Murine scent mark microbial communities are genetically determined

Scent marking in mice allows males to communicate information such as territory ownership, male competitive ability and current reproductive, nutritional, social and health status. It has been suggested that female mice eavesdrop on these olfactory cues, using them as a means of selecting mates with dissimilar major histocompatibility complex (MHC) genes, known as H2 in mice. The mechanisms underpinning MHC-dependent olfactory communication remain unresolved. Using congenic mouse strains and molecular methods we explore the involvement of the microbial communities, a known source of odourants, in scent marks to test the hypothesis that the microbial communities and hence the olfactory signals are genetically determined. Here we show that the indigenous microbial community of murine scent marks is genetically determined. Both background genotype and H2 haplotype influence the community structure of the scent mark flora, removing the possibility that community composition is solely orchestrated by the MHC. Qualitative and quantitative components of the bacterial community associated with MHC haplotype and background genotype were identified. The analyses confirm that the four groups of congenic mice tested are distinguishable on basis of the microbiology of their scent marks alone, strengthening the role of microorganisms in the development of MHC-dependent odours.     

Effects of spatial scale of sampling on food web structure

This study asks whether the spatial scale of sampling alters structural properties of food webs and whether any differences are attributable to changes in species richness and connectance with scale. Understanding how different aspects of sampling effort affect ecological network structure is important for both fundamental ecological knowledge and the application of network analysis in conservation and management. Using a highly resolved food web for the marine intertidal ecosystem of the Sanak Archipelago in the Eastern Aleutian Islands, Alaska, we assess how commonly studied properties of network structure differ for 281 versions of the food web sampled at five levels of spatial scale representing six orders of magnitude in area spread across the archipelago. Species (S) and link (L) richness both increased by approximately one order of magnitude across the five spatial scales. Links per species (L/S) more than doubled, while connectance (C) decreased by approximately two‐thirds. Fourteen commonly studied properties of network structure varied systematically with spatial scale of sampling, some increasing and others decreasing. While ecological network properties varied systematically with sampling extent, analyses using the niche model and a power‐law scaling relationship indicate that for many properties, this apparent sensitivity is attributable to the increasing S and decreasing C of webs with increasing spatial scale. As long as effects of S and C are accounted for, areal sampling bias does not have a special impact on our understanding of many aspects of network structure. However, attention does need be paid to some properties such as the fraction of species in loops, which increases more than expected with greater spatial scales of sampling.     

The Genetic Diversity of the Nguni Breed of African Cattle (Bos spp.): Complete Mitochondrial Genomes of Haplogroup T1

Domesticated cattle were commonplace in northern Africa by about 7,000 years ago. Archaeological evidence, however, suggests they were not established in southern Africa until much later, no earlier than 2,000 years ago. Genetic reconstructions have started to shed light on the movement of African cattle, but efforts have been frustrated by a lack of data south of Ethiopia and the nature of the mitochondrial haplogroup T1 which is almost fixed across the continent. We sequenced 35 complete mitochondrial genomes from a South African herd of Nguni cattle, a breed historically associated with Bantu speaking farmers who were among the first to bring cattle to southern Africa. As expected, all individuals in the study were found to be members of haplogroup T1. Only half of the sub-haplogroups of T1 (T1a-T1f) are represented in our sample and the overwhelming majority (94%) in this study belong to subhaplogroup T1b. A previous study of African cattle found frequencies of T1b of 27% in Egypt and 69% in Ethiopia. These results are consistent with serial multiple founder effects significantly shaping the gene pool as cattle were moved from north to south across the continent. Interestingly, these mitochondrial data give no indication that the impacts of the founder effects were ameliorated by gene flow from recently introduced Indian cattle breeds.     

The influence of radioiodination on the adsorption of IgG and serum albumin to polystyrene

The adsorption of radioiodinated rabbit IgG and bovine serum albumin (BSA) to polystyrene tubes was investigated. Adsorption isotherms where the proportion of the protein bound was relatively constant over a range of intermediate protein concentrations, and where the proportion bound was protein dependent, were obtained. To investigate the effects of radioiodination, proteins labeled to give a wide range of substitution ratios (0.03 to 3.7 125I/protein molecule) were employed. While labeling did not appear to affect BSA adsorption, the kinetics of IgG binding were altered in a number of ways. The proportion bound in the concentration independent region was decreased even at substitution ratios less than or equal to 0.2. In addition, while all preparations of iodinated BSA, and IgG preparations with less than or equal to 1.6 125I/IgG, gave bimodal adsorption isotherms, with more heavily labeled IgG (greater than or equal to 2.5 125I/IgG) the apparent high affinity binding to the plastic surface was abolished. These results indicate that radioiodination substantially alters the kinetics of the binding of IgG to polystyrene. In addition, the results obtained are discussed with respect to previous relevant and often apparently contradictory findings.     

A physical properties based approach for the exploration of a 4-hydroxybenzothiazolone series of β2-adrenoceptor agonists as inhaled long-acting bronchodilators

The chiral synthesis of a 4-hydroxybenzothiazolone based series of β₂-adrenoceptor agonists is described. Using this methodology a library of N-substituted analogues were prepared for the rapid identification of leads with the potential to be fast onset and long-acting inhaled bronchodilators with improved therapeutic margins. The design of the library to achieve the targeted profile was based upon lipophilicity and metabolism based hypotheses. This approach identified β-phenethyl, α-substituted cyclopentyl and monoterpene N-substituents to be of particular interest for further evaluation, as exemplified by structures 19, 29 and 33, respectively.     

Scale, environment, and trophic status: the context dependency of community saturation in rocky intertidal communities

Our understanding of the relative influence of different ecological drivers on the number of species in a place remains limited. Assessing the relative influence of local ecological interactions versus regional species pools on local species richness should help bridge this conceptual gap. Plots of local species richness versus regional species pools have been used to address this question, yet after an active quarter-century of research on the relative influence of local interactions versus regional species pools, consensus remains elusive. We propose a conceptual framework that incorporates spatial scale and ecological interaction strength to reconcile current disparities. We then test this framework using a survey of marine rocky intertidal algal and invertebrate communities from the northeast Pacific. We reach two main conclusions. First, these data show that the power of regional species pools to predict local richness disintegrates at small spatial scales coincident with the scale of biological interactions, when studying ecologically interactive groups of species, and in generally more abiotically stressful habitats (e.g., the high intertidal). Second, conclusions of past studies asserting that the regional species pool is the primary driver of local species richness may be artifacts of large spatial scales or ecologically noninteractive groups of species.     

Insight into the mechanism of inactivation and pH sensitivity in potassium channels from molecular dynamics simulations

Potassium (K (+)) channels can regulate ionic conduction through their pore by a mechanism, involving the selectivity filter, known as C-type inactivation. This process is rapid in the hERG K (+) channel and is fundamental to its physiological role. Although mutations within hERG are known to remove this process, a structural basis for the inactivation mechanism has yet to be characterized. Using MD simulations based on homology modeling, we observe that the carbonyl of the filter aromatic, Phe627, forming the S 0 K (+) binding site, swiftly rotates away from the conduction axis in the wild-type channel. In contrast, in well-characterized non-inactivating mutant channels, this conformational change occurs less frequently. In the non-inactivating channels, interactions with a water molecule located behind the selectivity filter are critical to the enhanced stability of the conducting state. We observe comparable conformational changes in the acid sensitive TASK-1 channel and propose a common mechanism in these channels for regulating efflux of K (+) ions through the selectivity filter.     

Risks of Hemolysis in Glucose-6-Phosphate Dehydrogenase Deficient Infants Exposed to Chlorproguanil-Dapsone,Mefloquine and Sulfadoxine-Pyrimethamine as Part of Intermittent Presumptive Treatment of Malaria in Infants

Background

Chlorproguanil-dapsone (CD) has been linked to hemolysis in symptomatic glucose-6-phosphate dehydrogenase deficient (G6PDd) children. Few studies have explored the effects of G6PD status on hemolysis in children treated with Intermittent Preventive Treatment in infants (IPTi) antimalarial regimens. We sought to examine the joint effects of G6PD status and IPTi antimalarial treatment on incidence of hemolysis in asymptomatic children treated with CD, sulfadoxine-pyrimethamine (SP), and mefloquine (MQ).

Methods

A secondary analysis of data from a double-blind, placebo-controlled trial of IPTi was conducted. Hemoglobin (Hb) measurements were made at IPTi doses, regular follow-up and emergency visits. G6PD genotype was determined at 9 months looking for SNPs for the A- genotype at coding position 202. Multivariable linear and logistic regression models were used to examine hemolysis among children with valid G6PD genotyping results. Hemolysis was defined as the absolute change in Hb or as any post-dose Hb <8 g/dL. These outcomes were assessed using either a single follow-up Hb on day 7 after an IPTi dose or Hb obtained 1 to 14 or 28 days after each IPTi dose.

Findings

Relative to placebo, CD reduced Hb by approximately 0.5 g/dL at day 7 and within 14 days of an IPTi dose, and by 0.2 g/dL within 28 days. Adjusted declines in the CD group were larger than in the MQ and SP groups. At day 7, homo-/hemizygous genotype was associated with higher odds of Hb <8 g/dL (adjusted odds ratio = 6.7, 95% CI 1.7 to 27.0) and greater absolute reductions in Hb (-0.6 g/dL, 95% CI -1.1 to 0.003). There was no evidence to suggest increased reductions in Hb among homo-/hemizygous children treated with CD compared to placebo, SP or MQ.

Conclusions

While treatment with CD demonstrated greater reductions in Hb at 7 and 14 days after an IPTi dose compared to both SP and MQ, there was no evidence that G6PD deficiency exacerbated the adverse effects of CD, despite evidence for higher hemolysis risk among G6PDd infants.     

Accounting for multiple ecosystem services in a simulation of land‐use decisions: Does it reduce tropical deforestation?

Conversion of tropical forests is among the primary causes of global environmental change. The loss of their important environmental services has prompted calls to integrate ecosystem services (ES) in addition to socio‐economic objectives in decision‐making. To test the effect of accounting for both ES and socio‐economic objectives in land‐use decisions, we develop a new dynamic approach to model deforestation scenarios for tropical mountain forests. We integrate multi‐objective optimization of land allocation with an innovative approach to consider uncertainty spaces for each objective. These uncertainty spaces account for potential variability among decision‐makers, who may have different expectations about the future. When optimizing only socio‐economic objectives, the model continues the past trend in deforestation (1975–2015) in the projected land‐use allocation (2015–2070). Based on indicators for biomass production, carbon storage, climate and water regulation, and soil quality, we show that considering multiple ES in addition to the socio‐economic objectives has heterogeneous effects on land‐use allocation. It saves some natural forest if the natural forest share is below 38%, and can stop deforestation once the natural forest share drops below 10%. For landscapes with high shares of forest (38%–80% in our study), accounting for multiple ES under high uncertainty of their indicators may, however, accelerate deforestation. For such multifunctional landscapes, two main effects prevail: (a) accelerated expansion of diversified non‐natural areas to elevate the levels of the indicators and (b) increased landscape diversification to maintain multiple ES, reducing the proportion of natural forest. Only when accounting for vascular plant species richness as an explicit objective in the optimization, deforestation was consistently reduced. Aiming for multifunctional landscapes may therefore conflict with the aim of reducing deforestation, which we can quantify here for the first time. Our findings are relevant for identifying types of landscapes where this conflict may arise and to better align respective policies.