A metabolomic strategy defines the regulation of lipid content and global metabolism by Δ9 desaturases in Caenorhabditis elegans.

BACKGROUND: Caenorhabditis elegans provides a genetically tractable model organism to investigate the network of genes involved in fat metabolism and how regulation is perturbed to produce the complex phenotype of obesity. C. elegans possess the full range of desaturases, including the Δ9 desaturases expressed by fat-5, fat-6 and fat-7. They regulate the biosynthesis of monounsaturated fatty acids, used for the synthesis of lipids including phospholipids, triglycerides and cholesteryl esters. RESULTS: Liquid chromatography mass spectrometry (LC-MS), gas chromatography mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy were used to define the metabolome of all the possible knock-outs for the Δ9 desaturases, including for the first time intact lipids. Despite the genes having similar enzymatic roles, excellent discrimination was achievable for all single and viable double mutants highlighting the distinctive roles of fat-6 and fat-7, both expressing steroyl-CoA desaturases. The metabolomic changes extend to aqueous metabolites demonstrating the influence Δ9 desaturases have on regulating global metabolism and highlighting how comprehensive metabolomics is more discriminatory than classically used dyes for fat staining. CONCLUSIONS: The propagation of metabolic changes across the network of metabolism demonstrates that modification of the Δ9 desaturases places C.elegans into a catabolic state compared with wildtype controls.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Machine-learning based reconstructions of primary and secondary climate variables from North American and European fossil pollen data

We test several quantitative algorithms as palaeoclimate reconstruction tools for North American and European fossil pollen data, using both classical methods and newer machine-learning approaches based on regression tree ensembles and artificial neural networks. We focus on the reconstruction of secondary climate variables (here, January temperature and annual water balance), as their comparatively small ecological influence compared to the primary variable (July temperature) presents special challenges to palaeo-reconstructions. We test the pollen-climate models using a novel and comprehensive cross-validation approach, running a series of h-block cross-validations using h values of 100-1500 km. Our study illustrates major benefits of this variable h-block cross-validation scheme, as the effect of spatial autocorrelation is minimized, while the cross-validations with increasing h values can reveal instabilities in the calibration model and approximate challenges faced in palaeo-reconstructions with poor modern analogues. We achieve well-performing calibration models for both primary and secondary climate variables, with boosted regression trees providing the overall most robust performance, while the palaeoclimate reconstructions from fossil datasets show major independent features for the primary and secondary variables. Our results suggest that with careful variable selection and consideration of ecological processes, robust reconstruction of both primary and secondary climate variables is possible.Peer reviewe

The (p,n) Reaction at Intermediate Energies with the Isotopes of Oxygen (16-O, 17-O, 18-O) and 9-Be as Part of a Unified Approach to the Study of These Nuclei

This work was supported by National Science Foundation Grants PHY 76-84033A01, PHY 78-22774, and Indiana Universit

The (p,n) Reaction at Intermediate Energies With the Isotopes of Oxygen (16-O, 17-O, 18-O) and 9-Be as Part of a Unified Approach to the Study of These Nuclei

This work was supported by National Science Foundation Grant PHY 76-84033 and Indiana Universit

Alterations in sperm long RNA contribute to the epigenetic inheritance of the effects of postnatal trauma

Abstract: Psychiatric diseases have a strong heritable component known to not be restricted to DNA sequence-based genetic inheritance alone but to also involve epigenetic factors in germ cells. Initial evidence suggested that sperm RNA is causally linked to the transmission of symptoms induced by traumatic experiences. Here, we show that alterations in long RNA in sperm contribute to the inheritance of specific trauma symptoms. Injection of long RNA fraction from sperm of males exposed to postnatal trauma recapitulates the effects on food intake, glucose response to insulin and risk-taking in adulthood whereas the small RNA fraction alters body weight and behavioural despair. Alterations in long RNA are maintained after fertilization, suggesting a direct link between sperm and embryo RNA

Isoscalar dipole coherence at low energies and forbidden E1 strength

In 16O and 40Ca an isoscalar, low-energy dipole transition (IS-LED) exhausting approximately 4% of the isoscalar dipole (ISD) energy-weighted sum rule is experimentally known, but conspicuously absent from recent theoretical investigations of ISD strength. The IS-LED mode coincides with the so-called isospin-forbidden E1 transition. We report that for N=Z nuclei up to 100Sn the fully self-consistent Random-Phase-Approximation with finite-range forces, phenomenological and realistic, yields a collective IS-LED mode, typically overestimating its excitation energy, but correctly describing its IS strength and electroexcitation form factor. The presence of E1 strength is solely due to the Coulomb interaction between the protons and the resulting isospin-symmetry breaking. The smallness of its value is related to the form of the transition density, due to translational invariance. The calculated values of E1 and ISD strength carried by the IS-LED depend on the effective interaction used. Attention is drawn to the possibility that in N-not-equal-Z nuclei this distinct mode of IS surface vibration can develop as such or mix strongly with skin modes and thus influence the pygmy dipole strength as well as the ISD strength function. In general, theoretical models currently in use may be unfit to predict its precise position and strength, if at all its existence.Comment: 9 pages, 6 figures, EPJA submitte

A genetically modified adenoviral vector with a phage display-derived peptide incorporated into fiber fibritin chimera prolongs survival in experimental glioma

The dismal clinical context of advanced-grade glioma demands the development of novel therapeutic strategies with direct patient impact. Adenovirus-mediated virotherapy represents a potentially effective approach for glioma therapy. In this research, we generated a novel glioma-specific adenovirus by instituting more advanced genetic modifications that can maximize the efficiency and safety of therapeutic adenoviral vectors. In this regard, a glioma-specific targeted fiber was developed through the incorporation of previously published glioma-specific, phage-panned peptide (VWT peptide) on a fiber fibritin-based chimeric fiber, designated as “GliomaFF.” We showed that the entry of this virus was highly restricted to glioma cells, supporting the specificity imparted by the phage-panned peptide. In addition, the stability of the targeting moiety presented by fiber fibritin structure permitted greatly enhanced infectivity. Furthermore, the replication of this virus was restricted in glioma cells by controlling expression of the E1 gene under the activity of the tumor-specific survivin promoter. Using this approach, we were able to explore the combinatorial efficacy of various adenoviral modifications that could amplify the specificity, infectivity, and exclusive replication of this therapeutic adenovirus in glioma. Finally, virotherapy with this modified virus resulted in up to 70% extended survival in an in vivo murine glioma model. These data demonstrate that this novel adenoviral vector is a safe and efficient treatment for this difficult malignancy

Differences in vertebrate microRNA expression

MicroRNAs (miRNAs) attenuate gene expression by means of translational inhibition and mRNA degradation. They are abundant, highly conserved, and predicted to regulate a large number of transcripts. Several hundred miRNA classes are known, and many are associated with cell proliferation and differentiation. Many exhibit tissue-specific expression, which aids in evaluating their functions, and it has been assumed that their high level of sequence conservation implies a high level of expression conservation. A limited amount of data supports this, although discrepancies do exist. By comparing the expression of ≈100 miRNAs in medaka and chicken with existing data for zebrafish and mouse, we conclude that the timing and location of miRNA expression is not strictly conserved. In some instances, differences in expression are associated with changes in miRNA copy number, genomic context, or both between species. Variation in miRNA expression is more pronounced the greater the differences in physiology, and it is enticing to speculate that changes in miRNA expression may play a role in shaping the physiological differences produced during animal development

Status of the PSF Reconstruction Work Package for MICADO ELT

MICADO is a workhorse instrument for the ESO ELT, allowing first light capability for diffraction limited imaging and long-slit spectroscopy at near-infrared wavelengths. The PSF Reconstruction (PSF-R) Team of MICADO is currently implementing, for the first time within all ESO telescopes, a software service devoted to the blind reconstruction of the PSF. This tool will work independently of the science data, using adaptive optics telemetry data, both for Single Conjugate (SCAO) and Multi-Conjugate Adaptive Optics (MCAO) allowed by the MORFEO module. The PSF-R service will support the state-of-the-art post-processing scientific analysis of the MICADO imaging and spectroscopic data. We provide here an update of the status of the PSF-R service tool of MICADO, after successfully fulfilling the Final Design Review phase, and discuss recent results obtained on simulated and real data gathered on instruments similar to MICADO.Comment: to appear in the Proceedings 12185-149 of the SPIE conference Adaptive Optics Systems VIII, Astronomical Telescopes+Instrumentation 2022 Montreal, Quebec, Canada; 6 pages, 1 figure, 1 table; updated affiliation

Loss of the Putative Catalytic Domain of HDAC4 Leads to Reduced Thermal Nociception and Seizures while Allowing Normal Bone Development

Histone deacetylase 4 (HDAC4) has been associated with muscle & bone development [1]–[6]. N-terminal MEF2 and RUNX2 binding domains of HDAC4 have been shown to mediate these effects in vitro. A complete gene knockout has been reported to result in premature ossification and associated defects resulting in postnatal lethality [6]. We report a viral insertion mutation that deletes the putative deacetylase domain, while preserving the N-terminal portion of the protein. Western blot and immuno-precipitation analysis confirm expression of truncated HDAC4 containing N-terminal amino acids 1-747. These mutant mice are viable, living to at least one year of age with no gross defects in muscle or bone. At 2–4 months of age no behavioral or physiological abnormalities were detected except for an increased latency to respond to a thermal nociceptive stimulus. As the mutant mice aged past 5 months, convulsions appeared, often elicited by handling. Our findings confirm the sufficiency of the N-terminal domain for muscle and bone development, while revealing other roles of HDAC4