PET Imaging of Post-infarct Myocardial Inflammation.

Funder: Department of HealthPurpose of reviewTo examine the use of positron emission tomography (PET) for imaging post-infarct myocardial inflammation and repair.Recent findingsDysregulated immune responses after myocardial infarction are associated with adverse cardiac remodelling and an increased likelihood of ischaemic heart failure. PET imaging utilising novel tracers can be applied to visualise different components of the post-infarction inflammatory and repair processes. This approach could offer unique pathophysiological insights that could prove useful for the identification and risk-stratification of individuals who would ultimately benefit most from emerging immune-modulating therapies. PET imaging could also bridge the clinical translational gap as a surrogate measure of drug efficacy in early-stage clinical trials in patients with myocardial infarction. The use of hybrid PET/MR imaging, in particular, offers the additional advantage of simultaneous in vivo molecular imaging and detailed assessment of myocardial function, viability and tissue characterisation. Further research is needed to realise the true clinical translational value of PET imaging after myocardial infarction

An unusual finding in a 57-year-old woman with new onset hypertension and a diastolic murmur.

CLINICAL INTRODUCTION: A 57-year-old woman presented to our clinic with breathlessness brought on while walking uphill. She had been recently diagnosed with systemic hypertension. There was no known family history of cardiac disease, or prior smoking habit. On examination, pulse was 73 bpm and blood pressure 155/73 mm Hg, which was asymmetrical in her arms. Auscultation revealed a readily audible early diastolic murmur in the aortic area and bilateral subclavian bruits. ECG showed sinus rhythm with no abnormality. Transthoracic echocardiography demonstrated mild-to-moderate aortic regurgitation, and normal left ventricular size and function. The ascending aorta was mildly dilated (41 mm), with para-aortic thickening noted. Owing to the abnormal appearance of the aortic wall, cardiac MRI, and subsequently 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scan was performed (figure 1). QUESTION: Which complication of the underlying disease is evident in figure 1, panel C? Aortic aneurysmAortic dissectionAortic thrombusCoronary artery aneurysmCoronary sinus fistula

The vanishing atrial mass.

HEFCEThis is the final version of the article. It first appeared from Oxford University Press via https://doi.org10.1093/ehjci/jew12

Buğdayda Sorun Olan Septorya Yaprak Lekesi (Zymoseptoria tritici) Patojeni'nde Fungal Efektör Adayı Bazı SSP (Small Secreted Protein) Genlerinin Fonksiyonel Analizi

TÜBİTAK TOVAG Proje15.12.2017Septorya yaprak leke hastalığı etmeni Zymoseptoria tritici ülkemizde buğdayın en önemliyaprak hastalıklarından birisidir. Askomiset, hemibiotrof bir fungus olan fungusun tam genom sekans analizleri tamamlanmış ve erişime açılmıştır. Fungusun genomundaki genlerin fonksiyonlarının ve bitkiyi hastalandırma sürecinde görev alan efektör genlerinin belirlenmesi fungusa karşı mücadele stratejilerinin geliştirilmesinde büyük önem arz etmektedir.Bu proje buğday yaprak lekesi etmeni Z. tritici genomunda yer alan bazı küçük, hücre arasına salınan proteinleri kodlayan, fungal efektör adayı genlerin (Small Secreted Protein- SSP) gen silme tekniği ile fungusun genomundan silinip, fungusun biyolojik ve patolojik özelliklerine etkilerinin belirlenmesi amacıyla gerçekleştirilmiştir. Hedef SSP genlerine ait nükleotid dizileri kullanılarak oluşturulan gen silme kasetleri ve Agrobacterium temelli transformasyon tekniği kullanılarak patojenin genomundan hedeflenen genlerin tamamı silinebilmiştir.Silinen SSP genlerinden biri (Zt-3) fungusun temel biyolojik özelliklerinden biri olan mayaformunda gelişim özelliğini önemli oranda etkilemiştir. Zt-3 geni silinmiş izolat sadece makro piknidiospor üretebilmiştir. Çalışılan genlerin fungusun hastalandırma yeteneği üzerinde etkili olup olmadığı, geni silinmiş izolatlar ile yapılan patojenisite testleri ile araştırılmıştır. Herhangi bir etki bulunamamıştır. Çalışma sonunda Z. tritici gen fonksiyonu çalışmalarında gen silme tekniği ülkemizde ilk defa kullanılmış ve optimize edilmiştir. Yapılan çalışma bu tekniğin fungal genlerin fonksiyonlarının belirlenmesinde başarılı ve etkin bir şekilde kullanılabileceğini ortaya koymuştur.Septoria leaf blotch is one of the most important leaf diseases of wheat in Turkey.Ascomycet and hemibiotrophic fungus was sequenced as whole genome andrelease in public. It is very important to find out functions of the fungal genes andeffector proteins having roles in pathogenicity to develop new managementstrategies against fungus.This project was carried out to knock out of some Small Secreted Proteins (SSP)genes and examine the effects of gene deletion process on biological andpathogenic characteristics of it. Target SSP genes were successfully deletedusing gene deletion cassettes produced using nucleotide sequences of SSPgenes and Agrobacterium mediated transformation.One of deleted SSP genes (Zt-3) effected to development of yeast form of thefungus in important scale. Mutant isolate could only produce macropicniospores.It was investigated for the selected SSP genes whether gene deletion causedany difference on fungal pathogenicity using plant tests. Results showed therewas no effects of deletion of these genes.At the end of the study, gene deletion technique was firstly optimized and used ingene function studies on Z. tritici. This study showed that this technology can beused properly and effectively on gene function studies of the fungi

OmniMapFree: A unified tool to visualise and explore sequenced genomes

<p>Abstract</p> <p>• Background</p> <p>Acquiring and exploring whole genome sequence information for a species under investigation is now a routine experimental approach. On most genome browsers, typically, only the DNA sequence, EST support, motif search results, and GO annotations are displayed. However, for many species, a growing volume of additional experimental information is available but this is rarely searchable within the landscape of the entire genome.</p> <p>• Results</p> <p>We have developed a generic software which permits users to view a single genome in entirety either within its chromosome or supercontig context within a single window. This software permits the genome to be displayed at any scales and with any features. Different data types and data sets are displayed onto the genome, which have been acquired from other types of studies including classical genetics, forward and reverse genetics, transcriptomics, proteomics and improved annotation from alternative sources. In each display, different types of information can be overlapped, then retrieved in the desired combinations and scales and used in follow up analyses. The displays generated are of publication quality.</p> <p>• Conclusions</p> <p>OmniMapFree provides a unified, versatile and easy-to-use software tool for studying a single genome in association with all the other datasets and data types available for the organism.</p

Noninvasive Molecular Imaging of Disease Activity in Atherosclerosis.

Major focus has been placed on the identification of vulnerable plaques as a means of improving the prediction of myocardial infarction. However, this strategy has recently been questioned on the basis that the majority of these individual coronary lesions do not in fact go on to cause clinical events. Attention is, therefore, shifting to alternative imaging modalities that might provide a more complete pan-coronary assessment of the atherosclerotic disease process. These include markers of disease activity with the potential to discriminate between patients with stable burnt-out disease that is no longer metabolically active and those with active atheroma, faster disease progression, and increased risk of infarction. This review will examine how novel molecular imaging approaches can provide such assessments, focusing on inflammation and microcalcification activity, the importance of these processes to coronary atherosclerosis, and the advantages and challenges posed by these techniques.M.R.D and D.E.N are supported by the British Heart Foundation (CH/09/002 to D.E.N., FS/14/78/31020 to M.R.D). M.R.D is the recipient of the Sir Jules Thorn Biomedical Research Award 2015 (M.R.D.) E.A. research is supported by R01HL 114805 and R01HL 109506.This is the final version of the article. It first appeared from Lippincott, Williams & Wilkins via http://dx.doi.org/10.1161/CIRCRESAHA.116.30797

Imaging Atherosclerosis.

Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however, these important vascular imaging methods additionally promise great scientific and translational applications beyond this quest. When combined with conventional anatomic- and hemodynamic-based assessments of disease severity, cross-sectional multimodal imaging incorporating molecular probes and other novel noninvasive techniques can add detailed interrogation of plaque composition, activity, and overall disease burden. In the catheterization laboratory, intravascular imaging provides unparalleled access to the world beneath the plaque surface, allowing tissue characterization and measurement of cap thickness with micrometer spatial resolution. Atherosclerosis imaging captures key data that reveal snapshots into underlying biology, which can test our understanding of fundamental research questions and shape our approach toward patient management. Imaging can also be used to quantify response to therapeutic interventions and ultimately help predict cardiovascular risk. Although there are undeniable barriers to clinical translation, many of these hold-ups might soon be surpassed by rapidly evolving innovations to improve image acquisition, coregistration, motion correction, and reduce radiation exposure. This article provides a comprehensive review of current and experimental atherosclerosis imaging methods and their uses in research and potential for translation to the clinic.J.M.T. is supported by a Wellcome Trust research training fellowship (104492/Z/14/Z). M.D is supported by the British Heart Foundation (FS/14/78/31020). N.R.E. is supported by a research training fellowship from the Dunhill Medical Trust (RTF44/0114). A.J.B. is supported by the British Heart Foundation. J.H.F.R. is part-supported by the HEFCE, the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation, and the Wellcome Trust.This is the final version of the article. It first appeared from the American Heart Association via http://dx.doi.org/10.1161/CIRCRESAHA.115.30624

A large bioassay identifies Stb resistance genes that provide broad resistance against Septoria tritici blotch disease in the UK

Introduction: Septoria tritici blotch (STB) is one of the most damaging fungal diseases of wheat in Europe, largely due to the paucity of effective resistance genes against it in breeding materials. Currently dominant protection methods against this disease, e.g. fungicides and the disease resistance genes already deployed, are losing their effectiveness. Therefore, it is vital that other available disease resistance sources are identified, understood and deployed in a manner that maximises their effectiveness and durability. Methods: In this study, we assessed wheat genotypes containing nineteen known major STB resistance genes (Stb1 through to Stb19) or combinations thereof against a broad panel of 93 UK Zymoseptoria tritici isolates. Seedlings were inoculated using a cotton swab and monitored for four weeks. Four infection-related phenotypic traits were visually assessed. These were the days post infection to the development of first symptoms and pycnidia, percentage coverage of the infected leaf area with chlorosis/necrosis and percentage coverage of the infected leaf area with pycnidia. Results: The different Stb genes were found to vary greatly in the levels of protection they provided, with pycnidia coverage at four weeks differing significantly from susceptible controls for every tested genotype. Stb10, Stb11, Stb12, Stb16q, Stb17, and Stb19 were identified as contributing broad spectrum disease resistance, and synthetic hexaploid wheat lines were identified as particularly promising sources of broadly effective STB resistances. Discussion: No single Z. tritici isolate was found to be virulent against all tested resistance genes. Wheat genotypes carrying multiple Stb genes were found to provide higher levels of resistance than expected given their historical levels of use. Furthermore, it was noted that disease resistance controlled by different Stb genes was associated with different levels of chlorosis, with high levels of early chlorosis in some genotypes correlated with high resistance to fungal pycnidia development, potentially suggesting the presence of multiple resistance mechanisms. The knowledge obtained here will aid UK breeders in prioritising Stb genes for future breeding programmes, in which optimal combinations of resistance genes could be pyramided. In addition, this study identified the most interesting Stb genes for cloning and detailed functional analysis