AIM: The aim of this study was to investigate the mode of action of the lavender essential oil (LV) on antimicrobial activity against multi‐drug‐resistant Escherichia coli J53 R1 when used singly and ...in combination with piperacillin. METHOD AND RESULTS: In the time‐kill analysis, a complete killing of bacteria was observed based on colony counts within 4 h when LV was combined with piperacillin during exposure at determined FIC concentrations. Analysis of the membrane permeabilizing effects of LV on treated cultures through their stability against sodium dodecyl sulphate revealed that the LV played a role in disrupting the bacterial cell membrane. The finding is further supported by scanning electron microscopy analysis and zeta potential measurement. In addition, reduction in light production expression of E. coli pSB1075 by the LV showed the presence of potential quorum sensing (QS) inhibitors. CONCLUSIONS: These results indicated that the LV has the potential to reverse bacterial resistance to piperacillin in E. coli J53 R1. It may operate via two mechanisms: alteration of outer membrane permeability and inhibition of bacterial QS. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings offer a novel approach to develop a new option of phytopharmaceuticals against multi‐drug‐resistant E. coli.
Bacterial microcompartments (BMCs) encapsulate enzymes within a selectively permeable, proteinaceous shell. Carboxysomes are BMCs containing ribulose-1,5-bisphosphate carboxylase oxygenase and ...carbonic anhydrase that enhance carbon dioxide fixation. The carboxysome shell consists of three structurally characterized protein types, each named after the oligomer they form: BMC-H (hexamer), BMC-P (pentamer), and BMC-T (trimer). These three protein types form cyclic homooligomers with pores at the center of symmetry that enable metabolite transport across the shell. Carboxysome shells contain multiple BMC-H paralogs, each with distinctly conserved residues surrounding the pore, which are assumed to be associated with specific metabolites. We studied the regulation of β-carboxysome shell composition by investigating the BMC-H genes
and
situated in a locus remote from other carboxysome genes. We made single and double deletion mutants of
and
in
PCC7942 and show that, unlike CcmK3, CcmK4 is necessary for optimal growth. In contrast to other CcmK proteins, CcmK3 does not form homohexamers; instead CcmK3 forms heterohexamers with CcmK4 with a 1:2 stoichiometry. The CcmK3-CcmK4 heterohexamers form stacked dodecamers in a pH-dependent manner. Our results indicate that CcmK3-CcmK4 heterohexamers potentially expand the range of permeability properties of metabolite channels in carboxysome shells. Moreover, the observed facultative formation of dodecamers in solution suggests that carboxysome shell permeability may be dynamically attenuated by "capping" facet-embedded hexamers with a second hexamer. Because β-carboxysomes are obligately expressed, heterohexamer formation and capping could provide a rapid and reversible means to alter metabolite flux across the shell in response to environmental/growth conditions.
The process wherein dividing cells exhaust proliferative capacity and enter into replicative senescence has become a prominent model for cellular aging in vitro. Despite decades of study, this ...cellular state is not fully understood in culture and even much less so during aging. Here, we revisit Leonard Hayflick's original observation of replicative senescence in WI-38 human lung fibroblasts equipped with a battery of modern techniques including RNA-seq, single-cell RNA-seq, proteomics, metabolomics, and ATAC-seq. We find evidence that the transition to a senescent state manifests early, increases gradually, and corresponds to a concomitant global increase in DNA accessibility in nucleolar and lamin associated domains. Furthermore, we demonstrate that senescent WI-38 cells acquire a striking resemblance to myofibroblasts in a process similar to the epithelial to mesenchymal transition (EMT) that is regulated by t YAP1/TEAD1 and TGF-β2. Lastly, we show that verteporfin inhibition of YAP1/TEAD1 activity in aged WI-38 cells robustly attenuates this gene expression program.
Cognitive Decline and Older Driver Crash Risk Fraade‐Blanar, Laura A.; Ebel, Beth E.; Larson, Eric B. ...
Journal of the American Geriatrics Society (JAGS),
June 2018, Letnik:
66, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Objectives
To examine automobile crash risk associated with cognition in older drivers without dementia.
Design
Retrospective secondary analysis of longitudinal cohort study.
Setting
Our study used ...data from the Adult Changes in Thought (ACT) Study merged with Washington State crash reports and licensure records. Data were available from 2002 to 2015.
Participants
Group Health enrollees from Washington State aged 65 and older with active driver's licenses (N=2,615).
Measurements
Cognitive function was assessed using the Cognitive Abilities Screening Instrument scored using item response theory (CASI‐IRT). The study outcome was police‐reported motor vehicle crash. We used a negative binomial mixed‐effects model with robust standard errors clustered on the individual and considered associations between crash risk, level of cognition, and amount of decline since the previous study visit. Covariates included age, sex, education, alcohol, depression, medical comorbidities, eyesight, hearing, and physical function. Individuals were censored at dementia diagnosis, death, or failure to renew their license.
Results
Over an average of 7 years of follow‐up, 350 (13%) people had at least one crash. A 1‐unit lower CASI‐IRT score was associated with a higher adjusted incidence rate ratio of crash of 1.26 (95% confidence interval=1.08–1.51). Beyond level of cognition, amount of cognitive decline between study visits was not associated with crash risk.
Conclusion
This study suggests that, in older drivers, poorer performance on the CASI‐IRT may be a risk factor for motor vehicle crashes, even in individuals without diagnosed dementia. Further research is needed to understand driving behavior and inform driving decisions for older adults with poor cognitive function.
Abstract Mesenchymal stem cells (MSCs)-based therapy is a promising approach in regenerative medicine and tissue engineering. However, the outcomes of existing treatments have not been satisfactory ...owing to suboptimal localization to implantation site, poor viability, low engraftment efficacy and lack of functional remodeling of the delivered cells. Therefore, adopting an effective cell delivery modality is among the biggest technological challenges for successful clinical applications of MSC-based therapy. We developed a novel microencapsulation technique producing self-assembled collagen–MSC microspheres and demonstrated that these microspheres could serve as excellent cell delivery devices as they were stable, injectable and able to provide a protective, growth- and migration-supporting matrix to MSCs. We also showed that MSCs could preserve their stem cell nature upon microencapsulation and easily be localized with retained viability upon in vivo implantation. These microspheres present novel cell delivery devices with optimal biological and functional profile that may facilitate clinical applications of MSC-based therapy.
Flowers of the hop plant provide both bitterness and "hoppy" flavor to beer. Hops are, however, both a water and energy intensive crop and vary considerably in essential oil content, making it ...challenging to achieve a consistent hoppy taste in beer. Here, we report that brewer's yeast can be engineered to biosynthesize aromatic monoterpene molecules that impart hoppy flavor to beer by incorporating recombinant DNA derived from yeast, mint, and basil. Whereas metabolic engineering of biosynthetic pathways is commonly enlisted to maximize product titers, tuning expression of pathway enzymes to affect target production levels of multiple commercially important metabolites without major collateral metabolic changes represents a unique challenge. By applying state-of-the-art engineering techniques and a framework to guide iterative improvement, strains are generated with target performance characteristics. Beers produced using these strains are perceived as hoppier than traditionally hopped beers by a sensory panel in a double-blind tasting.
In this paper, the technical applicability and treatment performance of physico-chemical techniques (individual and/or combined) for landfill leachate are reviewed. A particular focus is given to ...coagulation–flocculation, chemical precipitation, ammonium stripping, membrane filtration and adsorption. The advantages and limitations of various techniques are evaluated. Their operating conditions such as pH, dose required, characteristics of leachate in terms of chemical oxygen demand (COD) and NH
3–N concentration and treatment efficiency are compared. It is evident from the survey of 118 papers (1983–2005) that none of the individual physico-chemical techniques is universally applicable or highly effective for the removal of recalcitrant compounds from stabilized leachate. Among the treatments reviewed in this article, adsorption, membrane filtration and chemical precipitation are the most frequently applied and studied worldwide. Both activated carbon adsorption and nanofiltration are effective for over 95% COD removal with COD concentrations ranging from 5690 to 17,000
mg/L. About 98% removal of NH
3–N with an initial concentration ranging from 3260 to 5618
mg/L has been achieved using struvite precipitation. A combination of physico-chemical and biological treatments has demonstrated its effectiveness for the treatment of stabilized leachate. Almost complete removal of COD and NH
3–N has been accomplished by a combination of reverse osmosis (RO) and an upflow anaerobic sludge blanket (UASB) with an initial COD concentration of 35,000
mg/L and NH
3–N concentration of 1600
mg/L and/or RO and activated sludge with an initial COD concentration of 6440
mg/L and NH
3–N concentration of 1153
mg/L. It is important to note that the selection of the most suitable treatment method for landfill leachate depends on the characteristics of landfill leachate, technical applicability and constraints, effluent discharge alternatives, cost-effectiveness, regulatory requirements and environmental impact.
This article reviews the technical applicability and the treatment performance of various advanced oxidation technologies (AOTs) for landfill leachate. A particular focus is given to ozonation, ...homogeneous systems without irradiation (Fe
2+/H
2O
2, O
3/H
2O
2) and homogeneous systems with irradiation (UV/O
3, UV/H
2O
2, UV/O
3/H
2O
2, photo-Fenton oxidation). Their advantages and limitations in application are evaluated. The formation of
OH radicals in enhancing oxidation reactions is also elaborated. Selected information such as the pH, the dose of oxidants required, the characteristics of leachate in terms of COD and NH
3-N concentration and treatment performance is presented. It is evident from a review of 167 papers (1976–2005) that none of the individual AOTs is universally applicable or highly effective for leachate treatment. Among the individual AOTs reviewed, ozonation and/or Fenton oxidation are the most frequently studied and widely applied for leachate treatment. Both treatments are effective for 40–89% of COD removal with its concentrations ranging from 560 to 8894
mg/L. By combining the Fenton oxidation and coagulation–flocculation process, about 69–90% of COD removal with its concentrations ranging from 417 to 7400
mg/L was achieved. An almost complete COD removal (98%) was attained by combining the activated sludge (AS) and the Fenton oxidation (COD: 7000
mg/L) and/or the AS and wet air oxidation (WAO) (COD: 4140
mg/L). In general, the selection of the most suitable AOT for leachate treatment depends on the leachate characteristics, technical applicability and potential constraints, effluent discharge standard, cost-effectiveness, regulatory requirements and long-term environmental impacts.
Transthyretin-associated forms of cardiac amyloidosis are fatal protein misfolding diseases that can be inherited (ATTRm) or acquired (ATTRwt). An accurate diagnosis of ATTR amyloidosis can be ...challenging as biopsy evidence, usually from the affected organ, is required. Precise biomarkers for ATTR disease identification and monitoring are undiscovered, disease-specific therapeutic options are needed, and the current understanding of ATTR molecular pathogenesis is limited. The aim of this study was to investigate and compare the serum proteomes in ATTRm and ATTRwt cardiac amyloidosis to identify differentially expressed blood proteins that were disease-specific. Using multiple-reaction monitoring mass spectrometry (MRM-MS), the concentrations of 160 proteins were analyzed in serum samples from ATTRm and ATTRwt patients, and a healthy control group. Patient and control sera were matched to age (≥60 years), gender (male), and race (Caucasian). The circulating concentrations of 123/160 proteins were significantly different in patient vs control sera; TTR and retinol-binding protein (RBP4) levels were significantly decreased (p < 0.03) in ATTRm compared to controls. In ATTRm, 14/123 proteins were identified as unique to that group and found generally to be lower than controls; moreover, the concentrations of RBP4 and 6 other proteins in this group were significantly different (p < 0.04) compared to ATTRwt. Predicted interactions among the 14 proteins unique to ATTRm were categorized as reaction and binding associations. Alternatively, 27 proteins were found to be unique to ATTRwt with associated interactions defined as activation, catalysis, and inhibition, in addition to reaction and binding. This study demonstrates significant proteomic differences between ATTR patient and control sera, and disease-associated variations in circulating levels of several proteins including TTR and RBP4. The identification of serum proteins unique to ATTRm and ATTRwt cardiac amyloidosis may have diagnostic and prognostic utility, and may provide important clues about disease mechanisms.
Introduction
Sexual minority discrimination might lead to a higher risk of mild cognitive impairment (MCI) and dementia. The aim of this study was to assess the risk of MCI and dementia between older ...adults in same‐sex relationships (SSR) and opposite‐sex relationships (OSR).
Methods
We analyzed longitudinal data from the National Alzheimer's Coordinating Center up to September 2017. Analyses included cognitively normal individuals 55+ at baseline who had a spouse, partner, or companion as study partner at any assessment. Associations were calculated using survival analysis adjusting for demographics and APOE‐e4 carrier status.
Results
Hazard ratios of MCI and dementia did not differ statistically between SSR and OSR individuals in the total sample nor stratified by sex.
Conclusion
The lack of association between SSR and MCI and dementia warrants future research into their potential resilience mechanisms and the inclusion of sexual minority status questions in research and surveillance studies. The potential recruitment bias caused by nonprobabilistic sampling of the cohort and the reporting and ascertainment bias caused by using SSR to infer sexual minority status may have influenced our findings.
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