The discovery of radically different antifreeze proteins (AFPs) in fishes during the 1970s and 1980s suggested that these proteins had recently and independently evolved to protect teleosts from ...freezing in icy seawater. Early forays into the isolation and characterization of AFP genes in these fish showed they were massively amplified, often in long tandem repeats. The work of many labs in the 1980s onward led to the discovery and characterization of AFPs in other kingdoms, such as insects, plants, and many different microorganisms. The distinct ice-binding property that these ice-binding proteins (IBPs) share has facilitated their purification through adsorption to ice, and the ability to produce recombinant versions of IBPs has enabled their structural characterization and the mapping of their ice-binding sites (IBSs) using site-directed mutagenesis. One hypothesis for their ice affinity is that the IBS organizes surface waters into an ice-like pattern that freezes the protein onto ice. With access now to a rapidly expanding database of genomic sequences, it has been possible to trace the origins of some fish AFPs through the process of gene duplication and divergence, and to even show the horizontal transfer of an AFP gene from one species to another.
Early life nutrition is a vital determinant of an individual's life-long health and also directly influences the ecological and functional development of the gut microbiota. However, there are ...limited longitudinal studies examining the effect of diet on the gut microbiota development in early childhood. Here, up to seven stool samples were collected from each of 48 healthy children during their second year of life, and microbiota dynamics were assessed using 16S rRNA gene amplicon sequencing. Children's dietary information was also collected during the same period using a validated food frequency questionnaire designed for this age group, over five time points. We observed significant changes in gut microbiota community, concordant with changes in the children's dietary pattern over the 12-month period. In particular, we found differential effects on specific Firmicutes-affiliated lineages in response to frequent intake of either processed or unprocessed foods. Additionally, the consumption of fortified milk supplemented with a Bifidobacterium probiotic and prebiotics (synbiotics) further increased the presence of Bifidobacterium spp., highlighting the potential use of synbiotics to prolong and sustain changes in these lineages and shaping the gut microbiota community in young children.
Primary and acquired drug resistance imposes a major threat to achieving optimized clinical outcomes during cancer treatment. Aberrant changes in epigenetic modifications are closely involved in drug ...resistance of tumor cells. Using BET inhibitor (BETi) resistant leukemia cells as a model system, we demonstrated herein that genome-wide enhancer remodeling played a pivotal role in driving therapeutic resistance via compensational re-expression of pro-survival genes. Capitalizing on the CRISPR interference technology, we identified the second intron of IncRNA, PVT1, as a unique bona fide gained enhancer that restored MYC transcription independent of BRD4 recruitment in leukemia. A combined BETi and CDK7 inhibitor treatment abolished MYC transcription by impeding RNAPII loading without affecting PVT1-mediated chromatin looping at the MYC locus in BETi-resistant leukemia cells. Together, our findings have established the feasibility of targeting enhancer plasticity to overcome drug resistance associated with epigenetic therapies.
Despite ongoing investigation of children's eating behaviors to better understand the etiology of childhood obesity, few studies have aimed to determine differences in eating behavior based on ...psycho-social variables reflective of ‘stressful’ life circumstance.
Cross-sectional data collected from parents of 977 Australian children (2.0–5.0 years) in an online survey was used to determine associations between parent-reported Children's Eating Behavior Questionnaire CEBQ sub-scales, child BMI z-scores and psycho-social variables.
When examined individually, all CEBQ sub-scales, except Slowness in Eating, were associated with BMI z-score (Food Responsiveness B = 0.226, p = 0.003, Enjoyment of Food B = 0.169, p = 0.035, Food Fussiness B = −0.139, p = 0.024, Satiety Responsiveness B = −0.318, p = 0.001). On examining CEBQ sub-scales along with psycho-social demographic variables, only Food Responsiveness and Satiety Responsiveness were retained, along with being a boy, child age, and parent BMI.
Food Responsiveness was positively associated with parental stress and child age and negatively with parent BMI, while Enjoyment of Food was positively associated with child sleep duration, single parent status, and negatively with breastfeeding less than 6 months and parental depression. Satiety Responsiveness was positively associated with parent BMI and child age, and negatively with child sleep duration, while Food Fussiness was positively associated with child age and breastfeeding less than 6 months, and negatively with sleep duration, parental depression and single parent status.
Attention to eating behaviors and associated psycho-social variables may provide opportunity for targeted obesity prevention initiatives.
The mechanism by which antifreeze proteins (AFPs) irreversibly bind to ice has not yet been resolved. The ice-binding site of an AFP is relatively hydrophobic, but also contains many potential ...hydrogen bond donors/acceptors. The extent to which hydrogen bonding and the hydrophobic effect contribute to ice binding has been debated for over 30 years. Here we have elucidated the ice-binding mechanism through solving the first crystal structure of an Antarctic bacterial AFP. This 34-kDa domain, the largest AFP structure determined to date, folds as a Ca²âº-bound parallel beta-helix with an extensive array of ice-like surface waters that are anchored via hydrogen bonds directly to the polypeptide backbone and adjacent side chains. These bound waters make an excellent three-dimensional match to both the primary prism and basal planes of ice and in effect provide an extensive X-ray crystallographic picture of the AFP:ice interaction. This unobstructed view, free from crystal-packing artefacts, shows the contributions of both the hydrophobic effect and hydrogen bonding during AFP adsorption to ice. We term this mode of binding the "anchored clathrate" mechanism of AFP action.
Childhood obesity is an issue of public health concern that is understood to emerge due to disequilibrium in energy homeostasis. This commentary explores literature regarding neuro-biological ...mechanisms of energy homeostasis and the relationship between subjective measures of children’s eating behaviours and objective measures of appetite, in order to better understand the aetiology of childhood obesity. Early life influences, such as in utero exposure, breastfeeding, and general disadvantage, appear to have an important influence on neuro-biological mechanisms of appetite and may contribute to inequitable distributions of obesity within the population. Subject measures of eating behaviours appear to capture various aspects of neuro-biologically driven (objective) appetite systems, however, these systems are complex, interdependent and not yet fully understood. Future research focusing attention on early life influences on appetite and eating behaviours is warranted to increase understanding of differences in rates of obesity within the population, to determine opportunities for targeted obesity prevention initiatives, and to explore the potential to measure change in eating behaviours as a marker of appetite and obesity risk.
•Household fuel choices are rooted in their income, fuel access and occupation.•Socio-cultural traditions influence the choice of cooking fuel.•Reliable power supply unlocks the latent demand for ...cleaner fuel in rural areas.•Targeted and consistent policies form the pace and trajectory of energy transition.
Multiple fuel use, incorporated within the concept of fuel stacking is prevalent in households at the beginning and mid-way in their ascension up the energy ladder. However, households cannot fully let go of their traditional energy sources presenting inherent policy complexities and contradictions within energy transition theories. Empirical insights into the determinants of clean energy transitions are presented that highlight the need to recognise both fuel switching and stacking occurs in many rural households. It focuses on rural communities in India and illuminates policy dilemmas. The study reveals that fuel stacking is likely to remain a key part of the socio-cultural energy tradition that will impact progress towards low carbon and a cleaner energy transition. We therefore argue targeted policy interventions, multi-stakeholder collaboration and strong energy governance is needed to incorporate socio-cultural traditions particularly linked to cooking. This suggests new energy policy that must offer flexibility in order to achieve the twin goals of universal energy access and decarbonising energy systems.
Antifreeze proteins (AFPs) are a widespread class of proteins that bind to ice and facilitate the survival of organisms under freezing conditions. AFPs have enormous potential in applications that ...require control over ice growth. However, the nature of the binding interaction between AFPs and ice remains the subject of debate. Using a microfluidics system developed in-house we previously showed that hyperactive AFP from the Tenebrio molitor beetle, TmAFP, remains bound to an ice crystal surface after exchanging the solution surrounding the ice crystal to an AFP-free solution. Furthermore, these surface-adsorbed TmAFP molecules sufficed to prevent ice growth. These experiments provided compelling evidence for the irreversible binding of hyperactive AFPs to ice. Here, we tested a moderately active type III AFP (AFPIII) from a fish in a similar microfluidics system. We found, in solution exchange experiments that the AFPIIIs were also irreversibly bound to the ice crystals. However, some crystals displayed "burst" growth during the solution exchange. AFPIII, like other moderately active fish AFPs, is unable to bind to the basal plane of an ice crystal. We showed that although moderate AFPs bound to ice irreversibly, moderate AFPs in solution were needed to inhibit ice growth from the bipyramidal crystal tips. Instead of binding to the basal plane, these AFPs minimized the basal face size by stabilizing other crystal planes that converge to form the crystal tips. Furthermore, when access of solution to the basal plane was physically blocked by the microfluidics device walls, we observed enhancement of the antifreeze activity. These findings provide direct evidence that the weak point of ice growth inhibition by fish AFPs is the basal plane, whereas insect AFPs, which can bind to the basal plane, are able to inhibit its growth and thereby increase antifreeze activity.
We characterized the epidemiology, host–pathogen characteristics, and outcomes of severe adult pulmonary Streptococcus pyogenes infections that coincided with a high community caseload in central ...Scotland, UK. The pulmonary infections had high illness and death rates and were associated with socioeconomic deprivation, influenza A co-infection, and the M1UK lineage of S. pyogenes.
The hydropower sector is currently experiencing several technological developments. New technologies and practices are emerging to make hydropower more flexible and more sustainable. Novel materials ...have also been recently developed to increase performance, durability, and reliability; however, no systematic discussions can be found in the literature. Therefore, in this paper, novel materials for hydropower applications are presented, and their performance, advantages, and limitations are discussed. For example, composites can reduce the weight of steel equipment by 50% to 80%, polymers and superhydrophobic materials can reduce head losses by 4% to 20%, and novel bearing materials can reduce bearing wear by 6%. These improvements determine higher efficiencies, longer life span, waste reduction, and maintenance needs, although the initial cost of some materials is not yet competitive with respect to the costs of traditional materials. The novel materials are described here based on the following categories: novel materials for turbines, dams and waterways, bearings, seals, and ocean hydropower.
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