Miracle-dz/UniFAR-FTUs huggingface dataset:
The NBS-LRR architectures of plant R-proteins and metazoan NLRs evolved in independent events

Significance Instances of convergent evolution in innate immune systems can reveal fundamental principles of immunity. We use phylogenetic reconstruction and tests of alternative evolutionary hypotheses combined with ancestral state reconstruction and an analysis of the phylogenetic distribution of the nucleotide binding site–leucine rich repeat (NBS-LRR) architecture to demonstrate that most likely, two distinct and separate evolutionary events gave rise to the NBS-LRR architecture in plant resistance proteins (R-proteins) and metazoan NOD-like receptors (NLRs), and furthermore, the STAND NTPase of both protein families was likely inherited from ancestral proteins with an NBS–tetratricopeptide (TPR) architecture. The implication is that the NBS-LRR architecture has special functionality for innate immune receptors. There are intriguing parallels between plants and animals, with respect to the structures of their innate immune receptors, that suggest universal principles of innate immunity. The cytosolic nucleotide binding site–leucine rich repeat (NBS-LRR) resistance proteins of plants (R-proteins) and the so-called NOD-like receptors of animals (NLRs) share a domain architecture that includes a STAND (signal transduction ATPases with numerous domains) family NTPase followed by a series of LRRs, suggesting inheritance from a common ancestor with that architecture. Focusing on the STAND NTPases of plant R-proteins, animal NLRs, and their homologs that represent the NB-ARC (nucleotide-binding adaptor shared by APAF-1, certain R gene products and CED-4) and NACHT (named for NAIP, CIIA, HET-E, and TEP1) subfamilies of the STAND NTPases, we analyzed the phylogenetic distribution of the NBS-LRR domain architecture, used maximum-likelihood methods to infer a phylogeny of the NTPase domains of R-proteins, and reconstructed the domain structure of the protein containing the common ancestor of the STAND NTPase domain of R-proteins and NLRs. Our analyses reject monophyly of plant R-proteins and NLRs and suggest that the protein containing the last common ancestor of the STAND NTPases of plant R-proteins and animal NLRs (and, by extension, all NB-ARC and NACHT domains) possessed a domain structure that included a STAND NTPase paired with a series of tetratricopeptide repeats. These analyses reject the hypothesis that the domain architecture of R-proteins and NLRs was inherited from a common ancestor and instead suggest the domain architecture evolved at least twice. It remains unclear whether the NBS-LRR architectures were innovations of plants and animals themselves or were acquired by one or both lineages through horizontal gene transfer.
Sulfhydryls associated with H2O2-induced channel activation are on luminal side of ryanodine receptors.

The mechanism underlying H2O2-induced activation of frog skeletal muscle ryanodine receptors was studied using skinned fibers and by measuring single Ca2+-release channel current. Exposure of skinned fibers to 3-10 mM H2O2 elicited spontaneous contractures. H2O2 at 1 mM potentiated caffeine contracture. When the Ca2+-release channels were incorporated into lipid bilayers, open probability ( P o) and open time constants were increased on intraluminal addition of H2O2 in the presence of cis catalase, but unitary conductance and reversal potential were not affected. Exposure to cis H2O2 at 1.5 mM failed to activate the channel in the presence of trans catalase. Application of 1.5 mM H2O2 to the transside of a channel that had been oxidized by cis p-chloromercuriphenylsulfonic acid (pCMPS; 50 μM) still led to an increase in P o, comparable to that elicited by trans 1.5 mM H2O2 without pCMPS. Addition of cis pCMPS to channels that had been treated with or without trans H2O2 rapidly resulted in high P o followed by closure of the channel. These results suggest that oxidation of luminal sulfhydryls in the Ca2+-release channel may contribute to H2O2-induced channel activation and muscle contracture.
Spatially patterned gene expression for guided neurite extension

Axon pathfinding by localized expression of guidance molecules is critical for the proper development of the nervous system. In this report, we present a well‐defined spatially patterned gene expression system to investigate neurite guidance in vitro. Nonviral gene delivery was patterned by combining substrate‐mediated gene delivery with soft lithography techniques, and the amount of protein produced at the region of localized expression was varied by altering the vector concentration and the width of the pattern, highlighting the flexibility of the system. A neuronal coculture model was used to investigate responses to spatial patterns of nerve growth factor (NGF) expression. The soluble NGF gradient elicited a guidance cue, and the degree of guidance was governed by the distance a neuron was cultured from the pattern and the time between accessory cell and neuron seedings. A portion of the diffusible NGF bound to the culture surface in the extracellular space, and the surface‐associated NGF supported neuron survival and neurite outgrowth. However, the surface‐bound NGF gradient alone did not elicit a guidance signal, and in fact masked the guidance cue by soluble NGF gradients. Mathematical modeling of NGF diffusion was used to predict the concentration gradients, and both the absolute and fractional gradients capable of guiding neurites produced by patterned gene expression differed substantially from the values obtained with existing engineered protein gradients. Spatially patterned gene expression provides a versatile tool to investigate the factors that may promote neurite guidance. © 2008 Wiley‐Liss, Inc.
Long-term regulation of contractility and calcium current in smooth muscle.

Longitudinal smooth muscle strips from guinea pig ileum were cultured in vitro for 5 days, and the relationship between extracellular Ca2+ and force in high-K+ medium was evaluated. In strips cultured with 10% fetal calf serum (FCS), this relationship was shifted to the right (50% effective concentration changed by 2-3 mM) compared with strips cultured without FCS. The shift was prevented by inclusion of verapamil (1 μM) during culture and mimicked by ionomycin in the absence of FCS. The intracellular Ca2+ concentration ([Ca2+]i) during stimulation with high-K+solution or carbachol was reduced after culture with FCS, whereas the [Ca2+]i-force relationship was unaffected. Cells were isolated from cultured strips, and whole cell voltage-clamp experiments were performed. Maximum inward Ca2+ current (10 mM Ba2+), normalized to cell capacitance, was almost three times smaller in cells isolated from strips cultured with FCS. Culture with 1 μM verapamil prevented this reduction. These results suggest that increased [Ca2+]iduring culture downregulates Ca2+current density, with associated effects on contractility.
Myoglobin desaturation with exercise intensity in human gastrocnemius muscle.

The present study evaluated whether intracellular partial pressure of O2 ([Formula: see text]) modulates the muscle O2 uptake (V˙o 2) as exercise intensity increased. Indirect calorimetry followedV˙o 2, whereas nuclear magnetic resonance (NMR) monitored the high-energy phosphate levels, intracellular pH, and intracellular[Formula: see text] in the gastrocnemius muscle of four untrained subjects at rest, during plantar flexion exercise with a constant load at a repetition rate of 0.75, 0.92, and 1.17 Hz, and during postexercise recovery.V˙o 2 increased linearly with exercise intensity and peaked at 1.17 Hz (15.1 ± 0.37 watts), when the subjects could maintain the exercise for only 3 min.V˙o 2 reached a peak value of 13.0 ± 1.59 ml O2 ⋅ min-1 ⋅ 100 ml leg volume-1. The31P spectra indicated that phosphocreatine decreased to 32% of its resting value, whereas intracellular pH decreased linearly with power output, reaching 6.86. Muscle ATP concentration, however, remained constant throughout the exercise protocol. The 1H NMR deoxymyoglobin signal, reflecting the cellular[Formula: see text], decreased in proportion to increments in power output andV˙o 2. At the highest exercise intensity and peakV˙o 2, myoglobin was ∼50% desaturated. These findings, taken together, suggest that the O2 gradient from hemoglobin to the mitochondria can modulate the O2flux to meet the increasedV˙o 2 in exercising muscle, but declining cellular [Formula: see text]during enhanced mitochondrial respiration suggests that O2 availability is not limitingV˙o 2 during exercise.
JMY Functions as Actin Nucleation-Promoting Factor and Mediator for p53-Mediated DNA Damage in Porcine Oocytes

Junction-mediating and regulatory protein(JMY) is a multifunctional protein with roles in the transcriptional co-activation of p53 and the regulation of actin nucleation promoting factors and, hence, cell migration; however, its role in the maturation of porcine oocytes is unclear. In the current study, we investigated functional roles of JMY in porcine oocytes. Porcine oocytes expressed JMY mRNA and protein, and the mRNA expression level decreased during oocyte maturation. Knockdown of JMY by RNA interference decreased the rate of polar body extrusion, validating its role in the asymmetric division of porcine oocytes. JMY knockdown also down-regulated the mRNA and protein levels of actin and Arp2/3. Furthermore, JMY accumulated in the nucleus in response to DNA damage, and JMY knockdown suppressed DNA damage-mediated p53 activation. In conclusion, our results show that JMY has important roles in oocyte maturation as a regulator of actin nucleation-promoting factors and an activator of p53 during DNA damage during DNA damages in porcine oocytes.
Serum levels of β-hydroxybutyrate and pyruvate, metabolic changes and cognitive function in patients with schizophrenia during antipsychotic treatment: a preliminary study

Background β-hydroxybutyrate (β-HB) and pyruvate have been associated with the brain energy utilization, which may play a role in the pathophysiology of schizophrenia. In this prospective study, we aim to investigate the trends of β-HB and pyruvate levels, metabolic changes, and cognitive function in schizophrenia patients receiving antipsychotic treatment. Objective We recruited 38 schizophrenia patients who had been treated with antipsychotics for 12 weeks, as well as 38 healthy age- and gender-matched subjects. Blood samples were taken from the patients at baseline and week 12 to determine the serum levels of β-HB, pyruvate, and metabolic parameters, while blood samples of the healthy controls were taken at baseline. We evaluated the psychopathology using the Positive and Negative Syndrome Scale and cognitive function using the Brief Assessment of Cognition in Schizophrenia. Results During the 12-week follow-up period, the β-HB levels in patients with schizophrenia showed a decreasing trend, particularly in those undergoing treatment with aripiprazole or ziprasidone. The serum levels of β-HB in patients at baseline and week 12 were both higher than the levels in the healthy controls. Among the schizophrenia patients, changes in β-HB were positively correlated with changes in executive function. On the other hand, serum pyruvate levels remained steady during the 12-week follow-up period, and we found no significant correlation between pyruvate changes and changes in cognitive function or clinical symptoms. Conclusion Our findings indicate that β-HB may possess a potential indicator of energy utilization and have a protective role in executive function in patients with schizophrenia. Additional longitudinal studies with a larger sample size and longer follow-up periods are necessary to identify the relationship of metabolite regulation and cognitive function during schizophrenia patients’ exposure to antipsychotics.
THE EFFECTS OF STEEL AND PET FIBERS ON THE PROPERTIES OF FRESH AND HARDENED SELF-COMPACTING CONCRETE

Self-compacting concrete (SCC) due to several economical and technical advantages is increasingly used in construction industry. It can be improved on strength behavior when the fibers are added. Although the workability as a significant factor for this concrete must be maintained. This investigation experimentally evaluated the effects of steel and PET (polyethylene terephthalate) fibers separately on the properties of either fresh or hardened SCC. Fresh properties of concrete have been investigated by slump flow, V-funnel and Lbox tests. Hardended properties were tested for compressive strength, splitting tensile strength, flexural strength, shrinkage and ultrasonic pulse velocity (UPV) tests. The results showed that 30 Kg/m Steel and 3 Kg/m PET fibers can be considered as suitable contents regarding to fresh and hardened properties of SCC. However, the addition of PET fibers have caused a slight decrease in compressive strength.
Na-Pi cotransport sites in proximal tubule and collecting tubule of winter flounder ( Pleuronectes americanus).

Localization of a recently described and cloned Na-Pi cotransport system from flounder was investigated by reverse transcription-polymerase chain reaction (RT-PCR) of microdissected tubules and by immunocytochemistry of kidney of winter flounder. Histological examination showed a small glomerulus, an extremely short proximal tubule PI with a selective affinity to Lens culinaris agglutinin from lentils, and an extensive second proximal tubule segment PII (>90% of proximal tubules), consisting of cells with numerous apical clear vesicles and extensive amplification of basolateral cell membranes. PII merged with the collecting tubule/collecting duct (CT/CD) system without a distal segment. By RT-PCR, PII cells revealed high levels of NaPi-II related RNA; low levels were also observed in CTs. Previously characterized antisera against different epitopes of flounder NaPi-II specifically labeled the basolateral regions of PII and the apical cell portion of CT/CD cells and of some PII cells. These results suggest that tubular secretion of Pi occurs in PII of teleost fish with modulation of urinary Picontent in the subsequent CT/CD system.
Adenosine kinase inhibitor GP 515 attenuates hepatic leukocyte adhesion after hemorrhagic hypotension

Bauer, Clemens, Maarten G. Bouma, Isa Herrmann, Frans A. J. M. van den Wildenberg, Gary S. Firestein, Ingo Marzi, and Wim A. Buurman. Adenosine kinase inhibitor GP515 attenuates hepatic leukocyte adhesion after hemorrhagic hypotension. Am. J. Physiol. 273 (Gastrointest. Liver Physiol. 36): G1297–G1303, 1997. —Adhesion of leukocytes to the vascular endothelium hallmarks a key event in neutrophil-mediated organ injury after ischemia-reperfusion. The autacoid adenosine has been shown to inhibit activated neutrophil function and to interfere with leukocyte-endothelial adherence. Its therapeutic use in ischemia-reperfusion, however, has been limited by severe cardiovascular side effects. We therefore investigated the effects of the adenosine kinase inhibitor GP515 in vivo on hepatic leukocyte-endothelial interactions in a rat model of hemorrhagic hypotension and resuscitation, using intravital microscopy. Rats were pretreated with either GP515 (0.25 mg/kg) or saline in a randomized and blinded manner and subjected to pressurecontrolled hemorrhagic hypotension at a mean arterial pressure of 40 mmHg for 60 min followed by 5 h of resuscitation. Five hours after resuscitation in saline-treated animals, firm leukocyte-sinusoidal adhesion was strongly enhanced in the periportal and midzonal sublobular regions, and sinusoidal diameters were also markedly reduced. Compared with saline treatment, GP515 significantly attenuated shock and resuscitation-induced leukocyte adhesion in both sublobular regions. Moreover, although GP515 did not significantly affect macrohemodynamical and hematological parameters, it enlarged narrowed sinusoidal diameters and tended to improve sinusoidal blood flow. We propose that the adenosineregulating agent GP515 has a therapeutic potential to attenuate ischemia-reperfusion-induced inflammation by capitalizing on the beneficial anti-inflammatory effects of endogenous adenosine.
Fear and Disgust of Spiders: Factors that Limit University Preservice Middle School Science Teachers

Spiders perform many essential ecological services, yet humans often experience negative emotions toward spiders. These emotions can lead to the avoidance of beneficial events. These emotions may affect beliefs about what should or should not be included in a science curriculum. This study investigated how activities with living spiders affected preservice middle school science teachers’ emotions and beliefs. Prior to the activities both groups (i.e., treatment and control) had moderate to extreme fear and disgust toward the spider. The teachers that participated in the spider activities (i.e., treatment group) had much lower levels of fear and disgust after performing the spider activities than the control group that did not participate in the spider activities. The control group continued to have elevated levels of fear and disgust toward the spider throughout the study. Before the spider activities neither group planned to incorporate information about spiders or information about the essential ecological services of spiders into their science classroom. After the treatment group participated in the spider activities, the teachers had definitive plans to teach their students about spiders and the essential ecological services that they provide. The control group remained unchanged and had no plans to teach this information to their students.
Taurine depletion, a novel mechanism for cardioprotection from regional ischemia.

Three processes that have been implicated in ischemic injury are impaired Ca2+movement, altered osmoregulation, and membrane remodeling. Because the amino acid, taurine, affects all three processes, it seemed logical that changes in the myocardial content of taurine might affect ischemic injury. To test this hypothesis, infarct size and areas at risk were compared in isolated hearts from control and taurine-depleted rats after a 45-min ligation of the left anterior descending coronary artery and 2 h of reperfusion. Hearts of rats treated for 4 wk with the taurine inhibitor, β-alanine, exhibited a 57% reduction in the infarct size-to-risk area ratio. The degree of cardioprotection was found to correlate ( r = 0.85) with the extent of taurine depletion, the latter dependent on the length of β-alanine feeding. When the taurine-depleted rats were fed taurine, myocardial taurine levels were restored and the cardioprotection was lost. However, addition of neither β-alanine (3%) nor taurine (20 mM) to the perfusion medium altered infarct size. We conclude that taurine depletion renders the heart resistant to injury caused by regional ischemia.
Individual Differences Among Children in Sucrose Detection Thresholds

BackgroundLittle research has focused on whether there are individual differences among children in their sensitivity to sweet taste and, if so, the biological correlates of such differences. ObjectivesOur goal was to understand how variations in children’s sucrose detection thresholds relate to their age and gender, taste genotype, body composition, and dietary intake of added sugars. MethodsSucrose detection thresholds in 7- to 14-year-old children were tested individually using a validated, two-alternative, forced-choice, paired-comparison tracking method. Five genetic variants of taste genes were assayed: TAS1R3 and GNAT3 (sweet genes; one variant each) and the bitter receptor gene TAS2R38 (three variants). All children were measured for body weight and height. A subset of these children were measured for the percentage of body fat and waist circumference and provided added sugar intake by 24-hour dietary recall. ResultsSucrose thresholds ranged from 0.23 to 153.8 mM with most of the children completing the threshold task (216/235; 92%). Some children were biologically related (i.e., siblings), and for the genetic analysis, one sibling from each family was studied. Variants in the bitter but not the sweet genes were related to sucrose threshold and sugar intake; children with two bitter-sensitive alleles could detect sucrose at lower concentrations (F(2,165) = 4.55, p = . 01; rs1726866) and reported eating more added sugar (% kcal; F(2, 62) = 3.64, p = . 03) than did children with less sensitive alleles. Age, gender, and indices of obesity also were related to child-to-child differences in sucrose threshold; girls were more sensitive than boys (t(214) = 2.0, p = . 05), older children were more sensitive than younger children (r(214) = −. 16, p = . 02), and fatter (r(84) = −. 22, p = . 05) or more centrally obese children (r(84) = −. 26, p = . 02) were more sensitive relative to others. DiscussionInborn differences in bitter sensitivity may affect childhood dietary sugar intake with long-term health consequences. There may be a more complex interplay between the developing bitter and sweet taste systems than previously understood.
The Effects of Sentence Repetition-Based Working Memory Treatment on Sentence Comprehension Abilities in Individuals With Aphasia.

Purpose This study investigated whether sentence repetition-based working-memory (SR-WM) treatment increased sentence-repetition abilities and the treatment effects generalized to sentence-comprehension abilities, WM-span tasks, and general language-assessment tasks. Method Six individuals with aphasia participated in the study. The treatment consisted of 12 sessions of approximately 1 hr per day, 3 times per week. The SR-WM treatment protocol followed components including maintenance and computation of linguistic units by facilitating a chunking strategy. We manipulated the length and syntactic structures of the sentence-repetition stimuli using a limited set of vocabulary. Results Participants demonstrated significant increased repetition ability in treated and untreated sentences after treatment. Furthermore, they showed generalization effects on the sentence-comprehension task, WM measures, and general language tasks, but with some differential patterns, depending on task demands. Conclusions The SR-WM treatment approach, by manipulating syntactic structures and minimizing top-down semantic processing, elicited increased performance on sentence repetition as well as other linguistic domains. Results indicated that it is clinically and theoretically important to examine whether WM treatment serves as a potentially underlying treatment approach that facilitates the distributed network associated with language processing.