Actin polymerisation at the cytoplasmic face of eukaryotic nuclei

Background  

There exists abundant molecular and ultra-structural evidence to suggest that cytoplasmic actin can physically interact with the nuclear envelope (NE) membrane system. However, this interaction has yet to be characterised in living interphase cells.     

Choline and N,N-Dimethylethanolamine as Direct Substrates for Methanogens

Choline (N,N,N-trimethylethanolamine), which is widely distributed in membrane lipids and is a component of sediment biota, has been shown to be utilized anaerobically by mixed prokaryote cultures to produce methane but not by pure cultures of methanogens. Here, we show that five recently isolated Methanococcoides strains from a range of sediments (Aarhus Bay, Denmark; Severn Estuary mudflats at Portishead, United Kingdom; Darwin Mud Volcano, Gulf of Cadiz; Napoli mud volcano, eastern Mediterranean) can directly utilize choline for methanogenesis producing ethanolamine, which is not further metabolized. Di- and monomethylethanolamine are metabolic intermediates that temporarily accumulate. Consistent with this, dimethylethanolamine was shown to be another new growth substrate, but monomethylethanolamine was not. The specific methanogen inhibitor 2-bromoethanesulfonate (BES) inhibited methane production from choline. When choline and trimethylamine are provided together, diauxic growth occurs, with trimethylamine being utilized first, and then after a lag (∼7 days) choline is metabolized. Three type strains of Methanococcoides (M. methylutens, M. burtonii, and M. alaskense), in contrast, did not utilize choline. However, two of them (M. methylutens and M. burtonii) did metabolize dimethylethanolamine. These results extend the known substrates that can be directly utilized by some methanogens, giving them the advantage that they would not be reliant on bacterial syntrophs for their substrate supply.     

Interleukin-15 plays a central role in human kidney physiology and cancer through the γc signaling pathway

The ability of Interleukin-15 (IL-15) to activate many immune antitumor mechanisms renders the cytokine a good candidate for the therapy of solid tumors, particularly renal cell carcinoma. Although IL-15 is being currently used in clinical trials, the function of the cytokine on kidney's components has not been extensively studied; we thus investigated the role of IL-15 on normal and tumor renal epithelial cells. Herein, we analyzed the expression and the biological functions of IL-15 in normal renal proximal tubuli (RPTEC) and in their neoplastic counterparts, the renal clear cell carcinomas (RCC). This study shows that RPTEC express a functional heterotrimeric IL-15Rαβγc complex whose stimulation with physiologic concentrations of rhIL-15 is sufficient to inhibit epithelial mesenchymal transition (EMT) commitment preserving E-cadherin expression. Indeed, IL-15 is not only a survival factor for epithelial cells, but it can also preserve the renal epithelial phenotype through the γc-signaling pathway, demonstrating that the cytokine possess a wide range of action in epithelial homeostasis. In contrast, in RCC in vitro and in vivo studies reveal a defect in the expression of γc-receptor and JAK3 associated kinase, which strongly impacts IL-15 signaling. Indeed, in the absence of the γc/JAK3 couple we demonstrate the assembly of an unprecedented functional high affinity IL-15Rαβ heterodimer, that in response to physiologic concentrations of IL-15, triggers an unbalanced signal causing the down-regulation of the tumor suppressor gene E-cadherin, favoring RCC EMT process. Remarkably, the rescue of IL-15/γc-dependent signaling (STAT5), by co-transfecting γc and JAK3 in RCC, inhibits EMT reversion. In conclusion, these data highlight the central role of IL-15 and γc-receptor signaling in renal homeostasis through the control of E-cadherin expression and preservation of epithelial phenotype both in RPTEC (up-regulation) and RCC (down-regulation).     

Automatic detection of AutoPEEP during controlled mechanical ventilation

ABSTRACT: BACKGROUND: Dynamic hyperinflation, hereafter called AutoPEEP (auto-positive end expiratory pressure)with some slight language abuse, is a frequent deleterious phenomenon in patients undergoingmechanical ventilation. Although not readily quantifiable, AutoPEEP can be recognized onthe expiratory portion of the flow waveform. If expiratory flow does not return to zero beforethe next inspiration, AutoPEEP is present. This simple detection however requires the eye ofan expert clinician at the patient's bedside. An automatic detection of AutoPEEP should behelpful to optimize care. METHODS: In this paper, a platform for automatic detection of AutoPEEP based on the flow signalavailable on most of recent mechanical ventilators is introduced. The detection algorithms aredeveloped on the basis of robust non-parametric hypothesis testings that require no priorinformation on the signal distribution. In particular, two detectors are proposed: one is basedon SNT (Signal Norm Testing) and the other is an extension of SNT in the sequentialframework. The performance assessment was carried out on a respiratory system analog andex-vivo on various retrospectively acquired patient curves. RESULTS: The experiment results have shown that the proposed algorithm provides relevant AutoPEEPdetection on both simulated and real data. The analysis of clinical data has shown that theproposed detectors can be used to automatically detect AutoPEEP with an accuracy of 93%and a recall (sensitivity) of 90%. CONCLUSIONS: The proposed platform provides an automatic early detection of AutoPEEP. Such functionalitycan be integrated in the currently used mechanical ventilator for continuous monitoring of thepatient-ventilator interface and, therefore, alleviate the clinician task.     

Lysosomal dysfunction in Parkinson disease: ATP13A2 gets into the groove

Mutations in ATP13A2 (PARK9) cause an autosomal recessive form of early-onset parkinsonism with pyramidal degeneration and dementia called Kufor-Rakeb Syndrome (KRS). The ATP13A2 gene encodes a transmembrane lysosomal P5-type ATPase (ATP13A2) whose physiological function in mammalian cells, and hence its potential role in Parkinson disease (PD), remains elusive. In this context, we have recently shown that KRS-linked mutations in ATP13A2 leads to several lysosomal alterations in ATP13A2 KRS patient-derived fibroblasts, including impaired lysosomal acidification, decreased proteolytic processing of lysosomal enzymes, reduced degradation of lysosomal substrates and diminished lysosomal-mediated clearance of autophagosomes (AP). Similar alterations are observed in stable ATP13A2-knockdown dopaminergic cell lines, which are associated with cell death. Restoration of ATP13A2 levels in ATP13A2-mutant/depleted cells is able to restore lysosomal function and attenuate cell death. Relevant to PD, we have determined that ATP13A2 levels are decreased in dopaminergic nigral neurons from sporadic PD patients. Interestingly in these patients, the main signal of ATP13A2 is detected in the Lewy bodies. Our results unravel an instrumental role of ATP13A2 in lysosomal function and in cell viability. Altogether, our results validate ATP13A2 as a likely therapeutic target against PD degeneration.     

Life-cycle-generation-specific developmental processes are modified in the immediate upright mutant of the brown alga Ectocarpus siliculosus

Development of the sporophyte and gametophyte generations of the brown alga E. siliculosus involves two different patterns of early development, which begin with either a symmetric or an asymmetric division of the initial cell, respectively. A mutant, immediate upright (imm), was isolated that exhibited several characteristics typical of the gametophyte during the early development of the sporophyte generation. Genetic analyses showed that imm is a recessive, single-locus Mendelian factor and analysis of gene expression in this mutant indicated that the regulation of a number of life-cycle-regulated genes is specifically modified in imm mutant sporophytes. Thus, IMM appears to be a regulatory locus that controls part of the sporophyte-specific developmental programme, the mutant exhibiting partial homeotic conversion of the sporophyte into the gametophyte, a phenomenon that has not been described previously.     

Lorentz force electrical impedance tomography

This article describes a method called Lorentz Force Electrical Impedance Tomography. The electrical conductivity of biological tissues can be measured through their sonication in a magnetic field: the vibration of the tissues inside the field induces an electrical current by Lorentz force. This current, detected by electrodes placed around the sample, is proportional to the ultrasonic pressure, to the strength of the magnetic field and to the electrical conductivity gradient along the acoustic axis. By focusing at different places inside the sample, a map of the electrical conductivity gradient can be established. In this study, experiments were conducted on a gelatin phantom and on a beef sample, successively placed in a 300 mT magnetic field and sonicated with an ultrasonic transducer focused at 21 cm emitting 500 kHz bursts. Although all interfaces are not visible, in this exploratory study a good correlation is observed between the electrical conductivity image and the ultrasonic image. This method offers an alternative to detecting pathologies invisible to standard ultrasonography.     

The contrasting genetic patterns of two sympatric flying fox species from the Comoros and the implications for conservation

Pteropus livingstonii and Pteropus seychellensis comorensis are endemic fruit bat species that are among the most threatened animals in the Comoros archipelago. Both species are pollinators and seed dispersers of native and cultivated plants and are thus of crucial importance for the regeneration of natural forests as well as for cultivated plantations. However, these species are subject to strong anthropogenic pressures and face one of the highest rates of natural habitat loss reported worldwide. Yet little is known about the population genetic structure of these two species, making it difficult to define relevant conservation strategies. In this study, we investigated for the two flying fox species (1) the level of genetic diversity within islands, as well as across the archipelago and (2) the genetic structure between the two islands (Anjouan and Mohéli) for P. livingstonii and between the four islands of the archipelago (Anjouan, Mohéli, Grande Comore and Mayotte) for P. s. comorensis using mitochondrial and microsatellite markers. The results revealed contrasting patterns of genetic structure, with P. s. comorensis showing low genetic structure between islands, whereas P. livingstonii exhibited high levels of inter-island genetic differentiation. Overall, the genetic analyses showed low genetic diversity for both species. These contrasting genetic patterns may be the result of different dispersal patterns and the populations’ evolutionary histories. Our findings lead us to suggest that in terms of conservation strategy, the two populations of P. livingstonii (on Anjouan and Mohéli islands) should be considered as two separate management units. We recommend focusing conservation efforts on the Anjouan population, which is the largest, exhibits the highest genetic diversity, and suffers the greatest anthropogenic pressure. As for P. s. comorensis, its four populations could be considered as a single unit for conservation management purposes. For this species, we recommend protecting roosting trees to reduce population disturbance.     

The Tyrosine Phosphatase STEP Is Involved in Age-Related Memory Decline

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High‐Throughput DNA sequencing of ancient wood

Reconstructing the colonization and demographic dynamics that gave rise to extant forests is essential to forecasts of forest responses to environmental changes. Classical approaches to map how population of trees changed through space and time largely rely on pollen distribution patterns, with only a limited number of studies exploiting DNA molecules preserved in wooden tree archaeological and subfossil remains. Here, we advance such analyses by applying high‐throughput (HTS) DNA sequencing to wood archaeological and subfossil material for the first time, using a comprehensive sample of 167 European white oak waterlogged remains spanning a large temporal (from 550 to 9,800 years) and geographical range across Europe. The successful characterization of the endogenous DNA and exogenous microbial DNA of 140 (~83%) samples helped the identification of environmental conditions favouring long‐term DNA preservation in wood remains, and started to unveil the first trends in the DNA decay process in wood material. Additionally, the maternally inherited chloroplast haplotypes of 21 samples from three periods of forest human‐induced use (Neolithic, Bronze Age and Middle Ages) were found to be consistent with those of modern populations growing in the same geographic areas. Our work paves the way for further studies aiming at using ancient DNA preserved in wood to reconstruct the micro‐evolutionary response of trees to climate change and human forest management.