Tissue-engineered cellulose tubes for microvascular and lymphatic reconstruction: A translational and feasibility study.

BACKGROUND: Lymphedema microsurgery is an emerging treatment modality, with dissimilar long-term outcomes. One of the main technical challenges in lymphatic microsurgery is the identification and availability of suitable donor vessels for anastomosis. Tissue engineering using biomaterials has demonstrated promise in addressing vessel quality issues in other fields, but its application in microsurgery is still limited. METHODS: Decellularized cellulose tubes were developed and bioengineered by decellularizing stems of Taraxacum-Ruderalia. The microscopic structure, mechanical properties, and residual DNA content of the cellulose tubes were evaluated. Human and murine skin fibroblasts and dermal lymphatic endothelial cells were isolated and cultured for recellularization studies. Biocompatibility, proliferative capacity, and ex-vivo endothelialization of the cellulose tubes were assessed as potential interposition grafts. Finally, the engineered cellulose tubes were assessed as interposing xenografts for lymphovenous anastomoses (LVA) in an ex-vivo swine limb model. RESULTS: The decellularized cellulose tubes exhibited a suitable microscopic structure, mechanical properties, and low residual DNA content. The tubes showed adequate biocompatibility, supported cell proliferation, and facilitated spontaneous ex-vivo endothelialization of lymphatic endothelial cells. In the swine limb model, LVA using the engineered cellulose tubes was successfully performed. CONCLUSION: This translational study presents the use of decellularized cellulose tubes as an adjunct for micro and supermicrosurgical reconstruction. The developed tubes demonstrated favorable structural, mechanical, and biocompatible properties, making them a potential candidate for improving long-term outcomes in lymphedema surgical treatment. The next translational step would be trialing the obtained tubes in a microsurgical in-vivo model.

Surgical and endoscopic management of clinical T1b esophageal cancer.

OBJECTIVE: Esophageal cancers that invade the submucosa (T1b) have increased risk for occult lymph node metastases. To avoid the morbidity and recovery from esophagectomy, patients with cT1bN0 tumors have been increasingly managed endoscopically. We hypothesized that tumor attributes could predict upstaging and outcome associated with surgical and endoscopic treatment. Our objective was to evaluate the comparative effectiveness of esophagectomy across different cT1bN0 tumor attributes. METHODS: Treatment-naïve patients who underwent endoscopic management or esophagectomy for a clinical stage cT1bN0 esophageal cancer diagnosed between 2010 and 2018 in the National Cancer Database were identified. Factors associated with upstaging were assessed by logistic regression. Adjusted survival was assessed by Kaplan-Meier analysis of 528 propensity-matched pairs and accelerated time failure models, stratified across tumor attributes. RESULTS: Overall, 1469 patients classified as cT1bN0 were identified; 926 underwent esophagectomy and 543 were managed endoscopically. In general, patients who were managed endoscopically were older (median, 71; interquartile range, 63-78; vs 66; interquartile range, 60-72; P < .0001) with smaller tumors compared with the patients who were managed with esophagectomy. Nodal upstaging was associated with lymphovascular invasion (odds ratio [OR], 6.88; confidence interval [CI], 4.39-10.77; P < .0001), poor tumor differentiation (OR, 2.77; CI, 1.30-5.88; P = .0081), and tumor size >1 cm (OR, 3.19; CI, 1.49-6.83, P = .0028). Overall survival was better among propensity-matched patients who underwent esophagectomy (5-year 68.4% vs 59.7% endoscopic, P < .001). However, accelerated time failure models suggested similar outcomes among patients with well-differentiated tumors managed surgically or endoscopically. CONCLUSIONS: Esophagectomy was associated with improved survival for cT1bN0 esophageal cancer; however, endoscopic treatment may achieve similar survival in patients with favorable tumor attributes. Further study is warranted.

Are Geotextiles Silent Contributors of Ultrashort Chain PFASs to the Environment?

We investigated the presence of per- and poly fluoroalkyl substances (PFASs) in woven and nonwoven polypropylene geotextiles and four nonwoven polyester geotextiles commonly used in modern geosynthetic composite lining systems for waste containment facilities such as landfills. Targeted analysis for 23 environmentally significant PFAS molecules and methods for examining "PFAS total" concentrations were utilized to assess their occurrence in geotextiles. This analysis showed that most geotextile specimens evaluated in the current investigation contained the ultrashort chain PFAS compound pentafluoropropionic acid (PFPrA). While the concentrations ranged from nondetectable to 10.84 µg/g, the average measured concentrations of PFPrA were higher in polypropylene than in polyester geotextiles. "PFAS total" parameters comprising total fluorine (TF) and total oxidizable precursors (TOPs) indicate that no significant precursor mass nor untargeted intermediates were present in geotextiles. Therefore, this study identified geotextiles as a possible source of ultrashort PFASs in engineered lined waste containment facilities, which may contribute to the overall PFAS total concentrations in leachates or liquors they are in contact with. The findings reported for the first time herein may lead to further implications on the fate and migration of PFASs in geosynthetic composite liners, as previously unidentified concentrations, particularly of ultrashort-chain PFASs, may impact the extent of PFAS migration through and attenuation by constituents of geosynthetic composite liner systems. Given the widespread use of geotextiles in various engineering activities, these findings may have other unknown impacts. The significance of these findings needs to be further elucidated by more extensive studies with larger geotextile sample sizes to allow broader, generalized conclusions to be drawn.

Arabidopsis thaliana RHAMNOSE 1 condensate formation drives UDP-rhamnose synthesis.

Rhamnose is an essential component of the plant cell wall and is synthesized from uridine diphosphate (UDP)-glucose by the RHAMNOSE1 (RHM1) enzyme. RHM1 localizes to biomolecular condensates in plants, but their identity, formation, and function remain elusive. Combining live imaging, genetics, and biochemical approaches in Arabidopsis and heterologous systems, we show that RHM1 alone is sufficient to form enzymatically active condensates, which we name rhamnosomes. Rhamnosome formation is required for UDP-rhamnose synthesis and organ development. Overall, our study demonstrates a novel role for biomolecular condensation in metabolism and organismal development, and provides further support for how organisms have harnessed this biophysical process to regulate small molecule metabolism.

Succinate utilisation by Salmonella is inhibited by multiple regulatory systems.

Succinate is a potent immune signalling molecule that is present in the mammalian gut and within macrophages. Both of these infection niches are colonised by the pathogenic bacterium Salmonella enterica serovar Typhimurium during infection. Succinate is a C4-dicarboyxlate that can serve as a source of carbon for bacteria. When succinate is provided as the sole carbon source for in vitro cultivation, Salmonella and other enteric bacteria exhibit a slow growth rate and a long lag phase. This growth inhibition phenomenon was known to involve the sigma factor RpoS, but the genetic basis of the repression of bacterial succinate utilisation was poorly understood. Here, we use an experimental evolution approach to isolate fast-growing mutants during growth of S. Typhimurium on succinate containing minimal medium. Our approach reveals novel RpoS-independent systems that inhibit succinate utilisation. The CspC RNA binding protein restricts succinate utilisation, an inhibition that is antagonised by high levels of the small regulatory RNA (sRNA) OxyS. We discovered that the Fe-S cluster regulatory protein IscR inhibits succinate utilisation by repressing the C4-dicarboyxlate transporter DctA. Furthermore, the ribose operon repressor RbsR is required for the complete RpoS-driven repression of succinate utilisation, suggesting a novel mechanism of RpoS regulation. Our discoveries shed light on the redundant regulatory systems that tightly regulate the utilisation of succinate. We speculate that the control of central carbon metabolism by multiple regulatory systems in Salmonella governs the infection niche-specific utilisation of succinate.

Tunable Colloidal Properties of Lauramidopropyl Betaine and Li Co-modified Montmorillonite in Ethanol/Water.

Montmorillonite (Mt) is a hydrophilic clay mineral with a generally high cationic exchange capacity and a remarkable swellability in water. Yet the application of Mt in cosmetics, paints, polymer nanocomposites, drug delivery systems, and tissue engineering are limited due to its unfavorable swelling and dispersion in alcohol/water mixtures. Improving the swellability and dispersibility of Mt in mixtures of ethanol and water remains challenging. Here, we showed that the swellability and dispersibility of Mt in ethanol/water could be significantly enhanced when lithium-Mt (Li-Mt) was intercalated by zwitterionic surfactant lauramidopropyl betaine (LPB). The binding mechanism of the LPB intercalate to Li-Mt originated from a combination of van der Waals forces, ion-dipole interaction, and electrostatic attraction. Due to the synergistic effect of Li+ and LPB, the comodified Mt (LPB-Li-Mt) exhibited excellent swellability, dispersibility, and rheological properties. The structure, morphology, zeta potential, dispersibility, and gel-forming performance of LPB-Li-Mt can be modulated by the concentrations of ethanol in ethanol/water mixtures. When the ethanol concentration increased to 75% v/v ethanol solution, the free swelling of LPB-Li-Mt remained above 80%. The results from X-ray diffraction, thermogravimetric analysis, Fourier transform infrared spectroscopy, X-ray photoemission spectrometry, and small-angle X-ray scattering confirmed the full exfoliation of LPB-Li-Mt at 75% (v/v) ethanol solution. The formation of a stable colloidal LPB-Li-Mt dispersion in a mixture of ethanol/water might be derived from the association between water molecules and the Li+, the hydrophobic interaction, and the ion-dipole of ethanol with the LPB molecules. The findings provide a guide for improving dispersion and swelling of Mt and modified ones in water-miscible organic solvents.

Role of Exchange Cations and Layer Charge on the Dynamics of Confined Water.

Describing the dynamic behavior of water confined in clay minerals is a fascinating challenge and crucial in many research areas, ranging from materials science and geotechnical engineering to environmental sustainability. Water is the most abundant resource on Earth, and the high reactivity of naturally occurring hydrous clay minerals used since prehistoric times for a variety of applications means that water-clay interaction is a ubiquitous phenomenon in nature. We have attempted to experimentally distinguish the rotational dynamics and translational diffusion of two distinct populations of interlayer water, confined and ultraconfined, in the sodium (Na) forms of two smectite clay minerals, montmorillonite (Mt) and hectorite (Ht). Samples hydrated at a pseudo one-layer hydration (1LH) state under ambient conditions were studied with quasi-elastic neutron scattering (QENS) between 150 and 300 K. Using a simplified revised jump-diffusion and rotation-diffusion model (srJRM), we observed that while interlayer water near the ditrigonal cavity in Ht forms strong H-bonds to both adjacent surface O and structural OH, H-bonding of other more prevalent interlayer water with the surface O is weaker compared to Mt, inducing a higher temperature for dynamical changes of confined water. Given the lower layer charge and faster dynamics observed for Ht compared to Mt, we consider this strong evidence confirming the influence of the interlayer cation and surfaces on confined water dynamics.

Impact of the maximum ring difference on image quality and noise characteristics of a total-body PET/CT scanner.

The sensitivity of a PET system highly depends on the axial acceptance angle or maximum ring difference (MRD), which can be particularly high for total-body scanners due to their larger axial field of views (aFOVs). This study aims to evaluate the impact on image quality (IQ) and noise performance when MRD85 (18°), the current standard for clinical use, is increased to MRD322 (52°) for the Biograph Vision Quadra (Siemens Healthineers). METHODS: Studies with a cylindrical phantom covering the 106 cm aFOV and an IEC phantom filled with 18F, 68Ga and 89Zr were performed for acquisition times from 60 to 1800 s and activity concentrations from 0.4 to 3 kBq/ml to assess uniformity, contrast recovery coefficients (CRCs) and to characterize noise by coefficient of variation (CV). Spatial resolution was compared for both MRDs by sampling a quadrant of the FOV with a point source. Further IQ, CV, liver SUVmean and SUVmax were compared for a cohort of 5 patients scanned with [18F]FDG (3 MBq/kg, 1 h p.i.) from 30 to 300 s. RESULTS: CV was improved by a factor of up to 1.49 and is highest for short acquisition times, peaks at the center field of view and mitigates parabolic in axial direction with no difference to MRD85 beyond the central 80 cm. No substantial differences between the two evaluated MRDs in regards to uniformity, SUVmean or CRC for the different isotopes were observed. A degradation of the average spatial resolution of 0.9 ±â€¯0.2 mm in the central 40 cm FOV was determined with MRD322. Depending on the acquisition time MRD322 resulted in a decrease of SUVmax between 23.8% (30 s) and 9.0% (300 s). CONCLUSION: Patient and phantom studies revealed that scan time could be lowered by approximately a factor of two with MRD322 while maintaining similar noise performance. The moderate degradation in spatial resolution for MRD322 is worth to exploit the full potential of the Quadra by either shorten scan times or leverage noise performance in particular for low count scenarios such as ultra-late imaging or dynamic studies with high temporal resolution.

Nasal Septal Perforation Secondary to Graft-Versus-Host Disease.

Nasal septal perforation is a full-thickness defect of the nasal septum. There are many described etiologies of nasal septal perforation, including trauma, infectious, neoplastic, iatrogenic, and autoimmune. Graft-versus-host disease (GVHD) is a common and potentially life-threatening complication that can occur after an allogenic transplant. GVHD can result in the development of autoantibodies that lead to granulomatous inflammation with necrotizing vasculitis, causing perforation of the nasal septum. In this report, we describe a patient with nasal septal perforation secondary to GVHD and hope to provide novel insights into the association of GVHD and nasal septal perforation.

Suitability of remediated heat-treated soil in concrete applications.

Significant quantities of soil are adversely impacted by organic contaminants, including per- and poly-fluoroalkyl substances (PFAS). One proven technology for remediating PFAS affected soils is excavation and heat-treatment which destroys the PFAS, but renders the soil as an industrial waste that is normally diverted to landfill. This study investigated alternative uses for heat-treated industrial waste (HIW) soils as components in concrete, as aggregate replacement and as partial substitution of cement binder. At a replacement rate of 100% fine aggregate and ≈15% coarse aggregate, concretes made with HIW soil exhibited a strength of 47.2-48.3 MPa after 28 days' curing, compared with a reference concrete of 49.7-53.1 MPa, making the HIW ideal for aggregate replacement. Overall, the study demonstrated a novel, holistic approach to (1) remediating PFAS-affected soils, (2) diverting contaminated soil away from landfill, (3) reducing the use of high quality quarried concrete aggregates and (4) producing normal-strength concretes with a lower embodied carbon footprint than existing approaches. This study reveals that in Australia, up to 93% of all contaminated soil currently sent to landfill annually could instead be used a resource for mid-strength concretes, suitable for many applications.

Trafficking regulator of GLUT4-1 (TRARG1) is a GSK3 substrate.

Trafficking regulator of GLUT4-1, TRARG1, positively regulates insulin-stimulated GLUT4 trafficking and insulin sensitivity. However, the mechanism(s) by which this occurs remain(s) unclear. Using biochemical and mass spectrometry analyses we found that TRARG1 is dephosphorylated in response to insulin in a PI3K/Akt-dependent manner and is a novel substrate for GSK3. Priming phosphorylation of murine TRARG1 at serine 84 allows for GSK3-directed phosphorylation at serines 72, 76 and 80. A similar pattern of phosphorylation was observed in human TRARG1, suggesting that our findings are translatable to human TRARG1. Pharmacological inhibition of GSK3 increased cell surface GLUT4 in cells stimulated with a submaximal insulin dose, and this was impaired following Trarg1 knockdown, suggesting that TRARG1 acts as a GSK3-mediated regulator in GLUT4 trafficking. These data place TRARG1 within the insulin signaling network and provide insights into how GSK3 regulates GLUT4 trafficking in adipocytes.

Frequency Dependent Silica Dissolution Rate Enhancement under Oscillating Pressure via an Electrochemical Pressure Solution-like, Surface Resonance Mechanism.

From atomic force microscopy (AFM) experiments, we report a new phenomenon in which the dissolution rate of fused silica is enhanced by more than 5 orders of magnitude by simply pressing a second, dissimilar surface against it and oscillating the contact pressure at low kHz frequencies in deionized water. The silica dissolution rate enhancement was found to exhibit a strong dependence on the pressure oscillation frequency consistent with a resonance effect. This harmonic enhancement of the silica dissolution rate was only observed at asymmetric material interfaces (e.g., diamond on silica) with no evidence of dissolution rate enhancement observed at symmetric material interfaces (i.e., silica on silica) within the experimental time scales. The apparent requirement for interface dissimilarity, the results of analogous experiments performed in anhydrous dodecane, and the observation that the silica "dissolution pits" continue to grow in size under contact stresses well below the silica yield stress refute a mechanical deformation or chemo-mechanical origin to the observed phenomenon. Instead, the silica dissolution rate enhancement exhibits characteristics consistent with a previously described 'electrochemical pressure solution' mechanism, albeit, with greatly amplified kinetics. Using a framework of electrochemical pressure solution, an electrochemical model of mineral dissolution, and a recently proposed "surface resonance" theory, we present an electro-chemo-mechanical mechanism that explains how oscillating the contact pressure between dissimilar surfaces in water can amplify surface dissolution rates by many orders of magnitude. This reaction rate enhancement mechanism has implications not only for dissolution but also for potentially other reactions occurring at the solid-liquid interface, e.g. catalysis.

Characterization of Canine Adenovirus Type 2 Virus Infection Pattern in Canine and Human Cell Lines.

Canine adenovirus type 2 (CAV2) is a nonhuman adenovirus with a known ability to infect human and canine cells. The cell surface receptors involved in CAV2 transduction are still unknown. Identification of these would provide valuable information to develop enhanced gene delivery tools and better understand CAV2 biology. CAV2 is erroneously grouped with Ad5 based on the knowledge that CAV2 may transduce using CAR. Therefore, we have evaluated CAV2 and Ad5 (CAV2GFP, Ad5G/L) infection patterns in various canine and human cell lines to determine their different tropisms. Our research demonstrates that CAV2 can successfully infect cells that Ad5 does not infect, and CAV2 infections do not correlate with CAR expression. CAV2 can infect cells that have a low or minimal expression of CAR. Our data suggest that CAV2 transduction is not dependent on the CAR receptor, and thus, it is crucial to find novel CAV2 receptors.

Identification of canine circulating miRNAs as tumor biospecific markers using Next-Generation Sequencing and Q-RT-PCR.

Delay in cancer diagnosis often results in metastasis and an inability to successfully treat the tumor. The use of broadly cancer-specific biomarkers at an early stage may improve cancer treatment and staging. This study has explored circulatory exosomal miRNAs as potential diagnostic biomarkers to identify cancer patients. Secretory exosomal miRNAs were isolated from 13 canine cancer cell lines (lymphoma, mast cell tumor, histiocytic cell line, osteosarcoma, melanoma, and breast tumor) and were sequenced by Next-Generation sequencing (NGS). We have identified 6 miRNAs (cfa-miR-9, -1841, -1306, -345, -132, and -26b) by NGS that were elevated in all cancer cell types. The miRNAs identified by NGS were then examined by Q-RT-PCR. The PCR data demonstrated similar expression patterns to those seen with NGS but provided fold differences that were much lower than those seen for NGS. Cfa-miR-9 was found to be the most consistently elevated miRNA in NGS and PCR, making it the most likely miRNA to prove diagnostic. In this study, we have demonstrated that it is possible to identify exosomal miRNAs with elevated secretion across multiple tumor types that could be used as circulatory diagnostic biomarkers for liquid biopsy in the future.

In vitro functional genetic modification of canine adenovirus type 2 genome by CRISPR/Cas9.

Genetically modified oncolytic adenoviruses have been proposed as a vehicle for cancer therapy. However, several concerns, such as toxicity to normal cells and organs, lack of suitable cell surface receptors to allow viral entry to the desired cell type(s), and activation of both innate and adaptive immune systems in patients, restrict the successful clinical application of adenoviral-mediated cancer gene therapy. Successful virotherapy will require efficient transductional and transcriptional targeting to enhance therapeutic efficacy by ensuring targeted adenoviral infection, replication, and/or therapeutic transgene expression. Targeted modification of viral components, such as viral capsid, fiber knob, and the insertion of transgenes for expression, are prerequisites for the necessary transductional and transcriptional targeting of adenovirus. However, the conventional approach to modify the adenoviral genome is complex, time consuming, and expensive. It is dependent on the presence of unique restriction enzyme sites that may or may not be present in the target location. Clustered regularly interspaced short palindromic repeat (CRISPR) along with the RNA-guided nuclease Cas9 (CRISPR/Cas9) is one of the most powerful tools that has been adopted for precise genome editing in a variety of cells and organisms. However, the ability of the CRISPR/Cas9 system to precisely and efficiently make genetic modification, as well as introduce gene replacements, in adenoviral genomes, remains essentially unknown. Herein the ability of in vitro CRISPR/CAS9-mediated editing of the canine adenovirus type 2 (CAV2) genome to promote targeted modification of the viral genome was assessed. To demonstrate the feasibility of this goal, CRISPR/Cas9 has been used to successfully insert the RFP (red fluorescent protein) reporter construct into the CAV2 genome. Initial results demonstrated high efficiency and accuracy for in vitro CRISPR-mediated editing of the large CAV2 genome. Furthermore, this application was expanded, using multiple guide RNAs, to conduct gene replacement in the CAV2 genome by substituting a portion of the E3 gene with a construct designed to express a single chain antibody to canine PD-1. Thus, this work provides a significantly improved and efficient method for targeted editing of adenoviruses to generate altered and potentially therapeutic viral genomes in the shortest possible time.

CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance.

In response to the ongoing SARS-CoV-2 pandemic in the UK, the COVID-19 Genomics UK (COG-UK) consortium was formed to rapidly sequence SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of CLIMB-COVID, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network.

Genome-Wide Identification and Expression Analysis of SOS Response Genes in Salmonella enterica Serovar Typhimurium.

A bioinformatic search for LexA boxes, combined with transcriptomic detection of loci responsive to DNA damage, identified 48 members of the SOS regulon in the genome of Salmonella enterica serovar Typhimurium. Single cell analysis using fluorescent fusions revealed that heterogeneous expression is a common trait of SOS response genes, with formation of SOSOFF and SOSON subpopulations. Phenotypic cell variants formed in the absence of external DNA damage show gene expression patterns that are mainly determined by the position and the heterology index of the LexA box. SOS induction upon DNA damage produces SOSOFF and SOSON subpopulations that contain live and dead cells. The nature and concentration of the DNA damaging agent and the time of exposure are major factors that influence the population structure upon SOS induction. An analogy can thus be drawn between the SOS response and other bacterial stress responses that produce phenotypic cell variants.

Explainable AI reveals changes in skin microbiome composition linked to phenotypic differences.

Alterations in the human microbiome have been observed in a variety of conditions such as asthma, gingivitis, dermatitis and cancer, and much remains to be learned about the links between the microbiome and human health. The fusion of artificial intelligence with rich microbiome datasets can offer an improved understanding of the microbiome's role in human health. To gain actionable insights it is essential to consider both the predictive power and the transparency of the models by providing explanations for the predictions. We combine the collection of leg skin microbiome samples from two healthy cohorts of women with the application of an explainable artificial intelligence (EAI) approach that provides accurate predictions of phenotypes with explanations. The explanations are expressed in terms of variations in the relative abundance of key microbes that drive the predictions. We predict skin hydration, subject's age, pre/post-menopausal status and smoking status from the leg skin microbiome. The changes in microbial composition linked to skin hydration can accelerate the development of personalized treatments for healthy skin, while those associated with age may offer insights into the skin aging process. The leg microbiome signatures associated with smoking and menopausal status are consistent with previous findings from oral/respiratory tract microbiomes and vaginal/gut microbiomes respectively. This suggests that easily accessible microbiome samples could be used to investigate health-related phenotypes, offering potential for non-invasive diagnosis and condition monitoring. Our EAI approach sets the stage for new work focused on understanding the complex relationships between microbial communities and phenotypes. Our approach can be applied to predict any condition from microbiome samples and has the potential to accelerate the development of microbiome-based personalized therapeutics and non-invasive diagnostics.

Stepwise evolution of Salmonella Typhimurium ST313 causing bloodstream infection in Africa.

Bloodstream infections caused by nontyphoidal Salmonella are a major public health concern in Africa, causing ~49,600 deaths every year. The most common Salmonella enterica pathovariant associated with invasive nontyphoidal Salmonella disease is Salmonella Typhimurium sequence type (ST)313. It has been proposed that antimicrobial resistance and genome degradation has contributed to the success of ST313 lineages in Africa, but the evolutionary trajectory of such changes was unclear. Here, to define the evolutionary dynamics of ST313, we sub-sampled from two comprehensive collections of Salmonella isolates from African patients with bloodstream infections, spanning 1966 to 2018. The resulting 680 genome sequences led to the discovery of a pan-susceptible ST313 lineage (ST313 L3), which emerged in Malawi in 2016 and is closely related to ST313 variants that cause gastrointestinal disease in the United Kingdom and Brazil. Genomic analysis revealed degradation events in important virulence genes in ST313 L3, which had not occurred in other ST313 lineages. Despite arising only recently in the clinic, ST313 L3 is a phylogenetic intermediate between ST313 L1 and L2, with a characteristic accessory genome. Our in-depth genotypic and phenotypic characterization identifies the crucial loss-of-function genetic events that occurred during the stepwise evolution of invasive S. Typhimurium across Africa.

Durability Characterisation of Portland Cement-Carbon Nanotube Nanocomposites.

Multiwalled carbon nanotubes have outstanding mechanical properties that, when combined with Portland cement, can provide cementitious composites that could lead to the innovative construction of stronger, lighter, and thinner built infrastructure. This paper addresses a knowledge gap that relates to the durability of CNT-cement composites. The durability to corrosive chloride, uptake of water by sorption, and flow of the permeability of water acting under high water pressure are addressed. Flow simulations were undertaken through segmented 3D pore networks, based on X-ray computed microtomography measurements, the creation of a virtual microstructure, and fluid simulations that were compared with larger-scale samples. The investigation showed decreased water sorptivity of CNT-cement mixtures, indicating improved durability for the cover zone of concrete that is prone to the uptake of water and water-borne corrosives. Chloride diffusion of CNT-cement composites provided up to 63% improvement compared with control samples. The favourable durability bodes well for the construction of long-life CNT-reinforced concrete infrastructure.