The accurate inference of gene trees is a necessary step in many evolutionary studies. Although the problem of accurate gene tree inference has received considerable attention, most existing methods ...are only applicable to gene families unaffected by horizontal gene transfer. As a result, the accurate inference of gene trees affected by horizontal gene transfer remains a largely unaddressed problem.
In this study, we introduce a new and highly effective method for gene tree error correction in the presence of horizontal gene transfer. Our method efficiently models horizontal gene transfers, gene duplications and losses, and uses a statistical hypothesis testing framework Shimodaira-Hasegawa (SH) test to balance sequence likelihood with topological information from a known species tree. Using a thorough simulation study, we show that existing phylogenetic methods yield inaccurate gene trees when applied to horizontally transferred gene families and that our method dramatically improves gene tree accuracy. We apply our method to a dataset of 11 cyanobacterial species and demonstrate the large impact of gene tree accuracy on downstream evolutionary analyses.
An implementation of our method is available at http://compbio.mit.edu/treefix-dtl/
: mukul@engr.uconn.edu or manoli@mit.edu
Supplementary data are available at Bioinformatics online.
Phylogenetic analyses commonly assume that the species history can be represented as a tree. However, in the presence of hybridization, the species history is more accurately captured as a network. ...Despite several advances in modeling phylogenetic networks, there is no known polynomial-time algorithm for parsimoniously reconciling gene trees with species networks while accounting for incomplete lineage sorting. To address this issue, we present a polynomial-time algorithm for the case of level-1 networks, in which no hybrid species is the direct ancestor of another hybrid species. This work enables more efficient reconciliation of gene trees with species networks, which in turn, enables more efficient reconstruction of species networks.
To investigate the retinal sensitivity of highly myopic eyes with chorioretinal patchy atrophy (PA) using microperimetry.
Fifty-two eyes of 32 patients with high myopia were prospectively included. ...Twenty-two eyes of 16 patients had PA lesions; eyes without PA were analyzed as controls. Testing points on microperimetry in eyes with PA were designated as 3 zones: zone 1 as the PA lesion including its borders; zone 2 including testing points adjoining PA; zone 3 including all other testing points.
In the PA group, the mean retinal sensitivity in zone 1 was 2.1 ± 2.8 dB, zone 2 = 8.3 ± 4.3 dB, and zone 3 = 9.4 ± 4.1 dB. Sensitivity in zone 1 was significantly reduced than zones 2 and 3 (P < 0.001). The mean retinal sensitivity in the PA group was lower than controls (6.5 ± 4.3 vs 13.9 ± 4.1 dB, P < 0.001), and combined zone 2 and 3 in the PA group also presented lower retinal sensitivity (8.8 ± 4.0 dB).
Eyes with PA generate patchy scotoma in PA lesions and reduced retinal sensitivity in regions beyond atrophic lesion on microperimetry. The presence of PA may be an indicator to reflect both significantly anatomical and functional alterations on myopic macular degeneration.
Tissue-clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We ...introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain and is able to be used as the evaluation of disease treatment efficiency. HIF-Clear also supports expansion microscopy and can be performed on a non-sectioned 15-year-old FFPE specimen, as well as a 3-month formalin-fixed mouse brain. Thus, HIF-Clear represents a feasible approach for researching archived FFPE specimens for future neuroscientific and 3D neuropathological analyses.
Accurate gene tree-species tree reconciliation is fundamental to inferring the evolutionary history of a gene family. However, although it has long been appreciated that population-related effects ...such as incomplete lineage sorting (ILS) can dramatically affect the gene tree, many of the most popular reconciliation methods consider discordance only due to gene duplication and loss (and sometimes horizontal gene transfer). Methods that do model ILS are either highly parameterized or consider a restricted set of histories, thus limiting their applicability and accuracy. To address these challenges, we present a novel algorithm DLCpar for inferring a most parsimonious (MP) history of a gene family in the presence of duplications, losses, and ILS. Our algorithm relies on a new reconciliation structure, the labeled coalescent tree (LCT), that simultaneously describes coalescent and duplication-loss history. We show that the LCT representation enables an exhaustive and efficient search over the space of reconciliations, and, for most gene families, the least common ancestor (LCA) mapping is an optimal solution for the species mapping between the gene tree and species tree in an MP LCT. Applying our algorithm to a variety of clades, including flies, fungi, and primates, as well as to simulated phylogenies, we achieve high accuracy, comparable to sophisticated probabilistic reconciliation methods, at reduced run time and with far fewer parameters. These properties enable inferences of the complex evolution of gene families across a broad range of species and large data sets.
Chronic obstructive pulmonary disease (COPD) is a progressive lung disease with high morbidity and mortality worldwide. Although several mechanisms to account for deleterious immune effects were ...proposed, molecular description for the underlying alveolar structural alterations for COPD is lacking. Here, silencing of α1,6-fucosyltransferase (Fut8), the enzyme for core-fucosylation and highly expressed in lung stem cells, resulted in alveolar structural changes in lung organoids, recapitulating COPD. Site-specific mass spectrometry analysis demonstrated that the secreted protein acidic and rich in cysteine (SPARC), which binds collagen, contains a core-fucosylation site in its VCSNDN
cf
K glycopeptide. Biacore assay showed markedly reduced collagen binding of SPARC lacking core fucosylation. Molecular dynamics analysis revealed that core fucosylation of SPARC-induced dynamic conformational changes in its N-glycan, allowing terminal galactose and N-acetylglucosamine to interact with K150, P261 and H264 residues, thereby promoting collagen binding. Site-specific mutagenesis of these residues also resulted in low affinity for collagen binding. Moreover, loss of collagen and decline of core fucosylation were observed in COPD lung tissues. These findings provide a new mechanistic insight into the role of core fucosylation of SPARC in cell–matrix communication and contribution to the abnormal alveolar structures in COPD.
New neurons are continuously generated in hippocampal subgranular zone throughout life, and the amount of neurogenesis is suggested to be correlated with the hippocampus-dependent function. Several ...extrinsic stimuli are known to modulate the neurogenesis process. Among them, physical exercise has advantageous effects on neurogenesis and brain function, while inflammation shows the opposite. Herein we showed that a moderate running exercise successfully restored the peripheral lipopolysaccharide (LPS)-impaired neurogenesis in the dentate area. LPS treatment obstructed neuronal differentiation, but not proliferation. Exercise training facilitated both the proliferation of the neural stem cells and their differentiation into neurons. Interestingly, exercise replenished the LPS-reduced levels of brain-derived neurotrophic factor and its receptor, TrkB, and rescued the LPS-disturbed performance in water maze; while the LPS-elicited up-regulation of tumor necrosis factor-alpha and interleukin-1β remained unaltered. In conclusion, our findings suggest that running exercise effectively ameliorates the LPS-disturbed hippocampal neurogenesis and learning and memory performance. Such advantageous effects of running exercise are not due to the alteration of inflammatory response, but possibly by the restoring the LPS-lessened brain-derived neurotrophic factor signaling pathway.
The present study has used a variety of characterization techniques to determine the products and reaction pathways involved in the rechargeable Li–FeS2 system. We revisit both the initial lithiation ...and subsequent cycling of FeS2 employing an ionic liquid electrolyte to investigate the intermediate and final charge products formed under varying thermal conditions (room temperature to 100 °C). The detection of Li2S and hexagonal FeS as the intermediate phases in the initial lithiation and the electrochemical formation of greigite, Fe3S4, as a charge product in the rechargeable reaction differ significantly from previous reports. The conditions for Fe3S4 formation are shown to be dependent on both the temperature (∼60 °C) and the availability of sulfur to drive a FeS to Fe3S4 transformation. Upon further cycling, Fe3S4 transforms to a lower sulfur content iron sulfide phase, a process which coincides with the loss of sulfur based on the new reaction pathways established in this work. The connection between sulfur loss, capacity fade, and charge product composition highlights the critical need to retain sulfur in the active material upon cycling.
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