Does adult ADHD interact with COMT val 158 met genotype to influence working memory performance?

Peer reviewedPostprin

Seminal lipid profiling and antioxidant capacity : a species comparison

On their way to the oocyte, sperm cells are subjected to oxidative stress, which may trigger the oxidation of phospholipids (PL). Applying MALDI-TOF MS, HPTLC and ESI-IT MS, we comparatively analyzed the PL compositions of semen and blood of species differing in their reproductive systems and types of nutrition (bull, boar, stallion, lion and man) with regard to the sensitivity to oxidation as well as the accumulation of harmful lyso-PL (LPL), transient products of lipid oxidation. In addition, the protective capacity of seminal fluid (SF) was also examined. The PL composition of erythrocytes and blood plasma is similar across the species, while pronounced differences exist for sperm and SF. Since the blood function is largely conserved across mammalian species, but the reproductive systems may vary in many aspects, the obtained results suggest that the PL composition is not determined by the type of nutrition, but by the relatedness of species and by functional requirements of cell membranes such as fluidity. Sperm motion and fertilization of oocytes require a rather flexible membrane, which is accomplished by significant moieties of unsaturated fatty acyl residues in sperm lipids of most species, but implies a higher risk of oxidation. Due to a high content of plasmalogens (alkenyl ether lipids), bull sperm are most susceptible to oxidation. Our data indicate that bull sperm possess the most effective protective power in SF. Obviously, a co-evolution of PL composition and protective mechanisms has occurred in semen and is related to the reproductive characteristics. Although the protective capacity in human SF seems well developed, we recorded the most pronounced individual contaminations with LPL in human semen. Probably, massive oxidative challenges related to lifestyle factors interfere with natural conditions.SUPPLEMENTARY MATERIAL: S1 Fig. ESI spectra of lysophosphatidylcholine (LPC) fractions from boar, bull, stallion, lion and human samples.S2 Fig. ESI spectra of sphingomyelin (SM) fractions from boar, bull, stallion, lion and human samples. Lipid extracts were separated on a normal phase high performance thin-layer chromatography (HPTLC) plate with chloroform/ethanol/water/triethylamine (30:35:7:35, by vol.) as the mobile phase. Plates were air-dried and stained with primuline (Direct Yellow 59, Sigma-Aldrich, Taufkirchen, Germany) (50 mg/l dissolved in acetone/water 80:20, by vol.). Lipids were made visible under UV light and marked with a pencil. SM fractions were directly analyzed by coupling a TLC plate reader to an ESI mass spectrometer. Mass spectra were recorded in the positive ion mode. For further details on ESI-IT MS see main text. For peak assignment, please see S2 Table. https://doi.org/10.1371/journal.pone.0264675.s002S3 Fig. ESI spectra of phosphatidylcholine (PC) fractions from boar, bull, stallion, lion and human samples. Lipid extracts were separated on a normal phase high performance thin-layer chromatography (HPTLC) plate with chloroform/ethanol/water/triethylamine (30:35:7:35, by vol.) as the mobile phase. Plates were air-dried and stained with primuline (Direct Yellow 59, Sigma-Aldrich, Taufkirchen, Germany) (50 mg/l dissolved in acetone/water 80:20, by vol.). Lipids were made visible under UV light and marked with a pencil. PC fractions were directly analyzed by coupling a TLC plate reader to an ESI mass spectrometer. Mass spectra were recorded in the positive ion mode. For further details on ESI-IT MS see main text. For peak assignment, please see S3 Table. https://doi.org/10.1371/journal.pone.0264675.s003S4 Fig. ESI spectra of phosphatidylinositol (PI) fractions from boar, bull, stallion and human lipid samples. Lipid extracts were separated on a normal phase high performance thin-layer chromatography (HPTLC) plate with chloroform/ethanol/water/triethylamine (30:35:7:35, by vol.) as the mobile phase. Plates were air-dried and stained with primuline (Direct Yellow 59, Sigma-Aldrich, Taufkirchen, Germany) (50 mg/l dissolved in acetone/water 80:20, by vol.). Lipids were made visible under UV light and marked with a pencil. PI fractions were directly analyzed by coupling a TLC plate reader to an ESI mass spectrometer. Mass spectra were recorded in the negative ion mode. For further details on ESI-IT MS see main text. For peak assignment, please see S4 Table. https://doi.org/10.1371/journal.pone.0264675.s004S5 Fig. ESI spectra of phosphatidylethanolamine (PE) fractions from boar, bull and stallion samples. Lipid extracts were separated on a normal phase high performance thin-layer chromatography (HPTLC) plate with chloroform/ethanol/water/triethylamine (30:35:7:35, by vol.) as the mobile phase. Plates were air-dried and stained with primuline (Direct Yellow 59, Sigma-Aldrich, Taufkirchen, Germany) (50 mg/l dissolved in acetone/water 80:20, by vol.). Lipids were made visible under UV light and marked with a pencil. PE fractions were directly analyzed by coupling a TLC plate reader to an ESI mass spectrometer. Mass spectra were recorded in the negative ion mode. For further details on ESI-IT MS see main text. For peak assignment, please see S5 Table. https://doi.org/10.1371/journal.pone.0264675.s005S6 Fig. ESI spectra of phosphatidylethanolamine (PE) fractions from lion and human samples. Lipid extracts were separated on a normal phase high performance thin-layer chromatography (HPTLC) plate with chloroform/ethanol/water/triethylamine (30:35:7:35, by vol.) as the mobile phase. Plates were air-dried and stained with primuline (Direct Yellow 59, Sigma-Aldrich, Taufkirchen, Germany) (50 mg/l dissolved in acetone/water 80:20, by vol.). Lipids were made visible under UV light and marked with a pencil. PE fractions were directly analyzed by coupling a TLC plate reader to an ESI mass spectrometer. Mass spectra were recorded in the negative ion mode. For further details on ESI-IT MS see main text. For peak assignment, please see S5 Table. https://doi.org/10.1371/journal.pone.0264675.s006S7 Fig. Hydrolysis of selected seminal fluid samples over time. The plots of hydrolysis measurements from boar and stallion seminal fluid were fitted by a linear curve (f(x) = a + b×x) and the plots from bull, lion and human were fitted by an exponential growth to a maximum (f(x) = a×e-b×x). Due to these different courses of the hydrolysis reaction between the species, the absolute hydrolysis at a given time point (10 min) was used to compare the mean values of the investigated individuals between the species (see Table 2 of the main text). https://doi.org/10.1371/journal.pone.0264675.s007S8 Fig. Effect of artificial LPC on boar sperm. Beltsville Thawing Solution (BTS, Minitüb GmbH)-diluted boar semen (20 × 106 sperm/ml) was mixed with 20 μM lysophosphatidylcholine (LPC 16:0, Avanti Polar Lipids®, No 855675C). After incubation at 38°C for 30 min, the ratios of total motility (blank boxes) and sperm with an intact acrosome (striped boxes) were analyzed. The lipid extract of washed sperm of this experiment was analyzed by MALDI-TOF MS and the ratio of LPC to total GPC was calculated (for details see Material and Methods of the main text). Incubation with 20 μM LPC led to 2.4 ± 3.6% inserted LPC in sperm cell membranes. Significant differences in total motility and the percentage of sperm with an intact acrosome between the incubation with 20 μM LPC and controls are marked by asterisks (P = 0.006 and 0.003, respectively, Wilcoxon signed-rank test, n = 11). https://doi.org/10.1371/journal.pone.0264675.s008S9 Fig. Original TLC pictures. Lipid extracts were separated on normal phase high performance thin-layer chromatography (HPTLC) plates with chloroform/ethanol/water/triethylamine (30:35:7:35, by vol.) as the mobile phase. Plates were air-dried and stained with primuline (Direct Yellow 59, Sigma-Aldrich, Taufkirchen, Germany) (50 mg/l dissolved in acetone/water 80:20, by vol.). BP–blood plasma, SF–seminal fluid, st.–lipid standard mixture made of LPC16:0, SM16:0, PC16:0/18:1, PA 16:0/18:1, PI 16:1/18:1, PE 16:0/18:1, PG 16:0/18:1 (bottom up). https://doi.org/10.1371/journal.pone.0264675.s009S1 Table. Assignment of signals detected in ESI spectra from lysophosphatidylcholine (LPC) spots. https://doi.org/10.1371/journal.pone.0264675.s010S2 Table. Assignment of signals detected in ESI spectra from sphingomyelin (SM) spots. n.a.—not assigned. https://doi.org/10.1371/journal.pone.0264675.s011S3 Table. Assignment of signals detected in ESI spectra from phosphatidylcholine (PC) spots. https://doi.org/10.1371/journal.pone.0264675.s012S4 Table. Assignment of signals detected in ESI spectra from phosphatidylinositol (PI) spots. https://doi.org/10.1371/journal.pone.0264675.s013S5 Table. Assignment of signals detected in ESI spectra from phosphatidylethanolamine (PE) spots. https://doi.org/10.1371/journal.pone.0264675.s014The German Research Council.http://www.plosone.orgdm2022Veterinary Tropical Disease

Using metabolic networks to resolve ecological properties of microbiomes

The systematic collection, integration and modelling of high-throughput molecular data (multi-omics) allows the detailed characterisation of microbiomes in situ. Through metabolic trait inference, metabolic network reconstruction and modelling, we are now able to define ecological interactions based on metabolic exchanges, identify keystone genes, functions and species, and resolve ecological niches of constituent microbial populations. The resulting knowledge provides detailed information on ecosystem functioning. However, as microbial communities are dynamic in nature the field needs to move towards the integration of time- and space-resolved multi-omic data along with detailed environmental information to fully harness the power of community- and population-level metabolic network modelling. Such approaches will be fundamental for future targeted management strategies with wide-ranging applications in biotechnology and biomedicine

T cell derived IL-10 is dispensable for tolerance induction in a murine model of allergic airway inflammation

Regulatory mechanisms initiated by allergen specific immunotherapy are mainly attributed to T cell-derived IL-10. However, it has not been shown that T cell-derived IL-10 is required for successful tolerance induction. Here, we analyze cellular sources and the functional relevance of cell type specific IL-10 during tolerance induction in a murine model of allergic airway inflammation. While tolerance induction was effective in IL-10 competent mice, neutralizing IL-10 prior to tolerogenic treatment completely abrogated the beneficial effects. Cellular sources of IL-10 during tolerance induction were identified by using transcriptional reporter mice as T cells, B cells and to a lesser extent DCs. Interestingly, tolerance induction was still effective in mice with T cell-, B cell-, B and T cell- or DC-specific IL-10 deficiency. In contrast, tolerance induction was not possible in mice lacking IL-10 in all hematopoetic cells, while it was effective in bone marrow chimera that lacked IL-10 only in non-hematopoetic cells. Taken together, allergen specific tolerance depends on IL-10 from hematopoetic sources. The beneficial effects of allergen specific immunotherapy cannot solely be attributed to IL-10 from T cells, B cells or even DCs, suggesting a high degree of cellular redundancy in IL-10 mediated tolerance

Highly efficient intercellular spreading of protein misfolding mediated by viral ligand-receptor interactions

Protein aggregates associated with neurodegenerative diseases have the ability to transmit to unaffected cells, thereby templating their own aberrant conformation onto soluble homotypic proteins. Proteopathic seeds can be released into the extracellular space, secreted in association with extracellular vesicles (EV) or exchanged by direct cell-to-cell contact. The extent to which each of these pathways contribute to the prion-like spreading of protein misfolding is unclear. Exchange of cellular cargo by both direct cell contact or via EV depends on receptor-ligand interactions. We hypothesized that enabling these interactions through viral ligands enhances intercellular proteopathic seed transmission. Using different cellular models propagating prions or pathogenic Tau aggregates, we demonstrate that vesicular stomatitis virus glycoprotein and SARS-CoV-2 spike S increase aggregate induction by cell contact or ligand-decorated EV. Thus, receptor-ligand interactions are important determinants of intercellular aggregate dissemination. Our data raise the possibility that viral infections contribute to proteopathic seed spreading by facilitating intercellular cargo transfer. Pathologic protein aggregates associated with neurodegenerative diseases have the ability to transmit to unaffected cells via extracellular vesicles or direct cell-to-cell contact. Here, Liu et al. show that viral glycoproteins can contribute to intercellular proteopathic seed transmission via both routes

Towards the prediction of molecular parameters from astronomical emission lines using Neural Networks

Molecular astronomy is a field that is blooming in the era of large observatories such as the Atacama Large Millimeter/Submillimeter Array (ALMA). With modern, sensitive, and high spectral resolution radio telescopes like ALMA and the Square Kilometer Array, the size of the data cubes is rapidly escalating, generating a need for powerful automatic analysis tools. This work introduces MolPred, a pilot study to perform predictions of molecular parameters such as excitation temperature (T) and column density (log(N)) from input spectra by the use of neural networks. We used as test cases the spectra of CO, HCO, SiO and CHCN between 80 and 400 GHz. Training spectra were generated with MADCUBA, a state-of-the-art spectral analysis tool. Our algorithm was designed to allow the generation of predictions for multiple molecules in parallel. Using neural networks, we can predict the column density and excitation temperature of these molecules with a mean absolute error of 8.5% for CO, 4.1% for HCO, 1.5% for SiO and 1.6% for CHCN. The prediction accuracy depends on the noise level, line saturation, and number of transitions. We performed predictions upon real ALMA data. The values predicted by our neural network for this real data differ by 13% from the MADCUBA values on average. Current limitations of our tool include not considering linewidth, source size, multiple velocity components, and line blending.A.B. wishes to thank Dr. Diego Mardones for his contribution to the early stages of this work. Also, to acknowledge support from the Federico Santa María Technical University General Directorate for Research and Postgraduate Studies (DGIP). JH and SV are funded by the European Research Council (ERC) Advanced Grant MOPPEX 833460. V.M.R. acknowledges support from the Comunidad de Madrid through the Atracción de Talento Investigador Modalidad 1 (Doctores con experiencia) Grant (COOL: Cosmic Origins Of Life; 2019-T1/TIC-15379; PI: V.M. Rivilla)

Forecasting the dynamics of a complex microbial community using integrated meta-omics.

peer reviewedPredicting the behaviour of complex microbial communities is challenging. However, this is essential for complex biotechnological processes such as those in biological wastewater treatment plants (BWWTPs), which require sustainable operation. Here we summarize 14 months of longitudinal meta-omics data from a BWWTP anaerobic tank into 17 temporal signals, explaining 91.1% of the temporal variance, and link those signals to ecological events within the community. We forecast the signals over the subsequent five years and use 21 extra samples collected at defined time intervals for testing and validation. Our forecasts are correct for six signals and hint on phenomena such as predation cycles. Using all the 17 forecasts and the environmental variables, we predict gene abundance and expression, with a coefficient of determination ≥0.87 for the subsequent three years. Our study demonstrates the ability to forecast the dynamics of open microbial ecosystems using interactions between community cycles and environmental parameters.R-AGR-0369 - ATTRACT A09/03 Sysbionama (01/02/2010 - 31/01/2015) - WILMES Pau

A multicenter randomized-controlled trial of hypothermic oxygenated perfusion (HOPE) for human liver grafts before transplantation

Background &amp; Aims: Machine perfusion is a novel method intended to optimize livers before transplantation. However, its effect on morbidity within a 1-year period after transplantation has remained unclear. Methods: In this multicenter controlled trial, we randomly assigned livers donated after brain death (DBD) for liver transplantation (LT). Livers were either conventionally cold stored (control group), or cold stored and subsequently treated by 1-2 h hypothermic oxygenated perfusion (HOPE) before implantation (HOPE group). The primary endpoint was the occurrence of at least one post-transplant complication per patient, graded by the Clavien score of ≥III, within 1-year after LT. The comprehensive complication index (CCI), laboratory parameters, as well as duration of hospital and intensive care unit stay, graft survival, patient survival, and biliary complications served as secondary endpoints. Results: Between April 2015 and August 2019, we randomized 177 livers, resulting in 170 liver transplantations (85 in the HOPE group and 85 in the control group). The number of patients with at least one Clavien ≥III complication was 46/85 (54.1%) in the control group and 44/85 (51.8%) in the HOPE group (odds ratio 0.91; 95% CI 0.50-1.66; p = 0.76). Secondary endpoints were also not significantly different between groups. A post hoc analysis revealed that liver-related Clavien ≥IIIb complications occurred less frequently in the HOPE group compared to the control group (risk ratio 0.26; 95% CI 0.07-0.77; p = 0.027). Likewise, graft failure due to liver-related complications did not occur in the HOPE group, but occurred in 7% (6 of 85) of the control group (log-rank test, p = 0.004, Gray test, p = 0.015). Conclusions: HOPE after cold storage of DBD livers resulted in similar proportions of patients with at least one Clavien ≥III complication compared to controls. Exploratory findings suggest that HOPE decreases the risk of severe liver graft-related events. Impact and implications: This randomized controlled phase III trial is the first to investigate the impact of hypothermic oxygenated perfusion (HOPE) on cumulative complications within a 12-month period after liver transplantation. Compared to conventional cold storage, HOPE did not have a significant effect on the number of patients with at least one Clavien ≥III complication. However, we believe that HOPE may have a beneficial effect on the quantity of complications per patient, based on its application leading to fewer severe liver graft-related complications, and to a lower risk of liver-related graft loss. The HOPE approach can be applied easily after organ transport during recipient hepatectomy. This appears fundamental for wide acceptance since concurring perfusion technologies need either perfusion at donor sites or continuous perfusion during organ transport, which are much costlier and more laborious. We conclude therefore that the post hoc findings of this trial should be further validated in future studies.</p

A multicenter randomized-controlled trial of hypothermic oxygenated perfusion (HOPE) for human liver grafts before transplantation

Background &amp; Aims: Machine perfusion is a novel method intended to optimize livers before transplantation. However, its effect on morbidity within a 1-year period after transplantation has remained unclear. Methods: In this multicenter controlled trial, we randomly assigned livers donated after brain death (DBD) for liver transplantation (LT). Livers were either conventionally cold stored (control group), or cold stored and subsequently treated by 1-2 h hypothermic oxygenated perfusion (HOPE) before implantation (HOPE group). The primary endpoint was the occurrence of at least one post-transplant complication per patient, graded by the Clavien score of ≥III, within 1-year after LT. The comprehensive complication index (CCI), laboratory parameters, as well as duration of hospital and intensive care unit stay, graft survival, patient survival, and biliary complications served as secondary endpoints. Results: Between April 2015 and August 2019, we randomized 177 livers, resulting in 170 liver transplantations (85 in the HOPE group and 85 in the control group). The number of patients with at least one Clavien ≥III complication was 46/85 (54.1%) in the control group and 44/85 (51.8%) in the HOPE group (odds ratio 0.91; 95% CI 0.50-1.66; p = 0.76). Secondary endpoints were also not significantly different between groups. A post hoc analysis revealed that liver-related Clavien ≥IIIb complications occurred less frequently in the HOPE group compared to the control group (risk ratio 0.26; 95% CI 0.07-0.77; p = 0.027). Likewise, graft failure due to liver-related complications did not occur in the HOPE group, but occurred in 7% (6 of 85) of the control group (log-rank test, p = 0.004, Gray test, p = 0.015). Conclusions: HOPE after cold storage of DBD livers resulted in similar proportions of patients with at least one Clavien ≥III complication compared to controls. Exploratory findings suggest that HOPE decreases the risk of severe liver graft-related events. Impact and implications: This randomized controlled phase III trial is the first to investigate the impact of hypothermic oxygenated perfusion (HOPE) on cumulative complications within a 12-month period after liver transplantation. Compared to conventional cold storage, HOPE did not have a significant effect on the number of patients with at least one Clavien ≥III complication. However, we believe that HOPE may have a beneficial effect on the quantity of complications per patient, based on its application leading to fewer severe liver graft-related complications, and to a lower risk of liver-related graft loss. The HOPE approach can be applied easily after organ transport during recipient hepatectomy. This appears fundamental for wide acceptance since concurring perfusion technologies need either perfusion at donor sites or continuous perfusion during organ transport, which are much costlier and more laborious. We conclude therefore that the post hoc findings of this trial should be further validated in future studies.</p

Starburst Energy Feedback Seen through HCO+/HOC+Emission in NGC 253 from ALCHEMI

Molecular abundances are sensitive to the UV photon flux and cosmic-ray ionization rate. In starburst environments, the effects of high-energy photons and particles are expected to be stronger. We examine these astrochemical signatures through multiple transitions of HCO+ and its metastable isomer HOC+ in the center of the starburst galaxy NGC 253 using data from the Atacama Large Millimeter/submillimeter Array large program ALMA Comprehensive High-resolution Extragalactic Molecular inventory. The distribution of the HOC+(1-0) integrated intensity shows its association with "superbubbles,"cavities created either by supernovae or expanding H ii regions. The observed HCO+/HOC+ abundance ratios are ∼10-150, and the fractional abundance of HOC+ relative to H2 is ∼1.5 × 10-11-6 × 10-10, which implies that the HOC+ abundance in the center of NGC 253 is significantly higher than in quiescent spiral arm dark clouds in the Galaxy and the Galactic center clouds. Comparison with chemical models implies either an interstellar radiation field of G 0 ⪆ 103 if the maximum visual extinction is ⪆5, or a cosmic-ray ionization rate of ζ ⪆ 10-14 s-1 (3-4 orders of magnitude higher than that within clouds in the Galactic spiral arms) to reproduce the observed results. From the difference in formation routes of HOC+, we propose that a low-excitation line of HOC+ traces cosmic-ray dominated regions, while high-excitation lines trace photodissociation regions. Our results suggest that the interstellar medium in the center of NGC 253 is significantly affected by energy input from UV photons and cosmic rays, sources of energy feedback.N.H. acknowledges support from JSPS KAKENHI grant No. JP21K03634. K.S. has been supported by grants MOST 108-2112-M-001-015 and 109- 2112-M-001-020 from the Ministry of Science and Technology, Taiwan. Y.N. is supported by the NAOJ ALMA Scientific Research grant No. 2017-06B. V.M.R. and L.C. are funded by the Comunidad de Madrid through the Atracción de Talento Investigador (Doctores con experiencia) Grant (COOL: Cosmic Origins Of Life; 2019-T1/TIC-15379)