Miracle-dz/UniFAR-FTUs huggingface dataset:
Studies on the Role of Superoxide Anion Radicals for the Cardiotoxicity of Adrenochrome

Summary Adrenochrome is an oxidative product of adrenaline and possesses cardiotoxic properties. As oxygen free radicals play a role in the cytotoxic effects of catecholamines, the role of superoxide anion radicals, as mediators of adrenochrome toxicity, was investigated using electrically-driven Langendorff rabbit hearts with depleted catecholamine stores. Repetitive regional myocardial ischemia (MI) was induced by coronary artery branch ligature, and MI was quantitated from epicardial NADH-fluorescence photography. Adrenochrome (10−4 mol/l) was added to the perfusion solution after a reperfusion period of 20 min, 30 min before the 2nd coronary occlusion, with or without the additional application of SOD (30 U/ml). Left ventricular pressure was significantly enhanced by adrenochrome (p < 0.05), but it fell rapidly down below its initial value (p < 0.05). Coronary flow was significantly decreased by adrenochrome (p < 0.05). Whereas epicardial NADH-fluorescence was similar after repetitive coronary occlusions in untreated controls, it was significantly enhanced by adrenochrome (p < 0.05). The deleterious effects of adrenochrome on MI were not inhibited by SOD. Thus, there is no evidence for superoxide anion radicals as mediators of the deleterious effects of adrenochrome on MI in isolated rabbit hearts. The deleterious effects of adrenochrome on MI in isolated rabbit hearts might be caused by functional effects, impairing the oxygen consumption/oxygen supply balance.
Investigating insecticide susceptibility status of adult mosquitoes against some class of insecticides in Osogbo metropolis, Osun State, Nigeria

The study evaluates the resistance and susceptibility of adult female Anopheles gambiae s. l. , Aedes aegypti and Culex quinquefasciatus mosquitoes sourced within Osogbo metropolis, Osun State, Nigeria to four groups of insecticides [Permethrin, Deltamethrin, Pirimiphos-methyl and DDT (Dichlorodiphenyltrichloroethane)] and the distribution of their larval habitat within the metropolis. Mosquito larvae of the three genera were collected during the wet season and reared to adult stage in the laboratory. Emerged adult female mosquitoes were exposed to insecticide impregnated papers of the four insecticide groups for 60mins using WHO kits to determine the knock down rate (kdr). Thereafter, they were transferred into holding tubes and left for 24hrs to assess their resistance and susceptibility according to the WHO protocol. Four types of larval habitats were identified (tires, ground pools, gutters and plastic containers). Anopheles gambiae s. l. showed the highest resistance to Permethrin (49%) (p = 0.04, p<0.05) while the highest susceptibility was recorded with Pirimiphos-methyl (69%) with the lowest against Permethrin (16%) (P = 0.002; p<0.05). The highest resistance of A. aegypti was against OC-Control (45%) (p = 0.031; p<0.05). Permethrin had the highest susceptibility (60%) against A. aegypti while OC-control had the lowest (11%) (p = 0.005; p< 0.05). Culex quinquefasciatus had a lower resistance to OC-control (38%) as compared with Aedes aegypti (45%). However, it was least susceptible to Pirimiphos-methyl (52%) and DDT (17%) respectively (p = 0.013; p<0.05). The susceptibility of A. gambiae s. l. and C. quinquefasciatus to Pirimiphos-methyl and A. aegypti to Permethrin is an indication of the possibility of success if employed for vector control of A. gambiae s. l. , C. quinquefasciatus and A. aegypti respectively. This could be through their inclusion as active ingredients in insecticide treated nets (ITNs) and indoor residual spray (IRS) with a view to abating malaria and other life-threatening mosquito-borne diseases constituting global public health scourge.
Larger and Denser: An Optimal Design for Surface Grids of EMG Electrodes to Identify Greater and More Representative Samples of Motor Units

Abstract The spinal motor neurons are the only neural cells whose individual activity can be noninvasively identified. This is usually done using grids of surface electromyographic (EMG) electrodes and source separation algorithms; an approach called EMG decomposition. In this study, we combined computational and experimental analyses to assess how the design parameters of grids of electrodes influence the number and the properties of the identified motor units. We first computed the percentage of motor units that could be theoretically discriminated within a pool of 200 simulated motor units when decomposing EMG signals recorded with grids of various sizes and interelectrode distances (IEDs). Increasing the density, the number of electrodes, and the size of the grids, increased the number of motor units that our decomposition algorithm could theoretically discriminate, i.e., up to 83.5% of the simulated pool (range across conditions: 30.5–83.5%). We then identified motor units from experimental EMG signals recorded in six participants with grids of various sizes (range: 2–36 cm2) and IED (range: 4–16 mm). The configuration with the largest number of electrodes and the shortest IED maximized the number of identified motor units (56 ± 14; range: 39–79) and the percentage of early recruited motor units within these samples (29 ± 14%). Finally, the number of identified motor units further increased with a prototyped grid of 256 electrodes and an IED of 2 mm. Taken together, our results showed that larger and denser surface grids of electrodes allow to identify a more representative pool of motor units than currently reported in experimental studies.
Arousal state transitions occlude sensory-evoked neurovascular coupling in neonatal mice

In the adult sensory cortex, increases in neural activity elicited by sensory stimulation usually drives vasodilation mediated by neurovascular coupling. However, whether neurovascular coupling is the same in neonatal animals as adults is controversial, as both canonical and inverted responses have been observed. We investigated the nature of neurovascular coupling in unanesthetized neonatal mice using optical imaging, electrophysiology, and BOLD fMRI. We find in neonatal (postnatal day 15, P15) mice, sensory stimulation induces a small increase in blood volume/BOLD signal, often followed by a large decrease in blood volume. An examination of arousal state of the mice revealed that neonatal mice were asleep a substantial fraction of the time, and that stimulation caused the animal to awaken. As cortical blood volume is much higher during REM and NREM sleep than the awake state, awakening occludes any sensory-evoked neurovascular coupling. When neonatal mice are stimulated during an awake period, they showed relatively normal (but slowed) neurovascular coupling, showing that that the typically observed constriction is due to arousal state changes. These result show that sleep-related vascular changes dominate over any sensory-evoked changes, and hemodynamic measures need to be considered in the context of arousal state changes. Significance Statement In the adult brain, increases in neural activity are often followed by vasodilation, allowing activity to be monitored using optical or magnetic resonance imaging. However, in neonates, sensory stimulation can drive vasoconstriction, whose origin was not understood. We used optical and magnetic resonance imaging approaches to investigate hemodynamics in neonatal mice. We found that sensory-induced vasoconstriction occurred when the mice were asleep, as sleep is associated with dilation of the vasculature of the brain relative to the awake state. The stimulus awakens the mice, causing a constriction due to the arousal state change. Our study shows the importance of monitoring arousal state, particularly when investigating subjects that may sleep, and the dominance arousal effects on brain hemodynamics.
Distribution-Free Statistical Inference with Lorenz Curves and Income Shares

The paper considers the problem of statistical inference with estimated Lorenz curves and income shares. The full variance-covariance structure of the (asymptotic) normal distribution of a vector of Lorenz curve ordinates is derived and shown to depend only on conditional first and second moments that can be estimated consistently without prior specification of the population density underlying the sample data. Lorenz curves and income shares can thus be used as tools for statistical inference instead of simply as descriptive statistics.
Discovery of novel microRNA mimic repressors of ribosome biogenesis

While microRNAs and other non-coding RNAs are the next frontier of novel regulators of mammalian ribosome biogenesis (RB), a systematic exploration of microRNA-mediated RB regulation has not yet been undertaken. We carried out a high-content screen in MCF10A cells for changes in nucleolar number using a library of 2,603 mature human microRNA mimics. Following a secondary screen for nucleolar rRNA biogenesis inhibition, we identified 72 novel microRNA negative regulators of RB after stringent hit calling. Hits included 27 well-conserved microRNAs present in MirGeneDB, and were enriched for mRNA targets encoding proteins with nucleolar localization or functions in cell cycle regulation. Rigorous selection and validation of a subset of 15 microRNA hits unexpectedly revealed that most of them caused dysregulated pre-rRNA processing, elucidating a novel role for microRNAs in RB regulation. Almost all hits impaired global protein synthesis and upregulated CDKN1A (p21) levels, while causing diverse effects on RNA Polymerase 1 (RNAP1) transcription and TP53 protein levels. We discovered that the MIR-28 siblings, hsa-miR-28-5p and hsa-miR-708-5p, directly and potently target the ribosomal protein mRNA RPS28 via tandem primate-specific 3’ UTR binding sites, causing a severe pre-18S pre-rRNA processing defect. Our work illuminates novel microRNA attenuators of RB, forging a promising new path for microRNA mimic chemotherapeutics. Graphical Abstract
Pharmacokinetics of felodipine extended-release tablets in healthy Taiwanese subjects: a retrospective review

Abstract The objective of this study was to investigate the pharmacokinetics of felodipine (CAS 72509-76-3) in healthy male Taiwanese subjects. This is a retrospective review of five felodipine pharmacokinetic studies completed in Taiwan. A total of 100 evaluable healthy Taiwanese males were enrolled in these studies. The subjects received 5 mg (n = 80) or 10 mg (n = 20) of Plendil® (felodipine extended-release tablets; felodipine ER) once daily for 6 days. The mean ± SD tmax, ss, Cmax, ss and AUCτ of dose normalized to 10 mg felodipine was 3.32 ± 1.33 h, 13.12 ± 5.34 nmol/L and 136.33 ± 63.18 nmol · h/L, respectively. By using Kolmogorov-Smirnov’s test and probit plots, the results indicated that the frequency distribution of AUC/dose, Cmin/ dose and CL/F was bimodal. Compared to data from the literature, the mean Cmax, ss and AUCτ of 5 mg felodipine in healthy young Taiwanese subjects were similar to or slightly lower than data from Swedish, Danish, Turkish and Canadian studies in healthy young subjects who received 10 mg felodipine. Comparable Cmax values and approximately 30% lower AUC values were observed when comparing the 5 mg Taiwanese data to data in healthy elderly German subjects who also received 5 mg felodipine. Taiwanese subjects might have lower CYP3A4 activity to metabolize felodipine, which is similar to the phenomenon observed with nifedipine.
Normalizers of nilpotent subgroups of division rings

Let D be an arbitrary division ring and G a nilpotent subgroup of the multiplicative group D* of D of class at most 2 such that D is generated as a division ring by G and the centralizer in D of G. The normalizer of G in D* is computed precisely, which extends a theorem of M. Shirvani from finite-dimensional division algebras to arbitrary division rings.
Astrocytic TIMP-1 regulates production of Anastellin, a novel inhibitor of oligodendrocyte differentiation and FTY720 responses

Astrocyte activation is associated with neuropathology and the production of tissue inhibitor of metalloproteinase-1 (TIMP1). TIMP1 is a pleiotropic extracellular protein that functions both as a protease inhibitor and as a growth factor. We have previously demonstrated that murine astrocytes that lack expression of Timp1 do not support rat oligodendrocyte progenitor cell (rOPC) differentiation, and adult global Timp1 knockout (Timp1KO) mice do not efficiently remyelinate following a demyelinating injury. To better understand the basis of this, we performed unbiased proteomic analyses and identified a fibronectin-derived peptide called anastellin that is unique to the murine Timp1KO astrocyte secretome. Anastellin was found to block rOPC differentiation in vitro and enhanced the inhibitory influence of fibronectin on rOPC differentiation. Anastellin is known to act upon the sphingosine-1-phosphate receptor 1 (S1PR1), and we determined that anastellin also blocked the pro-myelinating effect of FTY720 (or fingolimod) on rOPC differentiation in vitro. Further, administration of FTY720 to wild-type C57BL/6 mice during MOG35-55-EAE ameliorated clinical disability while FTY720 administered to mice lacking expression of Timp1 in astrocytes (Timp1cKO) had no effect. Analysis of human TIMP1 and fibronectin (FN1) transcripts from healthy and multiple sclerosis (MS) patient brain samples revealed an inverse relationship where lower TIMP1 expression was coincident with elevated FN1 in MS astrocytes. Lastly, we analyzed proteomic databases of MS samples and identified anastellin peptides to be more abundant in the cerebrospinal fluid (CSF) of human MS patients with high versus low disease activity. The prospective role for anastellin generation in association with myelin lesions as a consequence of a lack of astrocytic TIMP-1 production could influence both the efficacy of fingolimod responses and the innate remyelination potential of the the MS brain. Significance Statement Astrocytic production of TIMP-1 prevents the protein catabolism of fibronectin. In the absence of TIMP-1, fibronectin is further digested leading to a higher abundance of anastellin peptides that can bind to sphingosine-1-phosphate receptor 1. The binding of anastellin with the sphingosine-1-phosphate receptor 1 impairs the differentiation of oligodendrocytes progenitor cells into myelinating oligodendrocytes in vitro, and negates the astrocyte-mediated therapeutic effects of FTY720 in the EAE model of chronic CNS inflammation. These data indicate that TIMP-1 production by astrocytes is important in coordinating astrocytic functions during inflammation. In the absence of astrocyte produced TIMP-1, elevated expression of anastellin may represent a prospective biomarker for FTY720 therapeutic responsiveness.
A cleaved METTL3 potentiates the METTL3–WTAP interaction and breast cancer progression

N6-methyladenosine (m6A) methylation of RNA by the methyltransferase complex (MTC), with core components including METTL3-METTL14 heterodimers and Wilms’ tumor 1-associated protein (WTAP), contributes to breast tumorigenesis, but the underlying regulatory mechanisms remain elusive. Here, we identify a novel cleaved form METTL3a (residues 239-580 of METTL3). We find that METTL3a is required for the METTL3-WTAP interaction, RNA m6A deposition, as well as cancer cell proliferation. Mechanistically, we find that METTL3a is essential for the METTL3-METTL3 interaction, which is a prerequisite step for recruitment of WTAP in MTC. Analysis of m6A sequencing data shows that depletion of METTL3a globally disrupts m6A deposition, and METTL3a mediates mTOR activation via m6A-mediated suppression of TMEM127 expression. Moreover, we find that METTL3 cleavage is mediated by proteasome in an mTOR-dependent manner, revealing positive regulatory feedback between METTL3a and mTOR signaling. Our findings reveal METTL3a as an important component of MTC, and suggest the METTL3a-mTOR axis as a potential therapeutic target for breast cancer.
Deep-body feelings: ingestible pills reveal gastric correlates of emotions

Although it is generally held that gastro-intestinal (GI) signals are related to emotions, direct evidence for such a link is currently lacking. One of the reasons why the internal milieu of the GI system is poorly investigated is because visceral organs are difficult to access and monitor. To directly measure the influence of endoluminal markers of GI activity on the emotional experience, we asked a group of healthy male participants to ingest a pill that measured pH, pressure, and temperature of their GI tract while they watched video-clips that consistently induced disgust, fear, happiness, sadness, or a control neutral state. In addition to the objective physiological markers of GI activity, subjective ratings of perceived emotions and visceral (i.e. gastric, respiratory and cardiac) sensations were recorded. We found that when participants observed fearful and disgusting video-clips, they reported to perceive not only cardiac and respiratory sensations but also gastric sensations, such as nausea. Moreover, we found that there was a clear relation between the physiology of the stomach and the perceived emotions. Specifically, when disgusting video-clips were displayed, the more acidic the pH, the more participants reported feelings of disgust and fear; the less acidic the pH, the more they reported happiness. Our findings suggest that gastric signals contribute to unique emotional states and that ingestible pills may open new avenues for exploring the deep-body physiology of emotions.
Chronic Alcohol Drinking Drives Sex-Specific Differences in Affective Behavior and Medial Prefrontal Cortex Activity in CRF1:Cre:tdTomato Transgenic Rats

Abstract In 2021, 131 million adult Americans reported drinking alcohol in the last month, despite the well-known consequences of alcohol consumption. While alcohol use disorders (AUDs) are associated with both mood and chronic pain disorders, the relationship between alcohol drinking and affective and nociceptive behaviors remains unclear. Corticotropin releasing factor receptor-1 (CRF1) has been implicated in alcohol drinking, affective states, and pain sensitivity, often in a sex-dependent manner. In order to probe the effects of alcohol drinking on activity of CRF1+ cells and to also test the hypothesis that alcohol drinking is associated with both basal and subsequent affective and nociceptive readouts, we put male and female CRF1:cre:tdTomato rats through a battery of behavioral tests before and after intermittent access to alcohol. Following baseline testing, rats began alcohol (or water) drinking. Females consumed more alcohol in the first week, but there was no effect of sex on overall alcohol intake. Following three to four weeks of drinking, behavioral tests were repeated. Alcohol drinking decreased mechanical sensitivity, but no other effects of alcohol drinking were observed between experimental groups. Individual alcohol intake correlated with affective behavior in both sexes but only correlated with thermal sensitivity in males. There were no main effects of alcohol drinking or sex on CRF1+ neuronal activity in the medial prefrontal cortex (PFC) but final session alcohol intake correlated with activity in CRF1+ neurons in the infralimbic (IL) subregion. Together, our results suggest complex interplay between affective state, alcohol drinking, and the role of prefrontal CRF1+ neurons in mediating these behaviors.
Nonlinear evolution of magnetic flux ropes. 2: Finite beta plasma

In this second paper on the evolution of magnetic flux ropes we study the effects of gas pressure. We assume that the energy transport is described by a poly tropic relationship and reduce the set of ideal MHD equations to a single, second-order, nonlinear, ordinary differential equation for the evolution function. For this conservative system we obtain a first integral of motion. To analyze the possible motions, we use a mechanical analogue—a one-dimensional, nonlinear oscillator. We find that the effective potential for such an oscillator depends on two parameters: the polytropic index γ and a dimensionless quantity κ the latter being a function of the plasma beta, the strength of the azimuthal magnetic field relative to the axial field of the flux rope, and γ. Through a study of this effective potential we classify all possible modes of evolution of the system. In the main body of the paper, we focus on magnetic flux ropes whose field and gas pressure increase steadily towards the symmetry axis. In this case, for γ>1 and all values of κ, only oscillations are possible. For γ 1. While in most cases the flux rope collapses, there are notable exceptions when, for certain ranges of κ and γ, collapse may be averted.
Impact of respiratory motion on the detection of solitary pulmonary nodules with SPECT tumor imaging of NeoTect

We have previously modeled the respiratory motion of solitary pulmonary nodules (SPN) based on the change of location of anatomic structures within the lungs identified on breath-held CT images of volunteers acquired at two different stages of respiration. The goal of this investigation is to make use of this modeling to investigate the impact of respiratory motion on the detection of solitary pulmonary nodules with single photon emission computed tomographic (SPECT) imaging using Tc-99m labeled NeoTect. To do this, end-expiration and respiration-averaged source and attenuation maps were created from the NCAT phantom and input to the SIMIND Monte Carlo package.
Limitations of a linear model for the hurricane boundary layer

The linear model for the steady boundary layer of a rapidly rotating axisymmetric vortex is derived from a detailed scale analysis of the full equations of motion. The previously known analytic solution is re‐appraised for vortices of hurricane scale and strength. The internal consistency of the linear approximation is investigated for such a vortex by calculating from the solution the magnitude of the nonlinear terms that are neglected in the approximation compared with the terms retained. It is shown that the nonlinear terms are not negligibly small in a large region of the vortex, a feature that is consistent with the scale analysis. We argue that the boundary‐layer problem is well‐posed only at outer radii where there is subsidence into the layer. At inner radii, where there is ascent, only the radial pressure gradient may be prescribed and not the wind components at the top of the boundary layer, but the linear problem cannot be solved in these circumstances. We examine the radius at which the vertical flow at the top of the boundary layer changes sign for different tangential wind profiles relevant to hurricanes and show that this is several hundred kilometres from the vortex centre. This feature represents a further limitation of the linear model applied to hurricanes. While the present analysis assumes axial symmetry, the same limitations presumably apply to non‐axisymmetric extensions to the linear model. Copyright © 2009 Royal Meteorological Society
Numerical analysis of soil plug behaviour inside open-ended piles during driving

The plugging mechanism of infinitely-long open-ended piles is examined using numerical simulation of the wave propagation inside the soil plug and pile. It is shown that the key parameters for the plugging mechanism are the pile radius, the shape of the impact load, the shear wave velocity of the soil inside the pile, and the friction at the pile–soil interface. Consequently, the tendency of the pile to plug during driving can be assessed prior to the driving process by consideration of these key parameters. Existing one-dimensional models for the shaft response of open-ended piles are discussed and an improved model is presented. The differences between using one-dimensional models and finite element models to simulate the plugging process are examined. The differences are found to vary with the key parameters. Pile-in-pile and lumped-mass one-dimensional models are found to give satisfactory performance for some parameter combinations, while for others an axisymmetric finite element model must be used. © 1998 John Wiley & Sons, Ltd.