DASH: Dynamic Attention-Based Substructure Hierarchy for Partial Charge Assignment

We present a robust and computationally efficient approach for assigning partial charges of atoms in molecules. The method is based on a hierarchical tree constructed from attention values extracted from a graph neural network (GNN), which was trained to predict atomic partial charges from accurate quantum-mechanical (QM) calculations. The resulting dynamic attention-based substructure hierarchy (DASH) approach provides fast assignment of partial charges with the same accuracy as the GNN itself, is software-independent, and can easily be integrated in existing parametrization pipelines as shown for the Open force field (OpenFF). The implementation of the DASH workflow, the final DASH tree, and the training set are available as open source / open data from public repositories

A Simple Test For The Possible Simultaneous Evolutionary Divergence Of Two Amino Acid Positions

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149712/1/tax00373.pd

Importance of exposure route for behavioural responses in Lumbriculus variegatus Müller (Oligochaeta: Lumbriculida) in short-term exposures to Pb

Abstract Goal, Scope and Background Lumbriculus variegatus Müller (Oligochaeta), a common freshwater sediment-dweller, has frequently been used in toxicokinetic studies, although has been less used in ecotoxicity tests. Methods For the first time the Multispecies Freshwater Biomonitor® (MFB) was applied in a short-term whole-sediment toxicity test. The MFB automatically and quantitatively recorded the spontaneous locomotory behaviour of Lumbriculus variegatus in exposures with two compartments, water and sediment. The study questioned, whether the animals altered their locomotion depending on the compartment which was spiked with lead (Pb). Results and Discussion As in the exposures to Pb-contaminated water/clean sediment, the animals exposed to Pb-contaminated sediment/clean water showed higher activities in intermediate Pb-concentrations. This indicates, that spontaneous locomotory activity is affected by Pb-concentrations at sublethal levels regardless of whether the Pb-concentration is found in the water or in the sediment, because these animals use both environmental compartments simultaneously. However, within the same Pb-levels, the animals showed higher locomotory activity in contaminated water compared with contaminated sediment. This indicates a possible tendency to withdraw from (‘avoidance’) contaminated water into the clean sediment compartment, whereas there was no withdrawal from contaminated sediment into clean water. The latter might be explained by the fact that withdrawal from sediment to water might increase the risk of predation and drift in nature, whereas retracting to sediment might provide shelter. Conclusions The study showed that spontaneous locomotory responses of L. variegatus to Pb depend on whether the water or sediment is contaminated. The study also concluded that the Multispecies Freshwater Biomonitor® can be applied effectively in sediment toxicity testing. Recommendations and Perspectives More emphasis should be given to the interactions of water/sediment in sediment ecotoxicity tests to better simulate field conditions and increase ecological realism in risk assessment, especially as quantitative recording methods exisit

Biological Responses of Lumbriculus variegatus Exposed to Fluoranthene-Spiked Sediment

Lumbriculus variegatus was used as a bioassay organism to examine the impact of the sediment-associated polycyclic aromatic hydrocarbon (PAH) fluoranthene on behavior, reproduction, and toxicokinetics. The number of worms increased between the beginning and end of the experiment at 59 μg g −1 fluoranthene, but at the next higher treatment (108 μg g −1 ) the number of worms found was lower and not different from the control. Worms exposed to 95 μg g −1 also exhibited increased reproduction when fed a yeast-cerophyl-trout chow mixture. On a total biomass basis, only the 95 μg g −1 exposure with food exhibited a statistically significant increase over the nonfed control. Evaluation of reproduction at the two highest treatments was compromised by a brief aeration failure 2 days before the end of the experiment. The behavioral responses were followed as changes in biological burial rate (sediment reworking rate) of a 137 Cs-labeled marker layer. The biological burial rate increased toward a plateau as the concentration increased from the control (3.9 μg g −1 dry weight total PAH) to 355 μg g −1 dry weight fluoranthene in sediment. The aeration failure had minimal impact on the determination of reworking rate because all the data for the rate determination were collected prior to the aeration failure. Uptake and elimination rates declined with increasing treatment concentration across the range of fluoranthene concentrations, 59–355 μg g −1 dry weight sediment. The disconnect between the increasing biological burial rates and the decreasing toxicokinetics rates with increasing exposure concentration demonstrates that the toxicokinetic processes are dominated by uptake and elimination to interstitial water. The bioaccumulation factor (concentration in the organisms on a wet weight basis divided by the concentration in sediment on a dry weight basis) ranged from 0.92 to 1.88 on day 10 and declined to a range of 0.52 to 0.99 on day 28 with the lowest value at the highest dose.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42373/1/244-42-3-292_20420292.pd

(193) Proposal to democratize aspects of the governance of the International Code of Nomenclature for algae, fungi, and plants

descripción no proporcionada por scopu

Effect of lutein and antioxidant dietary supplementation on contrast sensitivity in age-related macular disease:A randomized controlled trial

Objective: The aim of the study is to determine the effect of lutein combined with vitamin and mineral supplementation on contrast sensitivity in people with age-related macular disease (ARMD). Design: A prospective, 9-month, double-masked randomized controlled trial. Setting: Aston University, Birmingham, UK and a UK optometric clinical practice. Subjects: Age-related maculopathy (ARM) and atrophic age-related macular degeneration (AMD) participants were randomized (using a random number generator) to either placebo (n = 10) or active (n=15) groups. Three of the placebo group and two of the active group dropped out. Interventions: The active group supplemented daily with 6 mg lutein combined with vitamins and minerals. The outcome measure was contrast sensitivity (CS) measured using the Pelli-Robson chart, for which the study had 80% power at the 5% significance level to detect a change of 0.3log units. Results: The CS score increased by 0.07 ± 0.07 and decreased by 0.02 ± 0.18 log units for the placebo and active groups, respectively. The difference between these values is not statistically significant (z = 0.903, P = 0.376). Conclusion: The results suggest that 6 mg of lutein supplementation in combination with other antioxidants is not beneficial for this group. Further work is required to establish optimum dosage levels

RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord

ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Report of Seminar on Law and Medicine

Reports from the UK/CLE Seminar on Law and Medicine held May 26-28, 1976