Differential contribution of PB1-F2 to the virulence of highly pathogenic H5N1 influenza A virus in mammalian and avian species

Highly pathogenic avian influenza A viruses (HPAIV) of the H5N1 subtype occasionally transmit from birds to humans and can cause severe systemic infections in both hosts. PB1-F2 is an alternative translation product of the viral PB1 segment that was initially characterized as a pro-apoptotic mitochondrial viral pathogenicity factor. A full-length PB1-F2 has been present in all human influenza pandemic virus isolates of the 20(th) century, but appears to be lost evolutionarily over time as the new virus establishes itself and circulates in the human host. In contrast, the open reading frame (ORF) for PB1-F2 is exceptionally well-conserved in avian influenza virus isolates. Here we perform a comparative study to show for the first time that PB1-F2 is a pathogenicity determinant for HPAIV (A/Viet Nam/1203/2004, VN1203 (H5N1)) in both mammals and birds. In a mammalian host, the rare N66S polymorphism in PB1-F2 that was previously described to be associated with high lethality of the 1918 influenza A virus showed increased replication and virulence of a recombinant VN1203 H5N1 virus, while deletion of the entire PB1-F2 ORF had negligible effects. Interestingly, the N66S substituted virus efficiently invades the CNS and replicates in the brain of Mx+/+ mice. In ducks deletion of PB1-F2 clearly resulted in delayed onset of clinical symptoms and systemic spreading of virus, while variations at position 66 played only a minor role in pathogenesis. These data implicate PB1-F2 as an important pathogenicity factor in ducks independent of sequence variations at position 66. Our data could explain why PB1-F2 is conserved in avian influenza virus isolates and only impacts pathogenicity in mammals when containing certain amino acid motifs such as the rare N66S polymorphism

Prevalence of severe atopic dermatitis in adults in 3 areas of Spain

The study was sponsored by Sanof

SrfB, a member of the Serum Response factor family of transcription factors, regulates starvation response and early development in Dictyostelium

The Serum Response Factor (SRF) is an important regulator of cell proliferation and differentiation. Dictyostelium discoideum srfB gene codes for an SRF homologue and is expressed in vegetative cells and during development under the control of three alternative promoters, which show different cell-type specific patterns of expression. The two more proximal promoters directed gene transcription in prestalk AB, stalk and lower-cup cells. The generation of a strain where the srfB gene has been interrupted (srfB(−)) has shown that this gene is required for regulation of actin–cytoskeleton-related functions, such as cytokinesis and macropinocytosis. The mutant failed to develop well in suspension, but could be rescued by cAMP pulsing, suggesting a defect in cAMP signaling. srfB(−) cells showed impaired chemotaxis to cAMP and defective lateral pseudopodium inhibition. Nevertheless, srfB(−) cells aggregated on agar plates and nitrocellulose filters 2 h earlier than wild type cells, and completed development, showing an increased tendency to form slug structures. Analysis of wild type and srfB(−) strains detected significant differences in the regulation of gene expression upon starvation. Genes coding for lysosomal and ribosomal proteins, developmentally-regulated genes, and some genes coding for proteins involved in cytoskeleton regulation were deregulated during the first stages of development

Maternal care boosted by paternal imprinting in mammals.

In mammals, mothers are the primary caregiver, programmed, in part, by hormones produced during pregnancy. High-quality maternal care is essential for the survival and lifelong health of offspring. We previously showed that the paternally silenced imprinted gene pleckstrin homology-like domain family A member 2 (Phlda2) functions to negatively regulate a single lineage in the mouse placenta called the spongiotrophoblast, a major source of hormones in pregnancy. Consequently, the offspring's Phlda2 gene dosage may influence the quality of care provided by the mother. Here, we show that wild-type (WT) female mice exposed to offspring with three different doses of the maternally expressed Phlda2 gene-two active alleles, one active allele (the extant state), and loss of function-show changes in the maternal hypothalamus and hippocampus during pregnancy, regions important for maternal-care behaviour. After birth, WT dams exposed in utero to offspring with the highest Phlda2 dose exhibit decreased nursing and grooming of pups and increased focus on nest building. Conversely, 'paternalised' dams, exposed to the lowest Phlda2 dose, showed increased nurturing of their pups, increased self-directed behaviour, and a decreased focus on nest building, behaviour that was robustly maintained in the absence of genetically modified pups. This work raises the intriguing possibility that imprinting of Phlda2 contributed to increased maternal care during the evolution of mammals

On the universality of the fluctuation-dissipation ratio in non-equilibrium critical dynamics

The two-time nonequilibrium correlation and response functions in 1D kinetic classical spin systems with non-conserved dynamics and quenched to their zero-temperature critical point are studied. The exact solution of the kinetic Ising model with Glauber dynamics for a wide class of initial states allows for an explicit test of the universality of the non-equilibrium limit fluctuation-dissipation ratio X_{\infty}. It is shown that the value of X_{\infty} depends on whether the initial state has finitely many domain walls or not and thus two distinct dynamic universality classes can be identified in this model. Generic 1D kinetic spin systems with non-conserved dynamics fall into the same universality classes as the kinetic Glauber-Ising model provided the dynamics is invariant under the C-symmetry of simultaneous spin and magnetic-field reversal. While C-symmetry is satisfied for magnetic systems, it need not be for lattice gases which may therefore display hitherto unexplored types of non-universal kinetics

Synthesis of the Ti-Silicate Form of BEC Polymorph of B-Zeolite Assisted by Molecular Modeling

This document is the Accepted Manuscript version of a Published Work that appeared in final form in The Journal of Physical Chemistry C, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/jp805400u Published Work, see http://pubs.acs.org/page/policy/articlesonrequest/index.html[EN] The K(+) free pure silica form of polymorph C (BEC) of beta-zeolite has been synthesized with a cationic organic structure directing agent (SDA) that was predicted best, out of a series of nine potentials, by means of modeling techniques. On the bases of this synthesis method, the Ti-BEC zeolite has been obtained which owing to the pore topology and dimensions shows a higher epoxidation activity than the Ti-beta-polymorph either with H(2)O(2) or organic peroxides as oxidants.The authors thank the CICYT for financial support (Project MAT 2006-14274-CO2-01). G.S. thanks "Centro de Calculo de la Universidad Politecnica de Valencia" for the use of their computational facilities. M.M. and P.S. thank ITQ for a scholarship. We also thank intramural project CRENATUM.Moliner Marin, M.; Serna Merino, PM.; Cantin Sanz, A.; Sastre Navarro, GI.; Díaz Cabañas, MJ.; Corma Canós, A. (2008). Synthesis of the Ti-Silicate Form of BEC Polymorph of B-Zeolite Assisted by Molecular Modeling. The Journal of Physical Chemistry C. 112(49):19547-19554. https://doi.org/10.1021/jp805400uS19547195541124

Digitally Continuous Multivalued Functions, Morphological Operations and Thinning Algorithms

In a recent paper (Escribano et al. in Discrete Geometry for Computer Imagery 2008. Lecture Notes in Computer Science, vol. 4992, pp. 81–92, 2008) we have introduced a notion of continuity in digital spaces which extends the usual notion of digital continuity. Our approach, which uses multivalued functions, provides a better framework to define topological notions, like retractions, in a far more realistic way than by using just single-valued digitally continuous functions. In this work we develop properties of this family of continuous functions, now concentrating on morphological operations and thinning algorithms. We show that our notion of continuity provides a suitable framework for the basic operations in mathematical morphology: erosion, dilation, closing, and opening. On the other hand, concerning thinning algorithms, we give conditions under which the existence of a retraction F:X⟶X∖D guarantees that D is deletable. The converse is not true, in general, although it is in certain particular important cases which are at the basis of many thinning algorithms

Sinus elevation by in situ utilization of bone scrapers : technique and results

Objectives: The objective was to present a novel technique for antrostomy performed before sinus elevation in atrophic maxilla for subsequent implant placement. Material and methods: The study included 10 sinus elevations performed by the proposed technique in nine consecutive patients presenting with inadequate posterior maxillary height. The technique is described, calculating the antrostomy surface area, volume of bone tissue obtained and final height attained in each case. A total of 16 implants were placed. Results: All ten elevations were accomplished. Mean antrostomy surface area was 0.55 mm2 , mean bone volume obtained was 0.56 cm3 and mean height attained was 11.7 mm from a baseline mean height of 5.6 mm. Out of the 16 implants, 14 were inserted immediately after the elevation and 2 were inserted in a second step, after ossification; 93.7% of the implants were osseointegrated at 6 months after prosthesis placement. Conclusion: The use of bone scrapers to create antrostomy for sinus elevation is a simple and very safe procedure. It provides a variable amount of particulate bone graft that is easily handled and highly useful for packing the cavity that will elevate the sinus membrane