Major Histocompatibility Complex Class I Allele-specific Cooperative and Competitive Interactions between Immune Evasion Proteins of Cytomegalovirus

Cytomegaloviruses (CMVs) deploy a set of genes for interference with antigen presentation in the major histocompatibility complex (MHC) class I pathway. In murine CMV (MCMV), three genes were identified so far: m04/gp34, m06/gp48, and m152/gp40. While their function as immunoevasins was originally defined after their selective expression, this may not necessarily reflect their biological role during infection. The three immunoevasins might act synergistically, but they might also compete for their common substrate, the MHC class I complexes. To approach this question in a systematic manner, we have generated a complete set of mutant viruses with deletions of the three genes in all seven possible combinations. Surface expression of a set of MHC class I molecules specified by haplotypes H-2d (Kd, Dd, and Ld) and H-2b (Kb and Db) was the parameter for evaluation of the interference with class I trafficking. The data show the following: first, there exists no additional MCMV gene of major influence on MHC class I surface expression; second, the strength of the inhibitory effect of immunoevasins shows an allele-specific hierarchy; and third, the immunoevasins act not only synergistically but can, in certain combinations, interact antagonistically. In essence, this work highlights the importance of studying the immunosubversive mechanisms of cytomegaloviruses in the context of gene expression during the viral replicative cycle in infected cells

Combinatory cytotoxic effects produced by E1B-55kDa-deleted adenoviruses and chemotherapeutic agents are dependent on the agents in esophageal carcinoma

We examined possible combinatory antitumor effects of replication-competent type 5 adenoviruses (Ad) lacking E1B-55kDa molecules (Ad-delE1B55) and chemotherapeutic agents in nine human esophageal carcinoma cells. Ad-delE1B55 produced cytotoxic effects on all the carcinoma cells and the cytotoxicity is not directly linked with the p53 status of the tumors or with the infectivity to respective tumors. A combinatory treatment with Ad-delE1B55 and an anticancer agent, 5-fluorouracil (5-FU), mitomycin C or etoposide, produced greater cytotoxic effects than that with either the Ad or the agent. Administration of 5-FU could minimally inhibit the viral replication and a simultaneous treatment with the Ad and 5-FU achieved better cytotoxicity than sequential treatments. We also confirmed the antitumor effects by the combination of Ad-delE1B55 with 5-FU in vivo. Cisplatin, however, did not achieve the combinatory effects in most of the cells tested. These data indicate that the Ad-delE1B55 produce combinatory antitumor effects with a chemotherapeutic agent irrespective of the administration schedule, but the effects depend on an agent in esophageal carcinoma

Temporal profiling of the coding and noncoding murine cytomegalovirus transcriptomes

The global transcriptional program of murine cytomegalovirus (MCMV), involving coding, noncoding, and antisense transcription, remains unknown. Here we report an oligonucleotide custom microarray platform capable of measuring both coding and noncoding transcription on a genome-wide scale. By profiling MCMV wild-type and immediate-early mutant strains in fibroblasts, we found rapid activation of the transcriptome by 6.5 h postinfection, with absolute dependency on ie3, but not ie1 or ie2, for genomic programming of viral gene expression. Evidence is also presented to show, for the first time, genome-wide noncoding and bidirectional transcription at late stages of MCMV infection

Phase curve and geometric albedo of WASP-43b measured with CHEOPS, TESS, and HST WFC3/UVIS

Context. Observations of the phase curves and secondary eclipses of extrasolar planets provide a window onto the composition and thermal structure of the planetary atmospheres. For example, the photometric observations of secondary eclipses lead to the measurement of the planetary geometric albedo, Ag, which is an indicator of the presence of clouds in the atmosphere. Aims: In this work, we aim to measure the Ag in the optical domain of WASP-43b, a moderately irradiated giant planet with an equilibrium temperature of ~1400 K. Methods: For this purpose, we analyzed the secondary eclipse light curves collected by CHEOPS together with TESS along with observations of the system and the publicly available photometry obtained with HST WFC3/UVIS. We also analyzed the archival infrared observations of the eclipses and retrieve the thermal emission spectrum of the planet. By extrapolating the thermal spectrum to the optical bands, we corrected for the optical eclipses for thermal emission and derived the optical Ag. Results: The fit of the optical data leads to a marginal detection of the phase-curve signal, characterized by an amplitude of 160 ± 60 ppm and 80−50+60 ppm in the CHEOPS and TESS passbands, respectively, with an eastward phase shift of ~50° (1.5σ detection). The analysis of the infrared data suggests a non-inverted thermal profile and solar-like metallicity. The combination of the optical and infrared analyses allows us to derive an upper limit for the optical albedo of Ag< 0.087, with a confidence of 99.9%. Conclusions: Our analysis of the atmosphere of WASP-43b places this planet in the sample of irradiated hot Jupiters, with monotonic temperature-pressure profile and no indication of condensation of reflective clouds on the planetary dayside

The phase curve and the geometric albedo of WASP-43b measured with CHEOPS, TESS and HST WFC3/UVIS

peer reviewe

Update on hypertrophic cardiomyopathy and a guide to the guidelines

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, affecting 1 in 500 individuals worldwide. Existing epidemiological studies might have underestimated the prevalence of HCM, however, owing to limited inclusion of individuals with early, incomplete phenotypic expression. Clinical manifestations of HCM include diastolic dysfunction, left ventricular outflow tract obstruction, ischaemia, atrial fibrillation, abnormal vascular responses and, in 5% of patients, progression to a 'burnt-out' phase characterized by systolic impairment. Disease-related mortality is most often attributable to sudden cardiac death, heart failure, and embolic stroke. The majority of individuals with HCM, however, have normal or near-normal life expectancy, owing in part to contemporary management strategies including family screening, risk stratification, thromboembolic prophylaxis, and implantation of cardioverter-defibrillators. The clinical guidelines for HCM issued by the ACC Foundation/AHA and the ESC facilitate evaluation and management of the disease. In this Review, we aim to assist clinicians in navigating the guidelines by highlighting important updates, current gaps in knowledge, differences in the recommendations, and challenges in implementing them, including aids and pitfalls in clinical and pathological evaluation. We also discuss the advances in genetics, imaging, and molecular research that will underpin future developments in diagnosis and therapy for HCM

Incidence of brachial plexus injury after cardiac surgery : a retrospective study

Abstract: Background: Brachial plexopathy is a rare but debilitating injury associated with cardiac surgery. The reported incidence varies widely. Several risk factors have been described, including both patient and surgical factors.Objectives: The aim of this study is to (1) investigate the incidence of brachial plexus injury in cardiac surgery in a three-year period in our hospital, (2) give an overview of risk factors and possible mechanisms of brachial plexopathy, and (3) consider the legal ramifications of these injuries.Design and setting: single centre retrospective studyMethods: Data were collected retrospectively from all patients undergoing cardiac surgery in a major hospital in a three-year year period (N = 1305). Hospital records were screened for patients who underwent an electromyography after their surgery. Those cases were further investigated for brachial plexus injury. Patient characteristics and data applying to known risk factors for peroperative nerve injury were obtained.Results: Brachial plexus injury was observed in 7 out of 1305 patients (0.54%). All patients with brachial plexus injury underwent coronary artery bypass surgery with internal mammary artery harvesting at the side of the injury. No further analysis concerning risk factors was performed since only seven cases were identified and underreporting was suspected.Conclusion: Our data suggest that brachial plexus injury in cardiac surgery might be associated with asymmetrical sternal retraction during internal mammary artery harvesting. These findings correspond with previous reports, although it would be interesting to further investigate the importance of the exact placement and type of retractor used

Taxonomy and nomenclature of the polymorphic European high mountain species Androsace vitaliana (L.) Lapeyr. (Primulaceae)

Androsace vitaliana (syn. Vitaliana primuliflora; Primulaceae) has been subject to several taxonomic treatments, whose conclusions ranged from a single species with numerous infraspecific taxa to several species usually without infraspecific taxa. Here, following molecular investigation, several taxonomic changes are made. A single species with the following infraspecific taxa is recognized: subsp. vitaliana (Pyrenees), subsp. cinerea (south-western Alps), subsp. lepontina (Pennine Alps), subsp. sesleri (south-eastern Alps), subsp. praetutiana (Apennines) and subsp. assoana (Iberian Peninsula excluding the Pyrenees), the last of which is divided into the four allopatrically distributed varieties assoana, centriberica, flosjugorum and nevadensis. Contrary to some previous assertions, all taxa are allopatric and, especially for subspp. vitaliana, cinerea and lepontina, where clear diagnostic characters are lacking, they can best be determined by their geographic origin