Interleukin-22 signaling attenuates necrotizing enterocolitis by promoting epithelial cell regeneration

Necrotizing enterocolitis (NEC) is a deadly intestinal inflammatory disorder that primarily affects premature infants and lacks adequate therapeutics. Interleukin (IL)-22 plays a critical role in gut barrier maintenance, promoting epithelial regeneration, and controlling intestinal inflammation in adult animal models. However, the importance of IL-22 signaling in neonates during NEC remains unknown. We investigated the role of IL-22 in the neonatal intestine under homeostatic and inflammatory conditions by using a mouse model of NEC. Our data reveal tha

Heterogeneous nuclear ribonucleoprotein K is over expressed, aberrantly localised and is associated with poor prognosis in colorectal cancer

Heterogeneous ribonucleoprotein K (hnRNP K) is a member of the hnRNP family which has several different cellular roles including transcription, mRNA shuttling, RNA editing and translation. Several reports implicate hnRNP K having a role in tumorigenesis, for instance hnRNP K increases transcription of the oncogene c-myc and hnRNP K expression is regulated by the p53/MDM 2 pathway. In this study comparing normal colon to colorectal cancer by proteomics, hnRNP K was identified as being overexpressed in this type of cancer. Immunohistochemistry with a monoclonal antibody to hnRNP K (which we developed) on colorectal cancer tissue microarray, confirmed that hnRNP K was overexpressed in colorectal cancer (P<0.001) and also showed that hnRNP K had an aberrant subcellular localisation in cancer cells. In normal colon hnRNP K was exclusively nuclear whereas in colorectal cancer the protein localised both in the cytoplasm and the nucleus. There were significant increases in both nuclear (P=0.007) and cytoplasmic (P=0.001) expression of hnRNP K in Dukes C tumours compared with early stage tumours. In Dukes C patient's good survival was associated with increased hnRNP K nuclear expression (P=0.0093). To elaborate on the recent observation that hnRNP K is regulated by p53, the expression profiles of these two proteins were also analysed. There was no correlation between hnRNP K and p53 expression, however, patients who presented tumours that were positive for hnRNP K and p53 had a poorer survival outcome (P=0.045)

Continued Neurogenesis in Adult Drosophila as a Mechanism for Recruiting Environmental Cue-Dependent Variants

Background The skills used by winged insects to explore their environment are strongly dependent upon the integration of neurosensory information comprising visual, acoustic and olfactory signals. The neuronal architecture of the wing contains a vast array of different sensors which might convey information to the brain in order to guide the trajectories during flight. In Drosophila, the wing sensory cells are either chemoreceptors or mechanoreceptors and some of these sensors have as yet unknown functions. The axons of these two functionally distinct types of neurons are entangled, generating a single nerve. This simple and accessible coincidental signaling circuitry in Drosophila constitutes an excellent model system to investigate the developmental variability in relation to natural behavioral polymorphisms. Methodology/Principal Findings A fluorescent marker was generated in neurons at all stages of the Drosophila life cycle using a highly efficient and controlled genetic recombination system that can be induced in dividing precursor cells (MARCM system, flybase web site). It allows fluorescent signals in axons only when the neuroblasts and/or neuronal cell precursors like SOP (sensory organ precursors) undergo division during the precedent steps. We first show that a robust neurogenesis continues in the wing after the adults emerge from the pupae followed by an extensive axonal growth. Arguments are presented to suggest that this wing neurogenesis in the newborn adult flies was influenced by genetic determinants such as the frequency dependent for gene and by environmental cues such as population density. Conclusions We demonstrate that the neuronal architecture in the adult Drosophila wing is unfinished when the flies emerge from their pupae. This unexpected developmental step might be crucial for generating non-heritable variants and phenotypic plasticity. This might therefore constitute an advantage in an unstable ecological system and explain much regarding the ability of Drosophila to robustly adapt to their environment

Trade-Off between Toxicity and Signal Detection Orchestrated by Frequency- and Density-Dependent Genes

Behaviors in insects are partly highly efficient Bayesian processes that fulfill exploratory tasks ending with the colonization of new ecological niches. The foraging (for) gene in Drosophila encodes a cGMP-dependent protein kinase (PKG). It has been extensively described as a frequency-dependent gene and its transcripts are differentially expressed between individuals, reflecting the population density context. Some for transcripts, when expressed in a population at high density for many generations, concomitantly trigger strong dispersive behavior associated with foraging activity. Moreover, genotype-by-environment interaction (GEI) analysis has highlighted a dormant role of for in energetic metabolism in a food deprivation context. In our current report, we show that alleles of for encoding different cGMP-dependent kinase isoforms influence the oxidation of aldehyde groups of aromatic molecules emitted by plants via Aldh-III and a phosphorylatable adaptor. The enhanced efficiency of oxidation of aldehyde odorants into carboxyl groups by the action of for lessens their action and toxicity, which should facilitate exploration and guidance in a complex odor environment. Our present data provide evidence that optimal foraging performance requires the fast metabolism of volatile compounds emitted by plants to avoid neurosensory saturation and that the frequency-dependent genes that trigger dispersion influence these processes

Engrailed-2 (EN2) - a novel biomarker in epithelial ovarian cancer

YesBackground: Epithelial ovarian cancer is a common malignancy, with no clinically approved diagnostic biomarker. Engrailed-2 (EN2) is a homeodomain-containing transcription factor, essential during embryological neural development, which is dysregulated in several cancer types. We evaluated the expression of EN2 in Epithelial ovarian cancer, and reviewed its role as a biomarker. Methods: We evaluated 8 Epithelial ovarian cancer cell lines, along with > 100 surgical specimens from the Royal Surrey County Hospital (2009–2014). In total, 108 tumours and 5 normal tissue specimens were collected. En2 mRNA was evaluated by semi-quantitative RT-PCR. Histological sub-type, and platinum-sensitive/−resistant status were compared. Protein expression was assessed in cell lines (immunofluorescence), and in > 150 tumours (immunohistochemistry). Results: En2 mRNA expression was elevated in serous ovarian tumours compared with normal ovary (p < 0.001), particularly in high-grade serous ovarian cancer (p < 0.0001) and in platinum-resistant tumours (p = 0.0232). Median Overall Survival and Progression-free Survival were reduced with high En2 expression (OS = 28 vs 42 months, p = 0.0329; PFS = 8 vs 27 months; p = 0.0004). Positive cytoplasmic EN2 staining was demonstrated in 78% of Epithelial ovarian cancers, with absence in normal ovary. EN2 positive high-grade serous ovarian cancer patients had a shorter PFS (10 vs 17.5 months; p = 0.0103). Conclusion: The EN2 transcription factor is a novel ovarian cancer biomarker. It demonstrates prognostic value, correlating with worse Overall Survival and Progression-free Survival. It is hoped that further work will validate its use as a biomarker, and provide insight into the role of EN2 in the development, progression and spread of ovarian cancer.Oncology Research and Development Departments at the Royal Surrey County Hospital and the University of Surre

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS