Genetic modification of tomato with the tobacco lycopene β-cyclase gene produces high β-carotene and lycopene fruit

Transgenic Solanum lycopersicum plants expressing an additional copy of the lycopene beta-cyclase gene (LCYB) from Nicotiana tabacum, under the control of the Arabidopsis polyubiquitin promoter (UBQ3), have been generated. Expression of LCYB was increased some 10-fold in ripening fruit compared to vegetative tissues. The ripe fruit showed an orange pigmentation, due to increased levels (up to 5-fold) of beta-carotene, with negligible changes to other carotenoids, including lycopene. Phenotypic changes in carotenoids were found in vegetative tissues, but levels of biosynthetically related isoprenoids such as tocopherols, ubiquinone and plastoquinone were barely altered. Transformants showed tolerance to the bleaching herbicide beta-cyclase inhibitor, 2-(4-chlorophenylthio) triethylamine. The phenotype was inherited for at least three generations

Compensating Inhomogeneities of Neuromorphic VLSI Devices Via Short-Term Synaptic Plasticity

Recent developments in neuromorphic hardware engineering make mixed-signal VLSI neural network models promising candidates for neuroscientific research tools and massively parallel computing devices, especially for tasks which exhaust the computing power of software simulations. Still, like all analog hardware systems, neuromorphic models suffer from a constricted configurability and production-related fluctuations of device characteristics. Since also future systems, involving ever-smaller structures, will inevitably exhibit such inhomogeneities on the unit level, self-regulation properties become a crucial requirement for their successful operation. By applying a cortically inspired self-adjusting network architecture, we show that the activity of generic spiking neural networks emulated on a neuromorphic hardware system can be kept within a biologically realistic firing regime and gain a remarkable robustness against transistor-level variations. As a first approach of this kind in engineering practice, the short-term synaptic depression and facilitation mechanisms implemented within an analog VLSI model of I&F neurons are functionally utilized for the purpose of network level stabilization. We present experimental data acquired both from the hardware model and from comparative software simulations which prove the applicability of the employed paradigm to neuromorphic VLSI devices

A flower-specific Myb protein activates transcription of phenylpropanoid biosynthetic genes

10 pages, 9 figures.-- PMID: 8306956 [PubMed].-- PMCID: PMC394786.Synthesis of flavonoid pigments in flowers requires the co-ordinated expression of genes encoding enzymes in th phenylpropanoid biosynthetic pathway. Some cis-elements involved in the transcriptional control of these genes have been defined. We report binding of petal-specific activities from tobacco and Antirrhinum majus (snapdragon) to an element conserved in promoters of phenylpropanoid biosynthetic genes and implicated in expression in flowers. These binding activities were inhibited by antibodies raised against Myb305, a flower-specific Myb protein previously cloned from Antirrhinum by sequence homology. Myb305 bound to the same element and formed a DNA-protein complex with the same mobility as the Antirrhinum petal protein in electrophoretic mobility shift experiments. Myb305 activated expression from its binding site in yeast and in tobacco protoplasts. In protoplasts, activation also required a G-box-like element, suggesting co-operation with other elements and factors. The results strongly suggest a role for Myb305-related proteins in the activation of phenylpropanoid biosynthetic genes in flowers. This is consistent with the genetically demonstrated role of plant Myb proteins in the regulation of genes involved in flavonoid synthesis.We are grateful to Dr V.Chandler (University of Oregon) for anti-Cl serum, to Dr J.Lipsick (Stanford University) for anti-Cl and anti-v-Myb sera, to C.Smith for tobacco transformations, to Dr J.Munoz-Blanco and Dr M.Holdsworth for advice and vectors for yeast transformation, to Dr D.Hatton for advice on tobacco protoplast transformation, to Dr V.Hocher and Y.Kishima for access to unpublished data. R.W.M.S. received an EC pre-doctoral fellowship (ECLAIR programme, contract AGRE913013), E.M. was supported by a FEBS Fellowship and F.C-M. was supported by the EC Bridge Programme (contract BIOT0164CEDB).Peer reviewe

Engineering of tomato for the sustainable production of ketocarotenoids and its evaluation in aquaculture feed

Ketocarotenoids are high-value pigments used commercially across multiple industrial sectors as colorants and supplements. Chemical synthesis using petrochemical-derived precursors remains the production method of choice. Aquaculture is an example where ketocarotenoid supplementation of feed is necessary to achieve product viability. The biosynthesis of ketocarotenoids, such as canthaxanthin, phoenicoxanthin, or astaxanthin in plants is rare. In the present study, complex engineering of the carotenoid pathway has been performed to produce high-value ketocarotenoids in tomato fruit (3.0 mg/g dry weight). The strategy adopted involved pathway extension beyond β-carotene through the expression of the β-carotene hydroxylase (CrtZ) and oxyxgenase (CrtW) from Brevundimonas sp. in tomato fruit, followed by β-carotene enhancement through the introgression of a lycopene β-cyclase (β-Cyc) allele from a Solanum galapagense background. Detailed biochemical analysis, carried out using chromatographic, UV/VIS, and MS approaches, identified the predominant carotenoid as fatty acid (C14:0 and C16:0) esters of phoenicoxanthin, present in the S stereoisomer configuration. Under a field-like environment with low resource input, scalability was shown with the potential to deliver 23 kg of ketocarotenoid/hectare. To illustrate the potential of this “generally recognized as safe” material with minimal, low-energy bioprocessing, two independent aquaculture trials were performed. The plant-based feeds developed were more efficient than the synthetic feed to color trout flesh (up to twofold increase in the retention of the main ketocarotenoids in the fish fillets). This achievement has the potential to create a new paradigm in the renewable production of economically competitive feed additives for the aquaculture industry and beyond

Clinical guidelines for the use of lifestyle-based mental health care in major depressive disorder: World Federation of Societies for Biological Psychiatry (WFSBP) and Australasian Society of Lifestyle Medicine (ASLM) taskforce

Objectives: The primary objectives of these international guidelines were to provide a global audience of clinicians with (a) a series of evidence-based recommendations for the provision of lifestyle-based mental health care in clinical practice for adults with Major Depressive Disorder (MDD) and (b) a series of implementation considerations that may be applicable across a range of settings. Methods: Recommendations and associated evidence-based gradings were based on a series of systematic literature searches of published research as well as the clinical expertise of taskforce members. The focus of the guidelines was eight lifestyle domains: physical activity and exercise, smoking cessation, work-directed interventions, mindfulness-based and stress management therapies, diet, sleep, loneliness and social support, and green space interaction. The following electronic bibliographic databases were searched for articles published prior to June 2020: PubMed, EMBASE, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register), CINAHL, PsycINFO. Evidence grading was based on the level of evidence specific to MDD and risk of bias, in accordance with the World Federation of Societies for Biological Psychiatry criteria. Results: Nine recommendations were formed. The recommendations with the highest ratings to improve MDD were the use of physical activity and exercise, relaxation techniques, work-directed interventions, sleep, and mindfulness-based therapies (Grade 2). Interventions related to diet and green space were recommended, but with a lower strength of evidence (Grade 3). Recommendations regarding smoking cessation and loneliness and social support were based on expert opinion. Key implementation considerations included the need for input from allied health professionals and support networks to implement this type of approach, the importance of partnering such recommendations with behaviour change support, and the need to deliver interventions using a biopsychosocial-cultural framework. Conclusions: Lifestyle-based interventions are recommended as a foundational component of mental health care in clinical practice for adults with Major Depressive Disorder, where other evidence-based therapies can be added or used in combination. The findings and recommendations of these guidelines support the need for further research to address existing gaps in efficacy and implementation research, especially for emerging lifestyle-based approaches (e.g. green space, loneliness and social support interventions) where data are limited. Further work is also needed to develop innovative approaches for delivery and models of care, and to support the training of health professionals regarding lifestyle-based mental health care

The Effects of Dietary Improvement on Symptoms of Depression and Anxiety: A Meta-Analysis of Randomized Controlled Trials

OBJECTIVE: Poor diet can be detrimental to mental health. However, the overall evidence for the effects of dietary interventions on mood and mental well-being has yet to be assessed. We conducted a systematic review and meta-analysis examining effects of dietary interventions on symptoms of depression and anxiety. METHODS: Major electronic databases were searched through March 2018 for all randomized controlled trials of dietary interventions reporting changes in symptoms of depression and/or anxiety in clinical and nonclinical populations. Random-effects meta-analyses were conducted to determine effect sizes (Hedges' g with 95% confidence intervals [CI]) for dietary interventions compared with control conditions. Potential sources of heterogeneity were explored using subgroups and meta-regression analyses. RESULTS: Results: Sixteen eligible randomized controlled trials (published in English) with outcome data for 45,826 participants were included; the majority of which examined samples with nonclinical depression (n = 15 studies). Nonetheless, dietary interventions significantly reduced depressive symptoms (g = 0.162, 95% CI = 0.055 to 0.269, p = 0.003). Similar effects were observed among high-quality trials (g = 0.171, 95% C.I.=0.057 to 0.286, p=0.003) and when compared with both inactive (g = 0.114, 95% C.I.=0.008 to 0.219, p=0.035) and active controls (g = 0.224, 95% C.I.= 0.052 to 0.397, p = 0.011). No effect of dietary interventions was observed for anxiety (k = 11, n = 2270, g = 0.085, 95% C.I. = -0.031 to 0.202, p=0.151). Studies with female samples observed significantly greater benefits from dietary interventions, for symptoms of both depression and anxiety. CONCLUSIONS: Dietary interventions hold promise as a novel intervention for reducing symptoms of depression across the population. Future research is required to determine the specific components of dietary interventions that improve mental health, explore underlying mechanisms, and establish effective schemes for delivering these interventions in clinical and public health settings. REGISTRATION: PROSPERO Online Protocol: CRD42018091256

A variational method based on weighted graph states

In a recent article [Phys. Rev. Lett. 97 (2006), 107206], we have presented a class of states which is suitable as a variational set to find ground states in spin systems of arbitrary spatial dimension and with long-range entanglement. Here, we continue the exposition of our technique, extend from spin 1/2 to higher spins and use the boson Hubbard model as a non-trivial example to demonstrate our scheme.Comment: 36 pages, 13 figure

Distribution and Molecular Evolution of Bacillus anthracis Genotypes in Namibia

The recent development of genetic markers for Bacillus anthracis has made it possible to monitor the spread and distribution of this pathogen during and between anthrax outbreaks. In Namibia, anthrax outbreaks occur annually in the Etosha National Park (ENP) and on private game and livestock farms. We genotyped 384 B. anthracis isolates collected between 1983–2010 to identify the possible epidemiological correlations of anthrax outbreaks within and outside the ENP and to analyze genetic relationships between isolates from domestic and wild animals. The isolates came from 20 animal species and from the environment and were genotyped using a 31-marker multi-locus-VNTR-analysis (MLVA) and, in part, by twelve single nucleotide polymorphism (SNP) markers and four single nucleotide repeat (SNR) markers. A total of 37 genotypes (GT) were identified by MLVA, belonging to four SNP-groups. All GTs belonged to the A-branch in the cluster- and SNP-analyses. Thirteen GTs were found only outside the ENP, 18 only within the ENP and 6 both inside and outside. Genetic distances between isolates increased with increasing time between isolations. However, genetic distance between isolates at the beginning and end of the study period was relatively small, indicating that while the majority of GTs were only found sporadically, three genetically close GTs, accounting for more than four fifths of all the ENP isolates, appeared dominant throughout the study period. Genetic distances among isolates were significantly greater for isolates from different host species, but this effect was small, suggesting that while species-specific ecological factors may affect exposure processes, transmission cycles in different host species are still highly interrelated. The MLVA data were further used to establish a model of the probable evolution of GTs within the endemic region of the ENP. SNR-analysis was helpful in correlating an isolate with its source but did not elucidate epidemiological relationships

Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stopping antirheumatic therapy: interim results from the prospective randomised controlled RETRO study

Objective: To prospectively analyse the risk for disease relapses in patients with rheumatoid arthritis (RA) in sustained remission, either continuing, tapering or stopping disease-modifying antirheumatic drugs (DMARDs) in a prospective randomised controlled trial. Methods: Reduction of Therapy in patients with Rheumatoid arthritis in Ongoing remission is a multicentre, randomised controlled, parallel-group phase 3 trial evaluating the effects of tapering and stopping all conventional and/or biological DMARDs in patients with RA in stable remission. Patients (disease activity score 28 (DAS28)<2.6 for least 6 months) were randomised into three arms, either continuing DMARDs (arm 1), tapering DMARDs by 50% (arm 2) or stopping DMARDs after 6 months tapering (arm 3). The primary endpoint was sustained remission during 12 months. Results: In this interim analysis, the first 101 patients who completed the study were analysed. At baseline, all patients fulfilled DAS28 remission and 70% also American College of Rheumatology- European League Against Rheumatism Boolean remission. 82.2% of the patients received methotrexate, 40.6% biological DMARDs and 9.9% other DMARDs. Overall, 67 patients (66.3%) remained in remission for 12 months, whereas 34 patients (33.7%) relapsed. The incidence of relapses was related to study arms (p=0.007; arm 1: 15.8%; arm 2: 38.9%; arm 3: 51.9%). Multivariate logistic regression identified anticitrullinated protein antibodies (ACPA) positivity (p=0.038) and treatment reduction (in comparison to continuation) as predictors for relapse (arm 2: p=0.012; arm 3: p=0.003). Conclusions: This randomised controlled study testing three different treatment strategies in patients with RA in sustained remission demonstrated that more than half of the patients maintain in remission after tapering or stopping conventional and biological DMARD treatment. Relapses occurred particularly in the first 6 months after treatment reduction and were associated with the presence of ACPA. Trial registration number: 2009-015740-42