Graph-theoretic approach and sound engineering principles for design of district metered areas

Copyright © 2014 American Society of Civil EngineersThe design of district metered areas (DMAs) in existing water distribution networks, especially in urban areas, involves a high number of decision variables, and the effects of implementing them in districts have to be evaluated in order not to affect the quality of the service to customers. A new methodology for designing a given number of districts in looped water distribution networks is proposed here. It is based on graph theory and takes into account some important DMA design criteria: the maximum and minimum size recommended for a district, the connectedness of each district to the water supply source, and the absence of links between the districts. Therefore, it allows the creation of DMAs that are independent from each other. A recursive bisection procedure has been applied to create districts, while an algorithm for graph traversal has been used to verify whether each district can be reached from the water source and connectivity between the nodes. The successful application of the proposed methodology to a case study has proven its effectiveness for district metered areas design in real urban water distribution networks

CXCR3, CXCR5, CXCR6, and CXCR7 in Diabetes

Many studies have suggested that CXCR3, CXCR5, CXCR6 and CXCR7 chemokine receptors are determinant in type 1 diabetes (T1D), expecially in autoimmunity and β-cell destruction. In particular circulating CXCL10 level (the ligand of CXCR3) is high in T1D patients, and this suggests that CXCL10 may be a candidate for a predictive marker of T1D. Blocking the CXCL10/CXCR3 axis in newly onset of diabetes seems to be a potential strategy for the therapy of T1D. Attempts have been done in modulating or blocking CXCR5, CXCR6 and CXCR7 chemokine receptors in experimental settings of T1D. More researches are necessary to evaluate the interplay among cytokines, chemokines and the pathogenesis and therapy of T1D

Ancient mitochondrial and modern whole genomes unravel massive genetic diversity loss during near extinction of Alpine ibex

Population bottlenecks can have dramatic consequences for the health and long-term survival of a species. Understanding of historic population size and standing genetic variation prior to a contraction allows estimating the impact of a bottleneck on the species' genetic diversity. Although historic population sizes can be modelled based on extant genomics, uncertainty is high for the last 10–20 millenia. Hence, integrating ancient genomes provides a powerful complement to retrace the evolution of genetic diversity through population fluctuations. Here, we recover 15 high-quality mitogenomes of the once nearly extinct Alpine ibex spanning 8601 BP to 1919 CE and combine these with 60 published modern whole genomes. Coalescent demography simulations based on modern whole genomes indicate population fluctuations coinciding with the last major glaciation period. Using our ancient and historic mitogenomes, we investigate the more recent demographic history of the species and show that mitochondrial haplotype diversity was reduced to a fifth of the prebottleneck diversity with several highly differentiated mitochondrial lineages having coexisted historically. The main collapse of mitochondrial diversity coincides with elevated human population growth during the last 1–2 kya. After recovery, one lineage was spread and nearly fixed across the Alps due to recolonization efforts. Our study highlights that a combined approach integrating genomic data of ancient, historic and extant populations unravels major long-term population fluctuations from the emergence of a species through its near extinction up to the recent past

Differential modulation by vanadium pentoxide of the secretion of CXCL8 and CXCL11 chemokines in thyroid cells

Recently it has been hypothesized that vanadium serves a carcinogenic role in the thyroid. However, to date, no in vivo or in vitro studies have evaluated thyroid disruption in humans and/or animals following exposure to vanadium. The present study evaluated the effect of vanadium pentoxide (V2O5) on cell viability and proliferation, and chemokine (C-X-C motif) ligand (CXCL)8 and CXCL11 secretion in normal thyrocytes. The results demonstrated that V2O5had no effect on thyroid follicular cell viability and proliferation. However, V2O5was able to induce the secretion of CXCL8 and CXCL11 chemokines from thyrocytes. Notably, V2O5synergistically increased the effect of the interferon (IFN)-γ on CXCL11 secretion. In addition, V2O5synergistically increased the effect of tumor necrosis factor-alpha; on CXCL8 secretion, and abolished the inhibitory effect of IFN-γ. Overall this induction of CXCL8 and CXCL11 secretion may lead to the induction and perpetuation of an inflammatory reaction in the thyroid. Further studies are now required to evaluate thyroid function and nodule development in subjects who are occupationally exposed, or living in polluted areas

Antimicrobial peptides active in in vitro models of endodontic bacterial infections modulate inflammation in human cardiac fibroblasts

Endodontic and periodontal disease are conditions of infectious origin that can lead to tooth loss or develop into systemic hyperinflammation, which may be associated with a wide variety of diseases, including cardiovascular. Endodontic and periodontal treatment often relies on antibiotics. Since new antimicrobial resistances are a major threat, the use of standard antibiotics is not recommended when the infection is only local. Antimicrobial peptides were recently demonstrated to be valid alternatives for dental treatments. The antimicrobial peptide M33D is a tetrabranched peptide active against Gram-negative and Gram-positive bacteria. It has a long life, unusual for peptides, because its branched form provides resistance to proteases. Here the efficacy of M33D and of its analog M33i/l as antibiotics for local use in dentistry was evaluated. M33D and M33i/l were active against reference strains and multidrug-resistant clinical isolates of Gram-negative and Gram-positive species. Their minimum inhibitory concentration against different strains of dental interest was between 0.4 and 6.0 mu M. Both peptides acted rapidly on bacteria, impairing membrane function. They also disrupted biofilm effectively. Disinfection of the root canal is crucial for endodontic treatments. M33D and M33i/l reduced E. faecalis colonies to one-twentieth in a dentin slices model reproducing root canal irrigation. They both captured and neutralized lipopolysaccharide (LPS), a bacterial toxin responsible for inflammation. The release of IL-1 beta and TNF alpha by LPS-stimulated murine macrophages was reduced by both peptides. Human cardiac fibroblasts respond to different insults with the release of proinflammatory cytokines, and consequently, they are considered directly involved in atherogenic cardiovascular processes, including those triggered by infections. The presence of M33D and M33i/l at MIC concentration reduced IL6 release from LPS- stimulated human cardiac fibroblasts, hence proving to be promising in preventing bacteria-induced atherogenesis. The two peptides showed low toxicity to mammalian cells, with an EC50 one order of magnitude higher than the average MIC and low hemolytic activity. The development of antimicrobial peptides for dental irrigations and medication is a very promising new field of research that will provide tools to fight dental infections and their severe consequences, while at the same time protecting standard antibiotics from new outbreaks of antimicrobial resistance. © 2022 by the authors

An accurate assignment test for extremely low-coverage whole-genome sequence data.

Genomic assignment tests can provide important diagnostic biological characteristics, such as population of origin or ecotype. Yet, assignment tests often rely on moderate- to high-coverage sequence data that can be difficult to obtain for fields such as molecular ecology and ancient DNA. We have developed a novel approach that efficiently assigns biologically relevant information (i.e., population identity or structural variants such as inversions) in extremely low-coverage sequence data. First, we generate databases from existing reference data using a subset of diagnostic single nucleotide polymorphisms (SNPs) associated with a biological characteristic. Low-coverage alignment files are subsequently compared to these databases to ascertain allelic state, yielding a joint probability for each association. To assess the efficacy of this approach, we assigned haplotypes and population identity in Heliconius butterflies, Atlantic herring, and Atlantic cod using chromosomal inversion sites and whole-genome data. We scored both modern and ancient specimens, including the first whole-genome sequence data recovered from ancient Atlantic herring bones. The method accurately assigns biological characteristics, including population membership, using extremely low-coverage data (as low as 0.0001x) based on genome-wide SNPs. This approach will therefore increase the number of samples in evolutionary, ecological and archaeological research for which relevant biological information can be obtained

Human neural stem cell transplantation in ALS: initial results from a phase I trial

We report the initial results from a phase I clinical trial for ALS. We transplanted GMP-grade, fetal human neural stem cells from natural in utero death (hNSCs) into the anterior horns of the spinal cord to test for the safety of both cells and neurosurgical procedures in these patients. The trial was approved by the Istituto Superiore di Sanit\ue0 and the competent Ethics Committees and was monitored by an external Safety Board

Ancient DNA evidence for the ecological globalization of cod fishing in medieval and post-medieval Europe

Understanding the historical emergence and growth of long-range fisheries can provide fundamental insights into the timing of ecological impacts and the development of coastal communities during the last millennium. Whole-genome sequencing approaches can improve such understanding by determining the origin of archaeological fish specimens that may have been obtained from historic trade or distant water. Here, we used genome-wide data to individually infer the biological source of 37 ancient Atlantic cod specimens (ca 1050-1950 CE) from England and Spain. Our findings provide novel genetic evidence that eleventh- to twelfth-century specimens from London were predominantly obtained from nearby populations, while thirteenth- to fourteenth-century specimens were derived from distant sources. Our results further suggest that Icelandic cod was indeed exported to London earlier than previously reported. Our observations confirm the chronology and geography of the trans-Atlantic cod trade from Newfoundland to Spain starting by the early sixteenth century. Our findings demonstrate the utility of whole-genome sequencing and ancient DNA approaches to describe the globalization of marine fisheries and increase our understanding regarding the extent of the North Atlantic fish trade and long-range fisheries in medieval and early modern time

Developing the Protocol Infrastructure for DNA Sequencing Natural History Collections

Intentionally preserved biological material in natural history collections represents a vast repository of biodiversity. Advances in laboratory and sequencing technologies have made these specimens increasingly accessible for genomic analyses, offering a window into the genetic past of species and often permitting access to information that can no longer be sampled in the wild. Due to their age, preparation and storage conditions, DNA retrieved from museum and herbarium specimens is often poor in yield, heavily fragmented and biochemically modified. This not only poses methodological challenges in recovering nucleotide sequences, but also makes such investigations susceptible to environmental and laboratory contamination. In this paper, we review the practical challenges associated with making the recovery of DNA sequence data from museum collections more routine. We first review key operational principles and issues to address, to guide the decision-making process and dialogue between researchers and curators about when and how to sample museum specimens for genomic analyses. We then outline the range of steps that can be taken to reduce the likelihood of contamination including laboratory set-ups, workflows and working practices. We finish by presenting a series of case studies, each focusing on protocol practicalities for the application of different mainstream methodologies to museum specimens including: (i) shotgun sequencing of insect mitogenomes, (ii) whole genome sequencing of insects, (iii) genome skimming to recover plant plastid genomes from herbarium specimens, (iv) target capture of multi-locus nuclear sequences from herbarium specimens, (v) RAD-sequencing of bird specimens and (vi) shotgun sequencing of ancient bovid bone samples