Combining machine learning models of in vitro and in vivo bioassays improves rat carcinogenicity prediction.

In vitro genotoxicity bioassays are cost-efficient methods of assessing potential carcinogens. However, many genotoxicity bioassays are inappropriate for detecting chemicals eliciting non-genotoxic mechanisms, such as tumour promotion, this necessitates the use of in vivo rodent carcinogenicity (IVRC) assays. In silico IVRC modelling could potentially address the low throughput and high cost of this assay. We aimed to develop and combine computational QSAR models of novel bioassays for the prediction of IVRC results and compare with existing software. QSAR models were generated from existing Ames (n = 6512), Syrian Hamster Embryonic (SHE, n = 410), ISSCAN rodent carcinogenicity (ISC, n = 834) and GreenScreen GADD45a-GFP (n = 1415) chemical datasets. These models mapped the molecular descriptors of each compound to their respective assay result using machine learning algorithms (adaboost, k-Nearest Neighbours, C.45 Decision Tree, Multilayer Perceptron, Random Forest). The best performing models were combined with k-Nearest Neighbours to create a cascade model for IVRC prediction. High QSAR model performance was observed from ten time 10-fold cross-validation with above 80% accuracy and 0.85 AUC for each assay dataset. The cascade model predicted rat carcinogenicity with 69.3% accuracy and 0.700 AUC. This study demonstrates the novelty of a combined approach for IVRC prediction, with higher performance than existing software.

Depression and cardiac dysautonomia in eating disorders.

PURPOSE: Individuals with eating disorder (ED) are at an increased risk of cardiac arrhythmias due to cardiac dysautonomia, which may be exacerbated if depression is also present. The aim of the study was to use heart rate analysis as a marker for cardiac dysautonomia in patients with eating disorders and depression as a comorbidity. METHODS: Clinical data, including presence of depression, was obtained from all participants. A three-lead ECG was used to determine interbeat intervals, and these were analyzed using time domain, frequency domain, and nonlinear heart rate variability measures. RESULTS: Thirty ED patients and 44 healthy controls participated in the research. The presence of depression was associated with additional decreased time domain (RMSSD 36.8 ± 26 vs. 22.9 ± 12.3; p < 0.05), frequency domain (HF power 788 ± 1075 vs. 279 ± 261; p < 0.05), and nonlinear domain (DFAα2 0.82 ± 0.1 vs. 0.97 ± 0.1; p < 0.01) which results in the ED group compared to patients with no depression. CONCLUSIONS: The presence of depression in ED patients decreased HRV even further compared to the non-depressed patient group and controls, suggesting that higher vigilance and a holistic treatment approach may be required for these patients to avoid cardiac arrhythmia complications.

Corrigendum: Evolution, ecology, and zoonotic transmission of betacoronaviruses: A review.

[This corrects the article DOI: 10.3389/fvets.2021.644414.].

Corrigendum: Evolution, ecology, and zoonotic transmission of betacoronaviruses: a review.

[This corrects the article DOI: 10.3389/fvets.2021.644414.].

Playing a first-person shooter video game induces neuroplastic change.

Playing a first-person shooter (FPS) video game alters the neural processes that support spatial selective attention. Our experiment establishes a causal relationship between playing an FPS game and neuroplastic change. Twenty-five participants completed an attentional visual field task while we measured ERPs before and after playing an FPS video game for a cumulative total of 10 hr. Early visual ERPs sensitive to bottom-up attentional processes were little affected by video game playing for only 10 hr. However, participants who played the FPS video game and also showed the greatest improvement on the attentional visual field task displayed increased amplitudes in the later visual ERPs. These potentials are thought to index top-down enhancement of spatial selective attention via increased inhibition of distractors. Individual variations in learning were observed, and these differences show that not all video game players benefit equally, either behaviorally or in terms of neural change.

Acute antioxidant supplementation improves endurance performance in trained athletes.

This study examined the acute effects of a single dose of an antioxidant (AO; Lactaway® containing pycnogenol) on time to fatigue (TTF). Nine trained cyclists [mean ± SD age 35 ± 10 yrs; body mass 71.6 ± 10.2 kg; VO2 peak 63 ± 11 ml/kg/min] performed on two separate occasions a continuous protocol of 5 min at 50% of peak power output (PPO), 8 min at 70% of PPO, and then cycled to fatigue at 95% PPO. Four hours prior to the exercise protocol, the subjects consumed the supplement or a placebo (counterbalanced, double blind protocol). Cyclists, on average, rode for 80 s more in the Lactaway trial than they did in the placebo trial. There was considerable evidence (chances ≥94.5%) for substantial positive treatment effects for TTF and the other performance-related variables (excluding [BLa] at 95% PPO). Other studies are necessary to confirm these results and identify the mechanisms underlying the observed effects.

Evolution, Ecology, and Zoonotic Transmission of Betacoronaviruses: A Review.

Coronavirus infections have been a part of the animal kingdom for millennia. The difference emerging in the twenty-first century is that a greater number of novel coronaviruses are being discovered primarily due to more advanced technology and that a greater number can be transmitted to humans, either directly or via an intermediate host. This has a range of effects from annual infections that are mild to full-blown pandemics. This review compares the zoonotic potential and relationship between MERS, SARS-CoV, and SARS-CoV-2. The role of bats as possible host species and possible intermediate hosts including pangolins, civets, mink, birds, and other mammals are discussed with reference to mutations of the viral genome affecting zoonosis. Ecological, social, cultural, and environmental factors that may play a role in zoonotic transmission are considered with reference to SARS-CoV, MERS, and SARS-CoV-2 and possible future zoonotic events.

Women match men when learning a spatial skill.

Meta-analytic studies have concluded that although training improves spatial cognition in both sexes, the male advantage generally persists. However, because some studies run counter to this pattern, a closer examination of the anomaly is warranted. The authors investigated the acquisition of a basic skill (spatial selective attention) using a matched-pair two-wave longitudinal design. Participants were screened with the use of an attentional visual field task, with the objective of selecting and matching 10 male-female pairs, over a wide range (30% to 57% correct). Subsequently, 20 participants 17-23 years of age (selected from 43 screened) were trained for 10 hr (distributed over several sessions) by playing a first-person shooter video game. This genre is known to be highly effective in enhancing spatial skills. All 20 participants improved, with matched members of the male-female pairs achieving very similar gains, independent of starting level. This is consistent with the hypothesis that the learning trajectory of women is not inferior to that of men when acquiring a basic spatial skill. Training methods that develop basic spatial skills may be essential to achieve gender parity in both basic and complex spatial tasks.

Immunization with a synthetic robustoxin derivative lacking disulphide bridges protects against a potentially lethal challenge with funnel-web spider (Atrax robustus) venom.

The venom of male Atrax robustus spiders is potentially lethal to primates. These spiders have been responsible for a number of human deaths. Robustoxin is the lethal toxin in the venom. It is a highly cross-linked polypeptide that has 42 amino acid residues and four disulphide bridges. If these bridges are broken, the resulting polypeptide is non-toxic. Robustoxin was chemically synthesized with all of its eight cysteine residues protected with acetamidomethyl groups in order to avoid formation of disulphide bridges. The resulting derivative was co-polymerized with keyhole limpet haemocyanin. Two Macaca fascicularis monkeys were immunized with this conjugate. The monkeys were challenged,under anaesthesia,with a potentially lethal dose of male A.robustus crude venom. Both monkeys showed some minor symptoms of intoxication but recovered fully with no adverse after-effects. Immunization with the same immunogen, in the absence of keyhole limpet haemocyanin, did not protect a third monkey. The N-terminal 23 amino acid peptide derived from the sequence of robustoxin was synthesized and conjugated with ovalbumin. A fourth monkey was immunized with this conjugate. However,it was not protected against challenge.The implications of these results for the preparation of synthetic peptide vaccines are discussed.

QSAR ligand dataset for modelling mutagenicity, genotoxicity, and rodent carcinogenicity.

Five datasets were constructed from ligand and bioassay result data from the literature. These datasets include bioassay results from the Ames mutagenicity assay, Greenscreen GADD-45a-GFP assay, Syrian Hamster Embryo (SHE) assay, and 2 year rat carcinogenicity assay results. These datasets provide information about chemical mutagenicity, genotoxicity and carcinogenicity.

A novel methodology to probe endothelial differential gene expression profile reveals novel genes.

Endothelial dysfunction is a major feature of vascular diseases. A practical, minimally invasive method to effectively "probe" gene transcription for an individual patient's endothelium has potential to "customize" assessment for an individual at risk of vascular disease as well as pathophysiologic insight in an in vivo human, clinical context. Published literature lacks a methodology to identify endothelial differential gene expression in individuals with vascular disease. We describe a methodology to do so. The aim of this study was to specifically utilize (a) cutaneous microvascular biopsy, (b) laser capture microdissection, (c) cDNA amplification, (d) suppression subtractive hybridization, (e) high-throughput sequencing techniques, (f) real-time polymerase chain reaction (PCR), and (g) in combination of these methods, to profile differential gene expression in the context of cardiovascular and cerebrovascular disease. Endothelial cells were obtained by laser capture microdissection from a patient and a healthy sibling's microvascular biopsy tissues. Endothelial RNA was extracted, reverse transcribed, and amplified to ds cDNA. Suppression subtractive hybridization was used to establish an endothelial differential gene expression library. Real-time PCR confirmed SERP1, caspase 8, IGFBP7, S100A4, F85, and F147 up-regulation between 1.4- and 3.47-fold. The authors have successfully established a methodology to profile endothelial differential gene expression and identified six differentially expressed genes. This minimally invasive novel method has potential wide application in the customized assessment of many patients suffering vascular diseases.

The Effects of Spatial Endogenous Pre-cueing across Eccentricities.

Frequently, we use expectations about likely locations of a target to guide the allocation of our attention. Despite the importance of this attentional process in everyday tasks, examination of pre-cueing effects on attention, particularly endogenous pre-cueing effects, has been relatively little explored outside an eccentricity of 20°. Given the visual field has functional subdivisions that attentional processes can differ significantly among the foveal, perifoveal, and more peripheral areas, how endogenous pre-cues that carry spatial information of targets influence our allocation of attention across a large visual field (especially in the more peripheral areas) remains unclear. We present two experiments examining how the expectation of the location of the target shapes the distribution of attention across eccentricities in the visual field. We measured participants' ability to pick out a target among distractors in the visual field after the presentation of a highly valid cue indicating the size of the area in which the target was likely to occur, or the likely direction of the target (left or right side of the display). Our first experiment showed that participants had a higher target detection rate with faster responses, particularly at eccentricities of 20° and 30°. There was also a marginal advantage of pre-cueing effects when trials of the same size cue were blocked compared to when trials were mixed. Experiment 2 demonstrated a higher target detection rate when the target occurred at the cued direction. This pre-cueing effect was greater at larger eccentricities and with a longer cue-target interval. Our findings on the endogenous pre-cueing effects across a large visual area were summarized using a simple model to assist in conceptualizing the modifications of the distribution of attention over the visual field. We discuss our finding in light of cognitive penetration of perception, and highlight the importance of examining attentional process across a large area of the visual field.

The Commingled Division of Visual Attention.

Many critical activities require visual attention to be distributed simultaneously among distinct tasks where the attended foci are not spatially separated. In our two experiments, participants performed a large number of trials where both a primary task (enumeration of spots) and a secondary task (reporting the presence/absence or identity of a distinctive shape) required the division of visual attention. The spots and the shape were commingled spatially and the shape appeared unpredictably on a relatively small fraction of the trials. The secondary task stimulus (the shape) was reported in inverse proportion to the attentional load imposed by the primary task (enumeration of spots). When the shape did appear, performance on the primary task (enumeration) suffered relative to when the shape was absent; both speed and accuracy were compromised. When the secondary task required identification in addition to detection, reaction times increased by about 200 percent. These results are broadly compatible with biased competition models of perceptual processing. An important area of application, where the commingled division of visual attention is required, is the augmented reality head-up display (AR-HUD). This innovation has the potential to make operating vehicles safer but our data suggest that there are significant concerns regarding driver distraction.

Postmortem serotoninergic correlates of cognitive decline in Alzheimer's disease.

Serotonin1A receptor density and serotonin concentration were measured in the postmortem neocortex of 17 AD patients who had been prospectively assessed every four months with the Mini-Mental State Examination (MMSE) for a mean of 2.6 years till death. In the frontal cortex, serotonin levels correlated negatively with the annual rate of MMSE decline, while serotonin1A receptor density was positively correlated with the rate of MMSE decline. Our study suggests that reduced serotonin levels and increased serotonin1A receptor density are markers for accelerated cognitive decline in AD, and provides support for the use of serotonin1A antagonists in the treatment of AD.

Serotonin transporters are preserved in the neocortex of anxious Alzheimer's disease patients.

Densities of serotonin transporters (5-HTT) in the postmortem neocortex of behaviorally assessed Alzheimer's disease (AD) patients and aged controls were measured by radioligand binding with [3H]citalopram. It was found that 5-HTT sites in the temporal cortex of AD patients with prominent antemortem anxiety were unaltered compared with controls, but were reduced in non-anxious AD subjects. Furthermore, homozygosity for the high activity allele of a functional polymorphism in the 5-HTT gene promoter region (5-HTTLPR) was associated with both increased [3H]citalopram binding and occurrence of anxiety in the AD subjects. Since serotonin-synthesizing neurons are known to be lost in the AD cortex, this study suggests that the preservation of 5-HTT may exacerbate serotonergic deficits and underlie anxiety symptoms in AD.

Automated morphometric analysis of the cat retinal alpha/Y, beta/X and delta ganglion cells using wavelet statistical moment and clustering algorithms.

Computational morphological analysis comprises the development of measures (indicators) that describe different form attributes of a neuron and provides additional parameters for classification algorithms. Our work addressed the problem of small group sizes often encountered in neuromorphological and neurophysiological research, automated classification tasks (unsupervised learning) and introduced a new morphological measure: the wavelet statistical moment. We analysed cat alpha/Y, beta/X and delta Golgi-stained retinal ganglion cells using six different shape features (circularity, 2(nd) statistical moment and entropy of Gaussian blurred images, wavelet statistical moment, number of terminations and the fractal dimension). This allowed us to compare the sensitivity of the methods in uniquely describing morphological attributes of these cells.

Upper visual field advantage in localizing a target among distractors.

Biases exist in many perceptual and cognitive functions. Since visual attention plays an important role in a wide range of perceptual and cognitive processes, any bias in the spatial distribution of attention is likely to be a significant source of perceptual and cognitive asymmetries. An attentional visual field task (AVF) requiring localization of a target among distractors was used to assess possible asymmetries in attentional processing in the vertical meridian. The results showed a bias favoring the upper visual field, suggesting a potentially important role of attention in perceptual and cognitive asymmetries.

Playing shooter and driving videogames improves top-down guidance in visual search.

Playing action videogames is known to improve visual spatial attention and related skills. Here, we showed that playing action videogames also improves classic visual search, as well as the ability to locate targets in a dual search that mimics certain aspects of an action videogame. In Experiment 1A, first-person shooter (FPS) videogame players were faster than nonplayers in both feature search and conjunction search, and in Experiment 1B, they were faster and more accurate in a peripheral search and identification task while simultaneously performing a central search. In Experiment 2, we showed that 10 h of play could improve the performance of nonplayers on each of these tasks. Three different genres of videogames were used for training: two action games and a 3-D puzzle game. Participants who played an action game (either an FPS or a driving game) achieved greater gains on all search tasks than did those who trained using the puzzle game. Feature searches were faster after playing an action videogame, suggesting that players developed a better target template to guide search in a top-down manner. The results of the dual search suggest that, in addition to enhancing the ability to divide attention, playing an action game improves the top-down guidance of attention to possible target locations. The results have practical implications for the development of training tools to improve perceptual and cognitive skills.

A mixture distribution of spatial attention.

Although it may seem paradoxical, the unified-focus and multiple-foci theories of spatial selective attention are both well supported by experimental evidence. However, the apparent contradiction is illusory and the two competing views may be reconciled by a closer examination of the spatial mechanisms involved. We propose that the deployment of attention may be modeled as a mixture of individual distributions of attention and we tested this hypothesis in two experiments. Participants had to identify targets among distractors, with the targets presented at various distances from the cued locations. Experiment 1 confirmed that the distribution of attention may be described by a mixture of individual distributions, each centered at a cued location. Experiment 2 showed that cue separation is an important determinant of whether spatial attention is divided or not.

Attention and visuospatial working memory share the same processing resources.

Attention and visuospatial working memory (VWM) share very similar characteristics; both have the same upper bound of about four items in capacity and they recruit overlapping brain regions. We examined whether both attention and VWM share the same processing resources using a novel dual-task costs approach based on a load-varying dual-task technique. With sufficiently large loads on attention and VWM, considerable interference between the two processes was observed. A further load increase on either process produced reciprocal increases in interference on both processes, indicating that attention and VWM share common resources. More critically, comparison among four experiments on the reciprocal interference effects, as measured by the dual-task costs, demonstrates no significant contribution from additional processing other than the shared processes. These results support the notion that attention and VWM share the same processing resources.