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Peptidomics of the zebrafish Danio rerio: In search for neuropeptides

Publication date: Available online 2 October 2016
Source:Journal of Proteomics
Author(s): Kristien A. Van Camp, Geert Baggerman, Ronny Blust, Steven J. Husson
(Neuro)peptides are small messenger molecules that are derived from larger, inactive precursor proteins by the highly controlled action of processing enzymes. These biologically active peptides can be found in all metazoan species where they orchestrate a wide variety of physiological processes. Obviously, detailed knowledge on the actual peptide sequences, including the potential existence of truncated versions or presence of post-translation modifications, is of high importance when studying their function. A peptidomics approach therefore aims to identify and characterize the endogenously present peptide complement of a defined tissue or organism using liquid chromatography and mass spectrometry. While the zebrafish Danio rerio is considered as an important aquatic model for medical research, neuroscience, development and ecotoxicology, very little is known about their peptidergic signaling cascades. We therefore set out to biochemically characterize endogenously present (neuro)peptides from the zebrafish brain. This peptidomics setup yielded >60 different peptides in addition to various truncated versions.SignificanceThough the zebrafish is a well-established model organism to study vertebrate biology and gene functions in either a medical or (eco)toxicological context, very little knowledge about neuropeptidergic signaling cascades is available. We therefore set out to characterize endogenously present peptides from the zebrafish brain using a peptidomics setup yielding a total number of 105 peptide identifications. To our knowledge, it is the first attempt to biochemically isolate and characterize neuropeptides from a fish species in a high-throughput manner. This archive of identified endogenous peptides is likely to aid further functional elucidation of defined neuropeptidergic signaling systems (e.g. characterization of cognate G-protein coupled receptors). Furthermore, our methodology allows studying the changes in peptide expression in response to changes in the organism or the environment using differential peptidomics.

Graphical abstract

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Beyond the survival and death of the deltamethrin-threatened pollen beetle Meligethes aeneus: An in-depth proteomic study employing a transcriptome database

Publication date: Available online 2 October 2016
Source:Journal of Proteomics
Author(s): Tomas Erban, Karel Harant, Julie Chalupnikova, Frantisek Kocourek, Jitka Stara
Insecticide resistance is an increasingly global problem that hampers pest control. We sought the mechanism responsible for survival following pyrethroid treatment and the factors connected to paralysis/death of the pollen beetle Meligethes aeneus through a proteome-level analysis using nanoLC coupled with Orbitrap Fusion™ Tribrid™ mass spectrometry. A tolerant field population of beetles was treated with deltamethrin, and the ensuing proteome changes were observed in the survivors (resistant), dead (paralyzed) and control-treated beetles. The protein database consisted of the translated transcriptome, and the resulting changes were manually annotated via BLASTP. We identified a number of high-abundance changes in which there were several dominant proteins, e.g., the electron carrier cytochrome b5, ribosomal proteins 60S RPL28, 40S RPS23 and RPS26, eIF4E-transporter, anoxia up-regulated protein, 2 isoforms of vitellogenin and pathogenesis-related protein 5. Deltamethrin detoxification was influenced by different cytochromes P450, which were likely boosted by increased cytochrome b5, but glutathione-S-transferase ε and UDP-glucuronosyltransferases also contributed. Moreover, we observed changes in proteins related to RNA interference, RNA binding and epigenetic modifications. The high changes in ribosomal proteins and associated factors suggest specific control of translation. Overall, we showed modulation of expression processes by epigenetic markers, alternative splicing and translation. Future functional studies will benefit.Biological significanceInsects develop pesticide resistance, which has become one of the key issues in plant protection. This growing resistance increases the demand for pesticide applications and the development of new substances. Knowledge in the field regarding the resistance mechanism and its responses to pesticide treatment provides us the opportunity to propose a solution for this issue. Although the pollen beetle Meligethes aeneus was effectively controlled with pyrethroids for many years, there have been reports of increasing resistance. We show protein changes including production of isoforms in response to deltamethrin at the protein level. These results illustrate the insect's survival state as a resistant beetle and in its paralyzed state (evaluated as dead) relative to resistant individuals.

Graphical abstract

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Postural orthostatic tachycardia is not a useful diagnostic marker for chronic fatigue syndrome

Abstract

Background

Postural orthostatic tachycardia syndrome (POTS) is considered a diagnostic marker for chronic fatigue syndrome (CFS).

Objectives

The aims of this study were to (i) compare POTS prevalence in a CFS cohort with fatigued patients not meeting CFS criteria, and (ii) assess activity, impairment and response to cognitive behavioural therapy (CBT) in CFS patients with POTS (POTS-CFS) and without POTS (non-POTS-CFS).

Methods

Prospective cohort study at the Radboud University Medical Centre in the Netherlands. Between June 2013 and December 2014, 863 consecutive patients with persistent fatigue were screened. Patients underwent an active standing test, filled out questionnaires and wore an activity-sensing device for a period of 12 days.

Results

A total of 419 patients with CFS and 341 non-CFS fatigued patients were included in the study. POTS prevalence in adult patients with CFS was 5.7% vs. 6.9% in non-CFS adults (P = 0.54). In adolescents, prevalence rates were 18.2% and 17.4%, respectively (P = 0.93). Adult patients with POTS-CFS were younger (30 ± 12 vs. 40 ± 13 years, P = 0.001) and had a higher supine heart rate (71 ± 11 vs. 65 ± 9 beats per min, P = 0.009) compared with non-POTS-CFS patients. Severity and activity patterns did not differ between groups. In patients with CFS, criteria for Systemic Exertion Intolerance Disease (SEID) were met in 76% of adults and 67% of adolescents. In these patients with CFS fulfilling the SEID criteria, the prevalence of POTS was not different from that in the overall CFS population. POTS-CFS adolescents had less clinically significant improvement after CBT than non-POTS-CFS adolescents (58% vs. 88%, P = 0.017).

Conclusion

In adults with CFS, the prevalence of POTS was low, was not different from the rate in non-CFS fatigued patients and was not related to disease severity or treatment outcome. In POTS-CFS adolescents, CBT was less successful than in non-POTS-CFS patients. The evaluation of POTS appears to be of limited value for the diagnosis of CFS.

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A neural mechanism of cognitive control for resolving conflict between abstract task rules

Publication date: Available online 1 October 2016
Source:Cortex
Author(s): Yi-Shin Sheu, Susan M. Courtney
Conflict between multiple sensory stimuli or potential motor responses is thought to be resolved via bias signals from prefrontal cortex. However, population codes in the prefrontal cortex also represent abstract information, such as task rules. How is conflict between active abstract representations resolved? We used functional neuroimaging to investigate the mechanism responsible for resolving conflict between abstract representations of task rules. Participants performed two different tasks based on a cue. We manipulated the degree of conflict at the task-rule level by training participants to associate the color andshape dimensions of the cue with either the same task rule (congruent cues) or different ones (incongruent cues). Phonological and semantic tasks were used in which performance depended on learned, abstract representations of information, rather than sensory features of the target stimulus or on any habituated stimulus-response associations. In addition, these tasks activate distinct regions that allowed us to measure magnitude of conflict between tasks. We found that incongruent cues were associated with increased activity in several cognitive control areas, including the inferior frontal gyrus, inferior parietal lobule, insula, and subcortical regions. Conflict between abstract representations appears to be resolved by rule-specific activity in the inferior frontal gyrus that is correlated with enhanced activity related to the relevant information. Furthermore, multivoxel pattern analysis of the activity in the inferior frontal gyrus was shown to carry information about both the currently relevant rule (semantic/phonological) and the currently relevant cue context (color/shape). Similar to models of attentional selection of conflicting sensory or motor representations, the current findings indicate part of the frontal cortex provides a bias signal, representing task rules, that enhances task-relevant information. However, the frontal cortex can also be the target of these bias signals in order to enhance abstract representations that are independent of particular stimuli or motor responses.



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New York University School of Medicine Drug Development Educational Program: 2-Year Benchmark

Drug development (DD) is a multidisciplinary process that spans the translational continuum, yet remains an understudied entity in medical schools and biomedical science institutes. In response to a growing interest and unmet need, we implemented a DD course series that details identification of viable molecular targets, clinical trial design, intellectual property, and marketing. Enrollment is open to faculty, postdoctoral trainees, and MD, PhD, and MS students. After 2 years, 37 students and 23 students completed the fall and spring courses, respectively. Pre/post-surveys demonstrated gained knowledge across course topics, with mean survey scores increased by 66% (p < 0.001) after each course. Lectures for each course were consistently rated highly, with a mean course rating of 4.1/5. Through this program, trainees will have a more innovative approach toward identification of therapeutic targets and modalities. Furthermore, they will learn to integrate technology and biomedical informatics to find creative solutions in the DD process.

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Combustion Characterization and Model Fuel Development for Micro-tubular Flame-assisted Fuel Cells

A protocol for creating a model fuel-rich combustion exhaust is developed through combustion characterization and is applied for micro-tubular flame-assisted fuel cell testing and research.

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Hand Controlled Manipulation of Single Molecules via a Scanning Probe Microscope with a 3D Virtual Reality Interface

We demonstrate the precise manipulation of individual organic molecules on a metal surface with the tip of a scanning probe microscope driven in 3D by the experimenter's hand using a motion capture system and fully immersive virtual reality goggles.

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Rapid High-throughput Species Identification of Botanical Material Using Direct Analysis in Real Time High Resolution Mass Spectrometry

A method for species identification of botanical material by direct analysis in real time-high resolution mass spectrometry and multivariate statistical analysis is presented.

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Molecules, Vol. 21, Pages 1323: Anti-Inflammatory Effects of Aspalathus linearis and Cyclopia spp. Extracts in a UVB/Keratinocyte (HaCaT) Model Utilising Interleukin-1α Accumulation as Biomarker

Ultraviolet B (UVB) radiation is one of the major predisposing risk factors of skin cancer. The anticancer and photoprotective effects of unoxidized rooibos (Aspalathus linearis) and honeybush (Cyclopia) herbal teas, containing high levels of dihydrochalones and xanthones, respectively, have been demonstrated in skin cancer models in vivo. In the current study, the anti-inflammatory effects of methanol and aqueous extracts of these herbal teas were investigated in a UVB/HaCaT keratinocyte model with intracellular interleukin-1α (icIL-1α) accumulation as a biomarker. Extracts of green tea (Camellia sinensis) served as benchmark. Both extracts of green tea and rooibos, as well as the aqueous extract of C. intermedia, enhanced UVB-induced inhibition of cell viability, proliferation and induction of apoptosis, facilitating the removal of icIL-1α. The underlying mechanisms may involve mitochondrial dysfunction exhibiting pro-oxidant responses via polyphenol-iron interactions. The methanol extracts of honeybush, however, protected against UVB-induced reduction of cell growth parameters, presumably via antioxidant mechanisms that prevented the removal of highly inflamed icIL-1α-containing keratinocytes via apoptosis. The dual antioxidant and/or pro-oxidant role of the polyphenolic herbal tea constituents should be considered in developing preventive strategies against UVB-induced skin carcinogenesis. The indirect removal of UVB damaged keratinocytes by herbal tea extracts via apoptosis may find application in the prevention of photo-induced inflammation.

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Remote Sensing, Vol. 8, Pages 819: Urban Built-up Areas in Transitional Economies of Southeast Asia: Spatial Extent and Dynamics

Urban built-up area, one of the most important measures of an urban landscape, is an essential variable for understanding ecological and socioeconomic processes in urban systems. With an interest in urban development in transitional economies in Southeast Asia, we recognized a lack of high-to-medium resolution (<60 m) built-up information for countries in the region, including Vietnam, Laos, Cambodia and Myanmar. In this study, we combined multiple remote sensing data, including Landsat, DMSP/OLS night time light, MODIS NDVI data and other ancillary spatial data, to develop a 30-m resolution urban built-up map of 2010 for the above four countries. Following the trend analysis of the DMSP/OLS time series and the 2010 urban built-up extent, we also quantified the spatiotemporal dynamics of urban built-up areas from 1992 to 2010. Among the four countries, Vietnam had the highest proportion of urban built-up area (0.91%), followed by Myanmar (0.15%), Cambodia (0.12%) and Laos (0.09%). Vietnam was also the fastest in new built-up development (increased ~8.8-times during the 18-year study period), followed by Laos, Cambodia and Myanmar, which increased at 6.0-, 3.6- and 0.24-times, respectively.

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Sensors, Vol. 16, Pages 1636: Conditional Entropy and Location Error in Indoor Localization Using Probabilistic Wi-Fi Fingerprinting

Localization systems are increasingly valuable, but their location estimates are only useful when the uncertainty of the estimate is known. This uncertainty is currently calculated as the location error given a ground truth, which is then used as a static measure in sometimes very different environments. In contrast, we propose the use of the conditional entropy of a posterior probability distribution as a complementary measure of uncertainty. This measure has the advantage of being dynamic, i.e., it can be calculated during localization based on individual sensor measurements, does not require a ground truth, and can be applied to discrete localization algorithms. Furthermore, for every consistent location estimation algorithm, both the location error and the conditional entropy measures must be related, i.e., a low entropy should always correspond with a small location error, while a high entropy can correspond with either a small or large location error. We validate this relationship experimentally by calculating both measures of uncertainty in three publicly available datasets using probabilistic Wi-Fi fingerprinting with eight different implementations of the sensor model. We show that the discrepancy between these measures, i.e., many location estimates having a high location error while simultaneously having a low conditional entropy, is largest for the least realistic implementations of the probabilistic sensor model. Based on the results presented in this paper, we conclude that conditional entropy, being dynamic, complementary to location error, and applicable to both continuous and discrete localization, provides an important extra means of characterizing a localization method.

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Metals, Vol. 6, Pages 236: Influence of Hardness, Matrix and Carbides in Combination with Nitridation on Abrasive Wear Resistance of X210Cr12 Tool Steel

Materials used in abrasive wear conditions are usually selected according to their microstructure and hardness, however, other factors such as grain size, matrix saturation, carbides size and morphology are rarely considered. Therefore, the present study deals with the influence of different heat and chemical-heat treatments including their combination on abrasive wear resistance of X210Cr12 tool steel. The effects of material hardness, carbide morphology and microstructure on wear resistance after quenching and nitriding were also investigated. One sample series was quenched after austenitization at 960 °C for 20 min and tempered at 180 °C for 2 h. The second sample series was quenched from 1060 °C austenitization for 20 min and afterwards twice tempered at 530 °C for 1 h. From both the quenched and tempered states, one half of the samples was gas nitrided in NH3 atmosphere for 3 h and then diffusion annealed in N2 atmosphere for 4 h. Abrasion wear tests were performed by sliding the samples on Al2O3 paper. The samples weight loss was considered the main criterion for the wear resistance evaluation. The microstructures, nitrided layers and worn surfaces were observed using SEM microscopy. The highest abrasion wear resistance was obtained for the nitrided samples that were previously quenched from 1060 °C and tempered at 530 °C.

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Bioengineering, Vol. 3, Pages 24: Purification of Monoclonal Antibodies Using a Fiber Based Cation-Exchange Stationary Phase: Parameter Determination and Modeling

Monoclonal antibodies (mAb) currently dominate the market for protein therapeutics. Because chromatography unit operations are critical for the purification of therapeutic proteins, the process integration of novel chromatographic stationary phases, driven by the demand for more economic process schemes, is a field of ongoing research. Within this study it was demonstrated that the description and prediction of mAb purification on a novel fiber based cation-exchange stationary phase can be achieved using a physico-chemical model. All relevant mass-transport phenomena during a bind and elute chromatographic cycle, namely convection, axial dispersion, boundary layer mass-transfer, and the salt dependent binding behavior in the fiber bed were described. This work highlights the combination of model adaption, simulation, and experimental parameter determination through separate measurements, correlations, or geometric considerations, independent from the chromatographic cycle. The salt dependent binding behavior of a purified mAb was determined by the measurement of adsorption isotherms using batch adsorption experiments. Utilizing a combination of size exclusion and protein A chromatography as analytic techniques, this approach can be extended to a cell culture broth, describing the salt dependent binding behavior of multiple components. Model testing and validation was performed with experimental bind and elute cycles using purified mAb as well as a clarified cell culture broth. A comparison between model calculations and experimental data showed a good agreement. The influence of the model parameters is discussed in detail.

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The significance of extramural venous invasion in R1 positive rectal cancer

Abstract

Background and aims

Evidence has shown that a positive resection margin (R1) is a key determinant of subsequent local recurrence and a poor prognostic factor in rectal cancer. The aim of this study was to evaluate the outcomes and prognosticators in patients with R1 resection of rectal cancer.

Material and methods

Retrospective study of all patients operatively managed within our institution between April 2008 and April 2013 for rectal cancer. Baseline demographics and multiple outcome measures recorded. Overall survival (OS), disease-free survival (DFS) and recurrence were the primary outcome measures.

Results

Overall, there were 306 primary rectal cancers. Seventy-six percent were grade T3/4 tumours. OS was 30 months. R1 rate was 16 % (48 patients). Thirty-one patients underwent APR and 17 AR. In patients who responded to neoadjuvant chemotherapy (NAC), overall survival was 55 months, with no extramural venous invasion (EMV) seen in this cohort. In non-responders OS was 29 months, with EMV in 48 %. In patients who did not receive NAC, OS was 23 months, with EMV in 74 %. EMV is a strong predictor for poor survival following R1 (p = 0.001). We also found a correlation between number of positive nodes and OS/DFS (p = 0.004).

Conclusions

In this small cohort of patients with R1 positive rectal cancers, response to NAC is the strongest predictor of poor overall and disease-free survival. In patients who respond to NAC, OS and DFS has been shown to be positive, with a reduced rate of EMV.

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Light-curing units used in dentistry: factors associated with heat development—potential risk for patients

Abstract

Objectives

To investigate how heat development in the pulp chamber and coronal surface of natural teeth with and without cusps subjected to irradiance using light-emitting diode (LED)–light-curing units (LCUs) is associated with (i) irradiance, (ii) time, (iii) distance, and (iv) radiant exposure.

Materials and methods

Three different LED-LCUs were used. Their irradiance was measured with a calibrated spectrometer (BlueLight Analytics Inc., Halifax, Canada). An experimental rig was constructed to control the thermal environment of the teeth. The LED-LCU tip position was accurately controlled by a gantry system. Tooth surface temperature was measured by thermography (ThermaCAM S65 HS, FLIR Systems, Wilsonville, USA) and pulp chamber temperature with a thermocouple. LED-LCU tip distance and irradiation times tested were 0, 2, and 4 mm and 10, 20, and 30 s, respectively. Ethical permission was not required for the use of extracted teeth.

Results

Maximum surface and pulp chamber temperatures were recorded in tooth without cusps (58.1 °C  ± 0.9 °C and 43.1 °C ± 0.9 °C, respectively). Radiant exposure explained the largest amount of variance in temperature, being more affected by time than irradiance.

Conclusions

At all combinations of variables tested, repeated measurements produced consistent results indicating the reliability of the method used. Increased exposure time seems to be the factor most likely to cause tissue damage.

Clinical relevance

Risk of superficial tissue damage at irradiances >1200 mW/cm² is evident. There is a risk of pulp damage when only thin dentin is left at higher irradiances (>1200 mW/cm²). Clinicians should be aware of LED-LCU settings and possible high temperature generated.

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