Project description:The recent literature is replete with papers evaluating computational tools (often those operating on 3D structures) for their performance in a certain set of tasks. Most commonly these papers compare a number of docking tools for their performance in cognate re-docking (pose prediction) and/or virtual screening. Related papers have been published on ligand-based tools: pose prediction by conformer generators and virtual screening using a variety of ligand-based approaches. The reliability of these comparisons is critically affected by a number of factors usually ignored by the authors, including bias in the datasets used in virtual screening, the metrics used to assess performance in virtual screening and pose prediction and errors in crystal structures used.
Project description:The aim of this paper is to highlight coronary investigation by transthoracic Doppler evaluation. This application has recently been introduced into clinical practice and has received enthusiastic feedback in terms of coronary flow reserve evaluation on left anterior coronary artery disease diagnosis. Such diagnosis represents the most important clinical application but has in itself some limitations regarding anatomical and technological knowledge. The purpose of this paper is to offer a didactic approach on how to investigate the different segments of left anterior and posterior descending coronary arteries by transthoracic ultrasound using different anatomical key structures as markers. We will conclude by underlining that, nowadays, innovative technology allows complete evaluation of both major coronary arteries in many patients in a resting condition as well as during pharmacology stress-tests, but we often do not know it.
Project description:Ecological traps attract biota to low-quality habitats. Landscape traps are zones caught in a vortex of spiralling degradation. Here, we demonstrate how short-range endemic (SRE) traits may make such taxa vulnerable to ecological and landscape traps. Three SRE species of mygalomorph spider were used in this study: Idiommata blackwalli, Idiosoma sigillatum and an undescribed Aganippe sp. Mygalomorphs can be long-lived (>43 years) and select sites for permanent burrows in their early dispersal phase. Spiderlings from two species, I. blackwalli (n = 20) and Aganippe sp. (n = 50), demonstrated choice for microhabitats under experimental conditions, that correspond to where adults typically occur in situ. An invasive veldt grass microhabitat was selected almost exclusively by spiderlings of I. sigillatum. At present, habitat dominated by veldt grass in Perth, Western Australia, has lower prey diversity and abundance than undisturbed habitats and therefore may act as an ecological trap for this species. Furthermore, as a homogenising force, veldt grass can spread to form a landscape trap in naturally heterogeneous ecosystems. Selection of specialised microhabitats of SREs may explain high extinction rates in old, stable landscapes undergoing (human-induced) rapid change.
Project description:The number of macromolecular structures deposited in the Protein Data Bank now approaches 100,000, with the vast majority of them determined by crystallographic methods. Thousands of papers describing such structures have been published in the scientific literature, and 20 Nobel Prizes in chemistry or medicine have been awarded for discoveries based on macromolecular crystallography. New hardware and software tools have made crystallography appear to be an almost routine (but still far from being analytical) technique and many structures are now being determined by scientists with very limited experience in the practical aspects of the field. However, this apparent ease is sometimes illusory and proper procedures need to be followed to maintain high standards of structure quality. In addition, many noncrystallographers may have problems with the critical evaluation and interpretation of structural results published in the scientific literature. The present review provides an outline of the technical aspects of crystallography for less experienced practitioners, as well as information that might be useful for users of macromolecular structures, aiming to show them how to interpret (but not overinterpret) the information present in the coordinate files and in their description. A discussion of the extent of information that can be gleaned from the atomic coordinates of structures solved at different resolution is provided, as well as problems and pitfalls encountered in structure determination and interpretation.
Project description:Normal EEG variants, especially the epileptiform variants, can be challenging to interpret because they often have sharp contours and may be confused with "epileptic" interictal activities. However, they can be recognized by the fact that "most spikes or sharp wave discharges of clinical import are followed by a slow wave or a series of slow deflections" (Maulsby, 1971). If there is no wave after the spike, electroencephalographers should be suspicious of artifacts and normal EEG variants. Most normal EEG variants display a single rhythm with the same frequency within the pattern and the morphology remains stable throughout the entire EEG recording with repetition of the same pattern. In case of doubt or difficulties with a standard EEG, it is recommended to undergo an EEG that includes sleep stages with or without sleep deprivation. Finally, epileptiform is an ambiguous term corresponding to an electroencephalographic trait. Epileptiform does not imply a pathological condition, including epilepsy. The clinical context remains the most paramount in the diagnosis of epilepsy. In this article, we propose a set of rules and guidelines to identify normal EEG variants in EEG tracings and normal variation of the background activity. It is not easy to accurately assign a specific/precise name to all EEG activity, but with an orderly approach to EEG that involves using a set of criteria, nonepileptic activity can be identified.
Project description:Automated species identification based on data produced with metabarcoding offers an alternative for assessing biodiversity of bulk insect samples obtained with traps. We used a standard two-step PCR approach to amplify a 313 bp fragment of the barcoding region of the mitochondrial COI gene. The PCR products were sequenced on an Illumina MiSeq platform, and the OTUs production and taxonomic identifications were performed with a customized pipeline and database. The DNA used in the PCR procedures was extracted directly from the preservative ethanol of bulk insect samples obtained with automatic light traps in 12 sampling areas located in different biomes of Brazil, during wet and dry seasons. Agricultural field and forest edge habitats were collected for all sampling areas. A total of 119 insect OTUs and nine additional OTUs assigned to other arthropod taxa were obtained at a ≥97% sequence similarity level. The alpha and beta diversity analyses comparing biomes, habitats, and seasons were mostly inconclusive, except for a significant difference in beta diversity between biomes. In this study, we were able to metabarcode and HTS adult insects from their preservative medium. Notwithstanding, our results underrepresent the true magnitude of insect diversity expected from samples obtained with automatic light traps in Brazil. Although biological and technical factors might have impacted our results, measures to optimize and standardize eDNA HTS should be in place to improve taxonomic coverage of samples of unknown diversity and stored in suboptimal conditions, which is the case of most eDNA samples.
Project description:Sulfatases hydrolytically cleave sulfate esters through a unique catalytic aldehyde, which is introduced by a posttranslational oxidation. To profile active sulfatases in health and disease, activity-based proteomic tools are needed. Herein, quinone methide (QM) traps directed against sulfatases are evaluated as activity-based proteomic probes (ABPPs). Starting from a p-fluoromethylphenyl sulfate scaffold, enzymatically generated QM-traps can inactivate bacterial aryl sulfatases from Pseudomonas aeruginosa and Klebsiella pneumoniae, and human steroid sulfatase. However, multiple enzyme-generated QMs form, diffuse, and non-specifically label purified enzyme. In complex proteomes, QM labeling is sulfatase-dependent but also non-specific. Thus, fluoromethylphenyl sulfates are poor ABPPs for sulfatases.
Project description:BackgroundTo monitor adult mosquitoes several trapping devices are available. These are differently constructed and use various mechanisms for mosquito attraction, thus resulting in different trapping sensitivities and efficacies for the various species. Mosquito monitoring and surveillance programs in Europe use various types of mosquito traps, but only a few comparisons have been conducted so far. This study compared the performance of four commercial trapping devices, which are commonly used in Europe.MethodsFour different traps, Biogents Sentinel trap (BG trap), Heavy Duty Encephalitis Vector Survey trap (EVS trap), Centres for Disease Control miniature light trap (CDC trap) and Mosquito Magnet Patriot Mosquito trap (MM trap) were compared in a 4?×?4 latin square study. In the years 2012 and 2013, more than seventy 24-hour trap comparisons were conducted at ten different locations in northern and southern Germany, representing urban, forest and floodplain biotopes.ResultsPer 24-hour trapping period, the BG trap caught the widest range of mosquito species, the highest number of individuals of the genus Culex as well as the highest number of individuals of the species Ochlerotatus cantans, Aedes cinereus/geminus, Oc. communis and Culex pipiens/torrentium. The CDC trap revealed best performance for Aedes vexans, whereas the MM trap was most efficient for mosquitoes of the genus Anopheles and the species Oc. geniculatus. The EVS trap did not catch more individuals of any genus or species compared to the other three trapping devices. The BG trap caught the highest number of individuals per trapping period in urban environments as well as in wet forest, while the CDC trap caught the highest number of individuals in the floodplain biotopes. Additionally, the BG trap was most efficient for the number of mosquito species in urban locations.ConclusionThe BG trap showed a significantly better or similar performance compared to the CDC, EVS or MM trap with regard to trapping efficacy for most common mosquito species in Germany, including diversity of mosquito species and number of mosquitoes per trapping period. Thus, the BG trap is probably the best solution for general monitoring or surveillance programs of adult mosquitoes in Central Europe.
Project description:ObjectivesWe aimed to assess the quality of optical frequency domain imaging (OFDI) of the left main (LM) arterial wall and describe and analyse potential artefacts in this setting.BackgroundOFDI is increasingly used to assess ambiguous lesions and optimize LM percutaneous coronary intervention. However, its ability to provide artefact-free high-quality images of coronary ostia and large segments such as the LM remains uncertain.MethodsWe included 42 consecutive patients who underwent OFDI, including LM imaging. Each OFDI frame was subdivided into four quadrants and analysed. The number of quadrants with artifacts was calculated within the proximal, mid, and distal LM and the first 5 mm of the left anterior descending artery (LAD) and/or left circumflex artery (LCX).ResultsThe quadrants analysis showed an overall artifact rate of 8.9%, mostly out-of-field (45.1%) or residual blood (44.7%) artefacts. Most artifacts were located in the proximal LM (18.6%) with a stepwise reduction of artifact rates towards distal segments (mid LM 5.8%; distal LM 3.6%, ostial LAD 2.6%, and ostial LCX 0%; p < 0.001). While 20 (48.8%) patients had angiographically visible plaques, OFDI showed plaques in 32 patients (76.2%; p=0.007).ConclusionOFDI can accurately evaluate the LM and detect and assess angiographically unvisualized atherosclerotic plaques providing accurate assessment of >90% of the quadrants of the LM and the ostia of its bifurcation branches. However, artifacts mainly located in the proximal LM and decreasing distally in a stepwise fashion should be considered in the interpretation of OFDI in this setting.
Project description:In rheumatoid arthritis, an autoimmune inflammatory arthritis, citrullinated proteins are targeted by autoantibodies and thus thought to drive disease. Neutrophil extracellular traps (NETs) are a source of citrullinated proteins and are increased in rheumatoid arthritis and therefore also implicated in disease pathogenesis. However, not all NETs are citrullinated. One theory aiming to clarify the intersection of citrullination, NETs, and rheumatoid arthritis suggests that specific stimuli induce different types of NETs defined by citrullination status. However, most studies do not evaluate uncitrullinated NETs, only citrullinated or total NETs. Further, the requirement for peptidylarginine deiminase (PAD) 2 and 4, two important citrullinating enzymes in neutrophils and rheumatoid arthritis, in the formation of different NETs has not been clearly defined. To determine if specific stimulants induce citrullinated or uncitrullinated NETs and if those structures require PAD2 or PAD4, human and murine neutrophils, including from PAD4-/- and PAD2-/- mice, were stimulated in vitro and NETs imaged and quantified. In humans, phorbol myristate acetate (PMA), ionomycin, monosodium urate (MSU), and Candida albicans induced NETs with MSU and C. albicans inducing primarily citrullinated, PMA primarily uncitrullinated, and ionomycin a mix of NETs. Only ionomycin and C. albicans were strong inducers of NETs in mice with ionomycin-induced NETs mostly citrullinated and C. albicans-induced NETs a mix of citrullinated and uncitrullinated. Interestingly, no stimulus induced exclusively citrullinated or uncitrullinated NETs. Further, PAD4 was required for citrullinated NETs only, whereas PAD2 was not required for either NET in mice. Therefore, specific stimuli induce varying proportions of both citrullinated and uncitrullinated NETs with different requirements for PAD4. These findings highlight the complexity of NET formation and the need to further define the mechanisms by which different NETs form and their implications for autoimmune disease.