Redundant regulation of meristem identity and plant architecture by FRUITFULL, APETALA1 and CAULIFLOWER

The transition from vegetative to reproductive phases during Arabidopsis development is the result of a complex interaction of environmental and endogenous factors. One of the key regulators of this transition is LEAFY (LFY), whose threshold levels of activity are proposed to mediate the initiation of flowers. The closely related APETALA1 (AP1) and CAULIFLOWER (CAL) meristem identity genes are also important for flower initiation, in part because of their roles in upregulating LFY expression. We have found that mutations in the FRUITFULL (FUL) MADS-box gene, when combined with mutations in AP1 and GAL, lead to a dramatic non-flowering phenotype in which plants continuously elaborate leafy shoots in place of flowers. We demonstrate that this phenotype is caused both by the lack of LFY upregulation and by the ectopic expression of the TERMINAL FLOWER1 (TFL1) gene. Our results suggest that the FUL, AP1 and CAL genes act redundantly to control inflorescence architecture by affecting the domains of LFY and TFL1 expression as well as the relative levels of their activities

The FRUITFULL MADS-box gene mediates cell differentiation during Arabidopsis fruit development

Fruit morphogenesis is a process unique to flowering plants, and yet little is known about its developmental control, Following fertilization, fruits typically undergo a dramatic enlargement that is accompanied by differentiation of numerous distinct cell types. We have identified a mutation in Arabidopsis called fruitfull (ful-1), which abolishes elongation of the silique after fertilization. The ful-1 mutation is caused by the insertion of a DsE transposable enhancer trap element into the 5' untranslated leader of the AGL8 MADS-box gene. beta-glucuronidase (GUS) reporter gene expression in the enhancer trap line is observed specifically in all cell layers of the valve tissue, but not in the replum, the septum or the seeds, and faithfully mimics RNA in situ hybridization data reported previously, The lack of coordinated growth of the fruit tissues leads to crowded seeds, a failure of dehiscence and, frequently, the premature rupture of the carpel valves, The primary defect of ful-1 fruits is within the valves, whose cells fail to elongate and differentiate. Stomata, which are frequent along the epidermis of wild-type valves, are completely eliminated in the ful mutant valves. In addition to the effect on fruit development, ful cauline leaves are broader than those of wild type and show a reduction in the number of internal cell layers. These data suggest that AGL8/FUL regulates the transcription of genes required for cellular differentiation during fruit and leaf development

A change in SHATTERPROOF protein lies at the origin of a fruit morphological novelty and a new strategy for seed dispersal in Medicago genus

[EN] Angiosperms are the most diverse and numerous group of plants, and it is generally accepted that this evolutionary success owes in part to the diversity found in fruits, key for protecting the developing seeds and ensuring seed dispersal. Although studies on the molecular basis of morphological innovations are few, they all illustrate the central role played by transcription factors acting as developmental regulators. Here, we show that a small change in the protein sequence of a MADS-box transcription factor correlates with the origin of a highly modified fruit morphology and the change in seed dispersal strategies that occurred in Medicago, a genus belonging to the large legume family. This protein sequence modification alters the functional properties of the protein, affecting the affinities for other protein partners involved in high-order complexes. Our work illustrates that variation in coding regions can generate evolutionary novelties not based on gene duplication/subfunctionalization but by interactions in complex networks, contributing also to the current debate on the relative importance of changes in regulatory or coding regions of master regulators in generating morphological novelties.This work was supported by the Spanish Ministerio de Ciencia e Innovacion (grant no. BIO2009-09920 to C.Fe.), the European Union (grant no. FP7-PEOPLE-PIRSES-2009-247589 to C.Fe. and A.C.d.O.), and a Fellowship for Foreign Young Postdocs from the Spanish Ministerio de Ciencia e Innovacion (to C.Fo.).Fourquin, C.; Del Cerro Fernández, C.; Victoria, FC.; Vialette-Guiraud, A.; De Oliveira, AC.; Ferrandiz Maestre, C. (2013). A change in SHATTERPROOF protein lies at the origin of a fruit morphological novelty and a new strategy for seed dispersal in Medicago genus. Plant Physiology. 162(2):907-917. https://doi.org/10.1104/pp.113.217570S907917162

Reactive Oxygen Species Contribute to the Bactericidal Effects of the Fluoroquinolone Moxifloxacin in Streptococcus pneumoniae

We studied the transcriptomic response of Streptococcus pneumoniae to the fluoroquinolone moxifloxacin at a concentration that inhibits DNA gyrase. Treatment of the wild-type strain R6, at a concentration of 10× the MIC, triggered a response involving 132 genes after 30 min of treatment. Genes from several metabolic pathways involved in the production of pyruvate were upregulated. These included 3 glycolytic enzymes, which ultimately convert fructose 6-phosphate to pyruvate, and 2 enzymes that funnel phosphate sugars into the glycolytic pathway. In addition, acetyl coenzyme A (acetyl-CoA) carboxylase was downregulated, likely leading to an increase in acetyl-CoA. When coupled with an upregulation in formate acetyltransferase, an increase in acetyl-CoA would raise the production of pyruvate. Since pyruvate is converted by pyruvate oxidase (SpxB) into hydrogen peroxide (H2O2), an increase in pyruvate would augment intracellular H2O2. Here, we confirm a 21-fold increase in the production of H2O2 and a 55-fold increase in the amount of hydroxyl radical in cultures treated during 4 h with moxifloxacin. This increase in hydroxyl radical through the Fenton reaction would damage DNA, lipids, and proteins. These reactive oxygen species contributed to the lethality of the drug, a conclusion supported by the observed protective effects of an SpxB deletion. These results support the model whereby fluoroquinolones cause redox alterations. The transcriptional response of S. pneumoniae to moxifloxacin is compared with the response to levofloxacin, an inhibitor of topoisomerase IV. Levofloxacin triggers the transcriptional activation of iron transport genes and also enhances the Fenton reaction.This study was supported by grants BIO2011-25343 and BIO2014-55462-R from Plan Nacional de I+D+I of the Ministry of Economy and Competitiveness. A.J.M.-G. is the recipient of a Miguel Servet contract from the Spanish Ministry of Economy and Competitiveness.S

Hybrid fly ash-based geopolymeric foams: Microstructural, thermal and mechanical properties

This research investigates the preparation and characterization of new organic-inorganic geopolymeric foams obtained by simultaneously reacting coal fly ash and an alkali silicate solution with polysiloxane oligomers. Foaming was realized in situ using Si0 as a blowing agent. Samples with density ranging from0.3 to 0.7 g/cm3 that show good mechanical properties (with compressive strength up to ≈5 MPa for a density of 0.7 g/cm3) along with thermal performances (λ = 0.145 ± 0.001 W/m·K for the foamed sample with density 0.330 g/cm3) comparable to commercial lightweight materials used in the field of thermal insulation were prepared. Since these foams were obtained by valorizing waste byproducts, they could be considered as low environmental impact materials and, hence, with promising perspectives towards the circular economy

Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate‐to‐severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2)

SummaryBackground Apremilast, an oral phosphodiesterase 4 inhibitor, regulates immune responses associated with psoriasis. Objectives ESTEEM 2 evaluated the efficacy and safety of apremilast 30 mg twice daily for moderate-to-severe plaque psoriasis. Methods This phase III, double-blind, placebo-controlled trial randomized adults to apremilast or placebo (2 : 1). At week 16, placebo patients switched to apremilast. At week 32, apremilast patients achieving ≥ 50% reduction in Psoriasis Area and Severity Index (PASI 50) were rerandomized (1 : 1) to continue apremilast or receive placebo. Upon loss of 50% of PASI improvement obtained at week 32, patients rerandomized to placebo resumed apremilast. Results The modified intention-to-treat population (full analysis set) included 137 placebo and 274 apremilast patients. At week 16, significantly more apremilast patients achieved PASI 75 (28·8%), PASI 50 (55·5%) and static Physician's Global Assessment score of 0 or 1 (20·4%) vs. placebo (5·8%, 19·7%, 4·4%, respectively; P < 0·001). Most patients rerandomized to apremilast at week 32 had a PASI 50 response at week 52 (80%). Patients treated with apremilast showed significant improvements in quality of life (as assessed by the Dermatology Life Quality Index) and pruritus at week 16 compared with placebo (P < 0·001). The exposure-adjusted incidence of adverse events did not increase with continued apremilast treatment for up to 52 weeks. The most common adverse events were nausea, diarrhoea, nasopharyngitis and upper respiratory tract infection. Conclusions Apremilast was effective in the treatment of moderate-to-severe plaque psoriasis over 52 weeks

The fidelity of synaptonemal complex assembly is regulated by a signaling mechanism that controls early meiotic progression

© 2014 Elsevier Inc.Proper chromosome segregation during meiosis requires the assembly of the synaptonemal complex (SC) between homologous chromosomes. However, the SC structure itself is indifferent to homology, andpoorly understood mechanisms that depend on conserved HORMA-domain proteins prevent ectopic SC assembly. Although HORMA-domain proteins are thought to regulate SC assembly as intrinsic components of meiotic chromosomes, here we uncover a key role for nuclear soluble HORMA-domain protein HTP-1 in the quality control of SC assembly. We show that a mutant form of HTP-1 impaired in chromosome loading provides functionality of an HTP-1-dependent checkpoint that delays exit from homology search-competent stages until all homolog pairs are linked by the SC. Bypassing of this regulatory mechanism results in premature meiotic progression and licensing of homology-independent SC assembly. These findings identify nuclear soluble HTP-1 as a regulator of early meiotic progression, suggesting parallels with the mode of action of Mad2 in the spindle assembly checkpoint

Comparison of ixekizumab with ustekinumab in moderate-to-severe psoriasis: 24-week results from IXORA-S, a phase III study

Background It has been shown that the interleukin (IL)-23/IL-17 axis is critical in the pathogenesis of psoriasis. Objectives To present the primary end point (week 12) and safety and efficacy data up to week 24 from a head-to-head trial (IXORA-S) of the IL-17A inhibitor ixekizumab (IXE) vs. the IL-12/23 inhibitor ustekinumab (UST). Methods Randomized patients received IXE (160-mg starting dose, then 80 mg every 2 weeks for 12 weeks, then 80 mg every 4 weeks, n = 136) or UST (45 mg or 90 mg weight-based dosing per label, n = 166). The primary end point was the proportion of patients reaching ≥ 90% Psoriasis Area and Severity Index improvement (PASI 90). Hommel-adjusted key secondary end points at week 12 included PASI 75, PASI 100, static Physician's Global Assessment (sPGA) score of 0 or 1, sPGA score of 0, Dermatology Life Quality Index (DLQI) score of 0 or 1, ≥ 4-point reduction on the itch numerical rating scale (NRS) and changes in itch NRS and skin pain visual analogue scale. Results At week 12, IXE (n = 99, 72 8%) was superior to UST (n = 70, 42 2%) in PASI 90 response (response difference 32 1%, 97 5% confidence interval 19 8 44 5%, P < 0 001). Response rates for PASI 75, PASI 100 and sPGA (0,1) were significantly higher for IXE than for UST (adjusted P < 0 05). At week 24, IXEtreated patients had significantly higher response rates than UST-treated patients for PASI, sPGA and DLQI (unadjusted P < 0 05). No deaths were reported, and the treatments did not differ with regard to overall incidences of adverse events (P = 0 299). Conclusions The superior efficacy of IXE demonstrated at week 12 persisted up to week 24. The safety profiles were consistent with those previously reported for both treatments. peerReviewe