Artificial enzymes: learning from nature and beyond

Science China Life Sciences -     

Nanozymes: created by learning from nature

Nanozymes, a type of nanomaterials with enzyme-like activity, have shown great potential to replace natural enzymes in many fields such as biochemical detection, environmental management and disease treatment. However, the catalytic efficiency and substrate specificity of nanozymes still need improvement. To further optimize the enzymatic properties of nanozymes, recent studies have introduced the structural characteristics of natural enzymes into the rational design of nanozymes, either by employing small molecules to mimic the cofactors of natural enzymes to boost nanozymes' catalytic potential, or by simulating the active center of natural enzymes to construct the nanostructure of nanozymes. This review introduces the commonly used bio-inspired strategies to create nanozymes, aiming at clarifying the current progress and bottlenecks. Advances and challenges focusing on the research of bio-inspired nanozymes are outlined to provide ideas for the de novo design of ideal nanozymes.     

Protein--carbohydrate interactions: learning lessons from nature

Protein--carbohydrate interactions are at the heart of many important biological processes including signalling, recognition and catalysis. A deeper understanding of these interactions at the molecular level will enable the development of novel, effective and highly selective therapeutics. Glycosyltransferases and glycosidases, carbohydrate-processing enzymes responsible for the synthesis and breakdown of oligosaccharides, have emerged as important targets in the fight against bacterial and fungal pathogenesis, cancer and AIDS. Binding and recognition phenomena are essential processes by which the body exerts control over complex biological functions. In this regard, heparin has retained ongoing interest reflecting its importance as a major pharmaceutical. Recent studies on heparin have shed light onto the mechanisms of cross-reactivity that cause life-threatening side effects and have provided impetus for the development of more selective anti-clotting agents. Important targets for therapeutic intervention are the binding processes mediated through multivalent protein--carbohydrate interactions, such as the interactions of bacterial toxins with cell-surface receptors.     

Benefits of nature: what we are learning about why people respond to nature

People have positive aesthetic, emotional, and physiological responses to nature. Why is this so? The "savanna hypothesis," proposed by Gordon Orians, predicts that some human responses are based on innate knowledge of productive human habitats. To test this, researchers have examined particular aspects of nature that should be associated with productive human habitats to see if they trigger positive responses in people. Tree form has emerged as an important factor in these studies. People prefer looking at trees with spreading forms much more than looking at trees with other forms. Trees with spreading forms existed on the African savanna and were associated with habitats that were good for early human habitation. We have shown that subjects also feel happier when looking at these trees than when looking at other trees or non-tree objects. Color is another variable that might be associated with people's responses to nature. Bright green colors could be an important cue for healthy plants with good nutrient qualities. We measured subjects' physiological responses to tree canopies of various colors and found that all colors were calming, but bright green trees were more calming than other tree colors, including less bright greens and oranges. Adult responses to plants are also influenced by their childhood interactions with nature. We have shown that the more interaction people have with nature as children, the more positive are their attitudes towards nature as adults. These positive responses have been documented in people from a wide range of backgrounds.     

MspA nanopores from subunit dimers

Mycobacterium smegmatis porin A (MspA) forms an octameric channel and represents the founding member of a new family of pore proteins. Control of subunit stoichiometry is important to tailor MspA for nanotechnological applications. In this study, two MspA monomers were connected by linkers ranging from 17 to 62 amino acids in length. The oligomeric pore proteins were purified from M. smegmatis and were shown to form functional channels in lipid bilayer experiments. These results indicated that the peptide linkers did not prohibit correct folding and localization of MspA. However, expression levels were reduced by 10-fold compared to wild-type MspA. MspA is ideal for nanopore sequencing due to its unique pore geometry and its robustness. To assess the usefulness of MspA made from dimeric subunits for DNA sequencing, we linked two M1-MspA monomers, whose constriction zones were modified to enable DNA translocation. Lipid bilayer experiments demonstrated that this construct also formed functional channels. Voltage gating of MspA pores made from M1 monomers and M1-M1 dimers was identical indicating similar structural and dynamic channel properties. Glucose uptake in M. smegmatis cells lacking porins was restored by expressing the dimeric mspA M1 gene indicating correct folding and localization of M1-M1 pores in their native membrane. Single-stranded DNA hairpins produced identical ionic current blockades in pores made from monomers and subunit dimers demonstrating that M1-M1 pores are suitable for DNA sequencing. This study provides the proof of principle that production of single-chain MspA pores in M. smegmatis is feasible and paves the way for generating MspA pores with altered stoichiometries. Subunit dimers enable better control of the chemical and physical properties of the constriction zone of MspA. This approach will be valuable both in understanding transport across the outer membrane in mycobacteria and in tailoring MspA for nanopore sequencing of DNA.     

Microbial communities associated with plants: learning from nature to apply it in agriculture

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Effective field trips in nature: the interplay between novelty and learning

Educational field trips are common practice in environmental education and education for sustainable development, well recognised by researchers for their potential to achieve cognitive and affective educational outcomes. One of the factors that influences learning during field trips is their novelty. The current study focuses on the interplay between novelty, preparation and environmental learning outcomes of 5th and 6th grade students during a typical field trip in Flanders. Our dependent variables are Inclusion of Nature in the Self, the two major ecological values Preservation and Utilisation and ecosystem knowledge. The sample includes 484 students (10–12 years old) and their 24 teachers. Key questions addressed are: (1) What is learned during the field trip? (2) What is the level of novelty for students during a field trip? (3) How does the novelty effect relate to learning? Results show that participation in the field trip leads to a substantial increase in ecosystem knowledge, but fails in reaching the affective goals set out by the field trip organisers. Our results furthermore provide support for the hypothesised non-linear relationship between novelty and knowledge gain, showing that while a little novelty is positive, too much novelty can stand in the way of learning.     

On the nature of cultural transmission networks: evidence from Fijian villages for adaptive learning biases

Unlike other animals, humans are heavily dependent on cumulative bodies of culturally learned information. Selective processes operating on this socially learned information can produce complex, functionally integrated, behavioural repertoires-cultural adaptations. To understand such non-genetic adaptations, evolutionary theorists propose that (i) natural selection has favoured the emergence of psychological biases for learning from those individuals most likely to possess adaptive information, and (ii) when these psychological learning biases operate in populations, over generations, they can generate cultural adaptations. Many laboratory experiments now provide evidence for these psychological biases. Here, we bridge from the laboratory to the field by examining if and how these biases emerge in a small-scale society. Data from three cultural domains-fishing, growing yams and using medicinal plants-show that Fijian villagers (ages 10 and up) are biased to learn from others perceived as more successful/knowledgeable, both within and across domains (prestige effects). We also find biases for sex and age, as well as proximity effects. These selective and centralized oblique transmission networks set up the conditions for adaptive cultural evolution.     

Oilseed rape: learning about ancient and recent polyploid evolution from a recent crop species

Oilseed rape (Brassica napus) is one of our youngest crop species, arising several times under cultivation in the last few thousand years and completely unknown in the wild. Oilseed rape originated from hybridisation events between progenitor diploid species B. rapa and B. oleracea, both important vegetable species. The diploid progenitors are also ancient polyploids, with remnants of two previous polyploidisation events evident in the triplicated genome structure. This history of polyploid evolution and human agricultural selection makes B. napus an excellent model with which to investigate processes of genomic evolution and selection in polyploid crops. The ease of de novo interspecific hybridisation, responsiveness to tissue culture, and the close relationship of oilseed rape to the model plant Arabidopsis thaliana, coupled with the recent availability of reference genome sequences and suites of molecular cytogenetic and high‐throughput genotyping tools, allow detailed dissection of genetic, genomic and phenotypic interactions in this crop. In this review we discuss the past and present uses of B. napus as a model for polyploid speciation and evolution in crop species, along with current and developing analysis tools and resources. We further outline unanswered questions that may now be tractable to investigation.     

Biomimetic soluble collagen purified from bones

Type I collagen has been extensively exploited as a biomaterial for biomedical applications and drug delivery; however, small molecular alterations occurring during the isolation procedure and its interaction with residual bone extracellular matrix molecules or proteins might affect the overall material biocompatibility and performance. The aim of the current work is to study the potential alterations in collagen properties and organization associated with the absence of proteoglycans, which mimic pathological conditions associated with age‐related diseases. A new approach for evaluating the effect of proteoglycans on the properties of isolated type I collagen from the bone matrix is described. Additional treatment with guanidine hydrochloride was introduced to remove residual proteoglycans from the collagen matrix. The properties of the isolated collagen with/without guanidine hydrochloride treatment were investigated and compared with a commercial rabbit collagen as control. We demonstrate that the absence of proteoglycans in the isolated type I collagen affects its thermal properties, the extraction into its native structure, and its ability to hydrate and self‐assemble into fibers. The fine control and tuning of all these features, linked to the absence of non‐collagenous proteins as proteoglycans, offer the possibility of designing new strategies and biomaterials with advanced biomimetic properties aimed at regenerating bone tissue in the case of fragility and/or defects.     

Biomimetic and bioactive nanofibrous scaffolds from electrospun composite nanofibers

Electrospinning is an enabling technology that can architecturally (in terms of geometry, morphology or topography) and biochemically fabricate engineered cellular scaffolds that mimic the native extracellular matrix (ECM). This is especially important and forms one of the essential paradigms in the area of tissue engineering. While biomimesis of the physical dimensions of native ECM's major constituents (eg, collagen) is no longer a fabrication-related challenge in tissue engineering research, conveying bioactivity to electrospun nanofibrous structures will determine the efficiency of utilizing electrospun nanofibers for regenerating biologically functional tissues. This can certainly be achieved through developing composite nanofibers. This article gives a brief overview on the current development and application status of employing electrospun composite nanofibers for constructing biomimetic and bioactive tissue scaffolds. Considering that composites consist of at least two material components and phases, this review details three different configurations of nanofibrous composite structures by using hybridizing basic binary material systems as example. These are components blended composite nanofiber, core-shell structured composite nanofiber, and nanofibrous mingled structure.     

Antimalarials from nature

Malaria is a major public health problem mainly due to the development of resistance by the most lethal causative parasitic species, Plasmodium falciparum to the mainstay drugs like chloroquine. New drugs with unique structures and mechanism of action are urgently required to treat sensitive and drug-resistant strains of malaria. Historically, compounds containing novel structure from natural origin represent a major source for the discovery and development of new drugs for several diseases. This review presents recent advances in antimalarial drug discovery from natural sources, including plant extracts, and compounds isolated from plants, bacteria, fungi and marine organisms. These compounds offer new and novel scaffolds for development as antimalarials. The literature from 1998 to October 2008 is reviewed. The review present literature compilation from plant and marine extracts, alkaloids (naphthylisoquinolines, bisbenzylisoquinolines, protoberberines and aporphines, indoles, manzamines, and miscellaneous alkaloids) terpenes (sesquiterpenes, triterpenes, diterpenes, and miscellaneous terpenes) quassinoids, flavonoids, limonoids, chalcones, peptides, xanthones, quinones and coumarines, and miscellaneous antimalarials from nature. The review also provides an outlook to recent semisynthetic approaches to antimalarial drugs discovered from natural sources.     

Putting concerns about nature in context: the case of agricultural biotechnology

Concerns about nature are playing increasingly prominent roles in a variety of social debates, including medical biotechnology, environmental protection, and agricultural biotechnology. These concerns are often simply rejected as incoherent: critics argue that there is no good account for how natural states of affairs can have moral value, and that the concept of "nature" is too multifarious and vague to be deployed in moral argument anyway. When these concerns are defended, they are frequently formulated as strong claims that make implausible ontological commitments and that ignore the linkages between these different debates. Agricultural biotechnology provides an especially challenging case study for evaluating concerns about nature. I offer a qualified defense that recognizes these concerns as conceptually linked, attends to social context at appropriate points, and overcomes the charges of incoherence. This defense supports a restrained treatment of concerns about nature in public policy: public policy can neither endorse nor dismiss them. In the case of agricultural biotechnology, this stance probably mandates some form of labeling.     

Lessons from nature: stimuli-responsive polymers and their biomedical applications

Response to stimulus is a basic process of living systems. Based on the lessons from nature, scientists have been designing useful materials that respond to external stimuli such as temperature, pH, light, electric field, chemicals and ionic strength. These responses are manifested as dramatic changes in one of the following: shape, surface characteristics, solubility, formation of an intricate molecular self-assembly or a sol-to-gel transition. Applications of stimuli-responsive, or 'smart', polymers in delivery of therapeutics, tissue engineering, bioseparations, sensors or actuators have been studied extensively and numerous papers and patents are evidence of rapid progress in this area. Understanding the structure-property relationship is essential for the further development and rational design of new functional smart materials. For example, kinetic and thermodynamic control of the coil-to-globule transition could be achieved through changes in polymer composition and topology.     

Combinatorial biocatalysis: taking the lead from nature

Combinatorial biocatalysis is an emerging technology in the field of drug discovery. The biocatalytic approach to combinatorial chemistry uses enzymatic, chemoenzymatic, and microbial transformations to generate libraries from lead compounds. Important recent advances in combinatorial biocatalysis include iterative derivatization of small molecules and complex natural products, regioselectively controlled libraries, novel one-pot library syntheses, process automation, and biocatalyst enhancements.     

Biomimetic polyene cyclizations: A review

It has been shown that certain polyenic substances, having trans olefinic bonds in the 1,5 relationship, can be induced to undergo stereospecific, nonenzymic, cationic cyclization to give polycyclic products with the all trans (“natural”) configuration. These transformations appear to mimic in principle the biogenetic conversion of squalene into polycyclic triterpenoids, e.g., lanosterol. Acetal as well as allylic alcohol functions have proved to be effective initiators for such cyclizations, many of which proceed to a remarkable degree of completion giving mainly totally cyclized products. Thus, it has been possible to convert, in a single step, an open chain tetraenic acetal having no chiral centers, into a tetracyclic product having seven such centers. The process is highly stereoselective giving only two of 64 possible racemates.Methylacetylenic and also styryl end groups are particularly useful cyclization terminators as they provide a means of realizing five-membered ring formation. Systems with these terminators have been developed for effecting the total synthesis of the steroid nucleus in a single step starting from a substrate containing only one ring.The mechanism of these biomimetic as well as of the enzymic cyclizations is open to question, but the balance of the evidence is somewhat in favor of a synchronous process.     

Sciences of learning and development: Some thoughts from the learning sciences

ABSTRACT

This commentary extends and amplifies aspects of the Cantor, Osher, Berg, Steyer and Rose (2018 Cantor, P., Osher, D., Berg, J., Steyer, L., & Rose, T. (2018). Maleability, plasticity, and individuality: How children learn and develop in context. Applied Developmental Science. doi:10.1080/10888691.2017.1398649[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]) discussion about what we know about the nature of learning and its implications for how we educate students across the span from early childhood through advanced levels of formal education. The paper’s overall goal is to offer some guidance and clarification about how aspects of the Cantor et al. (2018 Cantor, P., Osher, D., Berg, J., Steyer, L., & Rose, T. (2018). Maleability, plasticity, and individuality: How children learn and develop in context. Applied Developmental Science. doi:10.1080/10888691.2017.1398649[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]) powerful vision of optimal and equitable development might be attained based on a view of what we mean by learning, the types of learning that matter, and ways to design environments for learning and development that allow all children to realize their potential. Three major topics are covered. The first concerns evolution of theories of learning as they relate to theories of development and the connection between the two. Emphasis is given to the power that comes from adopting a sociocultural perspective on the nature of learning and development. The second topic is a consideration of current targets of learning and development, including so-called 21^st century competencies and deep disciplinary learning. Emphasis is given to the cognitive, intrapersonal and interpersonal competency domains that integrate cognitive, affective, social and emotional processes. The third topic focuses on a set of research-based principles that can be used to design and implement powerful and equitable learning environments that align with sociocultural theories and learning and development while integrating the three major domains of competency.