Peripheral modulation of olfaction by physiological state in the Egyptian leaf worm Spodoptera littoralis (Lepidoptera: Noctuidae)

Insects show behavioural plasticity based on their physiological state. Deprivation from a resource will normally make them more responsive to it or to perform behaviour increasing the probability of encountering such a resource. Modulation of the olfactory system has been shown mainly in the central nervous system, but also in the periphery. In this study, antennal sensitivity of females of the Egyptian cotton leaf worm Spodoptera littoralis to different plant and sex pheromone odours was measured using electroantennography (EAG). Different mating status, age, and feeding status were used to investigate peripheral changes in olfactory responses. Virgin females were found to be more sensitive to plant odours and sex pheromone compared to mated females. Age also had an impact on antennal sensitivity, 2 and 4 days old females being more sensitive than just-emerged ones. Such an increase in sensitivity could be explained by maturation of olfactory receptor neurons after emergence or by an increase in motivation as the available expected life time remaining decreases. Finally, feeding status did not modify the antennal sensitivity of females. A peripheral modulation could thus be demonstrated in the olfactory system of female Spodoptera littoralis at certain life stages.     

Coexpression network analysis in abdominal and gluteal adipose tissue reveals regulatory genetic loci for metabolic syndrome and related phenotypes

Metabolic Syndrome (MetS) is highly prevalent and has considerable public health impact, but its underlying genetic factors remain elusive. To identify gene networks involved in MetS, we conducted whole-genome expression and genotype profiling on abdominal (ABD) and gluteal (GLU) adipose tissue, and whole blood (WB), from 29 MetS cases and 44 controls. Co-expression network analysis for each tissue independently identified nine, six, and zero MetS–associated modules of coexpressed genes in ABD, GLU, and WB, respectively. Of 8,992 probesets expressed in ABD or GLU, 685 (7.6%) were expressed in ABD and 51 (0.6%) in GLU only. Differential eigengene network analysis of 8,256 shared probesets detected 22 shared modules with high preservation across adipose depots (D_ABD-GLU = 0.89), seven of which were associated with MetS (FDR P<0.01). The strongest associated module, significantly enriched for immune response–related processes, contained 94/620 (15%) genes with inter-depot differences. In an independent cohort of 145/141 twins with ABD and WB longitudinal expression data, median variability in ABD due to familiality was greater for MetS–associated versus un-associated modules (ABD: 0.48 versus 0.18, P = 0.08; GLU: 0.54 versus 0.20, P = 7.8×10⁻⁴). Cis-eQTL analysis of probesets associated with MetS (FDR P<0.01) and/or inter-depot differences (FDR P<0.01) provided evidence for 32 eQTLs. Corresponding eSNPs were tested for association with MetS–related phenotypes in two GWAS of >100,000 individuals; rs10282458, affecting expression of RARRES2 (encoding chemerin), was associated with body mass index (BMI) (P = 6.0×10⁻⁴); and rs2395185, affecting inter-depot differences of HLA-DRB1 expression, was associated with high-density lipoprotein (P = 8.7×10⁻⁴) and BMI–adjusted waist-to-hip ratio (P = 2.4×10⁻⁴). Since many genes and their interactions influence complex traits such as MetS, integrated analysis of genotypes and coexpression networks across multiple tissues relevant to clinical traits is an efficient strategy to identify novel associations.     

Age-Dependent TLR3 Expression of the Intestinal Epithelium Contributes to Rotavirus Susceptibility

Rotavirus is a major cause of diarrhea worldwide and exhibits a pronounced small intestinal epithelial cell (IEC) tropism. Both human infants and neonatal mice are highly susceptible, whereas adult individuals remain asymptomatic and shed only low numbers of viral particles. Here we investigated age-dependent mechanisms of the intestinal epithelial innate immune response to rotavirus infection in an oral mouse infection model. Expression of the innate immune receptor for viral dsRNA, Toll-like receptor (Tlr) 3 was low in the epithelium of suckling mice but strongly increased during the postnatal period inversely correlating with rotavirus susceptibility, viral shedding and histological damage. Adult mice deficient in Tlr3 (Tlr3^−/−) or the adaptor molecule Trif (Trif^Lps2/Lps2) exerted significantly higher viral shedding and decreased epithelial expression of proinflammatory and antiviral genes as compared to wild-type animals. In contrast, neonatal mice deficient in Tlr3 or Trif did not display impaired cell stimulation or enhanced rotavirus susceptibility. Using chimeric mice, a major contribution of the non-hematopoietic cell compartment in the Trif-mediated antiviral host response was detected in adult animals. Finally, a significant age-dependent increase of TLR3 expression was also detected in human small intestinal biopsies. Thus, upregulation of epithelial TLR3 expression during infancy might contribute to the age-dependent susceptibility to rotavirus infection.     

Exploiting temporal network structures of human interaction to effectively immunize populations

Decreasing the number of people who must be vaccinated to immunize a community against an infectious disease could both save resources and decrease outbreak sizes. A key to reaching such a lower threshold of immunization is to find and vaccinate people who, through their behavior, are more likely than average to become infected and to spread the disease further. Fortunately, the very behavior that makes these people important to vaccinate can help us to localize them. Earlier studies have shown that one can use previous contacts to find people that are central in static contact networks. However, real contact patterns are not static. In this paper, we investigate if there is additional information in the temporal contact structure for vaccination protocols to exploit. We answer this affirmative by proposing two immunization methods that exploit temporal correlations and showing that these methods outperform a benchmark static-network protocol in four empirical contact datasets under various epidemic scenarios. Both methods rely only on obtainable, local information, and can be implemented in practice. For the datasets directly related to contact patterns of potential disease spreading (of sexually-transmitted and nosocomial infections respectively), the most efficient protocol is to sample people at random and vaccinate their latest contacts. The network datasets are temporal, which enables us to make more realistic evaluations than earlier studies--we use only information about the past for the purpose of vaccination, and about the future to simulate disease outbreaks. Using analytically tractable models, we identify two temporal structures that explain how the protocols earn their efficiency in the empirical data. This paper is a first step towards real vaccination protocols that exploit temporal-network structure--future work is needed both to characterize the structure of real contact sequences and to devise immunization methods that exploit these.     

Exceptionally preserved Cambrian trilobite digestive system revealed in 3D by synchrotron-radiation X-ray tomographic microscopy

The Cambrian 'Orsten' fauna comprises exceptionally preserved and phosphatised microscopic arthropods. The external morphology of these fossils is well known, but their internal soft-tissue anatomy has remained virtually unknown. Here, we report the first non-biomineralised tissues from a juvenile polymerid trilobite, represented by digestive structures, glands, and connective strands harboured in a hypostome from the Swedish 'Orsten' fauna. Synchrotron-radiation X-ray tomographic microscopy enabled three-dimensional internal recordings at sub-micrometre resolution. The specimen provides the first unambiguous evidence for a J-shaped anterior gut and the presence of a crop with a constricted alimentary tract in the Trilobita. Moreover, the gut is Y-shaped in cross section, probably due to a collapsed lumen of that shape, another feature which has not previously been observed in trilobites. The combination of anatomical features suggests that the trilobite hypostome is functionally analogous to the labrum of euarthropods and that it was a sophisticated element closely integrated with the digestive system. This study also briefly addresses the preservational bias of the 'Orsten' fauna, particularly the near-absence of polymerid trilobites, and the taphonomy of the soft-tissue-harbouring hypostome.     

Validation of noninvasive monitoring of adrenocortical endocrine activity in ground-feeding aardwolves (Proteles cristata): exemplifying the influence of consumption of inorganic material for fecal steroid analysis

Biologically inert material in feces may confound interpretations of noninvasive fecal endocrine data, because it may induce variance related to differences in foraging behavior rather than to differences in endocrine activity. We evaluated two different enzyme immunoassays (EIAs) for the noninvasive evaluation of adrenocortical activity in ground-feeding aardwolves (Proteles cristata) and tested the influence of soil content in aardwolf feces on the interpretation of fecal glucocorticoid metabolite data. Using adrenocorticotropic hormone (ACTH) challenges for validation, we successfully identified a cortisol EIA suitable for assessing adrenocortical activity in aardwolves. An alternatively tested 11-oxoetiocholanolone EIA failed to detect a biologically relevant signal after ACTH administration. Although the proportion of inorganic content in aardwolf feces did not alter qualitative conclusions from the endocrine data, the data related to mass of organic content had a larger amount of variance attributed to relevant biological contrasts and a lower amount of variance attributed to individual variation, compared with data related to total dry mass of extracted material. Compared with data expressed as dry mass of extracted material, data expressed as mass of organic content may provide a more refined and statistically powerful measure of endocrine activity in species that ingest large amounts of indigestible material.     

Acute knockdown of uncoupling protein-2 increases uncoupling via the adenine nucleotide transporter and decreases oxidative stress in diabetic kidneys

Increased O(2) metabolism resulting in chronic hypoxia is common in models of endstage renal disease. Mitochondrial uncoupling increases O(2) consumption but the ensuing reduction in mitochondrial membrane potential may limit excessive oxidative stress. The present study addressed the hypothesis that mitochondrial uncoupling regulates mitochondria function and oxidative stress in the diabetic kidney. Isolated mitochondria from kidney cortex of control and streptozotocin-induced diabetic rats were studied before and after siRNA knockdown of uncoupling protein-2 (UCP-2). Diabetes resulted in increased UCP-2 protein expression and UCP-2-mediated uncoupling, but normal mitochondria membrane potential. This uncoupling was inhibited by GDP, which also increased the membrane potential. siRNA reduced UCP-2 protein expression in controls and diabetics (-30-50%), but paradoxically further increased uncoupling and markedly reduced the membrane potential. This siRNA mediated uncoupling was unaffected by GDP but was blocked by ADP and carboxyatractylate (CAT). Mitochondria membrane potential after UCP-2 siRNA was unaffected by GDP but increased by CAT. This demonstrated that further increased mitochondria uncoupling after siRNA towards UCP-2 is mediated through the adenine nucleotide transporter (ANT). The increased oxidative stress in the diabetic kidney, manifested as increased thiobarbituric acids, was reduced by knocking down UCP-2 whereas whole-body oxidative stress, manifested as increased circulating malondialdehyde, remained unaffected. All parameters investigated were unaffected by scrambled siRNA. In conclusion, mitochondrial uncoupling via UCP-2 regulates mitochondria membrane potential in diabetes. However, blockade of the diabetes-induced upregulation of UCP- 2 results in excessive uncoupling and reduced oxidative stress in the kidney via activation of ANT.     

Potent intratype neutralizing activity distinguishes human immunodeficiency virus type 2 (HIV-2) from HIV-1

HIV-2 has a lower pathogenicity and transmission rate than HIV-1. Neutralizing antibodies could be contributing to these observations. Here we explored side by side the potency and breadth of intratype and intertype neutralizing activity (NAc) in plasma of 20 HIV-1-, 20 HIV-2-, and 11 dually HIV-1/2 (HIV-D)-seropositive individuals from Guinea-Bissau, West Africa. Panels of primary isolates, five HIV-1 and five HIV-2 isolates, were tested in a plaque reduction assay using U87.CD4-CCR5 cells as targets. Intratype NAc in HIV-2 plasma was found to be considerably more potent and also broader than intratype NAc in HIV-1 plasma. This indicates that HIV-2-infected individuals display potent type-specific neutralizing antibodies, whereas such strong type-specific antibodies are absent in HIV-1 infection. Furthermore, the potency of intratype NAc was positively associated with the viral load of HIV-1 but not HIV-2, suggesting that NAc in HIV-1 infection is more antigen stimulation dependent than in HIV-2 infection, where plasma viral loads typically are at least 10-fold lower than in HIV-1 infection. Intertype NAc of both HIV-1 and HIV-2 infections was, instead, of low potency. HIV-D subjects had NAc to HIV-2 with similar high potency as singly HIV-2-infected individuals, whereas neutralization of HIV-1 remained poor, indicating that the difference in NAc between HIV-1 and HIV-2 infections depends on the virus itself. We suggest that immunogenicity and/or antigenicity, meaning the neutralization phenotype, of HIV-2 is distinct from that of HIV-1 and that HIV-2 may display structures that favor triggering of potent neutralizing antibody responses.