycle, the motile promastigote form is transmitted from the sand fly vector to a mammalian host during a blood meal. Inside vertebrate host macrophages, the parasites can differentiate into the amastigote form and multiply, causing leishmaniasis, one of the most significant neglected tropical diseases. Leishmania parasites face different conditions throughout their development inside sand flies. Once in the mammalian host, the parasites have to overcome the microbicide repertoire of the cells of the immune system to successfully establish the infection. In this context, the expression of protein phosphatases is of particular interest. Several members of the serine/threonine-specific protein phosphatase (STP), protein tyrosine phosphatase (PTP), and histidine acid phosphatase (HAcP) families have been described in different Leishmania species. Although their physiological roles have not been fully elucidated, many studies suggest they have an involvement with parasite biology and pathogeny. Phosphatases play a role in adaptation to nutrient starvation during parasite passage through the sand fly midgut. They are also important to parasite virulence, mainly due to the modulation of host cytokine production and impairment of the microbiocidal potential of macrophages. Furthermore, recent whole-genome expression analyses have shown that different phosphatases are upregulated in metacyclic promastigotes, the infective form of the mammalian host. Leishmania phosphatases are also upregulated in drug-resistant strains, probably due to the increase in drug efflux related to the activation of ABC transporters. Throughout this review, we will describe the physiological roles that have been attributed to Leishmania endogenous phosphatases, including their involvement in the adaptation, survival, and proliferation of the parasites inside their hosts.

Festoons, edema e bolsas malares: existe consenso no tratamento estético? / Festoons, edema, and malar bags: is there a consensus on aesthetic treatment?

Introdução: As alterações periorbitais são alguns dos primeiros sinais detectáveis do envelhecimento. O destaque, atualmente, refere-se ao rejuvenescimento dessa região, envolvendo o tratamento desde as sobrancelhas até a transição órbito-malar, onde se encontram festoons, edemas e bolsas malares. Entretanto, este manejo é complexo, envolvendo várias abordagens: técnicas invasivas ou não invasivas. Assim, esta revisão objetiva descrever as evidências científicas relacionadas às técnicas mais atuais utilizadas no tratamento de festoons, edemas e bolsas malares e avaliar as complicações relacionadas à cada modalidade. Métodos: A pesquisa foi realizada em três bases de dados - PubMed, Cochrane e LILACS - utilizando os descritores "bolsa malar", "malar mounds", "festoons" e "malar bags" no período de 2014 a 2019, na língua inglesa e portuguesa. Resultados: Foram selecionados 13 artigos, a maioria dos estudos eram revisões retrospectivas (76,9%), sete versavam sobre técnicas não invasivas, 3 sobre invasivas e 3 sobre associação das técnicas. Em relação aos procedimentos descritos, os não invasivos foram representados pelo uso de Kinesio tape, injeção de tetraciclina, doxiciclina e de ácido hialurônico, e o uso de microagulhamento com radiofrequência. Já os invasivos foram representados por microaspiração, retalho miocutâneo, lift subperiosteal da face média e excisão direta. Conclusão: Existem inúmeras técnicas para tratamento de festoon e bolsas malares, mas cabe ao cirurgião plástico conhecer suas vantagens e desvantagens para decidir a mais adequada em cada situação. Assim, não há consenso, mas é vital diagnosticar corretamente para indicar o melhor tratamento.

Introduction: Periorbital changes are some of the first detectable signs of aging. The most outstanding currently, refers to the rejuvenation of this region, involving the treatment from the eyebrows to the transition orbital-malar, where are festoons, edemas, and malar bags. However, this management is complex, involving several approaches: invasive or noninvasive techniques. Thus, this review aims to describe the scientific evidence of the most current techniques used in the treatment of festoons, edema, and malar bags and to evaluate the complications related to each modality. Methods: The research was carried out in three databases, PubMed, Cochrane, and LILACS - using the descriptors "bolsa malar," "malar mounds," "festoons" and "malar bags" in the period from 2014 to 2019, in English and Portuguese. Results: We selected 13 articles; most of the studies were retrospective reviews (76.9%), seven dealt with noninvasive techniques, three about invasive, and three on the association of techniques. Regarding the procedures described, the noninvasive ones were represented by the use of Kinesio tape, tetracycline injection, doxycycline and hyaluronic acid, and the use of microneedling with radiofrequency. The invasive ones were represented by microaspiration, myocutaneous flap, subperiosteal lift of the middle face, and direct excision. Conclusion: There are numerous techniques for treating festoon and malar bags, but it is up to the plastic surgeon to know its advantages and disadvantages to decide the most appropriate in each situation. Thus, there is no consensus, but it is vital to diagnose correctly to indicate the best treatment.

Genome-Wide Selection Scan in an Arabian Peninsula Population Identifies a TNKS Haplotype Linked to Metabolic Traits and Hypertension.

Despite the extreme and varying environmental conditions prevalent in the Arabian Peninsula, it has experienced several waves of human migrations following the out-of-Africa diaspora. Eventually, the inhabitants of the peninsula region adapted to the hot and dry environment. The adaptation and natural selection that shaped the extant human populations of the Arabian Peninsula region have been scarcely studied. In an attempt to explore natural selection in the region, we analyzed 662,750 variants in 583 Kuwaiti individuals. We searched for regions in the genome that display signatures of positive selection in the Kuwaiti population using an integrative approach in a conservative manner. We highlight a haplotype overlapping TNKS that showed strong signals of positive selection based on the results of the multiple selection tests conducted (integrated Haplotype Score, Cross Population Extended Haplotype Homozygosity, Population Branch Statistics, and log-likelihood ratio scores). Notably, the TNKS haplotype under selection potentially conferred a fitness advantage to the Kuwaiti ancestors for surviving in the harsh environment while posing a major health risk to present-day Kuwaitis.

Generation of models from existing models composition: An application to agrarian sciences.

Mathematical models that describe gas production are widely used to estimate the rumen degradation digestibility and kinetics. The present study presents a method to generate models by combining existing models and to propose the von Bertalanffy-Gompertz two-compartment model based on this method. The proposed model was compared with the logistic two-compartment one to indicate which best describes the kinetic curve of gas production through the semi-automated in vitro technique from different pinto peanut cultivars. The data came from an experiment grown and harvested at the Far South Animal Sciences station (Essul) in Itabela, BA, Brazil and gas production was read at 2, 4, 6, 8, 10, 12, 14, 17, 20, 24, 28, 32, 48, 72, and 96 h after the start of the in vitro fermentation process. The parameters were estimated by the least squares method using the iterative Gauss-Newton process in the software R version 3.4.1. The best model to describe gas accumulation was based on the adjusted coefficient of determination, residual mean squares, mean absolute deviation, Akaike information criterion, and Bayesian information criterion. The von Bertalanffy-Gompertz two-compartment model had the best fit to describe the cumulative gas production over time according to the methodology and conditions of the present study.

Fructan and antioxidant metabolisms in plants of Lolium perenne under drought are modulated by exogenous nitric oxide.

Drought is a major environmental factor that can trigger oxidative stress and affect plant growth and productivity. Previous studies have shown that exogenous nitric oxide (NO) can minimize oxidative stress-related damage through the modulation of antioxidant enzyme activity. Fructan accumulation also has an important role in drought tolerance, since these carbohydrates participate in osmoregulation, membrane protection and oxidant scavenging. Currently, there are few studies investigating NO-regulated fructan metabolism in response to abiotic stresses. In the present study, we sought to determine if treating plants of Lolium perenne with S-nitrosoglutathione (GSNO), a NO donor, improved drought tolerance. Two-month-old plants received water (control), GSNO and reduced glutathione (GSH) as foliar spray treatments and were then maintained under drought or well-watered conditions for 23 days. At the end of drought period, we evaluated growth, pigment content and antioxidant and fructan metabolisms. None of these conditions influenced dry mass accumulation, but the leaves of plants treated with GSNO exhibited a slight increase in pigment content under drought. GSNO treatment also induced 1-SST activity, which was associated with a 3-fold increase in fructan content. GSNO-treated plants presented higher GR activity and, consequently, increased GSH levels. L. perenne cv. AberAvon was relatively tolerant to the water stress condition employed herein, maintaining ROS homeostasis and mitigating oxidative stress, possibly due to fructan, ascorbate and glutathione pools.

Inorganic phosphate as an important regulator of phosphatases.

Cellular metabolism depends on the appropriate concentration of intracellular inorganic phosphate (Pi). Pi starvation-responsive genes appear to be involved in multiple metabolic pathways, implying a complex Pi regulation system in microorganisms and plants. A group of enzymes is required for absorption and maintenance of adequate phosphate levels, which is released from phosphate esters and anhydrides. The phosphatase system is particularly suited for the study of regulatory mechanisms because phosphatase activity is easily measured using specific methods and the difference between the repressed and derepressed levels of phosphatase activity is easily detected. This paper analyzes the protein phosphatase system induced during phosphate starvation in different organisms.

Trypanosoma rangeli: differential expression of ecto-phosphatase activities in response to inorganic phosphate starvation.

In this work, we showed that living cells of Trypanosoma rangeli express different ecto-phosphatase activities in response to different inorganic phosphate (Pi) concentrations in the culture medium. The ecto-phosphatase activity from T. rangeli grown at low-Pi concentration was inhibited by the increase of the pH, while the ecto-phosphatase of the cells grown at high Pi concentration was not modulated by the change of the pH of the medium. Okadaic acid inhibited only the ecto-phosphatase activity from cells grown at low-Pi concentration but not the ecto-phosphatase activity from cells grown at high-Pi concentration. Accordingly, phosphatase activity from T. rangeli grown at low Pi concentration was able to hydrolyze P-serine and P-threonine at high rate but not P-tyrosine. The phosphatase activity from T. rangeli grown at high-Pi concentration was able to hydrolyze P-serine, P-threonine and P-tyrosine with the same rate. The addition of anterior midgut homogenate of Rhodnius prolixus on the epimastigotes suspension inhibited the enzyme activity of T. rangeli grown at low-Pi concentration. On the other hand, anterior midgut homogenate had no effect in the ecto-phosphatase of T. rangeli maintained at high-Pi concentration. Altogether, the results described here indicate that ecto-phosphatase activities hydrolyzing phosphorylated compounds present in the extracellular medium of T. rangeli are regulated by the external Pi concentration.

Trypanosoma rangeli: a possible role for ecto-phosphatase activity on cell proliferation.

Here we demonstrate for the first time that growth of Trypanosoma rangeli, a protozoa parasite, is strongly dependent on the presence of inorganic phosphate (Pi) in the culture medium and that the replacement of the inorganic phosphate in the culture medium by beta-glycerophosphate, a substrate for phosphatases lead the cells to achieve its maximal growth. The ecto-phosphatase activity present on the external surface of T. rangeli decreased during the growth phase of the parasite, suggesting that this enzyme could be important for the development. Accordingly, the inhibition of this ecto-phosphatase activity by sodium orthovanadate also inhibited the proliferation of T. rangeli. Parasites maintained in a Pi-starved culture medium (2 mM Pi) had 4-fold more ecto-phosphatase activity as compared to parasites maintained in a Pi-supplemented culture medium (50 mM Pi). Altogether, these results presented here suggest that this ecto-phosphatase activity leads to hydrolysis of phosphorylated compounds present in the extracellular medium, which could contribute to the acquisition of inorganic phosphate during the development of T. rangeli epimastigotes.

A Mg(2+)-dependent ecto-phosphatase activity on the external surface of Trypanosoma rangeli modulated by exogenous inorganic phosphate.

In this work, we characterized a Mg(2+)-dependent ecto-phosphatase activity present in live Trypanosoma rangeli epimastigotes. This enzyme showed capacity to hydrolyze the artificial substrate for phosphatases, p-nitrophenylphosphate (p-NPP). At saturating concentration of p-NPP, half-maximal p-NPP hydrolysis was obtained with 0.23mM Mg(2+). Ca(2+) had no effect on the basal phosphatase activity, could not substitute Mg(2+) as an activator and in contrast inhibited the p-NPP hydrolysis stimulated by Mg(2+). The dependence on p-NPP concentration showed a normal Michaelis-Menten kinetics for this phosphatase activity with values of V(max) of 8.94+/-0.36 nmol p-NP x h(-1) x 10(-7) cells and apparent K(m) of 1.04+/-0.16 mM p-NPP. Mg(2+)-dependent ecto-phosphatase activity was stimulated by the alkaline pH range. Experiments using inhibitors, such as, sodium fluoride, sodium orthovanadate and ammonium molybdate, inhibited the Mg(2+)-dependent ecto-phosphatase activity. Inorganic phosphate (Pi), a product of phosphatases, inhibited reversibly in 50% this activity. Okadaic acid and microcystin-LR, specific phosphoserine/threonine phosphatase inhibitors, inhibited significantly the Mg(2+)-dependent ecto-phosphatase activity. In addition, this phosphatase activity was able to recognize as substrates only o-phosphoserine and o-phosphothreonine, while o-phosphotyrosine was not a good substrate for this phosphatase. Epimastigote forms of T. rangeli exhibit a typical growth curve, achieving the stationary phase around fifth or sixth day and the Mg(2+)-dependent ecto-phosphatase activity decreased around 10-fold with the cell growth progression. Cells maintained at Pi-deprived medium (2 mM Pi) present Mg(2+)-dependent ecto-phosphatase activity approximately threefold higher than that maintained at Pi-supplemented medium (50 mM Pi).