Mathematics of Gravitational Lensing: Multiple Imaging and Magnification

The mathematical theory of gravitational lensing has revealed many generic and global properties. Beginning with multiple imaging, we review Morse-theoretic image counting formulas and lower bound results, and complex-algebraic upper bounds in the case of single and multiple lens planes. We discuss recent advances in the mathematics of stochastic lensing, discussing a general formula for the global expected number of minimum lensed images as well as asymptotic formulas for the probability densities of the microlensing random time delay functions, random lensing maps, and random shear, and an asymptotic expression for the global expected number of micro-minima. Multiple imaging in optical geometry and a spacetime setting are treated. We review global magnification relation results for model-dependent scenarios and cover recent developments on universal local magnification relations for higher order caustics.Comment: 25 pages, 4 figures. Invited review submitted for special issue of General Relativity and Gravitatio

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

MiR-205 hinders the malignant interplay between prostate cancer cells and associated fibroblasts

Aims: Tumor microenvironment is a strong determinant for the acquisition of metastatic potential of cancer cells. We have recently demonstrated that cancer-associated fibroblasts (CAFs) elicit a redox-dependent epithelial-mesenchymal transition (EMT) in prostate cancer (PCa) cells, driven by cycloxygenase-2/hypoxia-inducible factor-1 (HIF-1)/nuclear factor-\u3baB pathway and enhancing tumor aggressiveness. Here, we investigated the involvement of microRNAs (miRNAs) in tumor-stroma interplay to identify possible tools to counteract oxidative stress and metastasis dissemination. Results: We found that miR-205 is the most downmodulated miRNA in PCa cells upon CAF stimulation, due to direct transcriptional repression by HIF-1, a known redox-sensitive transcription factor. Rescue experiments demonstrated that ectopic miR-205 overexpression in PCa cells counteracts CAF-induced EMT, thus impairing enhancement of cell invasion, acquisition of stem cell traits, tumorigenicity, and metastatic dissemination. In addition, miR-205 blocks tumor-driven activation of surrounding fibroblasts by reducing pro-inflammatory cytokine secretion. Innovation: Overall, such findings suggest miR-205 as a brake against PCa metastasis by blocking both the afferent and efferent arms of the circuit between tumor cells and associated fibroblasts, thus interrupting the pro-oxidant and pro-inflammatory circuitries engaged by reactive stroma. Conclusion: The evidence that miR-205 replacement in PCa cells is able not only to prevent but also to revert the oxidative/pro-inflammatory axis leading to EMT induced by CAFs sets the rationale for developing miRNA-based approaches to prevent and treat metastatic disease. Antioxid. Redox Signal. 20, 1045\u20131059

Nucleolar organizing regions in some species of neotropical cichlid fish (Pisces, perciformes)

In the present study, 10 neotropical species of family Cichlidae (Pisces, Perciformes) were submitted to analysis of the nucleolar organizing regions (NORs). In 8 of these species, the NORs were located in the first pair in the complement and coincided with the secondary constrictions observed there, whereas in Cichlasoma facetum and Geophagus brasiliensis the NORs were located in another chromosome pair. The possibility that the predominant location of NORs in the 1st pair in the karyotype indicates a more primitive condition of this group of fish is discussed. Variations in NOR size between homologous chromosomes of some species were also observed. © 1985 Taylor & Francis Group, LLC

Challenges in developing a consensus definition of neonatal sepsis.

Sepsis remains a leading cause of morbidity and mortality in the neonatal population, and at present, there is no unified definition of neonatal sepsis. Existing consensus sepsis definitions within paediatrics are not suited for use in the NICU and do not address sepsis in the premature population. Many neonatal research and surveillance networks have criteria for the definition of sepsis within their publications though these vary greatly and there is typically a heavy emphasis on microbiological culture. The concept of organ dysfunction as a diagnostic criterion for sepsis is rarely considered in neonatal literature, and it remains unclear how to most accurately screen neonates for organ dysfunction. Accurately defining and screening for sepsis is important for clinical management, health service design and future research. The progress made by the Sepsis-3 group provides a roadmap of how definitions and screening criteria may be developed. Similar initiatives in neonatology are likely to be more challenging and would need to account for the unique presentation of sepsis in term and premature neonates. The outputs of similar consensus work within neonatology should be twofold: a validated definition of neonatal sepsis and screening criteria to identify at-risk patients earlier in their clinical course. IMPACT: There is currently no consensus definition of neonatal sepsis and the definitions that are currently in use are varied.A consensus definition of neonatal sepsis would benefit clinicians, patients and researchers.Recent progress in adults with publication of Sepsis-3 provides guidance on how a consensus definition and screening criteria for sepsis could be produced in neonatology.We discuss common themes and potential shortcomings in sepsis definitions within neonatology.We highlight the need for a consensus definition of neonatal sepsis and the challenges that this task poses