Additional Biological Data Research Articles

Hair testing to assess both known and unknown use of drugs amongst ecstasy users in the electronic dance music scene

BackgroundData on both known and unknown drug use in the electronic dance music (EDM) scene is important to inform prevention and harm reduction. While surveys are the most common method of querying drug use, additional biological data can help validate use and detect unknown/unintentional use of drugs such as new psychoactive substances (NPS). We sought to determine the extent of both known and unknown use of various substances in this high-risk scene. MethodsWe hair-tested 90 self-reported past-year ecstasy/MDMA/Molly users attending EDM parties in New York City during the summer of 2016 using UHPLC–MS/MS. Results were compared to self-reported past-year use. ResultsThree quarters (74.4%) tested positive for MDMA, a third (33.3%) tested positive for an NPS, and 27.8% tested positive specifically for one or more synthetic cathinones (e.g., butylone, ethylone, pentylone, methylone, alpha-PVP). Half (51.1%) of participants tested positive for a drug not self-reported, with most testing positive for synthetic cathinones (72.0%), methamphetamine (69.0%), other NPS stimulants (e.g., 4-FA, 5/6-APB; 66.7%), or new dissociatives (e.g., methoxetamine, diphenidine; 60.0%). Attending parties every other week or more often, reporting higher-frequency ecstasy pill use, having tested one’s ecstasy, and having found out one’s ecstasy was adulterated, were risk factors for testing positive for synthetic cathinones and NPS in general. ConclusionHair testing appears to be a valuable addition to drug epidemiology studies. Many EDM party attendees—even those who test their ecstasy—are unknowingly using NPS and/or other drugs. Prevention information and harm reduction may help reduce unknown/unintentional use.

Population genetics revisited - towards a multidisciplinary research field

Population genetic research has transformed from the study of genetic structures into a much wider and highly multidisciplinary research field. In this contribution, we outline the limitations of classic population genetic data and highlight the potential of combining molecular data with additional environmental, ecological and biological data sets in multidisciplinary approaches. The combination of data sets from various fields allows a more comprehensive understanding of extrinsic and intrinsic evolutionary processes affecting populations such as the distinction between genetic drift and natural selection. The integration of population size estimates and demographic dynamics as well as individual behaviour (embracing aspects like dispersal behaviour) allows for testing of adaptations to local environments and understanding time-lags frequently observed in molecular data. Modelling approaches are integrated at increasing rates into population genetic research to identify potential barriers and corridors. In our review, we therefore highlight multiple synergistic effects when combining population genetic data with morphological, ecological, behavioural data and modelling. We outline strengths and limitations and indicate future possibilities and challenges. © 2015 The Linnean Society of London, Biological Journal of the Linnean Society, 2015, 115, 1–12.

IntSide: a web server for the chemical and biological examination of drug side effects.

Drug side effects are one of the main health threats worldwide, and an important obstacle in drug development. Understanding how adverse reactions occur requires knowledge on drug mechanisms at the molecular level. Despite recent advances, the need for tools and methods that facilitate side effect anticipation still remains. Here, we present IntSide, a web server that integrates chemical and biological information to elucidate the molecular mechanisms underlying drug side effects. IntSide currently catalogs 1175 side effects caused by 996 drugs, associated with drug features divided into eight categories, belonging to either biology or chemistry. On the biological side, IntSide reports drug targets and off-targets, pathways, molecular functions and biological processes. From a chemical viewpoint, it includes molecular fingerprints, scaffolds and chemical entities. Finally, we also integrate additional biological data, such as protein interactions and disease-related genes, to facilitate mechanistic interpretations. Our data and web resource are available online (http://intside.irbbarcelona.org/). patrick.aloy@irbbarcelona.org Supplementary data are available at Bioinformatics online.

Evidence for synonymy between Tetranychus urticae and Tetranychus cinnabarinus (Acari, Prostigmata, Tetranychidae): Review and new data

The species status of Tetranychus cinnabarinus remains uncertain for some acarologists. In the present paper, we propose to examine the taxonomic status of this tetranychid mite through a review of studies that aimed to clarify its taxonomical position. We present and discuss the main results concerning the principal aspects investigated literature published since the description of Boisduval in 1867. These studies concern morphological, biological and molecular data which have been used to separate or to synonymise T. cinnabarinus and Tetranychus urticae. Additional new morphological and biological data are also included. In light of the data presented, the authors conclude that T. cinnabarinus should be considered as a synonym of the polymorphic species T. urticae to which it constitutes the red form.

Evidence for synonymy between Tetranychus urticae and Tetranychus cinnabarinus (Acari, Prostigmata, Tetranychidae): Review and new data

The species status of Tetranychus cinnabarinus remains uncertain for some acarologists. In the present paper, we propose to examine the taxonomic status of this tetranychid mite through a review of studies that aimed to clarify its taxonomical position. We present and discuss the main results concerning the principal aspects investigated throughout literature published since the description of Boisduval in 1867. These studies concern morphological, biological and molecular data which have been used to separate or to synonymise T. cinnabarinus and Tetranychus urticae. Additional new morphological and biological data are also included. In light of the data presented, the authors conclude that T. cinnabarinus should be considered as a synonym of the polymorphic species T. urticae to which it constitutes the red form.

BioSM: Metabolomics Tool for Identifying Endogenous Mammalian Biochemical Structures in Chemical Structure Space

The structural identification of unknown biochemical compounds in complex biofluids continues to be a major challenge in metabolomics research. Using LC/MS, there are currently two major options for solving this problem: searching small biochemical databases, which often do not contain the unknown of interest or searching large chemical databases which include large numbers of nonbiochemical compounds. Searching larger chemical databases (larger chemical space) increases the odds of identifying an unknown biochemical compound, but only if nonbiochemical structures can be eliminated from consideration. In this paper we present BioSM; a cheminformatics tool that uses known endogenous mammalian biochemical compounds (as scaffolds) and graph matching methods to identify endogenous mammalian biochemical structures in chemical structure space. The results of a comprehensive set of empirical experiments suggest that BioSM identifies endogenous mammalian biochemical structures with high accuracy. In a leave-one-out cross validation experiment, BioSM correctly predicted 95% of 1388 Kyoto Encyclopedia of Genes and Genomes (KEGG) compounds as endogenous mammalian biochemicals using 1565 scaffolds. Analysis of two additional biological data sets containing 2330 human metabolites (HMDB) and 2416 plant secondary metabolites (KEGG) resulted in biochemical annotations of 89% and 72% of the compounds, respectively. When a data set of 3895 drugs (DrugBank and USAN) was tested, 48% of these structures were predicted to be biochemical. However, when a set of synthetic chemical compounds (Chembridge and Chemsynthesis databases) were examined, only 29% of the 458,207 structures were predicted to be biochemical. Moreover, BioSM predicted that 34% of 883,199 randomly selected compounds from PubChem were biochemical. We then expanded the scaffold list to 3927 biochemical compounds and reevaluated the above data sets to determine whether scaffold number influenced model performance. Although there were significant improvements in model sensitivity and specificity using the larger scaffold list, the data set comparison results were very similar. These results suggest that additional biochemical scaffolds will not further improve our representation of biochemical structure space and that the model is reasonably robust. BioSM provides a qualitative (yes/no) and quantitative (ranking) method for endogenous mammalian biochemical annotation of chemical space and, thus, will be useful in the identification of unknown biochemical structures in metabolomics. BioSM is freely available at http://metabolomics.pharm.uconn.edu.

Alpha-Interferon Secreting Blastic Plasmacytoid Dendritic Cells Neoplasm

We report a new case of blastic plasmacytoid dendritic cell neoplasm (BPDCN) with extensive immunophenoptyping, genotyping (karyotype, array-comparative genomic hybridization, and fluorescent in situ hybridization), and long-term tumor cells culture. BPDCN is a very rare and aggressive disease clinically characterized by a skin revealing localization more or less rapidly disseminating to the bone marrow and other organs with or without and leukemia. The disease was initially phenotypically characterized by the expression of both CD4 and CD56 antigens, whereas lymphoid and myeloid lineage antigens were negative. A phenotypic link with alpha-interferon (IFN-I)-producing plasmacytoid dendritic cells was demonstrated. The data collected in this case report provide additional biological and genotypical data on tumor cells of BPDCN. This study confirms the capability of tumor cells to secrete IFN-I, demonstrated by biological IFN-I activity of cultured cells and immunohistochemical expression of Mx-1 protein. Although a common genetic profile involving chromosomes 5, 6, 9, 12, 13, and 15 has been identified, no specific genetic marker has been demonstrated that is specific to BPDCN. The demonstration of ETV6 gene deletion in this case deserves further investigations as a putative BPDCN marker.

Comparison of Puccinia acroptili from Eurasia and the USA

A rust disease caused by Puccinia acroptili P. Syd. & Syd. occurs throughout the range of Russian knapweed (Rhaponticum (syn. Acroptilon) repens), including North America. Differences in teliospore dimensions had been observed previously, but not quantified, between a specimen of P. acroptili from Turkey and one from the United States of America (USA). Similar differences were found during a recent evaluation of P. acroptili for biological control of R. repens in the USA; e.g., teliospores from eight USA isolates were 2.4 µm shorter (P = 0.05) than four isolates from Eurasia (two from Turkey, and one each from Russia and Kazakhstan). This inspired the generation of additional biological and DNA sequence data to clarify the significance of these differences between USA and Eurasian isolates. Although the USA isolates were found to have shorter teliospores, as noted in the description by Savile, teliospores of the USA isolates were also significantly wider in diameter than isolates from Eurasia; the latter in contrast to Savile’s observation. Biologically, the isolates were the same; all were equally aggressive in causing disease under common greenhouse test conditions, and fertile crosses occurred between isolates regardless of source. DNA sequence analyses of the nuclear rDNA large subunit and internal transcribed spacer regions supported the notion that P. acroptili is a single species, but it also revealed that small levels of variation may exist within the species. For these reasons, it has been concluded that USA and Eurasian accessions can be considered a single species, i.e., P. acroptili. Also, Savile’s observation about differences in spore dimensions is substantiated.

Clinical and biological effects of high-dose sodium selenite, continuously administered in septic shock

Sodium selenite (Na2SeO3) has been proposed as an early treatment of septic shock with discrepant results [1-3]. Beneficial action is mainly believed through improvement of major antioxidant selenoenzymes, but could on the contrary be related to a therapeutic oxidant action reducing activity of hyperactivated circulating phagocytic cells [4]. It has been suggested that the absence of beneficial effect of high-dose Na2SeO3 continuously administered [2] might be related to toxicity, especially on the lung, of too much selenium (Se) as mentioned in recent parenteral nutrition guidelines in intensive care [5]. On additional clinical and biological data, our purpose was to assess if there was argument for Na2SeO3 toxicity, especially on the lung, under continuous administration of high-dose Na2SeO3 in the SERENITE study.

In Vitro and In Vivo Profiles of ACH-702, an Isothiazoloquinolone, against Bacterial Pathogens

ACH-702, a novel isothiazoloquinolone (ITQ), was assessed for antibacterial activity against a panel of Gram-positive and Gram-negative clinical isolates and found to possess broad-spectrum activity, especially against antibiotic-resistant Gram-positive strains, including methicillin-resistant Staphylococcus aureus (MRSA). For Gram-negative bacteria, ACH-702 showed exceptional potency against Haemophilus influenzae, Moraxella catarrhalis, and a Neisseria sp. but was less active against members of the Enterobacteriaceae. Good antibacterial activity was also evident against several anaerobes as well as Legionella pneumophila and Mycoplasma pneumoniae. Excellent bactericidal activity was observed for ACH-702 against several bacterial pathogens in time-kill assays, and postantibiotic effects (PAEs) of >1 h were evident with both laboratory and clinical strains of staphylococci at 10 × MIC and similar in most cases to those observed for moxifloxacin at the same MIC multiple. In vivo efficacy was demonstrated against S. aureus with murine sepsis and thigh infection models, with decreases in the number of CFU/thigh equal to or greater than those observed after vancomycin treatment. Macromolecular synthesis assays showed specific dose-dependent inhibition of DNA replication in staphylococci, and biochemical analyses indicated potent dual inhibition of two essential DNA replication enzymes: DNA gyrase and topoisomerase IV. Additional biological data in support of an effective dual targeting mechanism of action include the following: low MIC values (≤0.25 μg/ml) against staphylococcal strains with single mutations in both gyrA and grlA (parC), retention of good antibacterial activity (MICs of ≤0.5 μg/ml) against staphylococcal strains with two mutations in both gyrA and grlA, and low frequencies for the selection of higher-level resistance (<10⁻¹⁰). These promising initial data support further study of isothiazoloquinolones as potential clinical candidates.

First record of Hermetia illucens (Diptera: Stratiomyidae) on human corpses in Iberian Peninsula

This article presents the first record of Hermetia illucens larvae on a human corpse in Spain (the second case report in Europe). Prepupae of H. illucens, and other insects, were recovered from the dead body of a 72-year-old man in an advanced stage of decomposition. The body was located in Reus (NE Spain), in October 1998. This article provides additional biological data on experimental studies and an update on the geographic distribution of this species in the Iberian Peninsula.

Are dietary restraint scales valid measures of dietary restriction? Additional objective behavioral and biological data suggest not

Prospective studies find that individuals with elevated dietary restraint scores are at increased risk for bulimic symptom onset, yet experiments find that assignment to energy-deficit diet interventions reduce bulimic symptoms. One explanation for the conflicting findings is that the dietary restraint scales used in the former studies do not actually identify individuals who are restraining their caloric intake. Thus, we tested whether dietary restraint scales showed inverse relations to objectively measured caloric intake in three studies. Four dietary restraint scales did not correlate with doubly labeled water estimates of caloric intake over a 2-week period ( M, r = .01). One scale showed a significant inverse correlation with objectively measured caloric intake during a regular meal ordered from an ecologically valid menu ( M, r = −.30), but a significant positive relation that was qualified by a significant quadratic effect, to objectively measured caloric intake during multiple eating episodes in the lab ( M, r = .32). In balance, results suggest that dietary restraint scales are not valid measures of dietary restriction, replicating findings from prior studies that examined objective measures of caloric intake.

Mathematical models of bipolar disorder

We use limit cycle oscillators to model bipolar II disorder, which is characterized by alternating hypomanic and depressive episodes and afflicts about 1% of the United States adult population. We consider two non-linear oscillator models of a single bipolar patient. In both frameworks, we begin with an untreated individual and examine the mathematical effects and resulting biological consequences of treatment. We also briefly consider the dynamics of interacting bipolar II individuals using weakly-coupled, weakly-damped harmonic oscillators. We discuss how the proposed models can be used as a framework for refined models that incorporate additional biological data. We conclude with a discussion of possible generalizations of our work, as there are several biologically-motivated extensions that can be readily incorporated into the series of models presented here.

The Blue Brain Project: calibrating the neocortical column

The Blue Brain Project is an attempt to reverse-engineer and model the neocortical column, to explore how it functions and to serve as a tool for neuroscientists and medical researchers. In order to achieve the goal of automatically fitting models to the latest data from clearly defined sources, a series of calibration steps have been developed. Each calibration step includes a physiological database, analysis technique and comparison to model data. All data is scored for completeness and quality. The aspects of the neocortical model for which calibration steps have been implemented are: the volume and composition of the column, ion channels, single cell electrical behavior, morphology repair and cloning, synaptic properties, short- and long-term plasticity, synaptic integration, polysynaptic loops, touch detection, structural and functional connectivity and emergent phenomena. The result of the calibration process is a score indicating the overall precision and quality of the fit. This system provides a means to identify those areas which require additional biological data as well as those areas where the model is biologically accurate or in need of refinement. The calibration process will continue to develop, as further biological details become known, and guide the refinement of the neocortical column model.

Hexapod Walking: an expansion to Walknet dealing with leg amputations and force oscillations

The control of the legs of a walking hexapod is a complex problem as the legs have three joints each, resulting in a total of 18 degrees of freedom. We addressed this problem using a decentralized architecture termed Walknet, which consists of peripheral pattern generators being coordinated through influences acting mainly between neighbouring legs. Both, the coordinating influences and the local control modules (each acting only on one leg), are biologically inspired. This investigation shows that it is possible to adapt this approach to account for additional biological data by (1) changing the structure of the selector net in a biological plausible way (including force as an analog variable), (2) introducing a biologically motivated coordination influence for coactivation between legs and (3) adding a hypothetical influence between hind and front legs. This network of controllers has been tested using a dynamic simulation. It is able to describe (a) the behaviour of animals walking with one or two legs being amputated and (b) force oscillations that occur in a specific experimental situation, the standing legs of a walking animal.

Transforming omics data into context: Bioinformatics on genomics and proteomics raw data

Differential gene expression analysis and proteomics have exerted significant impact on the elucidation of concerted cellular processes, as simultaneous measurement of hundreds to thousands of individual objects on the level of RNA and protein ensembles became technically feasible. The availability of such data sets has promised a profound understanding of phenomena on an aggregate level, expressed as the phenotypic response (observables) of cells, e.g., in the presence of drugs, or characterization of cells and tissue displaying distinct patho-physiological states. However, the step of transforming these data into context, i.e., linking distinct expression or abundance patterns with phenotypic observables - and furthermore enabling a sound biological interpretation on the level of reaction networks and concerted pathways, is still a major shortcoming. This finding is certainly based on the enormous complexity embedded in cellular reaction networks, but a variety of computational approaches have been developed over the last few years to overcome these issues. This review provides an overview on computational procedures for analysis of genomic and proteomic data introducing a sequential analysis workflow: Explorative statistics for deriving a first, from the purely statistical viewpoint, relevant candidate gene/protein list, followed by co-regulation and network analysis to biologically expand this core list toward functional networks and pathways. The review on these procedures is complemented by example applications tailored at identification of disease-associated proteins. Optimization of computational procedures involved, in conjunction with the continuous increase in additional biological data, clearly has the potential of boosting our understanding of processes on a cell-wide level.

Endoscopic management of post-laparoscopic cholecystectomy biliary strictures: Long-term outcome in a multicenter study

The aim of this retrospective study was to assess the long term results of long-lasting endoscopic stenting for benign biliary strictures related to laparoscopic cholecystectomy. Additional biological and morphological data were collected from these patients during follow-up. Patients undergoing ERCP for post-laparoscopic cholecystectomy biliary stricture in one of the three participating centers between 1990 and December 2001 were identified. Only patients with successful endoscopic stenting were subsequently included and analyzed. Follow-up data were obtained from referring centers, general practitioners and patients or relatives. Hepatic blood tests and abdominal ultrasound were proposed to all the patients who had not undergone further treatments after stent removal. Eight-eight patients had undergone ERCP for benign biliary stricture related to laparoscopic cholecystectomy. Stenting failed in 19 patients. Balloon dilatation alone was used in four patients. Strictures were successfully stented in 65 patients. The mean number of stents inserted at the same time was 1.6. The mean duration of stenting was 14 months (range 1-120 months). Eighteen patients (28%) developed biliary or pancreatic symptoms during stenting. ERCP was considered satisfactory at the end of stenting (i.e. no remaining stricture or minor remaining change on ERCP) in 45 patients (69%). Twenty-two patients were lost to follow-up. Twenty-nine out of forty-three patients (67%) remained symptom-free with normal updated blood tests and abdominal ultrasound during a mean follow-up of 28 months (range 12-117 months) after stent removal. None of the patients with a normal ERCP at the end of stenting developed stricture recurrence during follow-up. Eleven patients were operated (8 with persistence of stricture, 2 for stricture recurrence up to 63 months after stent removal, 1 for pancreatitis). Based on clinical, morphological and biological criteria, a long-term success was obtained in 70% of patients with post-laparoscopic cholecystectomy benign biliary strictures, after several months of endoscopic stenting.

An assessment of a light-attraction fishery in southern Lake Malawi

This study provides the first quantitative assessment of the light-attraction component of a small-scale purse seine, locally known as a chilimira net, fishery in two areas of southern Lake Malawi. For monitoring purposes the shoreline of Lake Malawi is divided into a number of statistical strata. Two strata ('2.1' in the southeast arm and '3.1' in the southwest arm of the lake) were selected for this study. Catch per unit effort in stratum 2.1 was generally lower than that recorded in stratum 3.1 but nets in stratum 2.1 fished more frequently, leading to similar annual catches in the two strata. Annual catch was estimated as 19.4 (CI = 15.9–23.5) tons net–1 year–1 in stratum 2.1 and 23.5 (CI = 19.5–28.1) tons net–1 year–1 in stratum 3.1 respectively. A total of 62 species from 28 cichlid genera, and 13 species from nine non-cichlid genera, were identified from the samples. Of the 37 genera identified, only five; Copadichromis, Dimidiochromis, Engraulicypris, Oreochromis and Rhamphochromis, contributed more than 5% to the total annual catch in either stratum. Their combined contribution to the annual catch was in excess of 85% in both strata. Comparisons showed that catch-composition was dependent on area. Length-frequency distributions of major target species in the catch showed that the fishery targeted juveniles in stratum 2.1, while in stratum 3.1 most individuals were harvested after reaching their length-at-maturity. The dependence of catch-composition and size-selection on area indicates that management interventions for this fishery need to be area-specific. Since the fishery targets a diverse species assemblage, effort limitation or area closure may be the only viable management options, until such time as additional biological and fisheries data are available for the application of stock assessment models.

A redescription of Cryptosporidium galli Pavlasek, 1999 (Apicomplexa: Cryptosporidiidae) from birds.

Cryptosporidium galli Pavlasek, 1999, described from the feces of birds, is redescribed with additional molecular and biological data. Oocysts are ellipsoidal, are passed fully sporulated, lack sporocysts, and measure 8.25 x 6.3 microm (range 8.0-8.5 x 6.2-6.4 microm) with a length-width ratio of 1.30 (n = 50). Oocysts are structurally similar to those of Cryptosporidium baileyi described from chickens, but in addition to being considerably larger than oocysts of C. baileyi, these oocysts infect the proventriculus in a variety of birds and not the respiratory tract. Oocysts were successfully transmitted from chickens to chickens, and morphologically similar oocysts also were observed in a variety of exotic and wild birds (Order Passeriformes, Phasianidae, Fringillidae, and Icteridae). Molecular and phylogenetic analyses at the 18S rRNA, HSP70, and actin gene loci demonstrate that this species is genetically distinct from all known species and genotypes of Cryptosporidium and, thus, was named C. galli.

BSD: the Biodegradative Strain Database.

The Biodegradative Strain Database (BSD) is a freely-accessible, web-based database providing detailed information on degradative bacteria and the hazardous substances that they degrade, including corresponding literature citations, relevant patents and links to additional web-based biological and chemical data. The BSD (http://bsd.cme.msu.edu) is being developed within the phylogenetic framework of the Ribosomal Database Project II (RDPII: http://rdp.cme.msu.edu/html) to provide a biological complement to the chemical and degradative pathway data of the University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD: http://umbbd.ahc.umn.edu). Data is accessible through a series of strain, chemical and reference lists or by keyword search. The web site also includes on-line data submission and user survey forms to solicit user contributions and suggestions. The current release contains information on over 250 degradative bacterial strains and 150 hazardous substances. The transformation of xenobiotics and other environmentally toxic compounds by microorganisms is central to strategies for biocatalysis and the bioremediation of contaminated environments. However, practical, comprehensive, strain-level information on biocatalytic/biodegradative microbes is not readily available and is often difficult to compile. Similarly, for any given environmental contaminant, there is no single resource that can provide comparative information on the array of identified microbes capable of degrading the chemical. A web site that consolidates and cross-references strain, chemical and reference data related to biocatalysis, biotransformation, biodegradation and bioremediation would be an invaluable tool for academic and industrial researchers and environmental engineers.