Long-Term Recovery After Endothelial Colony-Forming Cells or Human Umbilical Cord Blood Cells Administration in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy.

Neonatal hypoxic-ischemic encephalopathy (NHIE) is a dramatic perinatal complication, associated with poor neurological prognosis despite neuroprotection by therapeutic hypothermia, in the absence of an available curative therapy. We evaluated and compared ready-to-use human umbilical cord blood cells (HUCBC) and bankable but allogeneic endothelial progenitors (ECFC) as cell therapy candidate for NHIE. We compared benefits of HUCBC and ECFC transplantation 48 hours after injury in male rat NHIE model, based on the Rice-Vannucci approach. Based on behavioral tests, immune-histological assessment and metabolic imaging of brain perfusion using single photon emission computed tomography (SPECT), HUCBC, or ECFC administration provided equally early and sustained functional benefits, up to 8 weeks after injury. These results were associated with total normalization of injured hemisphere cerebral blood flow assessed by SPECT/CT imaging. In conclusion, even if ECFC represent an efficient candidate, HUCBC autologous criteria and easier availability make them the ideal candidate for hypoxic-ischemic cell therapy. Stem Cells Translational Medicine 2017;6:1987-1996

A grid-based infrastructure for distributed retrieval

In large-scale distributed retrieval, challenges of latency, heterogeneity, and dynamicity emphasise the importance of infrastructural support in reducing the development costs of state-of-the-art solutions. We present a service-based infrastructure for distributed retrieval which blends middleware facilities and a design framework to ‘lift’ the resource sharing approach and the computational services of a European Grid platform into the domain of e-Science applications. In this paper, we give an overview of the DILIGENT Search Framework and illustrate its exploitation in the field of Earth Science

Neonatal high protein intake enhances neonatal growth without significant adverse renal effects in spontaneous IUGR piglets.

In humans, early high protein (HP) intake has been recommended to prevent postnatal growth restriction and complications of intrauterine growth restriction (IUGR). However, the impact of such a strategy on the kidneys remains unknown, while significant renal hypertrophy, proteinuria, and glomerular sclerosis have been demonstrated in few experimental studies. The objective of this study was to evaluate the effects of a neonatal HP formula on renal structure in IUGR piglets. Spontaneous IUGR piglets were randomly allocated to normal protein (NP, javax.xml.bind.JAXBElement@68d5845e  = 10) formula or to HP formula (+50% protein content, javax.xml.bind.JAXBElement@3e768c15  = 10) up to day 28 after birth. Body weight, body composition, renal functions, and structure were assessed at the end of the neonatal period. While birth weights were similar, 28-day-old HP piglets were 18% heavier than NP piglets ( javax.xml.bind.JAXBElement@206b72ec < javax.xml.bind.JAXBElement@7f241a6d 0.01). Carcass protein content was 22% higher in HP than in NP offspring ( javax.xml.bind.JAXBElement@3b9786a3 < javax.xml.bind.JAXBElement@318ba3e0 0.01). Despite a HP intake, kidney weight and glomerular fibrosis were unaltered in HP piglets. Only a 20% increase in glomerular volume was noted in HP piglets ( javax.xml.bind.JAXBElement@4a0c5b2f  < 0.05) and restricted to the inner cortical area nephrons ( javax.xml.bind.JAXBElement@1524c771 = javax.xml.bind.JAXBElement@1281f9e8 0.03). Plasma urea/creatinine ratio and proteinuria were unchanged in HP piglets. In conclusion, neonatal HP feeding in IUGR piglets significantly enhanced neonatal growth and tissue protein deposition but mildly affected glomerular volume. It can be speculated that a sustained tissue protein anabolism in response to HP intake have limited single nephron glomerular hyperfiltration

Water Dynamics in Shewanella oneidensis at Ambient and High Pressure using Quasi-Elastic Neutron Scattering

Quasielastic neutron scattering (QENS) is an ideal technique for studying water transport and relaxation dynamics at pico-to nanosecond timescales and at length scales relevant to cellular dimensions. Studies of high pressure dynamic effects in live organisms are needed to understand Earth's deep biosphere and biotechnology applications. Here we applied QENS to study water transport in Shewanella oneidensis at ambient (0.1 MPa) and high (200 MPa) pressure using H/D isotopic contrast experiments for normal and perdeuterated bacteria and buffer solutions to distinguish intracellular and transmembrane processes. The results indicate that intracellular water dynamics are comparable with bulk diffusion rates in aqueous fluids at ambient conditions but a significant reduction occurs in high pressure mobility. We interpret this as due to enhanced interactions with macromolecules in the nanoconfined environment. Overall diffusion rates across the cell envelope also occur at similar rates but unexpected narrowing of the QENS signal appears between momentum transfer values Q = 0.7-1.1 Å-1 corresponding to real space dimensions of 6-9 Å. The relaxation time increase can be explained by correlated dynamics of molecules passing through Aquaporin water transport complexes located within the inner or outer membrane structures

Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6.

Senescent cells may exert detrimental effect on microenvironment through the secretion of soluble factors and the release of extracellular vesicles, such as microparticles, key actors in ageing and cardiovascular diseases. We previously reported that sirtuin-1 (SIRT1) deficiency drives accelerated senescence and dysfunction of endothelial colony-forming cells (ECFC) in PT neonates. Because preterm birth (PT) increases the risk for cardiovascular diseases during neonatal period as well as at adulthood, we hypothesized that SIRT1 deficiency could control the biogenesis of microparticles as part of a senescence-associated secretory phenotype (SASP) of PT-ECFC and investigated the related molecular mechanisms. Compared to control ECFC, PT-ECFC displayed a SASP associated with increased release of endothelial microparticles (EMP), mediating a paracrine induction of senescence in naïve endothelial cells. SIRT1 level inversely correlated with EMP release and drives PT-ECFC vesiculation. Global transcriptomic analysis revealed changes in stress response pathways, specifically the MAPK pathway. We delineate a new epigenetic mechanism by which SIRT1 deficiency regulates MKK6/p38 <sup>MAPK</sup> /Hsp27 pathway to promote EMP biogenesis in senescent ECFC. These findings deepen our understanding of the role of ECFC senescence in the disruption of endothelial homeostasis and provide potential new targets towards the control of cardiovascular risk in individuals born preterm

Lymphatic drainage mapping with indirect lymphography for canine mammary tumors

Mammary gland tumors are the most common canine neoplasms. They account for 25– 50% of all tumors diagnosed in bitches. Metastases and recurrences develop in about 35–70% of bitches following excision. The presence of regional lymph node metastases is a relevant factor affecting prognosis and treatment in cases of mammary gland tumors. The sentinel lymph node (SLN) is the first lymph node (or nodes) in the regional lymphatic basin that receives lymphatic flow from the primary neoplasm. The aim of this study is to investigate the SLN with indirect lymphography for a mammary tumor in dogs. The knowledge of the precise drainage pattern and SLN of the neoplastic mammary glands would provide clinically relevant information to the surgeon and to the oncologist, and it would be of high importance for the surgeon not only for performing the most adequate surgical excision but also for determining an accurate post-surgical prognosis

Investigation on the Emission of Volatile Organic Compounds from Heated Vegetation and Their Potential to Cause an Accelerating Forest Fire

International audienceAn experimental study is conducted on the emission of volatile organic compounds (VOCs) emitted by Rosmarinus officinalis plants when exposed to an external radiant flux. The thermal radiation heats the plant and causes the emission of VOCs. The thermal radiation simulates the radiant flux received by vegetation in a forest fire. The results of the experiments are used in a simplified analysis to determine if the emissions of VOCs in an actual forest fire situation could produce a flammable gas mixture and potentially lead to the onset of an accelerating forest fire. The experiments consist of placing a plant in a hermetic enclosure and heating it with a radiant panel. The VOCs produced are collected and analyzed with an automatic thermal desorber coupled with a gas chromatograph/mass spectrometer (ATD-GC/MS). The effects of the fire intensity (radiant panel heat flux) and the fire retardant on the VOCs emission are then investigated. Two thresholds of the VOCs emission are observed. The first is for plant temperatures of around 120C and appears to be caused by the evaporation of the water in the plant, which carries with it a certain amount of VOCs. The second one is around 175C, which is due to the vaporization of the major parts of VOCs. The application of a fire retardant increases the emission of VOCs due to the presence of the water (80%) in the fire retardant. However, the use of the retardant results in a lower production of VOCs than using water alone. The measurements are used to estimate the concentration of VOCs potentially produced during the propagation of a specific fire and compared to the flammability limits of a-pinene. It is concluded that the quantities of VOCs emitted by Rosmarinus officinalis shrubs under certain fire conditions are capable of creating an accelerating forest fir

Selective advantage of epigenetically disrupted cancer cells via phenotypic inertia.

The evolution of established cancers is driven by selection of cells with enhanced fitness. Subclonal mutations in numerous epigenetic regulator genes are common across cancer types, yet their functional impact has been unclear. Here, we show that disruption of the epigenetic regulatory network increases the tolerance of cancer cells to unfavorable environments experienced within growing tumors by promoting the emergence of stress-resistant subpopulations. Disruption of epigenetic control does not promote selection of genetically defined subclones or favor a phenotypic switch in response to environmental changes. Instead, it prevents cells from mounting an efficient stress response via modulation of global transcriptional activity. This "transcriptional numbness" lowers the probability of cell death at early stages, increasing the chance of long-term adaptation at the population level. Our findings provide a mechanistic explanation for the widespread selection of subclonal epigenetic-related mutations in cancer and uncover phenotypic inertia as a cellular trait that drives subclone expansion

Mutational and phenotypic characterisation of hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia. Care delivery for HHT patients is impeded by the need for laborious, repeated phenotyping and gaps in knowledge regarding the relationships between causal DNA variants in ENG, ACVRL1, SMAD4 and GDF2, and clinical manifestations. To address this, we analyzed DNA samples from 183 previously uncharacterized, unrelated HHT and suspected HHT cases using the ThromboGenomics high-throughput sequencing platform. We identified 127 rare variants across 168 heterozygous genotypes. Applying modified American College of Medical Genetics and Genomics Guidelines, 106 variants were classified as pathogenic/likely pathogenic and 21 as nonpathogenic (variant of uncertain significance/benign). Unlike the protein products of ACVRL1 and SMAD4, the extracellular ENG amino acids are not strongly conserved. Our inferences of the functional consequences of causal variants in ENG were therefore informed by the crystal structure of endoglin. We then compared the accuracy of predictions of the causal gene blinded to the genetic data using 2 approaches: subjective clinical predictions and statistical predictions based on 8 Human Phenotype Ontology terms. Both approaches had some predictive power, but they were insufficiently accurate to be used clinically, without genetic testing. The distributions of red cell indices differed by causal gene but not sufficiently for clinical use in isolation from genetic data. We conclude that parallel sequencing of the 4 known HHT genes, multidisciplinary team review of variant calls in the context of detailed clinical information, and statistical and structural modeling improve the prognostication and treatment of HHT

Utilization of remote sensing techniques for the quantification of fire behavior in two pine stands

Quantification of field-scale fire behavior is necessary to improve the current scientific understanding of wildland fires and to develop and test relevant, physics-based models. In particular, detailed descriptions of individual fires are required, for which the available literature is limited. In this work, two such field-scale experiments, carried out in pine stands under mild conditions, are presented. A particular focus was placed on non-intrusive measurement, as the capabilities of advanced remote sensing techniques, along with more traditional approaches, are explored. A description of the fires is presented, with spread occurring predominantly in the surface fuels with intensities in the range of 200–4400 kW m-1, and punctuated by isolated regions of crown fire. The occurrence of crown fire is investigated and linked to regions of greater canopy density, and it is found that the total fire intensity may increase locally to as much as 21,000 kW m-1. The light winds do not appear to play a direct role in the changes in fire behavior, while fuel structure may be important. The measurements described herein provided a reasonable overall description of the fires, however, the current resolution (both spatial and temporal) falls short of definitively explaining some transitional aspects of the fire behavior, and future improvements are suggested