scholarly journals Toxin Neutralization Using Alternative Binding Proteins

Toxins ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 53 ◽  
Author(s):  
Timothy Jenkins ◽  
Thomas Fryer ◽  
Rasmus Dehli ◽  
Jonas Jürgensen ◽  
Albert Fuglsang-Madsen ◽  
...  

Animal toxins present a major threat to human health worldwide, predominantly through snakebite envenomings, which are responsible for over 100,000 deaths each year. To date, the only available treatment against snakebite envenoming is plasma-derived antivenom. However, despite being key to limiting morbidity and mortality among snakebite victims, current antivenoms suffer from several drawbacks, such as immunogenicity and high cost of production. Consequently, avenues for improving envenoming therapy, such as the discovery of toxin-sequestering monoclonal antibodies against medically important target toxins through phage display selection, are being explored. However, alternative binding protein scaffolds that exhibit certain advantages compared to the well-known immunoglobulin G scaffold, including high stability under harsh conditions and low cost of production, may pose as possible low-cost alternatives to antibody-based therapeutics. There is now a plethora of alternative binding protein scaffolds, ranging from antibody derivatives (e.g., nanobodies), through rationally designed derivatives of other human proteins (e.g., DARPins), to derivatives of non-human proteins (e.g., affibodies), all exhibiting different biochemical and pharmacokinetic profiles. Undeniably, the high level of engineerability and potentially low cost of production, associated with many alternative protein scaffolds, present an exciting possibility for the future of snakebite therapeutics and merit thorough investigation. In this review, a comprehensive overview of the different types of binding protein scaffolds is provided together with a discussion on their relevance as potential modalities for use as next-generation antivenoms.

2006 ◽  
Vol 27 (2) ◽  
pp. 80
Author(s):  
Stewart D Nuttall ◽  
Suzy M Juraja ◽  
Jennifer A Carmichael

Isolation and production of highly specific protein-based binding molecules are crucial to the ever expanding diagnostics, therapeutics and protein array fields. Traditionally, such reagents have been sourced from vertebrate immune systems, where antibodies have evolved over millennia into highly effective molecules of immune surveillance capable of targeting a huge range of targets in response to infection and disease. Now, a growing number of alternative protein scaffolds are being investigated as specific binding molecules incorporating a diverse and powerful range of binding and recognition interfaces. These are being sourced from human proteins, from alternative immune molecules present in evolutionarily old vertebrates, and from highly evolved binding proteins in prokaryotic systems.


Author(s):  
Moema S. Santana ◽  
Rute Lopes ◽  
Isabela H. Peron ◽  
Carla R. Cruz ◽  
Ana M. M. Gaspar ◽  
...  

Background: Hepatitis C virus infection is a significant global health burden, which causes acute or chronic hepatitis. The acute hepatitis C is generally asymptomatic and progresses to cure, while persistent infection can progress to chronic liver disease and extrahepatic manifestations. Standard treatment is expensive, poorly tolerated, and has variable sustained virologic responses amongst the different viral genotypes. New therapies involve direct acting antivirals; however, it is also very expensive and may not be accessible for all patients worldwide. In order to provide a complementary approach to the already existing therapies, natural bioactive compounds are investigated as to their several biologic activities, such as direct antiviral properties against hepatitis C, and effects on mitigating chronic progression of the disease, which includes hepatoprotective, antioxidant, anticarcinogenic and anti-inflammatory activities; additionally, these compounds present advantages, as chemical diversity, low cost of production and milder or inexistent side effects. Objective: To present a broad perspective on hepatitis C infection, the chronic disease, and natural compounds with promising anti-HCV activity. Methods: This review consists of a systematic review study about the natural bioactive compounds as a potential therapy for hepatitis C infection. Results: The quest for natural products have yielded compounds with biologic activity, including viral replication inhibition in vitro, demonstrating antiviral activity against hepatitis C. Conclusion: One of the greatest advantages of using natural molecules from plant extracts is the low cost of production, not requiring chemical synthesis, which can lead to less expensive therapies available to low and middle-income countries.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Marceline F. Finda ◽  
Fredros O. Okumu ◽  
Elihaika Minja ◽  
Rukiyah Njalambaha ◽  
Winfrida Mponzi ◽  
...  

Abstract Background Different forms of mosquito modifications are being considered as potential high-impact and low-cost tools for future malaria control in Africa. Although still under evaluation, the eventual success of these technologies will require high-level public acceptance. Understanding prevailing community perceptions of mosquito modification is, therefore, crucial for effective design and implementation of these interventions. This study investigated community perceptions regarding genetically-modified mosquitoes (GMMs) and their potential for malaria control in Tanzanian villages where no research or campaign for such technologies has yet been undertaken. Methods A mixed-methods design was used, involving: (i) focus group discussions (FGD) with community leaders to get insights on how they frame and would respond to GMMs, and (ii) structured questionnaires administered to 490 community members to assess awareness, perceptions and support for GMMs for malaria control. Descriptive statistics were used to summarize the findings and thematic content analysis was used to identify key concepts and interpret the findings. Results Nearly all survey respondents were unaware of mosquito modification technologies for malaria control (94.3%), and reported no knowledge of their specific characteristics (97.3%). However, community leaders participating in FGDs offered a set of distinctive interpretive frames to conceptualize interventions relying on GMMs for malaria control. The participants commonly referenced their experiences of cross-breeding for selecting preferred traits in domestic plants and animals. Preferred GMMs attributes included the expected reductions in insecticide use and human labour. Population suppression approaches, requiring as few releases as possible, were favoured. Common concerns included whether the GMMs would look or behave differently than wild mosquitoes, and how the technology would be integrated into current malaria control policies. The participants emphasised the importance and the challenge of educating and engaging communities during the technology development. Conclusions Understanding how communities perceive and interpret novel technologies is crucial to the design and effective implementation of new vector control programmes. This study offers vital clues on how communities with no prior experience of modified mosquitoes might conceptualize or respond to such technologies when deployed in the context of malaria control programmes. Drawing upon existing interpretive frames and locally-resonant analogies when deploying such technologies may provide a basis for more durable public support in the future.


2016 ◽  
Author(s):  
Iain Lunney

ABSTRACT In a cost-sensitive market driven by depressed commodity prices, significant capital challenges exist for operators interested in pursuing exploration activities in remote environments to define their producible reserves. This paper explores the organizational and operational model developed by a service company over several remote area mobilizations; this model resulted in an optimized low-cost service delivery model characterized by top quartile operational key performance indicators (KPIs). The model centralizes critical functions of an operational organization into discrete service units that are located near the operational location or that provide remote assistance with communication and reporting lines in place to function effectively. Top quartile operational performance and tool availability is a result of placing a remote repair and maintenance facility that includes containerized specialty modules near the operational area. The upfront bottomhole assembly engineering, 24/7 monitoring, and proactive feedback of logged data, drillstring dynamics, and wellbore hydraulics are performed by a core team of subject matter experts in their respective disciplines from an established centralized operating center. The operational KPIs over the course of the six well exploration campaign provided substantial evidence to support the reliability of the model and the high level of experience used in both the remote maintenance facility and the operations center support team.


F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1947 ◽  
Author(s):  
Shane Miersch ◽  
Sachdev S. Sidhu

If the isolation, production, and clinical use of insulin marked the inception of the age of biologics as therapeutics, the convergence of molecular biology and combinatorial engineering techniques marked its coming of age. The first wave of recombinant protein-based drugs in the 1980s demonstrated emphatically that proteins could be engineered, formulated, and employed for clinical advantage. Yet despite the successes of protein-based drugs such as antibodies, enzymes, and cytokines, the druggable target space for biologics is currently restricted to targets outside the cell. Insofar as estimates place the number of proteins either secreted or with extracellular domains in the range of 8000 to 9000, this represents only one-third of the proteome and circumscribes the pathways that can be targeted for therapeutic intervention. Clearly, a major objective for this field to reach maturity is to access, interrogate, and modulate the majority of proteins found inside the cell. However, owing to the large size, complex architecture, and general cellular impermeability of existing protein-based drugs, this poses a daunting challenge. In recent years, though, advances on the two related fronts of protein engineering and drug delivery are beginning to bring this goal within reach. First, prompted by the restrictions that limit the applicability of antibodies, intense efforts have been applied to identifying and engineering smaller alternative protein scaffolds for the modulation of intracellular targets. In parallel, innovative solutions for delivering proteins to the intracellular space while maintaining their stability and functional activity have begun to yield successes. This review provides an overview of bioactive intrabodies and alternative protein scaffolds amenable to engineering for intracellular targeting and also outlines advances in protein engineering and formulation for delivery of functional proteins to the interior of the cell to achieve therapeutic action.


Drones ◽  
2020 ◽  
Vol 4 (2) ◽  
pp. 13 ◽  
Author(s):  
Margaret Kalacska ◽  
Oliver Lucanus ◽  
J. Pablo Arroyo-Mora ◽  
Étienne Laliberté ◽  
Kathryn Elmer ◽  
...  

The rapid increase of low-cost consumer-grade to enterprise-level unmanned aerial systems (UASs) has resulted in the exponential use of these systems in many applications. Structure from motion with multiview stereo (SfM-MVS) photogrammetry is now the baseline for the development of orthoimages and 3D surfaces (e.g., digital elevation models). The horizontal and vertical positional accuracies (x, y and z) of these products in general, rely heavily on the use of ground control points (GCPs). However, for many applications, the use of GCPs is not possible. Here we tested 14 UASs to assess the positional and within-model accuracy of SfM-MVS reconstructions of low-relief landscapes without GCPs ranging from consumer to enterprise-grade vertical takeoff and landing (VTOL) platforms. We found that high positional accuracy is not necessarily related to the platform cost or grade, rather the most important aspect is the use of post-processing kinetic (PPK) or real-time kinetic (RTK) solutions for geotagging the photographs. SfM-MVS products generated from UAS with onboard geotagging, regardless of grade, results in greater positional accuracies and lower within-model errors. We conclude that where repeatability and adherence to a high level of accuracy are needed, only RTK and PPK systems should be used without GCPs.


Agro Ekonomi ◽  
2021 ◽  
Vol 32 (2) ◽  
Author(s):  
Setia Sari Girsang ◽  
Agung B Santosa ◽  
Tommy Purba ◽  
Deddy R Siagian ◽  
Khadijah E Ramija

Accelerating the introduction of a new technological package is needed to increase the productivity of high elevation puddled rice in Humbang Hasundutan. The objectives of the study are to find out the perception of the existence of technological packages and farmers' preference for a new technological package. The study used a survey method with primary data gathered using questionnaires. The criteria of locations and respondents were used to obtain relevant respondents and data concerning their knowledge of high elevation puddled rice cultivation.  The collected data were processed by using Importance Performance Analysis in order to find out the level of Importance and Satisfaction of the indicators and the valued aspects in the technological package components. The results of the study showed that the socio-economic aspects had to be heeded in organizing the technological package. Indicators having a high level of importance and a low level of satisfaction consisted of production cost, quality of seeds, farmer groups empowerment, technology information institution, capital cost, agricultural tools and machines, pest control, sales price, irrigation canals, and farm roads. On the other hand, introducing new superior seeds, productivity attribute and planting age were important indicators for local farmers as to improve the quality of existing seeds. Farmers group expected that the technological package had a high level of productivity, better access to input, low cost, and good user-friendliness in its application.


2021 ◽  
Author(s):  
Benjamin Secker

Use of the Internet of Things (IoT) is poised to be the next big advancement in environmental monitoring. We present the high-level software side of a proof-of-concept that demonstrates an end-to-end environmental monitoring system,<br><div>replacing Greater Wellington Regional Council’s expensive data loggers with low-cost, IoT centric embedded devices, and it’s supporting cloud platform. The proof-of-concept includes a Micropython-based software stack running on an ESP32 microcontroller. The device software includes a built-in webserver that hosts a responsive Web App for configuration of the device. Telemetry data is sent over Vodafone’s NB-IoT network and stored in Azure IoT Central, where it can be visualised and exported.</div><br>While future development is required for a production-ready system, the proof-of-concept justifies the use of modern IoT technologies for environmental monitoring. The open source nature of the project means that the knowledge gained can be re-used and modified to suit the use-cases for other organisations.


Author(s):  
B. Bravo ◽  
M. Miranda ◽  
J. López

Quinoa is an ancestral plant, originally cultivated in the Andes. It is a product with exceptional nutritional value and it has been important in the socio-economic evolution of the Andean population. Food is considered a natural, ecological and economic product. Since quinoa has the same amount of protein as meat, it can complement people’s daily food at a very low cost. The objective of this work was to carry out market research to determine the knowledge of university students about the protein value of quinoa in their diet and its purchasing power. The design was semi-experimental and descriptive. The study population was students of the Agroindustry degree of the Faculty of Livestock Sciences of the Higher Polytechnic School of Chimborazo. Data were collected through a questionnaire, which contained ten open and closed questions. 192 people were surveyed. Data were also collected through direct observations in the food laboratory. The results indicated a high level of ignorance of the benefits of quinoa. A lack of knowledge about quinoa can result in smaller economic benefits for those who produce this high protein food, which in most cases are indigenous communities. Keywords: economic, consumption, quinoa, incidence. Resumen El presente trabajo, tiene por objetivo realizar una investigación de mercado, para determinar el conocimiento de los estudiantes universitarios, sobre el valor proteico de la quinua en su alimentación y el poder adquisitivo de la misma. El diseño es de tipo semi experimental y descriptiva. La población en estudio, son estudiantes de la carrera de Agroindustria de la Facultad de Ciencias Pecuarias de la Escuela Superior Politécnica de Chimborazo; para la recolección de datos se utilizó la técnica de la encuesta, apoyado en el cuestionario de la encuesta, como instrumento, la cual contiene diez preguntas abiertas y cerradas, basados en los objetivos de la investigación, se consideró una muestra de 192 personas, con la finalidad de obtener datos importantes que han sido analizados y explicados de forma descriptiva en el proceso, así mismo la observación directa que se realizó en el laboratorio de alimentos, mediante pruebas que se realizaron. La quinua es una planta ancestral, cultivada originariamente en los Andes, producto con excepcional valor nutritivo, e importante evolución socio económica de la población Andina. Alimentariamente es considerado un producto natural, ecológico y económico, ya que tiene la misma cantidad de proteína como la carne, puede complementar el alimento diario de cada persona a un costo muy bajo. Los resultados obtenidos, permitieron identificar el nivel de desconocimiento de los beneficios de la quinua, dando como resultado el mínimo impacto económico en quienes producen este alimento proteico, que, en la mayoría de los casos, son comunidades indígenas que buscan emprender. Palabras clave: economía, consumo, quinua, incidencia.


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