Ocean robots uncover microbial secrets

Life on Earth began in the sea, and the oceans continue to support life on our planet. Of particular importance is the ability of marine microbes to exist in a complex web of relationships where substances are continually transformed and exchanged

Hybrid digital/optical computer systems

A high-speed hybrid optical–digital correlator system was designed, constructed, modeled, and demonstrated experimentally. This correlator is capable of operation at approximately 3000 correlations/s. The input scene is digitized at a resolution of 512 × 512 pixels and the phase information of the two-dimensional fast Fourier transform calculated and displayed in the correlator filter plane at normal video frame rates. High-fidelity reference template images are stored in a phase-conjugating optical memory placed at the nominal input plane of the correlator and reconstructed with a high-speed acousto-optic scanner; this allows for cross correlation of the entire reference data set with the input scene within one frame period. A high-speed CCD camera is used to capture the correlation-plane image, and rapid correlation-plane processing is achieved with a parallel processing architecture

The initiator methionine tRNA drives cell migration and invasion leading to increased metastatic potential in melanoma

The cell's repertoire of transfer RNAs (tRNAs) has been linked to cancer. Recently, levels of the initiator methionine tRNA (tRNAiMet) in stromal fibroblasts have been shown to influence extracellular matrix (ECM) secretion to drive tumour growth and angiogenesis. Here we show that increased tRNAiMet within cancer cells does not influence tumour growth, but drives cell migration and invasion via a mechanism that is independent from ECM synthesis and dependent on α5β1 integrin and levels of the translation initiation ternary complex. In vivo and ex vivo migration (but not proliferation) of melanoblasts is significantly enhanced in transgenic mice which express additional copies of the tRNAiMet gene. We show that increased tRNAiMet in melanoma drives migratory, invasive behaviour and metastatic potential without affecting cell proliferation and primary tumour growth, and that expression of RNA polymerase III-associated genes (which drive tRNA expression) are elevated in metastases by comparison with primary tumours. Thus specific alterations to the cancer cell tRNA repertoire drive a migration/invasion programme that may lead to metastasis

Prevalence of alcohol-related attendance at an inner-city emergency department and its impact: a dual prospective and retrospective cohort study

Background: Alcohol-related hospital attendances at Emergency Departments (ED) are a potentially avoidable burden on National Health Services (NHS) resources. Understanding the number and type of patients attending EDs with alcohol intoxication is important in estimating the workload and cost implications. We used best practice from previous studies to establish the prevalence of adult alcohol-related ED attendances and estimate the costs of clinical management and subsequent health service use. Methods: The setting was a large inner-city ED in northeast England, United Kingdom. Data were collected via (i) retrospective review of hospital records for all ED attendances for four pre-specified weeks in 2010/11 to identify alcohol-related cases along with 12 months follow-up of the care episode, and (ii) prospective 24/7 assessment via breath alcohol concentration testing of patients presenting to ED in the corresponding weeks in 2012/13. Results: The prevalence rates of alcohol-related attendances were 12% and 15% for the retrospective and prospective cohorts. Prospectively, the rates ranged widely from 4% to 60% during the week, rising to over 70% at weekends. Younger males attending in the early morning hours at weekends made up the largest proportion of alcohol-related attendances. The mean cost per attendance was £249 (SD £1,064); the mean total cost for those admitted was £851 (SD £2,549). The most common reasons for attending were trauma-related injuries, followed by psychiatric problems. Conclusions: Alcohol-related attendances are a major and avoidable burden on emergency care. However, targeted interventions at weekends and early morning hours could capture the majority of cases and help prevent future re-attendance

The initiator methionine tRNA drives secretion of type II collagen from stromal fibroblasts to promote tumor growth and angiogenesis

Summary: Expression of the initiator methionine tRNA (tRNAi Met) is deregulated in cancer. Despite this fact, it is not currently known how tRNAi Met expression levels influence tumor progression. We have found that tRNAi Met expression is increased in carcinoma-associated fibroblasts, implicating deregulated expression of tRNAi Met in the tumor stroma as a possible contributor to tumor progression. To investigate how elevated stromal tRNAi Met contributes to tumor progression, we generated a mouse expressing additional copies of the tRNAi Met gene (2+tRNAi Met mouse). Growth and vascularization of subcutaneous tumor allografts was enhanced in 2+tRNAi Met mice compared with wild-type littermate controls. Extracellular matrix (ECM) deposited by fibroblasts from 2+tRNAi Met mice supported enhanced endothelial cell and fibroblast migration. SILAC mass spectrometry indicated that elevated expression of tRNAi Met significantly increased synthesis and secretion of certain types of collagen, in particular type II collagen. Suppression of type II collagen opposed the ability of tRNAi Metoverexpressing fibroblasts to deposit pro-migratory ECM. We used the prolyl hydroxylase inhibitor ethyl- 3,4-dihydroxybenzoate (DHB) to determine whether collagen synthesis contributes to the tRNAi Met-driven pro-tumorigenic stroma in vivo. DHB had no effect on the growth of syngeneic allografts in wild-type mice but opposed the ability of 2+tRNAi Met mice to support increased angiogenesis and tumor growth. Finally, collagen II expression predicts poor prognosis in high-grade serous ovarian carcinoma. Taken together, these data indicate that increased tRNAi Met levels contribute to tumor progression by enhancing the ability of stromal fibroblasts to synthesize and secrete a type II collagen-rich ECM that supports endothelial cell migration and angiogenesis

Host predisposition by endogenous Transforming Growth Factor-β1 overexpression promotes pulmonary fibrosis following bleomycin injury

<p>Abstract</p> <p>Background</p> <p>Idiopathic Pulmonary Fibrosis (IPF) is a progressive diffuse disease involving the lung parenchyma. Despite recent advances, the molecular mechanisms of the initiation and progression of this disease remain elusive. Previous studies have demonstrated TGFβ1 as a key effector cytokine in the development of lung fibrosis.</p> <p>Methods</p> <p>In this study we have used a transgenic mouse based strategy to identify the effect of overexpression of this key effector mediator on the development of pulmonary fibrosis in response to exogenous injury. We bred two lines (line 25 and 18) of transgenic mice (Tr+) that overexpressed active TGFβ1. Three-month old transgenic and wild type mice were subsequently wounded with intraperitoneal bleomycin. Mice were sacrificed at 6 weeks post-bleomycin and their lungs analysed histologically and biochemically.</p> <p>Results</p> <p>The severity of lung fibrosis was significantly greater in the Tr+ mice compared to the wild type mice. Using an oligonucleotide microarray based strategy we identified discrete patterns of gene expression contributing to TGFβ1 associated pulmonary fibrosis.</p> <p>Conclusion</p> <p>This data emphasises the importance of a host predisposition in the form of endogenous TGFβ1, in the development of pulmonary fibrosis in response to an exogenous injury.</p

An RxLR effector from phytophthora infestans prevents re-localisation of two plant NAC transcription factors from the endoplasmic reticulum to the nucleus

The plant immune system is activated following the perception of exposed, essential and invariant microbial molecules that are recognised as non-self. A major component of plant immunity is the transcriptional induction of genes involved in a wide array of defence responses. In turn, adapted pathogens deliver effector proteins that act either inside or outside plant cells to manipulate host processes, often through their direct action on plant protein targets. To date, few effectors have been shown to directly manipulate transcriptional regulators of plant defence. Moreover, little is known generally about the modes of action of effectors from filamentous (fungal and oomycete) plant pathogens. We describe an effector, called Pi03192, from the late blight pathogen Phytophthora infestans, which interacts with a pair of host transcription factors at the endoplasmic reticulum (ER) inside plant cells. We show that these transcription factors are released from the ER to enter the nucleus, following pathogen perception, and are important in restricting disease. Pi03192 prevents the plant transcription factors from accumulating in the host nucleus, revealing a novel means of enhancing host susceptibility

Setting up a Paediatric Rapid Access Outpatient Unit: Views of general practice teams

<p>Abstract</p> <p>Background</p> <p>Rapid Access Outpatient Units (RAOUs) have been suggested as an alternative to hospital inpatient units for the management of some acutely unwell children. These units can provide ambulatory care, delivered close to home, and may prevent unnecessary hospital admission. There are no qualitative data on the views of primary care practitioners regarding these types of facilities. The aim of the study was to explore the opinions of primary care practitioners regarding a newly established RAOU.</p> <p>Methods</p> <p>The RAOU was established locally at a district general hospital when inpatient beds were closed and moved to an inpatient centre, based six miles away at the tertiary teaching hospital.</p> <p>Qualitative, practice based group interviews with primary care practitioners (general practitioners (GPs), nurse practitioners and practice nurses) on their experiences of the RAOU. The data collection consisted of three practice based interviews with 14 participants. The interviews were recorded and transcribed verbatim. Thematic content analysis was used to evaluate the data.</p> <p>Results</p> <p>There was positive feedback regarding ease of telephone access for referral, location, and the value of a service staffed by senior doctors where children could be observed, investigated and discharged quickly. There was confusion regarding the referral criteria for the assessment unit and where to send certain children. A majority of the practitioners felt the utility of the RAOU was restricted by its opening hours. Most participants felt they lacked sufficient information regarding the remit and facilities of the unit and this led to some uneasiness regarding safety and long term sustainability.</p> <p>Conclusion</p> <p>Practitioners considered that the RAOU offered a rapid senior opinion, flexible short term observation, quick access to investigations and was more convenient for patients. There were concerns regarding opening hours, safety of patients and lack of information about the unit's facilities. There was confusion about which children should be sent to the unit. This study raises questions regarding policy in regard to the organisation of paediatric services. It highlights that when establishing alternative services to local inpatient units, continual communication and engagement of primary care is essential if the units are to function effectively.</p

Children’s Mental Health Need and Expenditures in Ontario: Findings from the 2014 Ontario Child Health Study

Objective: To estimate the alignment between the Ontario Ministry of Children and Youth Services (MCYS) expenditures for children’s mental health services and population need, and to quantify the value of adjusting for need in addition to population size in formula-based expenditure allocations. Two need definitions are used: “assessed need,” as the presence of a mental disorder, and “perceived need,” as the subjective perception of a mental health problem. Methods: Children’s mental health need and service contact estimates (from the 2014 Ontario Child Health Study), expenditure data (from government administrative data), and population counts (from the 2011 Canadian Census) were combined to generate formula-based expenditure allocations based on 1) population size and 2) need (population size adjusted for levels of need). Allocations were compared at the service area and region level and for the 2 need definitions (assessed and perceived). Results: Comparisons were made for 13 of 33 MCYS service areas and all 5 regions. The percentage of MCYS expenditure reallocation needed to achieve an allocation based on assessed need was 25.5% at the service area level and 25.6% at the region level. Based on perceived need, these amounts were 19.4% and 27.2%, respectively. The value of needs-adjustment ranged from 8.0% to 22.7% of total expenditures, depending on the definition of need. Conclusion: Making needs adjustments to population counts using population estimates of children’s mental health need (assessed or perceived) provides additional value for informing and evaluating allocation decisions. This study provides much-needed and current information about the match between expenditures and children’s mental health need

Children’s Mental Health Need and Expenditures in Ontario: Findings from the 2014 Ontario Child Health Study

Objective: To estimate the alignment between the Ontario Ministry of Children and Youth Services (MCYS) expenditures for children’s mental health services and population need, and to quantify the value of adjusting for need in addition to population size in formula-based expenditure allocations. Two need definitions are used: “assessed need,” as the presence of a mental disorder, and “perceived need,” as the subjective perception of a mental health problem. Methods: Children’s mental health need and service contact estimates (from the 2014 Ontario Child Health Study), expenditure data (from government administrative data), and population counts (from the 2011 Canadian Census) were combined to generate formula-based expenditure allocations based on 1) population size and 2) need (population size adjusted for levels of need). Allocations were compared at the service area and region level and for the 2 need definitions (assessed and perceived). Results: Comparisons were made for 13 of 33 MCYS service areas and all 5 regions. The percentage of MCYS expenditure reallocation needed to achieve an allocation based on assessed need was 25.5% at the service area level and 25.6% at the region level. Based on perceived need, these amounts were 19.4% and 27.2%, respectively. The value of needs-adjustment ranged from 8.0% to 22.7% of total expenditures, depending on the definition of need. Conclusion: Making needs adjustments to population counts using population estimates of children’s mental health need (assessed or perceived) provides additional value for informing and evaluating allocation decisions. This study provides much-needed and current information about the match between expenditures and children’s mental health need