Ethnic endotypes in paediatric atopic dermatitis depend on immunotype, lipid composition and microbiota of the skin.

BACKGROUND: Atopic dermatitis (AD) endotypes differ with ethnicity. We examined the skin microbiota, cytokine and lipid profiles in Greenlandic Inuit and Danish children with AD. METHODS: Twenty-five Inuit children with AD and 25 Inuit control children were clinically examined and compared to previously collected data from 25 Danish children with AD. Skin tape strips and skin swabs were collected from lesional and non-lesional skin. Levels of cutaneous immune biomarkers, free sphingoid bases and their (glycosyl)ceramides were analysed. Skin swabs were analysed with 16S rRNA and tuf gene for characterization of bacterial species communities. RESULTS: Bacterial ß-diversity was significantly different between Inuit and Danish AD skin, in both lesional (p < 0.001) and non-lesional (p < 0.001) AD skin, and there was a higher relative abundance of Staphylococcus aureus in Danish compared to Inuit lesional (53% vs. 8%, p < 0.01) and non-lesional skin (55% vs. 5%, p < 0.001). Danish AD children had a higher α-diversity than Inuit children in non-lesional (p < 0.05) but not in lesional skin. Significantly higher levels of type 2 immunity cytokine interleukin (IL)-4 (p < 0.05) and IL-5 (p < 0.01) were identified in Inuit compared to Danish AD children. In contrast, IL-33 (p < 0.01) was higher in Danish lesional and non-lesional AD skin. Higher levels of long-chain glucosylceramide (GlcCER)[S](d26:1) were found in lesional (p < 0.001) and non-lesional (p < 0.001) Inuit skin compared with Danish AD skin. NMF levels were similar in Inuit and Danish AD skin. CONCLUSION: Skin microbiota, cytokine and lipid composition differed significantly between Inuit and Danish children with AD and showed a stronger type 2 immune signature in Inuit children.

Bending Magnet Synchrotron Radiation Imaging with Large Orbital Collection Angles.

Synchrotron radiation (SR) from bending magnets, wigglers, and undulators is now extensively produced for users at storage ring based light sources, with unique properties in terms of average brightness and stability. We present a profound study of bending magnet SR intensity distribution in the image plane of a focusing optical system. Measurements of this intensity distribution at the MAX-IV low emittance storage ring are compared to theoretical predictions, and found to be in excellent agreement. This work shows upon the possibility of performing high resolution emittance diagnostics with visible or near-visible SR on upcoming low-emittance storage ring based light sources. As a byproduct of our study, we derive a closed analytical expression for the intensity distribution from a zero-emittance beam, in the limiting case of wide orbital collection angles. This expression finally allows us to demonstrate the meeting between classical electrodynamics applied to SR emission and focusing, and the Landau and Lifshitz prediction of radiation intensity distribution nearby a caustic.

Valveless On-Chip Aliquoting for Molecular Diagnosis.

The detection of nucleic acids as specific markers of infectious diseases is commonly implemented in molecular biology laboratories. The translation of these benchtop assays to a lab-on-a-chip format demands huge efforts of integration and automation. The present work is motivated by a strong requirement often posed by molecular assays that combine isothermal amplification and CRISPR/Cas-based detection: after amplification, a 2-8 microliter aliquot of the reaction products must be taken for the subsequent reaction. In order to fulfill this technical problem, we have designed and prototyped a microfluidic device that is able to meter and aliquot in the required range during the stepped assay. The operation is achieved by integrating a porous material that retains the desired amount of liquid after removing the excess reaction products, an innovative solution that avoids valving and external actuation. The prototypes were calibrated and experimentally tested to demonstrate the overall performance (general fluidics, metering, aliquoting, mixing and reaction). The proposed aliquoting method is fully compatible with additional functions, such as sample concentration or reagent storage, and could be further employed in alternative applications beyond molecular diagnosis.

Dose-dependent relationship between nocturnal gastroesophageal reflux and chronic rhinosinusitis in a middle-aged population: results from the SCAPIS pilot.

BACKGROUND: Gastroesophageal reflux (GER) has been associated with several upper- and lower-airway diseases. It would be plausible if nightly occurring reflux via laryngopharyngeal reflux (LPR) might affect the upper airways. Still, the role of nocturnal gastroesophageal reflux (nGER) in chronic rhinosinusitis (CRS) is not fully established. The aim of this population-based study was to investigate the association between nGER and CRS. METHODOLOGY: This cross-sectional population-based study comprises 1,111 randomly selected subjects from Gothenburg, Sweden, aged 50-64 years. The study is based on self-reported validated questionnaires. CRS was defined according to EPOS criteria. nGER was reported in relation to frequency. RESULTS: CRS was more common among subjects with nGER than in those without (13 vs. 4.8%). There was a dose-response association between the frequency of nGER episodes and the risk of having CRS. In the logistic regression adjusted for (age, sex, BMI, educational level, smoking, and asthma). CRS was associated with nGER, OR 1.43 and the odds ratio increased if episodes were reported 'almost every night' OR 4.6. CONCLUSIONS: The study shows an association between nocturnal GER and CRS in a middle-aged population. The revealed dose dependency supports, though does not prove causality.

Prenatal and postnatal exposures to endocrine disrupting chemicals and timing of pubertal onset in girls and boys: a systematic review and meta-analysis.

BACKGROUND: Globally, the ages at pubertal onset for girls and boys have been decreasing during recent decades, partly attributed to excess body fat accumulation. However, a growing body of literature has recognized that endocrine disrupting chemicals (EDCs) may play an important role in this global trend, but the association has not yet been fully established. OBJECTIVE AND RATIONALE: EDCs can interfere with normal hormone function and metabolism and play a role in pubertal onset. We aimed to systematically identify and evaluate the current evidence on the timing of pubertal onset in girls and boys following prenatal or postnatal exposures to xenobiotic EDCs. SEARCH METHODS: Following PRISMA guidelines, we performed a systematic literature search of original peer-reviewed publications in the PubMed database through a block search approach using a combination of index MeSH and free text search terms. Publications were considered if they covered biomarkers of prenatal or postnatal exposures to xenobiotic EDCs (European Commission's list of category 1 EDCs) measured in maternal or child biospecimen and pubertal onset defined by the progression of the following milestones (and assessed in terms of the following measures): menarche (age), thelarche (Tanner staging) and pubarche (Tanner staging), in girls, and genital stage (Tanner staging), testicular volume (ml) and pubarche (Tanner staging), in boys. OUTCOMES: The literature search resulted in 703 references, of which we identified 52 publications fulfilling the eligibility criteria for the qualitative trend synthesis and 23 publications for the meta-analysis. The qualitative trend synthesis provided data on 103 combinations of associations between prenatal or postnatal exposure to EDC compounds groups and puberty outcomes and the meta-analysis enabled 18 summary risk estimates of meta-associations. WIDER IMPLICATIONS: Statistically significant associations in the qualitative trend synthesis suggested that postnatal exposure to phthalates may be associated with earlier thelarche and later pubarche. However, we did not find consistent evidence in the meta-analysis for associations between timing of pubertal onset in girls and boys and exposures to any of the studied xenobiotic EDCs. We were not able to identify specific pre- or postnatal windows of exposure as particularly critical and susceptible for effects of EDCs. Current evidence is subject to several methodological challenges and inconsistencies and evidence on specific exposure-outcome associations remains too scarce to firmly confirm EDC exposure as a risk factor for changes in age of pubertal onset in the general child population. To create a more uniform foundation for future comparison of evidence and to strengthen pooled studies, we recommend the use of more standardized approaches in the choice of statistical analyses, with exposure transformations, and in the definitions and assessments of puberty outcomes. The impact of mixtures of EDC exposures on the association also remains unestablished and would be valuable to elucidate for prenatal and postnatal windows of exposure. Future large, longitudinal epidemiological studies are needed to clarify the overall association.

Atopic dermatitis among children and adolescents in the Arctic region - a systematic review and meta-analysis.

The prevalence of atopic dermatitis (AD) varies across the globe, and the clinical phenotype with racial background and ethnicity. AD in the Arctic region has only been scarcely studied. We performed a systematic review and meta-analysis to examine the prevalence, clinical manifestations and risk factors for AD among children and adolescents in the Arctic. Three medical databases PubMed, Embase and Web of Science were screened. All studies published between 1990 to 2020 with epidemiologic data on AD in children and adolescents in the Arctic region, were included. Data were extracted and a meta-analysis was performed to obtain pooled proportions and incidences with 95% confidence intervals (CI). We identified 21 studies from 8 different Arctic regions with 31 403 participants. The cumulative incidence of AD was 23% (95% CI 20-26) and 1-year prevalence was 19% (95% CI 15-25). The incidence of AD was higher in the Arctic parts of Scandinavia and lower in Greenland and Russia. Children of indigenous descent had a slightly lower incidence of AD (19%, 95% CI 13-26) compared to the overall population. The dominant phenotype of AD was mild to moderate flexural dermatitis with facial involvement. Asthma and allergic rhinitis were common and observed in 20-30% of children with AD. In conclusion, AD is highly prevalent in the Arctic, but varies between regions and races. Indigenous children living in less urbanized countries appear to have a slightly lower risk of AD. Future studies should confirm this and examine whether this correlation relates to behavioural differences or genetic signature.

Do modern types of wheat have lower quality for human health?

Wheat is the major staple food in Western Europe and an important source of energy, protein, dietary fibre, minerals, B vitamins and phytochemicals. Plant breeders have been immensely successful in increasing yields to feed the growing global population. However, concerns have been expressed that the focus on increasing yield and processing quality has resulted in reduced contents of components that contribute to human health and increases in adverse reactions. We review the evidence for this, based largely on studies in our own laboratories of sets of wheats bred and grown between the 18th century and modern times. With the exception of decreased contents of mineral micronutrients, there is no clear evidence that intensive breeding has resulted in decreases in beneficial components or increases in proteins which trigger adverse responses. In fact, a recent study of historic and modern wheats from the UK showed increases in the contents of dietary fibre components and a decreased content of asparagine in white flour, indicating increased benefits for health.

A Comparison of Patients with Hip Fracture, Ten Years Apart: Morbidity, Malnutrition and Sarcopenia.

OBJECTIVES: To investigate possible differences in morbidity, malnutrition, sarcopenia and specific drug use in patients with hip fracture, ten years apart. To analyse 1-year mortality and possible associations with variables. DESIGN: A prospective, observational study. SETTING: Örebro University Hospital, Sweden. PARTICIPANTS: Two cohorts of patients with hip fracture, included in 2008 (n=78) and 2018 (n=76). MEASUREMENTS: Presence of comorbidity according to the Elixhauser comorbidity measure, multimorbidity defined as ≥3 comorbidities, preoperative American Society of Anaesthesiologists Classification (ASA-class), malnutrition according to the definition by the Global Leadership Initiative on Malnutrition (GLIM), sarcopenia according to the most recently revised definition by the European Working Group on Sarcopenia in Older People (EWGSOP), polypharmacy defined as ≥5 prescribed medications, use of Potentially Inappropriate Medications (PIM) and Fall-Risk-Increasing-Drugs (FRID) and postoperative 1-year mortality. RESULTS: When comparing the cohorts, significant increases over time was seen for mean comorbidity-count (Difference -1; p=0.002), multimorbidity (Difference -15%; 95%CI -27;-2), ASA-class 3-4 (Difference -25%; 95%CI -39;-9) and polypharmacy (Difference -17%; 95%CI -32;-2). Prevalence of malnutrition and sarcopenia coherently decreased with 22% (95%CI 5;37) and 14% (95%CI 1;29) respectively. One-year mortality remained unchanged and a significant association was found for a higher ASA-class in 2008 (OR 3.5, 95%CI 1.1;11.6) when adjusted for age. Results on PIM exposure suggest a decrease while exposure to FRID remained high. CONCLUSION: Our findings support an increasing morbidity within the population over time. However, also presented is a coherent decrease in malnutrition and sarcopenia, suggesting a decrease in frailty as a possible explanation for the observed unaltered mortality, in turn suggesting advances in treatment of comorbidities.

Bisphenol A Diglycidyl Ether (BADGE) and Bisphenol Analogs, but Not Bisphenol A (BPA), Activate the CatSper Ca2+ Channel in Human Sperm.

Aim: Evidence suggests that bisphenol A diglycidyl ether (BADGE), bisphenol A (BPA), and BPA analogs can interfere with human male fertility. However, the effect directly on human sperm function is not known. The CatSper Ca2+ channel in human sperm controls important sperm functions and is necessary for normal male fertility. Environmental chemicals have been shown to activate CatSper and thereby affect Ca2+ signaling in human sperm. BPA has previously been investigated for effects on Ca2+ signaling human sperm, whereas the effects of other BPA analogs are currently unknown. The aim of this study is thus to characterize the effect of BADGE, BPA, and the eight analogs BPG, BPAF, BPC, BPB, BPBP, BPE, BPF, BPS on Ca2+ signaling, and CatSper in human sperm. Methods: Direct effects of the bisphenols on Ca2+ signaling in human sperm cells were evaluated using a Ca2+ fluorimetric assay measuring changes in intracellular Ca2+. Effects via CatSper were assessed using the specific CatSper inhibitor RU1968. Effects on human sperm function was assessed using an image cytometry-based acrosome reaction assay and the modified Kremer's sperm-mucus penetration assay. Results: At 10 µM the bisphenols BPG, BPAF, BPC, BADGE, BPB, and BPBP induced Ca2+ signals in human sperm cells, whereas BPE, BPF, BPS, and BPA had no effect. The efficacy of the chemicals at 10 µM is BPG > BPAF > BPC > BADGE > BPB > BPBP. Dose-response relations of BPG, BPAF, BPC, BADGE, BPB, and BPBP yielded EC50-values in the nM-µM range. The induced Ca2+ signals were almost completely abolished using the CatSper inhibitor RU1968, indicating an effect of the bisphenols on CatSper. All bisphenols, except BPBP, were found to dose-dependently inhibit progesterone-induced Ca2+ signals, with BPG and BPAF displaying inhibition even in low µM doses. BPG and BPAF were shown to affect human sperm function in a progesterone-like manner. Conclusion: Our results show that the bisphenols BPG, BPAF, BPC, BADGE, BPB, and BPBP can affect Ca2+ signaling in human sperm cells through activation of CatSper. This could potentially disrupt human sperm function by interfering with normal CatSper-signaling and thus be a contributing factor in human infertility, either alone or in mixtures with other chemicals.

Peptide hormone analysis in diagnosis and treatment of Differences of Sex Development: joint position paper of EU COST Action 'DSDnet' and European Reference Network on Rare Endocrine Conditions.

Differences of Sex Development (DSD) comprise a variety of congenital conditions characterized by atypical chromosomal, gonadal, or anatomical sex. Diagnosis and monitoring of treatment of patients suspected of DSD conditions include clinical examination, measurement of peptide and steroid hormones, and genetic analysis. This position paper on peptide hormone analyses in the diagnosis and control of patients with DSD was jointly prepared by specialists in the field of DSD and/or peptide hormone analysis from the European Cooperation in Science and Technology (COST) Action DSDnet (BM1303) and the European Reference Network on rare Endocrine Conditions (Endo-ERN). The goal of this position paper on peptide hormone analysis was to establish laboratory guidelines that may contribute to improve optimal diagnosis and treatment control of DSD. The essential peptide hormones used in the management of patients with DSD conditions are follicle-stimulating hormone, luteinising hormone, anti-Müllerian hormone, and Inhibin B. In this context, the following position statements have been proposed: serum and plasma are the preferred matrices; the peptide hormones can all be measured by immunoassay, while use of LC-MS/MS technology has yet to be implemented in a diagnostic setting; sex- and age-related reference values are mandatory in the evaluation of these hormones; and except for Inhibin B, external quality assurance programs are widely available.

Maternal serum concentrations of bisphenol A and propyl paraben in early pregnancy are associated with male infant genital development.

STUDY QUESTION: Are maternal serum phthalate metabolite, phenol and paraben concentrations measured at 10-17 weeks of gestation associated with male infant genital developmental outcomes, specifically cryptorchidism, anogenital distance (AGD), penile length and testicular descent distance, at birth and postnatally? SUMMARY ANSWER: Maternal serum bisphenol A (BPA) concentration at 10-17 weeks of gestation was positively associated with congenital or postnatally acquired cryptorchidism, and n-propyl paraben (n-PrP) concentration was associated with shorter AGD from birth to 24 months of age. WHAT IS KNOWN ALREADY: Male reproductive disorders are increasing in prevalence, which may reflect environmental influences on foetal testicular development. Animal studies have implicated phthalates, BPA and parabens, to which humans are ubiquitously exposed. However, epidemiological studies have generated conflicting results and have often been limited by small sample size and/or measurement of chemical exposures outside the most relevant developmental window. STUDY DESIGN, SIZE, DURATION: Case-control study of cryptorchidism nested within a prospective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at 10-17 postmenstrual weeks of gestation from a single UK maternity unit between 2001 and 2009 and 24 months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 330 mothers of 334 male infants (30 with congenital cryptorchidism, 25 with postnatally acquired cryptorchidism and 279 unmatched controls) were included in the present analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Maternal blood was collected at enrolment, and serum levels of 16 phthalate metabolites, 9 phenols (including BPA) and 6 parabens were measured using liquid chromatography/tandem mass spectrometry. Logistic regression was used to model the association of cryptorchidism with serum chemical concentrations, adjusting for putative confounders. Additionally, offspring AGD, penile length and testicular descent distance were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated. Associations between serum chemical levels and these outcomes were tested using linear mixed models. MAIN RESULTS AND THE ROLE OF CHANCE: Maternal serum BPA concentration was associated with offspring all-type cryptorchidism both when considered as a continuous exposure (adjusted odds ratio per log10 µg/l: 2.90, 95% CI 1.31-6.43, P = 0.009) and as quartiles (phet = 0.002). Detection of n-PrP in maternal serum was associated with shorter AGD (by 0.242 standard deviations, 95% CI 0.051-0.433, P = 0.01) from birth to 24 months of age; this reduction was independent of body size and other putative confounders. We did not find any consistent associations with offspring outcomes for the other phenols, parabens, and phthalate metabolites measured. LIMITATIONS, REASONS FOR CAUTION: We cannot discount confounding by other demographic factors or endocrine-disrupting chemicals. There may have been misclassification of chemical exposure due to use of single serum measurements. The cohort was not fully representative of pregnant women in the UK, particularly in terms of smoking prevalence and maternal ethnicity. WIDER IMPLICATIONS OF THE FINDINGS: Our observational findings support experimental evidence that intrauterine exposure to BPA and n-PrP during early gestation may adversely affect male reproductive development. More evidence is required before specific public health recommendations can be made. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), Newlife the Charity for Disabled Children, the Mothercare Group Foundation, Mead Johnson Nutrition and the National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre. Visiting Fellowship (J.M.): Regional Programme 'Jiménez de la Espada' for Research Mobility, Cooperation and Internationalization, Seneca Foundation-Science and Technology Agency for the Region of Murcia (No. 20136/EE/17). K.O. is supported by the Medical Research Council (UK) (Unit Programme number: MC_UU_12015/2). The authors declare no conflict of interest.

Gene amplification as a form of population-level gene expression regulation.

Organisms cope with change by taking advantage of transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. Here, we investigate whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using real-time monitoring of gene-copy-number mutations in Escherichia coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy-number and, therefore, expression-level polymorphisms. This amplification-mediated gene expression tuning (AMGET) occurs on timescales that are similar to canonical gene regulation and can respond to rapid environmental changes. Mathematical modelling shows that amplifications also tune gene expression in stochastic environments in which transcription-factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune the expression of any gene, without leaving any genomic signature.

Modeling vitamin B1 transfer to consumers in the aquatic food web.

Vitamin B1 is an essential exogenous micronutrient for animals. Mass death and reproductive failure in top aquatic consumers caused by vitamin B1 deficiency is an emerging conservation issue in Northern hemisphere aquatic ecosystems. We present for the first time a model that identifies conditions responsible for the constrained flow of vitamin B1 from unicellular organisms to planktivorous fishes. The flow of vitamin B1 through the food web is constrained under anthropogenic pressures of increased nutrient input and, driven by climatic change, increased light attenuation by dissolved substances transported to marine coastal systems. Fishing pressure on piscivorous fish, through increased abundance of planktivorous fish that overexploit mesozooplankton, may further constrain vitamin B1 flow from producers to consumers. We also found that key ecological contributors to the constrained flow of vitamin B1 are a low mesozooplankton biomass, picoalgae prevailing among primary producers and low fluctuations of population numbers of planktonic organisms.

Effects of thermal hydrolytic pre-treatment on biogas process efficiency and microbial community structure in industrial- and laboratory-scale digesters.

This study examined the impact of thermal hydrolysis process (THP) pre-treatment on anaerobic co-digestion of wastewater sludge and household waste and assessed whether THP was vital to achieve higher process capacity. Performance data were collected for both industrial- and laboratory-scale digesters and response in microbial community structure was evaluated by Illumina sequencing. Implementation of THP at the industrial-scale plant increased methane yield by 15% and enhanced substrate degradability. Possibility to extend the sludge retention time due to a higher solid content of the substrate, sanitisation of the digestate and improved fertiliser quality of the digestate were other industrial-scale benefits of THP installation. Continuously-fed laboratory-scale digesters were fed THP-treated or untreated substrate at an organic loading rate (OLR) of 5 g volatile solid (VS)/L/day, a feeding rate necessary at the corresponding industrial-scale plant to meet the estimated population increase within the municipality. The results indicated that the plant could have increased the capacity with unimpaired stability independently of THP installation, even though the retention time was significantly shortened during operation with untreated substrate. Microbial community analyses revealed increased contribution of the Clostridia class after THP installation in industrial-scale digesters and positive correlation between Firmicutes:Bacteriodetes and methane yield in all digesters. Differentiated profiles in laboratory-scale digesters indicated that a temperature increase from 37 to 42 °C in association with THP installation and altered substrate composition were strong determining factors shaping the microbial community. Overall, these findings can assist industrial-scale plants in choosing management strategies aimed at improving the efficiency of anaerobic digestion processes.

Individual Physiological Adaptations Enable Selected Bacterial Taxa To Prevail during Long-Term Incubations.

Enclosure experiments are frequently used to investigate the impact of changing environmental conditions on microbial assemblages. Yet, how the incubation itself challenges complex bacterial communities is thus far unknown. In this study, metaproteomic profiling, 16S rRNA gene analyses, and cell counts were combined to evaluate bacterial communities derived from marine, mesohaline, and oligohaline conditions after long-term batch incubations. Early in the experiment, the three bacterial communities were highly diverse and differed significantly in their compositions. Manipulation of the enclosures with terrigenous dissolved organic carbon resulted in notable differences compared to the control enclosures at this early phase of the experiment. However, after 55 days, bacterial communities in the manipulated and the control enclosures under marine and mesohaline conditions were all dominated by gammaproteobacterium Spongiibacter In the oligohaline enclosures, actinobacterial cluster I of the hgc group (hgc-I) remained abundant in the late phase of the incubation. Metaproteome analyses suggested that the ability to use outer membrane-based internal energy stores, in addition to the previously described grazing resistance, may enable the gammaproteobacterium Spongiibacter to prevail in long-time incubations. Under oligohaline conditions, the utilization of external recalcitrant carbon appeared to be more important (hgc-I). Enclosure experiments with complex natural microbial communities are important tools to investigate the effects of manipulations. However, species-specific properties, such as individual carbon storage strategies, can cause manipulation-independent effects and need to be considered when interpreting results from enclosures.IMPORTANCE In microbial ecology, enclosure studies are often used to investigate the effect of single environmental factors on complex bacterial communities. However, in addition to the manipulation, unintended effects ("bottle effect") may occur due to the enclosure itself. In this study, we analyzed the bacterial communities that originated from three different salinities of the Baltic Sea, comparing their compositions and physiological activities both at the early stage and after 55 days of incubation. Our results suggested that internal carbon storage strategies impact the success of certain bacterial species, independent of the experimental manipulation. Thus, while enclosure experiments remain valid tools in environmental research, microbial community composition shifts must be critically followed. This investigation of the metaproteome during long-term batch enclosures expanded our current understanding of the so-called "bottle effect," which is well known to occur during enclosure experiments.

Source apportionment of circum-Arctic atmospheric black carbon from isotopes and modeling.

Black carbon (BC) contributes to Arctic climate warming, yet source attributions are inaccurate due to lacking observational constraints and uncertainties in emission inventories. Year-round, isotope-constrained observations reveal strong seasonal variations in BC sources with a consistent and synchronous pattern at all Arctic sites. These sources were dominated by emissions from fossil fuel combustion in the winter and by biomass burning in the summer. The annual mean source of BC to the circum-Arctic was 39 ± 10% from biomass burning. Comparison of transport-model predictions with the observations showed good agreement for BC concentrations, with larger discrepancies for (fossil/biomass burning) sources. The accuracy of simulated BC concentration, but not of origin, points to misallocations of emissions in the emission inventories. The consistency in seasonal source contributions of BC throughout the Arctic provides strong justification for targeted emission reductions to limit the impact of BC on climate warming in the Arctic and beyond.

Environmental phenols and parabens in adipose tissue from hospitalized adults in Southern Spain.

Urinary concentrations of non-persistent environmental pollutants (npEPs) are widely assessed in biomonitoring studies under the assumption that they are metabolised and eliminated in urine. However, some of these chemicals are moderately lipophilic, and their presence in other biological matrices should also be evaluated to estimate mid/long-term exposure to npEPs and its impact on human health. The present study aims to explore concentrations and potential determinants of npEPs in adipose tissue from a hospital-based adult cohort (GraMo cohort, Southern Spain). Concentrations of bisphenol-A (BPA), benzophenone-3 (BP-3), triclosan (TCS), three chlorophenols (2,4-DCP, 2,5-DCP and 2,4,5-TCP) and two phenylphenols (2-PP and 4-PP), triclocarban (TCCB) and parabens [methyl- (MeP), ethyl- (EtP), propyl- (n-PrP and i-PrP), butyl- (n-BuP and i-BuP) and benzyl-paraben (BzP)] were analysed in adipose tissue samples from a subcohort of 144 participants. Spearman correlation tests were performed, followed by stepwise multivariable linear regression analyses to assess determinants of the exposure. Detection frequencies and median concentrations were: BPA (86.8%, 0.54 ng/g tissue), BP-3 (79.2%, 0.60 ng/g tissue), TCS (45.8%,

ERα expression in T lymphocytes is dispensable for estrogenic effects in bone.

Estrogen treatment has positive effects on the skeleton, and we have shown that estrogen receptor alpha (ERα) expression in cells of hematopoietic origin contributes to a normal estrogen treatment response in bone tissue. T lymphocytes are implicated in the estrogenic regulation of bone mass, but it is not known whether T lymphocytes are direct estrogen target cells. Therefore, the aim of this study was to determine the importance of ERα expression in T lymphocytes for the estrogenic regulation of the skeleton using female mice lacking ERα expression specifically in T lymphocytes (Lck-ERα-/-) and ERαflox/flox littermate (control) mice. Deletion of ERα expression in T lymphocytes did not affect bone mineral density (BMD) in sham-operated Lck-ERα-/- compared to control mice, and ovariectomy (ovx) resulted in a similar decrease in BMD in control and Lck-ERα-/- mice compared to sham-operated mice. Furthermore, estrogen treatment of ovx Lck-ERα-/- led to an increased BMD that was indistinguishable from the increase seen after estrogen treatment of ovx control mice. Detailed analysis of both the appendicular (femur) and axial (vertebrae) skeleton showed that both trabecular and cortical bone parameters responded to a similar extent regardless of the presence of ERα in T lymphocytes. In conclusion, ERα expression in T lymphocytes is dispensable for normal estrogenic regulation of bone mass in female mice.

Predators and nutrient availability favor protozoa-resisting bacteria in aquatic systems.

The long co-existence of bacteria and protozoa has led to the development of bacterial protozoa resistance strategies, which are suggested to serve as drivers for the evolution of pathogenic bacteria. However, the ecological mechanisms underpinning selection for protozoa-resistance in aquatic bacteria are poorly known. To assess the role of nutrient availability and predation-pressure on selection for protozoa-resisting bacteria (PRB), an enrichment-dilution experiment was designed using laboratory microcosms containing natural lake water. PRB was monitored by screening 16S rRNA amplicon sequence data for reads assigned to bacteria that previously has been shown to resist degradation by amoebae. To estimate the effects of the microbial food web dynamics (microscopy of; heterotrophic bacteria, phytoplankton, protozoa and rotifers) and physicochemical variables on the PRB abundance in the study system, a joint species distribution modelling approach was used. The predation-pressure (ratio between predator and bacterial biomass) had a positive effect on the abundance of the PRB genus Mycobacterium, while perturbation (enrichment and dilution) favored the PRB genus Pseudomonas that dominated the bacterial community in the disturbed systems. Our results show that PRB with different ecological strategies can be expected in water of high and intermediate nutrient levels and after major disturbances of an aquatic system.

Clinical testing of three novel transient receptor potential cation channel subfamily V member 1 antagonists in a pharmacodynamic intradermal capsaicin model.

BACKGROUND: The transient receptor potential cation channel subfamily V 1 (TRPV1) is involved in nociception and has thus been of interest for drug developers, as a target for novel analgesics. However, several oral TRPV1 antagonists have failed in development, and novel approaches to target TRPV1 with innovative chemistry are needed. METHOD: This work describes an intradermal microdosing approach in humans for pharmacodynamic deductions and pharmacological profiling of compounds. First, a human capsaicin model was developed, to generate pharmacodynamic translational data (Study Part A, n = 24). Then, three small molecule TRPV1 antagonists (AZ11760788, AZ12048189 and AZ12099548) were investigated in healthy volunteers (Study Part B, n = 36), applying the established model. Pain and flare were assessed by Visual Analogue Score and laser Doppler, respectively. RESULTS: The developed model proved useful for pharmacologic deductions; all compounds caused a dose-dependent inhibition of capsaicin-induced pain and flare responses, with a rank order potency of AZ11760788 > AZ12048189 â‰« AZ12099548. In addition, the dose-response data showed that the minimal antagonist concentrations needed to inhibit TRPV1 was ≥6-7 times the equilibrium dissociation constant for each compound. CONCLUSION: With careful design of a pharmacodynamic translational human pain model, it was possible to rank order TRPV1 efficacy among three investigational TRPV1 antagonists, and to estimate human efficacious concentrations. SIGNIFICANCE: This fast and cost-effective translational approach allows for generation of human target engagement information early in drug development. This could be of value for other development programmes where pharmacological targets are expressed in peripheral sensory nerves.