High temperatures can stress animals by raising the oxygen demand above the oxygen supply. Consequently, animals under hypoxia could be more sensitive to heating than those exposed to normoxia. Although support for this model has been limited to aquatic animals, oxygen supply might limit the heat tolerance of terrestrial animals during energetically demanding activities. We evaluated this model by studying the flight performance and heat tolerance of flies (Drosophila melanogaster) acclimated and tested at different concentrations of oxygen (12%, 21%, and 31%). We expected that flies raised at hypoxia would develop into adults that were more likely to fly under hypoxia than would flies raised at normoxia or hyperoxia. We also expected flies to benefit from greater oxygen supply during testing. These effects should have been most pronounced at high temperatures, which impair locomotor performance. Contrary to our expectations, we found little evidence that flies raised at hypoxia flew better when tested at hypoxia or tolerated extreme heat better than did flies raised at normoxia or hyperoxia. Instead, flies raised at higher oxygen levels performed better at all body temperatures and oxygen concentrations. Moreover, oxygen supply during testing had the greatest effect on flight performance at low temperature, rather than high temperature. Our results poorly support the hypothesis that oxygen supply limits performance at high temperatures, but do support the idea that hyperoxia during development improves performance of flies later in life.
Human Papillomavirus (HPV) infection has been recognized as the main etiologic factor in the development of various cancers including penile, vulva, oropharyngeal and cervical cancers. In the development of cancer, persistent HPV infections induce E6 and E7 oncoproteins, which promote cell proliferation and carcinogenesis resulting elevated levels of host antibodies (e.g., anti-HPV16 E7 antibody). Currently, these cancers are clinically diagnosed using invasive biopsy-based tests, which are performed only in centralized labs by experienced clinical staff using time-consuming and expensive tools and technologies. Therefore, these obstacles constrain their utilization at primary care clinics and in remote settings, where resources are limited. Here, we present a rapid, inexpensive, reliable, easy-to-use, customized immunoassay platform following a microfluidic filter device to detect and quantify anti-HPV16 E7 antibodies from whole blood as a non-invasive assisting technology for diagnosis of HPV-associated malignancies, especially, at primary healthcare and remote settings. The platform can detect and quantify anti-HPV16 E7 antibody down to 2.87 ng/mL. We further validated our immunoassay in clinical patient samples and it provided significantly high responses as compared to control samples. Thus, it can be potentially implemented as a pretesting tool to identify high-risk groups for broad monitoring of HPV-associated cancers in resource-constrained settings.
A novel joint decision making paradigm for assessing team coordination was developed and tested using baseball infielders. Balls launched onto an infield at different trajectories were filmed using four video cameras that were each placed at one of the typical positions of the four infielders. Each participant viewed temporally occluded videos for one of the four positions and were asked to say either “ball” if they would attempt to field it or the name of the bag that they would cover. The evaluation of two experienced coaches was used to assign a group coordination score for each trajectory and group decision times were calculated. Thirty groups of 4 current college baseball players were: (i) teammates (players from same team/view from own position), (ii) non-teammates (players from different teams/view from own position), or (iii) scrambled teammates (players from same team/view not from own position). Teammates performed significantly better (i.e., faster and more coordinated decisions) than the other two groups, whereas scrambled teammates performed significantly better than non-teammates. These findings suggest that team coordination is achieved through both experience with one’s teammates’ responses to particular events (e.g., a ball hit up the middle) and one’s own general action capabilities (e.g., running speed). The sensitivity of our joint decision making paradigm to group makeup provides support for its use as a method for studying team coordination.
Bismuth drugs, despite being clinically used for decades, surprisingly remain in use and effective for the treatment of Helicobacter pylori infection, even for resistant strains when co-administrated with antibiotics. However, the molecular mechanisms underlying the clinically sustained susceptibility of H. pylori to bismuth drugs remain elusive. Herein, we report that integration of in-house metalloproteomics and quantitative proteomics allows comprehensive uncovering of the bismuth-associated proteomes, including 63 bismuth-binding and 119 bismuth-regulated proteins from Helicobacter pylori, with over 60% being annotated with catalytic functions. Through bioinformatics analysis in combination with bioassays, we demonstrated that bismuth drugs disrupted multiple essential pathways in the pathogen, including ROS defence and pH buffering, by binding and functional perturbation of a number of key enzymes. Moreover, we discovered that HpDnaK may serve as a new target of bismuth drugs to inhibit bacterium-host cell adhesion. The integrative approach we report, herein, provides a novel strategy to unveil the molecular mechanisms of antimicrobial metals against pathogens in general. This study sheds light on the design of new types of antimicrobial agents with multiple targets to tackle the current crisis of antimicrobial resistance.
The most common evolutionary events at the molecular level are single-base substitutions, as well as insertions and deletions (indels) of short DNA segments. A large body of research has been devoted to develop probabilistic substitution models and to infer their parameters using likelihood and Bayesian approaches. In contrast, relatively little has been done to model indel dynamics, probably due to the difficulty in writing explicit likelihood functions. Here, we contribute to the effort of modeling indel dynamics by presenting SpartaABC, an approximate Bayesian computation (ABC) approach to infer indel parameters from sequence data (either aligned or unaligned). SpartaABC circumvents the need to use an explicit likelihood function by extracting summary statistics from simulated sequences. First, summary statistics are extracted from the input sequence data. Second, SpartaABC samples indel parameters from a prior distribution and uses them to simulate sequences. Third, it computes summary statistics from the simulated sets of sequences. By computing a distance between the summary statistics extracted from the input and each simulation, SpartaABC can provide an approximation to the posterior distribution of indel parameters as well as point estimates. We study the performance of our methodology and show that it provides accurate estimates of indel parameters in simulations. We next demonstrate the utility of SpartaABC by studying the impact of alignment errors on the inference of positive selection. A C ++ program implementing SpartaABC is freely available in http://spartaabc.tau.ac.il.
Many ecosystems experience strong temporal variability in environmental conditions; yet, a clear picture of how niche and neutral processes operate to determine community assembly in temporally variable systems remains elusive. In this study, we constructed neutral metacommunity models to assess the relative importance of neutral processes in a spatially and temporally variable ecosystem. We analyzed macroinvertebrate community data spanning multiple seasons and years from 20 sites in a Sonoran Desert river network in Arizona. The model goodness-of-fit was used to infer the importance of neutral processes. Averaging over eight stream flow conditions across three years, we found that neutral processes were more important in perennial streams than in non-perennial streams (intermittent and ephemeral streams). Averaging across perennial and non-perennial streams, we found that neutral processes were more important during very high flow and in low flow periods; whereas, at very low flows, the relative importance of neutral processes varied greatly. These findings were robust to the choice of model parameter values. Our study suggested that the net effect of disturbance on the relative importance of niche and neutral processes in community assembly varies non-monotonically with the severity of disturbance. In contrast to the prevailing view that disturbance promotes niche processes, we found that neutral processes could become more important when the severity of disturbance is beyond a certain threshold such that all organisms are adversely affected regardless of their biological traits and strategies.
Previous research examining social influences on driving behavior has primarily focused on the effects of passengers and surrounding vehicles (e.g., speed contagion). Of current interest was the interaction between drivers that occurs in a “following a friend” scenario, i.e., the driver of one vehicle (the leader) knows how to get to the desired destination while the driver of a second vehicle (the follower) does not. Sixteen participants drove through a simulated city in a driving simulator under three conditions: (i) a baseline condition in which they could choose their own route, (ii) a navigation system condition in which they were given audible route instructions, and (iii) a “follow a friend” condition in which they required to follow a simulated vehicle. In the follow a friend condition, drivers engaged in significantly more risky behaviors (in comparison to the other conditions) such as making more erratic and higher speed turns and lane changes, maintaining overall higher speed, as well as maintaining a shorter time headway when following a lead vehicle. These effects suggest a relationship to time pressure caused by a fear of getting lost.
Assistive and rehabilitation devices are a promising and challenging field of recent robotics research. Motivated by societal needs such as aging populations, such devices can support motor functionality and subject training. The design, control, sensing, and assessment of the devices become more sophisticated due to a human in the loop. This paper gives a human-robot interaction perspective on current issues and opportunities in the field. On the topic of control and machine learning, approaches that support but do not distract subjects are reviewed. Options to provide sensory user feedback that are currently missing from robotic devices are outlined. Parallels between device acceptance and affective computing are made. Furthermore, requirements for functional assessment protocols that relate to real-world tasks are discussed. In all topic areas, the design of human-oriented frameworks and methods is dominated by challenges related to the close interaction between the human and robotic device. This paper discusses the aforementioned aspects in order to open up new perspectives for future robotic solutions.
Four genomovirus genomes were recovered from thrips (Echinothrips americanus) collected in Florida, USA. These represent four new species which are members of the Gemycircularvirus (n = 2), Gemyduguivirus (n = 1), and Gemykibivirus (n = 1) genera. This is the first record, to our knowledge, of genomoviruses associated with a phytophagous insect.
Competing endogenous RNAs (ceRNAs) are RNA molecules that sequester shared microRNAs (miRNAs) thereby affecting the expression of other targets of the miRNAs. Whether genetic variants in ceRNA can affect its biological function and disease development is still an open question. Here we identified a large number of genetic variants that are associated with ceRNA's function using Geuvaids RNA-seq data for 462 individuals from the 1000 Genomes Project. We call these loci competing endogenous RNA expression quantitative trait loci or ‘cerQTL’, and found that a large number of them were unexplored in conventional eQTL mapping. We identified many cerQTLs that have undergone recent positive selection in different human populations, and showed that single nucleotide polymorphisms in gene 3΄UTRs at the miRNA seed binding regions can simultaneously regulate gene expression changes in both cis and trans by the ceRNA mechanism. We also discovered that cerQTLs are significantly enriched in traits/diseases associated variants reported from genome-wide association studies in the miRNA binding sites, suggesting that disease susceptibilities could be attributed to ceRNA regulation. Further in vitro functional experiments demonstrated that a cerQTL rs11540855 can regulate ceRNA function. These results provide a comprehensive catalog of functional non-coding regulatory variants that may be responsible for ceRNA crosstalk at the post-transcriptional level.