Differences in energy metabolism between trypanosomatidae

Although various members of the family Trypanosomatidae generate energy in a similar way, fundamental differences also exist and are not always recognized. In this review, Louis Tielens and Jaap Van Hellemond discuss the known differences in carbohydrate metabolism among trypanosomatids, and especially compare Leishmania with trypanosomatids such as Trypanosoma brucei and Phytomonas spp. Special attention will be paid to differences in end-products of carbohydrate degradation, to differences in anaerobic capacities between the various trypanosomatids and to the components of their respiratory chains, including the presence or absence of a plant-like alternative oxidase. Furthermore, evidence will be discussed which indicates that the succinate produced by trypanosomatids is formed mainly via an oxidative pathway and not via reduction of fumarate, a process known to occur in parasitic helminths.     

Energy generation in parasitic helminths

Although parasitic helminths are a very heterogeneous group of organisms, they share many interesting properties in their energy metabolism. In certain stages of their life cycle, they all have a large capacity for anaerobic functioning. In other stages, an aerobic energy metabolism prevails. Parasites have to adapt to different environments in which the availability of oxygen and food varies widely. These variations in their external conditions strongly influence their energy metabolism. Here, Louis Tielens presents an introduction to the current ideas on the bioenergetics of parasitic helminths, focusing on the differences in energy metabolism between various stages (free-living and parasitic), and paying special attention to the mechanisms involved in the transitions between the different methods of energy generation.     

A novel host-parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates toll-like receptor 2 and affects immune polarization

Schistosome infections are characterized by prominent T cell hyporesponsiveness during the chronic stage of infection. We found that schistosome-specific phosphatidylserine (PS) activated TLR2 and affected dendritic cells such that mature dendritic cells gained the ability to induce the development of IL-10-producing regulatory T cells. Using mass spectrometry, schistosomal lysophosphatidylserine (lyso-PS) was identified as the TLR2-activating molecule. This activity appears to be a unique property of schistosomal lyso-PS, containing specific acyl chains, because neither a synthetic lyso-PS (16:0) nor PS isolated from the mammalian host activates TLR2. Taken together, these findings provide evidence for a novel host-parasite interaction that may be central to long term survival of the parasite and limited host pathology with implications beyond parasitology.     

A new phylogeny of swiftlets (Aves: Apodidae) based on cytochrome-b DNA

Due to a lack of distinctive morphological characters, swift taxonomy and phylogeny has always been an area of disagreement. To shed more light on this subject, we reconstructed swift(let) phylogeny based on 1143 bp of mitochondrial cytochrome-b DNA sequence. Although this is not the first attempt to reconstruct swift phylogeny using molecular data, our results show higher support for many of the branches due to our much longer sequences. However, placement of Hydrochous is still unexpected. Implementation of more conservative genetic regions and sampling of more taxa could solve this problem. Most importantly, the Collocaliini resolve as a monophyletic group. The internal structure of the group shows that non-echolocating Collocalia and echolocating Aerodramus form two distinct clades. This is in congruence with earlier classifications based on morphological characters, but in contrast with more recent classifications.     

Quantifying long-term phenological patterns of aerial insectivores roosting in the Great Lakes region using weather surveillance radar

Organisms have been shifting their timing of life history events (phenology) in response to changes in the emergence of resources induced by climate change. Yet understanding these patterns at large scales and across long time series is often challenging. Here we used the US weather surveillance radar network to collect data on the timing of communal swallow and martin roosts and evaluate the scale of phenological shifts and its potential association with temperature. The discrete morning departures of these aggregated aerial insectivores from ground-based roosting locations are detected by radars around sunrise. For the first time, we applied a machine learning algorithm to automatically detect and track these large-scale behaviors. We used 21 years of data from 12 weather surveillance radar stations in the Great Lakes region to quantify the phenology in roosting behavior of aerial insectivores at three spatial levels: local roost cluster, radar station, and across the Great Lakes region. We show that their peak roosting activity timing has advanced by 2.26 days per decade at the regional scale. Similar signals of advancement were found at the station scale, but not at the local roost cluster scale. Air temperature trends in the Great Lakes region during the active roosting period were predictive of later stages of roosting phenology trends (75% and 90% passage dates). Our study represents one of the longest-term broad-scale phenology examinations of avian aerial insectivore species responding to environmental change and provides a stepping stone for examining potential phenological mismatches across trophic levels at broad spatial scales.     

The anaerobic chytridiomycete fungus Piromyces sp. E2 produces ethanol via pyruvate:formate lyase and an alcohol dehydrogenase E

Anaerobic chytridiomycete fungi possess hydrogenosomes, which generate hydrogen and ATP, but also acetate and formate as end-products of a prokaryotic-type mixed-acid fermentation. Notably, the anaerobic chytrids Piromyces and Neocallimastix use pyruvate:formate lyase (PFL) for the catabolism of pyruvate, which is in marked contrast to the hydrogenosomal metabolism of the anaerobic parabasalian flagellates Trichomonas vaginalis and Tritrichomonas foetus, because these organisms decarboxylate pyruvate with the aid of pyruvate:ferredoxin oxidoreductase (PFO). Here, we show that the chytrids Piromyces sp. E2 and Neocallimastix sp. L2 also possess an alcohol dehydrogenase E (ADHE) that makes them unique among hydrogenosome-bearing anaerobes. We demonstrate that Piromyces sp. E2 routes the final steps of its carbohydrate catabolism via PFL and ADHE: in axenic culture under standard conditions and in the presence of 0.3% fructose, 35% of the carbohydrates were degraded in the cytosol to the end-products ethanol, formate, lactate and succinate, whereas 65% were degraded via the hydrogenosomes to acetate and formate. These observations require a refinement of the previously published metabolic schemes. In particular, the importance of the hydrogenase in this type of hydrogenosome has to be revisited.     

A fibronectin-fibrinogen-tropoelastin coating reduces smooth muscle cell growth but improves endothelial cell function

Reendothelialization of the stent surface after percutaneous coronary intervention (PCI) is known to be an important determinant of clinical outcome. We compared the effects of biological stent coatings, fibronectin, fibrinogen and tropoelastin, on human umbilical vein endothelial cell (HUVEC) and vascular smooth muscle cell (VSMC) characteristics. Umbilical cord arterial segments were cultured on coated surfaces and VSMC outgrowth (indicating proliferation and migration) was measured after 12 days. mRNA was isolated from HUVEC and VSMC cultured on these coatings and gene expression was profiled by QPCR. Procoagulant properties of HUVEC were determined by an indirect chromogenic assay which detects tissue factor activity. The varying stent coatings influence VSMC outgrowth: 31.2 ± 4.0 mm(2) on fibronectin, 1.6 ± 0.3 mm(2) on tropoelastin and 8.1 ± 1.5 mm(2) on a mixture of fibronectin/fibrinogen/tropoelastin, although HUVEC migration remains unaffected. Culturing HUVEC on tropoelastin induces increased expression of VCAM-1 (13.1 ± 4.4 pg/ml), ICAM-1 (5.1 ± 1.3 pg/ml) and IL-8 (11.6 ± 3.1 pg/ml) compared to fibronectin (0.7 ± 0.2, 0.8 ± 0.2, 2.3 ± 0.5 pg/ml, respectively), although expression levels on fibronectin/fibrinogen/tropoelastin remain unaltered. No significant differences in VCAM-1, ICAM-1 and IL-8 mRNA expression are found in VSMC. Finally, HUVEC cultured on tropoelastin display a fivefold increased tissue factor activity (511.6 ± 26.7%), compared to cells cultured on fibronectin (100 ± 3.9%) or fibronectin/fibrinogen/tropoelastin (76.3 ± 25.0%). These results indicate that tropoelastin inhibits VSMC migration but leads to increased inflammatory and procoagulant markers on endothelial cells. Fibronectin/fibrinogen/tropoelastin inhibits VSMCs while compensating the inflammatory and procoagulant effects. These data suggest that coating a mixture of fibronectin/fibrinogen/tropoelastin on a stent may promote reendothelialization, while keeping unfavourable processes such as restenosis and procoagulant activity limited.     

Associations between Pathogens in the Upper Respiratory Tract of Young Children: Interplay between Viruses and Bacteria

Background

High rates of potentially pathogenic bacteria and respiratory viruses can be detected in the upper respiratory tract of healthy children. Investigating presence of and associations between these pathogens in healthy individuals is still a rather unexplored field of research, but may have implications for interpreting findings during disease.

Methodology/Principal Findings

We selected 986 nasopharyngeal samples from 433 6- to 24-month-old healthy children that had participated in a randomized controlled trial. We determined the presence of 20 common respiratory viruses using real-time PCR. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus were identified by conventional culture methods. Information on risk factors was obtained by questionnaires. We performed multivariate logistic regression analyses followed by partial correlation analysis to identify the overall pattern of associations. S. pneumoniae colonization was positively associated with the presence of H. influenzae (adjusted odds ratio 1.60, 95% confidence interval 1.18–2.16), M. catarrhalis (1.78, 1.29–2.47), human rhinoviruses (1.63, 1.19–2.22) and enteroviruses (1.97, 1.26–3.10), and negatively associated with S. aureus presence (0.59, 0.35–0.98). H. influenzae was positively associated with human rhinoviruses (1.63, 1.22–2.18) and respiratory syncytial viruses (2.78, 1.06–7.28). M. catarrhalis colonization was positively associated with coronaviruses (1.99, 1.01–3.93) and adenoviruses (3.69, 1.29–10.56), and negatively with S. aureus carriage (0.42, 0.25–0.69). We observed a strong positive association between S. aureus and influenza viruses (4.87, 1.59–14.89). In addition, human rhinoviruses and enteroviruses were positively correlated (2.40, 1.66–3.47), as were enteroviruses and human bocavirus, WU polyomavirus, parainfluenza viruses, and human parechovirus. A negative association was observed between human rhinoviruses and coronaviruses.

Conclusions/Significance

Our data revealed high viral and bacterial prevalence rates and distinct bacterial-bacterial, viral-bacterial and viral-viral associations in healthy children, hinting towards the complexity and potential dynamics of microbial communities in the upper respiratory tract. This warrants careful consideration when associating microbial presence with specific respiratory diseases.     

A proactive approach to migraine in primary care: a pragmatic randomized controlled trial

Background:

Migraine is a common, disabling headache disorder that leads to lost quality of life and productivity. We investigated whether a proactive approach to patients with migraine, including an educational intervention for general practitioners, led to a decrease in headache and associated costs.

Methods:

We conducted a pragmatic randomized controlled trial. Participants were randomized to one of two groups: practices receiving the intervention and control practices. Participants were prescribed two or more doses of triptan per month. General practitioners in the intervention group received training on treating migraine and invited participating patients for a consultation and evaluation of the therapy they were receiving. Physicians in the control group continued with usual care. Our primary outcome was patients’ scores on the Headache Impact Test (HIT-6) at six months. We considered a reduction in score of 2.3 points to be clinically relevant. We used the Kessler Psychological Distress Scale (K10) questionnaire to determine if such distress was a possible effect modifier. We also examined the interventions’ cost-effectiveness.

Results:

We enrolled 490 patients in the trial (233 to the intervention group and 257 to the control group). Of the 233 patients in the intervention group, 192 (82.4%) attended the consultation to evaluate the treatment of their migraines. Of these patients, 43 (22.3%) started prophylaxis. The difference in change in score on the HIT-6 between the intervention and control groups was 0.81 (p = 0.07, calculated from modelling using generalized estimating equations). For patients with low levels of psychological distress (baseline score on the K10 ≤ 20) this change was −1.51 (p = 0.008), compared with a change of 0.16 (p = 0.494) for patients with greater psychological distress. For patients who were not using prophylaxis at baseline and had two or more migraines per month, the mean HIT-6 score improved by 1.37 points compared with controls (p = 0.04). We did not find the intervention to be cost-effective.

Interpretation:

An educational intervention for general practitioners and a proactive approach to patients with migraine did not result in a clinically relevant improvement of symptoms. Psychological distress was an important confounder of success. (Current Controlled Trials registration no. ISRCTN72421511.)Migraine is a common, disabling headache disorder that results in lost quality of life and productivity, both during and between attacks.^1–8 Many patients with migraine suffer unnecessarily because they are not using their medications appropriately, or they are unaware of the possibility of prophylactic treatment. In the Netherlands, 3% of patients who take triptans consume 12 or more doses of the drug each month.⁹ These patients account for almost half of the costs associated with triptan use.¹⁰ In addition, although more than 25% of patients with migraine have two or more attacks each month, making them eligible for preventive treatment, only 8%–12% of patients use prophylaxis.^2,3,11–13 More than half of the patients with migraine in Dutch primary care who have an indication for prophylaxis have not discussed that option with their general practitioner.¹³We investigated whether a proactive approach to identifying patients with migraine who are receiving suboptimal treatment (i.e., inviting them to a consultation to evaluate their current treatment regimen and advising them about the options available for treating their migraine) could increase the use of preventive treatment and reduce the overuse of triptans, thereby reducing headache recurrence and associated costs. Our intervention involved educational sessions for general practitioners. Earlier studies aimed at reducing the overuse of other medications in primary care, such as benzodiazepines and acid-repressive drugs, showed that a proactive intervention led to a reduction in the use of medications.^14,15Because most patients with migraine in the Netherlands are treated by their general practitioner, we evaluated the costs and effects of a proactive approach to migraine in primary care. We included patients who had two or more attacks per month, because improvement could be reasonably expected in this group.