Over the past century, Escherichia coli has become one of the best studied organisms on earth. Features such as genetic tractability, favorable growth conditions, well characterized biochemistry and ...physiology, and availability of versatile genetic manipulation tools make E. coli an ideal platform host for development of industrially viable productions. In this review, we discuss the physiological attributes of E. coli that are most relevant for metabolic engineering, as well as emerging techniques that enable efficient phenotype construction. Further, we summarize the large number of native and non-native products that have been synthesized by E. coli, and address some of the future challenges in broadening substrate range and fighting phage infection.
•The well characterized physiology of E. coli allows for rapid strain development.•A plethora of genetic techniques have been developed for genomic edits in E. coli including the λ-Red recombinase system, CRISPR, and MAGE.•A wide variety of chemicals have been produced by E. coli both in the laboratory and for industrial scale production.
Summary Background The novel influenza A H7N9 virus emerged recently in mainland China, whereas the influenza A H5N1 virus has infected people in China since 2003. Both infections are thought to be ...mainly zoonotic. We aimed to compare the epidemiological characteristics of the complete series of laboratory-confirmed cases of both viruses in mainland China so far. Methods An integrated database was constructed with information about demographic, epidemiological, and clinical variables of laboratory-confirmed cases of H7N9 (130 patients) and H5N1 (43 patients) that were reported to the Chinese Centre for Disease Control and Prevention until May 24, 2013. We described disease occurrence by age, sex, and geography, and estimated key epidemiological variables. We used survival analysis techniques to estimate the following distributions: infection to onset, onset to admission, onset to laboratory confirmation, admission to death, and admission to discharge. Findings The median age of the 130 individuals with confirmed infection with H7N9 was 62 years and of the 43 with H5N1 was 26 years. In urban areas, 74% of cases of both viruses were in men, whereas in rural areas the proportions of the viruses in men were 62% for H7N9 and 33% for H5N1. 75% of patients infected with H7N9 and 71% of those with H5N1 reported recent exposure to poultry. The mean incubation period of H7N9 was 3·1 days and of H5N1 was 3·3 days. On average, 21 contacts were traced for each case of H7N9 in urban areas and 18 in rural areas, compared with 90 and 63 for H5N1. The fatality risk on admission to hospital was 36% (95% CI 26–45) for H7N9 and 70% (56–83%) for H5N1. Interpretation The sex ratios in urban compared with rural cases are consistent with exposure to poultry driving the risk of infection—a higher risk in men was only recorded in urban areas but not in rural areas, and the increased risk for men was of a similar magnitude for H7N9 and H5N1. However, the difference in susceptibility to serious illness with the two different viruses remains unexplained, since most cases of H7N9 were in older adults whereas most cases of H5N1 were in younger people. A limitation of our study is that we compared laboratory-confirmed cases of H7N9 and H5N1 infection, and some infections might not have been ascertained. Funding Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease and University Grants Committee, Hong Kong Special Administrative Region, China; and the US National Institutes of Health.
Severe malaria is caused by the apicomplexan parasite
Despite decades of research, the distinct biology of these parasites has made it challenging to establish high-throughput genetic approaches to ...identify and prioritize therapeutic targets. Using transposon mutagenesis of
in an approach that exploited its AT-rich genome, we generated more than 38,000 mutants, saturating the genome and defining mutability and fitness costs for over 87% of genes. Of 5399 genes, our study defined 2680 genes as essential for optimal growth of asexual blood stages in vitro. These essential genes are associated with drug resistance, represent leading vaccine candidates, and include approximately 1000
-conserved genes of unknown function. We validated this approach by testing proteasome pathways for individual mutants associated with artemisinin sensitivity.
The adiabatic, laminar flame speeds of gasoline surrogates at atmospheric pressure over a range of equivalence ratios of Φ = 0.8–1.3 and unburned gas temperatures of 298–400 K are measured with the ...flat flame method, which produces a one-dimensional flat flame free of stretch. Surrogates used in the current work are the primary reference fuels (PRFs, mixtures of n-heptane and isooctane), the toluene reference fuels (TRFs, mixtures of toluene and PRFs), and the ethanol reference fuels (ERFs, mixtures of ethanol and PRFs). In general, there is good agreement between the present work and the literature data for single-component fuel and PRF mixtures. Surrogates of TRF mixtures are found to exhibit comparable flame speeds to a real gasoline, while there is discrepancy observed between isooctane and gasoline. Moreover, the laminar flame speeds of TRF mixtures with similar fractions of n-heptane are found to be insensitive to the quantity of toluene in the mixture. Mixtures of ERFs exhibit comparable flame speeds to those of TRFs with similar mole fractions of n-heptane and isooctane.
Microstructures and mechanical properties of equal-channel angular pressing (ECAP) processed and naturally aged ultrafine grained (UFG) and coarse grained (CG) 7075 Al alloys as well as their ...evolutions during annealing were investigated. After the same natural aging, the tensile yield strength, ultimate strength, and microhardness of the UFG samples were 103%, 35%, and 48% higher, respectively, than those of the CG samples, because of higher densities of Guinier–Preston (G–P) zones and dislocations in the UFG sample. Upon annealing, the microhardness of the UFG sample decreased gradually, while a hardening peak appeared for the CG sample. The peak was caused by the precipitation hardening of the metastable η
′ phase. For the UFG sample, the precipitation hardening was overcompensated by the significant decrease of microstrain (dislocation density) upon annealing, resulting in a lack of precipitation hardening peak. Differential scanning calorimetry indicates that the ECAP process only accelerated the phase precipitations, but did not change the sequence of phase precipitation. This study shows that severe plastic deformation has the potential to significantly improve the mechanical properties of age-hardening Al alloys.
Summary Background Transmission of the novel avian influenza A H7N9 virus seems to be predominantly between poultry and people. In the major Chinese cities of Shanghai, Hangzhou, Huzhou, and ...Nanjing—where most human cases of infection have occurred—live poultry markets (LPMs) were closed in April, 2013, soon after the initial outbreak, as a precautionary public health measure. Our objective was to quantify the effect of LPM closure in these cities on poultry-to-person transmission of avian influenza A H7N9 virus. Methods We obtained information about every laboratory-confirmed human case of avian influenza A H7N9 virus infection reported in the four cities by June 7, 2013, from a database built by the Chinese Center for Disease Control and Prevention. We used data for age, sex, location, residence type (rural or urban area), and dates of illness onset. We obtained information about LPMs from official sources. We constructed a statistical model to explain the patterns in incidence of cases reported in each city on the basis of the assumption of a constant force of infection before LPM closure, and a different constant force of infection after closure. We fitted the model with Markov chain Monte Carlo methods. Findings 85 human cases of avian influenza A H7N9 virus infection were reported in Shanghai, Hangzhou, Huzhou, and Nanjing by June 7, 2013, of which 60 were included in our main analysis. Closure of LPMs reduced the mean daily number of infections by 99% (95% credibility interval 93–100%) in Shanghai, by 99% (92–100%) in Hangzhou, by 97% (68–100%) in Huzhou, and by 97% (81–100%) in Nanjing. Because LPMs were the predominant source of exposure to avian influenza A H7N9 virus for confirmed cases in these cities, we estimated that the mean incubation period was 3·3 days (1·4–5·7). Interpretation LPM closures were effective in the control of human risk of avian influenza A H7N9 virus infection in the spring of 2013. In the short term, LPM closure should be rapidly implemented in areas where the virus is identified in live poultry or people. In the long term, evidence-based discussions and deliberations about the role of market rest days and central slaughtering of all live poultry should be renewed. Funding Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease; Hong Kong University Grants Committee; China–US Collaborative Program on Emerging and Re-emerging Infectious Diseases; Harvard Center for Communicable Disease Dynamics; and the US National Institutes of Health.
Simultaneous increase of the ductility and strength of a bulk nanostructured Al alloy with an average grain size of ∼ 100 nm (curve NS) has been achieved by precipitating Guinier–Preston (G–P) zones, ...η′, and η particles (curve NS+P). Bulk nanostructured materials usually have high strength, but disappointingly low ductility. All previous attempts to enhance the ductility of nanostructured materials have sacrificed their yield strengths. This strategy is applicable to many nanostructured alloys and composites.
Objectives
To determine whether nutritional status can predict 3-year cognitive and functional decline, as well as 4-year all-cause mortality in older adults.
Design
Prospectively longitudinal cohort ...study.
Setting and participants
The study recruited 354 men aged 65 years and older in the veteran’s retirement community.
Measures
Baseline nutritional status was evaluated using the Mini-Nutritional Assessment-Short Form (MNA-SF). Cognitive function and Activities of Daily Living (ADL) function were determined by the Mini-Mental State Examination (MMSE) and the Barthel Index, respectively. Three-year cognitive and functional decline were respectively defined as a >3 point decrease in the MMSE scores and lower ADL scores than at baseline. Univariate and multivariable logistic regression analyses were conducted to identify nutritional status as a risk factor in poor outcome. The Kaplan-Meier method and Cox proportional regression models were used to estimate the effect of malnutrition risk on the mortality.
Results
According to MNS-SF, the prevalence of risk of malnutrition was 53.1% (188/354). Multivariate logistic regression found risk of malnutrition significantly associated with 3-year cognitive decline (Adjusted odds ratio OR 2.07, 95% Confidence Interval CI 1.05–4.08, P =0.036) and functional decline (Adjusted OR 1.83, 95% CI 1.01–3.34, P =0.047) compared with normal nutritional status. The hazard ratio (HR) for all-cause mortality was 1.8 times higher in residents at risk of malnutrition (Adjusted HR 1.82, 95% CI 1.19–2.79, P =0.006).
Conclusions
Our results provide strong evidence that risk of malnutrition can predict not only cognitive and functional decline but also risk of all-cause mortality in older men living in a veteran retirement’s community. Further longitudinal studies are needed to explore the causal relationship among nutrition, clinical outcomes, and the effect of an intervention for malnutrition.
Summary Background Itch is the cardinal symptom of atopic dermatitis (AD). β‐Endorphin, a neuropeptide, is increased in both AD skin and sera. Interleukin (IL)‐31, an itch‐relevant cytokine, ...activates IL‐31 receptors in keratinocytes. However, how IL‐31 and β‐endorphin interact in AD skin remains elusive.
Objectives To investigate the mechanistic interaction of IL‐31 and β‐endorphin in AD.
Methods This was a prospective cross‐sectional study. We recruited adult patients with AD and controls according to Hanifin’s AD criteria. Serum levels of IL‐31 and β‐endorphin were measured by enzyme‐linked immunosorbent assay. Expressions of IL‐31 receptor A (IL‐31RA) and β‐endorphin in the skin were assessed by immunohistochemistry. Their expression in the skin and blood was compared and correlated in patients with AD and in controls. We also treated primary keratinocytes with IL‐31 and measured calcium influx, β‐endorphin production and signalling pathways to define their mechanistic interactions.
Results β‐Endorphin was increased in the supernatant from IL‐31‐treated keratinocytes. IL‐31 receptor activation resulted in calcium influx and STAT3 activation; pretreatment with STAT3 inhibitor stopped the increase of β‐endorphin. Notably, either replacement of extracellular calcium or treatment with 2‐aminoethoxydiphenyl borate, an inhibitor for the store‐operated channel, blocked STAT3 activation. We found higher levels of blood β‐endorphin and IL‐31, which were significantly correlated, in patients with AD. Moreover, IL‐31RA and β‐endorphin were increased and colocalized both in AD human skin and TPA‐painted mouse skin.
Conclusions IL‐31 receptor activation in keratinocytes induces calcium influx and STAT3‐dependent production of β‐endorphin. These results might contribute to an understanding of the regulatory mechanisms underlying peripheral itch.
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