Pediocin PA-1, a wide-spectrum bacteriocin from lactic acid bacteria

Pediocin PA-1 is a broad-spectrum lactic acid bacteria bacteriocin that shows a particularly strong activity against Listeria monocytogenes, a foodborne pathogen of special concern among the food industries. This antimicrobial peptide is the most extensively studied class IIa (or pediocin family) bacteriocin, and it has been sufficiently well characterized to be used as a food biopreservative. This review focuses on the progress that have been made in the elucidation of its structure, mode of action, and biosynthesis, and includes an overview of its applications in food systems. The aspects that need further research are also addressed. In the future, protein engineering, genetic engineering and/or chemical synthesis may lead to the development of new antimicrobial peptides with improved properties, based on some features of the pediocin PA-1 molecule

Prediction of gait events in walking activities with a Bayesian perception system

In this paper, a robust probabilistic formulation for prediction of gait events from human walking activities using wearable sensors is presented. This approach combines the output from a Bayesian perception system with observations from actions and decisions made over time. The perception system makes decisions about the current gait events, while observations from decisions and actions allow to predict the most probable gait event during walking activities. Furthermore, our proposed method is capable to evaluate the accuracy of its predictions, which permits to obtain a better performance and trade-off between accuracy and speed. In our work, we use data from wearable inertial measurement sensors attached to the thigh, shank and foot of human participants. The proposed perception system is validated with multiple experiments for recognition and prediction of gait events using angular velocity data from three walking activities; level-ground, ramp ascent and ramp descent. The results show that our method is fast, accurate and capable to evaluate and adapt its own performance. Overall, our Bayesian perception system demonstrates to be a suitable high-level method for the development of reliable and intelligent assistive and rehabilitation robots

Manipulations of antibody galactosylation in a fed-batch adapted perfusion process

Perfusion processes have demonstrated significantly higher volumetric productivity while maintaining consistent product quality attributes (PQAs) throughout an extended harvest period. With this, a drastic decrease of the bioreactor footprint in future commercial plants can be achieved. Therefore, there are significant efforts in biopharmaceutical industry focused on developing high productivity perfusion process for both future biologics, as well as on developing new generation processes for legacy fed-batch processes. In this presentation, we will report the adaptation of an established 14-day fed-batch process for a therapeutic monoclonal antibody to a 30-day perfusion process using alternating tangential flow (ATF) technology. In the proof-of-concept perfusion process, a 6-fold viable cell density (VCD) was reached and maintained compared to the peak VCD in the fed-batch process. The productivity increased 3.5-fold as compared to the original fed-batch process after normalization to cell culture duration. The major PQAs from this perfusion process were consistent throughout the harvest period. Most of the PQAs from the perfusion process showed no significant differences from the original fed-batch process. However, significantly higher galactosylation level was observed in the perfusion process as compared to its fed-batch version. In the presentation, we will also detail the perfusion medium and process parameter optimization, which enabled the matching of the galactosylation profile of the last version perfusion process to the established fed-batch process without compromising target VCD, productivities, and other PQA profiles

A Complete Pipeline for Heart Rate Extraction from Infant ECGs

\ua9 2024 by the authors.Infant electrocardiograms (ECGs) and heart rates (HRs) are very useful biosignals for psychological research and clinical work, but can be hard to analyse properly, particularly longform (≥5 min) recordings taken in naturalistic environments. Infant HRs are typically much faster than adult HRs, and so some of the underlying frequency assumptions made about adult ECGs may not hold for infants. However, the bulk of publicly available ECG approaches focus on adult data. Here, existing open source ECG approaches are tested on infant datasets. The best-performing open source method is then modified to maximise its performance on infant data (e.g., including a 15 Hz high-pass filter, adding local peak correction). The HR signal is then subsequently analysed, developing an approach for cleaning data with separate sets of parameters for the analysis of cleaner and noisier HRs. A Signal Quality Index (SQI) for HR is also developed, providing insights into where a signal is recoverable and where it is not, allowing for more confidence in the analysis performed on naturalistic recordings. The tools developed and reported in this paper provide a base for the future analysis of infant ECGs and related biophysical characteristics. Of particular importance, the proposed solutions outlined here can be efficiently applied to real-world, large datasets

Validation of large-volume batch solar reactors for the treatment of rainwater in field trials in sub-Saharan Africa

The efficiency of two large-volume batch solar reactors [Prototype I (140 L) and II (88 L)] in treating rainwater on-site in a local informal settlement and farming community was assessed. Untreated [Tank 1 and Tank 2-(First-flush)] and treated (Prototype I and II) tank water samples were routinely collected from each site and all the measured physico-chemical parameters (e.g. pH and turbidity, amongst others), anions (e.g. sulphate and chloride, amongst others) and cations (e.g. iron and lead, amongst others) were within national and international drinking water guidelines limits. Culture-based analysis indicated that Escherichia coli, total and faecal coliforms, enterococci and heterotrophic bacteria counts exceeded drinking water guideline limits in 61%, 100%, 45%, 24% and 100% of the untreated tank water samples collected from both sites. However, an 8 hour solar exposure treatment for both solar reactors was sufficient to reduce these indicator organisms to within national and international drinking water standards, with the exception of the heterotrophic bacteria which exceeded the drinking water standard limit in 43% of the samples treated with the Prototype I reactor (1 log reduction). Molecular viability analysis subsequently indicated that mean overall reductions of 75% and 74% were obtained for the analysed indicator organisms (E. coli and enterococci spp.) and opportunistic pathogens (Klebsiella spp., Legionella spp., Pseudomonas spp., Salmonella spp. and Cryptosporidium spp. oocysts) in the Prototype I and II solar reactors, respectively. The large-volume batch solar reactor prototypes could thus effectively provide four (88 L Prototype II) to seven (144 L Prototype I) people on a daily basis with the basic water requirement for human activities (20 L). Additionally, a generic Water Safety Plan was developed to aid practitioners in identifying risks and implement remedial actions in this type of installation in order to ensure the safety of the treated water

Virulence behavior of uropathogenic Escherichia coli strains in the host model Caenorhabditis elegans

Urinary tract infections (UTIs) are among the most common bacterial infections in humans. Although a number of bacteria can cause UTIs, most cases are due to infection by uropathogenic Escherichia coli (UPEC). UPEC are a genetically heterogeneous group that exhibit several virulence factors associated with colonization and persistence of bacteria in the urinary tract. Caenorhabditis elegans is a tiny, free-living nematode found worldwide. Because many biological pathways are conserved in C. elegans and humans, the nematode has been increasingly used as a model organism to study virulence mechanisms of microbial infections and innate immunity. The virulence of UPEC strains, characterized for antimicrobial resistance, pathogenicity-related genes associated with virulence and phylogenetic group belonging was evaluated by measuring the survival of C. elegans exposed to pure cultures of these strains. Our results showed that urinary strains can kill the nematode and that the clinical isolate ECP110 was able to efficiently colonize the gut and to inhibit the host oxidative response to infection. Our data support that C. elegans, a free-living nematode found worldwide, could serve as an in vivo model to distinguish, among uropathogenic E. coli, different virulence behavior

Molecular characterization of multidrug resistant Enterobacterales strains isolated from liver and kidney transplant recipients in Spain

The objective of this study was to analyse the mechanisms of resistance to carbapenems and other extended-spectrum-?-lactams and to determine the genetic relatedness of multidrug-resistant Enterobacterales (MDR-E) causing colonization or infection in solid-organ transplantation (SOT) recipients. Prospective cohort study in kidney (n= 142), liver (n= 98) or kidney/pancreas (n= 7) transplant recipients between 2014 and 2018 in seven Spanish hospitals. We included 531 MDR-E isolates from rectal swabs obtained before transplantation and weekly for 4?6 weeks after the procedure and 10 MDR-E from clinical samples related to an infection. Overall, 46.2% Escherichia coli, 35.3% Klebsiella pneumoniae, 6.5% Enterobacter cloacae, 6.3% Citrobacter freundii and 5.7% other species were isolated. The number of patients with MDR-E colonization post-transplantation (176; 71.3%) was 2.5-fold the number of patients colonized pre-transplantation (71; 28.7%). Extended spectrum ?-lactamases (ESBLs) and carbapenemases were detected in 78.0% and 21.1% of MDR-E isolates respectively. In nine of the 247 (3.6%) transplant patients, the microorganism causing an infection was the same strain previously cultured from surveillance rectal swabs. In our study we have observed a low rate of MDR-E infection in colonized patients 4?6 weeks post-transplantation. E. coli producing blaCTX-M-G1 and K. pneumoniae harbouring blaOXA-48 alone or with blaCTX-M-G1 were the most prevalent MDR-E colonization strains in SOT recipients.Acknowledgements The authors thank Mª Jesús Lecea and Laura Álvarez for technical assistance. Tis research was supported by ‘Plan Nacional de I+D+i and Instituto de Salud Carlos III (Fondo de Investigaciones Sanitarias 13/01191), Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, and the Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0007, RD16/0016/0010, RD16/0016/0012, RD16/0016/0011, RD16/0016/0008, RD16/0016/0002). Te study was co-fnanced by the European Development Regional Fund “A way to achieve Europe” and the Operative Program Intelligent Growth 2014‐2020

Systemic insulin sensitivity is regulated by GPS2 inhibition of AKT ubiquitination and activation in adipose tissue

OBJECTIVE: Insulin signaling plays a unique role in the regulation of energy homeostasis and the impairment of insulin action is associated with altered lipid metabolism, obesity, and Type 2 Diabetes. The main aim of this study was to provide further insight into the regulatory mechanisms governing the insulin signaling pathway by investigating the role of non-proteolytic ubiquitination in insulin-mediated activation of AKT. METHODS: The molecular mechanism of AKT regulation through ubiquitination is first dissected in vitro in 3T3-L1 preadipocytes and then validated in vivo using mice with adipo-specific deletion of GPS2, an endogenous inhibitor of Ubc13 activity (GPS2-AKO mice). RESULTS: Our results indicate that K63 ubiquitination is a critical component of AKT activation in the insulin signaling pathway and that counter-regulation of this step is provided by GPS2 preventing AKT ubiquitination through inhibition of Ubc13 enzymatic activity. Removal of this negative checkpoint, through GPS2 downregulation or genetic deletion, results in sustained activation of insulin signaling both in vitro and in vivo. As a result, the balance between lipid accumulation and utilization is shifted toward storage in the adipose tissue and GPS2-AKO mice become obese under normal laboratory chow diet. However, the adipose tissue of GPS2-AKO mice is not inflamed, the levels of circulating adiponectin are elevated, and systemic insulin sensitivity is overall improved. CONCLUSIONS: Our findings characterize a novel layer of regulation of the insulin signaling pathway based on non-proteolytic ubiquitination of AKT and define GPS2 as a previously unrecognized component of the insulin signaling cascade. In accordance with this role, we have shown that GPS2 presence in adipocytes modulates systemic metabolism by restricting the activation of insulin signaling during the fasted state, whereas in absence of GPS2, the adipose tissue is more efficient at lipid storage, and obesity becomes uncoupled from inflammation and insulin resistance

Characteristics, management and outcome of a large necrotising otitis externa case series: need for standardised case definition

Background: Necrotising otitis externa (NOE) is a severe ear infection for which there are no established diagnostic or treatment guidelines. Objective: Describe clinical characteristics, management and outcomes for patients managed as NOE at a UK tertiary referral centre. Methods: Retrospective case series. Results: 58 (63%) patients were classified as definite NOE cases, 31 (34%) as probable and 3 (3%) as possible cases. Median duration of intravenous and oral antimicrobial therapy was 6.0 weeks (0.49-44.9). 6% of patients relapsed a median of 16.4 weeks (IQR 23-121) after stopping antimicrobials. 28% of cases had complex disease. These patients were older (p=0.042), had a longer duration of symptoms prior to imaging (p= 0.0001) and higher CRP at diagnosis (p=0.005). Despite longer courses of intravenous antimicrobials (23 days v 14 days; p=0.032), complex cases were more likely to relapse (p=0.016). Conclusion: A standardised case-definition of NOE is needed to optimise diagnosis, management and research