Human cytomegalovirus-encoded pUL7 is a novel CEACAM1-like molecule responsible for promotion of angiogenesis.

UNLABELLED: Persistent human cytomegalovirus (HCMV) infection has been linked to several diseases, including atherosclerosis, transplant vascular sclerosis (TVS), restenosis, and glioblastoma. We have previously shown that factors secreted from HCMV-infected cells induce angiogenesis and that this process is due, at least in part, to increased secretion of interleukin-6 (IL-6). In order to identify the HCMV gene(s) responsible for angiogenesis promotion, we constructed a large panel of replication-competent HCMV recombinants. One HCMV recombinant deleted for UL1 to UL10 was unable to induce secretion of factors necessary for angiogenesis. Fine mapping using additional HCMV recombinants identified UL7 as a viral gene required for production of angiogenic factors from HCMV-infected cells. Transient expression of pUL7 induced phosphorylation of STAT3 and ERK1/2 MAP kinases and production of proangiogenic factors, including IL-6. Addition of recombinant pUL7 to cells was sufficient for angiogenesis and was again associated with increased IL-6 expression. Analysis of the UL7 structure revealed a conserved domain similar to the immunoglobulin superfamily domain and related to the N-terminal V-like domain of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Our report therefore identifies UL7 as a novel HCMV-encoded molecule that is both structurally and functionally related to cellular CEACAM1, a proangiogenic factor highly expressed during vasculogenesis. IMPORTANCE: A hallmark of cytomegalovirus (CMV) infection is its ability to modulate the host cellular machinery, resulting in the secretion of factors associated with long-term diseases such as vascular disorders and cancer. We previously demonstrated that HCMV infection alters the types and quantities of bioactive proteins released from cells (designated the HCMV secretome) that are involved in the promotion of angiogenesis and wound healing. A key proangiogenic and antiapoptotic factor identified from a proteomic-based approach was IL-6. In the present report, we show for the first time that HCMV UL7 encodes a soluble molecule that is a structural and functional homologue of the CEACAM1 proangiogenic cellular factor. This report thereby identifies a critical component of the HCMV secretome that may be responsible, at least in part, for the vascular dysregulation associated with persistent HCMV infection

Can primary care data be used to monitor regional smoking prevalence? An analysis of The Health Improvement Network primary care data

<p>Abstract</p> <p>Background</p> <p>Accurate and timely regional data on smoking trends allow tobacco control interventions to be targeted at the areas most in need and facilitate the evaluation of such interventions. Electronic primary care databases have the potential to provide a valuable source of such data due to their size, continuity and the availability of socio-demographic data. UK electronic primary care data on smoking prevalence from The Health Improvement Network (THIN) have previously been validated at the national level, but may be less representative at the regional level due to reduced sample sizes. We investigated whether this database provides valid regional data and whether it can be used to compare smoking prevalence in different UK regions.</p> <p>Methods</p> <p>Annual estimates of smoking prevalence by government office region (GOR) from THIN were compared with estimates of smoking prevalence from the General Lifestyle Survey (GLF) from 2000 to 2008.</p> <p>Results</p> <p>For all regions, THIN prevalence data were generally found to be highly comparable with GLF data from 2006 onwards.</p> <p>Conclusions</p> <p>THIN primary care data could be used to monitor regional smoking prevalence and highlight regional differences in smoking in the UK.</p

Honeybee Colony Vibrational Measurements to Highlight the Brood Cycle

Insect pollination is of great importance to crop production worldwide and honey bees are amongst its chief facilitators. Because of the decline of managed colonies, the use of sensor technology is growing in popularity and it is of interest to develop new methods which can more accurately and less invasively assess honey bee colony status. Our approach is to use accelerometers to measure vibrations in order to provide information on colony activity and development. The accelerometers provide amplitude and frequency information which is recorded every three minutes and analysed for night time only. Vibrational data were validated by comparison to visual inspection data, particularly the brood development. We show a strong correlation between vibrational amplitude data and the brood cycle in the vicinity of the sensor. We have further explored the minimum data that is required, when frequency information is also included, to accurately predict the current point in the brood cycle. Such a technique should enable beekeepers to reduce the frequency with which visual inspections are required, reducing the stress this places on the colony and saving the beekeeper time

Functional Electrical Stimulation Leads to Increased Volume of the Aged Thyroarytenoid Muscle.

OBJECTIVES/HYPOTHESIS: To reverse sarcopenia and increase the volumes of atrophied laryngeal muscles by functional electrical stimulation (FES) using a minimal invasive surgical procedure in an aged ovine model. STUDY DESIGN: Prospective animal study. METHODS: A stimulation electrode was placed unilaterally near the terminal adduction branch of the recurrent laryngeal nerve (RLN) adjacent to the right cricothyroid joint. The electrode was connected to an implant located subcutaneously at the neck region. Predesigned training patterns were automatically delivered by a bidirectional radio frequency link using a programming device and were repeated automatically by the implant every other day over 11 weeks in the awake animal. Outcome parameters comprised volumetric measurements based on three-dimensional reconstructions of the entire thyroarytenoid muscle (TAM), as well as gene expression analyses. RESULTS: We found significant increases of the volumes of the stimulated TAM of 11% and the TAM diameter at the midmembranous parts of the vocal folds of nearly 40%. Based on gene expression, we did not detect a shift of muscle fiber composition. CONCLUSIONS: FES of the terminal branches of the RLN is a secure and effective way to reverse the effects of age-related TAM atrophy and to increase volumes of atrophied muscles. LEVEL OF EVIDENCE: NA Laryngoscope, 2018

Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine

Times Cited: 13

Two-Minute k-Space and Time–accelerated Aortic Four-dimensional Flow MRI: Dual-Center Study of Feasibility and Impact on Velocity and Wall Shear Stress Quantification

PURPOSE: To investigate the two-center feasibility of highly k-space and time (k-t)–accelerated 2-minute aortic four-dimensional (4D) flow MRI and to evaluate its performance for the quantification of velocities and wall shear stress (WSS). MATERIALS AND METHODS: This cross-sectional study prospectively included 68 participants (center 1, 11 healthy volunteers [mean age ± standard deviation, 61 years ± 15] and 16 patients with aortic disease [mean age, 60 years ± 10]; center 2, 14 healthy volunteers [mean age, 38 years ± 13] and 27 patients with aortic or cardiac disease [mean age, 78 years ± 18]). Each participant underwent highly accelerated 4D flow MRI (k-t acceleration, acceleration factor of 5) of the thoracic aorta. For comparison, conventional 4D flow MRI (acceleration factor of 2) was acquired in the participants at center 1 (n = 27). Regional aortic peak systolic velocities and three-dimensional WSS were quantified. RESULTS: k-t–accelerated scan times (center 1, 2:03 minutes ± 0:29; center 2, 2:06 minutes ± 0:20) were significantly reduced compared with conventional 4D flow MRI (center 1, 12:38 minutes ± 2:25; P < .0001). Overall good agreement was found between the two techniques (absolute differences ≤15%), but proximal aortic WSS was significantly underestimated in patients by using k-t–accelerated 4D flow when compared with conventional 4D flow (P ≤ .03). k-t–accelerated 4D flow MRI was reproducible (intra- and interobserver intraclass correlation coefficient ≥0.98) and identified significantly increased peak velocities and WSS in patients with stenotic (P ≤ .003) or bicuspid (P ≤ .04) aortic valves compared with healthy volunteers. In addition, k-t–accelerated 4D flow MRI–derived velocities and WSS were inversely related to age (r ≥−0.53; P ≤ .03) over all healthy volunteers. CONCLUSION: k-t–accelerated aortic 4D flow MRI providing 2-minute scan times was feasible and reproducible at two centers. Although consistent healthy aging- and disease-related changes in aortic hemodynamics were observed, care should be taken when considering WSS, which can be underestimated in patients

Structured feedback on students’ concept maps: the proverbial path to learning?

Good conceptual knowledge is an essential requirement for health professions students, in that they are required to apply concepts learned in the classroom to a variety of different contexts. However, the use of traditional methods of assessment limits the educator’s ability to correct students’ conceptual knowledge prior to altering the educational context. Concept mapping (CM) is an educational tool for evaluating conceptual knowledge, but little is known about its use in facilitating the development of richer knowledge frameworks. In addition, structured feedback has the potential to develop good conceptual knowledge. The purpose of this study was to use Kinchin’s criteria to assess the impact of structured feedback on the graphical complexity of CM’s by observing the development of richer knowledge frameworks. Fifty-eight physiotherapy students created CM’s targeting the integration of two knowledge domains within a case-based teaching paradigm. Each student received one round of structured feedback that addressed correction, reinforcement, forensic diagnosis, benchmarking, and longitudinal development on their CM’s prior to the final submission. The concept maps were categorized according to Kinchin’s criteria as either Spoke, Chain or Net representations, and then evaluated against defined traits of meaningful learning. The inter-rater reliability of categorizing CM’s was good. Pre-feedback CM’s were predominantly Chain structures (57%), with Net structures appearing least often. There was a significant reduction of the basic Spoke- structured CMs (P = 0.002) and a significant increase of Net-structured maps (P < 0.001) at the final evaluation (post-feedback). Changes in structural complexity of CMs appeared to be indicative of broader knowledge frameworks as assessed against the meaningful learning traits. Feedback on CM’s seemed to have contributed towards improving conceptual knowledge and correcting naive conceptions of related knowledge. Educators in medical education could therefore consider using CM’s to target individual student development

FUS-ALS mutants alter FMRP phase separation equilibrium and impair protein translation

FUsed in Sarcoma (FUS) is a multifunctional RNA binding protein (RBP). FUS mutations lead to its cytoplasmic mislocalization and cause the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Here, we use mouse and human models with endogenous ALS-associated mutations to study the early consequences of increased cytoplasmic FUS. We show that in axons, mutant FUS condensates sequester and promote the phase separation of fragile X mental retardation protein (FMRP), another RBP associated with neurodegeneration. This leads to repression of translation in mouse and human FUS-ALS motor neurons and is corroborated in vitro, where FUS and FMRP copartition and repress translation. Last, we show that translation of FMRP-bound RNAs is reduced in vivo in FUS-ALS motor neurons. Our results unravel new pathomechanisms of FUS-ALS and identify a novel paradigm by which mutations in one RBP favor the formation of condensates sequestering other RBPs, affecting crucial biological functions, such as protein translation

Social Structure Predicts Genital Morphology in African Mole-Rats

BACKGROUND:African mole-rats (Bathyergidae, Rodentia) exhibit a wide range of social structures, from solitary to eusocial. We previously found a lack of sex differences in the external genitalia and morphology of the perineal muscles associated with the phallus in the eusocial naked mole-rat. This was quite surprising, as the external genitalia and perineal muscles are sexually dimorphic in all other mammals examined. We hypothesized that the lack of sex differences in naked mole-rats might be related to their unusual social structure. METHODOLOGY/PRINCIPAL FINDINGS:We compared the genitalia and perineal muscles in three African mole-rat species: the naked mole-rat, the solitary silvery mole-rat, and the Damaraland mole-rat, a species considered to be eusocial, but with less reproductive skew than naked mole-rats. Our findings support a relationship between social structure, mating system, and sexual differentiation. Naked mole-rats lack sex differences in genitalia and perineal morphology, silvery mole-rats exhibit sex differences, and Damaraland mole-rats are intermediate. CONCLUSIONS/SIGNIFICANCE:The lack of sex differences in naked mole-rats is not an attribute of all African mole-rats, but appears to have evolved in relation to their unusual social structure and reproductive biology

Smoke-free legislation and the incidence of paediatric respiratory infections and wheezing/asthma: interrupted time series analyses in the four UK nations

We investigated the association between introduction of smoke-free legislation in the UK (March 2006 for Scotland, April 2007 for Wales and Northern Ireland, and July 2007 for England) and the incidence of respiratory diseases among children. We extracted monthly counts of new diagnoses of wheezing/asthma and RTIs among children aged 0–12 years from all general practices in the Clinical Practice Research Datalink during 1997–2012. Interrupted time series analyses were performed using generalised additive mixed models, adjusting for underlying incidence trends, population size changes, seasonal factors, and pandemic influenza, as appropriate. 366,642 new wheezing/asthma diagnoses and 4,324,789 RTIs were observed over 9,536,003 patient-years. There was no statistically significant change in the incidence of wheezing/asthma after introduction of smoke-free legislation in England (incidence rate ratio (IRR) 0.94, 95% CI 0.81–1.09) or any other UK country (Scotland: IRR 0.99, 95% CI 0.83–1.19; Wales: IRR 1.09, 95% CI 0.89–1.35; Northern Ireland: IRR 0.96, 95% CI 0.76–1.22). Similarly no statistically significant changes in RTI incidence were demonstrated (England: IRR 0.95, 95% CI 0.86–1.06; Scotland: IRR 0.96, 95% CI 0.83–1.11; Wales: IRR 0.97, 95% CI 0.86–1.09; Northern Ireland: IRR 0.90, 95% CI 0.79–1.03). There were no demonstrable reductions in the incidence of paediatric wheezing/asthma or RTIs following introduction of smoke-free legislation in the UK