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This service exclusively searches for literature that cites resources. Please be aware that the total number of searchable documents is limited to those containing RRIDs and does not include all open-access literature.
Advances in microfluidics technology has enabled many discoveries on microbial mechanisms and phenotypes owing to its exquisite controls over biological and chemical environments. However, emulating accurate ecologically relevant flow environments (e.g. microbes around a rising oil droplet) in microfluidics remains challenging. Here, we present a microfluidic platform, i.e. ecology-on-a-chip (eChip), that simulates environmental conditions around an oil droplet rising through ocean water as commonly occurred during a deep-sea oil spill or a natural seep, and enables detailed observations of microbe-oil interactions at scales relevant to marine ecology (i.e. spatial scales of individual bacterium in a dense suspension and temporal scales from milliseconds to weeks or months). Owing to the unique capabilities, we present unprecedented observations of polymeric microbial aggregates formed on rising oil droplets and their associated hydrodynamic impacts including flow fields and momentum budgets. Using the platform with Pseudomonas, Marinobacter, and Alcarnivorax, we have shown that polymeric aggregates formed by them present significant differences in morphology, growth rates, and hydrodynamic impacts. This platform enables us to investigate unexplored array of microbial interactions with oil drops.
The exchange proteins directly activated by cAMP 1 and 2 (Epac1 and Epac2) are expressed in a cell specific manner in the liver, but their biological functions in this tissue are poorly understood. The current study was undertaken to begin to determine the potential roles of Epac1 and Epac2 in liver physiology and disease. Male C57BL/6J mice in which expression of Epac1 and/or Epac2 are deleted, were subjected to partial hepatectomy and the regenerating liver was analyzed with regard to lipid accumulation, cell replication and protein expression. In response to partial hepatectomy, deletion of Epac1 and/or Epac2 led to increased hepatocyte proliferation 36 h post surgery, and the transient steatosis observed in wild type mice was virtually absent in mice lacking both Epac1 and Epac2. The expression of the protein cytochrome P4504a14, which is implicated in hepatic steatosis and fibrosis, was substantially reduced upon deletion of Epac1/2, while a number of factors involved in lipid metabolism were significantly decreased. Moreover, the number of Küpffer cells was affected, and Epac2 expression was increased in the liver of wild type mice in response to partial hepatectomy, further supporting a role for these proteins in liver function. This study establishes hepatic phenotypic abnormalities in mice deleted for Epac1/2 for the first time, and introduces Epac1/2 as regulators of hepatocyte proliferation and lipid accumulation in the regenerative process.
One of the strategies of integrated vector management is to lure gravid mosquitoes for surveillance purposes or to entice them to lay eggs in water containing toxins that kill the offspring (attract-and-kill or trap-and-kill). Typically, the major challenge of this approach is the development of a lure that stimulates oviposition plus a toxin with no deterrent effect. Bacillus thuringiensis var. israelensis (Bti) satisfies the latter criterion, but lures for these autocidal gravid traps are sorely needed. We observed that gravid Aedes aegypti, Ae. albopictus, and Culex quinquefasciatus laid significantly more eggs in cups with extracts from 4th-stage larvae (4 L) of the same or different species. No activity was found when 4 L were extracted with hexane, diethyl ether, methanol, or butanol, but activity was observed with dimethyl sulfoxide extracts. Larval extracts contained both oviposition stimulant(s)/attractant(s) and deterrent(s), which partitioned in the water and hexane phases, respectively. Lyophilized larval extracts were active after a month, but activity was reduced by keeping the sample at 4 °C. In the tested range of 0.1 to 1 larvae-equivalent per milliliter, oviposition activity increased in a dose-dependent manner. In field experiments, Ae. aegpti laid significantly more eggs in traps loaded with larval extracts plus Bti than in control traps with water plus Bti.
In single molecule localization-based super-resolution imaging, high labeling density or the desire for greater data collection speed can lead to clusters of overlapping emitter images in the raw super-resolution image data. We describe a Bayesian inference approach to multiple-emitter fitting that uses Reversible Jump Markov Chain Monte Carlo to identify and localize the emitters in dense regions of data. This formalism can take advantage of any prior information, such as emitter intensity and density. The output is both a posterior probability distribution of emitter locations that includes uncertainty in the number of emitters and the background structure, and a set of coordinates and uncertainties from the most probable model.
Keratoconus (KC) and chronic diabetes mellitus (DM) are both associated with significant defects in the human corneal structure. Studies have long suggested that DM is linked to KC, mainly via the crosslinking mechanism, but scientific evidences are lacking. The role of altered systemic metabolism is well-established in both DM and KC with studies suggesting localized altered cellular metabolism leading to the development of corneal pathologies. We have previously characterized the metabolic defects associated with both conditions using targeted metabolomics. To compare metabolic differences between KC and DM-derived corneal fibroblasts, we performed a respective study of two cohorts of the KC and DM populations using a retrospective analysis of targeted metabolomics data. The goal of this study was to identify the group of differentially regulated metabolites, in KC versus DM, so that we may unravel the link between the two devastating corneal pathologies.
Phase imaging techniques are an invaluable tool in microscopy for quickly examining thin transparent specimens. Existing methods are limited to either simple and inexpensive methods that produce only qualitative phase information (e.g. phase contrast microscopy, DIC), or significantly more elaborate and expensive quantitative methods. Here we demonstrate a low-cost, easy to implement microscopy setup for quantitative imaging of phase and bright field amplitude using collimated white light illumination.
We introduced a novel micro/nanofluidic chip platform (MNCP), which is based on an isothermal nucleic acid amplification method. This study aimed to evaluate the MNCP method for influenza A and B viruses detecting and subtyping using throat swab samples from patients with influenza-like illness (ILI). A total of 266 throat swab samples from 266 non-repeated patients with ILI were tested for influenza A and B viruses using three methods, MNCP, a rapid influenza diagnostic test (RIDT), and real-time reverse transcription polymerase chain reaction (rRT-PCR). The results of MNCP were compared to those obtained by rRT-PCR and RIDT and the performance of MNCP was further evaluated. Compared with rRT-PCR results, the rates of sensitivity, specificity, overall concordance, and the kappa value of MNCP were 98.89%, 96.97%, 97.65%, and 0.95 for influenza A virus; 94.95%, 99.38%, 97.68%, and 0.95 for influenza B virus, respectively. Subtypes of influenza A viruses, e.g., A(H1N1)pdm09, A(H3N2), and A(not subtyped), and influenza B viruses could be distinguished in one MNCP assay within 1 h. Compared with rRT-PCR and MNCP, RIDT showed poor clinical sensitivity for influenza virus detection. This study showed MNCP is rapid, sensitive and versatile detecting system with potential for clinical application in pathogen diagnosis for patients with ILI.
Copper-based fungicides have been used for a long time in viticulture and have accumulated in many vineyard soils. In this study, incrementing Cu(OH)2-based fungicide application from 0.05 to 5 g Cu kg-1 on two agricultural soils (an acidic sandy loam (L, pH 4.95) and an alkaline silt loam (D, pH 7.45)) resulted in 5 times more mobile Cu in the acidic soil. The most sensitive parameters of alfalfa (Medicago sativa) growing in these soils were the root nodule number, decreasing to 34% and 15% of the control at 0.1 g Cu kg-1 in soil L and at 1.5 g Cu kg-1 in soil D, respectively, as well as the nodule biomass, decreasing to 25% and 27% at 0.5 g Cu kg-1 in soil L and at 1.5 g Cu kg-1 in soil D, respectively. However, the enzymatic N2-fixation was not directly affected by Cu in spite of the presence of Cu in the meristem and the zone of effective N2-fixation, as illustrated by chemical imaging. The strongly different responses observed in the two tested soils reflect the higher buffering capacity of the alkaline silt loam and showed that Cu mitigation and remediation strategies should especially target vineyards with acidic, sandy soils.
The role of the endothelium in sepsis-associated disseminated intravascular coagulation (DIC) is multifaceted and may contribute substantially to disease severity and outcome. The purpose of this study was to quantify measures of endothelial function, including markers of activation (endocan, Angiopoietin-2 [Ang-2], and von Willebrand Factor), endogenous anticoagulants (tissue factor pathway inhibitor and protein C), and damage-associated factors (High Mobility Group Box 1 [HMGB-1]) in the plasma of patients with sepsis and DIC, and to determine the relationship of these factors with severity of illness and outcome. Plasma samples were collected from 103 adult patients with sepsis within 48 hours of intensive care unit admission. Biomarker levels were measured using commercially available, standardized methods. Disseminated intravascular coagulation was diagnosed according to the International Society of Thrombosis and Hemostasis scoring algorithm. Twenty-eight-day mortality was used as the primary end point. In this study, endothelial damage and dysfunction were associated with the severity of coagulopathy and mortality in DIC patients. Loss of the endogenous anticoagulant protein C and elevation in the vascular regulator Ang-2 were associated with the development of overt DIC. In addition to Ang-2 and protein C, endocan, a biomarker of endothelial activation, and HMGB-1, a mediator of endothelial damage and activation, were significantly associated with mortality. This underscores the contribution of the endothelium to the pathogenesis of sepsis-associated DIC.
Hypertension is a widespread chronic disease, and its effective treatment requires self-management by patients. Health-related apps provide an effective way of supporting hypertension self-management. However, the increasing range and variety of hypertension apps available on the market, owing to the global growth in apps, creates the need for patients and health care professionals to be informed about the effectiveness of these apps and the levels of privacy and security that they provide.
Many clinical questions arise during patient encounters that clinicians are unable to answer. An evidence-based medicine approach expects that clinicians will seek and apply the best available evidence to answer clinical questions. One commonly used source of such evidence is scientific literature, such as that available through MEDLINE and PubMed. Clinicians report that 2 key reasons why they do not use search systems to answer questions is that it takes too much time and that they do not expect to find a definitive answer. So, the question remains about how effectively scientific literature search systems support time-pressured clinicians in making better clinical decisions. The results of this study are important because they can help clinicians and health care organizations to better assess their needs with respect to clinical decision support (CDS) systems and evidence sources. The results and data captured will contribute a significant data collection to inform the design of future CDS systems to better meet the needs of time-pressured, practicing clinicians.
Postpartum depression (PPD) has a 20% 3-month prevalence rate. The consequences of PPD are significant for the mother, infant, and the family. There is a need for preventive interventions for PPD, which are effective and accessible; however, many barriers exist for women who attempt to access perinatal depression prevention programs. Internet interventions for the treatment and prevention of depression are widely accepted as efficacious and may overcome some of the issues pertaining to access to treatment barriers perinatal women face. However, internet interventions offered without any human support tend to have low adherence but positive outcomes for those who do complete treatment. Internet support groups often have high levels of adherence but minimal data supporting efficacy as a treatment for depression. Taken together, these findings suggest that combining the treatment components of individual interventions with the support provided by an internet support group might create an intervention with the scalability and cost-effectiveness of an individual intervention and the better outcomes typically found in supported interventions.
Myeloid differentiation 1 (MD-1) is a secreted protein that regulates the immune response of B cell through interacting with radioprotective 105 (RP105). Disrupted immune response may contribute to the development of cardiac diseases, while the roles of MD-1 remain elusive. Our studies aimed to explore the functions and molecular mechanisms of MD-1 in obesity-induced cardiomyopathy. H9C2 myocardial cells were treated with free fatty acid (FFA) containing palmitic acid and oleic acid to challenge high-fat stimulation and adenoviruses harbouring human MD-1 coding sequences or shRNA for MD-1 overexpression or knockdown in vitro. MD-1 overexpression or knockdown transgenic mice were generated to assess the effects of MD-1 on high-fat diet (HD) induced cardiomyopathy in vivo. Our results showed that MD-1 was down-regulated in H9C2 cells exposed to FFA stimulation for 48 hours and in obesity mice induced by HD for 20 weeks. Both in vivo and in vitro, silencing of MD-1 accelerated myocardial function injury induced by HD stimulation through increased cardiac hypertrophy and fibrosis, while overexpression of MD-1 alleviated the effects of HD by inhibiting the process of cardiac remodelling. Moreover, the MAPK and NF-κB pathways were overactivated in MD-1 deficient mice and H9C2 cells after high-fat treatment. Inhibition of MAPK and NF-κB pathways played a cardioprotective role against the adverse effects of MD-1 silencing on high-fat stimulation induced pathological remodelling. In conclusion, MD-1 protected myocardial function against high-fat stimulation induced cardiac pathological remodelling through negative regulation for MAPK/NF-κB signalling pathways, providing feasible strategies for obesity cardiomyopathy.
Patients under chronic obstructive pulmonary disease (COPD) has been reported to be associated with a higher prevalence of cognitive impairment (CI). However, it is still largely unknown whether the aberrant resting-state spontaneous neuronal activity pattern reflected by the amplitude of low-frequency fluctuation (ALFF) analysis will be associated with the CI in COPD patients.
Fluorescent transcriptional reporters are widely used as signaling reporters and biomarkers to monitor pathway activities and determine cell type identities. However, a large amount of dynamic information is lost due to the long half-life of the fluorescent proteins. To better detect dynamics, fluorescent transcriptional reporters can be destabilized to shorten their half-lives. However, applications of this approach in vivo are limited due to significant reduction of signal intensities. To overcome this limitation, we enhanced translation of a destabilized fluorescent protein and demonstrate the advantages of this approach by characterizing spatio-temporal changes of transcriptional activities in Drosophila. In addition, by combining a fast-folding destabilized fluorescent protein and a slow-folding long-lived fluorescent protein, we generated a dual-color transcriptional timer that provides spatio-temporal information about signaling pathway activities. Finally, we demonstrate the use of this transcriptional timer to identify new genes with dynamic expression patterns.
It is important to modulate the expression of glucocorticoids receptor (GR) in tress and maintain the immunity homeostasis in sepsis process. Rhubarb have been shown to have potential effects on anti-inflammatory and immune modulation. The present study was designed to investigate the effects of rhubarb on the expression of GR and cellular immunity in burn-induced septic rats.
Ctenophores, also known as comb jellies, live across extremely broad ranges of temperature and hydrostatic pressure in the ocean. Because various ctenophore lineages adapted independently to similar environmental conditions, Phylum Ctenophora is an ideal system for the study of protein adaptation to extreme environments in a comparative framework. We present such a study here, using a phylogenetically-informed method to compare sequences of four essential metabolic enzymes across gradients of habitat depth and temperature. This method predicts convergent adaptation to these environmental parameters at the amino acid level, providing a novel view of protein adaptation to extreme environments and demonstrating the power and relevance of phylogenetic comparison applied to multi-species transcriptomic datasets from early-diverging metazoa. Across all four enzymes analyzed, 46 amino acid sites were associated with depth-adaptation, 59 with temperature-adaptation, and 56 with both. Sites predicted to be depth- and temperature-adaptive occurred consistently near Rossmann fold cofactor binding motifs and disproportionately in solvent-exposed regions of the protein. These results suggest that the hydrophobic effect and ligand binding may mediate efficient enzyme function at different hydrostatic pressures and temperatures. Using predicted adaptive site maps, such mechanistic hypotheses can now be tested via mutagenesis.
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