Dual Function of the pUL7-pUL51 Tegument Protein Complex in Herpes Simplex Virus 1 Infection

The tegument of herpesviruses is a highly complex structural layer between the nucleocapsid and the envelope of virions. Tegument proteins play both structural and regulatory functions during replication and spread, but the interactions and functions of many of these proteins are poorly understood. Here we focus on two tegument proteins from herpes simplex virus 1 (HSV-1), pUL7 and pUL51, which have homologues in all other herpesviruses. We have now identified that HSV-1 pUL7 and pUL51 form a stable and direct protein-protein interaction, their expression levels rely on the presence of each other, and they function as a complex in infected cells. We demonstrate that expression of the pUL7-pUL51 complex is important for efficient HSV-1 assembly and plaque formation. Furthermore, we also discovered that the pUL7-pUL51 complex localizes to focal adhesions at the plasma membrane in both infected cells and in the absence of other viral proteins. The expression of pUL7-pUL51 is important to stabilize focal adhesions and maintain cell morphology in infected cells and cells infected with viruses lacking pUL7 and/or pUL51 round up more rapidly than cells infected with wild-type HSV-1. Our data suggest that, in addition to the previously reported functions in virus assembly and spread for pUL51, the pUL7-pUL51 complex is important for maintaining the attachment of infected cells to their surroundings through modulating the activity of focal adhesion complexes. $\textbf{IMPORTANCE}$: The $\textit{Herpesviridae }$ is a large family of highly successful human and animal pathogens. Virions of these viruses are composed of many different proteins, most of which are contained within the tegument, a complex structural layer between the nucleocapsid and the envelope within virus particles. Tegument proteins have important roles in assembling virus particles as well as modifying host cells to promote virus replication and spread. However, little is known about the function of many tegument proteins during virus replication. Our study focuses on two tegument proteins from herpes simplex virus 1 that are conserved in all herpesviruses: pUL7 and pUL51. We demonstrate that these proteins directly interact and form a functional complex that is important for both virus assembly and modulation of host cell morphology. Further, we identify for the first time that these conserved herpesvirus tegument proteins localize to focal adhesions in addition to cytoplasmic juxtanuclear membranes within infected cells.This work was supported by the Leverhulme Trust (grant RPG-2012-793 to C.M.C.), the Royal Society (University Research Fellowship UF090010 to C.M.C.), and the Royal Society and the Wellcome Trust (Sir Henry Dale Fellowship 098406/Z/12/Z to S.C.G.). L.D. was supported by Wellcome Trust Ph.D. Programme funding (086158/Z/08/Z). D.J.O. was supported by a John Lucas Walker studentship. M.F.A. was supported by a Commonwealth Scholarship Commission PhD scholarship (BDCA-2014-7)

Pregnant women and infants as sentinel populations to monitor prevalence of malaria: results of pilot study in Lake Zone of Tanzania

As malaria control interventions are scaled-up, rational approaches are needed for monitoring impact over time. One proposed approach includes monitoring the prevalence of malaria infection among pregnant women and children at the time of routine preventive health facility (HF) visits. This pilot explored the feasibility and utility of tracking the prevalence of malaria infection in pregnant women attending their first antenatal care (ANC) visit and infants presenting at 9-12 months of age for measles vaccination.; Pregnant women attending first ANC and infants nine to 12 months old presenting for measles vaccination at a non-probability sample of 54 HFs in Tanzania's Lake Zone (Mara, Mwanza and Kagera Regions) were screened for malaria infection using a malaria rapid diagnostic test (RDT) from December 2012 to November 2013, regardless of symptoms. Participants who tested positive were treated for malaria per national guidelines. Data were collected monthly.; Overall 89.9 and 78.1 % of expected monthly reports on malaria infection prevalence were received for pregnant women and infants, respectively. Among 51,467 pregnant women and 35,155 infants attending routine preventive HF visits, 41.2 and 37.3 % were tested with RDT, respectively. Malaria infection prevalence was 12.8 % [95 % confidence interval (CI) 11.3-14.3] among pregnant women and 11.0 % (95 % CI 9.5-12.5) among infants, and varied by month. There was good correlation of the prevalence of malaria among pregnant women and infants at the HF level (Spearman rho = 0.6; p < 0.001). This approach is estimated to cost $1.28 for every person tested, with the RDT accounting for 72 % of the cost.; Malaria infection was common and well correlated among pregnant women and infants attending routine health services. Routine screening of these readily accessible populations may offer a practical strategy for continuously tracking malaria trends, particularly seasonal variation. Positivity rates among afebrile individuals presenting for routine care offer an advantage as they are unaffected by the prevalence of other causes of febrile illness, which could influence positivity rates among febrile patients presenting to outpatient clinics. The data presented here suggest that in addition to contributing to clinical management, ongoing screening of pregnant women could be used for routine surveillance and detection of hotspots

Effects of Ropivacaine with and without Dexmedetomidine on Hemodynamic Responses During Laryngoscopy and Intubation: A Randomized Double-Blind Study

Introduction: The study compares the effectiveness of airway nebulization with ropivacaine 0.5% alone and in combination, highlighting the potential benefits of these medications. Aims: The study evaluates ropivacaine 0.5% nebulization\u27s effectiveness in reducing pressor response to intubation, assesses potential adverse effects, and compares the dose-sparing effect of propofol and sedation. Methodology: A randomized clinical study at Krishna Hospital compared airway nebulism with piroxicam and dexmedetomidine in 60 patients aged 18-60, focusing on treating hypotension and heart rate decline. Results: The study compared 60 participants in two treatment groups: RD and R alone, finding no significant difference in age, gender, weight, or ASA status. Discussion: The study compared the effectiveness of nebulized ropivacaine alone or combined with dexmedetomidine in reducing pressor response to laryngoscopy and intubation in 60 patients. Results showed that ropivacaine with dexmedetomidine significantly reduced heart rates and systolic blood pressure. Conclusion: The study shows that nebulized ropivacaine and dexmedetomidine significantly reduce pressor response during laryngoscopy and intubation, while also enhancing propofol\u27s dose-sparing benefits and increasing sedative effects

Effect of the dog positioning on X-ray table on hip dysplasia parameter evaluation

Research Areas: Veterinary Sciences; ZoologyABSTRACT - Objective The aim of this study was to evaluate the effect of pelvic tilting along the long axis and femoral rotation on Norberg angle (NA), subluxation index (SI) and subluxation category (SC) in the standard ventrodorsal hip extended (VDHE) radiographical view on live animals. Study Type This was a retrospective clinical study. Materials and Methods Pairs of VDHE views, one adequately positioned and the other with pelvic tilting or femoral internal or external rotation, were compared for the NA, SI and SC. Results On the malpositioned pelvis set, on the underside the mean +/- SD NA was 98.7 +/- 6.1 degrees, the SI was 0.27 +/- 0.12 and the SC was 2.8 +/- 0.8 versus, on the acceptable set, the NA was 99.2 +/- 6.4 degrees ( p > 0.05), the SI was 0.25 +/- 0.12 ( p 0.05). Conclusions In clinical practice, pelvic tilting along the long axis in VDHE view results in non-favourable hip changes in the NA, SI and SC on the underside and favourable on the upperside, and the internal or external femoral rotation did not affect these variables.info:eu-repo/semantics/publishedVersio

Renal Pelviceal Keratinizing Squamous Metaplasia with Sparing of Pyramidal Zones

Metaplastic changes in the urothelium of the upper urinary tract are relatively infrequent. Metaplasia may present as either squamous or less often glandular differentiation. The process may be associated with chronic inflammation or associated chronic infections. There may be malignant transformation to either squamous cell carcinoma or adenocarcinoma. The demarcation of the metaplastic process in the minor calyces has not been well documented to date. We report the case of a 74-year-old female patient who presented with a history of chronic renal disease and acute pyohydronephrosis. The patient underwent a nephroureterectomy which revealed keratinizing desquamative squamous metaplasia throughout the renal pelvis and upper urinary tract with abrupt termination of metaplasia at the junction of the renal pelvis and the minor calyx (pyramidal zone). Immunohistochemical evaluation documents metaplastic urothelium stained positive for CK5, before converting sharply to simple cuboidal epithelium in the minor calyx (pyramidal zones) which stained positive CK7. At the junction of the metaplastic components and low cuboidal lined minor calyceal surfaces, the underlying stroma showed loss of ureteral muscularis mucosa with transition to renal parenchymal type stroma. We believe that this observation is unique and potentially relevant to the etiology and pathophysiology of pelviceal metaplasia

Application of particle filters to regional-scale wildfire spread

European Conference on Thermophysical Properties (ECTP)European Conference on Thermophysical Properties (ECTP), Porto, PORTUGALPorto, PORTUGAL, SEP 05-05, 2014SEP 05-05, 2014International audienceThis paper demonstrates the capability of particle filters for sequentially improving the simulation and forecast of wildfire propagation as new fire front observations become available. Particle filters, also called Sequential Monte Carlo (SMC) methods, fit into the domain of inverse modeling procedures, where measurements are incorporated (assimilated) into a computational model so as to formulate some feedback information on the uncertain model state variables and/or parameters, through representations of their probability density functions (PDF). Based on a simple sampling importance distribution and resampling techniques, particle filters combine Monte Carlo samplings with sequential Bayesian filtering problems. This study compares the performance of the Sampling Importance Resampling (SIR) and of the Auxiliary Sampling Importance Resampling (ASIR) filters for the sequential estimation of a progress variable and of vegetation parameters of the Rate Of fire Spread (ROS) model, which are all treated as state variables. They are applied to a real-world case corresponding to a reduced-scale controlled grassland fire experiment for validation; results indicate that both the SIR and the ASIR filters are able to accurately track the observed fire fronts, with a moderate computational cost. Particle filters show, therefore, their good ability to predict the propagation of controlled fires and to significantly increase fire simulation accuracy. While still at an early stage of development, this data-driven strategy is quite promising for regional-scale wildfire spread forecasting

Examining the initial usability, acceptability and feasibility of a digital mental health intervention for college students in India

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156228/2/ijop12640_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156228/1/ijop12640.pd

Drug‐induced increase in lysobisphosphatidic acid reduces the cholesterol overload in Niemann–Pick type C cells and mice

Most cells acquire cholesterol by endocytosis of circulating lowdensity lipoproteins (LDLs). After cholesteryl ester de-esterification in endosomes, free cholesterol is redistributed to intracellular membranes via unclear mechanisms. Our previous work suggested that the unconventional phospholipid lysobisphosphatidic acid (LBPA) may play a role in modulating the cholesterol flux through endosomes. In this study, we used the Prestwick library of FDAapproved compounds in a high-content, image-based screen of the endosomal lipids, lysobisphosphatidic acid and LDL-derived cholesterol. We report that thioperamide maleate, an inverse agonist of the histamine H3 receptor HRH3, increases highly selectively the levels of lysobisphosphatidic acid, without affecting any endosomal protein or function that we tested. Our data also show that thioperamide significantly reduces the endosome cholesterol overload in fibroblasts from patients with the cholesterol storage disorder Niemann–Pick type C (NPC), as well as in liver of Npc1-1- mice. We conclude that LBPA controls endosomal cholesterol mobilization and export to cellular destinations, perhaps by fluidifying or buffering cholesterol in endosomal membranes, and that thioperamide has repurposing potential for the treatment of NPC

Digital strategies for nitrogen management in grain production systems: lessons from multi-method assessment using on-farm experimentation

During the past few decades, a range of digital strategies for Nitrogen (N) management using various types of input data and recommendation frameworks have been developed. Despite much research, the benefits accrued from such technology have been equivocal. In this work, thirteen methods for mid-season N recommendations in cereal production systems were evaluated simultaneously, ranging from simple mass balance through to non-mechanistic approaches based on machine learning. To achieve this, an extensive field research program was implemented, comprising twenty-one N strip trials implemented in wheat and barley fields across Australia over four cropping seasons. A moving window regression approach was used to generate crop response functions to applied N and calculate economically optimal N rates along the length of the strips. The N recommendations made using various methods were assessed based on the error against the optimal rate and expected profitability. The root mean squared error of the recommendations ranged from 15 to 57 kg/ha. The best performing method was a data-driven empirical strategy in which a multivariate input to characterise field and season conditions was abundantly available and used to predict optimal N rates using machine learning. This was the only approach with potential to substantially outperform the existing farmer management, reducing the recommendation error from 42 to 15 kg/ha and improving profitability by up to A$47/ha. Despite being reliant on extensive historical databases, such a framework shows a promising pathway to drive production systems closer towards season- and site-specific economically optimum recommendations. Automated on-farm experimentation is a key enabler for building the necessary crop response databases to run empirical data-driven decision tool