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Abstract Habitat loss due to climate change may cause the extinction of the clonal species with a limited distribution range. Thus, determining the genetic diversity required for adaptability by these species in sensitive ecosystems can help infer the chances of their survival and spread in changing climate. We studied the genetic diversity and population structure of Sambucus wightiana—a clonal endemic plant species of the Himalayan region for understanding its possible survival chances in anticipated climate change. Eight polymorphic microsatellite markers were used to study the allelic/genetic diversity and population structure. In addition, ITS1–ITS4 Sanger sequencing was used for phylogeny and SNP detection. A total number of 73 alleles were scored for 37 genotypes at 17 loci for 8 SSRs markers. The population structural analysis using the SSR marker data led to identifying two sub-populations in our collection of 37 S. wightiana genotypes, with 11 genotypes having mixed ancestry. The ITS sequence data show a specific allele in higher frequency in a particular sub-population, indicating variation in different S. wightiana accessions at the sequence level. The genotypic data of SSR markers and trait data of 11 traits of S. wightiana, when analyzed together, revealed five significant Marker-Trait Associations (MTAs) through Single Marker Analysis (SMA) or regression analysis. Most of the SSR markers were found to be associated with more than one trait, indicating the usefulness of these markers for working out marker-trait associations. Moderate to high genetic diversity observed in the present study may provide insurance against climate change to S. wightiana and help its further spread.

Biogenesis of the photosynthetic enzyme Rubisco, a complex of eight large (RbcL) and eight small (RbcS) subunits, requires assembly chaperones. Here we analyzed the role of Rubisco accumulation factor1 (Raf1), a dimer of ∼40-kDa subunits. We find that Raf1 from Synechococcus elongatus acts downstream of chaperonin-assisted RbcL folding by stabilizing RbcL antiparallel dimers for assembly into RbcL8 complexes with four Raf1 dimers bound. Raf1 displacement by RbcS results in holoenzyme formation. Crystal structures show that Raf1 from Arabidopsis thaliana consists of a β-sheet dimerization domain and a flexibly linked α-helical domain. Chemical cross-linking and EM reconstruction indicate that the β-domains bind along the equator of each RbcL2 unit, and the α-helical domains embrace the top and bottom edges of RbcL2. Raf1 fulfills a role similar to that of the assembly chaperone RbcX, thus suggesting that functionally redundant factors ensure efficient Rubisco biogenesis. [ABSTRACT FROM AUTHOR]

Aim: Screening for non-valvular atrial fibrillation (NVAF) is key in identifying patients with undiagnosed disease who may be eligible for anticoagulation therapy. Understanding the economic value of screening is necessary to assess optimal strategies for payers and healthcare systems. We evaluated the cost effectiveness of opportunistic screening with handheld digital devices and pulse palpation, as well as targeted screening predictive algorithms for UK patients ≥75 years of age., Methods: A previously developed Markov cohort model was adapted to evaluate clinical and economic outcomes of opportunistic screening including pulse palpation, Zenicor (extended 14 days), KardiaMobile (extended), and two algorithms compared to no screening. Key model inputs including epidemiology estimates, screening effectiveness, and risks for medical events were derived from the STROKESTOP, ARISTOTLE studies, and published literature, and cost inputs were obtained from a UK national cost database. Health and cost outcomes, annually discounted at 3.5%, were reported for a cohort of 10,000 patients vs. no screening over a time horizon equivalent to a patient's lifetime, Analyses were performed from a UK National Health Services and personal social services perspective., Results: Zenicor, pulse palpation, and KardiaMobile were dominant (providing better health outcomes at lower costs) vs. no screening; both algorithms were cost-effective vs. no screening, with incremental cost-effectiveness ratios per quality-adjusted life-year (QALY) of £1,040 and £1,166. Zenicor, pulse palpation, and KardiaMobile remained dominant options vs. no screening in all scenarios explored. Deterministic sensitivity analyses indicated long-term stroke care costs, prevalence of undiagnosed NVAF in patients 75-79 years of age, and clinical efficacy of anticoagulant on stroke prevention were the main drivers of the cost-effectiveness results., Conclusions: Screening for NVAF at ≥75 years of age could result in fewer NVAF-related strokes. NVAF screening is cost-effective and may be cost-saving depending on the program chosen.

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), the key enzyme of the Calvin-Benson-Bassham cycle of photosynthesis, requires conformational repair by Rubisco activase for efficient function. Rubisco mediates the fixation of atmospheric CO 2 by catalyzing the carboxylation of the five-carbon sugar ribulose-1,5-bisphosphate (RuBP). It is a remarkably inefficient enzyme, and efforts to increase crop yields by bioengineering Rubisco remain unsuccessful. This is due in part to the complex cellular machinery required for Rubisco biogenesis and metabolic maintenance. To function, Rubisco must undergo an activation process that involves carboxylation of an active site lysine by a non-substrate CO 2 molecule and binding of a Mg 2+ ion. Premature binding of the substrate RuBP results in an inactive enzyme. Moreover, Rubisco can also be inhibited by a range of sugar phosphates, some of which are "misfire" products of its multistep catalytic reaction. The release of the inhibitory sugar molecule is mediated by the AAA+ protein Rubisco activase (Rca), which couples hydrolysis of ATP to the structural remodeling of Rubisco. Rca enzymes are found in the vast majority of photosynthetic organisms, from bacteria to higher plants. They share a canonical AAA+ domain architecture and form six-membered ring complexes but are diverse in sequence and mechanism, suggesting their convergent evolution. In this review, we discuss recent advances in understanding the structure and function of this important group of client-specific AAA+ proteins.