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Toxicological and Safety Pharmacological Profiling of the Anti-Infective and Anti-Inflammatory Peptide Pep19-2.5
Get PDFAspidasept (Pep19-2.5) and its derivative Pep19-4LF (“Aspidasept II”) are anti-infective and anti-inflammatory synthetic polypeptides currently in development for application against a variety of moderate to severe bacterial infections that could lead to systemic inflammation, as in the case of severe sepsis and septic shock, as well as application to non-systemic diseases in the case of skin and soft tissue infections (SSTI). In the present study, Aspidasept and Aspidasept II and their part structures were analysed with respect to their toxic behavior in different established models against a variety of relevant cells, and in electrophysiological experiments targeting the hERG channel according to ICH S7B. Furthermore, the effects in mouse models of neurobiological behavior and the local lymph node according to OECD test guideline 429 were investigated, as well as a rat model of repeated dose toxicology according to ICH M3. The data provide conclusive information about potential toxic effects, thus specifying a therapeutic window for the application of the peptides. Therefore, these data allow us to define Aspidasept concentrations for their use in clinical studies as parenteral application
Effect of glycerol and sorbitol on the mechanical and barrier properties of films based on pea protein isolate produced by high-moisture extrusion processing
Get PDFDisposable food packaging accounts for a large proportion of the plastic waste in the environment. Bio-based and biodegradable alternatives could help to reduce plastic pollution but must perform similarly to current synthetic materials. Here, we investigated the effect of two plasticizers (glycerol and sorbitol) on the mechanical and barrier properties of films composed of extruded pea protein isolate. We evaluated physical properties such as tensile strength, elongation at break, moisture content, surface energy, residence time distribution, and gas barrier properties as a function of plasticizer concentration. The flexibility and workability of the films generally increased with higher concentrations of the plasticizer. The residence time distribution (RTD) showed that sorbitol mixtures remained in the extruder longer than glycerol mixtures, exacerbating the loss of quality. Glycerol films generally retained more moisture
than sorbitol films and the tensile strength declined with increasing glycerol content, but the elongation at break increased. The polar fraction of the surface energy increased with higher concentrations of sorbitol, indicating that sorbitol is more polar than the pea protein isolate. In terms of barrier properties, both the water vapor transmission rate (WVTR) and oxygen transmission rate (OTR) were higher for films plasticized with sorbitol. Specifically, the OTR
for sorbitol-plasticized films at 50% (vol/vol) was 519 cm3
*100 μm/(m2 *d*bar) compared to 300 cm3 *100 μm/(m2 *d*bar) for the glycerol-plasticized films, and the WVTR for sorbitol-plasticized films at 50% (vol/vol) was 2633 g*100 μm/(m2 *d)
compared to 895 g*100 μm/(m2 *d) for the glycerol-plasticized films. For both plasticizers, the WVTR increased with increasing plasticizer concentration. In contrast, the OTR declined with increasing glycerol concentrations, whereas no trend was observed for sorbitol. Our study shows that pea protein isolate is suitable for the manufacture of bio-based films and confirms that plasticizers influence the
resulting mechanical and barrier properties. Further research is necessary to optimize the properties of the films
Establishment of low-cost laboratory automation processes using AutoIt and 4-axis robots
Get PDFIn most small laboratories, many processes are not yet automated because existing laboratory automation solutions are usually expensive and inflexible to use. Examples of this are autosamplers that are only compatible with one specific laboratory instrument or larger liquid handling stations that are expensive and usually self-contained.
A flexible and inexpensive way to automate laboratory processes would be to automate existing laboratory equipment with the help of suitable robotic arms. In this study, we investigate the feasibility of such a strategy based on a low-cost 4-axis robot and freely available software. We used the scripting language AutoIt that automates any
Windows-based instrument control software. Using these tools, we automated three fundamentally different laboratory processes: a pipetting process, a use as an autosampler for an atomic absorption spectroscopy instrument, and a more complex process involving the inoculation of bacterial cultures. We also integrated a conventional webcam for 2D barcode recognition. Compared to a trained professional who performed all experiments manually, all setups showed no significant differences in accuracy and precision. In summary, the tested system consisting of a 4-axis robot and freely available software is suitable for flexible automation and has potential for even more complex laboratory processes. Limitations such as a lack of collaboration and speed will be addressed in follow-up studies. The system thus represents a well-suited flexible laboratory automation system for both research and teaching purposes
Spatial Proteomics Reveals Differences in the Cellular Architecture of Antibody-Producing CHO and Plasma Cell–Derived Cells
Get PDFMost of the recombinant biotherapeutics employed today to combat severe illnesses, for example, various types of cancer or autoimmune diseases, are produced by Chinese hamster ovary (CHO) cells. To meet the growing demand of these pharmaceuticals, CHO cells are under
constant development in order to enhance their stability and productivity. The last decades saw a shift from empirical cell line optimization toward rational cell engineering using a growing number of large omics datasets to alter cell physiology on various levels. Especially proteomics workflows reached new levels in proteome
coverage and data quality because of advances in high-resolution mass spectrometry instrumentation. One type of workflow concentrates on spatial proteomics by usage of subcellular fractionation of organelles with subsequent shotgun mass spectrometry proteomics and machine
learning algorithms to determine the subcellular localization of large portions of the cellular proteome at a certain time point. Here, we present the first subcellular spatial proteome of a CHO-K1 cell line producing high titers of recombinant antibody in comparison to the
spatial proteome of an antibody-producing plasma cell–derived myeloma cell line. Both cell lines show colocalization of immunoglobulin G chains with chaperones and proteins associated in protein glycosylation within the endoplasmic reticulum compartment. However,
we report differences in the localization of proteins associated to vesicle-mediated transport, transcription, and translation, which may affect antibody production in both cell lines. Furthermore, pairing subcellular localization data with protein expression data revealed elevated protein masses for organelles in the secretory pathway in
plasma cell–derived MPC-11 (Merwin plasma cell tumor-11) cells. Our study highlights the potential of subcellular spatial proteomics combined with protein expression as potent workflow to identify characteristics of highly efficient recombinant protein–expressing cell lines. Data are available via ProteomeXchange with identifier
PXD029115
Guided Internet-Delivered Treatment for Depression: Scoping Review
Get PDFBackground
Studies on guided internet-delivered treatment have demonstrated promising results for patients with depressive disorder.
Objective
The aim of this study was to provide an overview of this research area and identify potential gaps in the research.
Methods
In this scoping review, web-based databases were used to identify research papers published between 2010 and 2022 where guided internet-delivered treatment was administered to participants with depressive disorders, a standardized rating scale of depressive symptoms was used as the primary outcome measure, and the treatment was compared with a control condition.
Results
A total of 111 studies were included, and an overview of the studies was provided. Several gaps in the research were identified regarding the design of the studies, treatments delivered, participant representation, and treatment completion.
Conclusions
This review provides a comprehensive overview of the research area, and several research gaps were identified. The use of other designs and active control conditions is recommended. Future studies should provide access to treatment manuals, and more replications should be conducted. Researchers should aim to include underrepresented populations and provide reports of comorbidities. Definitions of adequate dosage, reports of completion rates, and reasons for treatment dropout are recommended for future studies
The Role of IT Background for Metacognitive Accuracy, Confidence and Overestimation of Deep Fake Recognition Skills
No full textThe emergence of synthetic media such as deep fakes is considered to be a disruptive technology shaping the fight against cybercrime as well as enabling political disinformation. Deep faked material exploits humans’ interpersonal trust and is usually applied where technical solutions of deep fake authentication are not in place, unknown, or unaffordable. Improving the individual’s ability to recognise deep fakes where they are not perfectly produced requires training and the incorporation of deep fake-based attacks into social engineering resilience training. Individualised or tailored approaches as part of cybersecurity awareness campaigns are superior to a one-size-fits-all approach, and need to identify persons in particular need for improvement. Research conducted in phishing simulations reported that persons with educational and/or professional background in information technology frequently underperform in social engineering simulations. In this study, we propose a method and metric to detect overconfident individuals in regards to deep fake recognition. The proposed overconfidence score flags individuals overestimating their performance and thus posing a previously unconsidered cybersecurity risk. In this study, and in line with comparable research from phishing simulations, individuals with IT background were particularly prone to overconfidence. We argue that this data-driven approach to identifying persons at risk enables educators to provide a more targeted education, evoke insight into own judgement deficiencies, and help to avoid the self-selection bias typical for voluntary participation
Bio-based packaging materials from waste or by-products designed for circular bioeconomy
No full textWorking from home during lockdown: the association between rest breaks and well-being
Get PDFOne of the challenges with working from home (WFH) is the question of its effect on health and well-being. The impact of home working on health has so far not been studied extensively. We address this gap by investigating the association between internal recovery, operationalised as rest break frequency (low, medium, and high) during the working day, on self-reported musculoskeletal pain, and post-work recovery symptoms in WFH knowledge workers (n¼382). The analysis showed that failing to take frequent breaks was associated with a dose-response increased risk of reporting headaches. For post-work recovery symptoms, failing to take rest breaks throughout the day was associated with an increased risk of reporting psychological fatigue, physical fatigue, and sleep problems, and a decreased risk of psychologically detaching from work and experiencing adequate rest. Our findings emphasise the importance of remote workers taking recovery breaks from work demands in the maintenance of health and well-being
Establishment of low-cost laboratory automation processes using AutoIt and 4-axis robots
Get PDFIn most small laboratories, many processes are not yet automated because existing laboratory automation solutions are usually expensive and inflexible to use. Examples of this are autosamplers that are only compatible with one specific laboratory instrument or larger liquid handling stations that are expensive and usually self-contained. A flexible and inexpensive way to automate laboratory processes would be to automate existing laboratory equipment with the help of suitable robotic arms. In this study, we investigate the feasibility of such a strategy based on a low-cost 4-axis robot and freely available software. We used the scripting language AutoIt that automates any Windows-based instrument control software. Using these tools, we automated three fundamentally different laboratory processes: a pipetting process, a use as an autosampler for an atomic absorption spectroscopy instrument, and a more complex process involving the inoculation of bacterial cultures. We also integrated a conventional webcam for 2D barcode recognition. Compared to a trained professional who performed all experiments manually, all setups showed no significant differences in accuracy and precision. In summary, the tested system consisting of a 4-axis robot and freely available software is suitable for flexible automation and has potential for even more complex laboratory processes. Limitations such as a lack of collaboration and speed will be addressed in follow-up studies. The system thus represents a well-suited flexible laboratory automation system for both research and teaching purposes