Miracle-dz/UniFAR-FTUs huggingface dataset:
Implication of the proprotein convertase NARC‐1/PCSK9 in the development of the nervous system

Neural apoptosis‐regulated convertase‐1/proprotein convertase subtilisin‐kexin like‐9 (NARC‐1/PCSK9) is a proprotein convertase recently described to play a major role in cholesterol homeostasis through enhanced degradation of the low‐density lipoprotein receptor (LDLR) and possibly in neural development. Herein, we investigated the potential involvement of this proteinase in the development of the CNS using mouse embryonal pluripotent P19 cells and the zebrafish as models. Time course quantitative RT–PCR analyses were performed following retinoic acid (RA)‐induced neuroectodermal differentiation of P19 cells. Accordingly, the mRNA levels of NARC‐1/PCSK9 peaked at day 2 of differentiation and fell off thereafter. In contrast, the expression of the proprotein convertases subtilisin kexin isozyme 1/site 1 protease and Furin was unaffected by RA, whereas that of PC5/6 and PC2 increased within and/or after the first 4 days of the differentiation period respectively. This pattern was not affected by the cholesterogenic transcription factor sterol regulatory element‐binding protein‐2, which normally up‐regulates NARC‐1/PCSK9 mRNA levels in liver. Furthermore, in P19 cells, RA treatment did not affect the protein level of the endogenous LDLR. This agrees with the unique expression pattern of NARC‐1/PCSK9 in the rodent CNS, including the cerebellum, where the LDLR is not significantly expressed. Whole‐mount in situ hybridization revealed that the pattern of expression of zebrafish NARC‐1/PCSK9 is similar to that of mouse both in the CNS and periphery. Specific knockdown of zebrafish NARC‐1/PCSK9 mRNA resulted in a general disorganization of cerebellar neurons and loss of hindbrain–midbrain boundaries, leading to embryonic death at ∼ 96 h after fertilization. These data support a novel role for NARC‐1/PCSK9 in CNS development, distinct from that in cholesterogenic organs such as liver.
Glutamate dehydrogenase from Escherichia coli: purification and properties

Glutamate dehydrogenase (L-glutamate:NADP+ oxidoreductase [deaminating], EC 1.4.1.4) has been purified from Escherichia coli B/r. The purity of the enzyme preparation has been established by polyacrylamide gel electrophoresis, ultracentrifugation, and gel filtration. A molecular weight of 300,000 +/- 20,000 has been calculated for the enzyme from sedimentation equilibrium measurements. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate and sedimentation equilibrium measurements in guanidine hydrochloride have revealed that glutamate dehydrogenase consists of polypeptide chains with the identical molecular weight of 50,000 +/- 5,000. The results of molecular weight determination lead us to propose that glutamate dehydrogenase is a hexamer of subunits with identical molecular weight. We also have studied the stability and kinetics of purified glutamate dehydrogenase. The enzyme remains active when heat treated or when left at room temperature for several months but is inactivated by freezing. The Michaelis constants of glutamate dehydrogenase are 1,100,640, and 40 muM for ammonia, 2-oxoglutarate, and reduced nicotinamide adenine dinucleotide phosphate, respectively.
From Small Space to Small Width in Resolution

In 2003, Atserias and Dalmau resolved a major open question about the resolution proof system by establishing that the space complexity of a Conjunctive Normal Form (CNF) formula is always an upper bound on the width needed to refute the formula. Their proof is beautiful but uses a nonconstructive argument based on Ehrenfeucht-Fraïssé games. We give an alternative, more explicit, proof that works by simple syntactic manipulations of resolution refutations. As a by-product, we develop a “black-box” technique for proving space lower bounds via a “static” complexity measure that works against any resolution refutation—previous techniques have been inherently adaptive. We conclude by showing that the related question for polynomial calculus (i.e., whether space is an upper bound on degree) seems unlikely to be resolvable by similar methods.
Synchrony and Causal Relations Between Permian-Triassic Boundary Crises and Siberian Flood Volcanism

The Permian-Triassic boundary records the most severe mass extinctions in Earth's history. Siberian flood volcanism, the most profuse known such subaerial event, produced 2 million to 3 million cubic kilometers of volcanic ejecta in approximately 1 million years or less. Analysis of 40Ar/39Ar data from two tuffs in southern China yielded a date of 250.0 � 0.2 million years ago for the Permian-Triassic boundary, which is comparable to the inception of main stage Siberian flood volcanism at 250.0 � 0.3 million years ago. Volcanogenic sulfate aerosols and the dynamic effects of the Siberian plume likely contributed to environmental extrema that led to the mass extinctions.
A New Distributed Time Synchronization Protocol for Multihop Wireless Networks

A distributed algorithm to achieve accurate time synchronization in large multihop wireless networks is presented. The central idea is to exploit the large number of global constraints that have to be satisfied by a common notion of time in a multihop network. If, at a certain instant, O<sub>ij</sub> is the clock offset between two neighboring nodes i and j, then for any loop i<sub>1</sub>, i<sub>2</sub>, i<sub>3 </sub>, . , i<sub>n</sub>, i<sub>n + 1</sub> - i<sub>1</sub> in the multihop network, these offsets must satisfy the global constraint Sigma <sub>k = 1</sub> <sup>n</sup>O<sub>ik</sub>, i<sub>k + 1</sub> = 0. Noisy estimates Ocirc <sub>ij</sub> of O<sub>ij</sub> are usually arrived at by bilateral exchanges of timestamped messages or local broadcasts. By imposing the large number of global constraints for all the loops in the multihop network, these estimates can be smoothed and made more accurate. A fully distributed and asynchronous algorithm which functions by simple local broadcasts is designed. Changing the time reference node for synchronization is also easy, consisting simply of one node switching on adaptation, and another switching it off. Implementation results on a forty node network, and comparative evaluation against a leading algorithm, are presented
The Facets of Hostile Attributional Bias: The Importance of Aggression Subtypes and Provocateur Motivation

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Load-Deflection Behavior of Lime-Stabilized Layers

The static and dynamic load-deflection response of soil-lime pavement layers was investigated. Soil-lime mixture layers 6, 9, and 12 in. thick were compacted over a stiff subgrade (k=450 psi/in.) and a soft subgrade (k=50 psi/in.). The soil-lime layers were statically and dynamically loaded after curing periods of 2, 14, 28, and 56 days. Supplemental subgrade soil and soil-lime mixture property data were also developed. The load-deflection data are summarized and analyzed. Various pavement behavior theories are evaluated to determine their capability to predict the load-deflection behavior of soil-lime pavement layers.
Relationship of brain morphine levels to analgesic activity in acutely treated mice and rats and in pellet implanted mice.

The relationship of brain morphine concentration, determined fluorometrically, to tail-flick activity was investigated after acute and chronic morphine treatment of mice and acute treatment of rats. Brain morphine levels were quantitatively related to the analgesic effect on acute administration, with levels of 100 and 140 ng/g of tissue corresponding to the ED50 in mice and rats, respectively. Over a 90-minute time course after acute s.c. injection, the analgesic effect of morphine in the tail-flick test lagged slightly behind morphine brain level in both species. In mice implanted s.c. with morphine pellets, significant analgesia and appreciable morphine brain levels appeared as early as 20 to 30 minutes after implantation. Increased brain morphine corresponded to increased analgesia at 1 and 4 hours after implantation. Tolerance was evident by 24 hours after implantation and was maximal at 72 hours. Brain morphine remained elevated up to 144 hours after implantation even though substantial encapsulation of the pellet occurred within 72 hours. If pellets were removed at 72 hours, brain morphine declined to control levels with 6 hours, but significant tolerance persisted for at least 24 hours after pellet removal. These results demonstrate that morphine is absorbed from the pellet up to 6 days after implantation and that the decreased analgesic activity observed in the latter times is due to tolerance to the narcotic and not to a decrease in absorption from the pellet.
Evidence for Differential Control of Posterior Hypothalamic, Supramammillary, and Medial Mammillary Theta-Related Cellular Discharge by Ascending and Descending Pathways

Single-unit discharge was recorded from cells in the posterior hypothalamic nucleus (PH), supramammillary nucleus (SuM), and medial mammillary nucleus (MM) during hippocampal theta (θ) elicited by stimulation of the reticular nucleus pontis oralis (RPO). In agreement with previously published work, θ-related cells in the PH (12 cells) were all classified as tonic θ-ON (increased tonic discharge rate during hippocampal θ), whereas those in the SuM (9 cells) and MM (15 cells) were all classified as phasic θ-ON (rhythmic discharge, in phase with ongoing θ). The effect of RPO stimulation on cell discharge was tested after hippocampal θ was abolished by infusion of procaine into the medial septum/vertical limb of the diagonal band. The RPO-elicited discharge patterns of all PH tonic θ-ON cells and all SuM phasic θ-ON cells survived septal procaine infusion. Further, the discharge rate of PH cells and the frequency of burst discharge of SuM cells during RPO stimulation both increased after the infusion. In contrast, septal procaine infusion abolished the RPO-elicited rhythmic discharge pattern in MM phasic θ-ON cells and attenuated their discharge rates. These results indicate that the PH and SuM form parts of an ascending system mediating hippocampal θ, whereas the MM receives (and perhaps relays to other parts of the limbic system) rhythmic input descending from the septo-hippocampal system. In addition, PH and SuM receive descending inputs that limit the discharge rates of their θ-related cells during hippocampal θ.
Lycopene supplementation prevents reactive oxygen species mediated apoptosis in Sertoli cells of adult albino rats exposed to polychlorinated biphenyls

Abstract Sertoli cell proliferation is attenuated before attaining puberty and the number is fixed in adult testes. Sertoli cells determine both testis size and daily sperm production by providing physical and metabolic support to spermatogenic cells. Polychlorinated biphenyls (PCBs) exposure disrupts functions of Sertoli cells causing infertility with decreased sperm count. On the other hand, lycopene is improving sperm count and motility by reducing oxidative stress in humans and animals. Hence we hypothesized that PCBs-induced infertility might be due to Sertoli cell apoptosis mediated by oxidative stress and lycopene might prevent PCBs-induced apoptosis by acting against oxidative stress. To test this hypothesis, animals were treated with vehicle control, lycopene, PCBs and PCBs + lycopene for 30 days. After the experimental period, the testes and cauda epididymidis were removed for isolation of Sertoli cells and sperm, respectively. We observed increased levels of oxidative stress markers (H2O2 and LPO) levels, increased expression of apoptotic molecules (caspase-8, Bad, Bid, Bax, cytochrome C and caspase-3), decreased anti-apoptotic (Bcl2) molecule and elevated apoptotic marker activity (caspase-3) in Sertoli cells of PCBs-exposed animals. These results were associated with decreased sperm count and motility in PCBs exposed animals. On the other hand, lycopene prevented the elevation of Sertoli cellular apoptotic parameters and prevented the reduction of sperm parameters (count and motility). The data confirmed that lycopene as an antioxidant scavenged reactive oxygen substances, prevented apoptosis, maintained normal function in Sertoli cells and helped to provide physical and metabolic support for sperm production, thereby treating infertility in men.
Neural interaction in cat primary auditory cortex II. Effects of sound stimulation.

1. The effect of auditory stimulation with click trains, noise bursts, amplitude-modulated noise bursts, and amplitude-modulated tone bursts on the correlation of firing of 1,290 neuron pairs recorded on one or two electrodes in primary auditory cortex of the cat was investigated. A distinction was made between neural synchrony (the correlation under stimulus conditions) and neural correlation (the correlation under spontaneous or under stimulus conditions after correction for stimulus-related correlations). For neural correlation 63% of the single-electrode pairs showed a unilateral excitation component, often combined with a common-input peak, and only 11% of the dual electrode pairs showed this unilateral excitation. 2. Under poststimulus conditions the incidence of correlograms with clear peaks was high for single-electrode pairs (80-90% range) and somewhat lower for dual-electrode pairs (50-60% range). The strength of the neural correlation for poststimulus conditions, from 0.5 to 2 s after a 1-s stimulus, was comparable with that obtained for 15-min continuous silence, suggesting that aftereffects of stimulation had largely disappeared after 0.5 s. A stationary analysis of the correlation coefficient corroborated this. 3. Two stimulus-correction procedures, one based on the shift predictor and the other based on the joint peristimulus-time histogram (JPSTH) were compared. The mean value of the neural correlation under stimulus conditions obtained after applying the poststimulus time (PST) predictor was on average 20% larger than the mean value obtained after application of the shift predictor; however, this was not significantly different at the 0.05 level. There were no differences in the shape of the correlograms. This suggests that the less time-consuming shift predictor-based stimulus-correction procedure can be used for cortical neurons. 4. Under stimulus conditions neural correlation coefficients could be < or = 50% smaller than for spontaneous conditions. The strength of the stimulus-corrected neural correlation was inversely related to the relative size of the stimulus predictor (compared with the neural synchrony) and thus to the effectiveness of stimulation. This suggests that the assumption of additivity of stimulus and connectivity effects on neural synchrony is generally violated both for shift predictor and PST predictor procedures. 5. The neural correlogram peaks were narrower for single-electrode pairs than for dual-electrode pairs both under stimulus and spontaneous conditions. Under stimulus conditions the peaks were generally narrower than under spontaneous firing conditions. (ABSTRACT TRUNCATED AT 400 WORDS)
Genome size of 14 species of fireflies (Insecta, Coleoptera, Lampyridae)

Eukaryotic genome size data are important both as the basis for comparative research into genome evolution and as estimators of the cost and difficulty of genome sequencing programs for non-model organisms. In this study, the genome size of 14 species of fireflies (Lampyridae) (two genera in Lampyrinae, three genera in Luciolinae, and one genus in subfamily incertae sedis) were estimated by propidium iodide (PI)-based flow cytometry. The haploid genome sizes of Lampyridae ranged from 0. 42 to 1. 31 pg, a 3. 1-fold span. Genome sizes of the fireflies varied within the tested subfamilies and genera. Lamprigera and Pyrocoelia species had large and small genome sizes, respectively. No correlation was found between genome size and morphological traits such as body length, body width, eye width, and antennal length. Our data provide additional information on genome size estimation of the firefly family Lampyridae. Furthermore, this study will help clarify the cost and difficulty of genome sequencing programs for non-model organisms and will help promote studies on firefly genome evolution.
Antileishmanial Activity of the Estrogen Receptor Modulator Raloxifene

Background The treatment of leishmaniasis relies mostly on parenteral drugs with potentially serious adverse effects. Additionally, parasite resistance in the treatment of leishmaniasis has been demonstrated for the majority of drugs available, making the search for more effective and less toxic drugs and treatment regimens a priority for the control of leishmaniasis. The aims of this study were to evaluate the antileishmanial activity of raloxifene in vitro and in vivo and to investigate its mechanism of action against Leishmania amazonensis. Methodology/Principal Findings Raloxifene was shown to possess antileishmanial activity in vitro against several species with EC50 values ranging from 30.2 to 38.0 µM against promastigotes and from 8.8 to 16.2 µM against intracellular amastigotes. Raloxifene's mechanism of action was investigated through transmission electron microscopy and labeling with propidium iodide, DiSBAC2(3), rhodamine 123 and monodansylcadaverine. Microscopic examinations showed that raloxifene treated parasites displayed autophagosomes and mitochondrial damage while the plasma membrane remained continuous. Nonetheless, plasma membrane potential was rapidly altered upon raloxifene treatment with initial hyperpolarization followed by depolarization. Loss of mitochondrial membrane potential was also verified. Treatment of L. amazonensis – infected BALB/c mice with raloxifene led to significant decrease in lesion size and parasite burden. Conclusions/Significance The results of this work extend the investigation of selective estrogen receptor modulators as potential candidates for leishmaniasis treatment. The antileishmanial activity of raloxifene was demonstrated in vitro and in vivo. Raloxifene produces functional disorder on the plasma membrane of L. amazonensis promastigotes and leads to functional and morphological disruption of mitochondria, which culminate in cell death.
HySIM: A hybrid spectrum and information market for TV white space networks

We propose a hybrid spectrum and information market for database-assisted TV white space networks, where a geo-location white space database serves as the platform for both the spectrum market and the information market. We study the interactions among the database operator, the spectrum licensee, and unlicensed users systematically, using a three-layer hierarchical model. In Layer I, the licensee negotiates with the database regarding the commission fee of using the spectrum market platform. In Layer II, the database and the licensee compete for selling information or channels to unlicensed users. In Layer III, unlicensed users determine whether to buy the exclusive usage right of licensed channels from the licensee, or to buy the information regarding unlicensed channels from the database. Analyzing such a three-layer model is challenging, due to the coexistence of both positive and negative network externalities in the information market. We characterize the market equilibrium systematically, and analyze how the network externalities affect the equilibrium behaviours of all parties involved. Our numerical results show that the proposed hybrid market can improve the network profit more than 80%, compared with a pure information market. Meanwhile, the achieved network profit is very close to the coordinated benchmark (e.g., the gap is less than 4%).
Development of a Novel Bioinformatics Tool for In Silico Validation of Protein Interactions

Protein interactions are crucial in most biological processes. Several in silico methods have been recently developed to predict them. This paper describes a bioinformatics method that combines sequence similarity and structural information to support experimental studies on protein interactions. Given a target protein, the approach selects the most likely interactors among the candidates revealed by experimental techniques, but not yet in vivo validated. The sequence and the structural information of the in vivo confirmed proteins and complexes are exploited to evaluate the candidate interactors. Finally, a score is calculated to suggest the most likely interactors of the target protein. As an example, we searched for GRB2 interactors. We ranked a set of 46 candidate interactors by the presented method. These candidates were then reduced to 21, through a score threshold chosen by means of a cross-validation strategy. Among them, the isoform 1 of MAPK14 was in silico confirmed as a GRB2 interactor. Finally, given a set of already confirmed interactors of GRB2, the accuracy and the precision of the approach were 75% and 86%, respectively. In conclusion, the proposed method can be conveniently exploited to select the proteins to be experimentally investigated within a set of potential interactors.
Stellar magnetism

A Sun-like star undergoes magnetic cyclic reversal shown by field lines colored by the longitudinal magnetic field. Shifts in positive and negative polarity demonstrate large-scale polarity changes in the star. One such cycle is shown, and at the end of the visualization, the magnetic poles are reversed. Wreath-like areas in the magnetic field could be the source of Sun spots which are an important area of study. Rendering was performed through the visualization tool VAPOR using the OpenGL interception program GLuRay which renders with the interactive ray tracer Manta. Visualizations were rendered on TACC Longhorn an NSF-XD Visualization resource.
Changes in the expression of melatonin receptors induced by melatonin treatment in hepatocarcinoma HepG2 cells

Abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers and its incidence is increasing worldwide. Melatonin, an indoleamine hormone, exerts anti‐oxidant, immunomodulatory, anti‐aging, and antitumor effects. Previous studies have shown that melatonin can act through specific receptors, including MT1, MT2, MT3 receptors as well as a nuclear receptor belonging to the orphan nuclear receptor family. Recently, we have described their role in the oncostatic and pro‐apoptotic effects of melatonin on HepG2 human HCC cells. However, the potential role of the different melatonin cellular receptors on its antiproliferative effects remains unknown. In the present study, we examined the effect of melatonin treatment on HepG2 human HCC cells, analyzing cell cycle arrest and melatonin receptor expression. Melatonin was administered for 2, 4, and 6 days at 1000 or 2500 μm. Melatonin induced a dose‐ and time‐dependent inhibition on cell proliferation. This treatment caused an alteration in the cell cycle, with an increase in the number of cells in G2/M phase at both 1000 and 2500 μm melatonin concentrations, and a significant increase on S phase cell percentage by the highest dose. Furthermore, increases in protein expression of MT1, MT3, and retinoic acid‐related orphan receptor‐α were found after melatonin treatments. These increases were coincident with a significant induction in the expression of p21 protein, which negatively regulates cell cycle progression. Our results confirm the antitumor effect of melatonin in HCC cells, suggesting that its oncostatic properties are related, at least in part, to changes on the expression of their different subtypes of receptors.