Protective vaccines elicit high-affinity, neutralizing antibodies by selection of somatically hypermutated B cell antigen receptors (BCR) on immune complexes (ICs). This implicates Fc-Fc receptor ...(FcR) interactions in affinity maturation, which, in turn, are determined by IgG subclass and Fc glycan composition within ICs. Trivalent influenza virus vaccination elicited regulation of anti-hemagglutinin (HA) IgG subclass and Fc glycans, with abundance of sialylated Fc glycans (sFc) predicting quality of vaccine response. We show that sFcs drive BCR affinity selection by binding the Type-II FcR CD23, thus upregulating the inhibitory FcγRIIB on activated B cells. This elevates the threshold requirement for BCR signaling, resulting in B cell selection for higher affinity BCR. Immunization with sFc HA ICs elicited protective, high-affinity IgGs against the conserved stalk of the HA. These results reveal a novel, endogenous pathway for affinity maturation that can be exploited for eliciting high-affinity, broadly neutralizing antibodies through immunization with sialylated immune complexes.
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•Dynamic changes in Fc glycan composition following influenza vaccination•Sialylated Fc glycan abundance on anti-HA IgG predicts vaccine response•Sialylated Fc immune complexes engage CD23 and BCR to modulate affinity maturation•IgGs elicited by sialylated Fc immune complexes protect broadly against H1 viruses
The glycan composition of the Fc region of anti-influenza antibodies changes following vaccination, with sialylated Fc glycan abundance predicting the quality of the vaccine response and production of high-affinity antibodies against the conserved stalk domain of the influenza HA.
Increases in intracellular free Ca2+ play a major role in many cellular processes. The deregulation of Ca2+ signaling is a feature of a variety of diseases, and modulators of Ca2+ signaling are used ...to treat conditions as diverse as hypertension to pain. The Ca2+ signal also plays a role in processes important in cancer, such as proliferation and migration. Many studies in cancer have identified alterations in the expression of proteins involved in the movement of Ca2+ across the plasma membrane and subcellular organelles. In some cases, these Ca2+ channels or pumps are potential therapeutic targets for specific cancer subtypes or correlate with prognosis.
► We discuss a wide number of methods for detection of explosives. ► Spectroscopic, electrochemical and biochemical methods are discussed. ► An overview of nanomaterials and their effects is ...presented. ► Current commercial devices are compared and future trends were discussed.
The detection of explosives and explosive-related compounds has become a heightened priority in recent years for homeland security and counter-terrorism applications. There has been a huge increase in research within this area—through both the development of new, innovative detection approaches and the improvement of existing techniques. Developments for miniaturisation, portability, field-ruggedisation and improvements in stand-off distances, selectivity and sensitivity have been necessary to develop and improve techniques. This review provides a consolidation of information relating to recent advances in explosive detection techniques without being limited to one specific research area or explosive type. The focus of this review will be towards advances in the last 5 years, with the reader being referred to earlier reviews where appropriate.
Skeletal muscle has a remarkable plasticity to adapt and remodel in response to environmental cues, such as physical exercise. Endurance exercise stimulates improvements in muscle oxidative capacity, ...while resistance exercise induces muscle growth. Here we show that the c-Jun N-terminal kinase (JNK) is a molecular switch that when active, stimulates muscle fibers to grow, resulting in increased muscle mass. Conversely, when muscle JNK activation is suppressed, an alternative remodeling program is initiated, resulting in smaller, more oxidative muscle fibers, and enhanced aerobic fitness. When muscle is exposed to mechanical stress, JNK initiates muscle growth via phosphorylation of the transcription factor, SMAD2, at specific linker region residues leading to inhibition of the growth suppressor, myostatin. In human skeletal muscle, this JNK/SMAD signaling axis is activated by resistance exercise, but not endurance exercise. We conclude that JNK acts as a key mediator of muscle remodeling during exercise via regulation of myostatin/SMAD signaling.
Small additions of rare-earth (RE) elements have been shown to have a powerful effect in modifying the texture of wrought magnesium alloys, giving a highly beneficial effect in improving their ...formability. Recent work has shown that segregation of RE atoms to grain boundaries is important in producing this texture change. In this work, two Mg-RE systems have been studied Mg-Y and Mg-Nd using high-resolution scanning transmission electron microscopy that permits both imaging and elemental analysis with a spatial resolution of better than 0.1 nm. The Mg-Y alloy, where the solubility and level of addition are relatively high, showed the RE texture change effect. This was accompanied by clustering of Y on the grain boundaries, consistent with previous studies of the Mg-Gd system. The Mg-Nd alloy, where the solubility and level of addition are relatively low, showed no texture change and no segregation. In this case, impurity elements binding the RE into insoluble particles, rendering it ineffective. The results are analyzed by modifying a previous model for the solute drag effect on boundaries expected due to the RE additions. This predicts that both Gd and Y will strongly inhibit boundary motion, with Gd being approximately twice as effective as Y.
The source of health information can have an impact on the manner and frequency of its use. In the arena of vaccine safety, a variety of sources promulgate information from very different ...perspectives. The spectrum runs from traditional sources such as public health officials and physicians to nontraditional sources, such as celebrities.
To assess what proportion of parents trust vaccine information from different sources and whether different groups of parents vary in their trust of such information.
In January 2009, as part of a larger study of parents and nonparents, 2521 online surveys were fielded to a nationally representative sample of parents of children aged ≤ 17 years. The main outcome measure was the source credibility of vaccine-safety information used by parents.
The response rate was 62%. Parents reported trusting their children's doctor for vaccine-safety information most often (76% endorsed a lot of trust), followed by other health care providers (26%), government vaccine experts/officials (23%), and family and friends (15%). In contrast, celebrities were trusted a lot by 2% of the respondents and not at all by 76% of the respondents. Levels of trust in specific sources of vaccine-safety information varied significantly by gender (women > men) and race/ethnicity (Hispanics > other groups).
Although most parents place a lot of trust in their child(ren)'s physician, parents' trust in non-health professional sources for such information should not be discounted. Those who design public health efforts to provide evidence-based information must recognize that different strategies may be required to reach some groups of parents who use other information sources.
Parental vaccine safety concerns in 2009 Freed, Gary L; Clark, Sarah J; Butchart, Amy T ...
Pediatrics (Evanston),
04/2010, Letnik:
125, Številka:
4
Journal Article
Recenzirano
Vaccine safety concerns can diminish parents' willingness to vaccinate their children. The objective of this study was to characterize the current prevalence of parental vaccine refusal and specific ...vaccine safety concerns and to determine whether such concerns were more common in specific population groups.
In January 2009, as part of a larger study of parents and nonparents, 2521 online surveys were sent to a nationally representative sample of parents of children who were aged </=17 years. The main outcome measures were parental opinions on vaccine safety and whether the parent had ever refused a vaccine that a doctor recommended for his or her child.
The response rate was 62%. Most parents agreed that vaccines protect their child(ren) from diseases; however, more than half of the respondents also expressed concerns regarding serious adverse effects. Overall, 11.5% of the parents had refused at least 1 recommended vaccine. Women were more likely to be concerned about serious adverse effects, to believe that some vaccines cause autism, and to have ever refused a vaccine for their child(ren). Hispanic parents were more likely than white or black parents to report that they generally follow their doctor's recommendations about vaccines for their children and less likely to have ever refused a vaccine. Hispanic parents were also more likely to be concerned about serious adverse effects of vaccines and to believe that some vaccines cause autism.
Although parents overwhelmingly share the belief that vaccines are a good way to protect their children from disease, these same parents express concerns regarding the potential adverse effects and especially seem to question the safety of newer vaccines. Although information is available to address many vaccine safety concerns, such information is not reaching many parents in an effective or convincing manner.
Hand, foot, and mouth disease (HFMD) is an enterovirus‐mediated condition that predominantly affects children under 5 years of age. The tendency for outbreaks to peak in warmer summer months suggests ...a relationship between HFMD and weather patterns. We reviewed the English‐language literature for articles describing a relationship between meteorological variables and HFMD. Seventy‐two studies meeting criteria were identified. A positive, statistically significant relationship was identified between HFMD cases and both temperature (61 of 67 studies, or 91.0%, reported a positive relationship) CI 81.8–95.8%, P = 0.0001 and relative humidity (41 of 54 studies, or 75.9%) CI 63.1–85.4%, P = 0.0001. No significant relationship was identified between HFMD and precipitation, wind speed, and/or sunshine. Most countries reported a single peak of disease each year (most commonly early Summer), but subtropical and tropical climate zones were significantly more likely to experience a bimodal distribution of cases throughout the year (two peaks a year; most commonly late spring/early summer, with a smaller peak in autumn). The rising global incidence of HFMD, particularly in Pacific Asia, may be related to climate change. Weather forecasting might be used effectively in the future to indicate the risk of HFMD outbreaks and the need for targeted public health interventions.
Biological invasions are a major driver of ecosystem change but causes of variation in their environmental impacts over space and time remain poorly understood. Most approaches used to quantify the ...impacts of non‐native species assume there are interactions among per capita (i.e. individual level) effects, species abundance and the area occupied by the species. However, studies rarely evaluate these factors and their interactions and often fail to recognize that the magnitude of impacts can be highly context dependent. Understanding what drives the context dependence of non‐native species impacts can improve our understanding and predictions of ecosystem change and better inform options for mitigation.
Conifers, especially pines, are among the most problematic non‐native plant species globally. We use Pinaceae to illustrate how context dependence in biodiversity and environmental impacts of non‐native plant species can be generated by at least four processes: nonlinear density effects; intraspecific variation in functional traits; shifts in impacts over time; and persistence of impacts as biological or ecosystem legacies following non‐native species removal. Using this understanding, we develop a framework to better quantify interactions of impacts along environmental gradients (e.g. soil fertility, climate, ecosystem age).
We demonstrate how impacts of non‐native species can occur at both low and high density, and that failing to account for intraspecific variation in effect traits can lead to significant errors in the prediction of impacts. By incorporating context dependence in regard to density and functional traits, we can measure how the interaction of this context dependence will shift along environmental gradients. Moreover, disentangling the roles of species and abundance along such gradients will provide new insights into the net effects of both the native and non‐native components of communities. We use a working example of our framework that incorporates all four processes to demonstrate how to measure fire risk impacts of Pinus contorta.
We show that ecosystem impacts of non‐native tree species are not fixed but rather vary predictably along major environmental gradients. Moreover, removal of non‐native species through management provides an important tool for revealing biological and ecosystem legacy effects. Although we focus here on relatively well‐documented Pinaceae, the new insights into context dependence of impacts can be widely applied across species, environments and regions.
A free Plain Language Summary can be found within the Supporting Information of this article.
A free Plain Language Summary can be found within the Supporting Information of this article.
Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a progressive late-onset, neurological disease. Recently, a pentanucleotide expansion in intron 2 of RFC1 was identified as ...the genetic cause of CANVAS. We screened an Asian-Pacific cohort for CANVAS and identified a novel RFC1 repeat expansion motif, (ACAGG)exp, in three affected individuals. This motif was associated with additional clinical features including fasciculations and elevated serum creatine kinase. These features have not previously been described in individuals with genetically-confirmed CANVAS. Haplotype analysis showed our patients shared the same core haplotype as previously published, supporting the possibility of a single origin of the RFC1 disease allele. We analysed data from >26 000 genetically diverse individuals in gnomAD to show enrichment of (ACAGG) in non-European populations.
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