Predator scent induces differing responses in two sympatric macropodids

When prey species encounter the scent of a predator they must make a decision on how to respond. This may be either to ignore, flee, hide or alarm call. While many species are able to derive detailed information from the chemical cues associated with predator scent, for some the decision to respond is often made without being able to identify the actual location and intentions of the predator. Depending on the sociality and ecology of the species, it may pay to flee or to engage in predator inspection where knowledge is impure. We tested for this in two sympatric marsupial macropodids, the parma wallaby (Macropus parma) and the red-necked pademelon (Thylogale thetis), as little is known of how these species detect and respond to olfactory cues of predation risk. We observed that, when presented with a synthetic predator scent mimicking dog urine, the social forager, T. thetis, tended to spend more time close to the predator odour, while the solitary forager, M. parma, exhibited an aversive response. The results suggest that social and ecological constraints on the sensory modalities used in predator detection may influence how macropodids respond to olfactory predator cues. © CSIRO 2005

A transient homotypic interaction model for the influenza A virus NS1 protein effector domain

Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins

Who Watches the Watchmen? An Appraisal of Benchmarks for Multiple Sequence Alignment

Multiple sequence alignment (MSA) is a fundamental and ubiquitous technique in bioinformatics used to infer related residues among biological sequences. Thus alignment accuracy is crucial to a vast range of analyses, often in ways difficult to assess in those analyses. To compare the performance of different aligners and help detect systematic errors in alignments, a number of benchmarking strategies have been pursued. Here we present an overview of the main strategies--based on simulation, consistency, protein structure, and phylogeny--and discuss their different advantages and associated risks. We outline a set of desirable characteristics for effective benchmarking, and evaluate each strategy in light of them. We conclude that there is currently no universally applicable means of benchmarking MSA, and that developers and users of alignment tools should base their choice of benchmark depending on the context of application--with a keen awareness of the assumptions underlying each benchmarking strategy.Comment: Revie

Climate Variability and Ross River Virus Transmission in Townsville Region, Australia 1985 to 1996

Background How climate variability affects the transmission of infectious diseases at a regional level remains unclear. In this paper, we assessed the impact of climate variation on the Ross River virus (RRv) transmission in the Townsville region, Queensland, north-east Australia. Methods Population-based information was obtained on monthly variations in RRv cases, climatic factors, sea level, and population growth between 1985 and 1996. Cross-correlations were computed for a series of associations between climate variables (rainfall, maximum temperature, minimum temperature, relative humidity and high tide) and the monthly incidence of RRv disease over a range of time lags. The impact of climate variability on RRv transmission was assessed using the seasonal auto-regressive integrated moving average (SARIMA) model. Results There were significant correlations of the monthly incidence of RRv to rainfall, maximum temperature, minimum temperature and relative humidity, all at a lag of 2 months, and high tide in the current month. The results of SARIMA models show that monthly average rainfall (β=0.0012, p=0.04) and high tide (β=0.0262, p=0.01) were significantly associated with RRv transmission, although temperature and relative humidity did not seem to have played an important role in the Townsville region. Conclusions Rainfall, and high tide were likely to be key determinants of RRv transmission in the Townsville region

Use of a Semi-field System to Evaluate the Efficacy of Topical Repellents under user Conditions Provides a Disease Exposure free Technique Comparable with Field Data.

Before topical repellents can be employed as interventions against arthropod bites, their efficacy must be established. Currently, laboratory or field tests, using human volunteers, are the main methods used for assessing the efficacy of topical repellents. However, laboratory tests are not representative of real life conditions under which repellents are used and field-testing potentially exposes human volunteers to disease. There is, therefore, a need to develop methods to test efficacy of repellents under real life conditions while minimizing volunteer exposure to disease. A lotion-based, 15% N, N-Diethyl-3-methylbenzamide (DEET) repellent and 15% DEET in ethanol were compared to a placebo lotion in a 200 sq m (10 m x 20 m) semi-field system (SFS) against laboratory-reared Anopheles arabiensis mosquitoes and in full field settings against wild malaria vectors and nuisance-biting mosquitoes. The average percentage protection against biting mosquitoes over four hours in the SFS and field setting was determined. A Poisson regression model was then used to determine relative risk of being bitten when wearing either of these repellents compared to the placebo. Average percentage protection of the lotion-based 15% DEET repellent after four hours of mosquito collection was 82.13% (95% CI 75.94-88.82) in the semi-field experiments and 85.10% (95% CI 78.97-91.70) in the field experiments. Average percentage protection of 15% DEET in ethanol after four hours was 71.29% (CI 61.77-82.28) in the semi-field system and 88.24% (84.45-92.20) in the field. Semi-field evaluation results were comparable to full-field evaluations, indicating that such systems could be satisfactorily used in measuring efficacy of topically applied mosquito repellents, thereby avoiding risks of exposure to mosquito-borne pathogens, associated with field testing

Evaluation of alternative mosquito sampling methods for malaria vectors in Lowland South - East Zambia.

Sampling malaria vectors and measuring their biting density is of paramount importance for entomological surveys of malaria transmission. Human landing catch (HLC) has been traditionally regarded as a gold standard method for surveying human exposure to mosquito bites. However, due to the risk of human participant exposure to mosquito-borne parasites and viruses, a variety of alternative, exposure-free trapping methods were compared in lowland, south-east Zambia. Centres for Disease Control and Prevention miniature light trap (CDC-LT), Ifakara Tent Trap model C (ITT-C), resting boxes (RB) and window exit traps (WET) were all compared with HLC using a 3 × 3 Latin Squares design replicated in 4 blocks of 3 houses with long lasting insecticidal nets, half of which were also sprayed with a residual deltamethrin formulation, which was repeated for 10 rounds of 3 nights of rotation each during both the dry and wet seasons. The mean catches of HLC indoor, HLC outdoor, CDC-LT, ITT-C, WET, RB indoor and RB outdoor, were 1.687, 1.004, 3.267, 0.088, 0.004, 0.000 and 0.008 for Anopheles quadriannulatus Theobald respectively, and 7.287, 6.784, 10.958, 5.875, 0.296, 0.158 and 0.458, for An. funestus Giles, respectively. Indoor CDC-LT was more efficient in sampling An. quadriannulatus and An. funestus than HLC indoor (Relative rate [95% Confidence Interval] = 1.873 [1.653, 2.122] and 1.532 [1.441, 1.628], respectively, P < 0.001 for both). ITT-C was the only other alternative which had comparable sensitivity (RR = 0.821 [0.765, 0.881], P < 0.001), relative to HLC indoor other than CDC-LT for sampling An. funestus. While the two most sensitive exposure-free techniques primarily capture host-seeking mosquitoes, both have substantial disadvantages for routine community-based surveillance applications: the CDC-LT requires regular recharging of batteries while the bulkiness of ITT-C makes it difficult to move between sampling locations. RB placed indoors or outdoors and WET had consistently poor sensitivity so it may be useful to evaluate additional alternative methods, such as pyrethrum spray catches and back packer aspirators, for catching resting mosquitoes

Using a New Odour-Baited Device to Explore Options for Luring and Killing Outdoor-Biting Malaria Vectors: A Report on Design and Field Evaluation of the Mosquito Landing Box.

Mosquitoes that bite people outdoors can sustain malaria transmission even where effective indoor interventions such as bednets or indoor residual spraying are already widely used. Outdoor tools may therefore complement current indoor measures and improve control. We developed and evaluated a prototype mosquito control device, the 'Mosquito Landing Box' (MLB), which is baited with human odours and treated with mosquitocidal agents. The findings are used to explore technical options and challenges relevant to luring and killing outdoor-biting malaria vectors in endemic settings. Field experiments were conducted in Tanzania to assess if wild host-seeking mosquitoes 1) visited the MLBs, 2) stayed long or left shortly after arrival at the device, 3) visited the devices at times when humans were also outdoors, and 4) could be killed by contaminants applied on the devices. Odours suctioned from volunteer-occupied tents were also evaluated as a potential low-cost bait, by comparing baited and unbaited MLBs. There were significantly more Anopheles arabiensis, An. funestus, Culex and Mansonia mosquitoes visiting baited MLB than unbaited controls (P<=0.028). Increasing sampling frequency from every 120 min to 60 and 30 min led to an increase in vector catches of up to 3.6 fold (P<=0.002), indicating that many mosquitoes visited the device but left shortly afterwards. Outdoor host-seeking activity of malaria vectors peaked between 7:30 and 10:30pm, and between 4:30 and 6:00am, matching durations when locals were also outdoors. Maximum mortality of mosquitoes visiting MLBs sprayed or painted with formulations of candidate mosquitocidal agent (pirimiphos-methyl) was 51%. Odours from volunteer occupied tents attracted significantly more mosquitoes to MLBs than controls (P<0.001). While odour-baited devices such as the MLBs clearly have potential against outdoor-biting mosquitoes in communities where LLINs are used, candidate contaminants must be those that are effective at ultra-low doses even after short contact periods, since important vector species such as An. arabiensis make only brief visits to such devices. Natural human odours suctioned from occupied dwellings could constitute affordable sources of attractants to supplement odour baits for the devices. The killing agents used should be environmentally safe, long lasting, and have different modes of action (other than pyrethroids as used on LLINs), to curb the risk of physiological insecticide resistance

Circumcision for prevention against HIV: marked seasonal variation in demand and potential public sector readiness in Soweto, South Africa

The public sector delivery of male circumcision in the only public sector hospital in Soweto, South Africa was examined to gauge local capacity to deliver this procedure as an intervention for prevention of HIV acquisition. During the period from July 1998 to March 2006, approximately 360 procedures were performed per annum. Striking seasonal variations and the relatively few procedures performed may create challenges for program planning, if male circumcision is increased to a level required to have an impact on the incidence of HIV among this population

False-negative PD-L1 immunostaining in ethanol-fixed EBUS-TBNA specimens of non-small cell lung cancer patients

Aims Programmed death-ligand 1 (PD-L1) immunostaining is used to predict which non-small-cell lung cancer (NSCLC) patients will respond best to treatment with programmed cell death protein 1/PD-L1 inhibitors. PD-L1 immunostaining is sometimes performed on alcohol-fixed cytological specimens instead of on formalin-fixed paraffin-embedded (FFPE) biopsies or resections. We studied whether ethanol prefixation of clots from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) results in diminished PD-L1 immunostaining as compared with formalin fixation. Methods and results FFPE cell blocks from EBUS-TBNA specimens of 54 NSCLC patients were identified. For each case, paired samples were available, consisting of clots directly immersed in formalin and clots prefixed in Fixcyt (50% ethanol). Serial sections were immunostained for PD-L1 by use of the standardised SP263 assay and the 22C3 antibody as a laboratory-developed test (LDT). PD-L1 positivity was determined with two cut-offs (1% and 50%). Concordance of PD-L1 positivity between the formalin-fixed (gold standard) and ethanol-prefixed material was assessed. When the 22C3 LDT was used, 30% and 36% of the ethanol-prefixed specimens showed false-negative results at the 1% and 50% cut-offs, respectively (kappa 0.64 and 0.68). When SP263 was used, 22% of the ethanol-prefixed specimens showed false-negative results at the 1% cut-off (kappa 0.67). At the 50% cut-off, concordance was higher (kappa 0.91), with 12% of the ethanol-prefixed specimens showing false-negative results. Conclusion Ethanol fixation of EBUS-TBNA specimens prior to formalin fixation can result in a considerable number of false-negative PD-L1 immunostaining results when a 1% cut-off is used and immunostaining is performed with SP263 or the 22C3 LDT. The same applies to use of the 50% cut-off when immunostaining is performed with the 22C3 LDT

Thinking outside the curve, part I: modeling birthweight distribution

<p>Abstract</p> <p>Background</p> <p>Greater epidemiologic understanding of the relationships among fetal-infant mortality and its prognostic factors, including birthweight, could have vast public health implications. A key step toward that understanding is a realistic and tractable framework for analyzing birthweight distributions and fetal-infant mortality. The present paper is the first of a two-part series that introduces such a framework.</p> <p>Methods</p> <p>We propose describing a birthweight distribution via a normal mixture model in which the number of components is determined from the data using a model selection criterion rather than fixed <it>a priori</it>.</p> <p>Results</p> <p>We address a number of methodological issues, including how the number of components selected depends on the sample size, how the choice of model selection criterion influences the results, and how estimates of mixture model parameters based on multiple samples from the same population can be combined to produce confidence intervals. As an illustration, we find that a 4-component normal mixture model reasonably describes the birthweight distribution for a population of white singleton infants born to heavily smoking mothers. We also compare this 4-component normal mixture model to two competitors from the existing literature: a contaminated normal model and a 2-component normal mixture model. In a second illustration, we discover that a 6-component normal mixture model may be more appropriate than a 4-component normal mixture model for a general population of black singletons.</p> <p>Conclusions</p> <p>The framework developed in this paper avoids assuming the existence of an interval of birthweights over which there are no compromised pregnancies and does not constrain birthweights within compromised pregnancies to be normally distributed. Thus, the present framework can reveal heterogeneity in birthweight that is undetectable via a contaminated normal model or a 2-component normal mixture model.</p