Genome-wide transcriptomic analysis of the response to nitrogen limitation in Streptomyces coelicolor A3(2)

<p>Abstract</p> <p>Background</p> <p>The present study represents a genome-wide transcriptomic analysis of the response of the model streptomycete <it>Streptomyces coelicolor </it>A3(2) M145 to fermentor culture in Modified Evans Media limited, respectively, for nitrogen, phosphate and carbon undertaken as part of the ActinoGEN consortium to provide a publicly available reference microarray dataset.</p> <p>Findings</p> <p>A microarray dataset using samples from two replicate cultures for each nutrient limitation was generated. In this report our analysis has focused on the genes which are significantly differentially expressed, as determined by Rank Products Analysis, between samples from matched time points correlated by growth phase for the three pairs of differently limited culture datasets. With a few exceptions, genes are only significantly differentially expressed between the N6/N7 time points and their corresponding time points in the C and P-limited cultures, with the vast majority of the differentially expressed genes being more highly expressed in the N-limited cultures. Our analysis of these genes indicated expression of several members of the GlnR regulon are induced upon nitrogen limitation, as assayed for by [NH₄⁺] measurements, and we are able to identify several additional genes not present in the GlnR regulon whose expression is induced in response to nitrogen limitation. We also note SCO3327 which encodes a small protein (32 amino acid residues) unusually rich in the basic amino acids lysine (31.25%) and arginine (25%) is significantly differentially expressed in the nitrogen limited cultures. Additionally, we investigate the expression of known members of the GlnR regulon and the relationship between gene organization and expression for the SCO2486-SCO2487 and SCO5583-SCO5585 operons.</p> <p>Conclusions</p> <p>We provide a list of genes whose expression is differentially expressed in low nitrogen culture conditions, including a putative nitrogen storage protein encoded by SCO3327. Our list includes several genes whose expression patterns are similar to up-regulated members of the GlnR regulon and are induced in response to nitrogen limitation. These genes represent likely targets for future studies into the nitrogen starvation response in <it>Streptomyces coelicolor</it>.</p

Oral administration of bovine milk-derived extracellular vesicles induces senescence in the primary tumor but accelerates cancer metastasis

The concept that extracellular vesicles (EVs) from the diet can be absorbed by the intestinal tract of the consuming organism, be bioavailable in various organs, and in-turn exert phenotypic changes is highly debatable. Here, we isolate EVs from both raw and commercial bovine milk and characterize them by electron microscopy, nanoparticle tracking analysis, western blotting, quantitative proteomics and small RNA sequencing analysis. Orally administered bovine milk-derived EVs survive the harsh degrading conditions of the gut, in mice, and is subsequently detected in multiple organs. Milk-derived EVs orally administered to mice implanted with colorectal and breast cancer cells reduce the primary tumor burden. Intriguingly, despite the reduction in primary tumor growth, milk-derived EVs accelerate metastasis in breast and pancreatic cancer mouse models. Proteomic and biochemical analysis reveal the induction of senescence and epithelial-to-mesenchymal transition in cancer cells upon treatment with milk-derived EVs. Timing of EV administration is critical as oral administration after resection of the primary tumor reverses the pro-metastatic effects of milk-derived EVs in breast cancer models. Taken together, our study provides context-based and opposing roles of milk-derived EVs as metastasis inducers and suppressors

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Antisite disorder and Berry curvature driven anomalous Hall effect in the spin gapless semiconducting Mn2_2CoAl Heusler compound

Spin gapless semiconductors exhibit a finite band gap for one spin channel and a closed gap for another spin channel, and they have emerged as a new state of magnetic materials with a great potential for spintronic applications. The first experimental evidence for spin gapless semiconducting behavior was observed in an inverse Heusler compound Mn$_2$CoAl. Here, we report a detailed investigation of the crystal structure and anomalous Hall effect in Mn$_2$CoAl using experimental and theoretical studies. The analysis of the high-resolution synchrotron x-ray diffraction data shows antisite disorder between Mn and Al atoms within the inverse Heusler structure. The temperature-dependent resistivity shows semiconducting behavior and follows Mooij's criteria for disordered metal. The scaling behavior of the anomalous Hall resistivity suggests that the anomalous Hall effect in Mn$_2$CoAl is primarily governed by an intrinsic mechanism due to the Berry curvature in momentum space. The experimental intrinsic anomalous Hall conductivity (AHC) is found to be ∼35 S/cm, which is considerably larger than the theoretically predicted value for ordered Mn$_2$CoAl. Our first-principles calculations conclude that the antisite disorder between Mn and Al atoms enhances the Berry curvature and hence the value of intrinsic AHC, which is in very good agreement with the experiment

Atomic disorder and Berry phase driven anomalous Hall effect in a Co 2 FeAl Heusler compound

Co$_2$-based Heusler compounds are promising materials for spintronics applications due to their high Curie temperature, large spin polarization, large magnetization density, and exotic transport properties. In the present paper, we report the anomalous Hall effect (AHE) in a polycrystalline Co$_2$FeAl Heusler compound using combined experimental and theoretical studies. The Rietveld analysis of high-resolution synchrotron x-ray diffraction data reveals a large degree (∼50%) of antisite disorder between Fe and Al atoms. The analysis of anomalous transport data provides the experimental anomalous Hall conductivity (AHC) about 227 S/cm at 2 K with an intrinsic contribution of 155 S/cm, which has nearly constant variation with temperature. The detailed scaling analysis of anomalous Hall resistivity suggests that the AHE in Co$_2$FeAl is governed by the Berry phase driven intrinsic mechanism. Our theoretical calculations reveal that the disorder present in the Co$_2$FeAl compound enhances the Berry curvature induced intrinsic AHC

Global, Regional, And National Burden Of Neurological Disorders, 1990-2016: A Systematic Analysis For The Global Burden Of Disease Study 2016

Background Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders. Methods We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach. Findings Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247-308]) and second leading cause of deaths (9.0 million [8.8-9.4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34-44] and DALYs by 15% [9-21]) whereas their age-standardised rates decreased (deaths by 28% [26-30] and DALYs by 27% [24-31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42.2% [38.6-46.1]), migraine (16.3% [11.7-20.8]), Alzheimer's and other dementias (10.4% [9.0-124]), and meningitis (7.9% [6.6-10.4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1.12 [1.05-1.20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0.7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88.8% (86.5-90.9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22.3% [11.8-35.1] of DALYs are risk attributable) and idiopathic epilepsy (14.1% [10.8-17.5] of DALYs are risk attributable). Interpretation Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies. Copyright (C) The Author(s). Published by Elsevier Ltd.WoSScopu