Nitric oxide in marine photosynthetic organisms

Nitric oxide is a versatile and powerful signaling molecule in plants. However, most of our understanding stems from studies on terrestrial plants and very little is known about marine autotrophs. This review summarizes current knowledge about the source of nitric oxide synthesis in marine photosynthetic organisms and its role in various physiological processes under normal and stress conditions. The interactions of nitric oxide with other stress signals and cross talk among secondary messengers are also highlighted

Deep Learning Body Region Classification of MRI and CT examinations

Standardized body region labelling of individual images provides data that can improve human and computer use of medical images. A CNN-based classifier was developed to identify body regions in CT and MRI. 17 CT (18 MRI) body regions covering the entire human body were defined for the classification task. Three retrospective databases were built for the AI model training, validation, and testing, with a balanced distribution of studies per body region. The test databases originated from a different healthcare network. Accuracy, recall and precision of the classifier was evaluated for patient age, patient gender, institution, scanner manufacturer, contrast, slice thickness, MRI sequence, and CT kernel. The data included a retrospective cohort of 2,934 anonymized CT cases (training: 1,804 studies, validation: 602 studies, test: 528 studies) and 3,185 anonymized MRI cases (training: 1,911 studies, validation: 636 studies, test: 638 studies). 27 institutions from primary care hospitals, community hospitals and imaging centers contributed to the test datasets. The data included cases of all genders in equal proportions and subjects aged from a few months old to +90 years old. An image-level prediction accuracy of 91.9% (90.2 - 92.1) for CT, and 94.2% (92.0 - 95.6) for MRI was achieved. The classification results were robust across all body regions and confounding factors. Due to limited data, performance results for subjects under 10 years-old could not be reliably evaluated. We show that deep learning models can classify CT and MRI images by body region including lower and upper extremities with high accuracy.Comment: 21 pages, 2 figures, 4 table

Metabolic control analysis is helpful for informed genetic manipulation of oilseed rape (Brassica napus) to increase seed oil content

Top–down control analysis (TDCA) is a useful tool for quantifying constraints on metabolic pathways that might be overcome by biotechnological approaches. Previous studies on lipid accumulation in oilseed rape have suggested that diacylglycerol acyltransferase (DGAT), which catalyses the final step in seed oil biosynthesis, might be an effective target for enhancing seed oil content. Here, increased seed oil content, increased DGAT activity, and reduced substrate:product ratio are demonstrated, as well as reduced flux control by complex lipid assembly, as determined by TDCA in Brassica napus (canola) lines which overexpress the gene encoding type-1 DGAT. Lines overexpressing DGAT1 also exhibited considerably enhanced seed oil content under drought conditions. These results support the use of TDCA in guiding the rational selection of molecular targets for oilseed modification. The most effective lines had a seed oil increase of 14%. Moreover, overexpression of DGAT1 under drought conditions reduced this environmental penalty on seed oil content

Decreased Insulin-Stimulated ATP Synthesis and Phosphate Transport in Muscle of Insulin-Resistant Offspring of Type 2 Diabetic Parents

BACKGROUND: Insulin resistance is the best predictor for the development of type 2 diabetes. Recent studies have shown that young, lean, insulin-resistant (IR) offspring of parents with type 2 diabetes have reduced basal rates of muscle mitochondrial phosphorylation activity associated with increased intramyocellular lipid (IMCL) content, which in turn blocks insulin signaling and insulin action in muscle. In order to further characterize mitochondrial activity in these individuals, we examined insulin-stimulated rates of adenosine triphosphate (ATP) synthesis and phosphate transport in skeletal muscle in a similar cohort of participants. METHODS AND FINDINGS: Rates of insulin-stimulated muscle mitochondrial ATP synthase flux and insulin-stimulated increases in concentrations of intramyocellular inorganic phosphate (P(i)) were assessed by (31)P magnetic resonance spectroscopy (MRS) in healthy, lean, IR offspring of parents with type 2 diabetes and healthy, lean control participants with normal insulin sensitivity. IMCL content in the soleus muscle of all participants was assessed by (1)H MRS. During a hyperinsulinemic-euglycemic clamp, rates of insulin-stimulated glucose uptake were decreased by approximately 50% in the IR offspring compared to the control participants (p = 0.007 versus controls) and were associated with an approximately 2-fold increase in IMCL content (p < 0.006 versus controls). In the control participants rates of ATP synthesis increased by approximately 90% during the hyperinsulinemic-euglycemic clamp. In contrast, insulin-stimulated rates of muscle mitochondrial ATP synthesis increased by only 5% in the IR offspring (p = 0.001 versus controls) and was associated with a severe reduction of insulin-stimulated increases in the intramyocellular P(i) concentrations (IR offspring: 4.7% ± 1.9% versus controls: 19.3% ± 5.7%; p = 0.03). Insulin-induced increases in intramyocellular P(i) concentrations correlated well with insulin-stimulated increases in rates of ATP synthesis (r = 0.67; p = 0.008). CONCLUSIONS: These data demonstrate that insulin-stimulated rates of mitochondrial ATP synthesis are reduced in IR offspring of parents with type 2 diabetes. Furthermore, these IR offspring also have impaired insulin-stimulated phosphate transport in muscle, which may contribute to their defects in insulin-stimulated rates of mitochondrial ATP synthesis

Vocal Tract Images Reveal Neural Representations of Sensorimotor Transformation During Speech Imitation

Imitating speech necessitates the transformation from sensory targets to vocal tract motor output, yet little is known about the representational basis of this process in the human brain. Here, we address this question by using real-time MR imaging (rtMRI) of the vocal tract and functional MRI (fMRI) of the brain in a speech imitation paradigm. Participants trained on imitating a native vowel and a similar nonnative vowel that required lip rounding. Later, participants imitated these vowels and an untrained vowel pair during separate fMRI and rtMRI runs. Univariate fMRI analyses revealed that regions including left inferior frontal gyrus were more active during sensorimotor transformation (ST) and production of nonnative vowels, compared with native vowels; further, ST for nonnative vowels activated somatomotor cortex bilaterally, compared with ST of native vowels. Using test representational similarity analysis (RSA) models constructed from participants' vocal tract images and from stimulus formant distances, we found that RSA searchlight analyses of fMRI data showed either type of model could be represented in somatomotor, temporal, cerebellar, and hippocampal neural activation patterns during ST. We thus provide the first evidence of widespread and robust cortical and subcortical neural representation of vocal tract and/or formant parameters, during prearticulatory ST

Assessing Biofuel Crop Invasiveness: A Case Study

BACKGROUND: There is widespread interest in biofuel crops as a solution to the world's energy needs, particularly in light of concerns over greenhouse-gas emissions. Despite reservations about their adverse environmental impacts, no attempt has been made to quantify actual, relative or potential invasiveness of terrestrial biofuel crops at an appropriate regional or international scale, and their planting continues to be largely unregulated. METHODOLOGY/PRINCIPAL FINDINGS: Using a widely accepted weed risk assessment system, we analyzed a comprehensive list of regionally suitable biofuel crops to show that seventy percent have a high risk of becoming invasive versus one-quarter of non-biofuel plant species and are two to four times more likely to establish wild populations locally or be invasive in Hawaii or in other locations with a similar climate. CONCLUSIONS/SIGNIFICANCE: Because of climatic and ecological similarities, predictions of biofuel crop invasiveness in Hawaii are applicable to other vulnerable island and subtropical ecosystems worldwide. We demonstrate the utility of an accessible and scientifically proven risk assessment protocol that allows users to predict if introduced species will become invasive in their region of interest. Other evidence supports the contention that propagule pressure created by extensive plantings will exacerbate invasions, a scenario expected with large-scale biofuel crop cultivation. Proactive measures, such as risk assessments, should be employed to predict invasion risks, which could then be mitigated via implementation of appropriate planting policies and adoption of the "polluter-pays" principle

Novel GLP-1 Fusion Chimera as Potent Long Acting GLP-1 Receptor Agonist

GLP-1 has a variety of anti-diabetic effects. However, native GLP-1 is not suitable for therapy of diabetes due to its short half-life (t1/2<2 min). To circumvent this, we developed a long-lasting GLP-1 receptor agonist by the fusion of GLP-1 with human IgG2 Fc (GLP-1/hIgG2). ELISA-based receptor binding assay demonstrated that GLP-1/hIgG2 had high binding affinity to the GLP-1R in INS-1 cells (Kd = 13.90±1.52 nM). Upon binding, GLP-1/hIgG2 was rapidly internalized by INS-1 cells in a dynamin-dependent manner. Insulin RIA showed that GLP-1/IgG2 dose-dependently stimulated insulin secretion from INS-1 cells. Pharmacokinetic studies in CD1 mice showed that with intraperitoneal injection (i.p.), the GLP-1/hIgG2 peaked at 30 minutes in circulation and maintained a plateau for >168 h. Intraperitoneal glucose tolerance test (IPGTT) in mice showed that GLP-1/hIgG2 significantly decreased glucose excursion. Furthermore, IPGTT performed on mice one week after a single drug-injection also displayed significantly reduced glucose excursion, indicating that GLP-1/hIgG2 fusion protein has long-lasting effects on the modulation of glucose homeostasis. GLP-1/hIgG2 was found to be effective in reducing the incidence of diabetes in multiple-low-dose streptozotocin-induced type 1 diabetes in mice. Together, the long-lasting bioactive GLP-1/hIgG2 retains native GLP-1 activities and thus may serve as a potent GLP-1 receptor agonist

The effect of peri-conception hyperglycaemia and the involvement of the hexosamine biosynthesis pathway in mediating oocyte and embryo developmental competence

The environment that the oocyte is exposed to during the peri-conception period can have a significant impact on oocyte developmental competence (the ability of the oocyte to support fertilisation and subsequent embryo development) and the long-term health of the resulting offspring. This is particularly true for maternal hyperglycaemia. While maternal hyperglycaemia during early pregnancy through term development has been extensively studied, the effects on the oocyte itself, and the underlying mechanisms, remain largely unknown. There is increasing evidence, however, for the role of the fuel-sensing hexosamine biosynthesis pathway in mediating the effects of hyperglycaemia in many different cell types. In this review, we will focus on the reproductive consequences of maternal hyperglycaemia during the peri-conceptual period and the role of the hexosamine pathway in mediating these processes.Laura A. Frank, Melanie L. Sutton-McDowall, Robert B. Gilchrist, and Jeremy G. Thompso

Dysregulation of neuronal iron homeostasis as an alternative unifying effect of mutations causing familial Alzheimer's disease

The overwhelming majority of dominant mutations causing early onset familial Alzheimer's disease (EOfAD) occur in only three genes, PSEN1, PSEN2, and APP. An effect-in-common of these mutations is alteration of production of the APP-derived peptide, amyloid ß (Aß). It is this key fact that underlies the authority of the Amyloid Hypothesis that has informed Alzheimer's disease research for over two decades. Any challenge to this authority must offer an alternative explanation for the relationship between the PSEN genes and APP. In this paper, we explore one possible alternative relationship - the dysregulation of cellular iron homeostasis as a common effect of EOfAD mutations in these genes. This idea is attractive since it provides clear connections between EOfAD mutations and major characteristics of Alzheimer's disease such as dysfunctional mitochondria, vascular risk factors/hypoxia, energy metabolism, and inflammation. We combine our ideas with observations by others to describe a "Stress Threshold Change of State" model of Alzheimer's disease that may begin to explain the existence of both EOfAD and late onset sporadic (LOsAD) forms of the disease. Directing research to investigate the role of dysregulation of iron homeostasis in EOfAD may be a profitable way forward in our struggle to understand this form of dementia

Bacterial laccases: some recent advances and applications

Laccases belong to the large family of multi-copper oxidases (MCOs) that couple the one-electron oxidation of substrates with the four-electron reduction of molecular oxygen to water. Because of their high relative non-specific oxidation capacity particularly on phenols and aromatic amines as well as the lack of requirement for expensive organic cofactors, they have found application in a large number of biotechnological fields. The vast majority of studies and applications were performed using fungal laccases, but bacterial laccases show interesting properties such as optimal temperature above 50 °C, optimal pH at the neutral to alkaline range, thermal and chemical stability and increased salt tolerance. Additionally, bacterial systems benefit from a wide range of molecular biology tools that facilitates their engineering and achievement of high yields of protein production and set-up of cost-effective bioprocesses. In this review we will provide up-to-date information on the distribution and putative physiological role of bacterial laccases and highlight their distinctive structural and biochemical properties, discuss the key role of copper in the biochemical properties, discuss thermostability determinants and, finally, review biotechnological applications with a focus on catalytic mechanisms on phenolics and aromatic amines.info:eu-repo/semantics/publishedVersio