Tropical dung beetle morphological traits predict functional traits and show intraspecific differences across land uses

Functional traits and functional diversity measures are increasingly being used to examine land use effects on biodiversity and community assembly rules. Morphological traits are often used directly as functional traits. However, behavioral characteristics are more difficult to measure. Establishing methods to derive behavioral traits from morphological measurements is necessary to facilitate their inclusion in functional diversity analyses. We collected morphometric data from over 1,700 individuals of 12 species of dung beetle to establish whether morphological measurements can be used as predictors of behavioral traits. We also compared morphology among individuals collected from different land uses (primary forest, logged forest, and oil palm plantation) to identify whether intraspecific differences in morphology vary among land use types. We show that leg and eye measurements can be used to predict dung beetle nesting behavior and period of activity and we used this information to confirm the previously unresolved nesting behavior for Synapsis ritsemae. We found intraspecific differences in morphological traits across different land use types. Phenotypic plasticity was found for traits associated with dispersal (wing aspect ratio and wing loading) and reproductive capacity (abdomen size). The ability to predict behavioral functional traits from morphology is useful where the behavior of individuals cannot be directly observed, especially in tropical environments where the ecology of many species is poorly understood. In addition, we provide evidence that land use change can cause phenotypic plasticity in tropical dung beetle species. Our results reinforce recent calls for intraspecific variation in traits to receive more attention within community ecology.     

Evidence of land‐sea transfer of the zoonotic pathogen Campylobacter to a wildlife marine sentinel species

Environmental pollution often accompanies the expansion and urbanization of human populations where sewage and wastewaters commonly have an impact on the marine environments. Here, we explored the potential for faecal bacterial pathogens, of anthropic origin, to spread to marine wildlife in coastal areas. The common zoonotic bacterium Campylobacter was isolated from grey seals (Halichoerus grypus), an important sentinel species for environmental pollution, and compared to isolates from wild birds, agricultural sources and clinical samples to characterize possible transmission routes. Campylobacter jejuni was present in half of all grey seal pups sampled (24/50 dead and 46/90 live pups) in the breeding colony on the Isle of May (Scotland), where it was frequently associated with histological evidence of disease. Returning yearling animals (19/19) were negative for C. jejuni suggesting clearance of infection while away from the localized colony infection source. The genomes of 90 isolates from seals were sequenced and characterized using a whole‐genome multilocus sequence typing (MLST) approach and compared to 192 published genomes from multiple sources using population genetic approaches and a probabilistic genetic attribution model to infer the source of infection from MLST data. The strong genotype‐host association has enabled the application of source attribution models in epidemiological studies of human campylobacteriosis, and here assignment analyses consistently grouped seal isolates with those from human clinical samples. These findings are consistent with either a common infection source or direct transmission of human campylobacter to grey seals, raising concerns about the spread of human pathogens to wildlife marine sentinel species in coastal areas.     

Natural killer cells and innate immunity to protozoan pathogens

Natural killer (NK) cells are lymphoid cells that mediate significant cytotoxic activity and produce high levels of pro-inflammatory cytokines in response to infection. During viral infection, NK cell cytotoxicity and cytokine production is induced principally by monocyte-macrophage- and dendritic cell-derived cytokines but virally encoded ligands for NK cells are also beginning to be described. NK derived interferon-gamma (IFN-gamma) production is also essential for control of several protozoal infections including toxoplasmosis, trypanosomiasis, leishmaniasis and malaria. The activation of NK cells by protozoan pathogens is also believed to be cytokine-mediated although some recent studies suggest that direct recognition of parasites by NK cells also occurs. Both indirect signalling via accessory cell-derived cytokines and direct signalling, presumably through NK receptors, are needed in order for human malaria parasites (Plasmodium falciparum) to optimally stimulate NK activity.     

Crystal structure of Mycobacterium tuberculosis YefM antitoxin reveals that it is not an intrinsically unstructured protein

Toxin-antitoxin modules are present on chromosomes of almost all free-living prokaryotes. Some are implicated to act as stress-responsive elements, among their many functional roles. The YefM-YoeB toxin-antitoxin system is present in many bacterial species, where YefM belongs to the Phd family antidote of phage P1, whereas YoeB is a homolog of the RelE toxin of the RelBE system, rather than the Doc system of phage P1. YoeB, a ribonuclease, is believed to be conformationally stable, whereas YefM has been proposed to be a member of intrinsically disordered proteins. The ribonucleolytic activity of YoeB is neutralized by YefM upon formation of the YefM-YoeB complex. We report here the crystal structure of Mycobacterium tuberculosis YefM from two crystal isoforms. Our crystallographic and biophysical studies reveal that YefM is not an intrinsically unfolded protein and instead forms a well-defined structure with significant secondary and tertiary structure conformations. The residues involved in core formation of the folded structure are evolutionarily conserved among many bacterial species, supporting our observation. The C-terminal end of its polypeptide is highly pliable, which adopts different conformations in different monomers. Since at the physiological level YefM controls the activity of YoeB through intricate protein-protein interactions, the conformational heterogeneity in YefM revealed by our structure suggests that these might act a master switch in controlling YoeB activity.     

A Tri-Modality Image Fusion Method for Target Delineation of Brain Tumors in Radiotherapy

Purpose

To develop a tri-modality image fusion method for better target delineation in image-guided radiotherapy for patients with brain tumors.

Methods

A new method of tri-modality image fusion was developed, which can fuse and display all image sets in one panel and one operation. And a feasibility study in gross tumor volume (GTV) delineation using data from three patients with brain tumors was conducted, which included images of simulation CT, MRI, and ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) examinations before radiotherapy. Tri-modality image fusion was implemented after image registrations of CT+PET and CT+MRI, and the transparency weight of each modality could be adjusted and set by users. Three radiation oncologists delineated GTVs for all patients using dual-modality (MRI/CT) and tri-modality (MRI/CT/PET) image fusion respectively. Inter-observer variation was assessed by the coefficient of variation (COV), the average distance between surface and centroid (ADSC), and the local standard deviation (SD_local). Analysis of COV was also performed to evaluate intra-observer volume variation.

Results

The inter-observer variation analysis showed that, the mean COV was 0.14(±0.09) and 0.07(±0.01) for dual-modality and tri-modality respectively; the standard deviation of ADSC was significantly reduced (p<0.05) with tri-modality; SD_local averaged over median GTV surface was reduced in patient 2 (from 0.57 cm to 0.39 cm) and patient 3 (from 0.42 cm to 0.36 cm) with the new method. The intra-observer volume variation was also significantly reduced (p = 0.00) with the tri-modality method as compared with using the dual-modality method.

Conclusion

With the new tri-modality image fusion method smaller inter- and intra-observer variation in GTV definition for the brain tumors can be achieved, which improves the consistency and accuracy for target delineation in individualized radiotherapy.     

The Chemokine CCL5 Regulates Glucose Uptake and AMP Kinase Signaling in Activated T Cells to Facilitate Chemotaxis

Recruitment of effector T cells to sites of infection or inflammation is essential for an effective adaptive immune response. The chemokine CCL5 (RANTES) activates its cognate receptor, CCR5, to initiate cellular functions, including chemotaxis. In earlier studies, we reported that CCL5-induced CCR5 signaling activates the mTOR/4E-BP1 pathway to directly modulate mRNA translation. Specifically, CCL5-mediated mTOR activation contributes to T cell chemotaxis by initiating the synthesis of chemotaxis-related proteins. Up-regulation of chemotaxis-related proteins may prime T cells for efficient migration. It is now clear that mTOR is also a central regulator of nutrient sensing and glycolysis. Herein we describe a role for CCL5-mediated glucose uptake and ATP accumulation to meet the energy demands of chemotaxis in activated T cells. We provide evidence that CCL5 is able to induce glucose uptake in an mTOR-dependent manner. CCL5 treatment of ex vivo activated human CD3(+) T cells also induced the activation of the nutrient-sensing kinase AMPK and downstream substrates ACC-1, PFKFB-2, and GSK-3β. Using 2-deoxy-d-glucose, an inhibitor of glucose uptake, and compound C, an inhibitor of AMPK, experimental data are presented that demonstrate that CCL5-mediated T cell chemotaxis is dependent on glucose, as these inhibitors inhibit CCL5-mediated chemotaxis in a dose-dependent manner. Altogether, these findings suggest that both glycolysis and AMPK signaling are required for efficient T cell migration in response to CCL5. These studies extend the role of CCL5 mediated CCR5 signaling beyond lymphocyte chemotaxis and demonstrate a role for chemokines in promoting glucose uptake and ATP production to match energy demands of migration.     

Defining the Minimal Important Difference for the Visual Analogue Scale Assessing Dyspnea in Patients with Malignant Pleural Effusions

Background

The minimal important difference (MID) is essential for interpreting the results of randomised controlled trials (RCTs). Despite a number of RCTs in patients with malignant pleural effusions (MPEs) which use the visual analogue scale for dyspnea (VASD) as an outcome measure, the MID has not been established.

Methods

Patients with suspected MPE undergoing a pleural procedure recorded their baseline VASD and their post-procedure VASD (24 hours after the pleural drainage), and in parallel assessed their breathlessness on a 7 point Likert scale.

Findings

The mean decrease in VASD in patients with a MPE reporting a ‘small but just worthwhile decrease’ in their dyspnea (i.e. equivalent to the MID) was 19mm (95% CI 14-24mm). The mean drainage volume required to produce a change in VASD of 19mm was 760ml.

Interpretation

The mean MID for the VASD in patients with a MPE undergoing a pleural procedure is 19mm (95% CI 14-24mm). Thus choosing an improvement of 19mm in the VASD would be justifiable in the design and analysis of future MPE studies.     

Teaching medical students basic neurotransmitter pharmacology using primary research resources

Teaching pharmacology to medical students has long been seen as a challenge, and one to which a number of innovative approaches have been taken. In this article, we describe and evaluate the use of primary research articles in teaching second-year medical students both in terms of the information learned and the use of the papers themselves. We designed a seminar where small groups of students worked on different neurotransmitters before contributing information to a plenary session. Student feedback suggested that when the information was largely novel, students learned considerably more. Crucially, this improvement in knowledge was seen even when they had not directly studied a particular transmitter in their work groups, suggesting a shared learning experience. Moreover, the majority of students reported that using primary research papers was easy and useful, with over half stating that they would use them in future study.