Phosphorylation of eIF2α on Threonine 169 is not required for Trypanosoma brucei cell cycle arrest during differentiation.

The trypanosome life cycle consists of a series of developmental forms each adapted to an environment in the relevant insect and/or mammalian host. The differentiation process from the mammalian bloodstream form to the insect-midgut procyclic form in Trypanosoma brucei occurs in two steps in vivo. First proliferating 'slender' bloodstream forms differentiate to non-dividing 'stumpy' forms arrested in G1. Second, in response to environmental cues, stumpy bloodstream forms re-enter the cell cycle and start to proliferate as procyclic forms after a lag during which both cell morphology and gene expression are modified. Nearly all arrested cells have lower rates of protein synthesis when compared to the proliferating equivalent. In eukaryotes, one mechanism used to regulate the overall rate of protein synthesis involves phosphorylation of the alpha subunit of initiation factor eIF2 (eIF2α). The effect of eIF2α phosphorylation is to prevent the action of eIF2B, the guanine nucleotide exchange factor that activates eIF2 for the next rounds of initiation. To investigate the role of the phosphorylation of eIF2α in the life cycle of T. brucei, a cell line was made with a single eIF2α gene that contained the phosphorylation site, threonine 169, mutated to alanine. These cells were capable of differentiating from proliferating bloodstream form cells into arrested stumpy forms in mice and into procyclic forms in vitro and in tsetse flies. These results indicate that translation attenuation mediated by the phosphorylation of eIF2α on threonine 169 is not necessary for the cell cycle arrest associated with these differentiation processes.This work was supported by Fapesp grants 09/52047-5 and 11/51973-3 to B.A.C. and S. S., respectively, and CNPq grants 309860/2011-3 and 478903/2012-0 to B.A.C. and 477143/2011-3 and 445655/2014-3 to S.S.. C.C.A. was supported by a Fapesp doctoral fellowship (2007/59753-7) and a CAPES-PSDE fellowship. Work in Cambridge and Bristol was supported by Wellcome Trust Project, Grants 085956 and 088099 respectively.This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/j.molbiopara.2016.03.00

Strategies to mitigate the emission of methane in pastures: Enteric methane: A review

The global population reached 7.9 billion in 2021, which represents a 160% increase in the number of people to be fed since 1960. Agricultural systems must sustainably meet food demand for this growing population while minimizing or mitigating potential environmental impacts, which are of growing concern to both consumers and the scientific community. High protein animal products (meat and milk) play a crucial part in human nutrition and pastures represent ~20% of the planet’s surface. Pastoral areas have a great influence on both ecological balance and human subsistence. Ruminant livestock production systems are hotly debated because of the emission of methane, which is produced during enteric fermentation of ingested food within the rumen. Methanogenesis is a naturally occurring process in the digestive system of ruminant animals and ingesting a high-quality diet has been shown to reduce methane production. An additional function of pastoral grasslands is the capacity of the soils to operate as carbon sinks. Well managed pastures absorb carbon from the atmosphere where it can add to soil organic matter directly, through residue decomposition or excrement returns. However, in Brazil and globally, the efficiency of animal productivity tends to be lower in extensively grazed farming systems. Changes to pasture and grazing management in combination with the adoption of technology is necessary to improve the quality of pastures, increase animal productivity, and consequently reduce methane emissions from ruminant livestock. This review will discuss how to improve the conversion efficiency using pasture management to reduce or mitigate enteric methane production

Registration of ultrasound volumes based on Euclidean distance transform

During neurosurgical operations, surgeons can decide to acquire intraoperative data to better proceed with the removal of a tumor. A valid option is given by ultrasound (US) imaging, which can be easily obtained at subsequent surgical stages, giving therefore multiple updates of the resection cavity. To improve the efficacy of the intraoperative guidance, neurosurgeons may benefit from having a direct correspondence between anatomical structures identified at different US acquisitions. In this context, the commonly available neuronavigation systems already provide registration methods, which however are not enough accurate to overcome the anatomical changes happening during resection. Therefore, our aim with this work is to improve the registration of intraoperative US volumes. In the proposed methodology, first a distance mapping of automatically segmented anatomical structures is computed and then the transformed images are utilized in the registration step. Our solution is tested on a public dataset of 17 cases, where the average landmark registration error between volumes acquired at the beginning and at the end of neurosurgical procedures is reduced from 3.55mm to 1.27mm

Traffic-Related Air Pollution and Perinatal Mortality: A Case–Control Study

BACKGROUND: Ambient levels of air pollution may affect the health of children, as indicated by studies of infant and perinatal mortality. Scientific evidence has also correlated low birth weight and preterm birth, which are important determinants of perinatal death, with air pollution. However, most of these studies used ambient concentrations measured at monitoring sites, which may not consider differential exposure to pollutants found at elevated concentrations near heavy-traffic roadways. OBJECTIVES: Our goal was to examine the association between traffic-related pollution and perinatal mortality. METHODS: We used the information collected for a case-control study conducted in 14 districts in the City of Sao Paulo, Brazil, regarding risk factors for perinatal deaths. We geocoded the residential addresses of cases (fetal and early neonatal deaths) and controls (children who survived the 28th day of life) and calculated a distance-weighted traffic density (DWTD) measure considering all roads contained in a buffer surrounding these homes. RESULTS: Logistic regression revealed a gradient of increasing risk of early neonatal death with higher exposure to traffic-related air pollution. Mothers exposed to the highest quartile of the DWTD compared with those less exposed exhibited approximately 50% increased risk (adjusted odds ratio = 1.47; 95% confidence interval, 0.67-3.19). Associations for fetal mortality were less consistent. CONCLUSIONS: These results suggest that motor vehicle exhaust exposures may be a risk factor for perinatal mortality

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality

Multivariate analysis reveals genetic diversity in Paspalum notatum Flügge

The objective of this study was to evaluate 94 Paspalum notatum genotypes over two growing seasons to estimate genetic dissimilarity through agronomic traits and the distance between genotypes. This information is used to create an ideotype from the best averages obtained for the set of characteristics evaluated. Seven apomitic, three sexual, and 81 hybrid genotypes were compared with native genotypes “André da Rocha”, “Bagual”, and cultivar “Pensacola” as controls. There is genetic variability in P. notatum for the studied characteristics, and distinct genotypes with superior characteristics can be used in new combinations between apomictic and sexual plants to obtain hybrids. The characters with the greatest relative contribution to the dissimilarity between the genotypes were tiller density, stem dry mass, and leaf dry mass yield. Thus, these characteristics are suitable criteria to infer genetic distance studies in P. notatum. The selection index based on the ideotype is an auxiliary tool in the breeding process. The ideotype must be based on characteristics of interest according to the objective of the breeding program, as well as on the breeder’s prior knowledge in relation to culture

The antiapoptotic gene survivin is highly expressed in human chondrosarcoma and promotes drug resistance in chondrosarcoma cells in vitro

Background Chondrosarcoma is virtually resistant to chemotherapy and radiation therapy. Survivin, the smallest member of the inhibitor of apoptosis protein family, is a critical factor for tumor progression and resistance to conventional therapeutic approaches in a wide range of malignancies. However, the role of survivin in chondrosarcoma has not been well studied. We examined the importance of survivin gene expression in chondrosarcoma and analysed its influences on proliferation, apoptosis and resistance to chemotherapy in vitro. Methods Resected chondrosarcoma specimens from which paraffin-embedded tissues could be extracted were available from 12 patients. In vitro experiments were performed in human chondrosarcoma cell lines SW1353 and Hs819.T. Immunohistochemistry, immunoblot, quantitative PCR, RNA interference, gene-overexpression and analyses of cell proliferation and apoptosis were performed. Results Expression of survivin protein was detected in all chondrosarcoma specimens analyzed, while undetectable in adult human cartilage. RNA interference targeting survivin resulted in a G2/M-arrest of the cell cycle and led to increased rates of apoptosis in chondrosarcoma cells in vitro. Overexpression of survivin resulted in pronounced resistance to doxorubicin treatment. Conclusions These findings indicate that survivin plays a role in the pathogenesis and pronounced chemoresistance of high grade chondrosarcoma. Survivin antagonizing therapeutic strategies may lead to new treatment options in unresectable and metastasized chondrosarcoma