Despite evidence linking the human microbiome to health and disease, how the microbiota affects human physiology remains largely unknown. Microbiota-encoded metabolites are expected to play an ...integral role in human health. Therefore, assigning function to these metabolites is critical to understanding these complex interactions and developing microbiota-inspired therapies. Here, we use large-scale functional screening of molecules produced by individual members of a simplified human microbiota to identify bacterial metabolites that agonize G-protein-coupled receptors (GPCRs). Multiple metabolites, including phenylpropanoic acid, cadaverine, 9-10-methylenehexadecanoic acid, and 12-methyltetradecanoic acid, were found to interact with GPCRs associated with diverse functions within the nervous and immune systems, among others. Collectively, these metabolite-receptor pairs indicate that diverse aspects of human health are potentially modulated by structurally simple metabolites arising from primary bacterial metabolism.
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•Metabolite library from human microbiota screened for direct agonism of 241 GPCRs•Taxa-specific primary metabolites agonize individual GPCRs or broad GPCR families•Bacteria agonize receptors linked to metabolism, neurotransmission, and immunity•Simple bacterial metabolites may play a role in modulating host pathways
Colosimo et al. use functional screening of small molecules produced by individual members of a simplified human microbiota to identify bacterial metabolites that agonize G protein-coupled receptors (GPCRs). These results indicate that diverse aspects of human health are potentially modulated by structurally simple metabolites arising from primary bacterial metabolism.
Transmission Network Expansion Planning (TNEP) in modern electricity systems is carried out on a cost-benefit analysis basis; the planner identifies investments that maximize the social welfare. As ...the integration of Renewable Energy Sources (RES) increases, there is a real challenge to accurately capture the vast variability that characterizes system operation within a planning problem. Conventional approaches that rely on a large number of scenarios for representing the variability of operating points can quickly lead to computational issues. An alternative approach that is becoming increasingly necessary is to select representative scenarios from the original population via clustering techniques. However, direct clustering of operating points in the input domain may not capture characteristics which are important for investment decision-making. This paper presents a novel objective-based scenario selection framework for TNEP to obtain optimal investment decisions with a significantly reduced number of operating states. Different clustering frameworks, clustering variable s and clustering techniques are compared to determine the most appropriate approach. The superior performance of the proposed framework is demonstrated through a case study on a modified IEEE 118-bus system.
•A novel objective-based scenario selection framework is proposed.•Power flows and investment decisions are proposed as new clustering variables.•Different clustering techniques are compared for scenario selection.•The bi-level clustering on investment variables with K-means exhibits the best performance.•The scheme results in large computation speedups at limited loss of accuracy.
•The neuroprotection of ketamine at subanesthetic-dosage.•ketamine at sub-anesthetic dose alleviates functional deficits after TBI.•Posttraumatic administration of ketamine exerts anti-inflammatory ...properties.•ketamine at sub-anesthetic dose may regulate autophagy and ameliorate secondary brain injury.•Administration of 10mg/kg ketamine, every 24h up to 7days.
As a complex disease, traumatic brain injury (TBI) can result in long-term psychiatric changes and sensorimotor and cognitive impairments. The TBI-induced loss of memory and long-term cognitive dysfunction are related to mechanistic factors including an increased inflammatory response, autophagy, edema, and ischemia. Many published studies have offered evidence for the neuroprotective effects and anti-inflammatory properties of ketamine for TBI patients. Nonetheless, there is a limited understanding of the accurate mechanism that underlies the potential neuroprotective effects of ketamine. Herein, it can be shown that posttraumatic administration of ketamine at a sub-anesthetic dose (10mg/kg ketamine, every 24h up to 7days) can prevent the TBI-induced production of IL-6 and TNF-α, attenuate deficits of dendrites and spines and exert beneficial effects on memory and behavior. Moreover, studies show that ketamine may activate the mTOR signaling pathway by p-mTOR induction to down-regulate the expression of crucial autophagic proteins such as LC3 and Beclin-1. According to these findings, ameliorating secondary brain injury and anti-inflammatory properties is closely related to the neuroprotection of ketamine, which supports the use of ketamine as a potential therapy for patients with TBI to alleviate functional deficits.
Cerium nitrate (Ce(NO3)3) and benzotriazole (BTA) were applied as immersion post-treatments for Plasma Electrolytic Oxidation (PEO) coatings on commercially pure magnesium. The surface morphology of ...the coated samples was characterised by Scanning Electron Microscopy (SEM), and it was found that the micro-pores on the coating surface can be effectively sealed by Ce(NO3)3 immersion post-treatment, whereas BTA did not show any significant effect on the coating microstructure. The corrosion resistance behaviour of the coated samples was examined by electrochemical tests in a 3.5 wt% NaCl solution. According to the results, the Ce(NO3)3 immersion post-treatment showed the better effect in enhancing the corrosion resistance of the PEO coating, compared with BTA immersion post-treatment. The insoluble Ce-containing compounds can provide both a sealing effect and continuous longer-term protection for the PEO-Ce(NO3)3 coating. At the same time, BTA provides only a short-term improvement in the corrosion resistance, due to adsorption on the coating surface.
•Immersion post-treatments of PEO coatings on Mg in Ce(NO3)3 and BTA solutions•BTA is adsorbed in the pores inhibiting anodic reaction in corrosion process.•Ce based compounds are deposited in the pores inhibiting cathodic reaction.•Ce post-treatment combines sealing and inhibition providing longer term effect.
ABSTRACT
Background
The incidence of persistent clinical symptoms and risk factors in Post-Acute Sequelae of SARS-CoV-2 (PASC) in diverse US cohorts is unclear. While there are a disproportionate ...share of COVID-19 deaths in older patients, ethnic minorities, and socially disadvantaged populations in the USA, little information is available on the association of these factors and PASC.
Objective
To evaluate the association of demographic and clinical characteristics with development of PASC.
Design
Prospective observational cohort of hospitalized and high-risk outpatients, April 2020 to February 2021.
Participants
One thousand thirty-eight adults with laboratory-confirmed symptomatic COVID-19 infection.
Main Measures
Development of PASC determined by patient report of persistent symptoms on questionnaires conducted 60 or 90 days after COVID-19 infection or hospital discharge. Demographic and clinical factors associated with PASC.
Key Results
Of 1,038 patients with longitudinal follow-up, 309 patients (29.8%) developed PASC. The most common persistent symptom was fatigue (31.4%) followed by shortness of breath (15.4%) in hospitalized patients and anosmia (15.9%) in outpatients. Hospitalization for COVID-19 (odds ratio OR 1.49, 95% CI 1.04–2.14), having diabetes (OR, 1.39; 95% CI 1.02–1.88), and higher BMI (OR, 1.02; 95% CI 1–1.04) were independently associated with PASC. Medicaid compared to commercial insurance (OR, 0.49; 95% CI 0.31–0.77) and having had an organ transplant (OR 0.44, 95% CI, 0.26–0.76) were inversely associated with PASC. Age, race/ethnicity, Social Vulnerability Index, and baseline functional status were not associated with developing PASC.
Conclusions
Three in ten survivors with COVID-19 developed a subset of symptoms associated with PASC in our cohort. While ethnic minorities, older age, and social disadvantage are associated with worse acute COVID-19 infection and greater risk of death, our study found no association between these factors and PASC.
ABSTRACT
Recent studies show that a universal relation between black hole (BH) growth and stellar mass (M⋆) or star formation rate (SFR) is an oversimplification of BH–galaxy coevolution, and that ...morphological and structural properties of host galaxies must also be considered. Particularly, a possible connection between BH growth and host-galaxy compactness was identified among star-forming (SF) galaxies. Utilizing ≈6300 massive galaxies with I814W < 24 at z < 1.2 in the Cosmic Evolution Survey (COSMOS) field, we perform systematic partial correlation analyses to investigate how sample-averaged BH accretion rate ($\rm \overline{BHAR}$) depends on host-galaxy compactness among SF galaxies, when controlling for morphology and M⋆ (or SFR). The projected central surface mass density within 1 kpc, Σ1, is utilized to represent host-galaxy compactness in our study. We find that the $\rm \overline{BHAR}$–Σ1 relation is stronger than either the $\rm \overline{BHAR}$–M⋆ or $\rm \overline{BHAR}$–SFR relation among SF galaxies, and this $\rm \overline{BHAR}$–Σ1 relation applies to both bulge-dominated galaxies and galaxies that are not dominated by bulges. This $\rm \overline{BHAR}$–Σ1 relation among SF galaxies suggests a link between BH growth and the central gas density of host galaxies on the kpc scale, which may further imply a common origin of the gas in the vicinity of the BH and in the central ∼kpc of the galaxy. This $\rm \overline{BHAR}$–Σ1 relation can also be interpreted as the relation between BH growth and the central velocity dispersion of host galaxies at a given gas content (i.e. gas mass fraction), indicating the role of the host-galaxy potential well in regulating accretion on to the BH.
Commensal bacteria are believed to have important roles in human health. The mechanisms by which they affect mammalian physiology remain poorly understood, but bacterial metabolites are likely to be ...key components of host interactions. Here we use bioinformatics and synthetic biology to mine the human microbiota for N-acyl amides that interact with G-protein-coupled receptors (GPCRs). We found that N-acyl amide synthase genes are enriched in gastrointestinal bacteria and the lipids that they encode interact with GPCRs that regulate gastrointestinal tract physiology. Mouse and cell-based models demonstrate that commensal GPR119 agonists regulate metabolic hormones and glucose homeostasis as efficiently as human ligands, although future studies are needed to define their potential physiological role in humans. Our results suggest that chemical mimicry of eukaryotic signalling molecules may be common among commensal bacteria and that manipulation of microbiota genes encoding metabolites that elicit host cellular responses represents a possible small-molecule therapeutic modality (microbiome-biosynthetic gene therapy).
lncRNAs play important roles in the epigenetic regulation of carcinogenesis and progression. Previous studies suggest that HOTAIR contributes to gastric cancer (GC) development, and the ...overexpression of HOTAIR predicts a poor prognosis. In this study, we found that HOTAIR was more highly expressed in diffuse-type GC than in intestinal type (P=0.048). In the diffuse type, there is significant relationship between HOTAIR expression and DFS (P<0.001). CDH1 was downregulated in diffuse-type GC tissues (P=0.0007) and showed a negative relationship with HOTAIR (r(2)=0.154, P=0.0354). In addition, HOTAIR knockdown significantly repressed migration, invasion and metastasis both in vitro and vivo and reversed the epithelial-to-mesenchymal transition in GC cells. We also showed that HOTAIR recruiting and binding to PRC2 epigenetically represses miR34a, which controls the targets C-Met (HGF/C-Met/Snail pathway) and Snail, thus contributing to GC cell-EMT process and accelerating tumor metastasis. Moreover, it is demonstrated that HOTAIR crosstalk with microRNAs during epigenetic regulation. Our results suggest that HOTAIR acts as an EMT regulator and may be a candidate prognostic biomarker and a target for new therapies in GC patients.
The nature and origin of the cold interstellar medium (ISM) in early-type galaxies are still a matter of debate, and understanding the role of this component in galaxy evolution and in fuelling the ...central supermassive black holes requires more observational constraints. Here, we present a multiwavelength study of the ISM in eight nearby, X-ray and optically bright, giant elliptical galaxies, all central dominant members of relatively low-mass groups. Using far-infrared spectral imaging with the Herschel Photodetector Array Camera & Spectrometer, we map the emission of cold gas in the cooling lines of C iiλ157 μm, O i λ63 μm and O ib λ145 μm. Additionally, we present Hα+N ii imaging of warm ionized gas with the Southern Astrophysical Research (SOAR) telescope, and a study of the thermodynamic structure of the hot X-ray emitting plasma with Chandra. All systems with extended Hα emission in our sample (6/8 galaxies) display significant C ii line emission indicating the presence of reservoirs of cold gas. This emission is cospatial with the optical Hα+N ii emitting nebulae and the lowest entropy soft X-ray emitting plasma. The entropy profiles of the hot galactic atmospheres show a clear dichotomy, with the systems displaying extended emission-line nebulae having lower entropies beyond r 1 kpc than the cold-gas-poor systems. We show that while the hot atmospheres of the cold-gas-poor galaxies are thermally stable outside of their innermost cores, the atmospheres of the cold-gas-rich systems are prone to cooling instabilities. This provides considerable weight to the argument that cold gas in giant ellipticals is produced chiefly by cooling from the hot phase. We show that cooling instabilities may develop more easily in rotating systems and discuss an alternative condition for thermal instability for this case. The hot atmospheres of cold-gas-rich galaxies display disturbed morphologies indicating that the accretion of clumpy multiphase gas in these systems may result in variable power output of the AGN jets, potentially triggering sporadic, larger outbursts. In the two cold-gas-poor, X-ray morphologically relaxed galaxies of our sample, NGC 1399 and NGC 4472, powerful AGN outbursts may have destroyed or removed most of the cold gas from the cores, allowing the jets to propagate and deposit most of their energy further out, increasing the entropy of the hot galactic atmospheres and leaving their cores relatively undisturbed.
Chirality of macrolide antibiotics (MA) are theoretically analyzed with absorption spectroscopy, electronic circular dichroism (ECD) and Raman optical activity (ROA) spectra. Physical mechanism of ...optical properties is revealed by the coupling interactions of transition electric dipole moments, transition magnetic dipole moments and transitional electric quadrupole moments. Our results demonstrate that S3 excited state is of strong linear optical absorption; while S1 excited state is of strong ECD. The ROA spectra excited with the resonance S3 electronic transition can well reveal the chirality of MA. Our two dimensional (2D) and three dimensional (3D) visualization analysis methods clearly demonstrate the relationship between vibrational modes of ROA and interactions of electric and magnetic coupling. Our results can visually promote deeper understanding physical mechanism of molecular chirality and extending potential applications on the analysis of molecular chirality.
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