A tail-like assembly at the portal vertex in intact herpes simplex type-1 virions

Herpes viruses are prevalent and well characterized human pathogens. Despite extensive study, much remains to be learned about the structure of the genome packaging and release machinery in the capsids of these large and complex double-stranded DNA viruses. However, such machinery is well characterized in tailed bacteriophage, which share a common evolutionary origin with herpesvirus. In tailed bacteriophage, the genome exits from the virus particle through a portal and is transferred into the host cell by a complex apparatus (i.e. the tail) located at the portal vertex. Here we use electron cryo-tomography of human herpes simplex type-1 (HSV-1) virions to reveal a previously unsuspected feature at the portal vertex, which extends across the HSV-1 tegument layer to form a connection between the capsid and the viral membrane. The location of this assembly suggests that it plays a role in genome release into the nucleus and is also important for virion architecture

Immunological responses in human papillomavirus 16 E6/E7-transgenic mice to E7 protein correlate with the presence of skin disease

The human papillomavirus (HPV) oncogenes, E6 and E7, are believed to contribute to the development of cervical cancers in women infected with certain HPV genotypes, most notably HPV-16 and HPV-18. Given their expression in tumor tissue, E6 and E7 have been implicated as potential tumor-specific antigens. We have examined an HPV-16 E6- and E7-transgenic mouse lineage for immune responses to these viral oncoproteins. Mice in this lineage express the HPV-16 E6 and E7 genes in their skin and eyes, and on aging, these mice frequently develop squamous cell carcinomas and lenticular tumors. Young transgenic mice, which had measurable E7 protein in the eye but not in the skin, were immunologically naive to E7 protein. They mounted an immune response to E7 on immunization comparable to that of nontransgenic controls, suggesting a lack of immune tolerance to this protein. Older line 19 mice, which are susceptible to skin disease associated with transcription of the E6 and E7 open reading frames, had measurable E7 protein in their skin. These older transgenic mice spontaneously developed antibody responses to endogenous E7 protein, particularly in association with skin disease. Also detected in older mice were delayed-type hypersensitivity responses to E7. These finding parallel the humoral immune response to E7 protein in patients with HPV-associated cervical cancer and suggest that line 19 mice may provide a model for studying the immunobiology of HPV-associated cancers

Nanoparticle inhalation augments particle-dependent systemic microvascular dysfunction

<p>Abstract</p> <p>Background</p> <p>We have shown that pulmonary exposure to fine particulate matter (PM) impairs endothelium dependent dilation in systemic arterioles. Ultrafine PM has been suggested to be inherently more toxic by virtue of its increased surface area. The purpose of this study was to determine if ultrafine PM (or nanoparticle) inhalation produces greater microvascular dysfunction than fine PM. Rats were exposed to fine or ultrafine TiO₂aerosols (primary particle diameters of ~1 μm and ~21 nm, respectively) at concentrations which do not alter bronchoalveolar lavage markers of pulmonary inflammation or lung damage.</p> <p>Results</p> <p>By histopathologic evaluation, no significant inflammatory changes were seen in the lung. However, particle-containing macrophages were frequently seen in intimate contact with the alveolar wall. The spinotrapezius muscle was prepared for in vivo microscopy 24 hours after inhalation exposures. Intraluminal infusion of the Ca²⁺ionophore A23187 was used to evaluate endothelium-dependent arteriolar dilation. In control rats, A23187 infusion produced dose-dependent arteriolar dilations. In rats exposed to fine TiO₂, A23187 infusion elicited vasodilations that were blunted in proportion to pulmonary particle deposition. In rats exposed to ultrafine TiO₂, A23187 infusion produced arteriolar constrictions or significantly impaired vasodilator responses as compared to the responses observed in control rats or those exposed to a similar pulmonary load of fine particles.</p> <p>Conclusion</p> <p>These observations suggest that at equivalent pulmonary loads, as compared to fine TiO₂, ultrafine TiO₂inhalation produces greater remote microvascular dysfunction.</p

A dynamical model for correlated two-pion-exchange in the pion-nucleon interaction

A microscopic model for the $N\bar N\to\pi\pi$ process is presented in the meson exchange framework, which in the pseudophysical region agrees with available quasiempirical information. The scalar ($\sigma$) and vector ($\rho$) piece of correlated two--pion exchange in the pion--nucleon interaction is then derived via dispersion integrals over the unitarity cut. Inherent ambiguities in the method and implications for the description of pion--nucleon scattering data are discussed.Comment: 20 pages, 11 postscript figure

Moments of the Virtual Photon Structure Function

The photon structure function is a useful testing ground for QCD. It is perturbatively computable apart from a contribution from what is usually called the hadronic component of the photon. There have been many proposals for this nonperturbative part of the real photon structure function. By studying moments of the virtual photon structure function, we explore the extent to which these proposed nonperturbative contributions can be identified experimentally.Comment: LaTeX, 16 pages + 14 compressed and uuencoded postscript figures, UMN-TH-1111/9

The size of the proton - closing in on the radius puzzle

We analyze the recent electron-proton scattering data from Mainz using a dispersive framework that respects the constraints from analyticity and unitarity on the nucleon structure. We also perform a continued fraction analysis of these data. We find a small electric proton charge radius, r_E^p = 0.84_{-0.01}^{+0.01} fm, consistent with the recent determination from muonic hydrogen measurements and earlier dispersive analyses. We also extract the proton magnetic radius, r_M^p = 0.86_{-0.03}^{+0.02} fm, consistent with earlier determinations based on dispersion relations.Comment: 4 pages, 2 figures, fit improved, small modifications, section on continued fractions modified, conclusions on the proton charge radius unchanged, version accepted for publication in European Physical Journal

Strong Coupling Constant from the Photon Structure Function

We extract the value of the strong coupling constant alpha_s from a single-parameter pointlike fit to the photon structure function F_2^gamma at large x and Q^2 and from a first five-parameter full (pointlike and hadronic) fit to the complete F_2^gamma data set taken at PETRA, TRISTAN, and LEP. In next-to-leading order and the MSbar renormalization and factorization schemes, we obtain alpha_s(m_Z)=0.1183 +/- 0.0050(exp.)^+0.0029_-0.0028(theor.) [pointlike] and alpha_s(m_Z)=0.1198 +/- 0.0028(exp.)^+0.0034_-0.0046(theor.) [pointlike and hadronic]. We demonstrate that the data taken at LEP have reduced the experimental error by about a factor of two, so that a competitive determination of alpha_s from F_2^gamma is now possible.Comment: 11 pages, 2 tables, 2 figures. Version accepted for publication by Phys. Rev. Let

Simple models of the chemical field around swimming plankton

Background. Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk. Methods. Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13 858 healthy controls of European decent. Results. The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio [OR], 1.24; P = 2.49 × 10−9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10−8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10−9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10−5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006). Conclusions. Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism

Dilepton Spectra from Decays of Light Unflavored Mesons

The invariant mass spectrum of the $e^{+}e^{-}$ and $\mu ^{+}\mu ^{-}$ pairs from decays of light unflavored mesons with masses below the $\phi (1020)$-meson mass to final states containing along with a dilepton pair one photon, one meson, and two mesons are calculated within the framework of the effective meson theory. The results can be used for simulations of the dilepton spectra in heavy-ion collisions and for experimental searches of dilepton meson decays.Comment: 73 pages, 19 figures, 3 tables, REVTeX, new references adde