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Sucrose (Sue) synthase (Sus) is the major enzyme of Sue breakdown for cellulose biosynthesis in cotton (Gossypium hirsutum) fiber, an important source of fiber for the textile industry. This study examines the tissue-specific expression, relative abundance, and temporal expression of various Sus transcripts and proteins present in cotton. A novel isoform of Sus (SusC) is identified that is expressed at high levels during secondary cell wall synthesis in fiber and is present in the cell wall fraction. The phylogenetic relationships of the deduced amino acid sequences indicate two ancestral groups of Sus proteins predating the divergence of monocots and dicots and that SusC sequences form a distinct branch in the phylogeny within the dicotspecific clade. The subcellular location of the Sus isoforms is determined, and it is proposed that cell wall-localized SusC may provide UDP-glucose for cellulose and callóse synthesis from extracellular sugars.

Lipid droplets (LDs) are composed of a monolayer of phospholipids (PLs), surrounding a core of non-polar lipids that consist mostly of triacylglycerols (TAGs) and to a lesser extent diacylglycerols. In this study, lipidome analysis illustrated striking differences in non-polar lipids and PL species between LDs derived from seed kernels and mesocarp. In mesocarp LDs, the most abundant species of TAG contained one C18:1 and two C16:0 and fatty acids, while TAGs containing three C18 fatty acids with higher level of unsaturation were dominant in the seed kernel LDs. This reflects the distinct differences in fatty acid composition of mesocarp (palmitate-rich) and seed-derived oil (α-linoleneate-rich) in . Major PLs in seed LDs were found to be rich in polyunsaturated fatty acids, in contrast to those with relatively shorter carbon chain and lower level of unsaturation in mesocarp LDs. The LD proteome analysis in identified 207 proteins from mesocarp, and 54 proteins from seed kernel, which belong to various functional classes including lipid metabolism, transcription and translation, trafficking and transport, cytoskeleton, chaperones, and signal transduction. Oleosin and lipid droplets associated proteins (LDAP) were found to be the predominant proteins associated with LDs in seed and mesocarp tissues, respectively. We also show that LDs appear to be in close proximity to a number of organelles including the endoplasmic reticulum, mitochondria, peroxisomes, and Golgi apparatus. This comparative study between seed and mesocarp LDs may shed some light on the structure of plant LDs and improve our understanding of their functionality and cellular metabolic networks in oleaginous plant tissues.

Honeybee larvae produce silken cocoons that provide mechanical stability to the hive. The silk proteins are small and non-repetitive and therefore can be produced at large scale by fermentation in E. coli. The recombinant proteins can be fabricated into a range of forms; however the resultant material is soluble in water and requires a post production stabilizing treatment. In this study, we describe the structural and mechanical properties of sponges fabricated from artificial honeybee silk proteins that have been stabilized in aqueous methanol baths or by dry heating. Aqueous methanol treatment induces formation of ß-sheets, with the amount of ß-sheet dictated by methanol concentration. Formation of ß-sheets renders sponges insoluble in water and generates a reversibly compressible material. Dry heat treatments at 190°C produce a water insoluble material, that is stiffer than the methanol treated equivalent but without significant secondary structural changes. Honeybee silk proteins are particularly high in Lys, Ser, Thr, Glu and Asp. The properties of the heat treated material are attributed to generation of lysinoalanine, amide (isopeptide) and/or ester covalent cross-links. The unique ability to stabilize material by controlling secondary structure rearrangement and covalent cross-linking allows us to design recombinant silk materials with a wide range of properties.

Esterase activities associated with organophosphate insecticide resistance in the Australian sheep blowfly, Lucilia cuprina, are compared with similar activities in other Diptera. The enzymes making the major contribution to methyl butyrate hydrolysis (\"ali-esterase\") in L. cuprina, M. domestica, and D. melanogaster comigrate during electrophoresis. The enzymes in L. cuprina and D. melanogaster correspond to the naphthyl acetate hydrolyzing E3 and EST23 isozymes of those species. These and previously published data suggest that the ali-esterases of all three species are orthologous. Strains of L. cuprina fall into four groups on the basis of quantitative determinations of their ali-estesterase, OP hydrolase, and malathion carboxylesterase activities and these groups correspond to their status with respect to two types of OP resistance. Strains susceptible to OP's have high ali-esterase, low OP hydrolase, and intermediate MCE activities; those resistant to malathion but not diazinon have low ali-esterase, intermediate OP hydrolase, and high MCE activities; those resistant to diazinon but not malathion have low ali-esterase, high OP hydrolase, and low MCE activities; those resistant to both OPs have low ali-esterase, high OP hydrolase, and high MCE activities. The correlated changes among the three biochemical and two resistance phenotypes suggest that they are all properties of one gene/enzyme system; three major allelic variants of that system explain OP susceptibility and the two types of OP resistance. Models are proposed to explain the joint contribution of OP hydrolase and MCE activities to malathion resistance and the invariant association of low ali-esterase and elevated OP hydrolase activities in either type of resistance.

A U-Pb-He double-dating method is applied to detrital zircons with core-rim structure from the Ganges River in order to de- termine average short and long-term exhumation rates for the Himalayas. Long-term rates are calculated from the U/Pb ages of metamorphic rims of the grains that formed during the Himalayan orogeny and their crystallization temperatures, which are calculated from the Ti-in-zircon thermometer. Short-term rates are calculated from （U-Th）/He ages of the grains with appro- priate closure temperatures. The results show that short-term rates for the Himalayas, which range from 0.70 ± 0.09 to 2.67 ± 0.40 km/Myr and average 1.75 ± 0.59 （1δ） km/Myr, are higher and more varied than the long-term rates, which range from 0.84 ±0.16 to 1.85 ± 0.35 km/Myr and average 1.26 ±0.25 （let） km/Myr. The differences between the long-term and short-term rates can be attributed to continuous exhumation of the host rocks in different mechanisms in continental collision orogen. The U/Pb ages of 44.0 ± 3.7 to 18.3 ±0.5 Ma for the zircon rims indicate a protracted episode of -：25 Myr for regional metamorphism of the host rocks at deeper crust, whereas the （U-Th）/He ages of 42.2 ± 1.8 to 1.3 ± 0.2 Ma for the zircon grains represent a protracted period of -40 Myr for exposure of the host rocks to shallower crustal level. In particular, the oldest （U-Th）/He ages of the zircon grains are close to the oldest U/Pb ages for the rims, indicating that some parcels of the rocks that contain zircons were rapidly exhumed from deep to shallow levels in the stage of collisional orogeny. On the other hand, some parcels of the rocks may have been carried upwards by thrust faults in the post-collisional stage. The parcels could be carried upwards by the thrust faults that steepen as they near the surface, or by transient movement faults so that areas of rapid exhu- mation became areas of slow exhumation and visa versa on a time scale of a few Myr in order to maintain the continuous ex- humation. In this regard, the Ganges River must be preferentially sampling areas that are currently undergoing above average rates of uplift.

The Consolidated Standards of Reporting Trials (CONSORT) statement is a guideline designed to improve the transparency and quality of the reporting of randomised controlled trials (RCTs). In this article we present an extension to that statement for randomised pilot and feasibility trials conducted in advance of a future definitive RCT. The checklist applies to any randomised study in which a future definitive RCT, or part of it, is conducted on a smaller scale, regardless of its design (eg, cluster, factorial, crossover) or the terms used by authors to describe the study (eg, pilot, feasibility, trial, study). The extension does not directly apply to internal pilot studies built into the design of a main trial, non-randomised pilot and feasibility studies, or phase II studies, but these studies all have some similarities to randomised pilot and feasibility studies and so many of the principles might also apply.The development of the extension was motivated by the growing number of studies described as feasibility or pilot studies and by research that has identified weaknesses in their reporting and conduct. We followed recommended good practice to develop the extension, including carrying out a Delphi survey, holding a consensus meeting and research team meetings, and piloting the checklist.The aims and objectives of pilot and feasibility randomised studies differ from those of other randomised trials. Consequently, although much of the information to be reported in these trials is similar to those in randomised controlled trials (RCTs) assessing effectiveness and efficacy, there are some key differences in the type of information and in the appropriate interpretation of standard CONSORT reporting items. We have retained some of the original CONSORT statement items, but most have been adapted, some removed, and new items added. The new items cover how participants were identified and consent obtained; if applicable, the prespecified criteria used to judge whether or how to proceed with a future definitive RCT; if relevant, other important unintended consequences; implications for progression from pilot to future definitive RCT, including any proposed amendments; and ethical approval or approval by a research review committee confirmed with a reference number.This article includes the 26 item checklist, a separate checklist for the abstract, a template for a CONSORT flowchart for these studies, and an explanation of the changes made and supporting examples. We believe that routine use of this proposed extension to the CONSORT statement will result in improvements in the reporting of pilot trials.Editor’s note: In order to encourage its wide dissemination this article is freely accessible on the BMJ and Pilot and Feasibility Studies journal websites.

The mRNA-1273 vaccine was approved for emergency use in December 2020; trial participants who received placebo were informed of the results and offered vaccination. At the close of the blinded phase of the trial, the vaccine efficacy in preventing Covid-19 illness was 93.2%, and the efficacy against severe disease was 98.2%. No new safety issues were identified.

How somatic mutations accumulate in normal cells is central to understanding cancer development but is poorly understood. We performed ultradeep sequencing of 74 cancer genes in small (0.8 to 4.7 square millimeters) biopsies of normal skin. Across 234 biopsies of sun-exposed eyelid epidermis from four individuals, the burden of somatic mutations averaged two to six mutations per megabase per cell, similar to that seen in many cancers, and exhibited characteristic signatures of exposure to ultraviolet light. Remarkably, multiple cancer genes are under strong positive selection even in physiologically normal skin, including most of the key drivers of cutaneous squamous cell carcinomas. Positively selected mutations were found in 18 to 32% of normal skin cells at a density of ∼140 driver mutations per square centimeter. We observed variability in the driver landscape among individuals and variability in the sizes of clonal expansions across genes. Thus, aged sun-exposed skin is a patchwork of thousands of evolving clones with over a quarter of cells carrying cancer-causing mutations while maintaining the physiological functions of epidermis.

In two randomized trials conducted under home conditions, investigators compared closed-loop insulin delivery with sensor-augmented pump therapy in adults and in children and adolescents for 12 weeks. The closed-loop approach improved glucose control and reduced hypoglycemia. Intensive insulin therapy is the standard of care for type 1 diabetes but is limited by the risk of hypoglycemia, 1 which leads to failure in achieving treatment goals for most patients in all age groups. 2 , 3 Among patients with type 1 diabetes, hypoglycemia is common, has a major effect on patients’ quality of life and psychological well-being, 4 and may cause seizures, which is of particular concern during the overnight hours in children and adolescents. 5 New approaches (e.g., continuous glucose monitoring) can improve glycemic control when the patient wears the sensors on a regular basis. 6 , 7 If insulin delivery is linked . . .