Plant and animal perception of microbes through pathogen surveillance proteins leads to MAP kinase signalling and the expression of defence genes. However, little is known about how plant MAP kinases regulate specific gene expression. We report that, in the absence of pathogens, Arabidopsis MAP kinase 4 (MPK4) exists in nuclear complexes with the WRKY33 transcription factor. This complex depends on the MPK4 substrate MKS1. Challenge with Pseudomonas syringae or flagellin leads to the activation of MPK4 and phosphorylation of MKS1. Subsequently, complexes with MKS1 and WRKY33 are released from MPK4, and WRKY33 targets the promoter of PHYTOALEXIN DEFICIENT3 (PAD3) encoding an enzyme required for the synthesis of antimicrobial camalexin. Hence, wrky33 mutants are impaired in the accumulation of PAD3 mRNA and camalexin production upon infection. That WRKY33 is an effector of MPK4 is further supported by the suppression of PAD3 expression in mpk4-wrky33 double mutant backgrounds. Our data establish direct links between MPK4 and innate immunity and provide an example of how a plant MAP kinase can regulate gene expression by releasing transcription factors in the nucleus upon activation.

TFs (transcription factors) are modular proteins minimally containing a DBD (DNA-binding domain) and a TRD (transcription regulatory domain). NAC [for NAM (no apical meristem), ATAF, CUC (cup-shaped cotyledon)] proteins comprise one of the largest plant TF families. They are key regulators of stress perception and developmental programmes, and most share an N-terminal NAC domain. On the basis of analyses of gene expression data and the phylogeny of Arabidopsis thaliana NAC TFs we systematically decipher structural and functional specificities of the conserved NAC domains and the divergent C-termini. Nine of the ten NAC domains analysed bind a previously identified conserved DNA target sequence with a CGT[GA] core, although with different affinities. Likewise, all but one of the NAC proteins analysed is dependent on the C-terminal region for transactivational activity. In silico analyses show that the NAC TRDs contain group-specific sequence motifs and are characterized by a high degree of intrinsic disorder. Furthermore, ANAC019 was identified as a new positive regulator of ABA (abscisic acid) signalling, conferring ABA hypersensitivity when ectopically expressed in plants. Interestingly, ectopic expression of the ANAC019 DBD or TRD alone also resulted in ABA hypersensitivity. Expression of stress-responsive marker genes [COR47 (cold-responsive 47), RD29b (responsive-to-desiccation 29b) and ERD11 (early-responsive-to-dehydration 11)] were also induced by full-length and truncated ANAC019. Domain-swapping experiments were used to analyse the specificity of this function. Chimaeric proteins, where the NAC domain of ANAC019 was replaced with the analogous regions from other NAC TFs, also have the ability to positively regulate ABA signalling. In contrast, replacing the ANAC019 TRD with other TRDs abolished ANAC019-mediated ABA hypersensitivity. In conclusion, our results demonstrate that the biochemical and functional specificity of NAC TFs is associated with both the DBDs and the TRDs.

This review recommends treatment options for CSP in clinical practice, based on efficacy and safety. The literature supports an interventional rather than medical approach. Present recommendations are primarily based on case series. Multicenter, well-designed studies are needed to draw definite conclusions on how to treat CSP.

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The Arabidopsis (Arabidopsis thaliana) MKK1 and MKK2 mitogen-activated protein kinase kinases have been implicated in biotic and abiotic stress responses as part of a signaling cascade including MEKK1 and MPK4. Here, the double loss-offunction mutant (mkk1/2) of MKK1 and MKK2 is shown to have marked phenotypes in development and disease resistance similar to those of the single mekk1 and mpk4 mutants. Because mkk1 or mkk2 single mutants appear wild type, basal levels of MPK4 activity are not impaired in them, and MKK1 and MKK2 are in part functionally redundant in unchallenged plants. These findings are confirmed and extended by biochemical and molecular analyses implicating the kinases in jasmonate-and salicylate-dependent defense responses, mediated in part via the MPK4 substrate MKS1. In addition, transcriptome analyses delineate overlapping and specific effects of the kinases on global gene expression patterns demonstrating both redundant and unique functions for MKK1 and MKK2.

Mammographic risk scoring has commonly been automated by extracting a set of handcrafted features from mammograms, and relating the responses directly or indirectly to breast cancer risk. We present a method that learns a feature hierarchy from unlabeled data. When the learned features are used as the input to a simple classifier, two different tasks can be addressed: i) breast density segmentation, and ii) scoring of mammographic texture. The proposed model learns features at multiple scales. To control the models capacity a novel sparsity regularizer is introduced that incorporates both lifetime and population sparsity. We evaluated our method on three different clinical datasets. Our state-of-the-art results show that the learned breast density scores have a very strong positive relationship with manual ones, and that the learned texture scores are predictive of breast cancer. The model is easy to apply and generalizes to many other segmentation and scoring problems.

The Nordic Obstetric Surveillance Study: a study of complete uterine rupture, abnormally invasive placenta, peripartum hysterectomy, and severe blood loss at delivery Colmorn, Lotte B.; Petersen, Kathrine B.; Jakobsson, Maija; Lindqvist, Pelle G.; Klungsoyr, Kari; Källén, Karin; Bjarnadottir, Ragnheidur I.; Tapper, Anna-Maija; Bordahl, Per E.; Gottvall, Karin; Thurn, Lars; Gissler, Mika; Krebs, Lone; Langhoff-Roos, Jens Link to publication Citation for published version (APA): Colmorn, L. B., Petersen, K. B., Jakobsson, M., Lindqvist, P. G., Klungsoyr, K., Källén, K., ... Langhoff-Roos, J. (2015). The Nordic Obstetric Surveillance Study: a study of complete uterine rupture, abnormally invasive placenta, peripartum hysterectomy, and severe blood loss at delivery. Acta Obstetricia et Gynecologica Scandinavica, 94(7), 734-744. DOI: 10.1111/aogs.12639 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal AOGS MAIN RESEARCH ARTICLEThe Nordic Obstetric Surveillance Study: a study of complete uterine rupture, abnormally invasive placenta, peripartum hysterectomy, and severe blood loss at delivery AbstractObjective. To assess the rates and characteristics of women with complete uterine rupture, abnormally invasive placenta, peripartum hysterectomy, and severe blood loss at delivery in the Nordic countries. Design. Prospective, Nordic collaboration. Setting. The Nordic Obstetric Surveillance Study (NOSS) collected cases of severe obstetric complications in the Nordic countries from April 2009 to August 2012. Sample and methods. Cases were reported by clinicians at the Nordic maternity units and retrieved from medical birth registers, hospital discharge registers, and transfusion databases by using International Classification of Diseases, 10th revision codes on diagnoses and the Nordic Medico-Statistical Committee Classification of Surgical Procedure codes. Main outcome measures. Rates of the studied complications and possible risk factors among parturients in the Nordic countries. Results. The studied complications were reported in 1019 instances among 605 362 deliveries during the study period. The reported rate of severe blood loss at delivery was 11.6/10 000 deliveries, complete uterine rupture was 5.6/10 000 deliveries, abnormally invasive placenta was 4.6/10 000 deliveries, and peripartum hysterectomy was 3.5/10 000 deliveries. Of the women, 25% had two or more complications. Women with complications were more often >35 years old, overweight, with a higher parity, a...

To establish infection, pathogens deploy effectors to modify or remove host proteins. Plant immune receptors with nucleotide-binding, leucine-rich repeat domains (NLRs) detect these modifications and trigger immunity. Plant NLRs thus guard host "guardees." A corollary is that autoimmunity may result from inappropriate NLR activation because mutations in plant guardees could trigger corresponding NLR guards. To explore these hypotheses, we expressed 108 dominant-negative (DN) Arabidopsis NLRs in various lesion mimic mutants, including camta3, which exhibits autoimmunity. CAMTA3 was previously described as a negative regulator of immunity, and we find that autoimmunity in camta3 is fully suppressed by expressing DNs of two NLRs, DSC1 and DSC2. Additionally, expression of either NLR triggers cell death that can be suppressed by CAMTA3 expression. These findings support a model in which DSC1 and DSC2 guard CAMTA3, and they suggest that other negative regulators of immunity may similarly represent guardees.