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Systematic review of the mutations in the active antigenic site Ø of the prefusion F protein of the Respiratory Syncytial Virus (RSV) following the implementation of monoclonal antibody prophylaxis.

BACKGROUND: Monoclonal antibody (mAb) nirsevimab, which targets the antigenic site &#xd8; of the prefusion F protein (pre-F) of RSV, was introduced for RSV prophylaxis in several countries. METHODS: A systematic search was conducted between January 1, 2022, and July 31, 2026 for studies analyzing substitutions within the epitope of pre-F RSV protein, which is the target of nirsevimab, after the implementation of the mAb. We searched across PubMed, Scopus, Web of Science and ClinicalTrial.gov for studies involving children with confirmed RSV infection, that conducted genomic analysis. RESULTS: Seven studies (five observational and two randomized controlled trials) including 2156 RSV-positive samples (RSV-A: 1347, RSV-B: 809) were analyzed. RSV-A strains showed limited variability within antigenic site &#xd8;, with K65R being the most common substitution and K209E being the only intermediate-resistance RSV-A substitution. RSV-B strains demonstrated substantially higher substitution frequencies, particularly involving I206M, Q209R, and S211N. Most identified substitutions appeared to represent naturally occurring polymorphisms and retained susceptibility to nirsevimab, while multiple RSV-B substitutions and combinations involving residues 64-68 and 204-208 demonstrated reduced susceptibility or high-level resistance. Resistance-associated variants were detected in 28 of 2156 (1.3%) RSV-positive samples and exclusively among nirsevimab breakthrough infections. In a sub-analysis restricted to nirsevimab-treated individuals, resistance-associated variants were significantly more frequent among RSV-B than RSV-A (9.8% vs 0.5%; p&#xa0;<&#xa0;0.001). CONCLUSION: Most substitutions that were detected within the nirsevimab antigenic site reflect ongoing natural RSV evolution and do not significantly affect nirsevimab susceptibility. However, detection of resistance-associated variants highlights the importance of continuous genomic and phenotypic surveillance.

Humans↗

Phylogenetic analysis of the formin homology 2 domain.

Formin proteins are key regulators of eukaryotic actin filament assembly and elongation, and many species possess multiple formin isoforms. A nomenclature system based on fundamental features would be desirable, to aid the rapid identification and characterization of novel formins. In this article, we attempt to systematize the formin family by performing phylogenetic analyses of the formin homology 2 (FH2) domain, an independently folding region common to all formins, which alone can influence actin dynamics. Through database searches, we identify 101 FH2 domains from 26 eukaryotic species, including 15 in mice. Sequence alignments reveal a highly conserved yeast-specific insert in the "knob loop" region of the FH2 domain, with unknown functional consequences. Phylogenetic analysis using minimum evolution (ME), maximum parsimony (MP), and maximum likelihood (ML) algorithms strongly supports the existence of seven metazoan groups. Yeast FH2 domains segregate from all other eukaryotes, including metazoans, other fungi, plants, and protists. Sequence comparisons of non-FH2 regions support relationships between three metazoan groups (Dia, DAAM, and FRL) and examine previously identified coiled-coil and Diaphanous auto-regulatory domain sequences. This analysis allows for a formin nomenclature system based on sequence relationships, as well as suggesting strategies for the determination of biochemical and cellular activities of these proteins.

Adaptor Proteins, Signal Transducing↗

The esthetic width in fixed prosthodontics.

With the evolution of adhesive dentistry and the increasing use of porcelain veneers, single-unit crowns generally are restricted to the replacement of pre-existing full-coverage crowns and the restoration of nonvital and/or severely damaged teeth. Porcelain-fused-to-metal restorations are still widely used to generate single-unit crowns and fixed partial dentures. Collarless metal-ceramic restorations represent the most successful evolution among efforts to meet maximum esthetic requirements using porcelain-fused-to-metal restorations. Extended metal frameworks and opaque aluminous ceramic cores are associated with unpleasant optical effects in the soft tissues surrounding such restorations. This problem is particularly evident in the presence of the upper lip, which can generate an "umbrella effect" characterized by gray marginal gingivae and dark interdental papillae. Based on the concept of the biologic width, a systematic approach is proposed for the elaboration of an "esthetic width," including: 1) positioning of preparation margins; 2) reduction of the metal framework; and (c) appropriate marginal design of porcelain-fused-to-metal restorations. Strategic features of pontics and a specific interdental design are suggested to compensate for deficient anatomical features of the soft tissue and the edentulous ridge.

Crowns↗

[Hepatitis C and alcohol: notes for consensus].

Alcohol abuse is accompanied by a high prevalence of hepatitis C virus (HCV) infection, which arise in the Great La Plata up to 20%. This condition worsen the histological necro-inflamatory activity of HCV chronic hepatitis patients, accelerating the evolution to liver cirrhosis, to cirrhosis decompensation, and surely facilitating the development of hepatocellular carcinoma. Besides of that, active alcohol abuse implies severe decrease in therapeutic response and yet more, a real contraindication for IFN mono-drug or combined treatment. All of that remarks the need for a correct investigation of alcohol consumption in HCV infected patients through a careful clinical examination, routine use of biological markers and incorporation of specialized systematic questionnaires, submitting the patient as early as possible to a special treatment (mental health team, self-help groups, naltrexone or similar trials). Alcohol abuse suppression is the first great therapeutic gesture in chronic hepatitis C patients to allow specific combined treatment and eventually a more successful liver transplant.

Alcoholism↗

[Decreasing trend of cardiovascular mortality in Poland in the years 1980-2001].

In Poland, mortality due to cardiovascular diseases (CVD) has been systematically decreasing since 1990. The apparent change has been subject to a number of investigations during the last decade. The potential explanatory factors include favorable effects of socio-political and economic changes in Poland, decrease in the occurrence of risk factors for cardiovascular diseases, modification of diet and lifestyle, as well as advances in the treatment of cardiovascular diseases, particularly in their acute, life-threatening stages. Hypothesis regarding a beneficial evolution of the occurrence of risk factors is not universally accepted. The lack of convincing explanation of the trend justified a revision of the mortality pattern, including analysis of the specific components of the overall category of CVD. The findings showed that during the period in question (1990-2001) some important specific mortality rates have increased and not decreased. The change was particularly apparent in terms of ischaemic heart disease and stroke. Assessment of available data reveals also a decrease in mortality rates due to hypertension and due to diseases of arteries. The results of analysis suggest a caution in exploring and interpreting of overall trend in cardiovascular mortality in Poland, during the last decade. Beneficial changes appear to be less promising when the mortality profile is examined via the contribution of specific diseases, components of the overall category of CVD, especially ischeamic heart disease and the stroke. The findings justify further exploration, involving also a potential effect of diagnostic shift in classification of causes of death.

Cardiovascular Diseases↗

[Morphological inversions during the ontogenesis of the ixodid ticks (Acari: Ixodidae) from the viewpoint of the hypermorphosis conception and their significance for systematics].

Morphological inversions during the ontogenesis of the ixodid ticks consist in the deranges of species-specific tendencies in the development of some external structures by the female line. The inversions, which included a wide range of organs and their fine structures, have been described for the first time in 14 species of 4 from 7 Palearctic ixodid genera. Emphasis is placed on the study of the structures, which serve as differential characters for closely related species. It is shown, that the using of the structures subjected to inversions is unavoidable in systematics because of the great similarity of closely related species, especially in immature stages. It is established by the data on the variability of all active stages in the species distribution ranges, that the degree of the inversions manifestation may somewhat fluctuate in different subspecies or geographic morphotypes of the same species, but the peculiarity of the inversions always remains a species-specific character. The cause of inversions origin is the evolution of the Ixodidae by the way of morpho-ecological specialization, namely hypertrophic, giantism, the growth of teguments in the period of nutrition act by pasture ambushing, which led to the derange of the development coordination of the organs during ontogenesis. Biological implication of the inversions is a guarantee of the adaptive potential of species during the process of microevolution. Even though the inversions make identification of closely related species difficult, their substantial importance is that they form integral species-specific character for the whole active part of the species ontogenesis.

Adaptation, Physiological↗

[Pericystic pathology and surgery of hepatic hydatidosis. Studies and personal experiences].

In the general study of the consequences of hydatid cysts on the parenchyma of the organ involved, particular interest was given to the conditions of the pericyst. Thus a genuine pericystic pathology was systematized for most evolved pericysts. The signs vary according to the various conditions, sometimes including simple fibrosis, sometimes calcifications with specific and different appearances, almost always chronic inflammation. Fissuration was rare and, more importantly, exogenous vesiculation, a frequent cause of recurrence, was more often noted. The treatment is chosen on these bases, and determined by the local situation, hepatobiliary complications and the general condition of the patient. The author demonstrates the surgical evolution he followed in relation with the progress made in liver surgery, from plain drainage methods to radical pericystectomy and hepatic resection procedures. The conclusions he has drawn as a Symposium moderator during the World Congress of Hydatology held in Madrid in 1985, which will be summed up in the report, still seem to be perfectly valid.

Calcinosis↗

Mitochondrial phylogeny of notothenioids: a molecular approach to Antarctic fish evolution and biogeography.

Antarctic waters represent a unique marine environment delimited by an oceanographic barrier, the Polar Front Zone, and characterized by constant subzero temperatures and presence of sea ice. A group of teleost fish, the Notothenioidei, have adapted to these challenging environmental conditions, undergoing a remarkable diversification. In the present study a total of 798 base pairs, generated from partial sequencing of 16S and 12S mitochondrial ribosomal RNA genes, were examined in 33 notothenioid species representative of all families included in the suborder Notothenioidei. Phylogenetic trees, reconstructed on the basis of sequence data by different methods, indicate that traditional hypotheses on notothenioid systematics and biogeography might be in need of reexamination. Molecular evidence suggests that vicariant speciation could be invoked to explain the early divergence of Eleginops maclovinus, a species previously included in the family Nototheniidae, which is now proposed as the closest sister group to all the rest of notothenioids apart from bovichtids. On the other hand, repeated, independent dispersal through the Polar Front is proposed for the divergence of other subantarctic notothenioid species. Likewise, multiple, independent transitions from benthic to pelagic habit are inferred from molecular data, at variance with the more conservative hypothesis based on cladograms reconstructed from morphological data.

Animals↗

Protein signatures distinctive of alpha proteobacteria and its subgroups and a model for alpha-proteobacterial evolution.

Alpha (alpha) proteobacteria comprise a large and metabolically diverse group. No biochemical or molecular feature is presently known that can distinguish these bacteria from other groups. The evolutionary relationships among this group, which includes numerous pathogens and agriculturally important microbes, are also not understood. Shared conserved inserts and deletions (i.e., indels or signatures) in molecular sequences provide a powerful means for identification of different groups in clear terms, and for evolutionary studies (see www.bacterialphylogeny.com). This review describes, for the first time, a large number of conserved indels in broadly distributed proteins that are distinctive and unifying characteristics of either all alpha-proteobacteria, or many of its constituent subgroups (i.e., orders, families, etc.). These signatures were identified by systematic analyses of proteins found in the Rickettsia prowazekii (RP) genome. Conserved indels that are unique to alpha-proteobacteria are present in the following proteins: Cytochrome c oxidase assembly protein Ctag, PurC, DnaB, ATP synthase alpha-subunit, exonuclease VII, prolipoprotein phosphatidylglycerol transferase, RP-400, FtsK, puruvate phosphate dikinase, cytochrome b, MutY, and homoserine dehydrogenase. The signatures in succinyl-CoA synthetase, cytochrome oxidase I, alanyl-tRNA synthetase, and MutS proteins are found in all alpha-proteobacteria, except the Rickettsiales, indicating that this group has diverged prior to the introduction of these signatures. A number of proteins contain conserved indels that are specific for Rickettsiales (XerD integrase and leucine aminopeptidase), Rickettsiaceae (Mfd, ribosomal protein L19, FtsZ, Sigma 70 and exonuclease VII), or Anaplasmataceae (Tgt and RP-314), and they distinguish these groups from all others. Signatures in DnaA, RP-057, and DNA ligase A are commonly shared by various Rhizobiales, Rhodobacterales, and Caulobacter, suggesting that these groups shared a common ancestor exclusive of other alpha-proteobacteria. A specific relationship between Rhodobacterales and Caulobacter is indicated by a large insert in the Asn-Gln amidotransferase. The Rhizobiales group of species are distinguished from others by a large insert in the Trp-tRNA synthetase. Signature sequences in a number of other proteins (viz. oxoglutarate dehydogenase, succinyl-CoA synthase, LytB, DNA gyrase A, LepA, and Ser-tRNA synthetase) serve to distinguish the Rhizobiaceae, Brucellaceae, and Phyllobacteriaceae families from Bradyrhizobiaceae and Methylobacteriaceae. Based on the distribution patterns of these signatures, it is now possible to logically deduce a model for the branching order among alpha-proteobacteria, which is as follows: Rickettsiales --> Rhodospirillales-Sphingomonadales --> Rhodobacterales-Caulobacterales --> Rhizobiales (Rhizobiaceaea-Brucellaceae-Phyllobacteriaceae, and Bradyrhizobiaceae). The deduced branching order is also consistent with the topologies in the 16 rRNA and other phylogenetic trees. Signature sequences in a number of other proteins provide evidence that alpha-proteobacteria is a late branching taxa within Bacteria, which branched after the delta,epsilon-subdivisions but prior to the beta,gamma-proteobacteria. The shared presence of many of these signatures in the mitochondrial (eukaryotic) homologs also provides evidence of the alpha-proteobacterial ancestry of mitochondria.

Alphaproteobacteria↗

Polymorphic chloroplast simple sequence repeat primers for systematic and population studies in the genus Hordeum

In this study we report the development of primers to amplify polymorphic chloroplast simple sequence repeats in the genus Hordeum, which includes cultivated barley (H. vulgare ssp. vulgare) and its wild progenitor H. vulgare ssp. spontaneum. Polymorphic products were amplified in a wide range of Hordeum spp. and intraspecific variation was detected in both cultivated and wild barley. A decrease in cytoplasmic diversity was observed between sspp. spontaneum and vulgare as well as between ssp. vulgare landraces and cultivars, which is characteristic of domestication processes in many corp species. We also observed possible evidence for reticulate evolution of H. brachyantherum polyploids, with apparent multiple cytoplasmic introgressions during successive polyploidization events.

Journal Article↗

Left-right asymmetry of fly wings and the evolution of body axes.

The body plan of Drosophila, and presumably that of other insects, develops under the control of anterio-posterior and dorsal ventral axes, but no evidence for a left-right axis has yet been found. We used geometric morphometrics to study the wings in three species of flies: Drosophila melanogaster, Musca domestica and Glossina palpalis gambiensis. In all three species, we found that both size and shape showed subtle, but statistically significant directional asymmetry. For size, these asymmetries were somewhat inconsistent within and between species, but for shape, highly significant directional asymmetry was found in all samples examined. These systematic left-right differences imply the existence of a left-right axis that conveys distinct positional identities to the wing imaginal discs on either body side. Hence, the wing discs of Drosophila may be a new model to study the developmental genetics of left-right asymmetry. The asymmetries of shape were similar among species, suggesting that directional asymmetry has been evolutionarily conserved since the three lineages diverged. We discuss the implications of this evolutionary conservatism in conjunction with results from earlier studies that showed a lack of genetic variation for directional asymmetry in Drosophila.

Animals↗

A phylogenetic analysis of monocotyledons based on the chloroplast gene rps4, using parsimony and a new numerical phenetics method.

We have sequenced the chloroplast gene rps4 of 72 species; the sequence of 6 more species was found in the databanks. The 78 species were chosen so as to be representative of two taxonomic levels: the family, with 39 Poaceae, and the class, with 28 additional monocot species. Eleven dicots and other land plants were used as outgroups to the monocots. The 78 sequences were aligned by eye. Phylogenetic reconstruction was performed using the Wagner parsimony method: our first results were in contradiction with classical systematics, due to a local minimum. We then used the results obtained with the new distance method Anataxis to redraw a new tree and carry on further the parsimony calculations starting from this Anataxis tree. Up to 20,000 most parsimonious trees were thus obtained. The robustness of our results was checked by the bootstrap test and decay analyses. The Anataxis and the strict consensus tree fitted the general features of land plant evolution. Some of our results concerning relationships within the monocots corroborated those obtained with the chloroplast gene rbcL. Both genes raise questions concerning the monocot superorders as defined in a previous classification. This study proves the rps4 gene to be a useful phylogenetic tool within the Poaceae family and the Monocotyledonae order.

Base Sequence↗

Beyond intuition and instinct blindness: toward an evolutionarily rigorous cognitive science.

Cognitive psychology has an opportunity to turn itself into a theoretically rigorous discipline in which a powerful set of theories organize observations and suggest focused new hypotheses. This cannot happen, however, as long as intuition and folk psychology continue to set our research agenda. This is because intuition systematically blinds us to the full universe of problems our minds spontaneously solve, restricting our attention instead to a minute class of unrepresentative "high-level" problems. In contrast, evolutionarily rigorous theories of adaptive function are the logical foundation on which to build cognitive theories, because the architecture of the human mind acquired its functional organization through the evolutionary process. Theories of adaptive function specify what problems our cognitive mechanisms were designed by evolution to solve, thereby supplying critical information about what their design features are likely to be. This information can free cognitive scientists from the blinders of intuition and folk psychology, allowing them to construct experiments capable of detecting complex mechanisms they otherwise would not have thought to test for. The choice is not between no-nonsense empiricism and evolutionary theory; it is between folk theory and evolutionary theory.

Animals↗

Homologous recombination in bovine pestiviruses. Phylogenetic and statistic evidence.

Bovine pestiviruses (Bovine Viral Diarrea Virus 1 (BVDV 1) and Bovine Viral Diarrea Virus 2 (BVDV 2)) belong to the genus Pestivirus (Flaviviridae), which is composed of positive stranded RNA viruses causing significant economic losses world-wide. We used phylogenetic and bootstrap analyses to systematically scan alignments of previously sequenced genomes in order to explore further the evolutionary mechanisms responsible for variation in the virus. Previously published data suggested that homologous crossover might be one of the mechanisms responsible for the genomic rearrangements observed in cytopathic (cp) strains of bovine pestiviruses. Nevertheless, homologous recombination involves not just homologous crossovers, but also replacement of a homologous region of the acceptor RNA. Furthermore, cytopathic strains represent dead paths in evolution, since they are isolated exclusively from the fatal cases of mucosal disease. Herein, we report evidence of homologous inter-genotype recombination in the genome of a non-cytopathic (ncp) strain of Bovine Viral Diarrea Virus 1, the type species of the genus Pestivirus. We also show that intra-genotype homologous recombination might be a common phenomenon in both species of Pestivirus. This evidence demonstrates that homologous recombination contribute to the diversification of bovine pestiviruses in nature. Implications for virus evolution, taxonomy and phylogenetics are discussed.

Algorithms↗

Critical behavior of an Ising system on the Sierpinski carpet: a short-time dynamics study.

The short-time dynamic evolution of an Ising model embedded in an infinitely ramified fractal structure with noninteger Hausdorff dimension was studied using Monte Carlo simulations. Completely ordered and disordered spin configurations were used as initial states for the dynamic simulations. In both cases, the evolution of the physical observables follows a power-law behavior. Based on this fact, the complete set of critical exponents characteristic of a second-order phase transition was evaluated. Also, the dynamic exponent theta of the critical initial increase in magnetization, as well as the critical temperature, were computed. The exponent theta exhibits a weak dependence on the initial (small) magnetization. On the other hand, the dynamic exponent z shows a systematic decrease when the segmentation step is increased, i.e., when the system size becomes larger. Our results suggest that the effective noninteger dimension for the second-order phase transition is noticeably smaller than the Hausdorff dimension. Even when the behavior of the magnetization (in the case of the ordered initial state) and the autocorrelation (in the case of the disordered initial state) with time are very well fitted by power laws, the precision of our simulations allows us to detect the presence of a soft oscillation of the same type in both magnitudes that we attribute to the topological details of the generating cell at any scale.

Journal Article↗

Dynamics of ultraslow optical solitons in a cold three-state atomic system.

We present a systematic study on the dynamics of a ultraslow optical soliton in a cold, highly resonant three-state atomic system under Raman excitation. Using a method of multiple scales we derive a modified nonlinear Schrödinger equation with high-order corrections that describe effects of linear and differential absorption, nonlinear dispersion, delay response of nonlinear refractive index, diffraction, and third-order dispersion. Taking these effects as perturbations we investigate in detail the evolution of the ultraslow optical soliton using a standard soliton perturbation theory. We show that due to these high-order corrections the ultraslow optical soliton undergoes deformation, change of propagating velocity, and shift of oscillating frequency. In addition, a small radiation superposed by dispersive waves is also generated from the soliton. The results of the present work may provide a guidance that is useful for experimental demonstration of ultraslow optical soliton in cold atomic systems.

Journal Article↗

The molecular-cytogenetic analysis of grasses and its application to studying relationships among species of the Triticeae.

An analysis of four species from the genus Secale, including the study of different accessions, has shown that the properties of DNA clones of monomer units from three repeated sequence loci, namely, Ter, Nor, and 5S DNA, proved to be representative of the entire loci from which they were isolated. This finding in Secale species, including the discovery of a new locus for 5S DNA on chromosome 5R, has been used to interpret information on the Ter, Nor, and 5S DNA loci from 15 species in the Triticeae complex. The evolutionary relationship among species suggested by the DNA sequence data has shown many consistencies with a number of other characters such as those used in classical systematics, as well as geographical distribution data and isozyme and chromosome-pairing studies. Apparent inconsistencies such as a close relationship between the R and P genomes at the Ter loci are interpreted in terms of amplification-deletion phenomena known to occur at repetitive sequence loci. In addition, this study included species endemic to Australia and thus provided a broad time span in which to consider some features of repeated sequence family evolution, such as the conservation of certain parts of 5S DNA spacer regions.

Base Sequence↗

Suppression of tubulin tyrosine ligase during tumor growth.

The C terminus of the tubulin alpha-subunit of most eukaryotic cells undergoes a cycle of tyrosination and detyrosination using two specific enzymes, a tubulin tyrosine ligase (TTL) and a tubulin carboxypeptidase. Although this enzyme cycle is conserved in evolution and exhibits rapid turnover, the meaning of this modification has remained elusive. We have isolated several NIH-3T3 derived clonal cell lines that lack TTL (TTL-). TTL- cells contain a unique tubulin isotype (delta2-tubulin) that can be detected with specific antibodies. When injected into nude mice, both TTL- cells and TTL- cells stably transfected with TTL cDNA form sarcomas. But in tumors formed from TTL rescued cells, TTL is systematically lost during tumor growth. A strong selection process has thus acted during tumor growth to suppress TTL activity. In accord with this result, we find suppression of TTL activity in the majority of human tumors assayed with delta2-tubulin antibody. We conclude there is a widespread loss of TTL activity during tumor growth in situ, suggesting that TTL activity may play a role in tumor cell regulation.

3T3 Cells↗

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