A network-based measure of functional diversity in food webs.

Biodiversity is measured from various perspectives. One of them, functional diversity, quantifies the heterogeneity in species traits and roles in an ecosystem. One important aspect of species roles is their interactions with other species, i.e. their network role. We therefore investigate here functional diversity from the network perspective. Species differ in their network positions in a food web, having different interaction patterns. We developed a measure for quantifying the diversity in species interaction patterns in a food web. We examined the relationship between interaction diversity and several global network properties for 92 food webs. Our results showed that high interaction diversity occurs in sparsely connected and less cohesive food webs. High interaction diversity also occurred in food webs with more clusters and high network modularity. We also quantified several conventional functional diversity indices and demonstrate that they show little or no correlation with interaction diversity. Our proposed diversity index therefore provides a measure complementary to current concepts of functional diversity.

Breaking Out of Surveillance Silos: Integrative Geospatial Data Collection for Child Injury Risk and Active School Transport.

The preponderance of active school transport (AST) and child injury research has occurred independently, yet they are inherently related. This is particularly true in urban areas where the environmental context of AST may pose risks to safety. However, it can be difficult to make these connections due to the often segregated nature in which these veins of research operate. Spatial video presents a geospatial approach for simultaneous data collection related to both issues. This article reports on a multi-sector pilot project among researchers, a children's hospital, and a police department, using spatial video to map child AST behaviors; a geographic information system (GIS) is used to analyze these data in the environmental context of child pedestrian injury and community violence.

Flavan-3-ols in Norway spruce: biosynthesis, accumulation, and function in response to attack by the bark beetle-associated fungus Ceratocystis polonica.

Proanthocyanidins (PAs) are common polyphenolic polymers of plants found in foliage, fruit, bark, roots, rhizomes, and seed coats that consist of flavan-3-ol units such as 2,3-trans-(+)-catechin and 2,3-cis-(-)-epicatechin. Although the biosynthesis of flavan-3-ols has been studied in angiosperms, little is known about their biosynthesis and ecological roles in gymnosperms. In this study, the genes encoding leucoanthocyanidin reductase, a branch point enzyme involved in the biosynthesis of 2,3-trans-(+)-flavan-3-ols, were identified and functionally characterized in Norway spruce (Picea abies), the most widespread and economically important conifer in Europe. In addition, the accumulation of flavan-3-ols and PAs was investigated in Norway spruce saplings after wounding or inoculation with the fungal pathogen Ceratocystis polonica, which is vectored by bark beetles (Ips typographus) and is usually present during fatal beetle attacks. Monomeric and dimeric flavan-3-ols were analyzed by reverse-phase high-pressure liquid chromatography, while the size and subunit composition of larger PAs were characterized using a novel acid hydrolysis method and normal phase chromatography. Only flavan-3-ol monomers with 2,3-trans stereochemistry were detected in spruce bark; dimeric and larger PAs contained flavan-3-ols with both 2,3-trans and 2,3-cis stereochemistry. Levels of monomers as well as PAs with a higher degree of polymerization increased dramatically in spruce bark after infection by C. polonica. In accordance with their role in the biosynthesis of 2,3-trans-(+)-flavan-3-ols, transcript abundance of Norway spruce LEUCOANTHOCYANIDIN REDUCTASE genes also increased significantly during fungal infection. Bioassays with C. polonica revealed that the levels of 2,3-trans-(+)-catechin and PAs that are produced in the tree in response to fungal infection inhibit C. polonica growth and can therefore be considered chemical defense compounds.

Pediatric acute osteomyelitis in the postvaccine, methicillin-resistant Staphylococcus aureus era.

OBJECTIVE: We sought to describe the causative organisms, bones involved, and complications in cases of pediatric osteomyelitis in the postvaccine age and in the era of increasing infection with community-associated methicillin-resistant Staphylococcus aureus (MRSA). METHODS: We reviewed the medical records of children 12 years and younger presenting to our pediatric emergency department between January 1, 2003, and December 31, 2012, with the diagnosis of osteomyelitis. We reviewed operative cultures, blood cultures, and imaging studies. We identified causative organisms, bone(s) involved, time to therapeutic antibiotic treatment, and local and hematogenous complications. RESULTS: The most common organism identified was methicillin-sensitive S aureus (26/55), followed by MRSA (21/55). Seventy-three bone areas were affected in 67 subjects. The most common bone area was the femur (24/73). Forty-six subjects had 75 local complications. The most common organism in cases with local complications was MRSA (49%). Three subjects had hematogenous complications of deep venous thrombosis, septic pulmonary embolus, and endophthalmitis. Subjects with complications had shorter time to therapeutic antibiotic treatment. When an operative culture was done after therapeutic antibiotics were given, an organism was identified from the operative culture in 84% of cases. CONCLUSION: Treatment of pediatric osteomyelitis should include antibiotic coverage for MRSA. Most cases of pediatric osteomyelitis occur in the long bones. Hematogenous complications may include deep venous thrombosis and may be related to treatment with a central venous catheter. Operative culture yield when antibiotics have already been given is high, and antibiotic treatment should not be delayed until operative cultures are obtained.

Prediction of Limb Salvage Following Percutaneous Vascular Intervention Using a Composite Tibial Artery Perfusion Score.

PURPOSE: To assess a novel tibial artery perfusion score (TPS) for predicting limb salvage in critical limb ischemia (CLI) patients undergoing percutaneous vascular intervention (PVI). PATIENTS AND METHODS: A consecutive cohort of 115 CLI patients undergoing PVI in 144 limbs from 2011 to 2016 was analyzed. TPS comprised a 27-point scale based on: (1) patent tibial vessels following PVI, (2) severity of calcification of the tibial arteries, (3) presence of an intact pedal arch following intervention, (4) whether or not revascularization was direct or indirect based on the target angiosome, (5) presence of angiosome blush at the completion of index intervention. Limbs were stratified into (1) High [21-27 points], (2) Medium [13-20 points], and (3) Low [0-12 points] TPS. Predictive value of TPS was evaluated using logistic regression and Cox proportional hazards models. RESULTS: The median follow-up was 15.7 months (range 0.4-69.9 months). Limb salvage in High, Medium, and Low TPS groups was 90.6%, 85.9%, and 55.6%, respectively, as freedom from the composite outcome: (1) limb complication resulting in death, (2) tibial bypass surgery, (3) above-the-knee amputation, or (4) below-the-knee amputation in patients without supratibial disease at the time of PVI. TPS was significantly associated with limb salvage defined as freedom from both the composite outcome and major amputation. CONCLUSIONS: Based on this preliminary investigation, TPS was associated with limb salvage in CLI limbs, particularly in high-risk limbs. Further validation in a prospective cohort may identify patients with high-risk limbs in need of closer surveillance and earlier reintervention. LEVEL OF EVIDENCE: Level IV, case series.

Circadian regulation of response to oxidative stress in Drosophila melanogaster.

Circadian rhythms are fundamental biological phenomena generated by molecular genetic mechanisms known as circadian clocks. There is increasing evidence that circadian synchronization of physiological and cellular processes contribute to the wellness of organisms, curbing pathologies such as cancer and premature aging. Therefore, there is a need to understand how circadian clocks orchestrate interactions between the organism's internal processes and the environment. Here, we explore the nexus between the clock and oxidative stress susceptibility in Drosophila melanogaster. We exposed flies to acute oxidative stress induced by hydrogen peroxide (H(2)O(2)), and determined that mortality rates were dependent on time at which exposure occurred during the day/night cycle. The daily susceptibility rhythm was abolished in flies with a null mutation in the core clock gene period (per) abrogating clock function. Furthermore, lack of per increased susceptibility to H(2)O(2) compared to wild-type flies, coinciding with enhanced generation of mitochondrial H(2)O(2) and decreased catalase activity due to oxidative damage. Taken together, our data suggest that the circadian clock gene period is essential for maintaining a robust anti-oxidative defense.

A network perspective on the topological importance of enzymes and their phylogenetic conservation.

BACKGROUND: A metabolic network is the sum of all chemical transformations or reactions in the cell, with the metabolites being interconnected by enzyme-catalyzed reactions. Many enzymes exist in numerous species while others occur only in a few. We ask if there are relationships between the phylogenetic profile of an enzyme, or the number of different bacterial species that contain it, and its topological importance in the metabolic network. Our null hypothesis is that phylogenetic profile is independent of topological importance. To test our null hypothesis we constructed an enzyme network from the KEGG (Kyoto Encyclopedia of Genes and Genomes) database. We calculated three network indices of topological importance: the degree or the number of connections of a network node; closeness centrality, which measures how close a node is to others; and betweenness centrality measuring how frequently a node appears on all shortest paths between two other nodes. RESULTS: Enzyme phylogenetic profile correlates best with betweenness centrality and also quite closely with degree, but poorly with closeness centrality. Both betweenness and closeness centralities are non-local measures of topological importance and it is intriguing that they have contrasting power of predicting phylogenetic profile in bacterial species. We speculate that redundancy in an enzyme network may be reflected by betweenness centrality but not by closeness centrality. We also discuss factors influencing the correlation between phylogenetic profile and topological importance. CONCLUSION: Our analysis falsifies the hypothesis that phylogenetic profile of enzymes is independent of enzyme network importance. Our results show that phylogenetic profile correlates better with degree and betweenness centrality, but less so with closeness centrality. Enzymes that occur in many bacterial species tend to be those that have high network importance. We speculate that this phenomenon originates in mechanisms driving network evolution. Closeness centrality reflects phylogenetic profile poorly. This is because metabolic networks often consist of distinct functional modules and some are not in the centre of the network. Enzymes in these peripheral parts of a network might be important for cell survival and should therefore occur in many bacterial species. They are, however, distant from other enzymes in the same network.

Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone: a potent, orally bioavailable human CB1/CB2 dual agonist with antihyperalgesic properties and restricted central nervous system penetration.

Selective activation of peripheral cannabinoid CB1 receptors has the potential to become a valuable therapy for chronic pain conditions as long as central nervous system effects are attenuated. A new class of cannabinoid ligands was rationally designed from known aminoalkylindole agonists and showed good binding and functional activities at human CB1 and CB2 receptors. This has led to the discovery of a novel CB1/CB2 dual agonist, naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (13), which displays good oral bioavailability, potent antihyperalgesic activity in animal models, and limited brain penetration.

Selective Impairment in Frequency Discrimination in a Mouse Model of Tinnitus.

Tinnitus is an auditory disorder, which affects millions of Americans, including active duty service members and veterans. It is manifested by a phantom sound that is commonly restricted to a specific frequency range. Because tinnitus is associated with hearing deficits, understanding how tinnitus affects hearing perception is important for guiding therapies to improve the quality of life in this vast group of patients. In a rodent model of tinnitus, prolonged exposure to a tone leads to a selective decrease in gap detection in specific frequency bands. However, whether and how hearing acuity is affected for sounds within and outside those frequency bands is not well understood. We induced tinnitus in mice by prolonged exposure to a loud mid-range tone, and behaviorally assayed whether mice exhibited a change in frequency discrimination acuity for tones embedded within the mid-frequency range and high-frequency range at 1, 4, and 8 weeks post-exposure. A subset of tone-exposed mice exhibited tinnitus-like symptoms, as demonstrated by selective deficits in gap detection, which were restricted to the high frequency range. These mice exhibited impaired frequency discrimination both for tones in the mid-frequency range and high-frequency range. The remaining tone exposed mice, which did not demonstrate behavioral evidence of tinnitus, showed temporary deficits in frequency discrimination for tones in the mid-frequency range, while control mice remained unimpaired. Our findings reveal that the high frequency-specific deficits in gap detection, indicative of tinnitus, are associated with impairments in frequency discrimination at the frequency of the presumed tinnitus.

Nonpeptide bradykinin B2 receptor antagonists: conversion of rodent-selective bradyzide analogues into potent, orally-active human bradykinin B2 receptor antagonists.

The 1-(2-nitrophenyl)thiosemicarbazide (TSC) derivative, (S)-1-[4-(4-benzhydrylthiosemicarbazido)-3-nitrobenzenesulfonyl]pyrrolidine-2-carboxylic acid [2-[(2-dimethylaminoethyl)methylamino]ethyl]amide (bradyzide; (S)-4), was recently disclosed as a novel, potent, orally active nonpeptide bradykinin (BK) B2 receptor antagonist. The compound inhibited the specific binding of [3H]BK to NG108-15 cell membrane preparations (rodent neuroblastoma-glioma) expressing B2 receptors with a K(i) of 0.5 +/- 0.2 nM. Compound (S)-4 also demonstrated oral efficacy against Freund's complete adjuvant (FCA)-induced mechanical hyperalgesia in rats with an ED50 value of 0.84 micromol/kg. After we optimized the terminal binding determinants projecting from the TSC framework, we found that it was possible to replace the potentially toxicophoric nitro and divalent sulfur moieties with only a 15-fold loss in binding affinity ((S)-14a). However, bradyzide and its congeners were found to have much lower affinities for cloned human B2 receptors, expressed in Cos-7 cells. The hitherto synthesized TSC series was screened against the human B2 receptor, and the dibenzosuberane (DBS) pharmacophore emerged as the key structural requirement for potency. Incorporation of this group resulted in a series of derivatives ((S)-14d,e and 19b-d) with K(i) ranges of 10.7-176 nM in NG108-15 cells (expressing the rodent B2 receptor) and 0.79-253 nM in Cos-7 cells (expressing the human B2 receptor). There was no evidence of agonist activity with any of the nonpeptides in any of the cell lines tested. In vivo, oral administration of compound 19c reversed FCA-induced and turpentine-induced mechanical hyperalgesia in rodents with ED50 values of 0.027 and 0.32 micromol/kg, respectively. The selectivity profiles of compounds (S)-14f and (S)-14g were also assessed to determine the conformational and/or steric preferences of the double-ring arrangement. The affinity of (S)-14 g for the human B2 receptor suggested that it may be a hydrophobic interaction with the ethane bridge of the DBS moiety that accounts for the increased potency of compounds (S)-14d,e and 19b,c at this receptor, by favoring a binding mode inaccessible to the unsubstituted diphenylmethyl derivative, (S)-4.

A severe case of ovarian hyperstimulation syndrome with liver dysfunction and malnutrition.

Ovarian hyperstimulation syndrome (OHSS) is a potentially fatal condition associated with the use of ovulation-inducing drugs. We describe a 28-year-old woman who presented with ascites, oliguria and vomiting. Over 2 weeks, the combination of intractable vomiting, intravenous rehydration, paracentesis, hypercatabolism and proteinuria led to severe hypoalbuminaemia with gross oedema and progressively worsening liver function. The patient's albumin dropped to 9 g/l with liver function abnormalities peaking at: alanine aminotransferase, 462 IU/l; alkaline phosphatase, 706 IU/l; bilirubin, 26 micromol/l; and prothrombin time, 19 s. The judicious use of paracentesis and commencement of total parenteral nutrition coincided with a rapid clinical improvement. One month after discharge, the patient was asymptomatic with normal liver function. This case demonstrates the severity of malnutrition and liver dysfunction that can occur with severe OHSS. Increasing use of in-vitro fertilization techniques makes it mandatory for clinicians to be aware of the clinical features, complications and treatment of this condition, and we would suggest that patients with severe OHSS should be jointly managed by physicians and obstetricians.

Oesophageal carcinoma and refractory idiopathic thrombocytopenic purpura: a challenging combination.

We report the case of a 72-year-old lady who presented with fatigue and bruising. Initial investigations were compatible with iron deficiency anaemia and idiopathic thrombocytopenic purpura (ITP). The anaemia and recent heartburn symptoms led to endoscopy, which revealed an extensive oesophageal squamous cell carcinoma. The tumour was inoperable due to local extension and the patient was not deemed fit enough for aggressive chemotherapy. A course of radical local radiotherapy was given. The patient's ITP, which had initially been responsive to high-dose intravenous immunoglobulin, subsequently became refractory to all therapeutic modalities. The patient developed significant dysphagia but therapeutic options were limited due to her severe thrombocytopenia. The patient eventually died from a combination of gastrointestinal and intrapulmonary haemorrhage. This case is of interest for two reasons. First, the development of refractory ITP appeared to mirror the progression of the carcinoma, and to our knowledge this is the first case of ITP associated with oesophageal carcinoma. Second, despite recent endoscopic advances in palliating oesophageal tumours, this case highlights the difficulties that can still occur.