Association study of single nucleotide polymorphisms in IL-10 and IL-17 genes with the severity of microbial keratitis

PURPOSE Exploratory analysis to assess the association of single nucleotide polymorphisms (SNPs) in the interleukin (IL) 10 and IL-17 genes with severity of contact lens keratitis. METHODS This was a retrospective case control study of 88 contact lens keratitis cases (25 severe) and 185 healthy contact lens wearers recruited from studies conducted at Moorfields Eye Hospital and in Australia-wide during 2003–2005. Buccal swab samples were collected on Whatman FTA cards and mailed by post for DNA extraction and SNP genotyping. IL-10 (rs1800871; rs1800896; rs1800872) and IL-17 (rs1800871; rs1800896; rs1800872) SNPs were screened by pyrosequencing. Genetic association analyses were performed via Cochran-Armitage trend tests and logistic regression models using PLINK software. RESULTS None of the SNPs tested showed evidence of association with severity of contact lens keratitis at P <  0.05. Nevertheless, minor allele G in SNP rs2397084 of the IL-17F gene was associated with increased risk of severe MK, with OR=2.1 (95% CI=0.9-4.8, P = 0.066). CONCLUSION Our study cannot exclude with confidence that genetic variation in the IL-17 F proinflammatory cytokine is associated with more severe outcomes of MK. However, there is general body of information that the IL-17 pathway is important in the mechanisms of MK. Studies with larger power and the expanded array of laboratory tools will elucidate the exact role of IL-17 in MK

Comparing aerosol number and mass exhalation rates from children and adults during breathing, speaking and singing

Aerosol particles of respirable size are exhaled when individuals breathe, speak and sing and can transmit respiratory pathogens between infected and susceptible individuals. The COVID-19 pandemic has brought into focus the need to improve the quantification of the particle number and mass exhalation rates as one route to provide estimates of viral shedding and the potential risk of transmission of viruses. Most previous studies have reported the number and mass concentrations of aerosol particles in an exhaled plume. We provide a robust assessment of the absolute particle number and mass exhalation rates from measurements of minute ventilation using a non-invasive Vyntus Hans Rudolf mask kit with straps housing a rotating vane spirometer along with measurements of the exhaled particle number concentrations and size distributions. Specifically, we report comparisons of the number and mass exhalation rates for children (12–14 years old) and adults (19–72 years old) when breathing, speaking and singing, which indicate that child and adult cohorts generate similar amounts of aerosol when performing the same activity. Mass exhalation rates are typically 0.002–0.02 ng s−1 from breathing, 0.07–0.2 ng s−1 from speaking (at 70–80 dBA) and 0.1–0.7 ng s−1 from singing (at 70–80 dBA). The aerosol exhalation rate increases with increasing sound volume for both children and adults when both speaking and singing

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Interleukin-6 and Cyclooxygenase-2 downregulation by fatty-acid fractions of Ranunculus constantinopolitanus

<p>Abstract</p> <p>Background</p> <p>Medicinal plants represent alternative means for the treatment of several chronic diseases, including inflammation. The genus <it>Ranunculus</it>, a representative of the Ranunculaceae family, has been reported to possess anti-inflammatory, analgesic, antiviral, antibacterial, antiparasitic and antifungal activities, possibly due to the presence of anemonin and other. Different studies have shown the occurrence of unusual fatty acids (FAs) in Ranunculaceae; however, their therapeutic role has not been investigated. The purpose of this study is to characterize potential anti-inflammatory bioactivities in <it>Ranunculus constantinopolitanus </it>D'Urv., traditionally used in Eastern Mediterranean folk medicine.</p> <p>Methods</p> <p>The aerial part of <it>R. constantinopolitanus </it>was subjected to methanol (MeOH) extraction and solvent fractionation. The bioactive fraction (I.2) was further fractionated using column chromatography, and the biologically active subfraction (Y₂₊₃) was identified using infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS). The effects of I.2 and Y₂₊₃on cell viability were studied in mouse mammary epithelial SCp2 cells using trypan blue exclusion method. To study the anti-inflammatory activities of I.2 and Y₂₊₃, their ability to reduce interleukin (IL)-6 levels was assessed in endotoxin (ET)-stimulated SCp2 cells using enzyme-linked immunosorbent assay (ELISA). In addition, the ability of Y₂₊₃to reduce cyclooxygenase (COX)-2 expression was studied in IL-1-treated mouse intestinal epithelial Mode-K cells via western blotting. Data were analyzed by one-way analysis of variance (ANOVA), Student-Newman-Keuls (SNK), Tukey HSD, two-sample t-test and Dunnett t-tests for multiple comparisons.</p> <p>Results</p> <p>The chloroform fraction (I.2) derived from crude MeOH extract of the plant, in addition to Y₂₊₃, a FA mix isolated from this fraction and containing palmitic acid, C18:2 and C18:1 isomers and stearic acid (1:5:8:1 ratio), reduced ET-induced IL-6 levels in SCp2 cells without affecting cell viability or morphology. When compared to fish oil, conjugated linoleic acid (CLA) and to individual FAs as palmitic, linoleic, oleic and stearic acid or to a mix of these FAs (1:5:8:1 ratio), Y₂₊₃exhibited higher potency in reducing ET-induced IL-6 levels within a shorter period of time. Y₂₊₃ also reduced COX-2 expression in IL-1-treated Mode-K cells.</p> <p>Conclusion</p> <p>Our studies demonstrate the existence of potential anti-inflammatory bioactivities in <it>R. constantinopolitanus </it>and attribute them to a FA mix in this plant.</p

Early maternal mirroring predicts infant motor system activation during facial expression observation.

Processing facial expressions is an essential component of social interaction, especially for preverbal infants. In human adults and monkeys, this process involves the motor system, with a neural matching mechanism believed to couple self- and other-generated facial gestures. Here, we used electroencephalography to demonstrate recruitment of the human motor system during observation and execution of facial expressions in nine-month-old infants, implicating this system in facial expression processing from a very young age. Notably, examination of early video-recorded mother-infant interactions supported the common, but as yet untested, hypothesis that maternal mirroring of infant facial gestures is central to the development of a neural matching mechanism for these gestures. Specifically, the extent to which mothers mirrored infant facial expressions at two months postpartum predicted infant motor system activity during observation of the same expressions at nine months. This suggests that maternal mirroring strengthens mappings between visual and motor representations of facial gestures, which increases infant neural sensitivity to particularly relevant cues in the early social environment

The Faces in Infant-Perspective Scenes Change over the First Year of Life

Mature face perception has its origins in the face experiences of infants. However, little is known about the basic statistics of faces in early visual environments. We used head cameras to capture and analyze over 72,000 infant-perspective scenes from 22 infants aged 1-11 months as they engaged in daily activities. The frequency of faces in these scenes declined markedly with age: for the youngest infants, faces were present 15 minutes in every waking hour but only 5 minutes for the oldest infants. In general, the available faces were well characterized by three properties: (1) they belonged to relatively few individuals; (2) they were close and visually large; and (3) they presented views showing both eyes. These three properties most strongly characterized the face corpora of our youngest infants and constitute environmental constraints on the early development of the visual system

Decoding Face Information in Time, Frequency and Space from Direct Intracranial Recordings of the Human Brain

Faces are processed by a neural system with distributed anatomical components, but the roles of these components remain unclear. A dominant theory of face perception postulates independent representations of invariant aspects of faces (e.g., identity) in ventral temporal cortex including the fusiform gyrus, and changeable aspects of faces (e.g., emotion) in lateral temporal cortex including the superior temporal sulcus. Here we recorded neuronal activity directly from the cortical surface in 9 neurosurgical subjects undergoing epilepsy monitoring while they viewed static and dynamic facial expressions. Applying novel decoding analyses to the power spectrogram of electrocorticograms (ECoG) from over 100 contacts in ventral and lateral temporal cortex, we found better representation of both invariant and changeable aspects of faces in ventral than lateral temporal cortex. Critical information for discriminating faces from geometric patterns was carried by power modulations between 50 to 150 Hz. For both static and dynamic face stimuli, we obtained a higher decoding performance in ventral than lateral temporal cortex. For discriminating fearful from happy expressions, critical information was carried by power modulation between 60–150 Hz and below 30 Hz, and again better decoded in ventral than lateral temporal cortex. Task-relevant attention improved decoding accuracy more than10% across a wide frequency range in ventral but not at all in lateral temporal cortex. Spatial searchlight decoding showed that decoding performance was highest around the middle fusiform gyrus. Finally, we found that the right hemisphere, in general, showed superior decoding to the left hemisphere. Taken together, our results challenge the dominant model for independent face representation of invariant and changeable aspects: information about both face attributes was better decoded from a single region in the middle fusiform gyrus

The role of diet in the aetiopathogenesis of inflammatory bowel disease

Crohn’s disease and ulcerative colitis, collectively known as IBD, are chronic inflammatory disorders of the gastrointestinal tract. Although the aetiopathogenesis of IBD is largely unknown, it is widely thought that diet has a crucial role in the development and progression of IBD. Indeed, epidemiological and genetic association studies have identified a number of promising dietary and genetic risk factors for IBD. These preliminary studies have led to major interest in investigating the complex interaction between diet, host genetics, the gut microbiota and immune function in the pathogenesis of IBD. In this Review, we discuss the recent epidemiological, gene–environment interaction, microbiome and animal studies that have explored the relationship between diet and the risk of IBD. In addition, we highlight the limitations of these prior studies, in part by explaining their contradictory findings, and review future directions

Effects of the total replacement of fish-based diet with plant-based diet on the hepatic transcriptome of two European sea bass (Dicentrarchus labrax) half-sibfamilies showing different growth rates with the plant-based diet

Background: Efforts towards utilisation of diets without fish meal (FM) or fish oil (FO) in finfish aquaculture have been being made for more than two decades. Metabolic responses to substitution of fishery products have been shown to impact growth performance and immune system of fish as well as their subsequent nutritional value, particularly in marine fish species, which exhibit low capacity for biosynthesis of long-chain poly-unsaturated fatty acids (LC-PUFA). The main objective of the present study was to analyse the effects of a plant-based diet on the hepatic transcriptome of European sea bass (Dicentrarchus labrax). Results: We report the first results obtained using a transcriptomic approach on the liver of two half-sibfamilies of the European sea bass that exhibit similar growth rates when fed a fish-based diet (FD), but significantly different growth rates when fed an all-plant diet (VD). Overall gene expression was analysed using oligo DNA microarrays (GPL9663). Statistical analysis identified 582 unique annotated genes differentially expressed between groups of fish fed the two diets, 199 genes regulated by genetic factors, and 72 genes that exhibited diet-family interactions. The expression of several genes involved in the LC-PUFA and cholesterol biosynthetic pathways was found to be up-regulated in fish fed VD, suggesting a stimulation of the lipogenic pathways. No significant diet-family interaction for the regulation of LC-PUFA biosynthesis pathways could be detected by microarray analysis. This result was in agreement with LC-PUFA profiles, which were found to be similar in the flesh of the two half-sibfamilies. In addition, the combination of our transcriptomic data with an analysis of plasmatic immune parameters revealed a stimulation of complement activity associated with an immunodeficiency in the fish fed VD, and different inflammatory status between the two half-sibfamilies. Biological processes related to protein catabolism, amino acid transaminations, RNA splicing and blood coagulation were also found to be regulated by diet, while the expression of genes involved in protein and ATP synthesis differed between the half-sibfamilies. Conclusions: Overall, the combined gene expression, compositional and biochemical studies demonstrated a large panel of metabolic and physiological effects induced by total substitution of both FM and FO in the diets of European sea bass and revealed physiological characteristics associated with the two half-sibfamilies