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Oral cancer is a paradigm of Slaughter's concept of field cancerization, where tumors are thought to originate within an area of cells containing genetic alterations that predispose to cancer development. The field size is unclear but may represent a large area of tissue, and the origin of mutations is also unclear. Here, we analyzed whole exome and transcriptome features in contralateral tumor-distal tongue (i.e. distant from the tumor, not tumor-adjacent) and corresponding tumor tissues of 15 patients with squamous cell carcinoma of the oral tongue. The number of point mutations ranged from 41 to 237 in tumors and from one to 78 in tumor-distal samples. Tumor-distal samples showed mainly clock-like (associated with aging) or tobacco smoking mutational signatures. Tumors additionally showed mutations that associate with cytidine deaminase AID/APOBEC enzyme activities or a UV-like signature. Importantly, no point mutations were shared between a tumor and the matched tumor-distal sample in any patient. TP53 was the most frequently mutated gene in tumors (67%), whereas a TP53 mutation was detected in only one tumor-distal sample, and this mutation was not shared with the matched tumor. Arm-level copy number variation (CNV) was found in 12 tumors, with loss of chromosome (Chr) 8p or gain of 8q being the most frequent events. Two tumor-distal samples showed a gain of Chr8, which was associated with increased expression of Chr8-located genes in these samples, although gene ontology did not show a role for these genes in oncogenic processes. In situ hybridization revealed a mixed pattern of Chr8 gain and neutral copy number in both tumor cells and adjacent nontumor epithelium in one patient. We conclude that distant field cancerization exists but does not present as tumor-related mutational events. The data are compatible with etiologic field effects, rather than classical monoclonal field cancerization theory. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

There is little information on the effect of temperature, relative humidity (RH) and vapour pressure deficit (VPD) on the viable populations of two commercial biocontrol strains, Bacillus subtilis QST 713 (recently classified as B. velezensis) and Gliocladium catenulatum J1446 (syn. Clonostachys rosea). The PMAxx-qPCR molecular assay was used to quantify the viable biocontrol agent (BCA) populations on fully extended lettuce and strawberry leaves under a range of temperature and RH combinations. Overall, there was a small decline in the population size of viable cells for the two biocontrol organisms on strawberry and lettuce leaves within 10 days of application. However, for most experimental runs, which contained general UK agronomy climates, such a decline was not statistically significant. Moreover, for a few runs, the viable populations increased significantly in optimal BCA growth temperatures with high RH. Only temperature (ambient) and dew point significantly affected the rate of temporal changes in the viable biocontrol population size. Thus, an increasing temperature led to decreased daily mortality. It should be noted that much of the variability in the estimated daily mortality rates remains unaccounted for, thus unless under extreme conditions, the biocontrol efficacy in practice is less likely to be affected by the survival of biocontrol microbes but more likely by other factors that influence the density of biocontrol cells in the phyllosphere, especially dilution due to rapid host leaf expansion, spray coverage and rain wash-off.

DATA AVAILABILITY STATEMENT The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available because of privacy or ethical restrictions., Background Periodontitis and erectile dysfunction (ED) have been linked with cardiovascular disease. The association of periodontitis and ED with the occurrence of major adverse cardiovascular events has not been previously assessed. The aim of this study was to determine if the presence of periodontitis and ED has any effect on the incidence of major adverse cardiovascular events. Methods Male patients that attended the Urology service were enrolled in a prospective study. Erectile dysfunction was diagnosed according to the International Index of Erectile Function. Sociodemographic data and periodontal clinical parameters were gathered (pocket probing depth, clinical attachment loss, bleeding on probing (BoP), plaque index and number of teeth) at baseline. Major adverse cardiovascular events occurred both before and during the follow-up time were registered. Bivariate analyses, as well as a multivariate analysis were performed, adjusting for potential confounders. Results A total of 158 patients were included, with a mean follow-up of 4.2 years. A greater number of major adverse cardiovascular events occurred in the group that presented periodontitis and ED (P = 0.038). After adjusting by age and previous cardiovascular disease in the multivariate analysis, the annual major adverse cardiovascular event rate was estimated to be 3.7 times higher in the same group (P = 0.049). Other periodontal clinical variables together with ED supported these results and were close to statistical significance. Conclusions Patients with periodontitis and ED, adjusted by age and a cardiovascular disease, showed 3.7 times more risk of suffering major adverse cardiovascular events after mean follow-up of 4.2 years., Research Group #CTS-583 (Junta de Andalucía, Granada, Spain)

Worldwide milk production is predominantly founded on indoor, high-concentrate feeding systems, whereas pasture-based feeding systems are most common in New Zealand and Ireland but have received greater attention recently in countries utilizing conventional systems. Consumer interest in 'pasture-fed' dairy products has also increased, arising from environmental, ethical, and nutritional concerns. A substantial body of research exists describing the effect of different feeding strategies on the composition of milk, with several recent studies focusing on the comparison of pasture- and concentrate-based feeding regimes. Significant variation is typically observed in the gross composition of milk produced from different supplemental feeds, but various changes in the discrete composition of macromolecular components in milk have also been associated with dietary influence, particularly in relation to the fatty acid profile. Changes in milk composition have also been shown to have implications for milk and dairy product processability, functionality and sensory properties. Methods to determine the traceability of dairy products or verify marketing claims such as 'pasture-fed' have also been established, based on compositional variation due to diet. This review explores the effects of feed types on milk composition and quality, along with the ultimate effect of diet-induced changes on milk and dairy product functionality, with particular emphasis placed on pasture- and concentrate-based feeding systems.

Some fungal epithiodiketopiperazine alkaloids display α,β-polysulfide bridges alongside diverse structural variations. However, the logic of their chemical diversity has rarely been explored. Here, we report the identification of three new (2, 3, 8) and five known (1, 4–7) epithiodiketopiperazines of this subtype from a marine-derived Penicillium sp. The structure elucidation was supported by multiple spectroscopic analyses. Importantly, we observed multiple nonenzymatic interconversions of these analogues in aqueous solutions and organic solvents. Furthermore, the same biosynthetic origin of these compounds was supported by one mined gene cluster. The dominant analogue (1) demonstrated selective cytotoxicity to androgen-sensitive prostate cancer cells and HIF-depleted colorectal cells and mild antiaging activities, linking the bioactivity to oxidative stress. These results provide crucial insight into the formation of fungal epithiodiketopiperazines through chemical interconversions.

In this review, we present the current information on development and applications of biological control against phytopathogenic organisms as well as mycotoxigenic fungi in Malaysia as part of the integrated pest management (IPM) programs in a collective effort to achieve food security. Although the biological control of phytopathogenic organisms of economically important crops is well established and widely practiced in Malaysia with considerable success, the same cannot be said for mycotoxigenic fungi. This is surprising because the year round hot and humid Malaysian tropical climate is very conducive for the colonization of mycotoxigenic fungi and the potential contamination with mycotoxins. This suggests that less focus has been made on the control of mycotoxigenic species in the genera Aspergillus, Fusarium, and Penicillium in Malaysia, despite the food security and health implications of exposure to the mycotoxins produced by these species. At present, there is limited research in Malaysia related to biological control of the key mycotoxins, especially aflatoxins, Fusarium-related mycotoxins, and ochratoxin A, in key food and feed chains. The expected threats of climate change, its impacts on both plant physiology and the proliferation of mycotoxigenic fungi, and the contamination of food and feed commodities with mycotoxins, including the discovery of masked mycotoxins, will pose significant new global challenges that will impact on mycotoxin management strategies in food and feed crops worldwide. Future research, especially in Malaysia, should urgently focus on these challenges to develop IPM strategies that include biological control for minimizing mycotoxins in economically important food and feed chains for the benefit of ensuring food safety and food security under climate change scenarios.

Cytochrome P450 enzymes generally functionalize inert C-H bonds, and thus, they are important biocatalysts for chemical synthesis. However, enzymes that catalyze both aliphatic and aromatic hydroxylation in the same biotransformation process have rarely been reported. A recent biochemical study demonstrated the P450 TxtC for the biosynthesis of herbicidal thaxtomins as the first example of this unique type of enzyme. Herein, the detailed characterization of substrate requirements and biocatalytic applications of TxtC are reported. The results reveal the importance of N-methylation of the thaxtomin diketopiperazine (DKP) core on enzyme reactions and demonstrate the tolerance of the enzyme to modifications on the indole and phenyl moieties of its substrates. Furthermore, hydroxylated, methylated, aromatic DKPs are synthesized through a biocatalytic route comprising TxtC and the promiscuous N-methyltransferase Amir_4628; thus providing a basis for the broad application of this unique P450.

Temperatures approaching or exceeding 20°C have been measured during summer in polar regions at the surfaces of barren fellfield soils under cloudless skies around solar noon. However, despite the upper temperature limit for the growth of cold‐adapted microbes—which are abundant in polar soils and have pivotal roles in nutrient cycling—typically being close to this temperature, previous studies have not addressed the consequences of climate change for the metabolism of these organisms in the natural environment. Here in a 5‐year field experiment on Alexander Island in the southern maritime Antarctic, we show that the abundance of Pseudogymnoascus roseus, the most widespread decomposer fungus in maritime Antarctic fellfield soils, is reduced by 1–2 orders of magnitude when irrigated and nutrient‐amended soils are warmed to >20°C during summer. Laboratory experiments under conditions mimicking those during midsummer in the natural environment indicated that the hyphal extension rates of P. roseus isolates and the activities of five extracellular enzymes are reduced by 54%–96% at high water availability after exposure to temperatures cycling daily from 2 to 21°C and 2 to 24°C, relative to temperatures cycling from 2 to 18°C. Given that the temperatures of surface soils at the study site already reach 19°C during midsummer, the observations reported here suggest that, at predicted rates of warming arising from moderate greenhouse gas emissions, inhibitory effects of climate change on the metabolism of P. roseus could manifest themselves within the next few decades. Furthermore, with peak temperatures at the surfaces of fellfield soils at other maritime Antarctic locations and in High Arctic and alpine regions already exceeding 20°C during summer, the observations suggest that climate warming has the potential to inhibit the growth of other cold‐adapted microbes, with negative effects on soils as the Earth's climate continues to warm., Summertime temperatures at the surfaces of barren maritime Antarctic soils can approach or exceed 20°C under cloudless skies around solar noon. Here we show that the metabolism of the cold‐adapted and widespread Antarctic soil fungus Pseudogymnoascus roseus is inhibited when it is exposed to temperatures cycling daily to more than 20°C, both in the natural environment and the laboratory, with substantial reductions in the in vitro growth rates of colonies and activities of extracellular enzymes. We propose that surface warming in cold regions has the potential to inhibit the growth of other cold‐adapted microbes, with negative effects on soils as the Earth's climate continues to warm.

To monitor the drift of the periosteal and endocortical surfaces during metacarpal growth longitudinally, radiogrammetry was carried out on hand-wrist X-rays of 572 children from the Birth to Twenty Bone Health Cohort annually from ages 9 to 21 years. This is the largest collection of longitudinal X-rays in African children. The second metacarpal bone length, bone width, and medullary width were measured using digital vernier calipers on a total of 4730 X-rays. Superimposition by Translation and Rotation (SITAR) was used to obtain age at peak metacarpal length velocity (PLV). Bone width and medullary width were modeled using SITAR against both chronological age and age from PLV. In black and white females, tempo and velocity of metacarpal length growth was synchronized. Black males, however, attained PLV 7 months later than white males (p

The study of in situ gas explosion to lyse the triglyceride-rich cells involves the solubilization of gas (e.g., carbon dioxide, CO2 ) in lipid-rich cells under pressure followed by a rapid decompression, which allows the gas inside the cell to rapidly expand and rupture the cell from inside out. The aim of this study was to perform the cell disruption using pressurized CO2 as well as to determine the solubility of CO2 in Rhodotorula glutinis cell suspension, sugar broth media, and spent media. Cell disruption of R. glutinis was performed at two pressures of 2,000 and 3,500 kPa, respectively, at 295.2 K, and it was found from both scanning electron microscopy (SEM) and plate count that a substantial amount of R. glutinis was disrupted due to the pressurized CO2 . We also found a considerable portion of lipid present in the aqueous phase after the disruption at P = 3,500 kPa compared to control (no pressure) and P = 2,000 kPa, which implied that more intracellular lipid was released due to the pressurized CO2 . Solubility of CO2 in R. glutinis cell suspension was found to be higher than the solubility of CO2 in both sugar broth media and spent media. Experimental solubility was correlated using the extended Henry's law, which showed a good agreement with the experimental data. Enthalpy and entropy of dissolution of CO2 were found to be -14.22 kJ mol-1 and 48.10 kJ mol-1 K-1 , 9.64 kJ mol-1 and 32.52 kJ mol-1 K-1 , and 7.50 kJ mol-1 and 25.22 kJ mol-1 K-1 in R. glutinis, spent media, and sugar broth media, respectively. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:737-748, 2017.

This study aimed at the isolation and characterization of metal(loid)-tolerant bacteria from the rhizosphere of Phragmites australis and Juncus effusus plants growing in two long-term contaminated sites in Northern Portugal. Site 1 had higher contamination than Site 3. Bacteria were isolated using metal(loid)-supplemented (Cd, Zn, and As) media. Isolates were grouped by random amplified polymorphic DNA and identified by 16S rRNA gene sequencing. Strains were also examined for their metal(loid) tolerance. The counts of metal(loid)-tolerant bacteria were higher in Site 1 and ranged between log 7.17 CFU g(-1) soil in As-containing medium and log 7.57 CFU g(-1) soil in Zn-containing medium, while counts at Site 3 varied between log 5.33 CFU g(-1) soil in Cd-containing medium and log 6.97 CFU g(-1) soil in As-containing medium. The composition of bacterial populations varied between locations. In Site 1, the classes Actinobacteria (36%) and Bacilli (24%) were well represented, while in Site 3 strains were mainly affiliated to classes Actinobacteria (35%), γ-Proteobacteria (35%), and β-Proteobacteria (12%). The order of metal(loid) toxicity for the isolated strains was Cd > As > Zn. Overall, 10 strains grew at 500 mg Cd L(-1) , 1000 mg Zn L(-1) , and 500 mg As L(-1) , being considered the most metal(loid)-tolerant bacteria. These strains belonged to genera Cupriavidus, Burkholderia, Novosphingobium, Sphingobacterium, Castellaniella, Mesorhizobium, Chryseobacterium, and Rhodococcus and were mainly retrieved from Site 1. The multiple metal(loid)-tolerant strains isolated in this study have potential to be used in bioremediation/phytoremediation.

Severity of recurrent hepatitis C virus (HCV) infection in liver transplant recipients (LTR) is variable and the influence of different factors, including the administration of antiviral therapy in the long-term outcome is controversial.We analyzed the outcome of a cohort of HCV-infected LTR who were transplanted in our institution. Patients were divided into 2 groups (severe and non-severe HCV disease) depending on the presence of a fibrosis score of F ≥ 2 in the Scheuer index and/or fibrosing cholestasic hepatitis (FCH) in a graft biopsy. Risk factors were studied using logistic regression analysis. Survival of patients was estimated using Kaplan-Meier plots. A total of 146 patients were followed for a mean of 58 months.Fifty-six (34%) patients developed severe HCV disease and showed shorter survival (P0.024). Donor age (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.02-1.06) and pre-transplant viral load (VL)10(6) UI/mL (OR: 3.5; 95% CI: 1.42-10.61) were the only factors associated with severe HCV infection. Over-immunosuppression (OR: 2.3; 95% CI: 1.2-4.41) was specifically associated with the development of FCH. Overall, patient survival in recipients who received a full course of anti-HCV therapy was higher than in patients who did not complete antiviral therapy (P = 0.004) or received no treatment (P = 0.007). Patients with non-severe HCV infection have a higher probability of receiving a full course of antiviral therapy (P = 0.033).In conclusion, donor age, pre-transplant VL, and over-immunosuppression were associated with the long-term development of severe HCV recurrence in liver grafts. Administration of a full course of antiviral therapy was associated with better survival.

This paper examines the available information on the potential for climate-change impacts on mycotoxigenic fungi and mycotoxin contamination of food crops pre- and postharvest. It considers the effect of changes in temperature/water availability on mycotoxin contamination, especially incidences where aflatoxin B1 and ochratoxin A production has been influenced. The potential of using preharvest models to predict risk from deoxynivalenol (DON) in wheat, fumonisin B1 in maize and aflatoxins in maize and peanuts in different continents are considered in the context of potential for adaptation to include climate-change scenarios. Available information suggests that slightly elevated CO2 concentrations and interactions with temperature and water availability may stimulate growth of some mycotoxigenic species, especially under water stress. The accumulated knowledge on interacting conditions of water/temperature effects on optimum and boundary conditions for growth and mycotoxin production has been used to predict the effects that +3 and +5°C increases under water stress would have on growth/mycotoxin production by mycotoxigenic species. Various spatial scales, from toxin gene expression to regional approaches using geostatistics, are examined for their use in understanding the impact that climate change may have on food contamination in developing and developed countries. The potential for using an integrated systems approach to link gene expression data, phenotypic toxin production under different interacting abiotic conditions is discussed using Fusarium species and DON as examples. Such approaches may be beneficial for more accurate predictions of risk from mycotoxins on a regional basis and also the potential for new emerging toxin threats.

Background Electronic nose (E-nose) technology has been successfully used to diagnose a number of microbial infections. We have investigated the potential use of an E-nose for the diagnosis of ventilator-associated pneumonia (VAP) by detecting micro-organisms in bronchoalveolar lavage (BAL) fluid in a prospective comparative study of E-nose analysis and microbiology. Materials and methods BAL samples were collected using a blind technique from 44 patients following a minimum of 72 h mechanical ventilation. Control samples were collected from six patients mechanically ventilated on the intensive care unit (ICU) immediately following elective surgery. Quantitative microbiological culture and E-nose headspace analysis of the BAL samples were undertaken. Multivariate analysis was applied to correlate E-nose response with microbiological growth. Results E-nose fingerprints correctly classified 77% of the BAL samples, with and without microbiological growth from patients not on antibiotics. Inclusion of patients on antibiotics resulted in 68% correct classification. Seventy per cent of isolates, cultured in the laboratory from the clinical samples, were accurately discriminated into four clinically significant groups.