Arginine methylation is a common post-translational modification functioning as an epigenetic regulator of transcription and playing key roles in pre-mRNA splicing, DNA damage signaling, mRNA ...translation, cell signaling, and cell fate decision. Recently, a wealth of studies using transgenic mouse models and selective PRMT inhibitors helped define physiological roles for protein arginine methyltransferases (PRMTs) linking them to diseases such as cancer and metabolic, neurodegenerative, and muscular disorders. This review describes the recent molecular advances that have been uncovered in normal and diseased mammalian cells.
Arginine methylation is a common modification regulating epigenetics and playing key roles in pre-mRNA splicing, translation, DNA damage, cell signaling, and cell fate decision. Blanc and Richard highlight studies that use transgenic mouse models and selective PRMT inhibitors to define physiological roles for protein arginine methyltransferases, linking them to diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
The functional role of Pax7-expressing satellite cells (SCs) in postnatal skeletal muscle development beyond weaning remains obscure. Therefore, the relevance of SCs during prepubertal growth, a ...period after weaning but prior to the onset of puberty, has not been examined. Here, we have characterized mouse skeletal muscle growth during prepuberty and found significant increases in myofiber cross-sectional area that correlated with SC-derived myonuclear number. Remarkably, genome-wide RNA-sequencing analysis established that post-weaning juvenile and early adolescent skeletal muscle have markedly different gene expression signatures. These distinctions are consistent with extensive skeletal muscle maturation during this essential, albeit brief, developmental phase. Indelible labeling of SCs with
;
mice demonstrated SC-derived myonuclear contribution during prepuberty, with a substantial reduction at puberty onset. Prepubertal depletion of SCs in
;
mice reduced myofiber size and myonuclear number, and caused force generation deficits to a similar extent in both fast and slow-contracting muscles. Collectively, these data demonstrate SC-derived myonuclear accretion as a cellular mechanism that contributes to prepubertal hypertrophic skeletal muscle growth.
Abstract
Muscle regeneration depends on a robust albeit transient inflammatory response. Persistent inflammation is a feature of age-related regenerative deficits, yet the underlying mechanisms are ...poorly understood. Here, we find inflammatory-related CC-chemokine-receptor 2 (Ccr2) expression in non-hematopoietic myogenic progenitors (MPs) during regeneration. After injury, the expression of Ccr2 in MPs corresponds to the levels of its ligands, the chemokines Ccl2, 7, and 8. We find stimulation of Ccr2-activity inhibits MP fusion and contribution to myofibers. This occurs in association with increases in MAPKp38δ/γ signaling, MyoD phosphorylation, and repression of the terminal myogenic commitment factor Myogenin. High levels of Ccr2-chemokines are a feature of regenerating aged muscle. Correspondingly, deletion of
Ccr2
in MPs is necessary for proper fusion into regenerating aged muscle. Finally, opportune Ccr2 inhibition after injury enhances aged regeneration and functional recovery. These results demonstrate that inflammatory-induced activation of Ccr2 signaling in myogenic cells contributes to aged muscle regenerative decline.
Bacterial sexually transmitted infections (STIs) pose a major public health problem. The emergence of antibiotic-resistant strains of Neisseria gonorrhoeae represents a serious threat to successful ...treatment and epidemiological control. The first extensively drug-resistant (XDR) strains (ceftriaxone-resistant and high-level azithromycin-resistant HLR AZY) have been reported. To identify molecular mechanisms implicated in azithromycin resistance in strains isolated from patients over a three-year period in a university hospital in Switzerland. From January 2020 to December 2022, 34 isolates (one per patient) were recovered from samples analyzed at the University Hospital of Lausanne. Eight genes involved in azithromycin resistance were sequenced: mtrR repressor (mtrCDE operon repressor) and his promotor mtrR-pr, rplD gene (L4 ribosomal protein), rplV gene (L22 ribosomal protein) and the four alleles of the rrl gene (23S rRNA). With a cutoff value of 1 mg/L, 15 isolates were considered as being resistant to azithromycin, whereas the remaining 19 were susceptible. The C2597T mutation in 3 or 4 of the rrl allele confer a medium-level resistance to azithromycin (MIC = 16 mg/L, N = 2). The following mutations were significantly associated with MIC values greater than or equal to1 mg/L: the three mutations V125A, A147G, R157Q in the rplD gene (N = 10) and a substitution A->C in the mtrR promotor (N = 9). Specific mutations in the mtrR repressor and its promotor were observed in both susceptible and resistant isolates. Resistance to azithromycin was explained by the presence of mutations in many different copies of 23S RNA ribosomal genes and their regulatory genes. Other mutations, previously reported to be associated with azithromycin resistance, were documented in both susceptible and resistant isolates, suggesting they play little role, if any, in azithromycin resistance.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Whole genome sequencing (WGS) is increasingly used for epidemiological investigations of pathogens. While SNP variant calling is currently considered as the most suitable method, the choice of a ...representative reference genome and the isolate dependency of results limit standardization and affect resolution in an unknown manner. Whole or core genome Multi Locus Sequence Typing (wg-, cg-MLST) represents an attractive alternative. Here, we assess the accuracy of wg- and cg-MLST by comparing results of four
Pseudomonas aeruginosa
datasets for which epidemiological and genomic data were previously described. Three datasets included 155 isolates from three different sequence types (ST) of
P. aeruginosa
collected in our ICUs over a 5-year period. The fourth dataset consisted of 10 isolates from an investigation of
P. aeruginosa
contaminated hand soap. All isolates were previously analyzed by a core SNP approach. In this study, wg- and cg-MLST were performed in BioNumerics
TM
using a scheme developed by Applied-Maths. Correlation between SNP calling and wg- or cg-MLST results were evaluated by calculating linear regressions and their coefficient of correlations (
R
2
) between the number of SNPs and the number of allele differences in pairwise comparison of isolates. The number of SNPs and allele difference between isolates with close epidemiological linkage varies between 0–26 and 0–13, respectively. When compared to core-SNP calling, a higher coefficient of correlation was obtained with cgMLST (
R
2
of 0.92–0.99) than with wgMLST (0.78–0.99). In one dataset, a putative homologous recombination of a large DNA fragment (202 loci) was identified among these isolates, affecting its phylogeny, but with no impact on the epidemiological analysis of outbreak isolates. In conclusion, we showed that the
P. aeruginosa
wgMLST scheme in BioNumerics
TM
is as discriminatory as the core-SNP calling approach and apparently useful for outbreak investigations. We also showed that epidemiological linked isolates showed less than 26 SNPs or 13 allele differences. These are important figures for the distinction between outbreak and non-outbreak isolates when interpreting WGS results. However, as
P. aeruginosa
is highly recombinant, a cgMLST approach is preferable and caution should be addressed to possible recombination of large DNA fragments.
Long-term outbreaks of multidrug-resistant Gram-negative bacilli related to hospital-building water systems have been described. However, successful mitigation strategies have rarely been reported. ...In particular, environmental disinfection or replacement of contaminated equipment usually failed to eradicate environmental sources of Pseudomonas aeruginosa.
We report the investigation and termination of an outbreak of P. aeruginosa producing VIM carbapenemase (PA-VIM) in the adult intensive care unit (ICU) of a Swiss tertiary care hospital with active case finding, environmental sampling and whole genome sequencing (WGS) of patient and environmental strains. We also describe the implemented control strategies and their effectiveness on eradication of the environmental reservoir.
Between April 2018 and September 2020, 21 patients became either infected or colonized with a PA-VIM strain. For 16 of them, an acquisition in the ICU was suspected. Among 131 environmental samples collected in the ICU, 13 grew PA-VIM in sink traps and drains. WGS confirmed the epidemiological link between clinical and environmental strains and the monoclonal pattern of the outbreak. After removing sinks from patient rooms and implementation of waterless patient care, no new acquisition was detected in the ICU within 8 months after the intervention.
Implementation of waterless patient care with removal of the sinks in patient rooms was successful for termination of a PA-VIM ICU outbreak linked to multiple environmental water sources. WGS provides highly discriminatory accuracy to investigate environment-related outbreaks.
The modern consumer is now more attentive towards animal welfare practices and this represents an important factor when purchasing meat, whereby ethical, sociological and economic implications are ...evaluated. In addition, the socio-demographic characteristics of consumers evidence different sensitivities with regard to selection patterns and consumption styles. This study aims to explore the role of Gender in beef meat purchasing preferences, assessing consumer awareness of responsibility towards animal welfare, through the use of cross-tabulation with χ
2
to test the different behaviour of men and women and the use of principal component analysis and cluster analysis to classify attitudes of choice according to gender. Among the research aims, this study examined consumer attitudes towards certain 'ethically incorrect' animal products, as well as their awareness of the institutional responsibility in controlling animal welfare standards during the meat production process. The study conducted in Northwest Italy, involving 512 respondents, shows that women are more sensitive to AW aspects and place trust in those responsible for certification of animal welfare standards, such as veterinarians and consumer associations, and also shows that it is possible to identify an 'animal welfare sensitive' profile of meat consumer.
HIGHLIGHTS
Modern consumer evaluates ethical, sociological and economic implications in animal friendly meat purchasing process
Gender affects awareness of the responsibilities of veterinary, public health control bodies and consumer associations to verify animal welfare
Cluster highlighted consumer differences in perception towards animal welfare
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Screening specimens were homogenised in saline 0.9% w/v before either direct inoculation or following enrichment in broth on three chromogenic media (MRSA-ID, CHROMagar MRSA and MRSA Select) and ...ORSAB medium for the detection of methicillin-resistant Staphylococcus aureus (MRSA). In total, 102 of 466 specimens yielded MRSA on at least one medium. After incubation for 16–18 h, the sensitivity was 51%, 59%, 47% and 65% on MRSA-ID, CHROMagar MRSA, ORSAB and MRSA Select, respectively, compared with 82%, 75%, 67% and 80%, respectively, after 42 h, and 93%, 95%, 79% and not tested, respectively, following broth enrichment. There were significantly more MRSA colonies on MRSA-Select after 16–18 h than on ORSAB or MRSA ID (p 0.001 and 0.0022, respectively), whereas there were more MRSA colonies after 42 h on MRSA-ID and MRSA-Select than on ORSAB (p 0.0004 and 0.012, respectively). The specificity of the media for identifying MRSA based on the colour of colonies after incubation for 16–18 h was 100%, 99%, 99% and 100%, respectively, compared with 98%, 97%, 98% and 98%, respectively, after 42 h, and 100%, 99%, 100% and not tested, respectively, following broth enrichment. The speed of detection (mean time to report a positive result) was 1.65, 1.72, 2.31 and 1.35 days, respectively. For each of the three media tested following enrichment, the use of an enrichment broth increased the detection rate of MRSA by 16–24%.
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BFBNIB, DOBA, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UKNU, UL, UM, UPUK, ZAGLJ, ZRSKP
Population-based studies directed at promoting physical activity in youth have shown limited success in obesity prevention.
To assess whether an intervention integrating environmental changes to ...induce sustained changes in physical activity, prevents overweight in adolescents.
Four-year randomized trial started in 2002 in eight middle schools of Eastern France. The intervention, randomized at school level, was designed to promote physical activity by changing attitudes through debates and attractive activities, and by providing social support and environmental changes encouraging physical activity.
Nine hundred and fifty four 12-year-old six-graders.
Body mass index (BMI), body composition, physical activity by questionnaire, plasma lipids and glucose, insulin resistance.
Intervention students had a lower increase in BMI (P=0.01) and age- and gender-adjusted BMI (P<0.02) over time than controls. The differences across groups of the age- and gender-adjusted BMI changes (95% confidence interval (CI)) were -0.29 (-0.51; -0.07) kg/m2 at 3 years, -0.25 (-0.51; 0.01) kg/m2 at 4 years. An interaction with baseline weight status was noted. The intervention had a significant effect throughout the study in initially non-overweight adolescents (-0.36 (-0.60;-0.11) kg/m2 for adjusted BMI at 4 years), corresponding to a lower increase in fat mass index (P<0.001). In initially overweight adolescents, the differences observed across groups at 2 years (-0.40 (-0.94; 0.13) kg/m2 for adjusted BMI) did not persist over time. At 4 years, 4.2% of the initially non-overweight adolescents were overweight in the intervention schools, 9.8% in the controls (odds ratio=0.41 (0.22; 0.75); P<0.01). Independent of initial weight status, compared with controls, intervention adolescents had an increase in supervised physical activity (P<0.0001), a decrease of TV/video viewing (P<0.01) and an increase of high-density cholesterol concentrations (P<0.0001).
Enhancing physical activity with a multilevel program prevents excessive weight gain in non-overweight adolescents. Our study provides evidence that prevention of obesity in youth is feasible.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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