Search

C4 photosynthesis is thought to have evolved via intermediate stages, with changes towards the C4 phenotype gradually enhancing photosynthetic performance. This hypothesis is widely supported by modelling studies, but experimental tests are missing. Mixing of C4 components to generate artificial intermediates can be achieved via crossing, and the grass Alloteropsis semialata represents an outstanding system since it includes C4 and non-C4 populations. Here, we analyse F1 hybrids between C3 and C4, and C3+C4 and C4 genotypes to determine whether the acquisition of C4 characteristics increases photosynthetic performance. The hybrids have leaf anatomical characters and C4 gene expression profiles that are largely intermediate between those of their parents. Carbon isotope ratios are similarly intermediate, which suggests that a partial C4 cycle coexists with C3 carbon fixation in the hybrids. This partial C4 phenotype is associated with C4-like photosynthetic efficiency in C3+C4 x C4, but not in C3 x C4 hybrids, which are overall less efficient than both parents. Our results support the hypothesis that the photosynthetic gains from the upregulation of C4 characteristics depend on coordinated changes in anatomy and biochemistry. The order of acquisition of C4 components is thus constrained, with C3+C4 species providing an essential step for C4 evolution.

Lateral gene transfer (LGT) has been reported in multiple eukaryotes. This process seems particularly widespread in the grass family, although we know very little about the underlying dynamics and how it impacts gene content variation within a species.Alloteropsis semialatais a tropical grass, and multiple LGT were detected in a reference genome assembled from an Australian individual. As part of this study we assemble three additionalde novogenomes forA. semialataand one for its sister speciesAlloteropsis angusta. In total we detect 168 LGT across the five reference genomes. Using whole-genome resequencing data for a further 40 individuals we establish the distribution of these transfers and map their origin along the species phylogeny. This shows that many LGTs were acquired relatively recently, with numerous secondary losses. Exponential decay models indicate that the rate of LGT acquisitions varied significantly among lineages [6-28 per Ma], with a high rate of subsequent LGT losses [11-24% per Ma] that largely exceeds that of native loci [0.02-0.8% per Ma]. This high turnover creates large intraspecific structural variants, with a preponderance of LGT occurring as accessory genes in theAlloteropsispangenome. The acquired genes represent unparalleled genetic novelties, having independently evolved for tens of millions of years before they were transferred. Ultimately, the rapid LGT turnover generates standing variation that can fuel local adaptation.

Purpose Cardiovascular disease (CVD) is the first cause of death in patients with non-alcoholic fatty liver disease (NAFLD) and risk stratification is recommended by current guidelines. The aim of this study is to assess the prevalence of peripheral arterial disease (PAD) in patients with NAFLD and its association with all-cause and cardiovascular disease (CVD) mortality. Methods 9145 participants 40 years or older attended a mobile examination center visit in the 1999–2004 cycles of the National Health and Nutrition Examination Survey. PAD was defined as an ankle-brachial index (ABI) Results The overall prevalence of PAD was 5.9% (95% CI 5.0–6.9). Over a median follow-up of 13 years, 876 participants died, 208 of cardiovascular causes. Incidence rates of all-cause mortality (for 1000 person-years) were 20.2 (95% CI 18.7–21.7) and 70.0 (95% CI 60.1–81.6) for participants without and with PAD, respectively. Multivariable-adjusted Cox proportional hazard models showed that PAD was associated with a higher risk of all-cause (1.8, 95% CI 1.4–2.4) and cardiovascular mortality (HR 2.5, 95% CI 1.5–4.3) after adjustment for potential confounders including prevalent CVD. Conclusion Current guidelines strongly encourage the screening of CVD in patients with NAFLD and the use of the simple and inexpensive measurement of ABI in routine clinical practice may find indication.

C

C4 photosynthesis is a complex trait that boosts productivity in warm environments. Paradoxically, it evolved independently in numerous plant lineages, despite requiring specialised leaf anatomy. The anatomical modifications underlying C4 evolution have previously been evaluated through interspecific comparisons, which capture numerous changes besides those needed for C4 functionality. Here, we quantify the anatomical changes accompanying the transition between non‐C4 and C4 phenotypes by sampling widely across the continuum of leaf anatomical traits in the grass Alloteropsis semialata. Within this species, the only trait that is shared among and specific to C4 individuals is an increase in vein density, driven specifically by minor vein development that yields multiple secondary effects facilitating C4 function. For species with the necessary anatomical preconditions, developmental proliferation of veins can therefore be sufficient to produce a functional C4 leaf anatomy, creating an evolutionary entry point to complex C4 syndromes that can become more specialised.

SummaryIn the absence of strong reproductive barriers, genetic exchanges between closely related groups of organisms with different adaptations have well-documented beneficial and detrimental consequences. In plants, pollen-mediated exchanges affect the sorting of alleles across physical landscapes, and influence rates of hybridisation. How these dynamics affect the emergence and spread of novel ecological strategies remains only partially understood.We use phylogenomics and population genomics to retrace the origin of two geographically overlapping ecotypes of the African grass Alloteropsis angusta.We report the existence of a previously undescribed ecotype inhabiting miombo woodlands and grasslands. The two ecotypes have divergent nuclear genomes. However, the seed-transported chloroplast genomes are consistently shared by distinct ecotypes inhabiting the same region. These patterns suggest that the nuclear genome of one ecotype can reach the seeds of the other via pollen movements, with strong selection subsequently sorting nuclear alleles by habitat.The contrasting ecotypes of A. angusta can use each other as a gateway to new locations across a large part of Africa. Coupled with newly discovered hybridisation with the sister species A. semialata, our results show that hybridisation can facilitate the geographical dispersal of distinct ecotypes of the same grass species.

Geographical isolation facilitates the emergence of distinct phenotypes within a single species, but reproductive barriers or selection are needed to maintain the polymorphism after secondary contact. Here, we explore the processes that maintain intraspecific variation of C4 photosynthesis, a complex trait that results from the combined action of multiple genes. The grass Alloteropsis semialata includes C4 and non-C4 populations, which have coexisted as a polyploid series for more than 1 million years in the miombo woodlands of Africa. Using population genomics, we show that there is genome-wide divergence for the photosynthetic types, but the current geographical distribution does not reflect a simple habitat displacement scenario as the genetic clusters overlap, being occasionally mixed within a given habitat. Despite evidence of recurrent introgression between non-C4 and C4 groups, in both diploids and polyploids, the distinct genetic lineages retain their identity, potentially because of selection against hybrids. Coupled with strong isolation by distance within each genetic group, this selection created a geographical mosaic of photosynthetic types. Diploid C4 and non-C4 types never grew together, and the C4 type from mixed populations constantly belonged to the hexaploid lineage. By limiting reproductive interactions between photosynthetic types, the ploidy difference probably allows their co-occurrence, reinforcing the functional diversity within this species. Together, these factors enabled the persistence of divergent physiological traits of ecological importance within a single species despite gene flow and habitat overlap., This work was funded by the European Research Council (grant ERC-2014-STG-638333) and the Natural Environment Research Council (grant NE/M00208X/1). M.E.B. is supported by the Royal Society (RGF\EA\181050) and P.A.C. is funded by a Royal Society University Research Fellowship (grant URF\R\180022)., 1 INTRODUCTION 2 MATERIAL AND METHODS 2.1 Population sampling and determination of photosynthetic types 2.2 Estimation of genome sizes 2.3 Population-level RAD sequencing and genotyping 2.4 Phylogenetic analyses, population structure and tests for isolation by distance 2.5 Tests for introgression 2.6 Genome scans 3 RESULTS 3.1 Different photosynthetic types can co-occur in the same location 3.2 C4 and non-C4 types correspond to different genetic groups 3.3 In mixed populations, photosynthetic types are associated with distinct ploidy levels 3.4 Distinct genetic groups are maintained despite gene flow 3.5 Genetic differentiation is widespread across the genome 4 DISCUSSION 4.1 Photosynthetic types can share the same habitat 4.2 Low dispersal probably prevents the homogenization of photosynthetic types among diploids 4.3 Polyploidization enables co-occurrence of different photosynthetic types 5 CONCLUSIONS ACKNOWLEDGEMENTS AUTHOR CONTRIBUTIONS

C 4 photosynthesis evolved multiple times independently in angiosperms, but most origins are relatively old so that the early events linked to photosynthetic diversification are blurred. The grass Alloteropsis semialata is an exception, as this species encompasses C 4 and non-C 4 populations. Using phylogenomics and population genomics, we infer the history of dispersal and secondary gene flow before, during and after photosynthetic divergence in A. semialata . We further analyse the genome composition of individuals with varied ploidy levels to establish the origins of polyploids in this species. Detailed organelle phylogenies indicate limited seed dispersal within the mountainous region of origin and the emergence of a C 4 lineage after dispersal to warmer areas of lower elevation. Nuclear genome analyses highlight repeated secondary gene flow. In particular, the nuclear genome associated with the C 4 phenotype was swept into a distantly related maternal lineage probably via unidirectional pollen flow. Multiple intraspecific allopolyploidy events mediated additional secondary genetic exchanges between photosynthetic types. Overall, our results show that limited dispersal and isolation allowed lineage divergence, with photosynthetic innovation happening after migration to new environments, and pollen-mediated gene flow led to the rapid spread of the derived C 4 physiology away from its region of origin.

Geographical isolation facilitates the emergence of distinct phenotypes within a single species, but reproductive barriers or selection is needed to maintain the polymorphism after secondary contact. Here, we explore the processes that maintain intraspecific variation of C4 photosynthesis, a complex trait that results from the combined action of multiple genes. The grass Alloteropsis semialata includes C4 and non-C4 populations, which have co-existed for more than one million years in the miombo woodlands of Africa. Using population genomics, we show that there is genome-wide divergence for the photosynthetic types, but the current distribution is not a result of a simple habitat displacement scenario as the genetic clusters overlap in ecology and geography, being occasionally mixed within a given habitat. We find evidence of introgression between photosynthetic types, but hybrids are rare and no clear hybrid zone is formed. Selection against hybrids likely limits gene flow and differentiation is accentuated in multiple parts of the genome pointing to selection on numerous genes. Coupled with strong isolation by distance within each genetic group, this selection created a geographical mosaic of photosynthetic types, which was further reinforced by recurrent polyploidization. Together, these factors enabled the persistence of divergent physiological traits of ecological importance within a single species despite gene flow and habitat overlap.

SummaryC4 photosynthesis evolved multiple times independently in angiosperms, but most origins are relatively old so that the early events linked to photosynthetic diversification are blurred. The grass Alloteropsis semialata is an exception, as this single species encompasses C4 and non-C4 populations.Using phylogenomics and population genomics, we infer the history of dispersal and secondary exchanges before, during, and after photosynthetic divergence in A. semialata. We further establish the genetic origins of polyploids in this species.Organelle phylogenies indicate limited seed dispersal within the Central Zambezian region of Africa, where the species originated ∼ 2–3 Ma. Outside this region, the species spread rapidly across the paleotropics to Australia. Comparison of nuclear and organelle phylogenies and analyses of whole genomes reveal extensive secondary gene flow. In particular, the genomic group corresponding to the C4 trait was swept into seeds from distinct geographic regions. Multiple segmental allopolyploidy events mediated additional secondary genetic exchanges between photosynthetic types.Limited dispersal and isolation allowed lineage divergence, while episodic secondary exchanges led to the pollen-mediated, rapid spread of the derived C4 physiology. Overall, our study suggests that local adaptation followed by recurrent secondary gene flow promoted physiological diversification in this grass species.

Single pdf containing six figures and one table.

To identify factors driving soil respiration (Rsoil) in a tropical C4-dominated perennial managed grassland ecosystem exposed to elevated carbon (C) dioxide concentration ([CO2]) and temperature. The perennial grass Panicum maximum was grown at 600 μmol CO2 mol−1 and + 2 °C above ambient temperatures for one full growing cycle (from grazing to regrowth for about ~30–45 days) using a free-air CO2 and infrared warming system. Plant growth and CO2 fluxes were measured during the growing cycle. Both high [CO2] and warming increased canopy photosynthesis but warming alone increased biomass by 53% and Rsoil by 26%. There was a strong diel effect on Rsoil, which was 16% greater at noon than at 18:00 h. Rsoil had low sensitivity to soil temperature (Q10 ~ 1) regardless of the CO2 treatment. In this tropical managed pasture, diel variation in photosynthesis strongly affected Rsoil, suggesting that Rsoil may be more limited by substrate availability than abiotic factors such as temperature. Predicted changes in climate for the region will likely affect the C dynamics of C4-dominated tropical pastures. Although, the short-term experiment may limit the extrapolations of our findings, the highly controlled settings of the experiment highlighted the role of canopy photosynthesis on Rsoil respiration in tropical C4-pastures.

Natural history collections are traditionally used for taxonomic research, but their relevance can extend into studies of molecular evolution as illustrated here using the example of C4 photosynthesis. This complex trait boosts growth in open and warm conditions and evolved numerous times, providing multiple comparisons among C3 and C4 relatives. Previous genomic studies relied on comparisons of model species which are often separated by long-time divergence. The large C4 group Andropogoneae (Poaceae) was usually compared to relatively distant C3 taxa. Early-diverging C4 Andropogoneae and closely related C3 taxa are known but are difficult to collect and hence have not been sequenced yet. We show here that genome scans generated from herbarium samples can be used to retrace the evolution of βca genes, which encode beta carbonic anhydrase, an enzyme of the C4 pathway. Genomic fragments encompassing βca genes were assembled for specimens of phylogenetic importance, and their comparison to model grasses made it possible to distinguish changes that happened during the transition to C4 from those that preceded or followed it. Tandem gene duplications occurred during the early grass diversification, and the duplicate that retained the ancestral alternative exon conferring chloroplast localization was later co-opted for C4 photosynthesis. Early transition to C4 photosynthesis apparently relied on an increase of the cytosolic alternative transcript without drastic changes in the βca gene, which occurred later during the diversification of C4 groups. These insights into the genomic rearrangements linked to the evolution of an adaptive trait highlight the potential of natural history collections for genomic analyses.

Background: Antithyroid drugs (ATDs) are first-line treatment for Graves’ hyperthyroidism worldwide, but relapses are frequent. The reliability of individual risk factors to predict at baseline subsequent relapse is poor. Predictive scores grouping single risk factors might help to select the best treatment (pharmacological vs. ablative). Objective: To assess the predictivity of a recently developed score (Clinical Severity Score, CSS) and to compare it with another score (GREAT score). Patients: A retrospective observational, single-center study was conducted of 387 consecutive, newly diagnosed Graves’ patients, who completed an 18–24 months ATD course and were followed for at least 2 years. Results: Hyperthyroidism relapsed in 185 patients (48%). At diagnosis and before treatment, the relapse group had higher serum TSH-receptor antibody and free thyroxine levels and larger goiters than the remission group, with no differences in Graves’ orbitopathy prevalence and severity. In the multivariate analyses, only large goiter size was significantly associated with an increased recurrence hazard ratio. Using CSS, the risk of relapse increased from 36% in the mild category and 49% in the moderate category to 59% in the severe category, with quite a good area under the curve (AUC) (0.60; 95% CI: 0.55; 0.66). GREAT score showed an increase in relapse from 34% for class I (mild) and 49% for class II (moderate) to 64% for class III (severe) (AUC, 0.63; CI: 0.58; 0.68). Conclusions: Both CSS and GREAT score are useful, although imperfect, tools to predict at baseline relapse of hyperthyroidism after treatment. In real life they may help the clinician to tailor a treatment for newly diagnosed Graves’ hyperthyroidism.

Recurrent duplication of two key C4 genes during the emergence of a C4 cycle in the grass genus Alloteropsis is correlated with increases in transcript abundance, The importance of gene duplication for evolutionary diversification has been mainly discussed in terms of genetic redundancy allowing neofunctionalization. In the case of C4 photosynthesis, which evolved via the co-option of multiple enzymes to boost carbon fixation in tropical conditions, the importance of genetic redundancy has not been consistently supported by genomic studies. Here, we test for a different role for gene duplication in the early evolution of C4 photosynthesis, via dosage effects creating rapid step changes in expression levels. Using genome-wide data for accessions of the grass genus Alloteropsis that recently diversified into different photosynthetic types, we estimate gene copy numbers and demonstrate that recurrent duplications in two important families of C4 genes coincided with increases in transcript abundance along the phylogeny, in some cases via a pure dosage effect. While increased gene copy number during the initial emergence of C4 photosynthesis probably offered a rapid route to enhanced expression, we also find losses of duplicates following the acquisition of genes encoding better-suited isoforms. The dosage effect of gene duplication might therefore act as a transient process during the evolution of a C4 biochemistry, rendered obsolete by the fixation of regulatory mutations increasing expression levels.

C\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$_{4}$\end{document} photosynthesis is a complex trait that sustains fast growth and high productivity in tropical and subtropical conditions and evolved repeatedly in flowering plants. One of the major C\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$_{4}$\end{document} lineages is Andropogoneae, a group of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\sim $\end{document}1200 grass species that includes some of the world’s most important crops and species dominating tropical and some temperate grasslands. Previous efforts to understand C\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$_{4}$\end{document} evolution in the group have compared a few model C\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$_{4}$\end{document} plants to distantly related C\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$_{3}$\end{document} species so that changes directly responsible for the transition to C\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$_{4}$\end{document} could not be distinguished from those that preceded or followed it. In this study, we analyze the genomes of 66 grass species, capturing the earliest diversification within Andropogoneae as well as their C\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$_{3}$\end{document} relatives. Phylogenomics combined with molecular dating and analyses of protein evolution show that many changes linked to the evolution of C\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$_{4}$\end{document} photosynthesis in Andropogoneae happened in the Early Miocene, between 21 and 18 Ma, after the split from its C\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$_{3}$\end{document} sister lineage, and before the diversification of the group. This initial burst of changes was followed by an extended period of modifications to leaf anatomy and biochemistry during the diversification of Andropogoneae, so that a single C\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$_{4}$\end{document} origin gave birth to a diversity of C\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$_{4}$\end{document} phenotypes during 18 million years of speciation events and migration across geographic and ecological spaces. Our comprehensive approach and broad sampling of the diversity in the group reveals that one key transition can lead to a plethora of phenotypes following sustained adaptation of the ancestral state. [Adaptive evolution; complex traits; herbarium genomics; Jansenelleae; leaf anatomy; Poaceae; phylogenomics.]

IgG4-related hypophysitis (IgG4-RH) is a rare disease, which can occur singularly or as manifestation of a systemic IgG4-related disease (IgG4-RD). Less than one hundred cases have been reported in the literature, very few of which were histopathologically documented. We analyzed the clinical, radiological, and histopathological features of two cases of IgG4-RH, the former observed in a 66-year-old man in the context of an IgG4-RD, and the latter affecting a 21-year-old woman, as an isolated lesion. In addition, we performed a comprehensive review of the previously published histopathologically documented cases of IgG4-RH. Pituitary samples from both patients showed dense lymphoplasmacytic infiltration, interstitial and storiform fibrosis, and high numbers of IgG4-positive plasma cells, consistent with IgG4-RH. From the literature review, we retrieved 18 papers reporting a total of 22 cases of histopathologically documented IgG4-RH. The revision of these cases, also including the two reported herein, showed an equal distribution of IgG4-RH in the two sexes, albeit significant clinico-pathological variation was found between cases arisen in female and male patients, respectively. In detail, IgG4-RH females were affected in their second-third decade of life, with a solitary pituitary lesion, low IgG4 serum level, and frequent association with autoimmune disorders. By contrast, IgG4-RH in men was a disease of the elderly, often in the context of a systemic IgG4-RD, with high IgG4 serum levels. Our study shows that IgG4-RH, as currently defined, is a clinically heterogenous disease, with different features in the two sexes. Indeed, cases diagnosed in young women, as our case 2, mostly do not present other evidence of IgG4-RD and might be better classified as lymphocytic hypophysitis with abundant IgG4+ plasma cells. For this reason, the histopathological examination of the pituitary lesion, particularly in female patients, may still be useful for a correct differential diagnosis with other variants of primary hypophysitis.

The ability to efficiently scavenge nutrients in the host is essential for the viability of any pathogen. All catabolic pathways must begin with the transport of substrate from the environment through the cytoplasmic membrane, a role executed by membrane transporters. Although several classes of cytoplasmic membrane transporters are described, high-affinity uptake of substrates occurs through Solute Binding-Protein (SBP) dependent systems. Three families of SBP dependant transporters are known; the primary ATP-binding cassette (ABC) transporters, and the secondary Tripartite ATP-independent periplasmic (TRAP) transporters and Tripartite Tricarboxylate Transporters (TTT). Far less well understood than the ABC family, the TRAP transporters are found to be abundant among bacteria from marine environments, and the TTT transporters are the most abundant family of proteins in many species of β-proteobacteria. In this review, recent knowledge about these families is covered, with emphasis on their physiological and structural mechanisms, relating to several examples of relevant uptake systems in pathogenicity and colonization, using the SiaPQM sialic acid uptake system from Haemophilus influenzae and the TctCBA citrate uptake system of Salmonella typhimurium as the prototypes for the TRAP and TTT transporters, respectively. High-throughput analysis of SBPs has recently expanded considerably the range of putative substrates known for TRAP transporters, while the repertoire for the TTT family has yet to be fully explored but both types of systems most commonly transport carboxylates. Specialized spectroscopic techniques and site-directed mutagenesis have enriched our knowledge of the way TRAP binding proteins capture their substrate, while structural comparisons show conserved regions for substrate coordination in both families. Genomic and protein sequence analyses show TTT SBP genes are strikingly overrepresented in some bacteria, especially in the β-proteobacteria and some α-proteobacteria. The reasons for this are not clear but might be related to a role for these proteins in signaling rather than transport.

Hypothyroidism is complicated by neuromuscular symptoms (myalgias, slowness of movements, and tiredness) and signs (easy fatigability and cramps), which may have a negative impact on general well-being and quality of life. In a pilot, prospective, controlled study, we investigated the features of muscle dysfunction in hypothyroidism by disease questionnaire, biochemical measures, and physical performance tests.Fifty-seven consecutive patients with newly diagnosed hypothyroidism were enrolled, 27 subclinical (S-Hypo) and 30 overt (O-Hypo). A series of 30 euthyroid subjects, with similar demographic characteristics, served as controls. Patients were administered a short disease questionnaire and underwent laboratory exams and standardized physical tests, both at baseline and after restoration of biochemical euthyroidism.Compared to euthyroid controls, the O-Hypo group showed significantly higher prevalence of neuromuscular symptoms and significantly higher serum creatine phosphokinase (CPK) levels (p value 0.0001). S-Hypo had slightly higher CPK levels and prevalence of neuromuscular symptoms than controls. Both S-Hypo and O-Hypo patients performed worse than controls in the six-minute walking test. Differences between patients and controls in handgrip strength test and timed chair standing test failed to reach statistical significance (although a trend was noticeable), possibly due to the small sample size. In O-Hypo, an inverse correlation was found between CPK levels and the handgrip strength test (p value 0.001). Restoration of euthyroidism was associated with normalization of questionnaire responses, six-minute walking test, as well as serum CPK levels.In addition to neuromuscular symptoms, hypothyroidism is associated with abnormalities of physical performance. The six-minute walking test is the most valuable test to assess this aspect. In the pilot study, levothyroxine therapy could reverse muscle functional abnormalities.

The Merseburg triad (hyperthyroidism, goiter, and orbitopathy) characterizes classical description of Graves’ disease (GD). Aim of this observational, longitudinal study was to evaluate the current clinical features of newly diagnosed GD in Italy. In two Northern Italy centers (Varese and Pavia), 283 consecutive patients (211 women, 72 men; mean age 47.4 years) with newly diagnosed GD were recruited in the years 2010–2014. Diagnosis was based on established criteria, and thyroid volume was assessed by ultrasonography. A clinical severity score (CSS) to assess the overall disease severity was developed by grading each component of the Merseburg triad. At diagnosis, 45 % of patients had no goiter, and 30 % had a small goiter. The proportion of goitrous patients was much lower than in two Italian studies performed 20–30 years ago. Hyperthyroidism was subclinical in 16 % and mild in 29 % of patients, and Graves’ orbitopathy was present in 20 %, usually mild, and active in only 2.5 % of patients. Using the CSS, less than half (44 %) of the patients had severe GD, while 22 % had mild and 34 % moderate disease. CSS was associated with a significantly higher risk of poorly controlled hyperthyroidism at 6 months. In Italy, a relevant proportion of Graves’ patients at diagnosis have mild to moderate GD; about half of them have no goiter, slightly less than one-fifth have subclinical hyperthyroidism, and only 20 % have GO. Thus, the clinical phenotype of GD is milder than in the past, possibly due to both earlier diagnosis and treatment, and improved iodine nutrition.

This paper introduces a novel maximum power point tracking (MPPT) technique aimed at maximizing the power produced by photovoltaic (PV) systems. The largest part of the MPPT approaches presented in the literature are based on the sensing of the PV generator voltage. On the contrary, in this paper, a current-based technique is proposed: the sensing of the current in the capacitor placed in parallel with the PV source is one of the innovative aspects of the proposal. A dual control technique based on an inner current loop plus an outer voltage loop allows to take profit of the fast current tracking capability of the inner current loop while the voltage loop benefits from the logarithmic dependency of the PV voltage on the irradiation level. The features of the proposed algorithm, particularly in terms of tracking of irradiation variations and disturbance rejection, are supported by theoretical analysis, simulations, and experimental results. The technique described in this paper is patent pending.

Stylosanthes capitata Vogel is an important forage legume in tropical and subtropical regions. To study the response of S. capitata to the moderate warming expected as a result of climate change, plants were subjected to elevated temperature (2 °C increase over the ambient temperature) in a temperature free-air controlled enhancement (T-FACE) facility. Photosystem II (PSII) performance, the activity of antioxidant enzymes, the chlorophyll index, the leaf area index (LAI) and the aboveground biomass production were evaluated. The maximum PSII quantum yield (FV/FM) and the quantum yield of regulated energy dissipation Y (NPQ) were not affected by the warming. However, we observed a significant increase in the electron transport rate (ETR), the non-photochemical energy dissipation (NPQ), the effective PSII quantum yield Y(II) and the coefficient of photochemical quenching (qP) in the warmed leaves compared with the control leaves. In contrast, a significant reduction in the quantum yield of the relative reduction state of QA (1-qP) and non-regulated power dissipation Y(NO) was observed in the warmed leaves. The increase in ETR under moderate warming was associated with the increase (31%) in chlorophyll content. The activities of antioxidant enzymes increased in the leaves of the warmed plants, but the malondialdehyde (MDA) content of the leaves was not affected by warming, suggesting that higher levels of the antioxidant defense system induced by warming may improve the protection of photosynthesis against oxidative damage and attenuate the destructive effects of reactive oxygen species. As a result of warming, leaf area index (LAI) and biomass production increased by 32% and 16%, respectively. The improved PSII functioning of the warmed leaves of S. capitata may reflect their capacity to acclimate better to warming growth conditions. We conclude that the warming induced by increasing the temperature by 2 °C, under non stressing conditions, was beneficial for the physiology and for the biophysical and physiological processes involved in plant growth of S. capitata, suggesting that slight increases in the leaf temperature may benefit some plants, especially those in tropical environments.

Today's solutions for motor control applications require more flexibility and a higher level of integration that could be achieved only through specialized products. This paper presents the analysis of the first results obtained from a new family of intelligent power modules developed specifically for servo motor drive applications. The module's architecture includes several key design features needed in these applications, such as motor phase current sensing, DC bus voltage control and short circuit protections while the embedded DSP allows easy realization of the current loop and even speed loop at the module level without any external components.

The authors report a rare case of Takayasu's arteritis with aortic arch and abdominal aorta involvement associated with Crohn's disease of the colon which both occurred in a young female patient. The coexistence of two immune mediated diseases in the same subject is unusual for they are generally considered to be independent of each other, however a hypothesis of their possible interrelationship is put forward.

One sporadic case of tularemia induced by direct contact with an infected hare is described. Human epidemiological data of the last ten years in Tuscany, emphasize that this infection, although at low incidence, shows the presence and persistence of Francisella tularensis in the animals and the ensuing transmission to humans so that it continues to be responsible for significant morbididy in "at risk" territories. Difficulties in the differential diagnosis, above all for glandular and pharyngeal forms, are reviewed.

Motor drives require complex power conversion and control. In this article, the authors describe the Programmable-Isolated Intelligent Power Module™ (PI-IPM) from International Rectifier, which shows how intelligent power modules can be implemented.

Genetic exchanges between closely related groups of organisms with different adaptations have well-documented beneficial and detrimental consequences. In plants, pollen-mediated exchanges affect the sorting of alleles across physical landscapes and influence rates of hybridization. How these dynamics affect the emergence and spread of novel phenotypes remains only partially understood. Here, we use phylogenomics and population genomics to retrace the origin and spread of two geographically overlapping ecotypes of the African grass Alloteropsis angusta . In addition to an ecotype inhabiting wetlands, we report the existence of a previously undescribed ecotype inhabiting Miombo woodlands and grasslands. The two ecotypes are consistently associated with different nuclear groups, which represent an advanced stage of divergence with secondary low-level gene flow. However, the seed-transported chloroplast genomes are consistently shared by distinct ecotypes inhabiting the same region. These patterns suggest that the nuclear genome of one ecotype can enter the seeds of the other via occasional pollen movements with sorting of nuclear groups in subsequent generations. The contrasting ecotypes of A. angusta can thus use each other as a gateway to new locations across a large part of Africa, showing that hybridization can facilitate the geographical dispersal of distinct ecotypes of the same grass species. Agence Nationale de la Recherche | Ref. ANR-10-LABX-25-01 Agence Nationale de la Recherche | Ref. ANR-10-LABX-41 Royal Society | Ref. RGF\EA\181050 Royal Society | Ref. URF\R\180022

In this paper a current controller is used to reject the 100-Hz oscillation of the voltage of the photovoltaic field taking place in any grid connected system. With respect to the classical linear voltage control the current-based sliding-mode approach ensures a wider regulation band but, unfortunately, in presence of a fast irradiance variation the sliding conditions might be violated, so that the operating point, which should be the maximum power point, might not be the expected one. In order to prevent such a drawback, an appropriate voltage compensation loop is used to interface the current-based sliding mode with the Maximum Power Point Tracking algorithm. Simulation and experimental results confirm the goodness of the proposed algorithm.

BACKGROUND: Zebrafish exhibits extraordinary ability for tissue regeneration. Despite growing investigations dissecting the molecular underpinning of such regenerative potential, little is known about the possibility to use the chemical inventory of the zebrafish embryo to modulate human stem cell dynamics. METHODS: Extracts from zebrafish embryo were collected at different developmental stages, referred to as ZF1, ZF2, ZF3 (early stages), and ZF4, ZF5 (late stages). Human adipose-derived stem cells (hASCs), isolated from microfractured fat tissue obtained with a novel non-enzymatic method (Lipogems), were cultured in absence or presence of each developmental stage extract. Cell viability was assessed by MTT assay. Nuclear morphology was investigated by cell-permeable dye 4’,6-DAPI. Caspase-3 activity was assessed by ELISA. Gene transcription was monitored by real-time PCR. RESULTS: Late developmental stage extracts decreased cell viability and elicited caspase-3 mediated apoptosis. This effect did not involve Bax or Bcl-2 transcription. Conversely, early developmental stage ZF1 did not affect cell viability or apoptosis, albeit increasing Bax/Bcl-2 mRNA ratio. ZF1 enhanced transcription of the stemness/pluripotency genes Oct-4, Sox-2 and c-Myc. ZF1 also induced the transcription of TERT, encoding the catalytic subunit of telomerase, as well as the gene expression of Bmi-1, a chromatin remodeler acting as a major telomerase-independent repressor of senescence. These transcriptional responses were restricted to the action of early stage factors, since they were not elicited by late developmental stage ZF5. CONCLUSIONS: Exposure to early developmental stage zebrafish embryo extracts may enhance stem cell expression of multipotency and activate both telomerase-dependent and -independent antagonists of cell senescence. These outcomes may prove rewarding during prolonged expansion in culture, as it occurs in most cell therapy protocols.

Cysteine/tyrosine-rich 1 (CYYR1) is a gene we previously identified on human chromosome 21 (Hsa21). CYYR1 was initially characterized as a four-exon gene that predicts a 154-amino acid product. We provide the first detailed description of the human CYYR1 locus. It is composed of a multigene system, which includes at least seven CYYR1 alternative spliced isoforms and a new CYYR1 antisense gene. In particular, we cloned the following isoforms: CYYR1-1,2,3,4b and CYYR1-1,2,3b present a different 3´ transcripted region; CYYR1-1,2,4 lacks exon 3; CYYR1-1,2,2bis,3,4 presents an additional exon between exon 2 and exon 3; CYYR1-1b,2,3,4 presents a different 5´ untranslated region when compared to CYYR1. The meaningful differences in the protein isoforms of CYYR1 locus could indicate different functions and localizations of the predicted proteins. Moreover, we cloned a long transcript overlapping with CYYR1 as an antisense RNA, probably a non-coding RNA. In order to verify the Hsa21 locus expression profile in altered conditions such as cancer and aneuploidy, expression analysis was performed in different tumour cell lines and in trisomy 21 (CCL54) and euploid fibroblasts (CCL110). The results obtained indicate a bare expression of the multi-transcript CYYR1 in all the tumour cell lines studied, with the exception of U2OS, as well as in CCL110, while it is clearly detectable in CCL54. The characterization of the CYYR1 locus is a first step to clarify a possible role of the human locus related to tumorigenesis and Down syndrome disease. For this purpose, U2OS and CCL could be cell model systems useful to verify the real expression of the predicted proteins by studying the differences in the localization and/or the functional interaction and competition between each CYYR1 isoform. The results of the present study highlight the necessity to analyse thoroughly human gene loci that are still orphaned of role comprehension, but that could be related to complex diseases.