Analysis of SIRT1 Gene SNPs and Clinical Characteristics in Medication-Related Osteonecrosis of the Jaw.

Certain genetic factors, including single-nucleotide polymorphisms (SNPs) in the SIRT1 gene, have been linked to medication-related osteonecrosis of the jaw (MRONJ). This study examined four SNPs in the SIRT1 gene and implemented multivariate statistical analysis to analyze genetic and clinical factors in MRONJ patients. Genomic DNA was isolated from peripheral blood samples of 63 patients of European origin treated for MRONJ, and four SNP genotypes in the gene encoding the SIRT-1 protein were determined by Sanger sequencing. The allele frequencies measured in the MRONJ population were compared with allele frequencies measured in the European population in the National Center for Biotechnology Information Allele Frequency Aggregator (NCBI ALFA) database. Genetic and clinical factors were examined with multivariate statistical analysis. A C:A allele distribution ratio of 77.8:22.2 was measured in the rs932658 SNP. In the ALFA project, a C:A allele distribution ratio of 59.9:40.1 was detected in the European population, which was found to be a significant difference (p = 4.5 × 10-5). Multivariate statistical analysis revealed a positive correlation (0.275) between the genotype of SNP rs932658 and the number of stages improved during appropriate MRONJ therapy. It is concluded that allele A in SNP rs932658 in the SIRT1 gene acts as a protective factor in MRONJ.

Multivariate study of lice (Insecta: Psocodea: Phthiraptera) assemblages hosted by hummingbirds (Aves: Trochilidae).

Lice were collected from 579 hummingbirds, representing 49 species, in 19 locations in Brazil, Costa Rica, Honduras, Paraguay and Peru, at elevations 0­3000 m above sea level. The following variables were included in an ecological analysis (1) host species' mean body mass, sexual size dimorphism, sexual dichromatism, migratory behaviour and dominance behaviour; (2) mean elevation, mean and predictability of temperature, mean and predictability of precipitation of the host species' geographic area; (3) prevalence and mean abundance of species of lice as measures of infestation. Ordination methods were applied to evaluate data structure. Since the traits are expressed at different scales (nominal, interval and ratio), a principal component analysis based on d-correlations for the traits and a principal coordinates analysis based on the Gower index for species were applied. Lice or louse eggs were found on 80 (13.8%) birds of 22 species. A total of 267 lice of 4 genera, Trochiloecetes, Trochiliphagus, Myrsidea and Leremenopon, were collected, with a total mean intensity of 4.6. There were positive interactions between migration behaviour and infestation indices, with elevational migrants having a higher prevalence and abundance of lice than resident birds. Further, we found weak negative correlations between host body mass and infestation indices and positive correlations between mean elevation and prevalence and abundance of Trochiliphagus. Thus, formerly unknown differences in the ecological characteristics and infestation measures of Trochiliphagus and Trochiloecetes lice were revealed, which allows a better understanding of these associations and their potential impacts on hummingbirds.

Components of functional diversity revisited: A new classification and its theoretical and practical implications.

Functional diversity is regarded as a key concept for understanding the link between ecosystem function and biodiversity. The different and ecologically well-defined aspects of the concept are reflected by the so-called functional components, for example, functional richness and divergence. Many authors proposed that components be distinguished according to the multivariate technique on which they rely, but more recent studies suggest that several multivariate techniques, providing different functional representations (such as dendrograms and ordinations) of the community can in fact express the same functional component. Here, we review the relevant literature and find that (1) general ecological acceptance of the field is hampered by ambiguous terminology and (2) our understanding of the role of multivariate techniques in defining components is unclear. To address these issues, we provide new definitions for the three basic functional diversity components namely functional richness, functional divergence and functional regularity. In addition, we present a classification of presence-/absence-based approaches suitable for quantifying these components. We focus exclusively on the binary case for its relative simplicity. We find illogical, as well as logical but unused combinations of components and representations; and reveal that components can be quantified almost independently from the functional representation of the community. Finally, theoretical and practical implications of the new classification are discussed.

Characterising functional strategies and trait space of freshwater macroinvertebrates.

We examined the functional strategies and the trait space of 596 European taxa of freshwater macroinvertebrates characterized by 63 fuzzy coded traits belonging to 11 trait groups. Principal component analysis was used to reduce trait dimensionality, to explain ecological strategies, and to quantify the trait space occupied by taxa. Null models were used to compare observed occupancy with theoretical models, and randomization-based analyses were performed to test whether taxonomic relatedness, a proxy of phylogenetic signal, constrains the functional trait space of freshwater macroinvertebrates. We identified four major strategies along which functional traits of the taxa examined show trade-offs. In agreement with expectations and in contrast to existing evidence we found that life cycles and aquatic strategies are important in shaping functional structure of freshwater macroinvertebrates. Our results showed that the taxonomic groups examined fill remarkably different niches in the functional trait space. We found that the functional trait space of freshwater macroinvertebrates is reduced compared to the range of possibilities that would exist if traits varied independently. The observed decrease was between 23.44 and 44.61% depending on the formulation of the null expectations. We demonstrated also that taxonomic relatedness constrains the functional trait space of macroinvertebrates.

Phylogeny of Crataegus (Rosaceae) based on 257 nuclear loci and chloroplast genomes: evaluating the impact of hybridization.

BACKGROUND: Hawthorn species (Crataegus L.; Rosaceae tribe Maleae) form a well-defined clade comprising five subgeneric groups readily distinguished using either molecular or morphological data. While multiple subsidiary groups (taxonomic sections, series) are recognized within some subgenera, the number of and relationships among species in these groups are subject to disagreement. Gametophytic apomixis and polyploidy are prevalent in the genus, and disagreement concerns whether and how apomictic genotypes should be recognized taxonomically. Recent studies suggest that many polyploids arise from hybridization between members of different infrageneric groups. METHODS: We used target capture and high throughput sequencing to obtain nucleotide sequences for 257 nuclear loci and nearly complete chloroplast genomes from a sample of hawthorns representing all five currently recognized subgenera. Our sample is structured to include two examples of intersubgeneric hybrids and their putative diploid and tetraploid parents. We queried the alignment of nuclear loci directly for evidence of hybridization, and compared individual gene trees with each other, and with both the maximum likelihood plastome tree and the nuclear concatenated and multilocus coalescent-based trees. Tree comparisons provided a promising, if challenging (because of the number of comparisons involved) method for visualizing variation in tree topology. We found it useful to deploy comparisons based not only on tree-tree distances but also on a metric of tree-tree concordance that uses extrinsic information about the relatedness of the terminals in comparing tree topologies. RESULTS: We obtained well-supported phylogenies from plastome sequences and from a minimum of 244 low copy-number nuclear loci. These are consistent with a previous morphology-based subgeneric classification of the genus. Despite the high heterogeneity of individual gene trees, we corroborate earlier evidence for the importance of hybridization in the evolution of Crataegus. Hybridization between subgenus Americanae and subgenus Sanguineae was documented for the origin of Sanguineae tetraploids, but not for a tetraploid Americanae species. This is also the first application of target capture probes designed with apple genome sequence. We successfully assembled 95% of 257 loci in Crataegus, indicating their potential utility across the genera of the apple tribe.

A study of community structure and beta diversity of epiphyllous liverwort assemblages in Sabah, Malaysian Borneo.

We evaluated the species richness and beta diversity of epiphyllous assemblages from three selected localities in Sabah, i.e. Mt. Silam in Sapagaya Forest Reserve, and Ulu Senagang and Mt. Alab in Crocker Range Park. A total of 98 species were found and a phytosociological survey was carried out based on the three study areas. A detailed statistical analysis including standard correlation and regression analyses, ordination of species and leaves using centered principal component analysis, and the SDR simplex method to evaluate the beta diversity, was conducted. Beta diversity is very high in the epiphyllous liverwort assemblages in Sabah, with species replacement as the major component of pattern formation and less pronounced richness difference. The community analysis of the epiphyllous communities in Sabah makes possible their detailed description and comparison with similar communities of other continents.

Targeted Mutational Profiling and a Powerful Risk Score as Additional Tools for the Diagnosis of Papillary Thyroid Cancer.

Nowadays, the complementary diagnostics based on the suspicious thyroid lesion specific mutational state analysis is indispensable in the clinical practice. We aimed to test and validate our novel 568-mutational hotspot panel (23 cancer-related genes) on papillary thyroid cancers (PTCs) and their tumor-free pairs to find the most powerful mutation pattern related to PTC. The sequencing method was carried on with Ion Torrent PGM on 67 thyroid tissue samples. The most commonly detected mutation was the BRAF c.1799 T > A in all non-classical PTC cases. We utilized a multivariate statistical method (CVA) to determine a discrimination score based on mutational data array and to assess malignancy risk. Based on variants, the BRAF gene has by far the highest indicative power, followed by TSHR and APC. We highlighted novel aspects of the mutational profile and genetic markers of PTC. CVA has correctly assigned most of the samples based on the mutation frequencies and different variables of the selected genes, with high analytical probabilities. The final goal is to set up a new comprehensive rule-in and rule-out test to support the clinical decision making mainly in inconclusive fine-needle aspiration biopsy cases.

Author Correction: Plant recording across two centuries reveals dramatic changes in species diversity of a Mediterranean archipelago.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

[Genetic testing of thyroid nodules using a gene panel developed on a new generation sequencing platform]. / A pajzsmirigygöbök genetikai vizsgálata újgenerációs szekvenáláson alapuló platformon kifejlesztett génpanel segítségével.

Introduction: Twenty-five percent of fine-needle aspiration biopsy samples of thyroid nodules produce indeterminate cytological results. Genetic testing of nodules can contribute to accurate diagnosis. Aim: Developing the first gene panel in Europe utilizing the 23 most relevant thyroid oncogenes with 568 mutations. Method: Examination of the isolated DNA from biopsy samples by Ion Torrent new generation sequencing. Results: The validation of our method was performed on tumor tissue samples, in which 127 genetic variations were identified, yet unknown in thyroid tumors. AXIN1 was the most polymorphic gene, while BRAF c.1799T>A (V600E) was the most frequently identified mutation. We detected 36 clinically relevant variants, 75% of which have not been described in the literature. Six of our 8 cytologically malignant and 8 of our 14 indeterminate as well as 20 of our 28 cytologically benign samples were identified as containing pathologic variants in a driver gene (BRAF c.1799T>A, NRAS c.181C>A). Conclusion: We have developed a validated, reliable new generation sequencing-based method with high positive predictive value (89%) and sensitivity (79%), suitable for the early detection of malignant lesions in the thyroid. Orv Hetil. 2019; 160(36): 1417-1425.

Long-term selective estrogen receptor-beta agonist treatment modulates gene expression in bone and bone marrow of ovariectomized rats.

Gonadal hormones including 17ß-estradiol exert important protective functions in skeletal homeostasis. However, numerous details of ovarian hormone deficiency in the common bone marrow microenvironment have not yet been revealed and little information is available on the tissue-specific acts either, especially those via estrogen receptor beta (ERß). The aim of the present study was therefore to examine the bone-related gene expression changes after ovariectomy (OVX) and long-term ERß agonist diarylpropionitrile (DPN) administration. We found that OVX produced strong and widespread changes of gene expression in both femoral bone and bone marrow. In the bone out of 22 genes, 20 genes were up- and 2 were downregulated after OVX. It is noteworthy that DPN restored mRNA expression of 10 OVX-induced changes (Aldh2, Col1a1, Daam1, Fgf12, Igf1, Il6r, Nfkb1, Notch1, Notch2 and Psen1) suggesting a modulatory role of ERß in bone physiology. In bone marrow, out of 37 categorized genes, transcription of 25 genes were up- and 12 were downregulated indicating that the marrow is highly responsive to gonadal hormones. DPN modestly affected transcription, only expression of two genes (Nfatc1 and Tgfb1) was restored by DPN action. The PI3K/Akt signaling pathway was the most affected gene cluster following the interventions in bone and bone marrow, as demonstrated by canonical variates analysis (CVA). We suggested that our results contribute to a deeper understanding of alterations in gene expression of bone and bone marrow niche elicited by ERß and selective ERß analogs.

How Fast Does Darwin's Elephant Population Grow?

In "The Origin of Species," Darwin describes a hypothetical example illustrating that large, slowly reproducing mammals such as the elephant can reach very large numbers if population growth is not affected by regulating factors. The elephant example has since been cited in various forms in a wide variety of books, ranging from educational material to encyclopedias. However, Darwin's text was changed over the six editions of the book, although some errors in the mathematics persisted throughout. In addition, full details of the problem remained hidden in his correspondence with readers of the Origin. As a result, Darwin's example is very often misinterpreted, misunderstood or presented as if it were a fact. We show that the population growth of Darwin's elephant population can be modeled by the Leslie matrix method, which we generalize here to males as well. Darwin's most often cited figure, about 19 million elephants after 750 years is not a typical outcome, actually a very unlikely result under more realistic, although still hypothetical situations. We provide a recursion formula suggesting that Darwin's original model corresponds to a tribonacci series, a proof showing that sex ratio is constant over all age classes, and a derivation of a generating function of the sequence.

Plant recording across two centuries reveals dramatic changes in species diversity of a Mediterranean archipelago.

Although islands are model systems for investigating assembly of biological communities, long-term changes in archipelago communities are not well understood because of the lack of reliable data. By using a vast amount of floristic data we assembled a dataset of the plant species occurring on 16 islands of the Tuscan Archipelago, Italy, across two periods, 1830-1950 and 1951-2015. We collected 10,892 occurrence records for 1,831 species. We found major changes in the island plant assemblages between the two periods, with native flora significantly decreasing (-10.7%) and alien flora doubling (+132.1%) in richness. The species-area relationships demonstrated the scale-dependence of the observed changes for native and alien species. The observed floristic changes were dependent on island area, with smaller islands displaying high variability in richness and compositional changes and larger islands having more stable species assemblages. The richness of species associated with open landscapes, that had been maintained for centuries by traditional practices, markedly reduced while the number of woody species, associated with afforestation processes and invasion by alien woody plants, significantly incresed. These results demonstrate the great power of floristic studies, often available in grey literature, for understanding long-term biotic changes in insular ecosystems.

Different from Trees, more than Metaphors: Branching Silhouettes-Corals, Cacti, and the Oaks.

There has long been ambiguity in the use of the term tree in phylogenetic systematics, which is a continuous source of misinterpretation of evolutionary relationships. The basic problem is that while many trees with phylogenetic or evolutionary relevance, such as cladograms, are consistent with graph theory, tree-like visualization of phylogeny may also be done via other types of graphics, especially botanical (or literal) tree drawings. As a consequence, the meaning of such diagrams is not always clear: a given picture may have multiple interpretations in its different parts and two figures that look similar may actually carry quite different information. I show that these are not merely metaphors of phylogeny and may be defined mathematically as geometric shapes called branching silhouette diagrams, the name referring to their most apparent features. They have four basic forms depending on whether the time factor is considered in their construction and the relationships portrayed are of the ancestor-descendant or sister group type. By revitalizing Darwin's early suggestions on the illustration of change in the living world, I propose the term coral for the most common forms of branching silhouette which consider time and show ancestry. The others appear rarely in present-day practice and are mostly of historical value-these are cacti (named after one of Bessey's diagrams) and two types of oaks (with reference to several of Haeckel's motifs used in depicting phylogeny in the nineteenth century). The use of these terms in phylogenetic systematics facilitates better understanding of how organization of biodiversity has been visualized in science [Bessey; cladograms; coral-thinking; Darwin; graph theory; Haeckel; phylogeny; tree thinking.].

A family of functional dissimilarity measures for presence and absence data.

Plot-to-plot dissimilarity measures are considered a valuable tool for understanding the complex ecological mechanisms that drive community composition. Traditional presence/absence coefficients are usually based on different combinations of the matching/mismatching components of the 2 × 2 contingency table. However, more recently, dissimilarity measures that incorporate information about the degree of functional differences between the species in both plots have received increasing attention. This is because such "functional dissimilarity measures" capture information on the species' functional traits, which is ignored by traditional coefficients. Therefore, functional dissimilarity measures tend to correlate more strongly with ecosystem-level processes, as species influence these processes via their traits. In this study, we introduce a new family of dissimilarity measures for presence and absence data, which consider functional dissimilarities among species in the calculation of the matching/mismatching components of the 2 × 2 contingency table. Within this family, the behavior of the Jaccard coefficient, together with its additive components, species replacement, and richness difference, is examined by graphical comparisons and ordinations based on simulated data.

Bad math in Linnaeus' Philosophia Botanica.

In Philosophia Botanica (1751), Carolus Linnaeus (1707-1778) presented a calculation of the number of plant genera that may be distinguished based on his taxonomic concepts. In order to derive that number, he relied upon the organs of fructification, which represent the flower and the fruit, by selecting over 30 elements from them, and then assuming that each could vary by four dimensions. However, while Linnaeus was good in counting stamens and pistils, he and many of his followers who edited or translated Philosophia Botanica were less careful, basing their calculations of the number of possible genera on flawed assumptions, or even introducing basic arithmetic errors. Furthermore, although mathematics was quite advanced in the eighteenth century, the gap between combinatorial and botanical thinking was too deep, preventing Linnaeus to seek a reasonable solution to the problem he raised. The authors demonstrate this by a historical analysis of 15 editions of Philosophia Botanica, plus many references to it, and conclude that the desired number almost always appeared in error during the past 265 years. The German botanist J. G. Gleditsch (1714-1786) was the most successful with respect to Linnaeus' original intention. Elementary mathematics demonstrates that if Linnaeus' assumptions were taken seriously, then the possible number of genera would be astronomical. The practice he followed in Genera Plantarum (1754) shows, however, that the fructification dimensions served as a universal set for Linnaeus from which he chose only the relevant ones for describing a particular genus empirically. Based on the corrections and modifications implemented in reworked editions, we suggest an evolutionary network for the historical and modern versions or translations of Philosophia Botanica.

The genetic diversity of Sardinian myrtle (Myrtus communis L. ) populations

Background: The myrtle (Myrtus communis) is a common shrub widespread in the Mediterranean Basin. Its fruit and leaves exhibit antioxidant, antibacterial and antifungal properties, and are used for their content of essential oils and for their medicinal properties, but most commonly as an ingredient in locally made liquor. The uncontrolled exploitation of natural stands has reduced both the species' geographical coverage and the size of individual populations. The selection of genotypes for controlled cultivation requires a characterization of the genetic diversity present both within and between populations. Results: Genotypic variation was evaluated using ISSR profiling and genetic diversity characterized using standard population genetics approaches. Two major clusters were identified: one capturing all the candidate cultivars selected from various Sardinian localities, and the other wild individuals collected from Asinara, Corsica and Surigheddu. A moderate level of gene flow between the Sardinian and Corsican populations was identified. Discriminant analysis of principal components revealed a level of separation among the wild populations, confirming the population structure identified by the clustering methods. Conclusions: The wild accessions were well differentiated from the candidate cultivars. The level of genetic variability was high. The genetic data were compatible with the notion that myrtle has a mixed pollination system, including both out-pollination by insects and self-pollination. The candidate cultivars are suggested to represent an appropriate basis for directed breeding.

Peripheral blood derived gene panels predict response to infliximab in rheumatoid arthritis and Crohn's disease.

BACKGROUND: Biological therapies have been introduced for the treatment of chronic inflammatory diseases including rheumatoid arthritis (RA) and Crohn's disease (CD). The efficacy of biologics differs from patient to patient. Moreover these therapies are rather expensive, therefore treatment of primary non-responders should be avoided. METHOD: We addressed this issue by combining gene expression profiling and biostatistical approaches. We performed peripheral blood global gene expression profiling in order to filter the genome for target genes in cohorts of 20 CD and 19 RA patients. Then RT-quantitative PCR validation was performed, followed by multivariate analyses of genes in independent cohorts of 20 CD and 15 RA patients, in order to identify sets ofinterrelated genes that can separate responders from non-responders to the humanized chimeric anti-TNFalpha antibody infliximab at baseline. RESULTS: Gene panels separating responders from non-responders were identified using leave-one-out cross-validation test, and a pool of genes that should be tested on larger cohorts was created in both conditions. CONCLUSIONS: Our data show that peripheral blood gene expression profiles are suitable for determining gene panels with high discriminatory power to differentiate responders from non-responders in infliximab therapy at baseline in CD and RA, which could be cross-validated successfully. Biostatistical analysis of peripheral blood gene expression data leads to the identification of gene panels that can help predict responsiveness of therapy and support the clinical decision-making process.

Tree thinking, time and topology: comments on the interpretation of tree diagrams in evolutionary/phylogenetic systematics.

This paper presents a graph theoretical overview of tree diagrams applied extensively in systematic biology. Simple evolutionary models involving three speciation processes (splitting, budding and anagenesis) are used for evaluating the ability of different rooted trees to demonstrate temporal and ancestor-descendant relationships within or among species. On this basis, they are classified into four types: (i) diachronous trees depict evolutionary history faithfully because the order of nodes along any path agrees with the temporal sequence of respective populations or species, (ii) achronous trees show ancestor-descendant relationships for species or higher taxa such that the time aspect is disregarded, (iii) synchronous trees attempt to reveal evolutionary pathways and/or distributional patterns of apomorphic characters for organisms living at the same point of time, and (iv) asynchronous trees may do the same regardless the time of origin (e.g. when extant and extinct species are evaluated together). Trees of the last two types are cladograms, the synchronous ones emphasizing predominantly-but not exclusively-the evolutionary process within a group, while asynchronous cladograms are usually focused on pattern and infrequently on process. Historical comments and the examples demonstrate that each of these tree types is useful on its own right in evolutionary biology and systematics. In practice, separation among them is not sharp, and their features are often combined into eclectic tree forms whose interpretation is not entirely free from problems.

Immune complex signatures of patients with active and inactive SLE revealed by multiplex protein binding analysis on antigen microarrays.

Systemic lupus erythematosus is characterized by dysfunctional clearance of apoptotic debris and the development of pathogenic autoantibodies. While the complement system is also involved in the disease no attempt has been made to generate a comprehensive view of immune complex formation from various autoantigens. We increased the complexity of autoantibody profiles by measuring the binding of two complement proteins, C3 and C4, in addition to two antibody classes, IgG and IgM, to a collection of autoantigens. These complement components covalently bind to those microarray features where antibodies and other serum components induce complement activation. Using this technology, we compared functional serum antibody profiles of control subjects (n = 31) and patients with lupus erythematosus (n = 61) in the active (n = 22) and inactive (n = 39) phase of the disease. Multivariate analysis was applied to identify contributions of binding data on 25 antigens to the discrimination of the study groups. Receiver operating characteristic analysis was used to portray the discriminative property of each measured parameter for each antigen in pairwise group comparisons. Complement C3 and C4 deposition increased on autoantibody targets in spite of the decreased serum complement concentrations, and decreased on other autoantigens, demonstrating the imbalance of complement function in patients with lupus erythematosus. Our observations confirmed previously known markers of disease and showed that C3 and C4 deposition data were at least as powerful as Ig binding data in separating the study groups.

Peripheral blood gene expression and IgG glycosylation profiles as markers of tocilizumab treatment in rheumatoid arthritis.

OBJECTIVE: Tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has recently been approved as a biological therapy for rheumatoid arthritis (RA) and other diseases. It is not known if there are characteristic changes in gene expression and immunoglobulin G glycosylation during therapy or in response to treatment. METHODS: Global gene expression profiles from peripheral blood mononuclear cells of 13 patients with RA and active disease at Week 0 (baseline) and Week 4 following treatment were obtained together with clinical measures, serum cytokine levels using ELISA, and the degree of galactosylation of the IgG N-glycan chains. Gene sets separating responders and nonresponders were tested using canonical variates analysis. This approach also revealed important gene groups and pathways that differentiate responders from nonresponders. RESULTS: Fifty-nine genes showed significant differences between baseline and Week 4 and thus correlated with treatment. Significantly, 4 genes determined responders after correction for multiple testing. Ten of the 12 genes with the most significant changes were validated using real-time quantitative polymerase chain reaction. An increase in the terminal galactose content of N-linked glycans of IgG was observed in responders versus nonresponders, as well as in treated samples versus samples obtained at baseline. CONCLUSION: As a preliminary report, gene expression changes as a result of tocilizumab therapy in RA were examined, and gene sets discriminating between responders and nonresponders were found and validated. A significant increase in the degree of galactosylation of IgG N-glycans in patients with RA treated with tocilizumab was documented.