P2Z/P2X7 receptor-dependent apoptosis of dendritic cells

Macrophages andthymocytes expressP_2Z/P2X₇nucleotide receptors that bind extracellular ATP. These receptors playa role in immune development and control of microbial infections, but their presence on dendritic cells has not been reported. Weinvestigated whether extracellular ATP could triggerP_2Z/P2X₇receptor-dependent apoptosis of dendritic cells. Apoptosis could beselectively triggered by tetrabasic ATP, since otherpurine/pyrimidine nucleotides were ineffective, and it wasmimicked by the P_2Z receptoragonist, benzoylbenzoyl ATP, and blocked by magnesium and theirreversible antagonist, oxidized ATP. RT-PCR analysis confirmed themRNA expression of theP_2Z/P2X₇receptor and the absence of P2X₁.Caspase inhibitors and cycloheximide had only a partial effect on theapoptosis, suggesting that a caspase-independent mechanism may also beoperative. Brief treatment with ATP led to an increase in theintracellular calcium concentration and permeabilization of the plasmamembrane to Lucifer yellow, which diffused throughout the dendriticcell cytosol. Other small extracellular molecules may thus attain a similar intracellular distribution, perhaps activating endogenous proteases that contribute to initiation of apoptosis.     

Origin and dispersion pathways of guava in the Galapagos Islands inferred through genetics and historical records

Guava (Psidium guajava) is an aggressive invasive plant in the Galapagos Islands. Determining its provenance and genetic diversity could explain its adaptability and spread, and how this relates to past human activities. With this purpose, we analyzed 11 SSR markers in guava individuals from Isabela, Santa Cruz, San Cristobal, and Floreana islands in the Galapagos, as well as from mainland Ecuador. The mainland guava population appeared genetically differentiated from the Galapagos populations, with higher genetic diversity levels found in the former. We consistently found that the Central Highlands region of mainland Ecuador is one of the most likely origins of the Galapagos populations. Moreover, the guavas from Isabela and Floreana show a potential genetic input from southern mainland Ecuador, while the population from San Cristobal would be linked to the coastal mainland regions. Interestingly, the proposed origins for the Galapagos guava coincide with the first human settlings of the archipelago. Through approximate Bayesian computation, we propose a model where San Cristobal was the first island to be colonized by guava from the mainland, and then, it would have spread to Floreana and finally to Santa Cruz; Isabela would have been seeded from Floreana. An independent trajectory could also have contributed to the invasion of Floreana and Isabela. The pathway shown in our model agrees with the human colonization history of the different islands in the Galapagos. Our model, in conjunction with the clustering patterns of the individuals (based on genetic distances), suggests that guava introduction history in the Galapagos archipelago was driven by either a single event or a series of introduction events in rapid succession. We thus show that genetic analyses supported by historical sources can be used to track the arrival and spread of invasive species in novel habitats and the potential role of human activities in such processes.     

Sea surface temperature,rather than land mass or geographic distance,may drive genetic differentiation in a species complex of highly dispersive seabirds

Seabirds, particularly Procellariiformes, are highly mobile organisms with a great capacity for long dispersal, though simultaneously showing high philopatry, two conflicting life‐history traits that may lead to contrasted patterns of genetic population structure. Landmasses were suggested to explain differentiation patterns observed in seabirds, but philopatry, isolation by distance, segregation between breeding and nonbreeding zones, and oceanographic conditions (sea surface temperatures) may also contribute to differentiation patterns. To our knowledge, no study has simultaneously contrasted the multiple factors contributing to the diversification of seabird species, especially in the gray zone of speciation. We conducted a multilocus phylogeographic study on a widespread seabird species complex, the little shearwater complex, showing highly homogeneous morphology, which led to considerable taxonomic debate. We sequenced three mitochondrial and six nuclear markers on all extant populations from the Atlantic (lherminieri) and Indian Oceans (bailloni), that is, five nominal lineages from 13 populations, along with one population from the eastern Pacific Ocean (representing the dichrous lineage). We found sharp differentiation among populations separated by the African continent with both mitochondrial and nuclear markers, while only mitochondrial markers allowed characterizing the five nominal lineages. No differentiation could be detected within these five lineages, questioning the strong level of philopatry showed by these shearwaters. Finally, we propose that Atlantic populations likely originated from the Indian Ocean. Within the Atlantic, a stepping‐stone process accounts for the current distribution. Based on our divergence time estimates, we suggest that the observed pattern of differentiation mostly resulted from historical and current variation in sea surface temperatures.     

Diagnostic performance of chest radiography measurements for the assessment of cardiac chamber enlargement

Background:The cardiothoracic ratio (CTR) is commonly assessed on chest radiography for detection of cardiac chamber enlargement, but the traditional cutpoint of 0.5 has low specificity. We sought to evaluate the diagnostic accuracy of new measurement techniques for the detection of cardiac enlargement on chest radiographs.Methods:We obtained retrospective cross-sectional data on consecutive patients who underwent both chest radiography and cardiac magnetic resonance imaging (MRI) within a 14-day interval between 2006 and 2016 at a large academic hospital network. We established the presence of cardiac chamber enlargement using cardiac MRI as the reference standard. We evaluated the diagnostic performance of different techniques for measuring heart size and CTR on frontal chest radiographs.Results:Of 152 patients included, 81 (53%) were men and the mean age was 52 years. Maximum heart diameter had the highest area under the receiver operating characteristic curve for detection of cardiac enlargement (0.827, 95% confidence interval 0.760–0.894). In the subgroup of posteroanterior chest radiography studies (n = 101), a CTR cutpoint of 0.50 had only moderate sensitivity (72%) and specificity (72%). In men, a maximum heart diameter cutpoint of 15 cm had a sensitivity of 86% and a negative likelihood ratio of 0.24, and a cutpoint of 19 cm had a specificity of 100% and a positive likelihood ratio of infinity. In women, a maximum heart diameter cutpoint of 13 cm had a sensitivity of 91% and a negative likelihood ratio of 0.15, and a cutpoint of 17 cm had a specificity of 91% and a positive likelihood ratio of 3.5.Interpretation:A traditional CTR cutpoint of 0.5 has limited diagnostic value. Simple heart diameter measurements have higher diagnostic performance measures than CTR.

Cardiac chamber enlargement is important to identify, given that it is a predictor of poor outcomes and may reflect potentially treatable underlying disease.¹ Cardiac chamber size can be assessed using multiple imaging modalities, including chest radiography, echocardiography, computed tomography and cardiac magnetic resonance imaging (MRI).^2–4 Although cardiac MRI is considered the reference standard for the evaluation of cardiac size and function, it is rarely performed as an initial investigation because of its relatively high cost and limited availability.⁵ On the other hand, chest radiography is frequently performed as the initial imaging investigation for suspected pulmonary and cardiac disease, including in patients presenting with shortness of breath and chest pain.^6,7 Therefore, accurate and reproducible measures of cardiac enlargement on chest radiography would help to identify patients with underlying cardiac disease who might benefit from further investigation.Cardiac enlargement is frequently evaluated on chest radiography using the cardiothoracic ratio (CTR), which was originally described in 1919.⁸ Although this sign is an accepted and frequently used marker of cardiac enlargement, it has not been validated against cardiac MRI or other contemporary methods of objectively assessing cardiac chamber size. Some studies have shown that the CTR, as assessed using the originally described cutpoint of 0.5, has low specificity and diagnostic accuracy for cardiac enlargement, and therefore may be of limited clinical utility.^9–11 The purpose of this study was to evaluate new measurement techniques and cutpoints for the detection of cardiac chamber enlargement on chest radiography in comparison with MRI.     

Molecular and mineral responses of corals grown under artificial Calcite Sea conditions

The formation of skeletal structures composed of different calcium carbonate polymorphs (e.g. aragonite and calcite) appears to be both biologically and environmentally regulated. Among environmental factors influencing aragonite and calcite precipitation, changes in seawater conditions—primarily in the molar ratio of magnesium and calcium during so-called ‘Calcite’ (mMg:mCa below 2) or ‘Aragonite’ seas (mMg:mCa above 2)—have had profound impacts on the distribution and performance of marine calcifiers throughout Earth's history. Nonetheless, the fossil record shows that some species appear to have counteracted such changes and kept their skeleton polymorph unaltered. Here, the aragonitic octocoral Heliopora coerulea and the aragonitic scleractinian Montipora digitata were exposed to Calcite Sea-like mMg:mCa with various levels of magnesium and calcium concentration, and changes in both the mineralogy (i.e. CaCO₃ polymorph) and gene expression were monitored. Both species maintained aragonite deposition at lower mMg:mCa ratios, while concurrent calcite presence was only detected in M. digitata. Despite a strong variability between independent experimental replicates for both species, the expression for a set of putative calcification-related genes, including known components of the M. digitata skeleton organic matrix (SkOM), was found to consistently change at lower mMg:mCa. These results support the previously proposed involvements of the SkOM in counteracting decreases in seawater mMg:mCa. Although no consistent expression changes in calcium and magnesium transporters were observed, down-regulation calcium channels in H. coerulea in one experimental replicate and at an mMg:mCa of 2.5, pointing to a possible active calcium uptake regulation by the corals under altered mMg:mCa.     

Increasing calling accuracy,coverage, and read-depth in sequence data by the use of haplotype blocks

High-throughput genotyping of large numbers of lines remains a key challenge in plant genetics, requiring geneticists and breeders to find a balance between data quality and the number of genotyped lines under a variety of different existing genotyping technologies when resources are limited. In this work, we are proposing a new imputation pipeline (“HBimpute”) that can be used to generate high-quality genomic data from low read-depth whole-genome-sequence data. The key idea of the pipeline is the use of haplotype blocks from the software HaploBlocker to identify locally similar lines and subsequently use the reads of all locally similar lines in the variant calling for a specific line. The effectiveness of the pipeline is showcased on a dataset of 321 doubled haploid lines of a European maize landrace, which were sequenced at 0.5X read-depth. The overall imputing error rates are cut in half compared to state-of-the-art software like BEAGLE and STITCH, while the average read-depth is increased to 83X, thus enabling the calling of copy number variation. The usefulness of the obtained imputed data panel is further evaluated by comparing the performance of sequence data in common breeding applications to that of genomic data generated with a genotyping array. For both genome-wide association studies and genomic prediction, results are on par or even slightly better than results obtained with high-density array data (600k). In particular for genomic prediction, we observe slightly higher data quality for the sequence data compared to the 600k array in the form of higher prediction accuracies. This occurred specifically when reducing the data panel to the set of overlapping markers between sequence and array, indicating that sequencing data can benefit from the same marker ascertainment as used in the array process to increase the quality and usability of genomic data.     

Signal transduction mechanisms in Trypanosoma cruzi

Trypanosoma cruzi, the etiological agent of Chagas disease, is an adequate model for studies on the evolution of signal transduction pathways. These pathways involve molecular entities such as membrane receptors, transduction G proteins, protein kinases and second messengers (Ca(2+), cyclic AMP, cyclic GMP, nitric oxide). In this article, Mirtha M. Flawiá, María T. Téllez-I?ón and Héctor N. Torres describe the studies performed on T. cruzi transduction pathways and their role in the control of metacyclogenesis and cell motility.     

Typing Tuber melanosporum and Chinese black truffle species by molecular markers

Morphologically similar species such as Chinese black truffles and Tuber melanosporum were typed by restriction length polymorphism of internal transcribed spacers. This analysis together with sequence comparison revealed the presence of high genetic variability among fruit bodies collected in China. Selection of primer pairs allowed the internal transcribed spacer region of both Chinese truffles and T. melanosporum to be specifically amplified.