Helminth infection impairs autophagy-mediated killing of bacterial enteropathogens by macrophages

Autophagy is an important mechanism used by macrophages to kill intracellular pathogens. The results reported in this study demonstrate that autophagy is also involved in the macrophage killing of the extracellular enteropathogen Citrobacter rodentium after phagocytosis. The process was significantly impaired in macrophages isolated from mice chronically infected with the helminth parasite Heligmosomoides polygyrus. The H. polygyrus-mediated inhibition of autophagy was Th2 dependent because it was not observed in macrophages isolated from helminth-infected STAT6-deficient mice. Moreover, autophagy of Citrobacter was inhibited by treating macrophages with IL-4 and IL-13. The effect of H. polygyrus on autophagy was associated with decreased expression and processing of L chain protein 3 (LC3), a key component of the autophagic machinery. The helminth-induced inhibition of LC3 expression and processing was STAT6 dependent and could be recapitulated by treatment of macrophages with IL-4 and IL-13. Knockdown of LC3 significantly inhibited autophagic killing of Citrobacter, attesting to the functional importance of the H. polygyrus-mediated downregulation of this process. These observations reveal a new aspect of the immunosuppressive effects of helminth infection and provide mechanistic insights into our earlier finding that H. polygyrus significantly worsens the in vivo course of Citrobacter infection.     

Predicting organismal vulnerability to climate warming: roles of behaviour, physiology and adaptation

A recently developed integrative framework proposes that the vulnerability of a species to environmental change depends on the species' exposure and sensitivity to environmental change, its resilience to perturbations and its potential to adapt to change. These vulnerability criteria require behavioural, physiological and genetic data. With this information in hand, biologists can predict organisms most at risk from environmental change. Biologists and managers can then target organisms and habitats most at risk. Unfortunately, the required data (e.g. optimal physiological temperatures) are rarely available. Here, we evaluate the reliability of potential proxies (e.g. critical temperatures) that are often available for some groups. Several proxies for ectotherms are promising, but analogous ones for endotherms are lacking. We also develop a simple graphical model of how behavioural thermoregulation, acclimation and adaptation may interact to influence vulnerability over time. After considering this model together with the proxies available for physiological sensitivity to climate change, we conclude that ectotherms sharing vulnerability traits seem concentrated in lowland tropical forests. Their vulnerability may be exacerbated by negative biotic interactions. Whether tropical forest (or other) species can adapt to warming environments is unclear, as genetic and selective data are scant. Nevertheless, the prospects for tropical forest ectotherms appear grim.     

Reduced biological control and enhanced chemical pest management in the evolution of fungus farming in ants

To combat disease, most fungus-growing ants (Attini) use antibiotics from mutualistic bacteria (Pseudonocardia) that are cultured on the ants'' exoskeletons and chemical cocktails from exocrine glands, especially the metapleural glands (MG). Previous work has hypothesized that (i) Pseudonocardia antibiotics are narrow-spectrum and control a fungus (Escovopsis) that parasitizes the ants'' fungal symbiont, and (ii) MG secretions have broad-spectrum activity and protect ants and brood. We assessed the relative importance of these lines of defence, and their activity spectra, by scoring abundance of visible Pseudonocardia for nine species from five genera and measuring rates of MG grooming after challenging ants with disease agents of differing virulence. Atta and Sericomyrmex have lost or greatly reduced the abundance of visible bacteria. When challenged with diverse disease agents, including Escovopsis, they significantly increased MG grooming rates and expanded the range of targets. By contrast, species of Acromyrmex and Trachymyrmex maintain abundant Pseudonocardia. When challenged, these species had lower MG grooming rates, targeted primarily to brood. More elaborate MG defences and reduced reliance on mutualistic Pseudonocardia are correlated with larger colony size among attine genera, raising questions about the efficacy of managing disease in large societies with chemical cocktails versus bacterial antimicrobial metabolites.     

Solution structure of lysine‐free (K0) ubiquitin

Lysine‐free ubiquitin (K0‐Ub) is commonly used to study the ubiquitin‐signaling pathway, where it is assumed to have the same structure and function as wild‐type ubiquitin (wt‐Ub). However, the K0‐Ub ¹⁵N heteronuclear single quantum correlation NMR spectrum differs significantly from wt‐Ub and the melting temperature is depressed by 19°C, raising the question of the structural integrity and equivalence to wt‐Ub. The three‐dimensional structure of K0‐Ub was determined by solution NMR, using chemical shift and residual dipolar coupling data. K0‐Ub adopts the same backbone structure as wt‐Ub, and all significant chemical shifts can be related to interactions impacted by the K to R mutations.     

Evidence against proteoglycan mediated collagen fibril load transmission and dynamic viscoelasticity in tendon

The glycosaminoglycan (GAG) dermatan sulfate and chondroitin sulfate side-chains of small leucine-rich proteoglycans have been increasingly posited to act as molecular cross links between adjacent collagen fibrils and to directly contribute to tendon elasticity. GAGs have also been implicated in tendon viscoelasticity, supposedly affecting frictional loss during elongation or fluid flow through the extra cellular matrix. The current study sought to systematically test these theories of tendon structure–function by investigating the mechanical repercussions of enzymatic depletion of GAG complexes by chondroitinase ABC in a reproducible tendon structure–function model (rat tail tendon fascicles). The extent of GAG removal (at least 93%) was verified by relevant spectrophotometric assays and transmission electron microscopy. Dynamic viscoelastic tensile tests on GAG depleted rat tail tendon fascicle were not mechanically different from controls in storage modulus (elastic behavior) over a wide range of strain-rates (0.05, 0.5, and 5% change in length per second) in either the linear or nonlinear regions of the material curve. Loss modulus (viscoelastic behavior) was only affected in the nonlinear region at the highest strain-rate, and even this effect was marginal (19% increased loss modulus, p = 0.035). Thus glycosaminoglycan chains of small leucine-rich proteoglycans do not appear to mediate dynamic elastic behavior nor do they appear to regulate the dynamic viscoelastic properties in rat tail tendon fascicles.     

Evolution and University-level Anthropology Textbooks: The “Missing Link”?

Although studies analyzing the content of evolution curriculum usually focus on courses within the context of a biological sciences department or program, research must also address students and courses outside of the biological sciences. For example, using data solely from biological courses will not fully represent the scope of coverage of evolution in university education, as other fields, like anthropology, also utilize evolutionary principles. We analyzed the content of 31 university-level anthropology textbooks for the following: (1) presence of a definition of evolution in various sections of the textbooks, (2) accuracy and consistency of the definitions provided in the textbook sections, and (3) differences between textbooks for cultural and physical anthropology. Results of this study suggest that anthropology textbooks do not necessarily (1) provide a single definition of evolution or (2) provide an accurate, “baseline” definition of evolution when present. Additionally, substantive differences were observed between definitions provided in different sections within a single textbook, as well as between textbooks written for cultural anthropology and physical anthropology/archaeology courses. Given the inclusion of anthropology courses in general education curriculum at the university-level, we conclude that this situation may further exacerbate the misunderstanding of the basic tenets of evolution that university students have been repeatedly shown to demonstrate. We stress the role of the instructor in choosing textbooks that provide accurate information for students, as well as the responsibility they hold in providing a concise, accurate definition of evolution in social sciences courses.     

Phytosociology as a tool for forest restoration: a study case in the extreme South of Atlantic Forest Biome

The biodiversity loss, due to anthropic activities, has generated the necessity of studies that enable the ecosystem conservation. Nevertheless, the majority of studies restrict themselves to the floristic composition and phytosociological structure from determined pre-established diameter, neglecting attributes of the species, such as its (their) niche (s) of occurrence in the forest, thus, making it difficult to identify potential species for restoration. In this way, the present study aimed to evaluate the structure of a forest fragment in the extreme South of Atlantic Forest Biome, through identification of species in the different layers. There were used 18 parcels of 10 m × 20 m, distributed systematically, where the vegetation was evaluated in four size classes. The characterization of the structure of the arboreal-shrub of the forest was performed by the data comparison of the floristic composition and phytosociological structure. In the fragment of forest studied, there were sampled a total of 2.176 individuals. The floristic composition of the area includes 74 species, belonging to 58 genera and 28 botanical families. We observed differences in relation of richness and diversity of species among the analyzed layers, the intermediate layer presented the lowest richness of species, being the pioneers and initial secondaries the least representatives. Trichilia claussenii, Sorocea bonplandii, Actinostemon concolor, Apuleia leiocarpa and Nectandra megapotamica were the most abundant species and well distributed in the different size classes, and they can be used in the enrichment of areas in process of restoration in the scope of the Deciduous Seasonal Forest in the extreme South of Atlantic Forest Biome. Ocotea puberula, Allophylus edulis, Cedrela fissillis and Machaerium paraguariense formed a group of species with expressive representativeness in the arboreal layer, thus they can be used in the moment of planting as species to the fast covering of the area.     

FTO gene associated fatness in relation to body fat distribution and metabolic traits throughout a broad range of fatness

Background

A common single nucleotide polymorphism (SNP) of FTO (rs9939609, T/A) is associated with total body fatness. We investigated the association of this SNP with abdominal and peripheral fatness and obesity-related metabolic traits in middle-aged men through a broad range of fatness present already in adolescence.

Methodology/Principal Findings

Obese young Danish men (n = 753, BMI≥31.0 kg/m²) and a randomly selected group (n = 879) from the same population were examined in three surveys (mean age 35, 46 and 49 years, respectively). The traits included anthropometrics, body composition, oral glucose tolerance test, blood lipids, blood pressure, fibrinogen and aspartate aminotransferase. Logistic regression analysis was used to assess the age-adjusted association between the phenotypes and the odds ratios for the FTO rs9939609 (TT and TA genotype versus the AA genotype), for anthropometrics and body composition estimated per unit z-score. BMI was strongly associated with the AA genotype in all three surveys: OR = 1.17, p = 1.1*10⁻⁶, OR = 1.20, p = 1.7*10⁻⁷, OR = 1.17, p = 3.4*10⁻³, respectively. Fat body mass index was also associated with the AA genotype (OR = 1.21, p = 4.6*10⁻⁷ and OR = 1.21, p = 1.0*10⁻³). Increased abdominal fatness was associated with the AA genotype when measured as waist circumference (OR = 1.21, p = 2.2*10⁻⁶ and OR = 1.19, p = 5.9*10⁻³), sagittal abdominal diameter (OR = 1.17, p = 1.3*10⁻⁴ and OR = 1.18, p = 0.011) and intra-abdominal adipose tissue (OR = 1.21, p = 0.005). Increased peripheral fatness measured as hip circumference (OR = 1.19, p = 1.3*10⁻⁵ and OR = 1.18, p = 0.004) and lower body fat mass (OR = 1.26, p = 0.002) was associated with the AA genotype. The AA genotype was significantly associated with decreased Stumvoll insulin sensitivity index (OR = 0.93, p = 0.02) and with decreased non-fasting plasma HDL-cholesterol (OR = 0.57, p = 0.037), but not with any other of the metabolic traits. However, all significant results for both body fat distribution and metabolic traits were explained by a mediating effect of total fat mass.

Conclusion

The association of the examined FTO SNP to general fatness throughout the range of fatness was confirmed, and this association explains the relation between the SNP and body fat distribution and decreased insulin sensitivity and HDL-cholesterol. The SNP was not significantly associated with other metabolic traits suggesting that they are not derived from the general accumulation of body fat.