Motivation: Bayesian analysis is one of the most popular methods in phylogenetic inference. The most commonly used methods fix a single multiple alignment and consider only substitutions as ...phylogenetically informative mutations, though alignments and phylogenies should be inferred jointly as insertions and deletions also carry informative signals. Methods addressing these issues have been developed only recently and there has not been so far a user-friendly program with a graphical interface that implements these methods. Results: We have developed an extendable software package in the Java programming language that samples from the joint posterior distribution of phylogenies, alignments and evolutionary parameters by applying the Markov chain Monte Carlo method. The package also offers tools for efficient on-the-fly summarization of the results. It has a graphical interface to configure, start and supervise the analysis, to track the status of the Markov chain and to save the results. The background model for insertions and deletions can be combined with any substitution model. It is easy to add new substitution models to the software package as plugins. The samples from the Markov chain can be summarized in several ways, and new postprocessing plugins may also be installed. Availability: The code is available from http://phylogeny-cafe.elte.hu/StatAlign/ Contact: miklosi@ramet.elte.hu
A standard procedure in many areas of bioinformatics is to use a single multiple sequence alignment (MSA) as the basis for various types of analysis. However, downstream results may be highly ...sensitive to the alignment used, and neglecting the uncertainty in the alignment can lead to significant bias in the resulting inference. In recent years, a number of approaches have been developed for probabilistic sampling of alignments, rather than simply generating a single optimum. However, this type of probabilistic information is currently not widely used in the context of downstream inference, since most existing algorithms are set up to make use of a single alignment.
In this work we present a framework for representing a set of sampled alignments as a directed acyclic graph (DAG) whose nodes are alignment columns; each path through this DAG then represents a valid alignment. Since the probabilities of individual columns can be estimated from empirical frequencies, this approach enables sample-based estimation of posterior alignment probabilities. Moreover, due to conditional independencies between columns, the graph structure encodes a much larger set of alignments than the original set of sampled MSAs, such that the effective sample size is greatly increased.
The alignment DAG provides a natural way to represent a distribution in the space of MSAs, and allows for existing algorithms to be efficiently scaled up to operate on large sets of alignments. As an example, we show how this can be used to compute marginal probabilities for tree topologies, averaging over a very large number of MSAs. This framework can also be used to generate a statistically meaningful summary alignment; example applications show that this summary alignment is consistently more accurate than the majority of the alignment samples, leading to improvements in downstream tree inference. Implementations of the methods described in this article are available at http://statalign.github.io/WeaveAlign .
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Following the return of Ladislaus the Posthumous, John Hunyadi, in recognition of his previous services, gained an extension to his coat of arms from the ruler, and, in addition, he was granted with ...the title Count of Bistrița (Hung. Beszterce). His eldest son Ladislaus also held the title. Pressed under texts, several copies of his red wax seal have survived; however, these are damaged, fragmented and blurred. Only a charter, dated Buda, March 31, 1456 in the charter collection of the counts of Celje (Cilli) in the Archives of the Republic of Slovenia (Arhiv Republike Slovenije) has a well preserved and intact pendant seal. It contains both seals of the counts of Bistrița, John Hunyadi and his son, Ladislaus Hunyadi. The aim of this paper is to present the brief historical background of the charter and to describe seals found on the charter.
In this paper, we introduce a progressive corner cutting method called Reticular Alignment for multiple sequence alignment. Unlike previous corner-cutting methods, our approach does not define a ...compact part of the dynamic programming table. Instead, it defines a set of optimal and suboptimal alignments at each step during the progressive alignment. The set of alignments are represented with a network to store them and use them during the progressive alignment in an efficient way. The program contains a threshold parameter on which the size of the network depends. The larger the threshold parameter and thus the network, the deeper the search in the alignment space for better scored alignments.
We implemented the program in the Java programming language, and tested it on the BAliBASE database. Reticular Alignment can outperform ClustalW even if a very simple scoring scheme (BLOSUM62 and affine gap penalty) is implemented and merely the threshold value is increased. However, this set-up is not sufficient for outperforming other cutting-edge alignment methods. On the other hand, the reticular alignment search strategy together with sophisticated scoring schemes (for example, differentiating gap penalties for hydrophobic and hydrophylic amino acids) overcome FSA and in some accuracy measurement, even MAFFT. The program is available from http://phylogeny-cafe.elte.hu/RetAlign/
Reticular alignment is an efficient search strategy for finding accurate multiple alignments. The highest accuracy achieved when this searching strategy is combined with sophisticated scoring schemes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mannans are components of the fungal wall attached to proteins via
- or
-linkages. In
, Och1 is an α1,6-mannosyltransferase that adds the first mannose unit to the
-linked mannan outer chain; whereas ...Pmr1 is an ion pump that imports Mn
into the Golgi lumen. This cation is the cofactor of Golgi-resident mannosyltransferases, and thus Pmr1 is involved in the synthesis of both
- and
-linked mannans. Since we currently have limited information about the genetic network behind the
protein mannosylation machinery, we disrupted
and
in this organism. The
Δ and
Δ mutants showed increased doubling times, aberrant colony and cellular morphology, reduction in the wall mannan content, and increased susceptibility to wall perturbing agents. These changes were accompanied by increased exposure of both β1,3-glucan and chitin at the wall surface of both mutant strains. Our results showed that
-linked mannans are dispensable for cytokine production by human mononuclear cells, but
-linked mannans and β1,3-glucan are key ligands to trigger cytokine production in a co-stimulatory pathway involving dectin-1 and mannose receptor. Moreover, we found that the
-linked mannan core found on the surface of
Δ null mutant was capable of inducing cytokine production; and that a mannan-independent pathway for IL-10 production is present in the
-mononuclear cell interaction. Both mutant strains showed virulence attenuation in the
and the mouse model of systemic candidiasis. Therefore, mannans are relevant for cell wall composition and organization, and for the
-host interaction.
For sequences that are highly divergent, there is often insufficient information to infer accurate alignments, and phylogenetic uncertainty may be high. One way to address this issue is to make use ...of protein structural information, since structures generally diverge more slowly than sequences. In this work, we extend a recently developed stochastic model of pairwise structural evolution to multiple structures on a tree, analytically integrating over ancestral structures to permit efficient likelihood computations under the resulting joint sequence-structure model. We observe that the inclusion of structural information significantly reduces alignment and topology uncertainty, and reduces the number of topology and alignment errors in cases where the true trees and alignments are known. In some cases, the inclusion of structure results in changes to the consensus topology, indicating that structure may contain additional information beyond that which can be obtained from sequences. We use the model to investigate the order of divergence of cytoglobins, myoglobins, and hemoglobins and observe a stabilization of phylogenetic inference: although a sequence-based inference assigns significant posterior probability to several different topologies, the structural model strongly favors one of these over the others and is more robust to the choice of data set.
The spleen tyrosine kinase (Syk) and the downstream adaptor protein CARD9 are crucial signaling molecules in antimicrobial immunity. Candida parapsilosis is an emerging fungal pathogen with a high ...incidence in neonates, while Candida albicans is the most common agent of candidiasis. While signaling through Syk/CARD9 promotes protective host mechanisms in response to C. albicans, its function in immunity against C. parapsilosis remains unclear. Here, we generated Syk
and CARD9
bone marrow chimeric mice to study the role of Syk/CARD9 signaling in immune responses to C. parapsilosis compared to C. albicans. We demonstrate various functions of this pathway (e.g., phagocytosis, phagosome acidification, and killing) in
-challenged, bone marrow-derived macrophages with differential involvement of Syk and CARD9 along with species-specific differences in cytokine production. We report that Syk
or CARD9
chimeras rapidly display high susceptibility to C. albicans, while C. parapsilosis infection exacerbates over a prolonged period in these animals. Thus, our results establish that Syk and CARD9 contribute to systemic resistance to C. parapsilosis and C. albicans differently. Additionally, we confirm prior studies but also detail new insights into the fundamental roles of both proteins in immunity against C. albicans. Our data further suggest that Syk has a more prominent influence on anti-
immunity than CARD9. Therefore, this study reinforces the Syk/CARD9 pathway as a potential target for anti-
immune therapy.
While C. albicans remains the most clinically significant
species, C. parapsilosis is an emerging pathogen with increased affinity to neonates. Syk/CARD9 signaling is crucial in immunity to C. albicans, but its role in
responses to other pathogenic
species is largely unexplored. We used mice with hematopoietic systems deficient in Syk or CARD9 to comparatively study the function of these proteins in anti-
immunity. We demonstrate that Syk/CARD9 signaling has a protective role against C. parapsilosis differently than against C. albicans. Thus, this study is the first to reveal that Syk can exert immune responses during systemic
infections species specifically. Additionally, Syk-dependent immunity to a nonalbicans
species in an
murine model has not been reported previously. We highlight that the contribution of Syk and CARD9 to fungal infections are not identical and underline this pathway as a promising immune-therapeutic target to fight
infections.
Comparative methods have been the standard techniques for in silico protein structure prediction. The prediction is based on a multiple alignment that contains both reference sequences with known ...structures and the sequence whose unknown structure is predicted. Intensive research has been made to improve the quality of multiple alignments, since misaligned parts of the multiple alignment yield misleading predictions. However, sometimes all methods fail to predict the correct alignment, because the evolutionary signal is too weak to find the homologous parts due to the large number of mutations that separate the sequences.
Stochastic sequence alignment methods define a posterior distribution of possible multiple alignments. They can highlight the most likely alignment, and above that, they can give posterior probabilities for each alignment column. We made a comprehensive study on the HOMSTRAD database of structural alignments, predicting secondary structures in four different ways. We showed that alignment posterior probabilities correlate with the reliability of secondary structure predictions, though the strength of the correlation is different for different protocols. The correspondence between the reliability of secondary structure predictions and alignment posterior probabilities is the closest to the identity function when the secondary structure posterior probabilities are calculated from the posterior distribution of multiple alignments. The largest deviation from the identity function has been obtained in the case of predicting secondary structures from a single optimal pairwise alignment. We also showed that alignment posterior probabilities correlate with the 3D distances between C alpha amino acids in superimposed tertiary structures.
Alignment posterior probabilities can be used to a priori detect errors in comparative models on the sequence alignment level.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
One might perceive the Middle Ages as an era of certain rights and privileges. Social stratification or the conformation of a group’s identity were all established around privileges in the Kingdom of ...Hungary. In the medieval period, as opposed to a modern state, the most important constructors of a group’s identity were privileges. When members of a social group bear identical prerogatives, that group can be recognized as an order or estate. The ecclesiastic order existed side-by-side with the noble estate. In possession of political power were strictly those who were at the top of the strongly hierarchical system. However, in the Kingdom of Hungary, the significance of the ecclesiastical order was dwarfed by the importance of landed nobility. Some five percent of the population was of nobles, who also held political power. Until the end of the 15th century, the members of this stratum were equal in law. Only distinctions in financial situation can be noticed during the 14th and 15th centuries. The first law differentiating the rights within nobility was enacted by the national assembly, the diet of Wladislaus II (1490–1516), in 1498. Only from then on can we speak of gentry and aristocracy. This almost two-century-long process can be observed by examining a representational tool, the usage of red wax in seals. Upon studying medieval Hungarian history, we must use all sources available due to their rapid destruction, hence examining seal usage to explain aristocratic representation. In this paper, we briefly summarize the social structure of medieval Hungary and its traditions in seal usage, and present several unique seals. Our goal is to highlight some connections that historiography would benefit from, to provide new data, and to arouse the interest of a broad spectrum of audiences in Hungarian social history.
The author deals with the legal regulation of the management of primary microplastics at the EU level. The article is mainly devoted to the comparison of the already existing legal regulation of some ...EU Member States, which have already adopted measures concerning the handling of so-called microbeads. Furthermore, the author deals with the comparison of these legal regulations with the prepared amendment to the REACH Regulation, which should fundamentally affect the management of primary microplastics within the EU and also serves as a harmonization regulation. Following this comparison, the author also briefly discusses the possibility of member states retaining their national legislation, especially if this legislation is broader than European legislation.
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