Ribosome display: next-generation display technologies for production of antibodies in vitro

Antibodies represent an important and growing class of biologic research reagents and biopharmaceutical products. They can be used as therapeutics in a variety of diseases. With the rapid expansion of proteomic studies and biomarker discovery, there is a need for the generation of highly specific binding reagents to study the vast number of proteins encoded by the genome. Display technologies provide powerful tools for obtaining antibodies. Aside from the preservation of natural antibody repertoires, they are capable of exploiting diversity by DNA recombination to create very large libraries for selection of novel molecules. In contrast to in vivo immunization processes, display technologies allow selection of antibodies under in vitro-defined selection condition(s), resulting in enrichment of antibodies with desired properties from large populations. In addition, in vitro selection enables the isolation of antibodies against difficult antigens including self-antigens, and this can be applied to the generation of human antibodies against human targets. Display technologies can also be combined with DNA mutagenesis for antibody evolution in vitro. Some methods are amenable to automation, permitting high-throughput generation of antibodies. Ribosome display is considered as representative of the next generation of display technologies since it overcomes the limitations of cell-based display methods by using a cell-free system, offering advantages of screening larger libraries and continuously expanding new diversity during selection. Production of display-derived antibodies can be achieved by choosing one of a variety of prokaryotic and eukaryotic cell-based expression systems. In the near future, cell-free protein synthesis may be developed as an alternative for large-scale generation of antibodies.     

Seed‐enhancement combinations improve germination and handling in two dominant native grass species

The use of native grasses for both restoration and commercial purposes is becoming increasingly important globally. Many native grasses have limited success in seed‐based restoration (e.g. post‐mine rehabilitation) and commercial industries (e.g. agriculture) due to poor seed germination and handling. Seed‐enhancement technologies can assist in overcoming these barriers. This study aimed to use combinations of seed enhancements to overcome the germination and handling challenges in two dominant Australian native grass species with demand in restoration and commercial industries (Triodia wiseana C.A Gardner and Rytidosperma caespitosum [Gaudich.] Connor & Edgar). Selected enhancements included hydropriming (including inoculation with karrikinolide [KAR₁]), flash flaming, and seed coating. Combinations of these seed enhancements allowed improvements in both germination (by up to 55% and 18% for T. wiseana and R. caespitosum, respectively) and floret geometry (flowability, as measured through a mechanized seeder, improved by up to 6‐fold and 17‐fold for T. wiseana and R. caespitosum, respectively), with the order of enhancement application being important. The responses of each species to enhancements corresponded with key biological processes and ecological cues required for recruitment events in nature, such as fire and rainfall events. Triodia wiseana germination was driven by fire‐related cues (i.e. KAR₁, flaming), while R. caespitosum germination was highest in response to moisture‐related cues (i.e. hydro‐priming). Responses to seed enhancements (and combinations of) may have implications for the management and scaled use of the targeted species. This can assist in improving the restoration and commercial success of the study species, and potentially other grasses with germination and handling challenges, into the future.     

Recent progress and future options in the development of GLP-1 receptor agonists for the treatment of diabesity

The dramatic rise of the twin epidemics, type 2 diabetes and obesity is associated with increased mortality and morbidity worldwide. Based on this global development there is clinical need for anti-diabetic therapies with accompanied weight reduction. From the approved therapies, the injectable glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are the only class of agents which are associated with a modest weight reduction. Physiological effects of the gastro-intestinal hormone GLP-1 are improvement of glycemic control as well as a reduction in appetite and food intake. Different approaches are currently under clinical evaluation to optimize the therapeutic potential of GLP-1 RAs directed to once-weekly up to once-monthly administration. The next generation of peptidic co-agonists comprises the activity of GLP-1 plus additional gastro-intestinal hormones with the potential for increased therapeutic benefits compared to GLP-1 RAs.     

Rational design and optimization of downstream processes of virus particles for biopharmaceutical applications: current advances

The advent of advanced therapies in the pharmaceutical industry has moved the spotlight into virus-like particles and viral vectors produced in cell culture holding great promise in a myriad of clinical targets, including cancer prophylaxis and treatment. Even though a couple of cases have reached the clinic, these products have yet to overcome a number of biological and technological challenges before broad utilization. Concerning the manufacturing processes, there is significant research focusing on the optimization of current cell culture systems and, more recently, on developing scalable downstream processes to generate material for pre-clinical and clinical trials. We review the current options for downstream processing of these complex biopharmaceuticals and underline current advances on knowledge-based toolboxes proposed for rational optimization of their processing. Rational tools developed to increase the yet scarce knowledge on the purification processes of complex biologicals are discussed as alternative to empirical, “black-boxed” based strategies classically used for process development. Innovative methodologies based on surface plasmon resonance, dynamic light scattering, scale-down high-throughput screening and mathematical modeling for supporting ion-exchange chromatography show great potential for a more efficient and cost-effective process design, optimization and equipment prototyping.     

THE CLAIM FROM ADOPTION REVISITED

In a recent paper published in this journal, Thomas S. Petersen makes a qualified defense of what he calls ‘the Claim from Adoption’, according to which, ‘instead of expending resources on bringing new children [in developed countries] into the world using reproductive technology and caring for these children, we ought to devote these resources to the adoption and care of existing destitute children’. My purpose in this paper is not to discuss Petersen’s argument in favor of that claim. Rather, I want to show that, even if the Claim from Adoption might be, other things being equal, true, it is not true all things considered. What is, all things considered, true is a much more complex set of statements, including a general prima facie obligation to adopt, as well as an obligation by the state of developed countries to discourage procreation and promote adoption of destitute children.     

Drier tropical forests are susceptible to functional changes in response to a long‐term drought

Climatic changes have profound effects on the distribution of biodiversity, but untangling the links between climatic change and ecosystem functioning is challenging, particularly in high diversity systems such as tropical forests. Tropical forests may also show different responses to a changing climate, with baseline climatic conditions potentially inducing differences in the strength and timing of responses to droughts. Trait‐based approaches provide an opportunity to link functional composition, ecosystem function and environmental changes. We demonstrate the power of such approaches by presenting a novel analysis of long‐term responses of different tropical forest to climatic changes along a rainfall gradient. We explore how key ecosystem's biogeochemical properties have shifted over time as a consequence of multi‐decadal drying. Notably, we find that drier tropical forests have increased their deciduous species abundance and generally changed more functionally than forests growing in wetter conditions, suggesting an enhanced ability to adapt ecologically to a drying environment.     

Normalizing Off-Label Experiments and the Pharmaceuticalization of Homebirths in Pakistan

Abstract

The off-label use of the drug misoprostol has effectively turned homebirths in ‘resource-poor’ nations into unmarked and un-enunciated zones of experimentation. Misoprostol has become the public health solution in response to medico-humanitarian discourses that construct homebirths as responsible for high maternal mortality. In the absence of proper safety tests, advocating its routine administration against postpartum haemorrhage in homes around Pakistan functions to erase the distinction between service delivery projects and experimentation. Drawing on ethnographic research in Balochistan, I argue that promoting misoprostol in contexts of structural inequality, particularly where excessive artificial labour induction prevails, constitutes the enactment of a kind of ‘medical relativism’. This medical relativism entails an experimental practice that burdens poor women with undue risk as misoprostol becomes a substitute for required structural and economic transformation of Pakistan's healthcare system. Overall, the paper concludes, the contemporary faith in pharmaceuticals perpetuates a colonial governmentality of bodies, medicines, and healthcare.     

Some like it cold: understanding the survival strategies of psychrophiles

Much of the Earth's surface, both marine and terrestrial, is either periodically or permanently cold. Although habitats that are largely or continuously frozen are generally considered to be inhospitable to life, psychrophilic organisms have managed to survive in these environments. This is attributed to their innate adaptive capacity to cope with cold and its associated stresses. Here, we review the various environmental, physiological and molecular adaptations that psychrophilic microorganisms use to thrive under adverse conditions. We also discuss the impact of modern “omic” technologies in developing an improved understanding of these adaptations, highlighting recent work in this growing field.     

Exploring the application of high-throughput genomics technologies in the field of maternal-embryo communication

Deciphering the complex molecular dialogue between the maternal tract and embryo is crucial to increasing our understanding of pregnancy failure, infertility problems and in the modulation of embryo development, which has consequences through adulthood. High-throughput genomic technologies have been applied to look for a holistic view of the molecular interactions occurring during this dialogue. Among these technologies, microarrays have been widely used, being one of the most popular tools in maternal-embryo communication. Today, next generation sequencing technologies are dwarfing the capabilities of microarrays. The application of these new technologies has broadened to almost all areas of genomics research, because of their massive sequencing capacity. We review the current status of high-throughput genomic technologies and their application to maternal-embryo communication research. We also survey next generation technologies and their huge potential in many research areas. Given the diversity of unanswered questions in the field of maternal-embryo communication and the wide range of possibilities that these technologies offer, here we discuss future perspectives on the use of these technologies to enhance maternal-embryo research.