Transmission electron microscopy offers structural and compositional information with atomic resolution, but its use is restricted to thin, solid samples. Liquid samples, particularly those involving ...water, have been challenging because of the need to form a thin liquid layer that is stable within the microscope vacuum. Liquid cell electron microscopy is a developing technique that allows us to apply the powerful capabilities of the electron microscope to imaging and analysis of liquid specimens. We describe its impact in materials science and biology. We discuss how its applications have expanded via improvements in equipment and experimental techniques, enabling new capabilities and stimuli for samples in liquids, and offering the potential to solve grand challenge problems.
Mammalian phospholipase C Kadamur, Ganesh; Ross, Elliott M
Annual review of physiology,
01/2013, Volume:
75
Journal Article
Peer reviewed
Phospholipase C (PLC) converts phosphatidylinositol 4,5-bisphosphate (PIP(2)) to inositol 1,4,5-trisphosphate (IP(3)) and diacylglycerol (DAG). DAG and IP(3) each control diverse cellular processes ...and are also substrates for synthesis of other important signaling molecules. PLC is thus central to many important interlocking regulatory networks. Mammals express six families of PLCs, each with both unique and overlapping controls over expression and subcellular distribution. Each PLC also responds acutely to its own spectrum of activators that includes heterotrimeric G protein subunits, protein tyrosine kinases, small G proteins, Ca(2+), and phospholipids. Mammalian PLCs are autoinhibited by a region in the catalytic TIM barrel domain that is the target of much of their acute regulation. In combination, the PLCs act as a signaling nexus that integrates numerous signaling inputs, critically governs PIP(2) levels, and regulates production of important second messengers to determine cell behavior over the millisecond to hour timescale.
Cell-mediated immunity stems from the proliferation of naive T lymphocytes expressing T cell antigen receptors (TCRs) specific for foreign peptides bound to host major histocompatibility complex ...(MHC) molecules. Because of the tremendous diversity of the T cell repertoire, naive T cells specific for any one peptide:MHC complex (pMHC) are extremely rare. Thus, it is not known how many naive T cells of any given pMHC specificity exist in the body or how that number influences the immune response. By using soluble pMHC class II (pMHCII) tetramers and magnetic bead enrichment, we found that three different pMHCII-specific naive CD4
+ T cell populations vary in frequency from 20 to 200 cells per mouse. Moreover, naive population size predicted the size and TCR diversity of the primary CD4
+ T cell response after immunization with relevant peptide. Thus, variation in naive T cell frequencies can explain why some peptides are stronger immunogens than others.
Behavioural weight management interventions consistently produce 8–10% reductions in body weight, yet most participants regain weight after treatment ends. One strategy for extending the effects of ...behavioural interventions has been the provision of extended care. The current study is a systematic review and meta‐analysis of the literature on the effect of extended care on maintenance of weight loss. Through database searches (using PubMED, PsychInfo and Cochrane Reviews) and manual searches through reference lists of related publications, 463 studies were identified. Of these, 11 were included in the meta‐analysis and an additional two were retained for qualitative analysis. The average effect of extended care on weight loss maintenance was g = 0.385 (95% confidence interval: 0.281, 0.489; P < 0.0001). This effect would lead to the maintenance of an additional 3.2 kg weight loss over 17.6 months post‐intervention in participants provided extended care compared with control. There was no significant heterogeneity between studies, Q = 5.63, P = 0.845, and there was minimal evidence for publication bias. These findings suggest that extended care is a viable and efficacious solution to addressing long‐term maintenance of lost weight. Given the chronic disease nature of obesity, extended care may be necessary for long‐term health benefits.
Climate change is impacting ecosystems worldwide. Estuaries are diverse and important aquatic ecosystems; and yet until now we have lacked information on the response of estuaries to climate change. ...Here we present data from a twelve-year monitoring program, involving 6200 observations of 166 estuaries along >1100 kilometres of the Australian coastline encompassing all estuary morphologies. Estuary temperatures increased by 2.16 °C on average over 12 years, at a rate of 0.2 °C year
, with waters acidifying at a rate of 0.09 pH units and freshening at 0.086 PSU year
. The response of estuaries to climate change is dependent on their morphology. Lagoons and rivers are warming and acidifying at the fastest rate because of shallow average depths and limited oceanic exchange. The changes measured are an order of magnitude faster than predicted by global ocean and atmospheric models, indicating that existing global models may not be useful to predict change in estuaries.
ABSTRACT
Minerals and vitamins in food staples eaten widely by the poor may be increased either through conventional plant breeding or through use of transgenic techniques, a process known as ...biofortification HarvestPlus seeks to develop and distribute cultivars of food staples (rice Oryza sativa L., wheat Triticum aestivum L., maize Zea mays L., cassava Manihot esculenta Crantz, pearl millet Pennisetum americanum Leeke, beans Phaseolus vulgaris L., sweet potato Ipomoea batatas L.) that are high in Fe, Zn, and provitamin A through an interdisciplinary global alliance of scientific institutions and implementing agencies in developing and developed countries. Biofortified crops offer a rural‐based intervention that, by design, initially reaches these more remote populations, which comprise a majority of the undernourished in many countries, and then penetrates to urban populations as production surpluses are marketed. Thus, biofortification complements fortification and supplementation programs, which work best in centralized urban areas and then reach into rural areas with good infrastructure. Initial investments in agricultural research at a central location can generate high recurrent benefits at low cost as adapted biofortified cultivars become widely available in countries across time at low recurrent costs. Overall, three things must happen for biofortification to be successful. First, the breeding must be successful—high nutrient density must be combined with high yields and high profitability. Second, efficacy must be demonstrated—the micronutrient status of human subjects must be shown to improve when consuming the biofortified cultivars as normally eaten. Third, the biofortified crops must be adopted by farmers and consumed by those suffering from micronutrient malnutrition in significant numbers.
Objective
To explore the modifications to maternity services across the UK, in response to the coronavirus disease 2019 (COVID‐19) pandemic, in the context of the pandemic guidance issued by the ...Royal College of Obstetricians and Gynaecologists (RCOG), Royal College of Midwives (RCM) and NHS England.
Design
National survey.
Setting
UK maternity services during the COVID‐19 pandemic.
Population or sample
Healthcare professionals working within maternity services.
Methods
A national electronic survey was developed to investigate local modifications to general and specialist maternity care during the COVID‐19 pandemic, in the context of the contemporaneous national pandemic guidance. After a pilot phase, the survey was distributed through professional networks by the RCOG and co‐authors. The survey results were presented descriptively in tabular and graphic formats, with proportions compared using chi‐square tests.
Main outcome measures
Service modifications made during the pandemic.
Results
A total of 81 respondent sites, 42% of the 194 obstetric units in the UK, were included. They reported substantial and heterogeneous maternity service modifications. Seventy percent of units reported a reduction in antenatal appointments and 56% reported a reduction in postnatal appointments; 89% reported using remote consultation methods. A change to screening pathways for gestational diabetes mellitus was reported by 70%, and 59% had temporarily removed the offer of births at home or in a midwife‐led unit. A reduction in emergency antenatal presentations was experienced by 86% of units.
Conclusions
This national survey documents the extensive impact of the COVID‐19 pandemic on maternity services in the UK. More research is needed to understand the impact on maternity outcomes and experience.
Tweetable
A national survey showed that UK maternity services were modified extensively and heterogeneously in response to COVID‐19.
Tweetable
A national survey showed that UK maternity services were modified extensively and heterogeneously in response to COVID‐19.
This article includes Author Insights, a video available at https://vimeo.com/rcog/authorinsights16547
Epigenetic mechanisms are emerging as mediators linking early environmental exposures during pregnancy with programmed changes in gene expression that alter offspring growth and development. There is ...irrefutable evidence from human and animal studies that nutrient and environmental agent exposures (for example, endocrine disruptors) during pregnancy may affect fetal/newborn development resulting in offspring obesity and obesity-associated metabolic abnormalities (metabolic syndrome). This concept of 'gestational programming' is associated with alterations to the epigenome (nongenomic) rather than changes in the DNA sequence (genomic). Epigenetic alterations induced by suboptimal maternal nutrition/endocrine factors include DNA methylation, histone modifications, chromatin remodeling and/or regulatory feedback by microRNAs, all of which have the ability to modulate gene expression and promote the metabolic syndrome phenotype. Recent studies have shown tissue-specific transcriptome patterns and phenotypes not only in the exposed individual, but also in subsequent progeny. Notably, the transmission of gestational programming effects to subsequent generations occurs in the absence of continued adverse environmental exposures, thus propagating the cycle of obesity and metabolic syndrome. This phenomenon may be attributed to an extrinsic process resulting from the maternal phenotype and the associated nutrient alterations occurring within each pregnancy. In addition, epigenetic inheritance may occur through somatic cells or through the germ line involving both maternal and paternal lineages. Since epigenetic gene modifications may be reversible, understanding how epigenetic mechanisms contribute to transgenerational transmission of obesity and metabolic dysfunction is crucial for the development of novel early detection and prevention strategies for programmed metabolic syndrome. In this review we discuss the evidence in human and animal studies for the role of epigenomic mechanisms in the transgenerational transmission of programmed obesity and metabolic syndrome.
Background
Diseases caused by Streptococcus pneumoniae (S. pneumoniae) continue to cause substantial morbidity and mortality globally. Whilst pneumococcal polysaccharide vaccines (PPVs) have the ...potential to prevent disease and death, the degree of protection afforded against various clinical endpoints and within different populations is uncertain.
Objectives
To assess the efficacy and effectiveness of PPVs in preventing pneumococcal disease or death in adults. We did not assess adverse events.
Search methods
We searched CENTRAL 2012, Issue 6, MEDLINE (January 1966 to June Week 2, 2012) and EMBASE (1974 to June 2012).
Selection criteria
We considered randomised controlled trials (RCTs) in adults, provided the study outcome met the definition of the outcome considered in the review. We also considered non‐RCTs in adults, where the study assessed PPV effectiveness against culture‐confirmed invasive pneumococcal disease (IPD), provided the study controlled for important confounding factors.
Data collection and analysis
Two review authors assessed trial quality of RCTs and three review authors extracted the data. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using a random‐effects model. Two review authors assessed study quality and extracted data for non‐RCTs. We calculated ORs and 95% CIs using a random‐effects model following the conversion of each study outcome to a log OR and standard error (SE).
Main results
Twenty‐five studies met our inclusion criteria (18 RCTs involving 64,852 participants and seven non‐RCTs involving 62,294 participants). Meta‐analysis of the RCTs found strong evidence of PPV efficacy against IPD with no statistical heterogeneity (OR 0.26, 95% CI 0.14 to 0.45; random‐effects model, I2 statistic = 0%). There was efficacy against all‐cause pneumonia in low‐income (OR 0.54, 95% CI 0.43 to 0.67, I2 statistic = 19%) but not high‐income countries in either the general population (OR 0.71, 95% CI 0.45 to 1.12, I2 statistic = 93%) or in adults with chronic illness (OR 0.93, 95% CI 0.73 to 1.19, I2 statistic = 10%). PPV was not associated with substantial reductions in all‐cause mortality (OR 0.90, 95% CI 0.74 to 1.09; random‐effects model, I2 statistic = 69%). Vaccine efficacy against primary outcomes appeared poorer in adults with chronic illness. Non‐RCTs provided evidence for protection against IPD in populations for whom the vaccine is currently utilised (OR 0.48, 95% CI 0.37 to 0.61; random‐effects model, I2 statistic = 31%). This review did not consider adverse events as it was outside the scope of the review.
Authors' conclusions
This meta‐analysis provides evidence supporting the recommendation for PPV to prevent IPD in adults. The evidence from RCTs is less clear with respect to adults with chronic illness. This might be because of lack of effect or lack of power in the studies. The meta‐analysis does not provide evidence to support the routine use of PPV to prevent all‐cause pneumonia or mortality.
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