129 research outputs found
Ultrastructural and functional fate of recycled vesicles in hippocampal synapses
Efficient recycling of synaptic vesicles is thought to be critical for sustained information transfer at central terminals. However, the specific contribution that retrieved vesicles make to future transmission events remains unclear. Here we exploit fluorescence and time-stamped electron microscopy to track the functional and positional fate of vesicles endocytosed after readily releasable pool (RRP) stimulation in rat hippocampal synapses. We show that most vesicles are recovered near the active zone but subsequently take up random positions in the cluster, without preferential bias for future use. These vesicles non-selectively queue, advancing towards the release site with further stimulation in an actin-dependent manner. Nonetheless, the small subset of vesicles retrieved recently in the stimulus train persist nearer the active zone and exhibit more privileged use in the next RRP. Our findings reveal heterogeneity in vesicle fate based on nanoscale position and timing rules, providing new insights into the origins of future pool constitution
Genome Wide Transcriptome Analysis of Dendritic Cells Identifies Genes with Altered Expression in Psoriasis
Activation of dendritic cells by different pathogens induces the secretion of proinflammatory mediators resulting in
local inflammation. Importantly, innate immunity must be properly controlled, as its continuous activation leads to the
development of chronic inflammatory diseases such as psoriasis. Lipopolysaccharide (LPS) or peptidoglycan (PGN)
induced tolerance, a phenomenon of transient unresponsiveness of cells to repeated or prolonged stimulation,
proved valuable model for the study of chronic inflammation. Thus, the aim of this study was the identification of the
transcriptional diversity of primary human immature dendritic cells (iDCs) upon PGN induced tolerance. Using SAGESeq
approach, a tag-based transcriptome sequencing method, we investigated gene expression changes of primary
human iDCs upon stimulation or restimulation with Staphylococcus aureus derived PGN, a widely used TLR2 ligand.
Based on the expression pattern of the altered genes, we identified non-tolerizeable and tolerizeable genes. Gene
Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (Kegg) analysis showed marked enrichment of
immune-, cell cycle- and apoptosis related genes. In parallel to the marked induction of proinflammatory mediators,
negative feedback regulators of innate immunity, such as TNFAIP3, TNFAIP8, Tyro3 and Mer are markedly
downregulated in tolerant cells. We also demonstrate, that the expression pattern of TNFAIP3 and TNFAIP8 is
altered in both lesional, and non-lesional skin of psoriatic patients. Finally, we show that pretreatment of immature
dendritic cells with anti-TNF-Ξ± inhibits the expression of IL-6 and CCL1 in tolerant iDCs and partially releases the
suppression of TNFAIP8. Our findings suggest that after PGN stimulation/restimulation the host cell utilizes different
mechanisms in order to maintain critical balance between inflammation and tolerance. Importantly, the transcriptome
sequencing of stimulated/restimulated iDCs identified numerous genes with altered expression to date not associated
with role in chronic inflammation, underlying the relevance of our in vitro model for further characterization of IFNprimed
iDCs
Effect of Coenzyme Q10 on ischemia and neuronal damage in an experimental traumatic brain-injury model in rats
<p>Abstract</p> <p>Background</p> <p>Head trauma is one of the most important clinical issues that not only can be fatal and disabling, requiring long-term treatment and care, but also can cause heavy financial burden. Formation or distribution of free oxygen radicals should be decreased to enable fixing of poor neurological outcomes and to prevent neuronal damage secondary to ischemia after trauma. Coenzyme Q<sub>10 </sub>(CoQ<sub>10</sub>), a component of the mitochondrial electron transport chain, is a strong antioxidant that plays a role in membrane stabilization. In this study, the role of CoQ<sub>10 </sub>in the treatment of head trauma is researched by analyzing the histopathological and biochemical effects of CoQ<sub>10 </sub>administered after experimental traumatic brain injury in rats. A traumatic brain-injury model was created in all rats. Trauma was inflicted on rats by the free fall of an object of 450 g weight from a height of 70 cm on the frontoparietal midline onto a metal disc fixed between the coronal and the lambdoid sutures after a midline incision was carried out.</p> <p>Results</p> <p>In the biochemical tests, tissue malondialdehyde (MDA) levels were significantly higher in the traumatic brain-injury group compared to the sham group (<it>p </it>< 0.05). Administration of CoQ<sub>10 </sub>after trauma was shown to be protective because it significantly lowered the increased MDA levels (<it>p </it>< 0.05). Comparing the superoxide dismutase (SOD) levels of the four groups, trauma + CoQ<sub>10 </sub>group had SOD levels ranging between those of sham group and traumatic brain-injury group, and no statistically significant increase was detected. Histopathological results showed a statistically significant difference between the CoQ<sub>10 </sub>and the other trauma-subjected groups with reference to vascular congestion, neuronal loss, nuclear pyknosis, nuclear hyperchromasia, cytoplasmic eosinophilia, and axonal edema (<it>p </it>< 0.05).</p> <p>Conclusion</p> <p>Neuronal degenerative findings and the secondary brain damage and ischemia caused by oxidative stress are decreased by CoQ<sub>10 </sub>use in rats with traumatic brain injury.</p
Genetic and Physiological Analysis of Iron Biofortification in Maize Kernels
BACKGROUND: Maize is a major cereal crop widely consumed in developing countries, which have a high prevalence of iron (Fe) deficiency anemia. The major cause of Fe deficiency in these countries is inadequate intake of bioavailable Fe, where poverty is a major factor. Therefore, biofortification of maize by increasing Fe concentration and or bioavailability has great potential to alleviate this deficiency. Maize is also a model system for genomic research and thus allows the opportunity for gene discovery. Here we describe an integrated genetic and physiological analysis of Fe nutrition in maize kernels, to identify loci that influence grain Fe concentration and bioavailability. METHODOLOGY: Quantitative trait locus (QTL) analysis was used to dissect grain Fe concentration (FeGC) and Fe bioavailability (FeGB) from the Intermated B73 Γ Mo17 (IBM) recombinant inbred (RI) population. FeGC was determined by ion coupled argon plasma emission spectroscopy (ICP). FeGB was determined by an in vitro digestion/Caco-2 cell line bioassay. CONCLUSIONS: Three modest QTL for FeGC were detected, in spite of high heritability. This suggests that FeGC is controlled by many small QTL, which may make it a challenging trait to improve by marker assisted breeding. Ten QTL for FeGB were identified and explained 54% of the variance observed in samples from a single year/location. Three of the largest FeGB QTL were isolated in sister derived lines and their effect was observed in three subsequent seasons in New York. Single season evaluations were also made at six other sites around North America, suggesting the enhancement of FeGB was not specific to our farm site. FeGB was not correlated with FeGC or phytic acid, suggesting that novel regulators of Fe nutrition are responsible for the differences observed. Our results indicate that iron biofortification of maize grain is achievable using specialized phenotyping tools and conventional plant breeding techniques
Accounting, Soci(et)al Risks, and Public Reason: Governmental Risk Discourses About the ILVA Steel Plant in Taranto (Italy)
The case of the ILVA steel plant in Taranto represents an example of con- trasting, incommensurable sustainability issues, explored in terms of βsocialβ and βsocietalβ risks (Asenova et al. in Managing the risks of public spending cuts in Scotland, 2013; Redistribution of social and societal risk: the impact on individuals, their networks and communities, 2015) [Asenova et al. (2015) refer to social risks as the risks of unemployment, and to societal risks as environmental and health risks.]. The case of ILVA has received significant attention for the great amount of dangerous pollutants spread in the environment, as well as the evidence of higher illness and mortality rates in the districts nearest to the plant. In July 2012, the Italian Judiciary halted activity in the steel plant. Four months after, the Italian Government declared the steel plant site as a βStrategic National Interest Siteβ, and allowed the company to restart its activity. Drawing on governmentality (Foucault in Questions of method, 1991), the paper aims to explore the role of accountingβhere broadly intended as calculative practices (Miller in Soc Res 68:379β396, 2001)βin moulding ministerial discourse to support decisions when the governance of contrasting risks is needed to safeguard public interest. Supported by discourse analysis of governmental speech, the research shows that the Italian Government based its decision on various expertsβ risk appraisals: accounting shaped governmental discourse by giving more visibility and relevance to βsocialβ risks (i.e. unemployment, economic development, produc- tivity and competitiveness risks), while silencing βsocietalβ ones (i.e. environmental and health risks). Focusing on a case of incommensurable contrasting issues, the findings contribute to show that accounting concurrently plays a significant role in government decisions legitimizing the business continuity through the creation of a specific risk discourse
BMP signaling components in embryonic transcriptomes of the hover fly Episyrphus balteatus (Syrphidae)
<p>Abstract</p> <p>Background</p> <p>In animals, signaling of Bone Morphogenetic Proteins (BMPs) is essential for dorsoventral (DV) patterning of the embryo, but how BMP signaling evolved with changes in embryonic DV differentiation is largely unclear. Based on the extensive knowledge of BMP signaling in <it>Drosophila melanogaster</it>, the morphological diversity of extraembryonic tissues in different fly species provides a comparative system to address this question. The closest relatives of <it>D. melanogaster </it>with clearly distinct DV differentiation are hover flies (Diptera: Syrphidae). The syrphid <it>Episyrphus balteatus </it>is a commercial bio-agent against aphids and has been established as a model organism for developmental studies and chemical ecology. The dorsal blastoderm of <it>E. balteatus </it>gives rise to two extraembryonic tissues (serosa and amnion), whereas in <it>D. melanogaster</it>, the dorsal blastoderm differentiates into a single extraembryonic epithelium (amnioserosa). Recent studies indicate that several BMP signaling components of <it>D. melanogaster</it>, including the BMP ligand Screw (Scw) and other extracellular regulators, evolved in the dipteran lineage through gene duplication and functional divergence. These findings raise the question of whether the complement of BMP signaling components changed with the origin of the amnioserosa.</p> <p>Results</p> <p>To search for BMP signaling components in <it>E. balteatus</it>, we generated and analyzed transcriptomes of freshly laid eggs (0-30 minutes) and late blastoderm to early germband extension stages (3-6 hours) using Roche/454 sequencing. We identified putative <it>E. balteatus </it>orthologues of 43% of all annotated <it>D. melanogaster </it>genes, including the genes of all BMP ligands and other BMP signaling components.</p> <p>Conclusion</p> <p>The diversification of several BMP signaling components in the dipteran linage of <it>D. melanogaster </it>preceded the origin of the amnioserosa.</p> <p>[Transcriptome sequence data from this study have been deposited at the NCBI Sequence Read Archive (SRP005289); individually assembled sequences have been deposited at GenBank (<ext-link ext-link-id="JN006969" ext-link-type="gen">JN006969</ext-link>-<ext-link ext-link-id="JN006986" ext-link-type="gen">JN006986</ext-link>).]</p
The recommendations of Chinese Parkinsonβs disease and movement disorder society consensus on therapeutic management of Parkinsonβs disease
Stochastic upscaling of hydrodynamic dispersion and retardation factor in a physically and chemically heterogeneous tropical soil
[EN] Stochastic upscaling of flow and reactive solute transport in a tropical soil is performed using real data collected in the laboratory. Upscaling of hydraulic conductivity, longitudinal hydrodynamic dispersion, and retardation factor were done using three different approaches of varying complexity. How uncertainty propagates after upscaling was also studied. The results show that upscaling must be taken into account if a good reproduction of the flow and transport behavior of a given soil is to be attained when modeled at larger than laboratory scales. The results also show that arrival time uncertainty was well reproduced after solute transport upscaling. This work represents a first demonstration of flow and reactive transport upscaling in a soil based on laboratory data. It also shows how simple upscaling methods can be incorporated into daily modeling practice using commercial flow and transport codes.The authors thank the financial support by the Brazilian National Council for Scientific and Technological Development (CNPq) (Project 401441/2014-8). The doctoral fellowship award to the first author by the Coordination of Improvement of Higher Level Personnel (CAPES) is acknowledged. The first author also thanks the international mobility grant awarded by CNPq, through the Sciences Without Borders program (Grant Number: 200597/2015-9). The international mobility grant awarded by Santander Mobility in cooperation with the University of Sao Paulo is also acknowledged. DHI-WASI is gratefully thanked for providing a FEFLOW license.Almeida De-Godoy, V.; Zuquette, L.; GΓ³mez-HernΓ‘ndez, JJ. (2019). Stochastic upscaling of hydrodynamic dispersion and retardation factor in a physically and chemically heterogeneous tropical soil. 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Spontaneous Reaction Silencing in Metabolic Optimization
Metabolic reactions of single-cell organisms are routinely observed to become
dispensable or even incapable of carrying activity under certain circumstances.
Yet, the mechanisms as well as the range of conditions and phenotypes
associated with this behavior remain very poorly understood. Here we predict
computationally and analytically that any organism evolving to maximize growth
rate, ATP production, or any other linear function of metabolic fluxes tends to
significantly reduce the number of active metabolic reactions compared to
typical non-optimal states. The reduced number appears to be constant across
the microbial species studied and just slightly larger than the minimum number
required for the organism to grow at all. We show that this massive spontaneous
reaction silencing is triggered by the irreversibility of a large fraction of
the metabolic reactions and propagates through the network as a cascade of
inactivity. Our results help explain existing experimental data on
intracellular flux measurements and the usage of latent pathways, shedding new
light on microbial evolution, robustness, and versatility for the execution of
specific biochemical tasks. In particular, the identification of optimal
reaction activity provides rigorous ground for an intriguing knockout-based
method recently proposed for the synthetic recovery of metabolic function.Comment: 34 pages, 6 figure
Tempo and Mode in Evolution of Transcriptional Regulation
Perennial questions of evolutionary biology can be applied to gene regulatory systems using the abundance of experimental data addressing gene regulation in a comparative context. What is the tempo (frequency, rate) and mode (way, mechanism) of transcriptional regulatory evolution? Here we synthesize the results of 230 experiments performed on insects and nematodes in which regulatory DNA from one species was used to drive gene expression in another species. General principles of regulatory evolution emerge. Gene regulatory evolution is widespread and accumulates with genetic divergence in both insects and nematodes. Divergence in cis is more common than divergence in trans. Coevolution between cis and trans shows a particular increase over greater evolutionary timespans, especially in sex-specific gene regulation. Despite these generalities, the evolution of gene regulation is gene- and taxon-specific. The congruence of these conclusions with evidence from other types of experiments suggests that general principles are discoverable, and a unified view of the tempo and mode of regulatory evolution may be achievable
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