Selection of cross-reactive T cells by commensal and food-derived yeasts drives cytotoxic TH1 cell responses in Crohn's disease.

Aberrant CD4+ T cell reactivity against intestinal microorganisms is considered to drive mucosal inflammation in inflammatory bowel diseases. The disease-relevant microbial species and the corresponding microorganism-specific, pathogenic T cell phenotypes remain largely unknown. In the present study, we identified common gut commensal and food-derived yeasts, as direct activators of altered CD4+ T cell reactions in patients with Crohn's disease (CD). Yeast-responsive CD4+ T cells in CD display a cytotoxic T helper cell (TH1 cell) phenotype and show selective expansion of T cell clones that are highly cross-reactive to several commensal, as well as food-derived, fungal species. This indicates cross-reactive T cell selection by repeated encounter with conserved fungal antigens in the context of chronic intestinal disease. Our results highlighted a role of yeasts as drivers of aberrant CD4+ T cell reactivity in patients with CD and suggest that both gut-resident fungal commensals and daily dietary intake of yeasts might contribute to chronic activation of inflammatory CD4+ T cell responses in patients with CD.

Chemical Doping by Fluorination and Its Impact on All Energy Levels of π-Conjugated Systems.

Halogenation of organic molecules causes chemical shifts of C1s core-level binding energies that are commonly used as fingerprints to identify chemical species. Here, we use synchrotron-based X-ray photoelectron spectroscopy and density functional theory calculations to unravel such chemical shifts by examining different partially fluorinated pentacene derivatives. Core-level shifts occur even for carbon atoms distant from the fluorination positions, yielding a continuous shift of about 1.8 eV with increasing degree of fluorination for pentacenes. Since also their LUMO energies shift markedly with the degree of fluorination of the acenes, core-level shifts result in a nearly constant excitation energy of the leading π* resonance as obtained in complementary recorded K-edge X-ray absorption spectra, hence demonstrating that local fluorination affects the entire π-system, including valence and core levels. Our results thus challenge the common picture of characteristic chemical core-level energies as fingerprint signatures of fluorinated π-conjugated molecules.

The Relation of Mental Rotation and Postural Stability.

Main goal of this study was to investigate the influence of mental rotation tasks on postural stability. 84 participants were tested with two object-based mental rotation tasks (cube vs. human figures), an egocentric mental rotation task with one human figure, a math- (cognitive control) and a neutral task, while standing on a force plate in a both-legged narrow stance. Parameters related to the Center of Pressure course over time were used to quantify postural stability. The simultaneous solution of mental rotation tasks has led to postural stabilisation compared to the neutral condition. Egocentric tasks provoked more postural stability than object-based tasks with cube figures. Furthermore, a more stable stance was observed for embodied stimuli than for cube figures. An explorative approach showed the tendency that higher rotation angles of the object-based mental rotation task stimuli lead to more postural sway. These results contribute to a better understanding of the interaction between mental rotation and motor skills and emphasize the role of type of task and embodiment in dual task research.

Embodied Mental Rotation - Does It Affect Postural Stability?

The effect of different human body part stimuli in mental rotation tasks (MRTs) on postural stability was investigated in two dual-task experiments. There were significant differences within egocentric MRTs (Experiment 1, N = 46): Hand and foot stimuli tended to cause more body sway than whole-body figures and showed increased body sway for higher rotation angles in the MRTs. In object-based MRTs (Experiment 2, N = 109) different stimuli did not evoke different levels of body sway, but higher rotation angles led to higher body sway. Both experiments showed a stabilizing effect of MRTs compared to the control condition. Exploratorily analyses identified reaction time in MRTs as a significant predictor of body sway. The results suggest a heterogeneous impact of mental rotation on postural stability.

Regioselective Fluorination of Acenes: Tailoring of Molecular Electronic Levels and Solid-State Properties.

Optoelectronic properties of molecular solids are important for organic electronic devices and are largely determined by the adopted molecular packing motifs. In this study, we analyzed such structure-property relationships for the partially regioselective fluorinated tetracenes 1,2,12-trifluorotetracene, 1,2,10,12-tetrafluorotetracene and 1,2,9,10,11-pentafluorotetracene that were further compared with tetracene and perfluoro-tetracene. Quantum chemical DFT calculations in combination with optical absorption spectroscopy data show that the frontier orbital energies are lowered with the degree of fluorination, while their optical gap is barely affected. However, the crystal structure changes from a herringbone packing motif of tetracene towards a planar stacking motif of the fluorinated tetracene derivatives, which is accompanied by the formation of excimers and leads to strongly red-shifted photoluminescence with larger lifetimes.

Are explicit and implicit affective attitudes toward different body shape categories related to the own body-satisfaction in young women? The role of mindfulness, self-compassion and social media activity.

Implicit and explicit attitudes influence our behavior. Accordingly, it was the main goal of the paper to investigate if those attitudes are related to body image satisfaction. 134 young women between 18 and 34 years completed an explicit affective rating and an implicit affective priming task with pictures of women with different BMIs. Because it is well known that mindfulness, self-compassion and social media activity influence body image satisfaction, these variables were registered as well. The results confirmed an explicit positive affective bias toward pictures of slim women and a negative bias toward emaciated and obese body pictures. It adds to the literature that the explicit positive bias does not hold true for the strongest form of underweight, suggesting that instead of dividing different body shapes into two groups, different gradings of under- and overweight should be considered. Concerning the affective priming task, no significant differences between the different pictures could be carved out. Implicit and explicit affective attitudes were not related to the body satisfaction of the participating women. In line with former studies, body satisfaction was predicted by the actual-ideal weight discrepancy, the BMI, aspects of mindfulness and self-compassion. This study indicates that implicit and explicit affective attitudes toward underweight and overweight women are unrelated to the participants' body satisfaction.

Correction: Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease.

[This corrects the article DOI: 10.1371/journal.pgen.1009679.].

High ESBL-E colonization rate among children in Gabon: a follow-up study.

A previous study conducted in Gabon, Central Africa, in 2010/11 found a high colonization rate with extended-spectrum ß-lactamase-producing enterobacterales (ESBL-E) among children of ~34 %. Eight years later, we aimed to reassess the ESBL-E rate and previously identified risk factors for colonization in children from Gabon. We conducted a cross-sectional cohort study in 2018 on 92 outpatients under 5 years of age with diarrhoea in Lambaréné, Gabon, in whom a rectal swab was obtained at the initial medical encounter (baseline). Fifty-eight of these provided a further rectal swab 1 week afterwards. ESBL-E colonization was assessed [following the European Committee on Antimicrobial Susceptibility Testing (EUCAST)], and in confirmed ESBL-E isolates the susceptibility to meropenem and the prevalence of the most abundant ESBL genes, bla CTX-M, bla SHV, and bla TEM, were investigated. At baseline, the ESBL-E colonization rate was 57 % (52/92; 95 % CI: 46-67). Hospitalization during the previous year, chicken consumption in the past week and young age were identified as independent risk factors for ESBL-E colonization at baseline. On day 7, the ESBL-E carriage rate was 72 % (42/58; 95 % CI: 59-83). All ESBL-E isolates (n=293) were susceptible to meropenem and bla CTX-M was the most frequently detected ß-lactamase gene. The ESBL-E colonization rate among children from Gabon is alarmingly high, with indications of further increase over recent years. While all ESBL-E strains remain currently susceptible to meropenem, in practice no adequate treatment is available locally for severe infections with such isolates. It is thus of the utmost importance to invest in improved hospital infection prevention and control measures to combat ESBL-E effectively.

Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease.

Numerous genetic studies have established a role for rare genomic variants in Congenital Heart Disease (CHD) at the copy number variation (CNV) and de novo variant (DNV) level. To identify novel haploinsufficient CHD disease genes, we performed an integrative analysis of CNVs and DNVs identified in probands with CHD including cases with sporadic thoracic aortic aneurysm. We assembled CNV data from 7,958 cases and 14,082 controls and performed a gene-wise analysis of the burden of rare genomic deletions in cases versus controls. In addition, we performed variation rate testing for DNVs identified in 2,489 parent-offspring trios. Our analysis revealed 21 genes which were significantly affected by rare CNVs and/or DNVs in probands. Fourteen of these genes have previously been associated with CHD while the remaining genes (FEZ1, MYO16, ARID1B, NALCN, WAC, KDM5B and WHSC1) have only been associated in small cases series or show new associations with CHD. In addition, a systems level analysis revealed affected protein-protein interaction networks involved in Notch signaling pathway, heart morphogenesis, DNA repair and cilia/centrosome function. Taken together, this approach highlights the importance of re-analyzing existing datasets to strengthen disease association and identify novel disease genes and pathways.

Prevalence of Pathogens in Young Children Presenting to Hospital with Diarrhea from Lambaréné, Gabon.

Diarrheal disease is the second most frequent cause of mortality in children younger than 5 years worldwide, causing more than half a million deaths each year. Our knowledge of the epidemiology of potentially pathogenic agents found in children suffering from diarrhea in sub-Saharan African countries is still patchy, and thereby hinders implementation of effective preventative interventions. The lack of cheap, easy-to-use diagnostic tools leads to mostly symptomatic and empirical case management. An observational study with a total of 241 participants was conducted from February 2017 to August 2018 among children younger than 5 years with diarrhea in Lambaréné, Gabon. Clinical and demographic data were recorded, and a stool sample was collected. The samples were examined using a commercial rapid immunoassay to detect Rotavirus/adenovirus, conventional bacterial culture for Salmonella spp., and multiplex real-time PCR for Cryptosporidium spp., Giardia lamblia, Cyclospora cayetanensis, enterotoxigenic Escherichia coli (ETEC), and enteroinvasive Escherichia coli (EIEC)/Shigella. At least one infectious agent was present in 121 of 241 (50%) samples. The most frequently isolated pathogens were EIEC/Shigella and ETEC (54/179; 30.2% and 44/179; 24.6%, respectively), followed by G. lamblia (33/241; 13.7%), Cryptosporidium spp. (31/241; 12.9%), and Rotavirus (23/241; 9.5%). Coinfection with multiple pathogens was observed in 33% (40/121) of the positive cases with EIEC/Shigella, ETEC, and Cryptosporidium spp. most frequently identified. Our results provide new insight into the possible causes of diarrheal disease in the Moyen-Ogooué region of Gabon and motivate further research on possible modes of infection and targeted preventive measures.

The Individual Green-Washing Effect in E-Mobility: Emotional Evaluations of Electric and Gasoline Cars.

In this study, the affective explicit and implicit attitudes toward electric and gasoline cars are investigated. One hundred sixty-five participants (103 cisgender women, 62 cisgender men) completed an explicit and implicit affective rating task toward pictures of electric and gasoline cars, measurements of sustainability, future and past behaviors, and mindfulness. The results showed a positive emotional attitude for the electric cars compared with the gasoline cars only for the explicit rating but not for the implicit one. Furthermore, factors that correlated to the attitudes were investigated: explicit ratings in car owners correlated with age, degree, sustainability in general, and the expressed intention to purchase an electric car in the future. Implicit attitudes in car owners correlated with the overall score of mindfulness and the dimension of "non-reactivity." For the non-car owners, explicit attitudes correlated with the expressed intention to purchase an electric car in the future and the mindfulness dimension of "describing". In this group, the implicit attitude correlated negatively with the mindfulness intention of acting with awareness. This indicates that several different factors should be considered in the development of promotion campaigns for the advantage of sustainable mobility behavior.

Effect of low-temperature drying on the nitrogenous compounds and inositol phosphates in broiler chickens and cecectomized laying hen excreta.

We investigated how the chemical composition of broiler chicken and cecectomized laying hen excreta is affected by drying in a forced-air drying chamber at low temperatures. Excreta that was immediately frozen after voiding provided the reference values. The excreta were dried in drying chambers for 4 hr, 6 hr, and 12 hr at 23°C or 33°C in the broiler experiment and 19°C or 29°C in the cecectomized laying hen experiment. The total N and inositol phosphate concentrations in the excreta of broiler chickens and cecectomized laying hens were not influenced (p > .050), except for one inositol tetrakisphosphate isomer (p = .026) in broilers. Compared to fresh excreta, drying did not affect the ammonia concentrations in the cecectomized laying hen experiment (p > .050), but the ammonia concentration was lower when dried for 12 hr at 33°C in the broiler experiment (p = .002). Amino acid concentrations in cecectomized laying hen excreta decreased until 4 hr of drying and then increased at both drying temperatures (p < .001). The results indicate that the applicability of drying poultry excreta at low temperatures in forced-air drying chambers to determine the chemical compound concentrations is trait-dependent. Future studies are necessary to investigate whether these results are also dependent upon the amount of excreta stored in the drying chambers.

Effects of supplemented nonessential amino acids and nonprotein nitrogen on growth and nitrogen excretion characteristics of broiler chickens fed diets with very low crude protein concentrations.

Reducing dietary CP for broiler chickens below a certain threshold results in decreased growth, even when the supply of essential amino acids and glycine equivalent (Glyequi) is adequate, probably because other nonessential amino acids (neAA) are growth-limiting. Nonprotein nitrogen (NPN) might be used for the synthesis of neAA. Therefore, the effects of specific neAA and ammonium chloride (NH4Cl) supplementation on the growth and N-excretion characteristics of broiler chickens were investigated. Nine male Ross 308 broiler chickens were kept in each of 81 metabolism units from day 7 to 21 and received 1 of 9 diets in 9 replicates in a one-factorial arrangement of treatments. Two diets with different neAA concentrations, except for Glyequi, were mixed resulting in CP levels of 180 (CP180) and 160 (CP160) g/kg. In six other diets, CP160 was supplemented with either l-Ala, l-Pro, l-Asp, a mix of l-Asp and l-Asn·H2O, l-Glu, or a mix of l-Glu and l-Gln to achieve concentrations of the respective neAA as formulated in CP180. In a further diet, NH4Cl was added to CP160 to achieve the CP concentration of CP180. The ADG and gain:feed ratio (G:F) from day 7 to 21 were highest at CP180. Reduced neAA concentrations in CP160 decreased ADG and G:F. Supplementation of Asp+Asn, Glu, and Glu+Gln to CP160 increased ADG and G:F, but not to the level found for CP180. Compared with CP160, addition of Asp increased G:F but not ADG. Supplementation of Asp+Asn caused higher ADG and G:F than supplementation of Asp alone. The N-utilization efficiency was highest at CP160 and at CP160 supplemented with Ala, Pro, and Glu. Lower N-utilization efficiency was found at CP180 than at CP160, without and with supplemented neAA. The treatment containing NH4Cl presented the lowest ADG, G:F, and N-utilization efficiency. These results showed that individual supplementation of Asp+Asn, Glu, and Glu+Gln partly compensates for the growth-reducing effects of very low CP diets. Supplementation of NH4Cl as NPN source is not suitable for broiler chickens.

Interactive Effects of Glycine Equivalent, Cysteine, and Choline on Growth Performance, Nitrogen Excretion Characteristics, and Plasma Metabolites of Broiler Chickens Using Neural Networks Optimized with Genetic Algorithms.

Responses of broiler chickens to dietary glycine equivalent (Glyequi) are affected by dietary cysteine and choline. Hence, this study investigated interactive effects among dietary Glyequi, cysteine, and choline on the growth of broiler chickens. Male Ross 308 broiler chickens were maintained in 105 metabolism units (10 birds/unit) from days 7 to 22. Excreta were collected in 12-h intervals from days 18 to 21. Blood was sampled on day 22 (1 bird/unit). Five levels each of Glyequi (9-21 g/kg), cysteine (2-5 g/kg), and choline (0.5-1.7 g/kg) were tested under 15 diets in 7 replicates each following a fractional central composite design. Another diet was provided to five metabolism units (15 birds/unit) to measure prececal amino acid digestibility. Data were evaluated using neural networks. The gain:feed ratio (G:F) increased with digestible Glyequi intake. Differences between low and high digestible cysteine intake were low. Effects of choline intake on G:F were low. Nitrogen-utilization efficiency (NUE) was high (≥77%), with low variation among treatments. Plasma metabolites varied among treatments and indicated that metabolism of Glyequi, cysteine, and choline was influenced. These findings showed that interactive effects of dietary Glyequi, cysteine, and choline on growth were small, possibly because NUE was barely influenced.

Unilaterally Fluorinated Acenes: Synthesis and Solid-State Properties.

The rapid development of organic electronics is closely related to the availability of molecular materials with specific electronic properties. Here, we introduce a novel synthetic route enabling a unilateral functionalization of acenes along their long side, which is demonstrated by the synthesis of 1,2,10,11,12,14-hexafluoropentacene (1) and the related 1,2,9,10,11-pentafluorotetracene (2). Quantum chemical DFT calculations in combination with optical and X-ray absorption spectroscopy data indicate that the single-molecule properties of 1 are a connecting link between the organic semiconductor model systems pentacene (PEN) and perfluoropentacene (PFP). In contrast, the crystal structure analysis reveals a different packing motif than for the parent molecules. This can be related to distinct F⋅⋅⋅H interactions identified in the corresponding Hirshfeld surface analysis and also affects solid-state properties such as the exciton binding energy and the sublimation enthalpy.

Loss of ADAMTS19 causes progressive non-syndromic heart valve disease.

Valvular heart disease is observed in approximately 2% of the general population1. Although the initial observation is often localized (for example, to the aortic or mitral valve), disease manifestations are regularly observed in the other valves and patients frequently require surgery. Despite the high frequency of heart valve disease, only a handful of genes have so far been identified as the monogenic causes of disease2-7. Here we identify two consanguineous families, each with two affected family members presenting with progressive heart valve disease early in life. Whole-exome sequencing revealed homozygous, truncating nonsense alleles in ADAMTS19 in all four affected individuals. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype. Expression analysis using a lacZ reporter and single-cell RNA sequencing highlight Adamts19 as a novel marker for valvular interstitial cells; inference of gene regulatory networks in valvular interstitial cells positions Adamts19 in a highly discriminatory network driven by the transcription factor lymphoid enhancer-binding factor 1 downstream of the Wnt signaling pathway. Upregulation of endocardial Krüppel-like factor 2 in Adamts19 knockout mice precedes hemodynamic perturbation, showing that a tight balance in the Wnt-Adamts19-Klf2 axis is required for proper valve maturation and maintenance.

Very Low Crude Protein and Varying Glycine Concentrations in the Diet Affect Growth Performance, Characteristics of Nitrogen Excretion, and the Blood Metabolome of Broiler Chickens.

BACKGROUND: The minimum to which dietary crude protein (CP) level for broiler chickens can be reduced without decreasing growth and the glycine equivalent (Glyequi) concentration required are not known. The plasma metabolome might reflect dietary influences on physiological processes. OBJECTIVE: The aim of this study was to investigate the effect of 3 low CP levels with 4 Glyequi concentrations on growth and characteristics of nitrogen excretion, and to identify plasma metabolome variations. METHODS: Male Ross308 broiler chickens were provided 1 of 12 dietary treatments in 84 metabolism cages (10/cage) from days 7 to 21. Three diets with 163 (CP163), 147 (CP147), and 132 (CP132) g CP/kg were formulated, each containing 12, 15, 18, and 21 g Glyequi/kg. Essential amino acid concentrations were the same in all diets. Animals and feed were weighed on days 7 and 21 to determine average daily gain (ADG) and gain:feed ratio (G:F). Excreta were collected from days 18 to 21 to analyze nitrogenous components, and blood was obtained on day 21 to conduct a metabolome analysis. RESULTS: Two-factor ANOVA showed significant interaction effects for ADG, G:F, and nitrogen efficiency (P < 0.001). Reduction of CP decreased ADG and G:F, and increased nitrogen efficiency. Glyequi supplementation increased ADG (by 7.9 g/d) and G:F (by 0.07 g/g) at CP132. The ADG (by 2.4 g/d) at CP147 and G:F (by 0.02 g/g) at CP147 and CP163 increased up to 15 g Glyequi/kg. Multivariate statistical analysis showed an influence of Glyequi on plasma acylcarnitine and lysophosphatidylcholine concentrations, and a decrease of plasma phosphatidylcholine and sphingomyelin concentrations with reduced CP. CONCLUSIONS: These results suggest that a nutrient other than Glyequi limited growth when CP was reduced from CP163 to CP147, and that the response of broiler chickens to Glyequi is dependent on the dietary CP level. Plasma metabolites indicate dietary influences on the physiological state of the animals.

Oil adsorption ability of three-dimensional epicuticular wax coverages in plants.

Primary aerial surfaces of terrestrial plants are very often covered with three-dimensional epicuticular waxes. Such wax coverages play an important role in insect-plant interactions. Wax blooms have been experimentally shown in numerous previous studies to be impeding locomotion and reducing attachment of insects. Among the mechanisms responsible for these effects, a possible adsorption of insect adhesive fluid by highly porous wax coverage has been proposed (adsorption hypothesis). Recently, a great decrease in insect attachment force on artificial adsorbing materials was revealed in a few studies. However, adsorption ability of plant wax blooms was still not tested. Using a cryo scanning electron microscopy approach and high-speed video recordings of fluid drops behavior, followed by numerical analysis of experimental data, we show here that the three-dimensional epicuticular wax coverage in the waxy zone of Nepenthes alata pitcher adsorbs oil: we detected changes in the base, height, and volume of the oil drops. The wax layer thickness, differing in samples with untreated two-layered wax coverage and treated one-layered wax, did not significantly affect the drop behavior. These results provide strong evidence that three-dimensional plant wax coverages due to their adsorption capability are in general anti-adhesive for insects, which rely on wet adhesion.

Evaluation of bone mineral density of the lumbar spine using a novel phantomless dual-energy CT post-processing algorithm in comparison with dual-energy X-ray absorptiometry.

BACKGROUND: Current techniques for evaluation of bone mineral density (BMD) commonly require phantom calibration. The purpose of this study was to evaluate a novel algorithm for phantomless in vivo dual-energy computed tomography (DECT)-based assessment of BMD of the lumbar spine in comparison with dual-energy X-ray absorptiometry (DEXA). METHODS: Data from clinically indicated DECT and DEXA examinations within two months comprising the lumbar spine of 47 patients were retrospectively evaluated. By using a novel automated dedicated post-processing algorithm for DECT, the trabecular bone of lumbar vertebrae L1-L4 was selected and analysed. Linear correlation was analysed using Pearson's product-moment correlation coefficient for the comparison of the results from DECT and DEXA. RESULTS: A total of 186 lumbar vertebrae in 47 patients (mean age, 58 years; age range, 24-85 years) were analysed, 24 men (mean age, 55 years; age range, 24-85 years) and 23 women (mean age, 59 years; age range, 31-80 years). Mean BMD of L1-L4 determined with DEXA was 0.985 g/cm2 and 20/47 patients (42.6%) showed an osteoporotic BMD (T score lower than - 2.5) of at least two vertebrae. Average DECT-based BMD of L1-L4 was 86.8 mg/cm3. Regression analysis demonstrated a lack of correlation between DECT- and DEXA-based BMD values with a Pearson's product-moment correlation coefficient r = 0.4205. CONCLUSIONS: Dedicated post-processing of DECT data using a novel algorithm for retrospective phantomless BMD assessment of the trabecular bone of lumbar vertebrae from clinically indicated DECT examinations is feasible.

Efficient Syntheses of Novel Fluoro-Substituted Pentacenes and Azapentacenes: Molecular and Solid-State Properties.

Non-symmetrical 6,13-disubstituted pentacenes bearing trifluoromethyl and aryl substituents have been synthesized starting from pentacenequinone. Diazapentacenes with a variety of fluorine substituents were prepared either via a Hartwig-Buchwald aryl amination route or by a SNAr strategy. As a result of a non-symmetric substitution pattern containing electron-donating substituents in combination with electron-accepting fluorine substituents, the synthesized compounds feature distinct molecular dipoles. All compounds are analyzed regarding their optoelectronic properties in solution with special focus on the frontier orbital energies as well as their molecular packing in the crystal structures. The analyses of isolated molecules are complemented by thin-film studies to examine their solid-state properties. A precise comparison between these and the molecular properties gave detailed insights into the exciton binding energies of these compounds, which are explained by means of a simple model considering the molecular packing and polarizabilities.