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Healthy aging is associated with a multitude of structural changes in the brain. These physical age-related changes are accompanied by increased variability in neural activity of all kinds, and this increased variability, collectively referred to as "neural noise," is argued to contribute to age-related cognitive decline. In this study, we examine the relationship between two particular types of neural noise in aging. We recorded scalp EEG from younger (20-30 years old) and older (60-70 years old) adults performing a spatial visual discrimination task. First, we used the 1/f-like exponent of the EEG power spectrum, a putative marker of neural noise, to assess baseline shifts toward a noisier state in aging. Next, we examined age-related decreases in the trial-by-trial consistency of visual stimulus processing. Finally, we examined to what extent these two age-related noise markers are related, hypothesizing that greater baseline noise would increase the variability of stimulus-evoked responses. We found that visual cortical baseline noise was higher in older adults, and the consistency of older adults' oscillatory alpha (8-12 Hz) phase responses to visual targets was also lower than that of younger adults. Crucially, older adults with the highest levels of baseline noise also had the least consistent alpha phase responses, whereas younger adults with more consistent phase responses achieved better behavioral performance. These results establish a link between tonic neural noise and stimulus-associated neural variability in aging. Moreover, they suggest that tonic age-related increases in baseline noise might diminish sensory processing and, as a result, subsequent cognitive performance.

Cyclotides, cysteine‐rich peptides, are derived from various plant sources. Within the Fabaceae family, Clitoria ternatea Linn distinguishes itself as the only species that has been confirmed to contain cyclotides in its tissues. Several investigations have been undertaken to identify and evaluate the activity of cyclotides derived from the plant. However, the investigation of cyclotides derived from mature pods of C. ternatea remains unexplored. To fill this gap, this study utilized three different extraction methods and employed LC–MS analysis to evaluate their effectiveness in extracting cyclotides. A solution comprising 70 % ethanol and 30 % water exhibited the highest efficacy for cyclotide extraction. A total of 14 cyclotide‐like molecules were successfully identified using this approach. Mixtures of cyclotides M1 and M2 demonstrated significant antibacterial efficacy against Bacillus subtilis (inhibition diameters: 17.83–19.67 mm) and Pseudomonas aeruginosa (inhibition diameters: 19.33–20.33 mm). The minimum inhibitory concentration (MIC) of semi‐purified sample E70‐F2 is 1.56 mg/mL, while the MIC of semi‐purified E70‐F3 is 0.78 mg/mL. The MS tandem technique was utilized to sequence a total of seven known cyclotides. The findings of this study demonstrate considerable potential for the application of cyclotides derived from mature pods of C. ternatea as an environmentally friendly antimicrobial agent. [ABSTRACT FROM AUTHOR]

The goal of this study was to (a) determine the minimum selection concentrations of tetracycline family antibiotics necessary to maintain plasmids carrying tetracycline-resistant genes and (b) correlate these results to environmental hotspot concentrations reported in previous studies. This study used two plasmids (pT295A and pT413A) originating from dairy manure in a surrogate Escherichia coli host CV601. The minimum selection concentrations of antibiotics tested in nutrient-rich medium were determined as follows: 0.1 mg/L for oxytetracycline, 0.45 mg/L for chlortetracycline, and 0.13–0.25 mg/L for tetracycline. Mixing oxytetracycline and chlortetracycline had minimum selection concentration values increased 2-fold compared to those in single antibiotic tests. Minimum selection concentrations found in this study were lower than reported environmental hotspot concentrations, suggesting that tetracycline family antibiotics were likely to be the driver for the selection and maintenance of these plasmids. Relatively high plasmid loss rates (>90%) were observed when culturing a strain carrying a tetracycline-resistant plasmid in antibiotic-free nutrient-rich and nutrient-defined media. Overall, results suggested that these plasmids can be maintained at concentrations environmentally relevant in wastewater treatment plants, sewage, manure, and manured soil; however, they are unstable and easily lost in the absence of antibiotics. [ABSTRACT FROM AUTHOR]

Objectives We aimed to assess whether a pharmacist-led intervention enhances knowledge, medication adherence and glycemic control in patients with type 2 diabetes mellitus (T2DM). Methods We conducted a single-blinded randomized controlled trial in Vietnam. Individuals with T2DM were recruited from a general hospital and randomly allocated to intervention and routine care. The intervention group received routine care plus counselling intervention by a pharmacist, including providing drug information and answering individual patients' queries relating to T2DM and medications, which had not been done in routine care. We assessed the outcomes: knowledge score as measured by the Diabetes Knowledge Questionnaire, self-reported adherence and fasting blood glucose (FBG) at the 1-month follow-up. Key findings A total of 165 patients (83 intervention, 82 control) completed the study; their mean age was 63.33 years, and 49.1% were males. The baseline characteristics of the patients were similar between the groups. At 1-month follow-up, the pharmacist's intervention resulted in an improvement in all three outcomes: knowledge score [B = 5.527; 95% confidence intervals (CI): 3.982 to 7.072; P < 0.001], adherence [odds ratio (OR) = 9.813; 95% CI: 2.456 to 39.205; P = 0.001] and attainment of target FBG (OR = 1.979; 95% CI: 1.029 to 3.806; P = 0.041). Conclusions The pharmacist-led intervention enhanced disease knowledge, medication adherence and glycemic control in patients with T2DM. This study provides evidence of the benefits of pharmacist counselling in addition to routine care for T2DM outpatients in a Vietnam population. [ABSTRACT FROM AUTHOR]

The present study investigated the impact of on-farm anaerobic digestion on the abundance of enteric bacteria, antibiotic resistance-associated gene targets, and the horizontal transfer potential of extended-spectrum b-lactamase (ESBL) genes. Samples of raw and digested manure were obtained from six commercial dairy farms in Ontario, Canada. Digestion significantly abated populations of viable coliforms in all six farms. Conjugative transfer of plasmids carrying b-lactamase genes from manure bacteria enriched overnight with buffered peptone containing 4mg/liter cefotaxime into a b-lactam-sensitive green fluorescent protein (GFP)-labeled Escherichia coli recipient strain was evaluated in patch matings. Digestion significantly decreased the frequency of the horizontal transfer of ESBL genes. Twenty-five transconjugants were sequenced, revealing six distinct plasmids, ranging in size from 40 to 180 kb. A variety of ESBL genes were identified: blaCTX-M-1, blaCTX-M-14, blaCTX-M-15, blaCTX-M-27, blaCTX-M-55, and blaPER-1. blaCTX-M-15 was the most prevalent ESBL gene detected on plasmids harbored by transconjugants. Various mobile genetic elements were found located proximal to resistance genes. Ten gene targets, including sul1, str(A), str(B), erm(B), erm(F), intI1, aadA, incW, blaPSE, and blaOXA-20, were quantified by quantitative PCR on a subset of 18 raw and 18 digested samples. Most targets were significantly more abundant in raw manure; however, erm(B) and erm(F) targets were more abundant in digested samples. Overall, on-farm digestion of dairy manure abated coliform bacteria, a number of antibiotic resistance-associated gene targets, and the potential for in vitro conjugation of plasmids conferring resistance to extended-spectrum b-lactams and other classes of antibiotics into E. coli CV601. [ABSTRACT FROM AUTHOR]

This study demonstrates that novel polymer production can be achieved by introducing pTAM, a broad-host-range plasmid expressing codon-optimized genes encoding Clostridium propionicum propionate CoA transferase (PctCp, Pct532) and a modified Pseudomonas sp. MBEL 6–19 polyhydroxyalkanoate (PHA) synthase 1 (PhaC1Ps6-19, PhaC1400), into phaC mutant strains of the native polymer producers Sinorhizobium meliloti and Pseudomonas putida. Both phenotypic analysis and gas chromatography analysis indicated the synthesis and accumulation of biopolymers in S. meliloti and P. putida strains. Expression in S. meliloti resulted in the production of PLA homopolymer up to 3.2% dried cell weight (DCW). The quaterpolymer P (3HB-co-LA-co-3HHx-co-3HO) was produced by expression in P. putida. The P. putida phaC mutant strain produced this type of polymer the most efficiently with polymer content of 42% DCW when cultured in defined media with the addition of sodium octanoate. This is the first report, to our knowledge, of the production of a range of different biopolymers using the same plasmid-based system in different backgrounds. In addition, it is the first time that the novel polymer (P(3HB-co-LA-co-3HHx-co-3HO)), has been reported being produced in bacteria. [ABSTRACT FROM AUTHOR]

Background Vitamin K has multiple important physiological roles, including blood coagulation and beneficial effects on myelin integrity in the brain. Some intestinal microbes possess the genes to produce vitamin K in the form of menaquinone (MK). MK appears in higher concentration in tissues, such as the brain, particularly MK4, than the dietary form of phylloquinone (PK). Lower PK concentrations have been reported in patients with Alzheimer disease while higher serum PK concentrations have been positively associated with verbal episodic memory. Despite knowledge of the importance of vitamin K for various health parameters, few studies have measured MK concentration and biosynthesis by gut commensals. Objective The aim of the current study was to investigate the relation between genes involved in gut-microbiota derived MK, concentrations of MK isoforms, and cognitive function. Methods Shotgun metagenomic sequencing of the gut microbiome of 74 elderly individuals with different cognitive ability levels was performed. From this, gene counts for microbial MK biosynthesis were determined. Associations between clusters of individuals, grouped based on a similar presence and prevalence of MK biosynthesis genes, and cognitive ability were investigated. Fecal MK concentrations were quantified by HPLC to investigate correlations with subject clusters. Results Separation of subject groups defined by banded quantification of the genetic potential of their microbiome to biosynthesize MK was associated with significant differences in cognitive ability [assessed using the Mini-Mental State Examination (MMSE)]. Three MK isoforms were found to be positively associated with MMSE, along with the identification of key components of the MK pathway that drive this association. Although the causality and direction of these associations remain unknown, these findings justify further studies. Conclusions This study provides evidence that although total concentrations of MK did not covary with cognition, certain MK isoforms synthesized by the gut microbiome, particularly the longer chains, are positively associated with cognition. [ABSTRACT FROM AUTHOR]

To improve risk assessment there is increasing attention for the effect of climate change on the sensitivity to contaminants and vice versa. Two important and connected topics have been largely ignored in this context: (i) the increase of daily temperature variation (DTV) as a key component of climate change, and (ii) differences in sensitivity to climate change and contaminants between developmental stages. We therefore investigated whether DTV magnified the negative effects of the organophosphate insecticide chlorpyrifos on mortality and heat tolerance and whether this effect was stronger in aquatic larvae than in terrestrial adults of the mosquito Culex pipiens. Exposure to chlorpyrifos at a constant temperature imposed mortality and reduced the heat tolerance in both larvae and adult males, but not in adult females. This provides the first evidence that the TICS ("toxicant-induced climate change sensitivity") concept can be sex-specific. DTV had no direct negative effects. Yet, consistent with the CITS ("climate-induced toxicant sensitivity") concept, DTV magnified the toxicity of the pesticide in terms of larval mortality. This was not the case in the adult stage indicating the CITS concept to be dependent on the developmental stage. Notably, chlorpyrifos reduced the heat tolerance of adult females only in the presence of DTV, thereby providing support for the reciprocal effects between DTV and contaminants, hence the coupling of the TICS and CITS concepts. Taken together, our results highlight the importance of integrating DTV and the developmental stage to improve risk assessment of contaminants under climate change. Unlabelled Image • Risk assessment ignores daily temperature variation (DTV) and developmental stage. • We studied single and combined effects of DTV and chlorpyrifos (CPF) on mosquitoes. • DTV increased the CPF-induced mortality, but only in the larval stage. • CPF decreased the heat tolerance in larvae and adult males. • Only under DTV, CPF decreased the heat tolerance in adult females. [ABSTRACT FROM AUTHOR]

Apolipoprotein E (APOE) genotype is the strongest prevalent genetic risk factor for Alzheimer's disease (AD). Numerous studies have provided insights into the pathologic mechanisms. However, a comprehensive understanding of the impact of APOE genotype on microflora speciation and metabolism is completely lacking. In this study, we investigated the association between APOE genotype and the gut microbiome composition in human and APOE-targeted replacement (TR) transgenic mice. Fecal microbiota amplicon sequencing from matched individuals with different APOE genotypes revealed no significant differences in overall microbiota diversity in group-aggregated human APOE genotypes. However, several bacterial taxa showed significantly different relative abundance between APOE genotypes. Notably, we detected an association of Prevotellaceae and Ruminococcaceae and several butyrate-producing genera abundances with APOE genotypes. These findings were confirmed by comparing the gut microbiota of APOE-TR mice. Furthermore, metabolomic analysis of murine fecal water detected significant differences in microbe-associated amino acids and short-chain fatty acids between APOE genotypes. Together, these findings indicate that APOE genotype is associated with specific gut microbiome profiles in both humans and APOE-TR mice. This suggests that the gut microbiome is worth further investigation as a potential target to mitigate the deleterious impact of the APOE4 allele on cognitive decline and the prevention of AD.--Tran, T. T. T., Corsini, S., Kellingray, L., Hegarty, C., Le Gall, G., Narbad, A., Müller, M., Tejera, N., O'Toole, P. W., Minihane, A.-M., Vauzour, D. APOE genotype influences the gut microbiome structure and function in humans and mice: relevance for Alzheimer's disease pathophysiology. [ABSTRACT FROM AUTHOR]

Abstract While many studies on the toxicity of pesticides looked at the effects of a higher mean temperature, effects of the realistic scenario of daily temperature variation are understudied. Moreover, despite the increasing interest for the toxicity of pesticide mixtures how this is influenced by temperature has been largely ignored. We tested whether daily temperature variation (DTV) magnifies the toxicity of two pesticides with a different mode of action, the organophosphate pesticide chlorpyrifos (CPF) and the biopesticide Bacillus thuringiensis var. israelensis (Bti), and of their mixture in the vector mosquito Culex pipiens. Single exposure to CPF and Bti increased mortality and reduced female development time, and exposure to CPF also increased female wing length. DTV was not lethal and did not change the toxicity of the individual pesticides. Yet, a key novel finding was that high DTV increased the mortality of the mixture by changing the interaction between both pesticides from additive to synergistic. Given that in nature daily temperature variation is omnipresent, this is important both for vector control and for ecological risk assessment. The higher toxicity of the mixture at high DTV compared to the typically used constant test temperatures in the laboratory urges caution when evaluating the environmental impact of pesticide mixtures. Graphical abstract Unlabelled Image Highlights • The influence of temperature on the toxicity of mixtures has largely been ignored. • Mosquitoes were exposed to two pesticides under daily temperature variation (DTV). • DTV did not increase the toxicity of the single pesticides. • DTV increased the toxicity of the pesticide mixture. • DTV is omnipresent in nature, hence important for risk assessment of mixtures. [ABSTRACT FROM AUTHOR]

Abstract The impact of pesticides on organisms may strongly depend on temperature. While many species will be exposed to pesticides and warming both in the parental and offspring generations, transgenerational effects of pesticides under warming are still poorly studied, particularly for behaviour. We therefore studied the single and combined effects of exposure to the pesticide chlorpyrifos (CPF) and warming both within and across generations on antipredator behaviour of larvae of the vector mosquito Culex pipiens. Within each generation pesticide exposure and warming reduced the escape diving time, making the larvae more susceptible to predation. Pesticide exposure of the parents did not affect offspring antipredator behaviour. Yet, parental exposure to warming determined how warming and the pesticide interacted in the offspring generation. When parents were reared at 24 °C, warming no longer reduced offspring diving times in the solvent control, suggesting an adaptive transgenerational effect to prepare the offspring to better deal with a higher predation risk under warming. Related to this, the CPF-induced reduction in diving time was stronger at 20 °C than at 24 °C, except in the offspring whose parents had been exposed to 24 °C. This dependency of the widespread interaction between warming and pesticide exposure on an adaptive transgenerational effect of warming is an important finding at the interface of global change ecology and ecotoxicology. Graphical abstract Image 1 Highlights • We studied transgenerational effects of pesticide and warming on mosquito behaviour. • Exposure to chlorpyrifos (CPF) and warming reduced antipredator behaviour. • The effect of CPF on antipredator behaviour was smaller under warming. • Parental exposure to warming shaped combined effect of CPF and warming in offspring. An adaptive transgenerational effect of exposure to warming, but not to a pesticide determines how pesticide and warming interact for antipredator behaviour in the offspring. [ABSTRACT FROM AUTHOR]

Abstract: While transgenerational plasticity may buffer ectotherms to warming and pesticides separately, it remains unknown how combined exposure to warming and pesticides in the parental generation shapes the vulnerability to these stressors in the offspring. We studied the transgenerational effects of single and combined exposure to warming (4°C increase) and the pesticide chlorpyrifos on life‐history traits of the vector mosquito Culex pipiens. Parental exposure to a single stressor, either warming or the pesticide, had negative effects on the offspring: parental exposure to both warming and the pesticide resulted in an overall lower offspring survival, and a delayed offspring metamorphosis. Parental exposure to a single stressor did, however, not alter the vulnerability of the offspring to the same stressor in terms of survival. Parental pesticide exposure resulted in larger offspring when the offspring experienced the same stressor as the parents. Within both the parental and offspring generations, warming made the pesticide more toxic in terms of survival. Yet, this synergism disappeared in the offspring of parents exposed to both stressors simultaneously because in this condition, the pesticide was already more lethal at the lower temperature. Our results indicate that transgenerational effects will not increase the ability of this vector species to deal with pesticides in a warming world. Bifactorial transgenerational experiments are crucial to understand the combined impact of warming and pesticides across generations, hence to assess the efficacy of vector control in a warming world. [ABSTRACT FROM AUTHOR]

Thioredoxin reductase (TR) regulates the intracellular redox environment by reducing thioredoxin (Trx). In anaerobes, recent findings indicate that the Trx redox network is implicated in the global redox regulation of metabolism but also actively participates in protecting cells against O2. In the anaerobe Desulfovibrio vulgaris Hildenborough (DvH), there is an intriguing redundancy of the Trx system which includes a classical system using NADPH as electron source, a non-canonical system using NADH and an isolated TR (DvTRi). The functionality of DvTRi was questioned due to its lack of reactivity with DvTrxs. Structural analysis shows that DvTRi is a NAD(P)H-independent TR but its reducer needs still to be identified. Moreover, DvTRi reduced by an artificial electron source is able to reduce in turn DvTrx1 and complexation experiments demonstrate a direct interaction between DvTRi and DvTrx1. The deletion mutant tri exhibits a higher sensitivity to disulfide stress and the gene tri is upregulated by O2 exposure. Having DvTRi in addition to DvTR1 as electron source for reducing DvTrx1 must be an asset to combat oxidative stress. Large-scale phylogenomics analyses show that TRi homologs are confined within the anaerobes. All TRi proteins displayed a conserved TQ/NGK motif instead of the HRRD motif, which is selective for the binding of the 20-phosphate group of NADPH. The evolutionary history of TRs indicates that tr1 is the common gene ancestor in prokaryotes, affected by both gene duplications and horizontal gene events, therefore leading to the appearance of TRi through subfunctionalization over the evolutionary time. [ABSTRACT FROM AUTHOR]

Alpha oscillations (7–14 Hz) are modulated in response to visual temporal and spatial cues. However, the neural response to alerting cues is less explored, as is how this response is affected by healthy aging. Using scalp EEG, we examined how visual cortical alpha activity relates to working memory performance. Younger (20–30 years) and older (60–70 years) participants were presented with a visual alerting cue uninformative of the position or size of a lateralized working memory array. Older adults showed longer response times overall and reduced accuracy when memory load was high. Older adults had less consistent cue-evoked alpha phase resetting than younger adults, which predicted worse performance. Alpha phase prior to memory array presentation predicted response time, but the relationship between phase and response time was weaker in older adults. These results suggest that changes in alpha phase dynamics, especially prior to presentation of task-relevant stimuli, potentially contribute to age-related cognitive decline. [ABSTRACT FROM AUTHOR]

How evolution may mitigate the effects of global warming and pesticide exposure on predator-prey interactions is directly relevant for vector control. Using a space-for-time substitution approach, we addressed how 4°C warming and exposure to the pesticide endosulfan shape the predation on Culex pipiens mosquitoes by damselfly predators from replicated low- and high-latitude populations. Although warming was only lethal for the mosquitoes, it reduced predation rates on these prey. Possibly, under warming escape speeds of the mosquitoes increased more than the attack efficiency of the predators. Endosulfan imposed mortality and induced behavioral changes (including increased filtering and thrashing and a positional shift away from the bottom) in mosquito larvae. Although the pesticide was only lethal for the mosquitoes, it reduced predation rates by the low-latitude predators. This can be explained by the combination of the evolution of a faster life history and associated higher vulnerabilities to the pesticide (in terms of growth rate and lowered foraging activity) in the low-latitude predators and pesticide-induced survival selection in the mosquitoes. Our results suggest that predation rates on mosquitoes at the high latitude will be reduced under warming unless predators evolve toward the current low-latitude phenotype or low-latitude predators move poleward. [ABSTRACT FROM AUTHOR]

Economically competitive commercial production of biodegradable bioplastics with desirable properties is an important goal. In this study, we demonstrate the use of chromosome engineering of an alternative bacterial host, Sinorhizobium meliloti, for production of the copolymer, poly(lactate- co-3-hydroxybutyrate). Codon-optimized genes for 2 previously engineered enzymes, Clostridium propionicum propionate CoA transferase (Pct532Cp) and Pseudomonas sp. strain MBEL 6-19 polyhydroxyalkanoate (PHA) synthase 1 (PhaC1400Ps6-19), were introduced into S. meliloti Rm1021 by chromosome integration, replacing the native phbC gene. On the basis of phenotypic analysis and detection of polymer product by gas chromatography analysis, synthesis and accumulation of the copolymer was confirmed. The chromosome integrant strain, with the introduced genes under the control of the native phbC promoter, is able to produce over 15% cell dry mass of poly(lactate- co-3-hydroxybutyrate), containing 30 mol% lactate, from growth on mannitol. We were also able to purify the polymer from the culture and confirm the structure by NMR and GC-MS. To our knowledge, this is the first demonstration of production of this copolymer in the Alphaproteobacteria. Further optimization of this system may eventually yield strains that are able to produce economically viable commercial product. [ABSTRACT FROM AUTHOR]

Considering the importance of tRNAs in the translation machinery, scant attention has been paid to tRNA array units defined as genomic regions containing at least 20 tRNA genes with a minimal tRNA gene density of two tRNA genes per kilobase. Our analysis of Acidithiobacillus ferrivorans CF27 and Acidithiobacillus ferrooxidans ATCC 23270T genomes showed that both display a tRNA array unit with syntenic conservation which mainly contributed to the tRNA gene redundancy in these two organisms. Our investigations into the occurrence and distribution of tRNA array units revealed that 1) this tRNA organization is limited to few phyla and mainly found in Gram-positive bacteria; and 2) the presence of tRNA arrays favors the redundancy of tRNA genes, in particular those encoding the core tRNA isoacceptors. Finally, comparative array organization revealed that tRNA arrays were acquired through horizontal gene transfer (from Firmicutes or unknown donor), before being subjected to tRNA rearrangements, deletions, and duplications. In Bacilli, the most parsimonious evolutionary history involved two common ancestors and the acquisition of their arrays arose late in evolution, in the genera branches. Functional roles of the array units in organism lifestyle, selective genetic advantage and translation efficiency, as well as the evolutionary advantages of organisms harboring them were proposed. Our study offers new insight into the structural organization and evolution of tRNA arrays in prokaryotic organisms. [ABSTRACT FROM AUTHOR]

Promoter engineering has been employed as a strategy to enhance and optimize the production of bio-products. Availability of promoters with predictable activities is needed for downstream application. However, whether promoter activity remains the same in different gene contexts remains unknown. Six consecutive promoters that have previously been determined to have different activity levels were used to construct six different versions of plasmid backbone pTH1227, followed by inserted genes encoding two polymer-producing enzymes. In some cases, promoter activity in the presence of inserted genes did not correspond to the reported activity levels in a previous study. After removing the inserted genes, the activity of these promoters returned to their previously reported level. These changes were further confirmed to occur at the transcriptional level. Polymer production using our newly constructed plasmids showed polymer accumulation levels corresponding to the promoter activity reported in our study. Our study demonstrated the importance of re-assessing promoter activity levels with regard to gene context, which could influence promoter activity, leading to different outcomes in downstream applications. • Six promoters with different previously reported activity levels were used to express genes encoding two polymerase enzymes • Some promoter activity did not correspond to the reported levels when downstream sequences were inserted • Removing inserted sequences returned promoter activity to reported levels • The change of promoter activity occurred at the level of transcription [ABSTRACT FROM AUTHOR]

Despite the increased attention for temporal aspects of stressor interactions and for effects of warming in ecotoxicological studies, we lack knowledge on how different exposure durations to warming may affect pesticide sensitivity. We tested how three types of exposure duration to 4 °C warming (acute, developmental and transgenerational exposure to 24 °C vs 20 °C) shape the effect of the pesticide chlorpyrifos on two ecologically relevant fitness-related traits of mosquito larvae: heat tolerance and antipredator behaviour. Transgenerational (from the parental generation) and developmental (from the egg stage) warming appeared energetically more stressful than acute warming (from the final instar), because (i) only the latter resulted in an adaptive increase of heat tolerance, and (ii) especially developmental and transgenerational warming reduced the diving responsiveness and diving time. Exposure to chlorpyrifos decreased the heat tolerance, diving responsiveness and diving time. The impact of chlorpyrifos was lower at 24 °C than at 20 °C indicating that the expected increase in toxicity at 24 °C was overruled by the observed increase in pesticide degradation. Notably, although our results suggest that transgenerational warming was energetically more stressful, it did reduce the chlorpyrifos-induced negative effects at 24 °C on heat tolerance and the alarm escape response compared to acute warming. Our results provide important evidence that the exposure duration to warming may determine the impact of a pesticide under warming, thereby identifying a novel temporal aspect of stressor interactions in risk assessment. [Display omitted] • Chlorpyrifos decreased the heat tolerance, diving responsiveness and diving time. • The impact of chlorpyrifos was lower at 24 °C than at 20 °C because more degradation. • Transgenerational warming was energetically more stressful than acute warming. • Transgenerational warming reduced the pesticide impact compared to acute warming. • Our results highlight the importance of temporal aspects of stressor interactions. Under transgenerational exposure to warming the negative impact of chlorpyrifos was smaller than under acute warming. [ABSTRACT FROM AUTHOR]

Blueberry (BB) consumption is linked to improved health. The bioconversion of the polyphenolic content of BB by fermentative bacteria in the large intestine may be a necessary step for the health benefits attributed to BB consumption. The identification of specific gut microbiota taxa that respond to BB consumption and that mediate the bioconversion of consumed polyphenolic compounds into bioactive forms is required to improve our understanding of how polyphenols impact human health. We tested the ability of polyphenol-rich fractions purified from whole BB—namely, anthocyanins/flavonol glycosides (ANTH/FLAV), proanthocyanidins (PACs), the sugar/acid fraction (S/A), and total polyphenols (TPP)—to modulate the fecal microbiota composition of healthy adults in an in vitro colon system. In a parallel pilot study, we tested the effect of consuming 38 g of freeze-dried BB powder per day for 6 weeks on the fecal microbiota of 17 women in two age groups (i.e., young and older). The BB ingredients had a distinct effect on the fecal microbiota composition in the artificial colon model. The ANTH/FLAV and PAC fractions were more effective in promoting microbiome alpha diversity compared to S/A and TPP, and these effects were attributed to differentially responsive taxa. Dietary enrichment with BB resulted in a moderate increase in the diversity of the microbiota of the older subjects but not in younger subjects, and certain health-relevant taxa were significantly associated with BB consumption. Alterations in the abundance of some gut bacteria correlated not only with BB consumption but also with increased antioxidant activity in blood. Collectively, these pilot data support the notion that BB consumption is associated with gut microbiota changes and health benefits. [ABSTRACT FROM AUTHOR]

• We studied the interplay between warming and chlorpyrifos (CPF) in different stages. • Warming increased or reduced the effect of CPF depending on the developmental stage. • Mortality during and after exposure showed similar stage-specific interactions. • Delayed effects of larval exposure to CPF strongly reduced survival to emergence. A better understanding of interactions between pesticides and warming is important to improve ecological risk assessment in a warming world. Current insights are almost exclusively based on studies that exposed animals simultaneously to both warming and a pesticide and focused on effects during the pesticide exposure period and within a single developmental stage. We studied two ignored aspects of the interplay between warming and pesticide exposure: (i) the role of delayed effects after the pesticide exposure period, and (ii) the dependence on the developmental stage. We carried out a longitudinal experiment from the egg stage to the adult stage in the mosquito Culex pipiens where we crossed a warming treatment (20 °C vs 24 °C) with 48 h exposures to the pesticide chlorpyrifos in three developmental stages (early L1 larvae, late L4 larvae and adults). Chlorpyrifos induced mild to moderate mortality in all developmental stages (10–30%). A key finding was that warming shaped the chlorpyrifos-induced mortality but in opposite directions between stages. Chlorpyrifos was 7% less toxic under warming in L1 larvae, yet more toxic under warming in L4 larvae (22%) and in adult males (33%), while toxicity did not change under warming in adult females. We hypothesize that the general, stage-specific differences in the effects of warming on body size (increased size in early larvae, decreased size in later stages) caused the reversal of the effects of warming on toxicity between stages. Previous larval exposure to chlorpyrifos caused delayed effects that strongly reduced survival to the adult stage (̰25% at 24 °C). Notably, warming also modulated these delayed mortality effects in opposite ways between developmental stages, matching the patterns of mortality during the pesticide exposure periods. Integrating the general stage-specific patterns of how warming shapes body size is important to advance our mechanistic understanding of the interactions between pesticides and warming. [ABSTRACT FROM AUTHOR]

• Pesticide control needs to consider both target and non-target species. • Control can reduce resistance by more impacting resistant strains of target species. • A cost of chlorpyrifos resistance was only visible when exposed to the pesticide Bti. • Bti exposure caused more direct mortality and predation in the resistant strain. • Chlorpyrifos and Bti interacted antagonistically in the mixture. Pesticide mixtures are increasingly used to fight pest species that developed resistance to pesticides. To assess the pesticide control efficiency and to reduce ecological damage to non-target species, it is important to quantify the effect of these mixtures and compare them with the effect of their single pesticides on pest species, non-target species and their predator-prey interactions. We studied the effects of the chemical pesticide chlorpyrifos (CPF), the biopesticide Bacillus thuringiensis israelensis (Bti) and their mixture both on the direct mortality and on the mortality by predation. We focused on larvae of a CPF-resistant and a non-resistant strain of the vector mosquito Culex quinquefasciatus and its predator, the pygmy backswimmer Plea minutissima. In the CPF-Bti mixture, both pesticides interacted antagonistically for direct mortality. Exposure to the mixture caused equal direct mortality and equal mortality by predation in both strains. As expected, exposure to CPF resulted in less direct mortality and less mortality by predation in the CPF-resistant mosquito strain compared to the non-resistant strain. Notably, Bti caused a higher mortality in the mosquito larvae of the CPF-resistant strain compared to the non-resistant strain. Furthermore, the predator killed more mosquito larvae of the resistant strain compared to the non-resistant strain when exposed before to Bti alone. These observations identify a novel cost of resistance to a chemical pesticide in terms of increased vulnerability to a biopesticide. [ABSTRACT FROM AUTHOR]

While poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] is a biodegradable commodity plastic with broad applications, its microbial synthesis is hindered by high production costs primarily associated with the supplementation of related carbon substrates (e.g. propionate or valerate). Here we report construction of engineered Escherichia coli strains for direct synthesis of P(3HB-co-3HV) from an unrelated carbon source (e.g. glucose or glycerol). First, an E. coli strain with an activated sleeping beauty mutase (Sbm) operon was used to generate propionyl-CoA as a precursor. Next, two acetyl-CoA moieties or acetyl-CoA and propionyl-CoA were condensed to form acetoacetyl-CoA and 3-ketovaleryl-CoA, respectively, by functional expression of β-ketothiolases from Cupriavidus necator (i.e. PhaA and BktB). The resulting thioester intermediates were channeled into the polyhydroxyalkanoate (PHA) biosynthetic pathway through functional expression of acetoacetyl-CoA reductase (PhaB) for thioester reduction and PHA synthase (PhaC) for subsequent polymerization. Metabolic engineering of E. coli host strains was further conducted to enhance total PHA content and the 3-hydroxyvaleryl (3HV) monomer fraction in the copolymer. Using a selection of engineered E. coli strains for batch cultivation with an unrelated carbon source, we achieved high-level P(3HB-co-3HV) production with the 3HV monomer fraction ranging from 3 to 19 mol%, demonstrating the potential industrial applicability of these whole-cell biocatalysts. [ABSTRACT FROM AUTHOR]

Cyclotides, plant-derived cysteine-rich peptides, exhibit a wide range of beneficial biological activities and possess exceptional structural stability. Cyclotides are commonly distributed throughout the Violaceae family. Viola dalatensis Gagnep, a Vietnamese species, has not been well studied, especially for cyclotides. This pioneering research explores cyclotides from V. dalatensis as antimicrobials. This study used a novel approach to enhance cyclotides after extraction. The approach combined 30% ammonium sulfate salt precipitation and RP-HPLC. A comprehensive analysis was performed to ascertain the overall protein content, flavonoids content, polyphenol content, and free radical scavenging capacity of compounds derived from V. dalatensis. Six known cyclotides were sequenced utilizing MS tandem. Semi-purified cyclotide mixtures (M1, M2, and M3) exhibited antibacterial efficacy against Bacillus subtilis (inhibitory diameters: 19.67-23.50 mm), Pseudomonas aeruginosa (22.17-23.50 mm), and Aspergillus flavus (14.67-21.33 mm). The enriched cyclotide precipitate from the stem extract demonstrated a minimum inhibitory concentration (MIC) of 0.08 mg/mL against P. aeruginosa, showcasing significant antibacterial effectiveness compared to the stem extract (MIC: 12.50 mg/mL). Considerable advancements have been achieved in the realm of cyclotides, specifically in their application as antimicrobial agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aim : Dietary fibre is important for shaping gut microbiota. The aim of this pilot study was to investigate the impact of dietary fibres on pathogen performance in the presence of gut microbiota. Methods : In an ex vivo gut model, pooled faecal samples were spiked with a cocktail of representative gastrointestinal pathogens and fermented with yeast β-glucan for 24 hours, after which 16S rRNA amplicon sequencing and short-chain and branched-chain fatty acid (SCFA and BCFA) analyses were performed. In addition, oat β-glucan, arabinoxylan, yeast β-glucan, and galactooligosaccharides were each tested against individual representative pathogens and pathogen growth was assessed via qPCR. Glucose served as a control carbon source. Results : Based on 16S rRNA amplicon sequencing, yeast β-glucan selected for higher proportions of Bacteroides ( P = 0.0005, ~6 fold) and Clostridia ( P = 0.005, ~3.6 fold) while species of Escherichia/Shigella ( P = 0.021, ~2.8 fold) and Lactobacillus ( P = 0.007, ~ 15.7-fold) were higher in glucose. Pathogen relative abundance did not differ between glucose and yeast β-glucan. In the absence of pathogens, higher production of BCFAs ( P = 0.002) and SCFAs ( P = 0.002) fatty acids was observed for fibre group(s). For individual pathogens, yeast β-glucan increased growth of Escherichia coli , Salmonella typhimurium , and Listeria monocytogenes ( P < 0.05), arabinoxylan increased S. typhimurium ( P < 0.05). Tested fibres decreased vancomycin-resistant Enterococcus faecium ( P < 0.05), with yeast β-glucan causing a 1-log reduction ( P < 0.01), while galactooligosaccharides decreased L . monocytogenes ( P < 0.05). Conclusion : Tested fibres differentially influenced the growth of pathogens, but yeast β-glucan could represent a dietary strategy to help limit vancomycin-resistant enterococci (VRE) expansion in the gut., Competing Interests: None., (© The Author(s) 2023.)

Objectives: We aimed to assess whether a pharmacist-led intervention enhances knowledge, medication adherence and glycemic control in patients with type 2 diabetes mellitus (T2DM)., Methods: We conducted a single-blinded randomized controlled trial in Vietnam. Individuals with T2DM were recruited from a general hospital and randomly allocated to intervention and routine care. The intervention group received routine care plus counselling intervention by a pharmacist, including providing drug information and answering individual patients' queries relating to T2DM and medications, which had not been done in routine care. We assessed the outcomes: knowledge score as measured by the Diabetes Knowledge Questionnaire, self-reported adherence and fasting blood glucose (FBG) at the 1-month follow-up., Key Findings: A total of 165 patients (83 intervention, 82 control) completed the study; their mean age was 63.33 years, and 49.1% were males. The baseline characteristics of the patients were similar between the groups. At 1-month follow-up, the pharmacist's intervention resulted in an improvement in all three outcomes: knowledge score [B = 5.527; 95% confidence intervals (CI): 3.982 to 7.072; P < 0.001], adherence [odds ratio (OR) = 9.813; 95% CI: 2.456 to 39.205; P = 0.001] and attainment of target FBG (OR = 1.979; 95% CI: 1.029 to 3.806; P = 0.041)., Conclusions: The pharmacist-led intervention enhanced disease knowledge, medication adherence and glycemic control in patients with T2DM. This study provides evidence of the benefits of pharmacist counselling in addition to routine care for T2DM outpatients in a Vietnam population., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Mutations in DNA mismatch repair (MMR) genes are causative in Lynch syndrome and a significant proportion of sporadic colorectal cancers (CRCs). MMR-deficient (dMMR) CRCs display increased mutation rates, with mutations frequently accumulating at short repetitive DNA sequences throughout the genome (microsatellite instability). The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs. Therefore, we generated an animal model to study how the loss of both TGFBR2 signaling impacts dMMR-driven intestinal tumorigenesis in vivo and explore the impact of the gut microbiota., Methods: We generated VCMsh2/Tgfbr2 mice in which Msh2 loxP and Tgfbr2 loxP alleles are inactivated by Villin-Cre recombinase in the intestinal epithelium. VCMsh2/Tgfbr2 mice were analyzed for their rate of intestinal cancer development and for the mutational spectra and gene expression profiles of tumors. In addition, we assessed the impact of chemically induced chronic inflammation and gut microbiota composition on colorectal tumorigenesis., Results: VCMsh2/Tgfbr2 mice developed small intestinal adenocarcinomas and CRCs with histopathological features highly similar to CRCs in Lynch syndrome patients. The CRCs in VCMsh2/Tgfbr2 mice were associated with the presence of colitis and displayed genetic and histological features that resembled inflammation-associated CRCs in human patients. The development of CRCs in VCMsh2/Tgfbr2 mice was strongly modulated by the gut microbiota composition, which in turn was impacted by the TGFBR2 status of the tumors., Conclusions: Our results demonstrate a synergistic interaction between MMR and TGFBR2 inactivation in inflammation-associated colon tumorigenesis and highlight the crucial impact of the gut microbiota on modulating the incidence of inflammation-associated CRCs., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The iron-oxidizing species Acidithiobacillus ferrivorans is one of few acidophiles able to oxidize ferrous iron and reduced inorganic sulfur compounds at low temperatures (<10°C). To complete the genome of At. ferrivorans strain CF27, new sequences were generated, and an update assembly and functional annotation were undertaken, followed by a comparative analysis with other Acidithiobacillus species whose genomes are publically available. The At. ferrivorans CF27 genome comprises a 3,409,655 bp chromosome and a 46,453 bp plasmid. At. ferrivorans CF27 possesses genes allowing its adaptation to cold, metal(loid)-rich environments, as well as others that enable it to sense environmental changes, allowing At. ferrivorans CF27 to escape hostile conditions and to move toward favorable locations. Interestingly, the genome of At. ferrivorans CF27 exhibits a large number of genomic islands (mostly containing genes of unknown function), suggesting that a large number of genes has been acquired by horizontal gene transfer over time. Furthermore, several genes specific to At. ferrivorans CF27 have been identified that could be responsible for the phenotypic differences of this strain compared to other Acidithiobacillus species. Most genes located inside At. ferrivorans CF27-specific gene clusters which have been analyzed were expressed by both ferrous iron-grown and sulfur-attached cells, indicating that they are not pseudogenes and may play a role in both situations. Analysis of the taxonomic composition of genomes of the Acidithiobacillia infers that they are chimeric in nature, supporting the premise that they belong to a particular taxonomic class, distinct to other proteobacterial subgroups.

Considering the importance of tRNAs in the translation machinery, scant attention has been paid to tRNA array units defined as genomic regions containing at least 20 tRNA genes with a minimal tRNA gene density of two tRNA genes per kilobase. Our analysis of Acidithiobacillus ferrivorans CF27 and Acidithiobacillus ferrooxidans ATCC 23270(T) genomes showed that both display a tRNA array unit with syntenic conservation which mainly contributed to the tRNA gene redundancy in these two organisms. Our investigations into the occurrence and distribution of tRNA array units revealed that 1) this tRNA organization is limited to few phyla and mainly found in Gram-positive bacteria; and 2) the presence of tRNA arrays favors the redundancy of tRNA genes, in particular those encoding the core tRNA isoacceptors. Finally, comparative array organization revealed that tRNA arrays were acquired through horizontal gene transfer (from Firmicutes or unknown donor), before being subjected to tRNA rearrangements, deletions, and duplications. In Bacilli, the most parsimonious evolutionary history involved two common ancestors and the acquisition of their arrays arose late in evolution, in the genera branches. Functional roles of the array units in organism lifestyle, selective genetic advantage and translation efficiency, as well as the evolutionary advantages of organisms harboring them were proposed. Our study offers new insight into the structural organization and evolution of tRNA arrays in prokaryotic organisms., (© The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)