Translocation of tRNA and mRNA during protein synthesis is believed to be coupled to structural changes in the ribosome. The "ratchet model," based on cryo-EM reconstructions of ribosome complexes, ...invokes relative movement of the 30S and 50S ribosomal subunits in this process; however, evidence that directly demonstrates a requirement for intersubunit movement during translocation is lacking. To address this problem, we created an intersubunit disulfide cross-link to restrict potential movement. The cross-linked ribosomes were unable to carry out polypeptide synthesis; this inhibition was completely reversed upon reduction of the disulfide bridge. In vitro assays showed that the cross-linked ribosomes were specifically blocked in elongation factor G-dependent translocation. These findings show that intersubunit movement is required for ribosomal translocation, accounting for the universal two-subunit architecture of ribosomes.
The aim of this paper was to systematically review the published evidence on the relationship between the type of childcare and risk of childhood overweight or obesity. The databases PubMed, MEDLINE, ...Cochrane Library and EMBASE were searched using combinations of the various search terms to identify eligible observational studies published between 2000 and May 2016 in English. Fifteen publications from 7 countries matched the inclusion criteria. The most commonly reported childcare arrangements were centre-based (e.g. crèche) and informal care (e.g. relatives, neighbours, friends). Informal care was most frequently associated with an increased risk of childhood overweight and obesity. Associations were also found for other lifestyle variables such as low maternal education, high birth-weight, maternal employment, ethnicity, maternal overweight/obesity and father’s Body Mass Index (BMI).
Conclusion
: The relationship between childcare and childhood overweight/obesity is multi-faceted with many aspects linked to childhood adiposity, in particular the age of initiation to care, type of care (i.e. informal care) and shorter breastfeeding duration were related with infant adiposity.
What is known:
• Lifestyle factors during early years affect health outcomes in adulthood, particularly in children with low birth weight.
• Pre-school stage influences children’s body composition and growth.
What is new:
• This is the first systematic review of observational studies examining the association between childcare and childhood overweight and obesity in preschool children.
• ‘Informal’ care is linked to early introduction to solid foods, less physical activity and obesity.
Australia has a role to play in future global food security as it contributes 0·12 of global wheat exports. How much more can it contribute with current technology and varieties? The present paper ...seeks to quantify the gap between water-limited yield potential (Yw) and farmer yields (Ya) for wheat in Australia by implementing a new protocol developed by the Global Yield Gap and Water Productivity Atlas (GYGA) project. Results of past Australian yield gap studies are difficult to compare with studies in other countries because they were conducted using a variety of methods and at a range of scales. The GYGA project protocols were designed to facilitate comparisons among countries through the application of a consistent yet flexible methodology. This is the first implementation of GYGA protocols in a country with the high spatial and temporal climatic variability that exists in Australia. The present paper describes the application of the GYGA protocol to the whole Australian grain zone to derive estimates of rainfed wheat yield gap. The Australian grain zone was partitioned into six key agro-climatic zones (CZs) defined by the GYGA Extrapolation Domain (GYGA-ED) zonation scheme. A total of 22 Reference Weather Stations (RWS) were selected, distributed among the CZs to represent the entire Australian grain zone. The Agricultural Production Systems sIMulator (APSIM) Wheat crop model was used to simulate Yw of wheat crops for major soil types at each RWS from 1996 to 2010. Wheat varieties, agronomy and distribution of wheat cropping were held constant over the 15-year period. Locally representative dominant soils were selected for each RWS and generic sowing rules were specified based on local expertise. Actual yield (Ya) data were sourced from national agricultural data sets. To upscale Ya and Yw values from RWS to CZs and then to national scale, values were weighted according to the area of winter cereal cropping within RWS buffer zones. The national yield gap (Yg = Yw–Ya) and relative yield (Y% = 100 × Ya/Yw) were then calculated from the weighted values. The present study found that the national Yg was 2·0 tonnes (t)/ha and Y% was 47%. The analysis was extended to consider factors contributing to the yield gap. It was revealed that the RWS 15-year average Ya and Yw were strongly correlated (R
2 = 0·76) and that RWS with higher Yw had higher Yg. Despite variable seasonal conditions, Y% was relatively stable over the 15 years. For the 22 RWS, average Yg correlated positively and strongly with average annual rainfall amount, but surprisingly it correlated poorly with RWS rainfall variability. Similarly, Y% correlated negatively but less strongly (R
2 = 0·33) with RWS average annual rainfall, and correlated poorly with RWS rainfall variability, which raises questions about how Australian farmers manage climate risk. Interestingly a negative relationship was found between Yg and variability of Yw for the 22 RWS (R
2 = 0·66), and a positive relationship between Y% and Yw variability (R
2 = 0·23), which suggests that farmers in lower yielding, more variable sites are achieving yields closer to Yw. The Yg estimates appear to be quite robust in the context of estimates from other Australian studies, adding confidence to the validity of the GYGA protocol. Closing the national yield gap so that Ya is 0·80 of Yw, which is the level of Yg closure achieved consistently by the most progressive Australian farmers, would increase the average annual wheat production (20·9 million t in 1996/07 to 2010/11) by an estimated 15·3 million t, which is a 72% increase. This indicates substantial potential for Australia to increase wheat production on existing farmland areas using currently available crop varieties and farming practices and thus make a substantial contribution to achieving future global food security.
Vascular malformations that circumferentially surround end or near-end arteries are challenging to manage. Minimally invasive treatment options such as sclerotherapy can directly damage these vessels ...and cause ischemia. Surgical resection is desired without sacrificing or injuring a patent artery, especially in end organs like the upper limb. Microsurgical resection of these lesions provides a viable option for treatment.
The records of nine patients who presented with vascular malformations that circumferentially surrounded an artery in the upper limb were reviewed. The main indications for surgical intervention were pain or persistent growth. In each case, microsurgical technique using a microscope and microsurgical instruments was used to dissect the lesions free from the affected end arteries. Four digital arteries, three radial arteries, one brachial artery and one palmar arch were involved.
There were six venous malformations, two fibro-adipose vascular anomalies, and one lymphatic malformation. There were no cases of distal ischemia, bleeding, or functional compromise. Two patients experienced delayed wound healing. After a minimum follow-up of 1 year, only one patient experienced a small area of recurrence but had no pain.
Microsurgical dissection using a microscope and microsurgical instruments is a viable technique for resection of difficult vascular malformations that surround major arterial channels in the upper limb. This technique allows preservation of maximum blood supply while treating problematic lesions.
Climate risk assessment in cropping is generally undertaken in a top-down approach using climate records while critical farmer experience is often not accounted for. In the present study, set in ...south India, farmer experience of climate risk is integrated in a bottom-up participatory approach with climate data analysis. Crop calendars are used as a boundary object to identify and rank climate and weather risks faced by smallhold farmers. A semi-structured survey was conducted with experienced farmers whose income is predominantly from farming. Interviews were based on a crop calendar to indicate the timing of key weather and climate risks. The simple definition of risk as consequence × likelihood was used to establish the impact on yield as consequence and chance of occurrence in a 10-year period as likelihood. Farmers’ risk experience matches well with climate records and risk analysis. Farmers’ rankings of ‘good’ and ‘poor’ seasons also matched up well with their independently reported yield data. On average, a ‘good’ season yield was 1·5–1·65 times higher than a ‘poor’ season. The main risks for paddy rice were excess rains at harvesting and flowering and deficit rains at transplanting. For cotton, farmers identified excess rain at harvest, delayed rains at sowing and excess rain at flowering stages as events that impacted crop yield and quality. The risk assessment elicited from farmers complements climate analysis and provides some indication of thresholds for studies on climate change and seasonal forecasts. The methods and analysis presented in the present study provide an experiential bottom-up perspective and a methodology on farming in a risky rainfed climate. The methods developed in the present study provide a model for end-user engagement by meteorological agencies that strive to better target their climate information delivery.
The sarcin-ricin loop (SRL) of 23S rRNA in the large ribosomal subunit is a factor-binding site that is essential for GTP-catalyzed steps in translation, but its precise functional role is thus far ...unknown. Here, we replaced the 15-nucleotide SRL with a GAAA tetraloop and affinity purified the mutant 50S subunits for functional and structural analysis in vitro. The SRL deletion caused defects in elongation-factor-dependent steps of translation and, unexpectedly, loss of EF-Tu-independent A-site tRNA binding. Detailed chemical probing analysis showed disruption of a network of rRNA tertiary interactions that hold together the 23S rRNA elements of the functional core of the 50S subunit, accompanied by loss of ribosomal protein L16. Our results reveal an influence of the SRL on the higher-order structure of the 50S subunit, with implications for its role in translation.
Structured RNAs embedded in the untranslated regions (UTRs) of messenger RNAs can regulate gene expression. In bacteria, control of a metabolite gene is mediated by the self-cleaving activity of a ...ribozyme embedded in its 5′ UTR. This discovery has raised the question of whether gene-regulating ribozymes also exist in eukaryotic mRNAs. Here we show that highly active hammerhead ribozymes are present in the 3′ UTRs of rodent C-type lectin type II (Clec2) genes. Using a hammerhead RNA motif search with relaxed delimitation of the non-conserved regions, we detected ribozyme sequences in which the invariant regions, in contrast to the previously identified continuous hammerheads, occur as two fragments separated by hundreds of nucleotides. Notably, a fragment pair can assemble to form an active hammerhead ribozyme structure between the translation termination and the polyadenylation signals within the 3′ UTR. We demonstrate that this hammerhead structure can self-cleave both in vitro and in vivo, and is able to reduce protein expression in mouse cells. These results indicate that an unrecognized mechanism of post-transcriptional gene regulation involving association of discontinuous ribozyme sequences within an mRNA may be modulating the expression of several CLEC2 proteins that function in bone remodelling and the immune response of several mammals.
The hammerhead ribozyme has long been considered a prototype for understanding RNA catalysis, but discrepancies between the earlier crystal structures of a minimal hammerhead self-cleaving motif and ...various biochemical investigations frustrated attempt to understand hammerhead ribozyme catalysis in terms of structure. With the discovery that a tertiary contact distal from the ribozyme's active site greatly enhances its catalytic prowess, and the emergence of new corresponding crystal structures of full-length hammerhead ribozymes, a unified understanding of catalysis in terms of the structure is now possible. A mechanism in which the invariant residue G12 functions as a general base, and the 2'-OH moiety of the invariant G8, itself forming a tertiary base pair with the invariant C3, is the general acid, appears consistent with both the crystal structure and biochemical experimental results. Originally discovered in the context of plant satellite RNA viruses, the hammerhead more recently has been found embedded in the 3'-untranslated region of mature mammalian mRNAs, suggesting additional biological roles in genetic regulation.
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