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Oncothermia (OTM) is based on electromagnetic interactions with the living matter. Its nano-targeting approach establishes a new paradigm. OTM could be applied not only to treat malignancies but it is feasible to apply for other diseases too. OTH is well proven method from the laboratory level to the clinical applications, promoting the natural processes, re-establishing of the synchronization between the cells. This approach allows therapy of some non-malignant diseases too. Our objective is to use OTM for the irregularities of tissue-growth and for pain syndromes as well. OTM uses precisely tuned radiofrequency (RF) current flowing through the treated part of the body. We made extensive study, proving in details the applicability of the OTM for Dupuytren's contracture and chronic low back pain, in conjunction with permanent acupuncture method, a modified process of traditional Chinese Medicine (TCM). The synergy of the ancient and the state-of-art medical knowledges is the basic method of the present research. Our results with application of OTM for chronic low back pain and Dupuytren's contracture shows definite improvements of the patients involved in the study. We measured the success with the Visual Analog Scale (VAS), with anecdotic quality of life (QoL), and the shortening of the of-work period due to the disease. We measured that VAS decreased significantly, the hand contracture became less rigid and less contracted. The QoL of patients improved and their complaints which blocked their regular activity has significantly reduced. OTM method was safe & no adverse effects were observed. Recognition of the distortions in the healthy tissue have some common principles and possibilities in TCM and OTM: both the methods recognize the loss of complexity of the living organization. Data of our recent study verified the relevant end-points of our present study: the safety, the quality of life (QoL), the prolonged painless status of the patient.

Eight new β-resorcylic acid lactones (RALs), including the hypothemycin-type compounds paecilomycins N-P (1-3) and the radicicol-type metabolites dechloropochonin I (4), monocillins VI (5) and VII (6), 4′-hydroxymonocillin IV (7), and 4′-methoxymonocillin IV (8), along with nine known RALs (9-17), were isolated from the cultures of Paecilomyces sp. SC0924. Compounds 1 and 2 feature a novel 6/11/5 ring system, and 3 is the first 5′-keto RAL. The structures of 1-8 were elucidated on the basis of extensive spectroscopic analysis, X-ray diffraction analysis, and theoretical calculations of ECD spectra. Compounds 3, 5, and 6 exhibit cytotoxicity against MCF-7, A549, and HeLa cells, and compounds 5 and 7 display antifungal activity against Peronophythora litchii.

Monascus azaphilone pigments (MonAzPs) are very widely used as food colorants, but their biosynthetic pathway has remained poorly characterized for more than half a century. In this study, the individual steps of MonAzPs biosynthesis in Monascus ruber M7 were elucidated by a combination of targeted gene knockouts, heterologous gene expression, and in vitro chemical and enzymatic reactions. This study describes the first rational engineering of MonAzPs biosynthesis and provides a roadmap for future pathway engineering efforts directed towards the selective production of the most valuable pigments and serves as a model for the biosynthesis of fungal azaphilones in general.

The photosynthetic responses to salt stress were examined in a wheat (Triticum aestivum L. cv. Asakaze)–barley (Hordeum vulgare L. cv. Manas) 7H addition line having elevated salt tolerance and compared to the parental wheat genotype. For this purpose, increasing NaCl concentrations up to 300 mM were applied and followed by a 7-day recovery period. Up to moderate salt stress (200 mM NaCl), forcible stomatal closure, parallel with a reduction in the net assimilation rate (P N), was only observed in wheat, but not in the 7H addition line or barley. Since the photosynthetic electron transport processes of wheat were not affected by NaCl, the impairment in P N could largely be accounted for the salt-induced decline in stomatal conductance (g s), accompanied by depressed intercellular CO2 concentration and carboxylation efficiency. Both, P N and nonstomatal limitation factors (Lns) were practically unaffected by moderate salt stress in barley and in the 7H addition line due to the sustained g s, which might be an efficient strategy to maintain the efficient photosynthetic activity and biomass production. At 300 mM NaCl, both P N and g s decreased significantly in all the genotypes, but the changes in P N and Lns in the 7H addition line were more favourable similar to those in wheat. The downregulation of photosynthetic electron transport processes around PSII, accompanied by increases in the quantum yield of regulated energy dissipation and of the donor side limitation of PSI without damage to PSII, was observed in the addition line and barley during severe stress. Incomplete recovery of P N was observed in the 7H addition line as a result of declined PSII activity probably caused by enhanced cyclic electron flow around PSI. These results suggest that the better photosynthetic tolerance to moderate salt stress of barley can be manifested in the 7H addition line which may be a suitable candidate for improving salt tolerance of wheat.

The spatiotemporal dynamics of the bromate-sulfite-ferrocyanide (BSF) reaction-diffusion system in a open one-side-fed reactor (OSFR) is investigated by numerical simulations. The results of the simulations are compared with experiments performed in an annular shape OSFR. Both kinetic and diffusion-driven instabilities are identified in the model. There are two hydrogen ion consuming pathways in the mechanism: the partial oxidation of sulfite to dithionate and the oxidation of ferrocyanide by bromate ions. Their dynamical effects are similar, as they support the same negative feedback loop via sulfite ion. However, the time scale of the oxidation of ferrocyanide by bromate ions can be conveniently controlled by the input feed concentrations, thus it provides a more flexible way to find spatiotemporal oscillations. Long-range activation due to the relative fast diffusion of hydrogen ions compared to the other reactants can also result in oscillations in this mechanism. We show that the spatial extent of the reaction-diffusion medium along the direction of the diffusive feed (the thickness) acts as a general control parameter of the dynamics. Oscillations, either originated in kinetic or in diffusive instabilities, can only develop in a narrow range of the thickness. This property explains the experimentally often observed spatial localization of the oscillations. A reciprocal relationship is found between two main control parameters of the dynamics, which are the thickness and the hydrogen ion input feed concentration.

This abstract was withdrawn by the authors.

This abstract was withdrawn by the authors.

Photorhabdus luminescens subsp. sonorensis strain Caborca is an entomopathogenic bacterium with a dual lifestyle, namely, as a mutualist of the Heterorhabditis sonorensis nematode and a pathogen to a wide range of insect species. The genome assembly, in 231 contigs, is 5.2 Mbp long and includes 25 putative gene clusters for secondary metabolism.

Lr76 and Yr70 have been fine mapped using the sequence of flow-sorted recombinant 5D chromosome from wheat-Ae. umbellulata introgression line. The alien introgression has been delineated to 9.47-Mb region on short arm of wheat chromosome 5D. Leaf rust and stripe rust are among the most damaging diseases of wheat worldwide. Wheat cultivation based on limited number of rust resistance genes deployed over vast areas expedites the emergence of new pathotypes warranting a continuous deployment of new resistance genes. In this paper, fine mapping of Aegilops umbellulata-derived leaf rust and stripe rust resistance genes Lr76 and Yr70 is being reported. We flow sorted and paired-end sequenced 5U chromosome of Ae. umbellulata, recombinant chromosome 5D (5DIL) from wheat-Ae. umbellulata introgression line pau16057 and 5DRP of recurrent parent WL711. Chromosome 5U reads were mapped against the reference Chinese Spring chromosome 5D sequence, and alien-specific SNPs were identified. Chromosome 5DIL and 5DRP sequences were de novo assembled, and alien introgression-specific markers were designed by selecting 5U- and 5D-specific SNPs. Overall, 27 KASP markers were mapped in high-resolution population consisting of 1404 F5 RILs. The mapping population segregated for single gene each for leaf rust and stripe rust resistance. The physical order of the SNPs in pau16057 was defined by projecting the 27 SNPs against the IWGSC RefSeq v1.0 sequence. Based on this physical map, the size of Ae. umbellulata introgression was determined to be 9.47 Mb on the distal most end of the short arm of chromosome 5D. This non-recombining alien segment carries six NB-LRR encoding genes based on NLR annotation of assembled chromosome 5DIL sequence and IWGSC RefSeq v1.1 gene models. The presence of SNPs and other sequence variations in these genes between pau16057 and WL711 suggested that they are candidates for Lr76 and Yr70.

Covering: up to June 2018 Understanding the biosynthetic mechanisms that generate the astounding structural complexity and variety of fungal secondary metabolites (FSMs) remains a challenge. As an example, the biogenesis of the Monascus azaphilone pigments (MonAzPs) has remained obscure until recently despite the significant medical potential of these metabolites and their long history of widespread use as food colorants. However, a considerable progress has been made in recent years towards the elucidation of MonAzPs biosynthesis in various fungi. In this highlight, we correlate a unified biosynthetic pathway with the diverse structures of the 111 MonAzPs congeners reported until June 2018. We also discuss the origins of structural diversity amongst MonAzPs analogues and summarize new research directions towards exploring novel MonAzPs. The case of MonAzPs illuminates the various ways that FSMs metabolic complexity emerges by the interplay of biosynthetic pathway determinism with metabolic and chemical serendipity.

O-Methylation modulates the pharmacokinetic and pharmacodynamic (PK/PD) properties of small-molecule natural products, affecting their bioavailability, stability, and binding to targets. Diversity-oriented combinatorial biosynthesis of new chemical entities for drug discovery and optimization of known bioactive scaffolds during drug development both demand efficient O-methyltransferase (OMT) biocatalysts with considerable substrate promiscuity and tunable regioselectivity that can be deployed in a scalable and sustainable manner. Here we demonstrate efficient total biosynthetic and biocatalytic platforms that use a pair of fungal OMTs with orthogonal regiospecificity to produce unnatural O-methylated benzenediol lactone polyketides. We show that rational, structure-guided active-site cavity engineering can reprogram the regioselectivity of these enzymes. We also characterize the interplay of engineered regioselectivity with substrate plasticity. These findings will guide combinatorial biosynthetic tailoring of unnatural products toward the generation of diverse chemical matter for drug discovery and the PK/PD optimization of bioactive scaffolds for drug development.

To assess the extent to which pain therapy can improve chronic pain in a heterogeneous group of patients, its impact on their quality of life and the correlation of the changes with their age and the underlying disease. The investigation has its actuality by its impact on public health.a prospective, non-randomized, interventional, clinical cohort study was conducted under real-life conditions in a general pain clinic, which lasted for 6 months. Changes in pain intensity (VAS) and related quality of life changes (SF-36 HRQoL) were measured using validated internationally accepted questionnaires. The questionnaires were filled out by all patients on their own, so they provided information of self-esteem on their own. All patient post-treatment results were compared to pre-treatment results. The general quality of life changes found in our patients were compared to the representative norms of healthy population in Hungary. Subjects - patients participated voluntarily at their own decision in the survey. The underlying disease of chronic pain, age and gender of the patients did not limit the inclusion into the study.Data of 231 patients were evaluated. After pain therapy, the decrease in intensity of pain was confirmed by VAS at p=0.002. This was linked to a quality of life change that has been shown to be p=0.003 for men, with p=0.002 in women with SF-36 HRQoL. Based on the correlation coefficients, the changes in quality of life improved regardless of the age of the patients and the nature of the underlying conditions causing the pain.Although analgesia is basicly a symptomatic therapy, our findings suggest that the reduction of pain improves the quality of life of patients independently from their, and the curability of the underlying and accompanying diseases.Annak felmérése, hogy heterogén beteg­csoportban a fájdalomterápia milyen szinten képes befolyásolni az idült fájdalmakat, ez milyen hatással van a betegek életminőségére, és az elért változások milyen összefüggésben állnak az életkorral és az alapbetegségekkel. A felmérés annak népegészségügyi vonzata miatt is aktuális.Általános fájdalomambulancián végzett prospektív, nem randomizált, valós helyzetű, intervencionális, klinikai kohortvizsgálat, ami hat hónapon át zajlott. A fájdalom intenzitásának változását vizuális analóg skála (VAS) és az életminőségi változásokat rövidített formájú, egészséggel összefüggő életminőséget felmérő kérdőív (SF-36 HRQoL) alkalmazásával követtük. Mindkét módszer validált és nemzetközileg elfogadott. A kérdőívek kitöltését minden beteg saját kezűleg végezte - így önértékeléssel közöltek információt állapotukról. Minden beteg kezelés utáni eredményeit hasonlítottuk össze a kezelés előttiekkel. A különbségek alapján megállapított életminőségi változásokat a magyar­országi egészséges populáció reprezentatív normáihoz viszonyítottuk. A vizsgálat alanyai - A felmérésben a betegek ön­kéntesen, saját elhatározásuk alapján vettek részt. A krónikus fájdalmakat kiváltó kórfolyamat, a betegek kora, neme nem korlátozta a vizsgálatba történő beválasztást.231 beteg adatait értékeltük. Az alkalmazott fájdalomterápiás kezelések után a fájdalom intenzitásának csökkenése VAS alapján p = 0,002 szinten igazolódott szignifikánsnak. Az SF-36 HRQoL segítségével mért életminőségi változások férfiaknál p = 0,003, nőbetegeinknél p = 0,002 szignifikanciaszintű javulást igazoltak. A korrelációs együtthatók alapján az életminőségi változások a betegek életkorától és a fájdalmakat kiváltó alapbetegségek jellegétől függetlenül jöttek létre.Annak ellenére, hogy a fájdalomcsillapítás alapjában tüneti terápia, eredményeink arra engednek következtetni, hogy függetlenül a kezelt személyek életkorától, az alap- és kísérőbetegségek gyógyíthatóságától, a fájdalom csökkentése javít a betegek életminőségén.

István Molnár,1 Gabriella Hegyi,1,2 Lajos Zsom,3 Christine Saahs,4,5 Jan Vagedes,6,7 Gábor Kapócs,8 Zoltán Kovács,1 Martin-Günther Sterner,9 Henrik Szőke1,2 1Doctoral School of Health Sciences, Faculty of Health Sciences, University of Pécs, Pécs, Hungary; 2Department of CAM, Faculty of Health Sciences, University of Pécs, Pécs, Hungary; 3Department of Nephrology, Fresenius Medical Care, Cegléd, Hungary; 4Department of Pediatrics, University of Vienna, Vienna, Austria; 5Pediatric Outpatient Department, Krems, Austria; 6University Children’s Hospital, University of Tuebingen, Tuebingen, Germany; 7Department of Complementary and Integrative Medicine, ARCIM Institute (Academic Research in Complementary and Integrative Medicine), Filderstadt, Germany; 8Department of Psychiatry and Psychiatric Rehabilitation, Saint John Hospital, Budapest, Hungary; 9Department of Medical Clinics I, Klinikum Niederlausitz, Lauchhammer, Germany Background: Pancreatic cancer is a malignant disease with a high mortality rate and severe pain that is challenging to manage. To reduce the excruciating abdominal pain, opioids and adjuvant agents are conventionally used.Objectives: PRNCPB is a treatment of neural therapy. The number of studies assessing the effect on patients’ QoL is limited and inconsistent. With this study, we intended to address this issue.Study design: A prospective nonrandomized study with a series of cases of unresectable pancreatic cancer was conducted.Setting: The study was performed at our pain clinic under real life conditions.Materials and methods: A total number of 16 patients with severe abdominal pain were enrolled in the study all of whom had responded to combined systemic analgesic therapy inadequately and had intolerable side effects contraindicating further increase in dose. The efficacy of this invasive, palliative analgesic procedure was evaluated 35 days after PRNCPB was performed. Primary outcomes were changed in pain intensity using the VAS questionnaire. Secondary outcomes were improved in QoL using the SF-36 questionnaire. Changes in pain medications and adverse reactions were monitored.Results: After PRNCPB patients experienced a significant decrease (P=0.002) in pain intensity as shown by the VAS score, and a decreased opiate demand. Their QoL scores considering effect sizes also improved (P

Our aim was to evaluate the effects of percutaneous neurolysis of lumbal sympathetic ganglions on pain and the resulting changes in quality of life with validated objective and subjective methods. To follow the adverse effects and complications of the procedure.A prospective, non-randomized, interventional, clinical cohort study under real life conditons was conducted. The time of the observation was 6 months. Palliative neural therapy was performed to reduce the ischemic pain of the affected leg of the patients involved in the study. Prior to treatment and after 35 days, Visual Analogue Scale (VAS) was used to measure the intensity of lower limb pain. The related changes in the quality of life were followed by a general 36-Item Short-Form Health Survey (SF-36) questionnaire. We measured the changes of the patients' skin temperature and ankle/arm index. The post-treatment results were compared to the pre-treatment results. We compared the results of objective and subjective measures. We followed the side effects and complications of the pain therapy. Each of the examined subjects had obliterative (Fontaine II/b stage) arterial disease of the lower limbs, in which no revascularization intervention was feasible and their ischemic pain was of VAS≥7.Data of 124 patients (69 male, 55 female) could be evaluated. The decrease in intensity of limb pain in the post-treatment period was significant (p=0.001). Quality of life also indicated a significant improvement (p=0.004). Changes in skin temperature and ankle/arm index demonstrated significant improvement (p≤0.005): skin temperature increased from 27.6°C to 31.2°C, the ankle/arm index inceased from 0.67 to 0.83 on average. Changes in objective and subjective measures correlated with each other. No worthening of symptoms, serious adverse events or complications were observed.The chemical denervation of the lumbar sympathetic ganglions with percutaneous application is a minimally invasive intervention, useful in outpatient care, which can be well tolerated by the patient without any significant side effect or complication. Its hyperaemic effect and the pain reduction of the leg can improve the quality of life of the patients.Validált objektív és szubjektív módszerekkel felmérni a lumbalis szimpatikus dúcok percutan neurolysisének fájdalomra gyakorolt hatásait és az ebből eredő életminőségi változásokat. Követni a beavatkozás mellékhatásait, szövődményeit.Prospektív, nem randomizált, valós helyzetű, intervencionális, klinikai kohortvizsgálatunk időtartama hat hónap volt. A vizsgálatba bevont betegek érintett lábának terheléses ischaemiás fájdalmainak csökkentésére palliatív jellegű neurálterápiát végeztünk. A kezelés előtt, majd átlagosan 35 ± 2 nappal azt követően Vizuális Analóg Skála (VAS) alkalmazásával mértük az alsó végtagi fájdalmak intenzitásának változását és az ehhez köthető életminőségi változásokat 36-Item Short-Form Healthy Survey (SF-36) általános életminőséget meghatározó kérdőív segítségével követtük. Mértük a beteg végtag bőrhőmérsékletét és boka-kar indexét. A kezelés utáni eredményeket hasonlítottuk a kezelés előttiekhez. Összevetettük az objektív és a szubjektív mérések eredményeit. Követtük a fájdalomterápiás beavatkozás mellékhatásait és szövődményeit. A vizsgálatba bevont személyek mindegyikénél előre­- ha­ladott (Fontaine II/b stádiumú) alsó végtagi obliteratív verőérbetegség állt fenn, ami miatt a kezelés előtti ischaemiás fájdalmak VAS ≥ 7 erősségűek voltak és már semmilyen revascularisatiós intervenció nem volt kivitelezhető.Összesen 124 beteg (69 férfi, 55 nő) adata volt feldolgozható. A kezelés utáni időszakban a végtagi fájdalom intenzitása szignifikánsan csökkent (p = 0,001) és ebből adódóan az életminőségi mutatók is szignifikáns mértékű javulást igazoltak (p = 0,004). A neurálterápiás kezelés utáni ellenőrző vizsgálat során, a kezelés előtti értékekhez viszonyítva, mindegyik betegnél az érintett láb bőrhőmérséklete 27,6 °C-ról 31,2 °C-ig emelkedett (p ≤ 0,005), a boka-kar index átlagosan 0,67-ról 0,83-ra javult (p ≤ 0,005). Az objektív és szubjektív mérések változásai korreláltak egymással. A be­avatkozáshoz köthető állapotromlás, súlyos mellékhatás vagy szövődmény nem volt észlelhető.A lumbalis szimpatikus dúcok percutan kémiai denerválása minimálisan invazív módszer, a betegek számára jól tolerálható, érdemi mellékhatások és szövődmények nélkül kivitelezhető, járóbeteg-ellátás formájában alkalmazható. Palliatív jellege ellenére hyperaemizáló hatása és a láb fájdalmainak csökkentése által javíthat a beteg életminőségén.

Wild relatives of wheat, such as Aegilops spp. are potential sources of genes conferring tolerance to drought stress. As drought stress affects seed composition, the main goal of the present study was to determine the effects of drought stress on the content and composition of the grain storage protein (gliadin (Gli), glutenin (Glu), unextractable polymeric proteins (UPP%) and dietary fiber (arabinoxylan, β-glucan) components of hexaploid bread wheat (T. aestivum) lines containing added chromosomes from Ae. biuncialis or Ae. geniculata. Both Aegilops parents have higher contents of protein and β-glucan and higher proportions of water-soluble arabinoxylans (determined as pentosans) than wheat when grown under both well-watered and drought stress conditions. In general, drought stress resulted in increased contents of protein and total pentosans in the addition lines, while the β-glucan content decreased in many of the addition lines. The differences found between the wheat/Aegilops addition lines and wheat parents under well-watered conditions were also manifested under drought stress conditions: Namely, elevated β-glucan content was found in addition lines containing chromosomes 5Ug, 7Ug and 7Mb, while chromosomes 1Ub and 1Mg affected the proportion of polymeric proteins (determined as Glu/Gli and UPP%, respectively) under both well-watered and drought stress conditions. Furthermore, the addition of chromosome 6Mg decreased the WE-pentosan content under both conditions. The grain composition of the Aegilops accessions was more stable under drought stress than that of wheat, and wheat lines with the added Aegilops chromosomes 2Mg and 5Mg also had more stable grain protein and pentosan contents. The negative effects of drought stress on both the physical and compositional properties of wheat were also reduced by the addition of these. These results suggest that the stability of the grain composition could be improved under drought stress conditions by the intraspecific hybridization of wheat with its wild relatives.

Hong Qu glutinous rice wine (HQ wine) is a traditional alcoholic beverage produced in China by fermenting cooked rice using a fermentation starter prepared with the fungus Monascus purpureus. This starter (Hong Qu, HQ) is made empirically by open spontaneous fermentation that is hard to control and standardize, resulting in inconsistent wine quality. This study investigates representative HQ samples from a large geographic region. It explores fungal microbiome compositions, identifies characteristic differences important for the production of various HQ wine styles, and reveals the key fungi responsible for HQ wine fermentation characteristics. The source of the HQ inoculum was found to be the main factor influencing fungal community composition and diversity, followed by processing technology and geographical distribution. Linear discriminant analysis effect size (LEfSe) uncovered 14 genera as potential biomarkers to distinguish regional varieties of HQ. Significant differences were also found in fermentation characteristics such as liquefying power (LP), saccharifying power (SP), fermenting power (FP), total acid content (TA) and liquor-producing power (LPP). The key fungi responsible for LP (5 genera), SP (3 genera), FP (1 genera), LPP (4 genera), and TA (4 genera) were determined using redundancy correlation analysis. Finally, Spearman's correlation analysis indicated that LPP shows a strong positive correlation with FP and LP, while TA displays a strong negative correlation with FP. The results of this study may be utilized to prepare consistently high quality, next-generation HQ by better controlling fungal community structures, and to design fermentation processes for HQ wines with desirable oenological characteristics.

Crude extracts of in vitro and in vivo cultures of two strains of Photorhabdus l. sonorensis (Enterobacteriaceae) were analyzed by TLC, HPLC-UV and LC-MS. Nine unique compounds with mass/charge ratios (m/z) ranging from 331.3 to 713.5 were found in MS analyses. Bioactivity of extracts was assessed on a selection of plant pathogens/pests and non-target species. Caborca strain extracts showed the highest activity against Helicoverpa zea (Lepidoptera: Noctuidae) neonates at all concentrations tested. Mortality ranged from 11% (at 10 μg/ml) to 37% (at 40 μg/ml). Strain CH35 extracts showed the highest nematicidal activity on Meloidogyne incognita (Tylenchida: Meloidogynidae) at 40 μg/ml. Low to no nematicidal activity was observed against the non-target species Steinernema carpocapsae (Rhabditida: Steinernematidae) and Caenorhabditis elegans (Rhabditida: Rhabditidae). Caborca extracts exhibited a strong antibiotic effect on Pseudomonas syringae (Pseudomonadales: Pseudomonadacedae) at 40 μg/ml, while both Caborca and CH35 extracts inhibited the growth of Bacillus subitillis (Bacillales: Bacillaceae) at 40 μg/ml. All extracts strongly inhibited the growth of the fungus Fusarium oxysporum (Hypocreales: Nectriceae) but not that of Alternaria alternata (Pleosporales: Pleosporaceae). Contrastingly, a moderate to high inhibitory effect was denoted on the non-target biocontrol fungus Beauveria bassiana (Hypocreales: Clavivipitaceae).

Metabolomics is a rapidly emerging field of post-genomic research that aims to comprehensively analyze all metabolites in biological samples. Potential biomarkers that distinguish prostate cancer samples were successfully identified through metabolomics analysis (Sreekumar et al., 2009). Metabolome quantitative trait loci (mQTL) and genome-wide association studies coupled with metabolomics analysis (mGWAS) also became efficient tools to decipher the genetic basis of complex metabolic traits in large populations (Gong et al., 2013; Chen et al., 2014).

The cytomolecular discrimination of the Am- and A-genome chromosomes facilitates the selection of wheat-Triticum monococcum introgression lines. Fluorescence in situ hybridisation (FISH) with the commonly used DNA probes Afa family, 18S rDNA and pSc119.2 showed that the more complex hybridisation pattern obtained in T. monococcum relative to bread wheat made it possible to differentiate the Am and A chromosomes within homoeologous groups 1, 4 and 5. In order to provide additional chromosomal landmarks to discriminate the Am and A chromosomes, the microsatellite repeats (GAA)n, (CAG)n, (CAC)n, (AAC)n, (AGG)n and (ACT)n were tested as FISH probes. These showed that T. monococcum chromosomes have fewer, generally weaker, simple sequence repeat (SSR) signals than the A-genome chromosomes of hexaploid wheat. A differential hybridisation pattern was observed on 6Am and 6A chromosomes with all the SSR probes tested except for the (ACT)n probe. The 2Am and 2A chromosomes were differentiated by the signals given by the (GAA)n, (CAG)n and (AAC)n repeats, while only (GAA)n discriminated the chromosomes 3Am and 3A. Chromosomes 7Am and 7A could be differentiated by the lack of (GAA)n and (AGG)n signals on 7A. As potential landmarks for identifying the Am chromosomes, SSR repeats will facilitate the introgression of T. monococcum chromatin into wheat.

Two disparate polyketide families, the benzenediol lactones and the azaphilones, are produced by fungi using iterative polyketide synthase (iPKS) enzymes consisting of collaborating partner subunits. Exploitation of this common biosynthetic logic using iPKS subunit shuffling allowed the diversity-oriented combinatorial biosynthesis of unprecedented polyketide scaffolds new to nature, bearing structural motifs from both of these orthogonal natural product families. Starter unit acyltransferase domain replacements proved necessary but not sufficient to guarantee communication between iPKS subunits.

During 2008 and 2009 we excavated 9 early new age burials near Kaposvár. According to the find material and the burial practices the cemetery can be connected to inhabitants arriving from the Balkans during the Turkish era. A strange peculiarity was a young woman placed in sitting po-sition into the grave with an iron horseshoe under her legs.

In the first half of the study excavation projects fi-nanced through grants are described during the 2012-2015 period (Bárdudvarnok, Iharos, szőkedencs, őrtilos, zamár-di). In the second half the archaeological results of those pre-liminary excavations are dealt with which are connected to a given project e.g. the construction of Route No. 67., of the gas pipeline between Csombárd and Edde, and of the southern Balaton sewage pipeline. At the end of the paper the outcome of various other projects - further preliminary excavations, find protection and archaeological observation are mentioned.

The Benedictine abbey of Kaposszentjakab (Zselicszentjakab) was founded in 1061. Its remains were excavated by Emese Nagy in 1960–1966. Although the reconstruction of the abbey church has since long intrigued research, it is still uncertain whether the earliest abbey church had an axial or a central structure. The new excavations in 2013–2014 unearthed sections of the foundations of a church built prior to the abbey’s foundation. The remains of this early church were incorporated into the new building. The church was rebuilt during the Gothic period, when it received a vaulting.

Interspecific hybridization between bread wheat (Triticum aestivum, 2n = 42) and related species allows the transfer of agronomic and quality traits, whereby subsequent generations comprise an improved genetic background and can be directly applied in wheat breeding programmes. While wild relatives are frequently used as sources of agronomically favourable traits, cultivated species can also improve wheat quality and stress resistance. A salt-tolerant ‘Asakaze’/‘Manas’ 7H disomic addition line (2n = 44) with elevated β-glucan content, but with low fertility and an unstable genetic background was developed in an earlier wheat-barley prebreeding programme. The aim of the present study was to take this hybridization programme further and transfer the favourable barley traits into a more stable genetic background. Taking advantage of the breakage-fusion mechanism of univalent chromosomes, the ‘Rannaya’ winter wheat 7B monosomic line was used as female partner to the 7H addition line male, leading to the development of a compensating wheat/barley Robertsonian translocation line (7BS.7HL centric fusion, 2n = 42) exhibiting higher salt tolerance and elevated grain β-glucan content. Throughout the crossing programme, comprising the F1-F4 generations, genomic in situ hybridization, fluorescence in situ hybridization and chromosome-specific molecular markers were used to trace and identify the wheat and barley chromatin. Investigations on salt tolerance during germination and on the (1,3;1,4)-β-D-glucan (mixed-linkage glucan [MLG]) content of the seeds confirmed the salt tolerance and elevated grain MLG content of the translocation line, which can be directly applied in current wheat breeding programmes.

Glycosylation is a prominent strategy to optimize the pharmacokinetic and pharmacodynamic properties of drug-like small-molecule scaffolds by modulating their solubility, stability, bioavailability, and bioactivity. Glycosyltransferases applicable for “sugarcoating” various small-molecule acceptors have been isolated and characterized from plants and bacteria, but remained cryptic from filamentous fungi until recently, despite the frequent use of some fungi for whole-cell biocatalytic glycosylations. Here, we use bioinformatic and genomic tools combined with heterologous expression to identify a glycosyltransferase–methyltransferase (GT–MT) gene pair that encodes a methylglucosylation functional module in the ascomycetous fungus Beauveria bassiana. The GT is the founding member of a family nonorthologous to characterized fungal enzymes. Using combinatorial biosynthetic and biocatalytic platforms, we reveal that this GT is a promiscuous enzyme that efficiently modifies a broad range of drug-like substrates, including polyketides, anthraquinones, flavonoids, and naphthalenes. It yields both O- and N-glucosides with remarkable regio- and stereospecificity, a spectrum not demonstrated for other characterized fungal enzymes. These glucosides are faithfully processed by the dedicated MT to afford 4-O-methyl-glucosides. The resulting “unnatural products” show increased solubility, while representative polyketide methylglucosides also display increased stability against glycoside hydrolysis. Upon methylglucosi-dation, specific polyketides were found to attain cancer cell line-specific antiproliferative or matrix attachment inhibitory activities. These findings will guide genome mining for fungal GTs with novel substrate and product specificities, and empower the efficient combinatorial biosynthesis of a broad range of natural and unnatural glycosides in total biosynthetic or biocatalytic formats.

Barley chromosome 5H, carrying important QTLs for plant adaptation and tolerance to abiotic stresses, is extremely instable in the wheat genetic background and is eliminated in the early generations of wheat-barley crosses. A spontaneous wheat-barley 5HS-7DS.7DL translocation was previously obtained among the progenies of the Mv9kr1 x Igri hybrid. The present work reports on the transfer of the 5HS-7DS.7DL translocation into a modern wheat cultivar, Mv Bodri, in order to use it in the wheat breeding program. The comparison of the hybridization bands of DNA repeats HvT01, pTa71, (GAA)n and the barley centromere-specific (AGGGAG)n in Igri barley and the 5HS-7DS.7DL translocation, together with the visualization of the barley chromatin made it possible to determine the size of the introgressed barley segment, which was approximately 74% of the whole 5HS. Of the 29 newly developed PCR markers, whose source ESTs were selected from the Genome Zipper of barley chromosome 5H, 23 were mapped in the introgressed 1-0.26 FL 5HS bin, three were located in the missing C-0.26 FL region, while three markers were specific for 5HL. The translocation breakpoint was flanked by markers Hv7502 and Hv3949. A comparison of the parental wheat cultivars and the wheat-barley introgression lines indicated that the presence of the translocation improved tillering ability in the Mv9kr1 and Mv Bodri genetic background. The similar or better yield components under high- or low-input cultivation environments, respectively, indicated that the 5HS-7DS.7DL translocation had little or no negative effect on yield components, making it a promising genotype to improve wheat genetic diversity. These results promise to accelerate functional genomic studies on barley chromosome 5H and to support pre-breeding and breeding research on wheat.

Thinopyrum elongatum (Host) D.R. Dewey has served as an important gene source for wheat breeding improvement for many years. The exact characterization of its chromosomes is important for the detailed analysis of prebreeding materials produced with this species. The major aim of this study was to identify and characterize new molecular markers to be used for the rapid analysis of E genome chromatin in wheat background. Sixty of the 169 conserved orthologous set (COS) markers tested on diverse wheat-Th. elongatum disomic/ditelosomic addition lines were assigned to various Th. elongatum chromosomes and will be used for marker-assisted selection. The macrosyntenic relationship between the wheat and Th. elongatum genomes was investigated using EST sequences. Several rearrangements were revealed in homoeologous chromosome groups 2, 5, 6 and 7, while chromosomes 1 and 4 were conserved. Molecular cytogenetic and marker analysis showed the presence of rearranged chromosome involved in 6ES and 2EL arms in the 6E disomic addition line. The selected chromosome arm-specific COS markers will make it possible to identify gene introgressions in breeding programmes and will also be useful in the development of new chromosome-specific markers, evolutionary analysis and gene mapping.

Mixed Landolt-type pH oscillators are versatile systems that allow the experimental study of a wide range of nonlinear phenomena including multistability, oscillations, and spatiotemporal patterns. We report on the dynamics of the bromate-sulfite-ferrocyanide reaction operated in a open one-side-fed reactor, where spatial bistability, spatiotemporal oscillations, front and Turing-type patterns have been observed. The role of different experimental parameters, like the input flow concentrations of the hydrogen and the ferrocyanide ions, the temperature and the thickness of the gel medium (which affects the rate of the diffusive feed) have been investigated. We point out that all these parameters can be efficiently used to control the spatiotemporal dynamics. We show that the increase of ionic strength stabilizes the uniform states at the expense of the patterned one. Some general aspects of the spatiotemporal dynamics of mixed Landolt type systems, which are based on the oxidation of sulfite ions by strong oxidants, are emphasized.

The carotenoid deinoxanthin is a crucial resistance factor against various stresses in the radiation-resistant bacterium Deinococcus radiodurans. Disruption of the gene dr2473 encoding the cytochrome P450 CYP287A1 led to the accumulation of 2-deoxydeinoxanthin in D. radiodurans, demonstrating that CYP287A1 is a novel β-carotene 2-hydroxylase. The dr2473 knockout mutant was shown to be more sensitive to UV radiation and oxidative stress than the wild-type strain D. radiodurans R1, indicating that the C2 alcohol of deinoxanthin is important for antioxidant activity.

Enzyme-linked immunosorbent assays (ELISAs) are widely used to determine gluten contamination in gluten-free and low gluten food samples. ELISA assays developed using monoclonal antibodies against known toxic peptides have an advantage in the identification of toxic prolamin content in protein extracts of different food samples, as well as raw materials. R5 and G12 monoclonal antibodies specific for two known toxic peptides used in commercially available gluten ELISA assays were applied to test toxic peptide contents in wheat relatives and wild wheat species with different genome composition and complexity. Although the R5 peptide content showed some correlation with ploidy levels in Triticum species, there was a high variance among Aegilops species. Some of the analysed diploid Aegilops species showed extremely high R5 peptide contents. Based on the bioinformatics analyses, the R5 peptide was present in most of the sulphur rich prolamins in all the analysed species, whereas the G12 epitope was exclusively present in alpha gliadins. High variation was detected in the position and frequency of epitopes in sequences originating from the same species, thus highlighting the importance of genotypic variation within species. Identification of new prolamin alleles of wheat relatives and wild wheat species is of great importance in order to find germplasm for special end-use quality purposes as well as development of food with reduced toxicity.

The hypocrealean fungus Claviceps paspali is a parasite of wild grasses. This fungus is widely utilized in the pharmaceutical industry for the manufacture of ergot alkaloids, but also produces tremorgenic and neurotoxic indole-diterpene (IDT) secondary metabolites such as paspalitrems A and B. IDTs cause significant losses in agriculture and represent health hazards that threaten food security. Conversely, IDTs may also be utilized as lead compounds for pharmaceutical drug discovery. Current protoplast-mediated transformation protocols of C. paspali are inadequate as they suffer from inefficiencies in protoplast regeneration, a low frequency of DNA integration, and a low mitotic stability of the nascent transformants. We adapted and optimized Agrobacterium tumefaciens-mediated transformation (ATMT) for C. paspali and validated this method with the straightforward creation of a mutant strain of this fungus featuring a targeted replacement of key genes in the putative IDT biosynthetic gene cluster. Complete abrogation of IDT production in isolates of the mutant strain proved the predicted involvement of the target genes in the biosynthesis of IDTs. The mutant isolates continued to produce ergot alkaloids undisturbed, indicating that equivalent mutants generated in industrial ergot producers may have a better safety profile as they are devoid of IDT-type mycotoxins. Meanwhile, ATMT optimized for Claviceps spp. may open the door for the facile genetic engineering of these industrially and ecologically important organisms.

Salinity-induced osmotic, ionic and oxidative stress responses were investigated on Asakaze/Manas wheat/barley addition lines 7H, 7HL and 7HS, together with their barley (salt-tolerant) and wheat (relatively salt-sensitive) parents. Growth, photosynthetic activity, chlorophyll degradation, proline, glycine betaine accumulation, sugar metabolism, Na+ and K+ uptake and transport processes and the role of polyamines and antioxidants were studied in young plants grown in hydroponic culture with or without salt treatment. Changes in plant growth and photosynthetic activity of plants demonstrated that the salt tolerance of the addition lines 7H and 7HL was similar to that of barley parent cv. Manas, while the sensitivity of the addition line 7HS was similar to that of the wheat parent cv. Asakaze. The Na accumulation in the roots and shoots did not differ between the addition lines and wheat parent. The activation of various genes related to Na uptake and transport was not correlated with the salt tolerance of the genotypes. These results indicated that the direct regulation of Na transport processes is not the main reason for the salt tolerance of these genotypes. Salt treatment induced a complex metabolic rearrangement in both the roots and shoots of all the genotypes. Elevated proline accumulation in the roots and enhanced sugar metabolism in the shoots were found to be important for salt tolerance in the 7H and 7HL addition lines and in barley cv. Manas. In wheat cv. Asakaze and the 7HS addition line the polyamine metabolism was activated. It seems that osmotic adjustment is a more important process in the improvement of salt tolerance in 7H addition lines than the direct regulation of Na transport processes or antioxidant defence.

In 2010, when the National Alliance for Advanced Biofuels and Bioproducts (NAABB) consortium began, little was known about the molecular basis of algal biomass or oil production. Very few algal genome sequences were available and efforts to identify the best-producing wild species through bioprospecting approaches had largely stalled after the U.S. Department of Energy's Aquatic Species Program. This lack of knowledge included how reduced carbon was partitioned into storage products like triglycerides or starch and the role played by metabolite remodeling in the accumulation of energy-dense storage products. Furthermore, genetic transformation and metabolic engineering approaches to improve algal biomass and oil yields were in their infancy. Genome sequencing and transcriptional profiling were becoming less expensive, however; and the tools to annotate gene expression profiles under various growth and engineered conditions were just starting to be developed for algae. It was in this context that an integrated algal biology program was introduced in the NAABB to address the greatest constraints limiting algal biomass yield. This review describes the NAABB algal biology program, including hypotheses, research objectives, and strategies to move algal biology research into the twenty-first century and to realize the greatest potential of algae biomass systems to produce biofuels.

Cereal grain fiber is an important health-promoting component in the human diet. One option to improve dietary fiber content and composition in wheat is to introduce genes from its wild relatives Aegilops biuncialis and Aegilops geniculata. This study showed that the addition of chromosomes 2Ug, 4Ug, 5Ug, 7Ug, 2Mg, 5Mg, and 7Mg of Ae. geniculata and 3Ub, 2Mb, 3Mb, and 7Mb of Ae. biuncialis into bread wheat increased the seed protein content. Chromosomes 1Ug and 1Mg increased the proportion of polymeric glutenin proteins, while the addition of chromosomes 1Ub and 6Ub led to its decrease. Both Aegilops species had higher proportions of β-glucan compared to arabinoxylan (AX) than wheat lines, and elevated β-glucan content was also observed in wheat chromosome addition lines 5U, 7U, and 7M. The AX content in wheat was increased by the addition of chromosomes 5Ug, 7Ug, and 1Ub while water-soluble AX was increased by the addition of chromosomes 5U, 5M, and 7M, and to a lesser extent by chromosomes 3, 4, 6Ug, and 2Mb. Chromosomes 5Ug and 7Mb also affected the structure of wheat AX, as shown by the pattern of oligosaccharides released by digestion with endoxylanase. These results will help to map genomic regions responsible for edible fiber content in Aegilops and will contribute to the efficient transfer of wild alleles in introgression breeding programs to obtain wheat varieties with improved health benefits. Key Message: Addition of Aegilops U- and M-genome chromosomes 5 and 7 improves seed protein and fiber content and composition in wheat.

Each major step leading to the classical yellow, orange and red constituents of Monascus azaphilone pigments was defined., Monascus azaphilone pigments (MonAzPs) are very widely used as food colorants, but their biosynthetic pathway has remained poorly characterized for more than half a century. In this study, the individual steps of MonAzPs biosynthesis in Monascus ruber M7 were elucidated by a combination of targeted gene knockouts, heterologous gene expression, and in vitro chemical and enzymatic reactions. This study describes the first rational engineering of MonAzPs biosynthesis and provides a roadmap for future pathway engineering efforts directed towards the selective production of the most valuable pigments and serves as a model for the biosynthesis of fungal azaphilones in general.

Cereal grain fiber is an important health-promoting component in the human diet. One option to improve dietary fiber content and composition in wheat is to introduce genes from its wild relatives Aegilops biuncialis and Aegilops geniculata. This study showed that the addition of chromosomes 2Ug, 4Ug, 5Ug, 7Ug, 2Mg, 5Mg, and 7Mg of Ae. geniculata and 3Ub, 2Mb, 3Mb, and 7Mb of Ae. biuncialis into bread wheat increased the seed protein content. Chromosomes 1Ug and 1Mg increased the proportion of polymeric glutenin proteins, while the addition of chromosomes 1Ub and 6Ub led to its decrease. Both Aegilops species had higher proportions of β-glucan compared to arabinoxylan (AX) than wheat lines, and elevated β-glucan content was also observed in wheat chromosome addition lines 5U, 7U, and 7M. The AX content in wheat was increased by the addition of chromosomes 5Ug, 7Ug, and 1Ub while water-soluble AX was increased by the addition of chromosomes 5U, 5M, and 7M, and to a lesser extent by chromosomes 3, 4, 6Ug, and 2Mb. Chromosomes 5Ug and 7Mb also affected the structure of wheat AX, as shown by the pattern of oligosaccharides released by digestion with endoxylanase. These results will help to map genomic regions responsible for edible fiber content in Aegilops and will contribute to the efficient transfer of wild alleles in introgression breeding programs to obtain wheat varieties with improved health benefits. Key Message: Addition of Aegilops U- and M-genome chromosomes 5 and 7 improves seed protein and fiber content and composition in wheat.

The salt stress responses of wheat–barley addition lines (2H, 3H, 3HS, 4H, 6H, 7H and 7HL) were compared to those of the parental genotypes wheat cv. Asakaze and barley cv. Manas and two other wheat genotypes [Chinese Spring (CS) and Mv9kr1] during germination and in young plants grown in hydroponic culture with or without salt treatment. Among the wheat genotypes frequently used for interspecific hybridization, Asakaze possesses relatively high salt tolerance, as indicated by the less pronounced reduction in germination % and in root and shoot growth and the retention of high leaf water content and photosynthetic activity, as compared to CS and Mv9kr1. The barley cv. Manas showed better salt tolerance than wheat cv. Asakaze, although Manas accumulated more Na in the root, but its transport to the shoots is restricted. Among the addition lines tested, the disomic addition line 7H and ditelosomic line 7HL exhibited higher salt tolerance both during germination and in the early developmental stages than the wheat parent, which may be related to the elevated osmotic adjustment capacity of these addition lines, similar to that found for barley cv. Manas. The paper also discusses the effects of other chromosomes on the salt stress response.

A recently developed synthetic amphiploid, Triticum timococcum Kost., nom. nud. (2n = 6x = 42, AtAtGGAmAm) is described in the present study. This hexaploid taxon was developed by colchicine treatment in Martonvasar from the hybrid of a selected accession of Triticum timopheevii Zhuk. (2n = 4x = 28, AtAtGG) and a prebred semi-dwarf line of Triticum monococcum L. (2n = 2x = 14, AmAm). A detailed cytomolecular examination was carried out using the sequential multicolour fluorescence and genomic in situ hybridization techniques (FISH and mcGISH). It was proved that T. timococcum has 42 chromosomes originating from its parents. The chromosomes of the A genomes of T. monococcum and T. timopheevii could be distinguished in the amphiploid using FISH. The successful discrimination of the chromosomes was supported by the karyotypes of the three genomes and the successful optimization of the mcGISH technique for the A and G chromosomes achieved in the present study. A phenotypic evaluation was also carried out under natural and artificial growing conditions in 2012 and 2013. Based on the results, T. timococcum has intermediate characteristics in terms of spike (spikelet) shape and plant height, while it is similar to the female parent, T. timopheevii regarding pubescence. Like its parents, T. timococcum showed outstanding resistance to the main fungal diseases of wheat. T. timococcum headed later and developed longer and looser spikes, fewer tillers and only a third as many seeds than its parents. The third generation of T. timococcum was able to develop an acceptable number of seeds, even taking into account the reduced germination ability in the field.

Osmotic stress responses of water content, photosynthetic parameters and biomass production were investigated in wheat-Aegilops biuncialis amphiploids and in wheat genotypes to clarify whether they can use to improve the drought tolerance of bread wheat. A decrease in the osmotic pressure of the medium resulted in considerable water loss, stomatal closure and a decreased CO2 assimilation rate for the wheat genotypes, while the changes in these parameters were moderate for the amphiploids. Maximal assimilation rate was maintained at high level even under severe osmotic stress in the amphiploids, while it decreased substantially in the wheat genotypes. Nevertheless, the effective quantum yield of PS II was higher and the quantum yield of non-photochemical quenching of PS II and PS I was lower for the amphiploids than for the wheat cultivars. Parallel with this, higher cyclic electron flow was detected in wheat than in the amphiploids. The elevated photosynthetic activity of amphiploids under osmotic stress conditions was manifested in higher biomass production by roots and shoots as compared to wheat genotypes. These results indicate that the drought-tolerant traits of Ae. biuncialis can be manifested in the wheat genetic background and these amphiploids are suitable genetic materials for improving drought tolerance of wheat.

Chromosomes 5A (u) , 5S and 5D can be isolated from wild progenitors, providing a chromosome-based approach to develop tools for breeding and to study the genome evolution of wheat. The three subgenomes of hexaploid bread wheat originated from Triticum urartu (A(u)A(u)), from a species similar to Aegilops speltoides (SS) (progenitor of the B genome), and from Ae. tauschii (DD). Earlier studies indicated the potential of chromosome genomics to assist gene transfer from wild relatives of wheat and discover novel genes for wheat improvement. This study evaluates the potential of flow cytometric chromosome sorting in the diploid progenitors of bread wheat. Flow karyotypes obtained by analysing DAPI-stained chromosomes were characterized and the contents of the chromosome peaks were determined. FISH analysis with repetitive DNA probes proved that chromosomes 5A(u), 5S and 5D could be sorted with purities of 78-90 %, while the remaining chromosomes could be sorted in groups of three. Twenty-five conserved orthologous set (COS) markers covering wheat homoeologous chromosome groups 1-7 were used for PCR with DNA amplified from flow-sorted chromosomes and genomic DNA. These assays validated the cytomolecular results as follows: peak I on flow karyotypes contained chromosome groups 1, 4 and 6, peak II represented homoeologous group 5, while peak III consisted of groups 2, 3 and 7. The isolation of individual chromosomes of wild progenitors provides an attractive opportunity to investigate the structure and evolution of the polyploid genome and to deliver tools for wheat improvement.

3MbTriticum aestivum L. (Mv9kr1) – Aegilops biuncialis Vis. (MvGB642) addition lines were crossed with the Chinese Spring ph1b mutant genotype (CSph1b) to produce 3Mb–wheat chromosome rearrangements. In the F3generation, 3Mb(4B) substitution lines and 3Mb.4BS centric fusions were identified with in situ hybridization using repetitive and genomic DNA probes, and with SSR markers. Grain micronutrient analysis showed that the investigated Ae. biuncialis accession MvGB382 and the parental line MvGB642 are suitable gene sources for improving the grain micronutrient content of wheat, as they have higher K, Zn, Fe, and Mn contents. The results suggested that the Ae. biuncialis chromosome 3Mbcarries genes determining the grain micronutrient content, as the 3Mb.4BS centric fusion had significantly higher Zn and Mn contents compared with the recipient wheat cultivar. As yield-related traits, such as the number of tillers, the length of main spike, and spikelets per main spike, were similar in the 3Mb.4BS centric fusion and the parental wheat genotype, it can be concluded that this line could be used in pre-breeding programs aimed at enriching elite wheat cultivars with essential micronutrients.

The paper deals with the abbey founded in the 11. Century, with its periods and remains of an earlier building.

This paper reports detailed FISH-based karyotypes for three diploid wheatgrass species Agropyron cristatum (L.) Beauv., Thinopyrum bessarabicum (Savul.&Rayss) A. Love, Pseudoroegneria spicata (Pursh) A. Love, the supposed ancestors of hexaploid Thinopyrum intermedium (Host) Barkworth & D.R.Dewey, compiled using DNA repeats and comparative genome analysis based on COS markers. Fluorescence in situ hybridization (FISH) with repetitive DNA probes proved suitable for the identification of individual chromosomes in the diploid JJ, StSt and PP genomes. Of the seven microsatellite markers tested only the (GAA)n trinucleotide sequence was appropriate for use as a single chromosome marker for the P. spicata AS chromosome. Based on COS marker analysis, the phylogenetic relationship between diploid wheatgrasses and the hexaploid bread wheat genomes was established. These findings confirmed that the J and E genomes are in neighbouring clusters.

TPS3152 Background: Type I insulin-like growth factor receptor (IGF-1R) is a transmembrane protein which is overexpressed in solid tumors including non–small cell lung, prostate, and breast cancers. [225Ac]-FPI-1434 is a radioimmunoconjugate consisting of a humanized monoclonal antibody that binds to the external domain of IGF-1R, a proprietary bifunctional chelate, and an alpha-emitting radionuclide actinium-225 (Ac-225), which binds to the external domain of IGF-1R. Internalization of the conjugate and decay of Ac-225 causes tumor cell death primarily through double stranded DNA breaks. The indium-111 analog, [111In]-FPI-1547, with the identical antibody and bifunctional chelate is used for patient selection, in-vivo imaging, and quantification of IGF-1R targets prior to therapy. Based on anti-tumor activity of [225Ac]-FPI-1434 in preclinical models, favorable toxicology studies in cynomolgus monkeys, and prior human experience with the unconjugated antibody, the first in human clinical evaluation was initiated. Methods: This open-label multi-center phase I study (NCT03746431) follows a modified 3+3 dose-escalation design to characterize the safety profile, determine a maximum tolerated dose (MTD), evaluate dose-limiting toxicities (DLT), describe pharmacokinetics, derive radiation dose estimates to normal organs, and evaluate the objective response rate of [225Ac]-FPI-1434 therapy in patients with IGF-1R expressing solid tumors. Eligibility requirements for therapy include: presence of at least one measurable lesion as determined by sufficient tumor uptake using SPECT/CT of an imaging analog [111In]-FPI-1547; radiation dose estimates of the planned therapeutic activity within prespecified limits; and adequate bone marrow reserves, hepatic, and renal function. Dose cohorts begin with 10 kBq [225Ac]-FPI-1434 per kilogram (kg) patient weight and successively increase to 20, 40, 80, and 120 kBq/kg as a single intravenous injection per patient followed by an 8-week DLT evaluation period. This trial is currently enrolling patients. Clinical trial information: NCT03746431.