The formation of well-defined protein bioconjugates is critical for many studies and technologies in chemical biology. Tried-and-true methods for accomplishing this typically involve the targeting of ...cysteine residues, but the rapid growth of contemporary bioconjugate applications has required an expanded repertoire of modification techniques. One very powerful set of strategies involves the modification of proteins at their N termini, as these positions are typically solvent exposed and provide chemically distinct sites for many protein targets. Several chemical techniques can be used to modify N-terminal amino acids directly or convert them into unique functional groups for further ligations. A growing number of N-terminus-specific enzymatic ligation strategies have provided additional possibilities. This Perspective provides an overview of N-terminal modification techniques and the chemical rationale governing each. Examples of specific N-terminal protein conjugates are provided, along with their uses in a number of diverse biological applications.
The collection of chemical techniques that can be used to attach synthetic groups to proteins has expanded substantially in recent years. Each of these approaches allows new protein targets to be ...addressed, leading to advances in biological understanding, new protein-drug conjugates, targeted medical imaging agents and hybrid materials with complex functions. The protein modification reactions in current use vary widely in their inherent site selectivity, overall yields and functional group compatibility. Some are more amenable to large-scale bioconjugate production, and a number of techniques can be used to label a single protein in a complex biological mixture. This review examines the way in which experimental circumstances influence one's selection of an appropriate protein modification strategy. It also provides a simple decision tree that can narrow down the possibilities in many instances. The review concludes with example studies that examine how this decision process has been applied in different contexts.
This paper makes a case for conviviality as a currency for frontier Africans. It argues that incompleteness is the normal order of things, and that conviviality invites us to celebrate and preserve ...incompleteness and mitigate the delusions of grandeur that come with ambitions and claims of completeness. Conviviality encourages frontier Africans to reach out, encounter and explore ways of enhancing or complementing themselves with the added possibilities of potency brought their way by the incompleteness of others, never as a ploy to becoming complete, but to make them more efficacious in their relationships and sociality. Frontier Africans and conviviality suggest alternative and complementary modes of influence over and above the current predominant mode of coercive violence and control.
Soil property and class maps for the continent of Africa were so far only available at very generalised scales, with many countries not mapped at all. Thanks to an increasing quantity and ...availability of soil samples collected at field point locations by various government and/or NGO funded projects, it is now possible to produce detailed pan-African maps of soil nutrients, including micro-nutrients at fine spatial resolutions. In this paper we describe production of a 30 m resolution Soil Information System of the African continent using, to date, the most comprehensive compilation of soil samples (Formula: see text) and Earth Observation data. We produced predictions for soil pH, organic carbon (C) and total nitrogen (N), total carbon, effective Cation Exchange Capacity (eCEC), extractable-phosphorus (P), potassium (K), calcium (Ca), magnesium (Mg), sulfur (S), sodium (Na), iron (Fe), zinc (Zn)-silt, clay and sand, stone content, bulk density and depth to bedrock, at three depths (0, 20 and 50 cm) and using 2-scale 3D Ensemble Machine Learning framework implemented in the mlr (Machine Learning in R) package. As covariate layers we used 250 m resolution (MODIS, PROBA-V and SM2RAIN products), and 30 m resolution (Sentinel-2, Landsat and DTM derivatives) images. Our fivefold spatial Cross-Validation results showed varying accuracy levels ranging from the best performing soil pH (CCC = 0.900) to more poorly predictable extractable phosphorus (CCC = 0.654) and sulphur (CCC = 0.708) and depth to bedrock. Sentinel-2 bands SWIR (B11, B12), NIR (B09, B8A), Landsat SWIR bands, and vertical depth derived from 30 m resolution DTM, were the overall most important 30 m resolution covariates. Climatic data images-SM2RAIN, bioclimatic variables and MODIS Land Surface Temperature-however, remained as the overall most important variables for predicting soil chemical variables at continental scale. This publicly available 30-m Soil Information System of Africa aims at supporting numerous applications, including soil and fertilizer policies and investments, agronomic advice to close yield gaps, environmental programs, or targeting of nutrition interventions.
ABSTRACT
Hepatic de novo lipogenesis (DNL) is the biochemical process of synthesising fatty acids from acetyl‐CoA subunits that are produced from a number of different pathways within the cell, most ...commonly carbohydrate catabolism. In addition to glucose which most commonly supplies carbon units for DNL, fructose is also a profoundly lipogenic substrate that can drive DNL, important when considering the increasing use of fructose in corn syrup as a sweetener. In the context of disease, DNL is thought to contribute to the pathogenesis of non‐alcoholic fatty liver disease, a common condition often associated with the metabolic syndrome and consequent insulin resistance. Whether DNL plays a significant role in the pathogenesis of insulin resistance is yet to be fully elucidated, but it may be that the prevalent products of this synthetic process induce some aspect of hepatic insulin resistance.
Currently, there are no medications that effectively treat the core symptoms of Autism Spectrum Disorder (ASD). We recently found that the bacterial species Lactobacillus (L.) reuteri reverses social ...deficits in maternal high-fat-diet offspring. However, whether the effect of L. reuteri on social behavior is generalizable to other ASD models and its mechanism(s) of action remains unknown. Here, we found that treatment with L. reuteri selectively rescues social deficits in genetic, environmental, and idiopathic ASD models. Interestingly, the effects of L. reuteri on social behavior are not mediated by restoring the composition of the host’s gut microbiome, which is altered in all of these ASD models. Instead, L. reuteri acts in a vagus nerve-dependent manner and rescues social interaction-induced synaptic plasticity in the ventral tegmental area of ASD mice, but not in oxytocin receptor-deficient mice. Collectively, treatment with L. reuteri emerges as promising non-invasive microbial-based avenue to combat ASD-related social dysfunction.
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•Treatment with L. reuteri rescues social deficits in several ASD mouse models•L. reuteri reverses social deficits via the vagus nerve•L. reuteri reverses social deficits even in germ-free mice•OXTR inhibition prevents L. reuteri’s effects on social behavior and VTA plasticity
Precision microbial-based therapy rescues social deficits in genetic, environmental, and idiopathic mouse models of ASD. This rescue depends upon the vagus nerve as well as the oxytocinergic and dopaminergic signaling in the brain.
Clostridium difficile spores must germinate in vivo to become actively growing bacteria in order to produce the toxins that are necessary for disease. C. difficile spores germinate in vitro in ...response to certain bile acids and glycine. In other sporulating bacteria, proteins embedded within the inner membrane of the spore sense the presence of germinants and trigger the release of Ca⁺⁺-dipicolinic acid (Ca⁺⁺-DPA) from the spore core and subsequent hydrolysis of the spore cortex, a specialized peptidoglycan. Based upon homology searches of known germinant receptors from other spore-forming bacteria, C. difficile likely uses unique mechanisms to recognize germinants. Here, we identify the germination-specific protease, CspC, as the C. difficile bile acid germinant receptor and show that bile acid-mediated germination is important for establishing C. difficile disease in the hamster model of infection. These results highlight the importance of bile acids in triggering in vivo germination and provide the first description of a C. difficile spore germinant receptor. Blocking the interaction of bile acids with the C. difficile spore may represent an attractive target for novel therapeutics.
This book questions colonial and apartheid ideologies on being human and being African, ideologies that continue to shape how research is conceptualised, taught and practiced in universities across ...Africa. Africans immersed in popular traditions of meaning-making are denied the right, by those who police the borders of knowledge, to think and represent their realities in accordance with the civilisations and universes they know best. Often, the ways of life they cherish are labelled and dismissed too eagerly as traditional knowledge by some of the very African intellectual elite they look to for protection. The book makes a case for sidestepped traditions of knowledge. It draws attention to Africa's possibilities, prospects and emergent capacities for being and becoming in tune with its creativity and imagination. It speaks to the nimble-footed flexible-minded 'frontier African' at the crossroads and junctions of encounters, facilitating creative conversations and challenging regressive logics of exclusionary identities. The book uses Amos Tutuola's stories to question dualistic assumptions about reality and scholarship, and to call for conviviality, interconnections and interdependence between competing knowledge traditions in Africa.
ObjectiveTo inform international research and policy, we conducted a meta-analysis of the experimental literature on pictorial cigarette pack warnings.Data sourcesWe systematically searched 7 ...computerised databases in April 2013 using several search terms. We also searched reference lists of relevant articles.Study selectionWe included studies that used an experimental protocol to test cigarette pack warnings and reported data on both pictorial and text-only conditions. 37 studies with data on 48 independent samples (N=33 613) met criteria.Data extraction and synthesisTwo independent coders coded all study characteristics. Effect sizes were computed from data extracted from study reports and were combined using random effects meta-analytic procedures.ResultsPictorial warnings were more effective than text-only warnings for 12 of 17 effectiveness outcomes (all p<0.05). Relative to text-only warnings, pictorial warnings (1) attracted and held attention better; (2) garnered stronger cognitive and emotional reactions; (3) elicited more negative pack attitudes and negative smoking attitudes and (4) more effectively increased intentions to not start smoking and to quit smoking. Participants also perceived pictorial warnings as being more effective than text-only warnings across all 8 perceived effectiveness outcomes.ConclusionsThe evidence from this international body of literature supports pictorial cigarette pack warnings as more effective than text-only warnings. Gaps in the literature include a lack of assessment of smoking behaviour and a dearth of theory-based research on how warnings exert their effects.
Polymer sequence programmability is required for the diverse structures and complex properties that are achieved by native biological polymers, but efforts towards controlling the sequence of ...synthetic polymers are, by comparison, still in their infancy. Traditional polymers provide robust and chemically diverse materials, but synthetic control over their monomer sequences is limited. The modular and step‐wise synthesis of peptoid polymers, on the other hand, allows for precise control over the monomer sequences, affording opportunities for these chains to fold into well‐defined nanostructures. Hundreds of different side chains have been incorporated into peptoid polymers using efficient reaction chemistry, allowing for a seemingly infinite variety of possible synthetically accessible polymer sequences. Combinatorial discovery techniques have allowed the identification of functional polymers within large libraries of peptoids, and newly developed theoretical modeling tools specifically adapted for peptoids enable the future design of polymers with desired functions. Work towards controlling the three‐dimensional structure of peptoids, from the conformation of the amide bond to the formation of protein‐like tertiary structure, has and will continue to enable the construction of tunable and innovative nanomaterials that bridge the gap between natural and synthetic polymers.
Sequence programmable polymers are a new class of materials that include the chemical diversity and robustness available to synthetic polymers, while maintaining the precise molecular architectures and enhanced functionality available to biological polymers. Recent advances in peptoid synthesis, characterization, modeling, and applications demonstrate how peptoid polymers have the sequence control required to build an exciting new class of nanostructured materials.
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