Metabolic modelling of polyhydroxyalkanoate copolymers production by mixed microbial cultures

Background: This paper presents a metabolic model describing the production of polyhydroxyalkanoate (PHA) copolymers in mixed microbial cultures, using mixtures of acetic and propionic acid as carbon source material. Material and energetic balances were established on the basis of previously elucidated metabolic pathways. Equations were derived for the theoretical yields for cell growth and PHA production on mixtures of acetic and propionic acid as functions of the oxidative phosphorylation efficiency, P/O ratio. The oxidative phosphorylation efficiency was estimated from rate measurements, which in turn allowed the estimation of the theoretical yield coefficients. Results: The model was validated with experimental data collected in a sequencing batch reactor (SBR) operated under varying feeding conditions: feeding of acetic and propionic acid separately (control experiments), and the feeding of acetic and propionic acid simultaneously. Two different feast and famine culture enrichment strategies were studied: (i) either with acetate or (ii) with propionate as carbon source material. Metabolic flux analysis (MFA) was performed for the different feeding conditions and culture enrichment strategies. Flux balance analysis (FBA) was used to calculate optimal feeding scenarios for high quality PHA polymers production, where it was found that a suitable polymer would be obtained when acetate is fed in excess and the feeding rate of propionate is limited to ∼0.17 C-mol/ (C-mol.h). The results were compared with published pure culture metabolic studies. Conclusion: Acetate was more conducive toward the enrichment of a microbial culture with higher PHA storage fluxes and yields as compared to propionate. The P/O ratio was not only influenced by the selected microbial culture, but also by the carbon substrate fed to each culture, where higher P/O ratio values were consistently observed for acetate than propionate. MFA studies suggest that when mixtures of acetate and propionate are fed to the cultures, the catabolic activity is primarily guaranteed through acetate uptake, and the characteristic P/O ratio of acetate prevails over that of propionate. This study suggests that the PHA production process by mixed microbial cultures has the potential to be comparable or even more favourable than pure cultures.publishersversionpublishe

UPDATE trial: investigating the effects of ultra-processed versus minimally processed diets following UK dietary guidance on health outcomes: a protocol for an 8-week community-based cross-over randomised controlled trial in people with overweight or obesity, followed by a 6-month behavioural intervention

INTRODUCTION: Obesity increases the risk of morbidity and mortality. A major driver has been the increased availability of ultra-processed food (UPF), now the main UK dietary energy source. The UK Eatwell Guide (EWG) provides public guidance for a healthy balanced diet but offers no UPF guidance. Whether a healthy diet can largely consist of UPFs is unclear. No study has assessed whether the health impact of adhering to dietary guidelines depends on food processing. Furthermore, our study will assess the impact of a 6-month behavioural support programme aimed at reducing UPF intake in people with overweight/obesity and high UPF intakes. METHODS AND ANALYSIS: UPDATE is a 2×2 cross-over randomised controlled trial with a 6-month behavioural intervention. Fifty-five adults aged ≥18, with overweight/obesity (≥25 to <40 kg/m2), and ≥50% of habitual energy intake from UPFs will receive an 8-week UPF diet and an 8-week minimally processed food (MPF) diet delivered to their home, both following EWG recommendations, in a random order, with a 4-week washout period. All food/drink will be provided. Participants will then receive 6 months of behavioural support to reduce UPF intake. The primary outcome is the difference in weight change between UPF and MPF diets from baseline to week 8. Secondary outcomes include changes in diet, waist circumference, body composition, heart rate, blood pressure, cardiometabolic risk factors, appetite regulation, sleep quality, physical activity levels, physical function/strength, well-being and aspects of behaviour change/eating behaviour at 8 weeks between UPF/MPF diets, and at 6-month follow-up. Quantitative assessment of changes in brain MRI functional resting-state connectivity between UPF/MPF diets, and qualitative analysis of the behavioural intervention for feasibility and acceptability will be undertaken. ETHICS AND DISSEMINATION: Sheffield Research Ethics Committee approved the trial (22/YH/0281). Peer-reviewed journals, conferences, PhD thesis and lay media will report results. TRIAL REGISTRATION NUMBER: NCT05627570

A realistic assessment of methods for extracting gene/protein interactions from free text

Background: The automated extraction of gene and/or protein interactions from the literature is one of the most important targets of biomedical text mining research. In this paper we present a realistic evaluation of gene/protein interaction mining relevant to potential non-specialist users. Hence we have specifically avoided methods that are complex to install or require reimplementation, and we coupled our chosen extraction methods with a state-of-the-art biomedical named entity tagger. Results: Our results show: that performance across different evaluation corpora is extremely variable; that the use of tagged (as opposed to gold standard) gene and protein names has a significant impact on performance, with a drop in F-score of over 20 percentage points being commonplace; and that a simple keyword-based benchmark algorithm when coupled with a named entity tagger outperforms two of the tools most widely used to extract gene/protein interactions. Conclusion: In terms of availability, ease of use and performance, the potential non-specialist user community interested in automatically extracting gene and/or protein interactions from free text is poorly served by current tools and systems. The public release of extraction tools that are easy to install and use, and that achieve state-of-art levels of performance should be treated as a high priority by the biomedical text mining community

Individual variation in levels of haptoglobin-related protein in children from Gabon

Background: Haptoglobin related protein (Hpr) is a key component of trypanosome lytic factors (TLF), a subset of highdensity lipoproteins (HDL) that form the first line of human defence against African trypanosomes. Hpr, like haptoglobin (Hp) can bind to hemoglobin (Hb) and it is the Hpr-Hb complexes which bind to these parasites allowing uptake of TLF. This unique form of innate immunity is primate-specific. To date, there have been no population studies of plasma levels of Hpr, particularly in relation to hemolysis and a high prevalence of ahaptoglobinemia as found in malaria endemic areas. Methods and Principal Findings: We developed a specific enzyme-linked immunosorbent assay to measure levels of plasma Hpr in Gabonese children sampled during a period of seasonal malaria transmission when acute phase responses (APR), malaria infection and associated hemolysis were prevalent. Median Hpr concentration was 0.28 mg/ml (range 0.03-1.1). This was 5-fold higher than that found in Caucasian children (0.049 mg/ml, range 0.002-0.26) with no evidence of an APR. A general linear model was used to investigate associations between Hpr levels, host polymorphisms, parasitological factors and the acute phase proteins, Hp, C-reactive protein (CRP) and albumin. Levels of Hpr were associated with Hp genotype, decreased with age and were higher in females. Hpr concentration was strongly correlated with that of Hp, but not CRP

Viral vectored transmission blocking vaccines against Plasmodium falciparum

Background: Transmission blocking vaccines (TBVs) target sexual develop¬ment of the parasite within the mosquito and aim to prevent transmission of malaria from one individual to another. Antibodies raised against Pfs48/45, Pfs230 Region C, PfHAP2, and Anopheles gambiae Alanyl Aminopeptidase N1 (AgAPN1) proteins reduce transmission i.e. have transmission blocking activity [1–5]. Recombinant simian Adenovirus (AdC63 serotype) and Modified Vaccinia Ankara (MVA) viral vectors have been shown to induce high antibody titres to asexual parasite antigens in animal studies [6]. Materials and methods: Protein sequences for each of the antigens were codon optimised for expression in humans and cloned into shuttle vectors, which were then recombined with the parental virus and purified to obtain virus expressing the antigen of interest. Mice were vaccinated with AdC63 (i.m.), sera was taken after 2 weeks, and will be followed by an MVA boost (i.d.) eight weeks after the prime. Antibodies were assayed by a standardised ELISA, and transmission blocking activity assessed using a standardised membrane feeding assay (SMFA). Conclusion: Induction of high antibody tires using this vaccine platform could be used together with other control measures to achieve elimination and/or eradication of the disease at a local or national level

Prevalence, pattern of distribution and characterization of respiratory syncytial virus associated acute respiratory tract infections in hospitalized children less than 5 years in a general hospital in Sri Lanka from 2016–2018

Respiratory Syncytial Virus (RSV) is one of the most common respiratory viruses causing acute respiratory tract infections (ARTI) in children. Detailed data on RSV infections including the RSV types circulating in Sri Lanka are not available. This study aimed to determine the prevalence, patterns and characterization of RSV associated ARTI in hospitalized children less than 5 years in a general hospital in Sri Lanka. We tested 500 nasopharyngeal aspirate (NPA) samples collected from children with suspected viral ARTI from May 2016 to July 2018 from Kegalle General Hospital, Sri Lanka for RSV using antigen detection by an immunofluorescence assay (IFA). RSV positive samples were further characterized using the real time RT-PCR. RSV was the predominant virus associated with ARTI with a prevalence of 28% (140/500) in the study sample. RSV in was also detected in more co-infections with other respiratory viruses. RSV was detected throughout the year with peak periods from June to August 2016, March to July 2017 and May to July 2018. Of the 140 RSV positive children tested, 72.14% had RSV-B, while 27.86% had RSV-A infection. Both RSV subtypes were detected throughout the study period with overlapping patterns. A few co-infections between RSV-A and RSV-B were detected during the co-circulation. RSV was the most prevalent virus and RSV-B was the predominant subgroup associated with ARTI in the childre

HASIl PLAGIASI BUKU STRATEGI MODEL PERBANKAN SYARIAH MENGHADAPI PERSAINGAN DI ERA MASYARAKAT EKONOMI ASEAN (MEA)

HASIl PLAGIASI BUKU STRATEGI MODEL PERBANKAN SYARIAH MENGHADAPI PERSAINGAN DI ERA MASYARAKAT EKONOMI ASEAN (MEA

Two chemically similar stellar overdensities on opposite sides of the plane of the Galaxy

Our Galaxy is thought to have undergone an active evolutionary history dominated by star formation, the accretion of cold gas, and, in particular, mergers up to 10 gigayear ago. The stellar halo reveals rich fossil evidence of these interactions in the form of stellar streams, substructures, and chemically distinct stellar components. The impact of dwarf galaxy mergers on the content and morphology of the Galactic disk is still being explored. Recent studies have identified kinematically distinct stellar substructures and moving groups, which may have extragalactic origin. However, there is mounting evidence that stellar overdensities at the outer disk/halo interface could have been caused by the interaction of a dwarf galaxy with the disk. Here we report detailed spectroscopic analysis of 14 stars drawn from two stellar overdensities, each lying about 5 kiloparsecs above and below the Galactic plane - locations suggestive of association with the stellar halo. However, we find that the chemical compositions of these stars are almost identical, both within and between these groups, and closely match the abundance patterns of the Milky Way disk stars. This study hence provides compelling evidence that these stars originate from the disk and the overdensities they are part of were created by tidal interactions of the disk with passing or merging dwarf galaxies.Comment: accepted for publication in Natur

Mass hierarchy discrimination with atmospheric neutrinos in large volume ice/water Cherenkov detectors

Large mass ice/water Cherenkov experiments, optimized to detect low energy (1-20 GeV) atmospheric neutrinos, have the potential to discriminate between normal and inverted neutrino mass hierarchies. The sensitivity depends on several model and detector parameters, such as the neutrino flux profile and normalization, the Earth density profile, the oscillation parameter uncertainties, and the detector effective mass and resolution. A proper evaluation of the mass hierarchy discrimination power requires a robust statistical approach. In this work, the Toy Monte Carlo, based on an extended unbinned likelihood ratio test statistic, was used. The effect of each model and detector parameter, as well as the required detector exposure, was then studied. While uncertainties on the Earth density and atmospheric neutrino flux profiles were found to have a minor impact on the mass hierarchy discrimination, the flux normalization, as well as some of the oscillation parameter (\Delta m^2_{31}, \theta_{13}, \theta_{23}, and \delta_{CP}) uncertainties and correlations resulted critical. Finally, the minimum required detector exposure, the optimization of the low energy threshold, and the detector resolutions were also investigated.Comment: 23 pages, 16 figure