222 research outputs found
Supply chain challenges for sustainability: the case of waste textiles as raw materials
Purpose: This paper addresses the growing problem of textile waste in the rapidly developing cities of subSaharan
Africa and examines, from a supply chain perspective, the potential for waste textile materials to
be transformed into the raw materials for new consumer products.
Research Approach: The paper reflects on the outcomes of a field trip to Dar es Salaam in which
stakeholders in a hypothesised textile waste supply chain were interviewed and waste textile materials
were analysed in order to determine their content and appropriateness for reuse. Findings from the field
study have been compared with current literature on logistics and market creation, waste generation,
management and recycling in sub-Saharan Africa.
Findings and Originality: The findings show that a rudimentary system has been in place for many years to
collect and recycle textiles in Dar es Salaam. However, at the same time as textile waste is projected to
increase in the city, collection rates are falling. The chief reasons for the falling rates are failures in the
‘modernised mixture’ approach to waste collection employed by Dar es Salaam City Council and market
failure for the collected materials. Alternative combinations of ‘modernised mixtures’, incorporating
community-based organisations, are likely to increase textile yields from unplanned urban areas but
previous high-profile failures in such systems within Dar es Salaam mean there is caution on both sides in
entering into such a relationship. The more pressing problem is to identify appropriate end markets for the
textile materials, since in a country where recycling is entirely market-driven, failure to do so will
undermine any attempt to improve the collection system. Whilst many studies have considered general
recycling practices in sub-Saharan Africa, there are few investigations into textile waste. Furthermore,
those existing studies do not consider the importance of understanding fibre composition of the materials
in order to determine the most appropriate end markets.
Research Impact: The research contributes to the growing body of knowledge on ‘bottom of the pyramid’
approaches to sustainable futures.
Practical Impact: The work presented considers supply chain problems and offers approaches to tackling
the increasing waste management issues of Dar es Salaam and proposes a mechanism for doing so which
has the potential to provide income for the poorest sectors of the urban society
Transposon Insertion Sequencing Elucidates Novel Gene Involvement in Susceptibility and Resistance to Phages T4 and T7 in Escherichia coli O157.
Experiments using bacteriophage (phage) to infect bacterial strains have helped define some basic genetic concepts in microbiology, but our understanding of the complexity of bacterium-phage interactions is still limited. As the global threat of antibiotic resistance continues to increase, phage therapy has reemerged as an attractive alternative or supplement to treating antibiotic-resistant bacterial infections. Further, the long-used method of phage typing to classify bacterial strains is being replaced by molecular genetic techniques. Thus, there is a growing need for a complete understanding of the precise molecular mechanisms underpinning phage-bacterium interactions to optimize phage therapy for the clinic as well as for retrospectively interpreting phage typing data on the molecular level. In this study, a genomics-based fitness assay (TraDIS) was used to identify all host genes involved in phage susceptibility and resistance for a T4 phage infecting Shiga-toxigenic Escherichia coli O157. The TraDIS results identified both established and previously unidentified genes involved in phage infection, and a subset were confirmed by site-directed mutagenesis and phenotypic testing of 14 T4 and 2 T7 phages. For the first time, the entire sap operon was implicated in phage susceptibility and, conversely, the stringent starvation protein A gene (sspA) was shown to provide phage resistance. Identifying genes involved in phage infection and replication should facilitate the selection of bespoke phage combinations to target specific bacterial pathogens.IMPORTANCE Antibiotic resistance has diminished treatment options for many common bacterial infections. Phage therapy is an alternative option that was once popularly used across Europe to kill bacteria within humans. Phage therapy acts by using highly specific viruses (called phages) that infect and lyse certain bacterial species to treat the infection. Whole-genome sequencing has allowed modernization of the investigations into phage-bacterium interactions. Here, using E. coli O157 and T4 bacteriophage as a model, we have exploited a genome-wide fitness assay to investigate all genes involved in defining phage resistance or susceptibility. This knowledge of the genetic determinants of phage resistance and susceptibility can be used to design bespoke phage combinations targeted to specific bacterial infections for successful infection eradication.This work was supported by the Wellcome Trust (grant number WT098051). A.K.C. and C.J.B. were supported by the Medical Research Council (grant number G1100100/1). D.L.G. and A.S.L. were supported by BBSRC (UKRI) funding (programme number P013740)
Age-Dependent Changes in Heparan Sulfate in Human Bruch's Membrane: Implications for Age-Related Macular Degeneration
Citation: Keenan TDL, Pickford CE, Holley RJ, et al. Age-dependent changes in heparan sulfate in human Bruch's membrane: implications for age-related macular degeneration. Invest Ophthalmol Vis Sci. 2014;55:5370-5379. DOI:10.1167/ iovs.14-14126 PURPOSE. Heparan sulfate (HS) has been implicated in age-related macular degeneration (AMD), since it is the major binding partner for complement factor H (CFH) in human Bruch's membrane (BrM), and CFH has a central role in inhibiting complement activation on extracellular matrices. The aim was to investigate potential aging changes in HS quantity and composition in human BrM. METHODS. Postmortem human ocular tissue was obtained from donors without known retinal disease. The HS was purified from BrM and neurosensory retina, and after digestion to disaccharides, fluorescently labeled and analyzed by reverse-phase HPLC. The HS and heparanase-1 were detected by immunohistochemistry in macular tissue sections from young and old donors, and binding of exogenously applied recombinant CCP6-8 region of CFH (402Y and 402H variants) was compared. RESULTS. Disaccharide analysis demonstrated that the mean quantity of HS in BrM was 50% lower (P ¼ 0.006) in old versus young donors (average 82 vs. 32 years). In addition, there was a small, but significant decrease in HS sulfation in old BrM. Immunohistochemistry revealed approximately 50% (P ¼ 0.02) less HS in macular BrM in old versus young donors, whereas heparanase-1 increased by 24% in old macular BrM (P ¼ 0.56). In young donor tissue the AMD-associated 402H CCP6-8 bound relatively poorly to BrM, compared to the 402Y form. In BrM from old donors, this difference was significantly greater (P ¼ 0.019). CONCLUSIONS. The quantity of HS decreases substantially with age in human BrM, resulting in fewer binding sites for CFH and especially affecting the ability of the 402H variant of CFH to bind BrM. Keywords: Bruch's membrane, heparan sulfate, AMD A ge-related macular degeneration (AMD) is the leading cause of blindness in developed countries. 1,2 Genetic and biochemical evidence has strongly implicated dysregulation of the complement system in disease pathogenesis. 20 Importantly, the amount of MAC in human BrM/choroid is significantly higher in individuals who are homozygous for the CFH 402H polymorphism. 21 A novel potential mechanism linking the Y402H polymorphism and AMD risk was suggested by the finding that the main binding partner of CFH in human macular BrM is heparan sulfate (HS), and that the 402H form of CFH binds poorly to human BrM HS, in comparison with the 402Y form
Use of genome sequencing to investigate the molecular basis of bacteriaphage interaction of the Escherichia coli O157 typing phages and the elucidation of the biological and public health significance of phage type
Background
Shiga toxin producing Escherichia coli (STEC) O157 causes severe gastrointestinal
disease and haemolytic uremic syndrome, and has a major impact on public health
worldwide with regular outbreaks and sporadic infection. Phage typing, i.e. the
susceptibility of STEC O157 strains to a bank of 16 bacteriophages, has been used in the UK to differentiate STEC O157 for the past 25 years and the phage type (PT)
can be an epidemiological marker of strains associated with severe disease or
associated with cases that occur from foreign travel. However, little is known
about the molecular interactions between the typing phages (TP) and STEC O157.
The aims of this thesis were to use whole genome sequencing to elucidate the
genetic basis for phage typing of STEC O157 and through this understand genetic
differences between strains relevant to disease severity and epidemiology.
Results
Sequencing the STEC O157 TPs revealed that they were clustered into 4 groups
based on sequence similarity that corresponded with their infectivity. Long read
sequencing revealed microevolutionary events occuring in STEC O157 genomes
over a short time period (approximately 1 year), evidenced by the loss and gain of
prophage regions and plasmids. An IncHI2 plasmid was found responsible for a
change in Phage Type (PT) from PT8 to PT54 during two related outbreaks at the
same restaurant. These changes resulted in a strain (PT54) that was fitter under
certain growth conditions and associated with a much larger outbreak (140 as
opposed to 4 cases). TraDIS (Transposon directed Insertion site sequencing) was
used to identify 114 genes associated with phage sensitivity and 44 genes involved
in phage resistance, emphasising the complex nature of identifying specific
genetic markers of phage susceptibility or resistance. Further work is required to
prove their phage-related functions but several are likely to encode novel phage
receptors. Deletion of a Stx2a prophage from a PT21/28 strain led to a strain that
typed as PT32, supporting the concept that the highly pathogenic PT21/28 lineage
I strains emerged from Stx2c+ PT32 strains in the last two decades by acquisition
of Stx2a-encoding prophages.
Conclusions
This body of work has highlighted the complexity of bacteriophage interaction and
investigated the genetic basis for susceptibility and resistance in E. coli. The
grouping of the TPs showed that resistance or susceptibility to all members of a
typing group was likely to be caused by one mechanism. IncHI2 was identified as
one of the markers for the PT54 phenotype. The Stx2a prophage region was
associated with the switch from PT32 to PT21/28, although PT32 strains
containing both Stx2a and Stx2c-encoding prophages have been isolated and can
provide insights into phage variation underpinning the susceptibility to the
relevant typing phages. The TraDIS results indicated that susceptibility or
resistance was governed by multiple genetic factors and not controlled by a single
gene. The significance of LPS for initial protection from phage adsorption was
evident and a number of novel genes controlling phage susceptibility and
resistance identified including the Sap operon and stringent starvation protein A
respectively. While SNP-based typing provides an excellent indication of the
evolution and relatedness of strains, phage typing can provide real insights into
short term evolution of the bacteria as PTs can be altered by mobile elements
such as prophages and plasmids. This study has shown that, although complex,
genetic determinants for PT can be mined from the genome and allow us to
understand the evolution of this zoonotic pathogen between host species and
during outbreaks
Internet-based randomised controlled trials for the evaluation of complementary and alternative medicines: probiotics in spondyloarthropathy
<b>Background</b>
The clinical effectiveness of complementary and alternative medicines (CAMs) is widely debated because of a lack of clinical trials. The internet may provide an effective and economical approach for undertaking randomised controlled trials (RCTs) of low-risk interventions. We investigated whether the internet could be used to perform an internet-based RCT of a CAM fulfilling the revised CONSORT (Consolidated Standards of Reporting Trials) statement quality checklist for reporting of RCTs. A secondary aim was to examine the effect of probiotics compared to placebo in terms of well-being over 12 weeks.<p></p>
<b>Methods</b>
People aged ≥18 years with confirmed spondyloarthropathy living in the United Kingdom with internet access were invited to participate in an internet-based RCT of probiotic compared to placebo for improving well-being and bowel symptoms. The intervention was a probiotic containing 4 strains of live bacteria or identical placebo taken by mouth daily for 3 months. The primary outcome measure was the performance of the trial according to the revised CONSORT statement.<p></p>
<b>Results</b>
147 people were randomised into the trial. The internet-based trial of the CAM fulfilled the revised CONSORT statement such as efficient blinding, allocation concealment, intention to treat analysis and flow of participants through the trial. Recruitment of the required number of participants was completed in 19 months. Sixty-five percent (96/147) completed the entire 3 months of the trial. The trial was low cost and demonstrated that in an intention to treat analysis, probiotics did not improve well-being or bowel symptoms.<p></p>
<b>Conclusion</b>
The internet-based RCT proved to be a successful and economical method for examining this CAM intervention. Recruitment, adherence and completion rate were all similar to those reported with conventional RCTs but at a fraction of the cost. Internet-based RCTs can fulfil all the criteria of the revised CONSORT statement and are an appropriate method for studying low-risk interventions
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BioTIME: A database of biodiversity time series for the Anthropocene.
MotivationThe BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene.Main types of variables includedThe database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record.Spatial location and grainBioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km2 (158 cm2) to 100 km2 (1,000,000,000,000 cm2).Time period and grainBioTIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year.Major taxa and level of measurementBioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates.Software format.csv and .SQL
Is adolescent body mass index and waist circumference associated with the food environments surrounding schools and homes? A longitudinal analysis
Background: There has been considerable interest in the role of access to unhealthy food options as a determinant of weight status. There is conflict across the literature as to the existence of such an association, partly due to the dominance of cross-sectional study designs and inconsistent definitions of the food environment. The aim of our study is to use longitudinal data to examine if features of the food environment are associated to measures of adolescent weight status. Methods: Data were collected from secondary schools in Leeds (UK) and included measurements at school years 7 (ages 11/12), 9 (13/14), and 11 (15/16). Outcome variables, for weight status, were standardised body mass index and standardised waist circumference. Explanatory variables included the number of fast food outlets, supermarkets and ‘other retail outlets’ located within a 1 km radius of an individual’s home or school, and estimated travel route between these locations (with a 500 m buffer). Multi-level models were fit to analyse the association (adjusted for confounders) between the explanatory and outcome variables. We also examined changes in our outcome variables between each time period. Results: We found few associations between the food environment and measures of adolescent weight status. Where significant associations were detected, they mainly demonstrated a positive association between the number of amenities and weight status (although effect sizes were small). Examining changes in weight status between time periods produced mainly non-significant or inconsistent associations. Conclusions: Our study found little consistent evidence of an association between features of the food environment and adolescent weight status. It suggests that policy efforts focusing on the food environment may have a limited effect at tackling the high prevalence of obesity if not supported by additional strategies
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