Isolation and characterization of the herpes simplex virus 1 terminase complex

During herpes simplex virus 1 (HSV-1) infection, empty procapsids are assembled and subsequently filled with the viral genome by means of a protein complex called the terminase, which is comprised of the HSV-1 UL15, UL28, and UL33 proteins. Biochemical studies of the terminase proteins have been hampered by the inability to purify the intact terminase complex. In this study, terminase complexes were isolated by tandem-affinity purification (TAP) using recombinant viruses expressing either a full-length NTAP-UL28 fusion protein (vFH476) or a C-terminally truncated NTAP-UL28 fusion protein (vFH499). TAP of the UL28 protein from vFH476-infected cells, followed by silver staining, Western blotting, and mass spectrometry, identified the UL15, UL28, and UL33 subunits, while TAP of vFH499-infected cells confirmed previous findings that the C terminus of UL28 is required for UL28 interaction with UL33 and UL15. Analysis of the oligomeric state of the purified complexes by sucrose density gradient ultracentrifugation revealed that the three proteins formed a complex with a molecular mass that is consistent with the formation of a UL15-UL28-UL33 heterotrimer. In order to assess the importance of conserved regions of the UL15 and UL28 proteins, recombinant NTAP-UL28 viruses with mutations of the putative UL28 metal-binding domain or within the UL15 nuclease domain were generated. TAP of UL28 complexes from cells infected with each domain mutant demonstrated that the conserved cysteine residues of the putative UL28 metal-binding domain and conserved amino acids within the UL15 nuclease domain are required for the cleavage and packaging functions of the viral terminase, but not for terminase complex assembly

Patient focused registries can improve health, care, and science.

Eugene Nelson and colleagues call for registries of care data to be transformed into patient centred interactive learning systemsThis work is supported by funding from the Robert Wood Johnson Foundation (Grants: #71211 and 72313), the Cystic Fibrosis Foundation (Grant #OCONNO04Q10), and the Crohn’s and Colitis Foundation of America Quality of Care Initiative (Grant #3372). TSM was funded by the Multidisciplinary Clinical Research Center for Musculoskeletal Diseases at Dartmouth (P60 AR-062799, A. Tosteson, PI), sponsored by the National Institute for Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. EE was funded by The Swedish Research Council for Health, Work Life and Welfare (#2014-4238). MDW is supported by a Wellcome Trust Senior Investigator award (WT09789).This is the final version of the article. It first appeared from BMJ Group via https://doi.org/10.1136/bmj.i331

Performance of turbulence and cavitation models in prediction of incipient and developed cavitation

The aim of this article is to assess the impact of turbulence and cavitation models on the prediction of diesel injector nozzle flow. Two nozzles are examined, an enlarged one, operating at incipient cavitation, and an industrial injector tip, operating at developed cavitation. The turbulence model employed includes the re-normalization group k–ε, realizable k–ε and k–ω shear stress transport Reynolds-averaged Navier–Stokes models; linear pressure–strain Reynolds stress model and the wall adapting local eddy viscosity large eddy simulation model. The results indicate that all Reynolds-averaged Navier–Stokes and the Reynolds stress turbulence models have failed to predict cavitation inception due to their limitation to resolve adequately the low pressure existing inside vortex cores, which is responsible for cavitation development in this particular flow configuration. Moreover, Reynolds-averaged Navier–Stokes models failed to predict unsteady cavitation phenomena in the industrial injector. However, the wall adapting local eddy viscosity large eddy simulation model was able to predict incipient and developed cavitation, while also capturing the shear layer instability, vortex shedding and cavitating vortex formation. Furthermore, the performance of two cavitation methodologies is discussed within the large eddy simulation framework. In particular, a barotropic model and a mixture model based on the asymptotic Rayleigh–Plesset equation of bubble dynamics have been tested. The results indicate that although the solved equations and phase change formulation are different in these models, the predicted cavitation and flow field were very similar at incipient cavitation conditions. At developed cavitation conditions, standard cavitation models may predict unrealistically high liquid tension, so modifications may be essential. It is also concluded that accurate turbulence representation is crucial for cavitation in nozzle flows

Ocular inflammatory disease and ocular tuberculosis in a cohort of patients co-infected with HIV and multidrug-resistant tuberculosis in Mumbai, India: a cross-sectional study.

The prevalence and the patterns of ocular inflammatory disease and ocular tuberculosis (TB) are largely undocumented among Multidrug Resistant TB (MDR-TB) patients co-infected with Human Immunodeficiency Virus (HIV) and on antituberculosis and antiretroviral therapy (ART)

High Rate of Hypothyroidism in Multidrug-Resistant Tuberculosis Patients Co-Infected with HIV in Mumbai, India.

Adverse events (AEs) among HIV-infected patients with multidrug-resistant tuberculosis (MDR-TB) receiving anti-TB and antiretroviral treatments (ART) are under-researched and underreported. Hypothyroidism is a common AE associated with ethionamide, p-aminosalicylic acid (PAS), and stavudine. The aim of this study was to determine the frequency of and risk factors associated with hypothyroidism in HIV/MDR-TB co-infected patients

Supervised versus unsupervised categorization: Two sides of the same coin?

Supervised and unsupervised categorization have been studied in separate research traditions. A handful of studies have attempted to explore a possible convergence between the two. The present research builds on these studies, by comparing the unsupervised categorization results of Pothos et al. (submitted; 2008) with the results from two procedures of supervised categorization. In two experiments, we tested 375 participants with nine different stimulus sets, and examined the relation between ease of learning of a classification, memory for a classification, and spontaneous preference for a classification. After taking into account the role of the number of category labels (clusters) in supervised learning, we found the three variables to be closely associated with each other. Our results provide encouragement for researchers seeking unified theoretical explanations for supervised and unsupervised categorization, but raise a range of challenging theoretical questions

The Novel Object and Unusual Name (NOUN) database: a collection of novel images for use in experimental research

Many experimental research designs require images of novel objects. Here we introduce the Novel Object and Unusual Name (NOUN) Database. This database contains 64 primary novel object images and additional novel exemplars for ten basic- and nine global-level object categories. The objects’ novelty was confirmed by both self-report and a lack of consensus on questions that required participants to name and identify the objects. We also found that object novelty correlated with qualifying naming responses pertaining to the objects’ colors. Results from a similarity sorting task (and subsequent multidimensional scaling analysis on the similarity ratings) demonstrated that the objects are complex and distinct entities that vary along several featural dimensions beyond simply shape and color. A final experiment confirmed that additional item exemplars comprise both sub- and superordinate categories. These images may be useful in a variety of settings, particularly for developmental psychology and other research in language, categorization, perception, visual memory and related domains

Recurrent Scedosporium apiospermum mycetoma successfully treated by surgical excision and terbinafine treatment: a case report and review of the literature

Background: Scedosporium apiospermum is an emerging opportunistic filamentous fungus, which is notorious for its high levels of antifungal ‑resistance. It is able to cause localized cutaneous or subcutaneous infections in both immu‑ nocompromised and immunocompetent persons, pulmonary infections in patients with predisposing pulmonary diseases and invasive mycoses in immunocompromised patients. Subcutaneous infections caused by this fungus frequently show chronic mycetomatous manifestation. Case report: We report the case of a 70 ‑year ‑old immunocompromised man, who developed a fungal mycetoma‑ tous infection on his right leg. There was no history of trauma; the aetiological agent was identified by microscopic examination and ITS sequencing. This is the second reported case of S. apiospermum subcutaneous infections in Hungary, which was successfully treated by surgical excision and terbinafine treatment. After 7 months, the patient remained asymptomatic. Considering the antifungal susceptibility and increasing incidence of the fungus, Sce - dosporium related subcutaneous infections reported in the past quarter of century in European countries were also reviewed. Conclusions: Corticosteroid treatment represents a serious risk factor of S. apiospermum infections, especially if the patient get in touch with manure ‑enriched or polluted soil or water. Such infections have emerged several times in European countries in the past decades. The presented data suggest that besides the commonly applied voricona‑ zole, terbinafine may be an alternative for the therapy of mycetomatous Scedosporium infections