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Leishmania rely heavily on glycans to complete their digenetic life cycle in both mammalian and phlebotomine sand fly hosts. Leishmania promastigotes secrete a proteophosphoglycan-rich gel (Promastigote Secretory Gel, PSG) that is regurgitated during transmission and can exacerbate infection in the skin. Here we explored the role of PSG from natural Leishmania-sand fly vector combinations by obtaining PSG from Leishmania (L.) major-infected Phlebotomus (P.) papatasi and P. duboscqi and L. tropica-infected P. arabicus. We found that, in addition to the vector's saliva, the PSG from L. major and L. tropica potently exacerbated cutaneous infection in BALB/c mice, improved the probability of developing a patent cutaneous lesion, parasite growth and the evolution of the lesion. Of note, the presence of PSG in the inoculum more than halved the prepatent period of cutaneous L. tropica infection from an average of 32 weeks to 13 weeks. In addition, L. major and L. tropica PSG extracted from the permissive experimental vector, Lutzomyia (Lu.) longipalpis, also exacerbated infections in mice. These results reinforce and extend the hypothesis that PSG is an important and evolutionarily conserved component of Leishmania infection that can be used to facilitate experimental infection for drug and vaccine screening.
Gilt progeny (GP) are born and weaned lighter than sow progeny (SP) and tend to have higher rates of mortality and morbidity. This study quantified the lifetime growth performance differences between GP and SP and, additionally, evaluated whether segregating GP and SP in the grower–finisher period compared to mixing them within common pens reduced this variation. It was hypothesised that GP would be lighter than SP at every stage and segregation would improve growth performance of both GP and SP. All piglets born to 61 gilts (parity 1) and 47 sows (parities 2 to 7; mean 3.5 ± 0.2) were allocated to four treatments at 10 weeks of age: (i) GP housed together (GG), (ii) GP mixed (M) with SP (GM), (iii) SP housed together (SS) and (iv) SP mixed with GP (SM). The GM and SM pigs were housed together in common pens after movement into the grower–finisher facility. Individual live weight of all progeny was recorded at birth, weaning (WWT), 10 weeks of age (10WT) and sale (SWT). Individual hot carcass weight (HCW), fat depth at the head of the last rib (P2) and dressing percentage were measured at slaughter. Gilt progeny were lighter at birth (P = 0.038), weaning (P < 0.001) and through to sale (P = 0.001) than SP. Nursery and grower–finisher performance differences in GP were highly attributable to their lower WWT compared to SP (P < 0.001 when fitted as a covariate). Segregation of GP and SP increased grower–finisher average daily gain (ADG) in SP but decreased ADG and SWT in GP (P < 0.10). Segregated SP had increased average daily feed intake but only in males (P = 0.007); HCW (P < 0.001) and P2 fat depth (P = 0.055) were higher in mixed female GP, but there was no difference (P > 0.10) in female SP, or in males. In conclusion, GP were lighter at every stage than SP and differences after weaning were highly related to the lighter WWT of GP. Under the conditions of this study, overall segregation of GP and SP showed no consistent advantages in growth performance for both groups and differed significantly between males and females.
The phenomenon of buying-shopping disorder (BSD) was described over 100 years ago. Definitions of BSD refer to extreme preoccupation with shopping and buying, to impulses to purchase that are experienced as irresistible, and to recurrent maladaptive buying excesses that lead to distress and impairments. Efforts to stop BSD episodes are unsuccessful, despite the awareness of repeated break-downs in self-regulation, experiences of post-purchase guilt and regret, comorbid psychiatric disorders, reduced quality of life, familial discord, work impairment, financial problems, and other negative consequences. A recent meta-analysis indicated an estimated point prevalence of BSD of 5%. In this narrative review, the authors offer a perspective to consider BSD as a mental health condition and to classify this disorder as a behavioral addiction, based on both research data and on long-standing clinical experience.
Roundup is a glyphosate-based herbicide (GBH) widely used in agriculture and may cause toxic effects in non-target organisms. Model organisms, as zebrafish, and analysis of gene expression by reverse transcription-quantitative PCR (RT-qPCR) could be used to better understand the Roundup toxicity. A prerequisite for RT-qPCR is the availability of appropriate reference genes; however, they have not been described for Roundup-exposed fish. The aim of this study was to evaluate the expression stability of six reference genes (rpl8, β-act, gapdh, b2m, ef1α, hprt1) and one expressed repetitive element (hatn10) in organs of males (brain, gill, testis) and females (ovary) of zebrafish exposed to Roundup WG at three concentrations (0.065, 0.65 and 6.5 mg N-(phosphonomethyl) glycine/l) for 7 days. Genes were ranked by geNorm, NormFinder, BestKeeper, Delta Ct and RefFinder, and their best combinations were determined by geNorm and NormFinder programs. The two most stable ranked genes were specific to each organ: gill (β-act; rpl8); brain (rpl8; β-act); testis (ef1α; gapdh); and ovary (rpl8; hprt1). The cat transcript level was used to evaluate the effect of normalization with these reference genes. These are the first suitable reference genes described for the analysis of gene expression in organs of Roundup-exposed zebrafish, and will allow investigations of the molecular mechanisms of Roundup toxicity.
Recent evidence shows that the serotonin 2A receptor (5-hydroxytryptamine2A receptor, 5-HT2AR) is critically involved in the formation of visual hallucinations and cognitive impairments in lysergic acid diethylamide (LSD)-induced states and neuropsychiatric diseases. However, the interaction between 5-HT2AR activation, cognitive impairments and visual hallucinations is still poorly understood. This study explored the effect of 5-HT2AR activation on response inhibition neural networks in healthy subjects by using LSD and further tested whether brain activation during response inhibition under LSD exposure was related to LSD-induced visual hallucinations.
In a double-blind, randomized, placebo-controlled, cross-over study, LSD (100 µg) and placebo were administered to 18 healthy subjects. Response inhibition was assessed using a functional magnetic resonance imaging Go/No-Go task. LSD-induced visual hallucinations were measured using the 5 Dimensions of Altered States of Consciousness (5D-ASC) questionnaire.
Relative to placebo, LSD administration impaired inhibitory performance and reduced brain activation in the right middle temporal gyrus, superior/middle/inferior frontal gyrus and anterior cingulate cortex and in the left superior frontal and postcentral gyrus and cerebellum. Parahippocampal activation during response inhibition was differently related to inhibitory performance after placebo and LSD administration. Finally, activation in the left superior frontal gyrus under LSD exposure was negatively related to LSD-induced cognitive impairments and visual imagery.
Our findings show that 5-HT2AR activation by LSD leads to a hippocampal–prefrontal cortex-mediated breakdown of inhibitory processing, which might subsequently promote the formation of LSD-induced visual imageries. These findings help to better understand the neuropsychopharmacological mechanisms of visual hallucinations in LSD-induced states and neuropsychiatric disorders.
We have compiled the X-ray characteristic properties for a unique and homogeneous sample of Type 2 AGN with water megamaser activity observed by XMM-Newton and for a control sample of non-maser galaxies, both analyzed in a uniform way. A comparison of the luminosity distributions confirms previous results (from smaller and/or less systematic studies) that water maser galaxies appear more luminous than non-maser sources. In addition, the maser phenomenon is associated with more complex X-ray spectra, higher column densities and higher equivalent widths of the Fe Kα line. Both a sufficiently luminous X-ray source and a high absorbing column density in the line of sight favor the appearance of the water megamaser phenomenon in AGN.
Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.
To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.
The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.
In the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β=0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO.
This meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.
We explore spatial aliasing of non-Gaussian distributions of sea-ice thickness. Using a heuristic model and >1000 measurements, we show how different instrument footprint sizes and shapes can cluster thickness distributions into artificial modes, thereby distorting frequency distribution, making it difficult to compare and communicate information across spatial scales. This problem has not been dealt with systematically in sea ice until now, largely because it appears to incur no significant change in integrated thickness which often serves as a volume proxy. Concomitantly, demands are increasing for thickness distribution as a resource for modeling, monitoring and forecasting air–sea fluxes and growing human infrastructure needs in a changing polar environment. New demands include the characterization of uncertainties both regionally and seasonally for spaceborne, airborne, in situ and underwater measurements. To serve these growing needs, we quantify the impact of spatial aliasing by computing resolution error (Er) over a range of horizontal scales (x) from 5 to 500 m. Results are summarized through a power law (Er= bxm) with distinct exponents (m) from 0.3 to 0.5 using example mathematical functions including Gaussian, inverse linear and running mean filters. Recommendations and visualizations are provided to encourage discussion, new data acquisitions, analysis methods and metadata formats.