Galacto-Oligosaccharides Modulate the Juvenile Gut Microbiome and Innate Immunity To Improve Broiler Chicken Performance

Copyright © 2020 Richards et al Improvements in growth performance and health are key goals in broiler chicken production. Inclusion of prebiotic galacto-oligosaccharides (GOS) in broiler feed enhanced the growth rate and feed conversion of chickens relative to those obtained with a calorie-matched control diet. Comparison of the cecal microbiota identified key differences in abundances of Lactobacillus spp. Increased levels of Lactobacillus johnsonii in GOS-fed juvenile birds at the expense of Lactobacillus crispatus were linked to improved performance (growth rate and market weight). Investigation of the innate immune responses highlighted increases of ileal and cecal interleukin-17A (IL-17A) gene expression counterposed to a decrease in IL-10. Quantification of the autochthonous Lactobacillus spp. revealed a correlation between bird performance and L. johnsonii abundance. Shifts in the cecal populations of key Lactobacillus spp. of juvenile birds primed intestinal innate immunity without harmful pathogen challenge. IMPORTANCE Improvements in the growth rate of broiler chickens can be achieved through dietary manipulation of the naturally occurring bacterial populations while mitigating the withdrawal of antibiotic growth promoters. Prebiotic galactooligosaccharides (GOS) are manufactured as a by-product of dairy cheese production and can be incorporated into the diets of juvenile chickens to improve their health and performance. This study investigated the key mechanisms behind this progression and pinpointed L. johnsonii as a key species that facilitates the enhancements in growth rate and gut health. The study identified the relationships between the GOS diet, L. johnsonii intestinal populations, and cytokine immune effectors to improve growth

Phage Biocontrol of Campylobacter jejuni in Chickens Does Not Produce Collateral Effects on the Gut Microbiota

Bacteriophage biocontrol to reduce Campylobacter jejuni levels in chickens can reduce human exposure and disease acquired through the consumption of contaminated poultry products. Investigating changes in the chicken microbiota during phage treatment has not previously been undertaken but is crucial to understanding the system-wide effects of such treatments to establish a sustainable application. A phage cocktail containing two virulent Campylobacter phages was used to treat broiler chickens colonized with C. jejuni HPC5. Campylobacter counts from cecal contents were significantly reduced throughout the experimental period but were most effective 2 days post-treatment showing a reduction of 2.4 log10 CFU g-1 relative to mock-treated Campylobacter colonized controls. The administered phages replicated in vivo to establish stable populations. Bacteriophage predation of C. jejuni was not found to affect the microbiota structure but selectively reduced the relative abundance of C. jejuni without affecting other bacteria

An automated fitting procedure and software for dose-response curves with multiphasic features.

In cancer pharmacology (and many other areas), most dose-response curves are satisfactorily described by a classical Hill equation (i.e. 4 parameters logistical). Nevertheless, there are instances where the marked presence of more than one point of inflection, or the presence of combined agonist and antagonist effects, prevents straight-forward modelling of the data via a standard Hill equation. Here we propose a modified model and automated fitting procedure to describe dose-response curves with multiphasic features. The resulting general model enables interpreting each phase of the dose-response as an independent dose-dependent process. We developed an algorithm which automatically generates and ranks dose-response models with varying degrees of multiphasic features. The algorithm was implemented in new freely available Dr Fit software (sourceforge.net/projects/drfit/). We show how our approach is successful in describing dose-response curves with multiphasic features. Additionally, we analysed a large cancer cell viability screen involving 11650 dose-response curves. Based on our algorithm, we found that 28% of cases were better described by a multiphasic model than by the Hill model. We thus provide a robust approach to fit dose-response curves with various degrees of complexity, which, together with the provided software implementation, should enable a wide audience to easily process their own data.This work was funded by Cancer Research UK grant C14303/A17197.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/srep1470

Experimental validation of a modeling framework for upconversion enhancement in 1D-photonic crystals

Photonic structures can be designed to tailor luminescence properties of materials, which becomes particularly interesting for non-linear phenomena, such as photon upconversion. However, there is no adequate theoretical framework to optimize photonic structure designs for upconversion enhancement. Here, we present a comprehensive theoretical model describing photonic effects on upconversion and confirm the model’s predictions by experimental realization of 1D-photonic upconverter devices with large statistics and parameter scans. The measured upconversion photoluminescence enhancement reaches 82 ± 24% of the simulated enhancement, in the mean of 2480 separate measurements, scanning the irradiance and the excitation wavelength on 40 different sample designs. Additionally, the trends expected from the modeled interaction of photonic energy density enhancement, local density of optical states and internal upconversion dynamics, are clearly validated in all experimentally performed parameter scans. Our simulation tool now opens the possibility of precisely designing photonic structure designs for various upconverting materials and applications

Quantifying the Detrimental Impacts of Land-Use and Management Change on European Forest Bird Populations

The ecological impacts of changing forest management practices in Europe are poorly understood despite European forests being highly managed. Furthermore, the effects of potential drivers of forest biodiversity decline are rarely considered in concert, thus limiting effective conservation or sustainable forest management. We present a trait-based framework that we use to assess the detrimental impact of multiple land-use and management changes in forests on bird populations across Europe. Major changes to forest habitats occurring in recent decades, and their impact on resource availability for birds were identified. Risk associated with these changes for 52 species of forest birds, defined as the proportion of each species' key resources detrimentally affected through changes in abundance and/or availability, was quantified and compared to their pan-European population growth rates between 1980 and 2009. Relationships between risk and population growth were found to be significantly negative, indicating that resource loss in European forests is an important driver of decline for both resident and migrant birds. Our results demonstrate that coarse quantification of resource use and ecological change can be valuable in understanding causes of biodiversity decline, and thus in informing conservation strategy and policy. Such an approach has good potential to be extended for predictive use in assessing the impact of possible future changes to forest management and to develop more precise indicators of forest health

The Effects of Structural Alterations in the Polyamine and Amino Acid Moieties of Philanthotoxins on Nicotinic Acetylcholine Receptor Inhibition in the Locust, Schistocerca gregaria

Alterations in the polyamine and amino acid (tyrosine) moieties of philanthotoxin‐343 (PhTX‐343) were investigated for their effects on the antagonism of nicotinic acetylcholine receptors (nAChRs) isolated from the locust (Schistocerca gregaria) mushroom body. Through whole‐cell patch‐clamp recordings, the philanthotoxin analogues in this study were shown to cause inhibition of the inward current when co‐applied with acetylcholine (ACh). PhTX‐343 (IC50 = 0.80 μM at −75 mV) antagonised locust nAChRs in a use‐dependent manner, suggesting that it acts as an open-channel blocker. The analogue in which both the secondary amine functionalities were replaced with methylene groups (i.e., PhTX‐12) was ~6‐fold more potent (IC50 (half‐maximal inhibitory con-centration) = 0.13 μM at −75 mV) than PhTX‐343. The analogue containing cyclohexylalanine as a substitute for the tyrosine moiety of PhTX‐343 (i.e., Cha‐PhTX‐343) was also more potent (IC50 = 0.44 μM at −75 mV). A combination of both alterations to PhTX‐343 generated the most potent analogue, i.e., Cha‐PhTX‐12 (IC50 = 1.71 nM at −75 mV). Modulation by PhTX‐343 and Cha‐PhTX‐343 fell into two distinct groups, indicating the presence of two pharmacologically distinct nAChR groups in the locust mushroom body. In the first group, all concentrations of PhTX‐343 and Cha‐PhTX‐343 inhibited responses to ACh. In the second group, application of PhTX‐343 or Cha‐PhTX‐343 at concentrations ≤100 nM caused potentiation, while concentrations ≥1 μM inhibited responses to ACh. Cha‐PhTX‐12 may have potential to be developed into insecticidal compounds with a novel mode of action

Diminished Neural and Cognitive Responses to Facial Expressions of Disgust in Patients with Psoriasis: A Functional Magnetic Resonance Imaging Study

Psoriasis produces significant psychosocial disability; however, little is understood about the neurocognitive mechanisms that mediate the adverse consequences of the social stigma associated with visible skin lesions, such as disgusted facial expressions of others. Both the feeling of disgust and the observation of disgust in others are known to activate the insula cortex. We investigated whether the social impact of psoriasis is associated with altered cognitive processing of disgust using (i) a covert recognition of faces task conducted using functional magnetic resonance imaging (fMRI) and (ii) the facial expression recognition task (FERT), a decision-making task, conducted outside the scanner to assess the ability to recognize overtly different intensities of disgust. Thirteen right-handed male patients with psoriasis and 13 age-matched male controls were included. In the fMRI study, psoriasis patients had significantly (P<0.005) smaller signal responses to disgusted faces in the bilateral insular cortex compared with healthy controls. These data were corroborated by FERT, in that patients were less able than controls to identify all intensities of disgust tested. We hypothesize that patients with psoriasis, in this case male patients, develop a coping mechanism to protect them from stressful emotional responses by blocking the processing of disgusted facial expressions

GLP-1 action in the mouse bed nucleus of the stria terminalis

Glucagon-like peptide-1 (GLP-1) injected into the brain reduces food intake. Similarly, activation of preproglucagon (PPG) cells in the hindbrain which synthesize GLP-1, reduces food intake. However, it is far from clear whether this happens because of satiety, nausea, reduced reward, or even stress. Here we explore the role of the bed nucleus of the stria terminalis (BNST), an area involved in feeding control as well as stress responses, in GLP-1 responses. Using cre-expressing mice we visualized projections of NTS PPG neurons and GLP-1R-expressing BNST cells with AAV-driven Channelrhodopsin-YFP expression. The BNST displayed many varicose YFP+ PPG axons in the ventral and less in the dorsal regions. Mice which express RFP in GLP-1R neurons had RFP+ cells throughout the BNST with the highest density in the dorsal part, suggesting that PPG neuron-derived GLP-1 acts in the BNST. Indeed, injection of GLP-1 into the BNST reduced chow intake during the dark phase, whereas injection of the GLP-1 receptor antagonist Ex9 increased feeding. BNST-specific GLP-1-induced food suppression was less effective in mice on high fat (HF, 60%) diet, and Ex9 had no effect. Restraint stress-induced hypophagia was attenuated by BNST Ex9 treatment, further supporting a role for endogenous brain GLP-1. Finally, whole-cell patch clamp recordings of RFP+ BNST neurons demonstrated that GLP-1 elicited either a depolarizing or hyperpolarizing reversible response that was of opposite polarity to that under dopamine. Our data support a physiological role for BNST GLP-1R in feeding, and suggest complex cellular responses to GLP-1 in this nucleus

The Formaldehyde Masers in NGC 7538 and G29.96-0.02: VLBA, MERLIN, and VLA Observations

The 6 cm formaldehyde (H2CO) maser sources in the compact HII regions NGC 7538-IRS1 and G29.96-0.02 have been imaged at high resolution (beams < 50 mas). Using the VLBA and MERLIN, we find the angular sizes of the NGC 7538 masers to be ~10 mas (30 AU) corresponding to brightness temperatures ~10^8 K. The angular sizes of the G29.96-0.02 masers are ~20 mas (130 AU) corresponding to brightness temperatures ~10^7 K. Using the VLA, we detect 2 cm formaldehyde absorption from the maser regions. We detect no emission in the 2 cm line, indicating the lack of a 2 cm maser and placing limits on the 6 cm excitation process. We find that both NGC 7538 maser components show an increase in intensity on 5-10 year timescales while the G29.96-0.02 masers show no variability over 2 years. A search for polarization provides 3-sigma upper limits of 1% circularly polarized and 10% linearly polarized emission in NGC 7538 and of 15% circularly polarized emission in G29.96-0.02. A pronounced velocity gradient of 28 km/s/arcsecond (1900 km/s/pc) is detected in the NGC 7538 maser gas.Comment: accepted to ApJ, 15 figures, 11 table