Miracle-dz/UniFAR-FTUs huggingface dataset:
Multisite Interactions Between Pb2+ and Protein Kinase C and Its Role in Norepinephrine Release from Bovine Adrenal Chromaffin Cells

Abstract: We investigated the interaction between Pb2+ and protein kinase C (PKC) in the Pb2+‐induced release of norepinephrine (NE) from permeabilized adrenal chromaffin cells. Our analysis of endogenous PKC activity in permeabilized cells suggests that Pb2+ interacts with the adrenal enzyme at multiple sites. Pb2+ activates the enzyme through high‐affinity (KA(Pb) = 2.4 × 10−12M) interactions and inhibits the enzyme by competitive and noncompetitive interactions with nanomolar‐(Ki = 7.1 × 10−9M) and micromolar‐ (K′i = 2.8 × 10−7M) affinity sites, respectively. Activation of PKC by 12‐O‐tetradecanoylphorbol 13‐acetate (TPA) in Ca2+‐deficient, Pb2+‐containing medium, enhances the Pb2+‐induced NE release from permeabilized chromaffin cells by lowering the concentration of Pb2+ required for half‐maximal activation of the secretory response from 7.5 × 10−10 to 5.7 × 10−11M. The PKC inhibitors staurosporine and pseudosubstrate PKC (19–36) abolish the effect of TPA without affecting the Pb2+‐induced secretion in the absence of TPA. These results indicate that (a) Pb2+ is a partial agonist of PKC, capable of both activating and inhibiting the enzyme and (b) synergistic activation of PKC by TPA and Pb2+ results in increased sensitivity of exocytosis to Pb2+ but is not obligatory for Pb2+‐triggered secretion.
Serological responses to various Coccidioides antigen preparations in a new enzyme immunoassay

A new enzyme immunoassay (EIA) was used to investigate immunoglobulin M (IgM) and IgG responses to various coccidioidal antigen preparations. Direct binding and inhibition assays both revealed that the IgG responses of many serum specimens were directed largely to the tube precipitin (TP) antigen even when the microwells were coated with a combination of coccidioidal antigens (CCAs). From a panel of 28 serum specimens containing antibodies to CCAs, 4 serum specimens yielded high IgG signals (absorbance, greater than 1.0) and were negative for IgM (absorbance, less than 0.2), yet all four IgG responses were inhibited by at least 90% with partially purified TP antigens (2.4 micrograms/ml). The IgM and IgG fractions of several serum specimens were separated by ion-exchange chromatography and assayed by using different antigen preparations adsorbed to the microwells. The binding of both IgM and IgG peaks to the microwells coated with the CCA preparation was inhibited significantly by preincubation with TP antigens. One serum specimen (specimen 26) yielded a large IgG response (absorbance, greater than 2.0) with the CCA preparation and also bound directly to microwells coated only with TP antigens. The IgG signal (absorbance) of serum specimen 26 was reduced by 98% when it was preincubated with TP antigens prior to the assay. Significant IgG signals from several other serum specimens were observed when microwells were coated with TP antigen preparations, but they were absent when periodate-treated preparations were used. Two cerebrospinal fluid specimens yielded IgG signals with CCA-coated microwells, which were not inhibited by TP antigens, and yielded no signal with microwells coated only with TP antigens. The results are consistent with the concept that the typical serologic response to TP antigens occurs early in disease progression, but they suggest that TP antigens stimulate both IgM and IgG responses.
Glutamate‐induced protease‐mediated loss of plasma membrane Ca2+ pump activity in rat hippocampal neurons

Ca2+ dysregulation is a hallmark of excitotoxicity, a process that underlies multiple neurodegenerative disorders. The plasma membrane Ca2+ ATPase (PMCA) plays a major role in clearing Ca2+ from the neuronal cytoplasm. Here, we show that the rate of PMCA‐mediated Ca2+ efflux from rat hippocampal neurons decreased following treatment with an excitotoxic concentration of glutamate. PMCA‐mediated Ca2+ extrusion following a brief train of action potentials exhibited an exponential decay with a mean time constant (τ) of 8.8 ± 0.2 s. Four hours following the start of a 30 min treatment with 200 µm glutamate, a second population of cells emerged with slowed recovery kinetics (τ = 16.5 ± 0.3 s). Confocal imaging of cells expressing an enhanced green fluorescent protein (EGFP)‐PMCA4b fusion protein revealed that glutamate treatment internalized EGFP and that cells with reduced plasma membrane fluorescence had impaired Ca2+ clearance. Treatment with inhibitors of the Ca2+‐activated protease calpain protected PMCA function and prevented EGFP‐PMCA internalization. PMCA internalization was triggered by activation of NMDA receptors and was less pronounced for a non‐toxic concentration of glutamate relative to one that produces excitotoxicity. PMCA isoform 2 also internalized following exposure to glutamate, although the Na+/K+ ATPase did not. These data suggest that glutamate exposure initiated protease‐mediated internalization of PMCAs with a corresponding loss of function that may contribute to the Ca2+ dysregulation that accompanies excitotoxicity.
Recreational football as a health promoting activity: a topical review

The present review addresses the physiological demands during recreational football training and the effects on central health variables that influence the risk of life‐style diseases of young and middle‐aged men. Recent studies have established that recreational football, carried out as small‐sided games can be characterized as having a high aerobic component with mean heart rates of 80–85% of maximum heart rate, which is similar to values observed for elite football players. In addition, the training includes multiple high‐speed runs, sprints, turns, jumps and tackles, which provide a high impact on muscles and bones. Recreational football training in untrained men results in marked improvements in maximum aerobic power, blood pressure, muscle capillarization and intermittent exercise performance, and those effects are similar to interval training and more pronounced than moderate‐intensity continuous running and strength training. Further, recreational football training enhances fat oxidation during exercise and results in a higher fat loss than interval training and strength training, and results in marked muscle hypertrophy and elevates bone mass, more than interval and continuous running. Taken together, recreational football appears to effectively stimulate musculoskeletal, metabolic and cardiovascular adaptations of importance for health and thereby reduces the risk of developing life‐style diseases.
HilD-mediated transcriptional cross-talk between SPI-1 and SPI-2

The acquisition of new genetic traits by horizontal gene transfer and their incorporation into preexisting regulatory networks have been essential events in the evolution of bacterial pathogens. An example of successful assimilation of virulence traits is Salmonella enterica, which acquired, at distinct evolutionary times, Salmonella pathogenicity island 1 (SPI-1), required for efficient invasion of the intestinal epithelium and intestinal disease, and SPI-2, essential for Salmonella replication and survival within macrophages and the progression of a systemic infection. A positive regulatory cascade mainly composed of HilD, HilA, and InvF, encoded in SPI-1, controls the expression of SPI-1 genes, whereas the two-component regulatory system SsrA/B, encoded in SPI-2, controls expression of SPI-2 genes. In this study, we report a previously undescribed transcriptional cross-talk between SPI-1 and SPI-2, where the SPI-1–encoded regulator HilD is essential for the activation of both the SPI-1 and SPI-2 regulons but at different times during the stationary phase of growth in Luria-Bertani medium. Our data indicate that HilD counteracts the H-NS–mediated repression exerted on the OmpR-dependent activation of the ssrAB operon by specifically interacting with its regulatory region. In contrast, HilD is not required for SPI-2 regulon expression under the in vitro growth conditions that are thought to resemble the intracellular environment. Our results suggest that two independent SPI-2 activation pathways evolved to take advantage of the SPI-2–encoded information at different niches and, in consequence, in response to different growth conditions.
Exploring lymphocyte differentiation pathways

Summary: Highlights in a 4‐decade exploration of lymphocyte differentiation begin with comparative studies in birds and mammals leading to recognition of the separate T‐ and B‐cell differentiation pathways and their cooperative interaction. The global effects of aborting IgM B‐cell development with anti‐µ antibodies indicated that B cells can undergo immunoglobulin isotype switching. A search for the mammalian bursa equivalent that began with an extended excursion through the gut‐associated lymphoepithelial tissues ultimately led to the hematopoietic tissue origin of mammalian B cells. The identification of the precursors of B cells in hematopoietic tissues provided an expanded view of the life history of B cells. A recurring theme in this essay is the interplay between understanding normal lymphocyte differentiation and the defects that underlie immunodeficiency diseases and lymphoid malignancies.
Potential Curative Role of Hypericum Perforatum in an Experimental Rat Model of Tympanic Membrane Perforation.

OBJECTIVE Our aim was to investigate the curative role of topical Hypericum perforatum (HP) in a rat model of tympanic membrane perforation in a histopathological manner. MATERIALS AND METHODS This study was conducted on 30 female Sprague-Dawley rats. An HP extract was prepared as a suspension in pure olive oil. In all rats, the right and left tympanic membranes were perforated by a fine puncture under a microscope. Rats were randomly assigned to three groups. The HP extract was given as drops on a daily basis in Group 1, while olive oil alone was given on a daily basis in Group 2. In Group 3, the rats were allowed spontaneous recovery without any intervention. Three rats from each group were sacrificed on days 7, 14, and 21. Temporal bullae were removed for histopathological examination to evaluate fibroblast proliferation, leukocyte infiltration, neovascularization, and subepithelial thickness and to compare these among the groups. RESULTS In histopathological examination of the rats from each group on days 7, 14, and 21, there were significant differences in leukocyte infiltration, fibroblast proliferation, and subepithelial thickness. No significant difference was observed in neovascularization among the groups. CONCLUSION Compared with the spontaneous recovery group, HP was found to be more effective in a wound-healing model of the tympanic membrane. HP may be applied in clinical practice if it is shown to be safe with regard to ototoxicity.
Effect of obesity and metabolic syndrome on severity, quality of life, sleep quality and inflammatory markers in patients of asthma in India.

INTRODUCTION The study aimed to compare the effect of obesity with and without metabolic syndrome on asthma severity, quality of life, sleep quality, sleep disordered breathing and inflammatory markers as compared to non-obese asthma patients. MATERIAL AND METHODS 60 asthma patients recruited for the study were divided equally into non-obese (NOA), obese without metabolic syndrome (OANMS) and obese with metabolic syndrome (OAMS) groups. Study cohorts were assessed for severity of asthma, quality of life and quality of sleep using questionnaires and inflammatory markers (FENO, hs-CRP, IL-5, IL-6 and leptin). Institutional ethical committee approved the study. RESULTS The results suggests OAMS patients may be a subtype of asthmatics having significantly severe asthma (p < 0.05), poor quality of life (p < 0.05), high risk of OSA (p< 0.05), decreased lung volumes (FRC) (p< 0.05), higher levels of inflammatory markers (leptin and IL-6) (p < 0.05), and high incidence of sleep disordered breathing (p < 0.05) in comparison to NOA and OANMS patients. CONCLUSIONS The present study has shown that obese asthmatics especially with metabolic syndrome represent a subtype of asthmatic population. Hence, the treatment of metabolic syndrome may be necessary in addition to asthma to achieve optimal control.
Bitcoin: competitor or complement to gold?

This study seeks to address whether Bitcoin ever match or even replace gold as a safe haven. To this end, we use a dynamic Markov-switching copula model to test the complementarity and substitutability among Bitcoin and gold within two risk scenarios (i.e., low- and high-risk regimes). Our results reveal a positive and strong correlation between gold and Bitcoin returns coinciding with specific economic and political events. Gold and Bitcoin benefit from the same economic conditions. This suggests that gold and Bitcoin are likely to be complementary, rather than in competition with each other. Gold could act as a diversifier for investors in digital assets. But the Bitcoin have a lot to teach gold in terms of the efficient transfer of value.
Spermidine Synthase Genes Are Essential for Survival of Arabidopsis

The cellular polyamines putrescine, spermidine, and spermine are ubiquitous in nature and have been implicated in a wide range of growth and developmental processes. There is little information, however, on mutant plants or animals defective in the synthesis of polyamines. The Arabidopsis genome has two genes encoding spermidine synthase, SPDS1 and SPDS2. In this paper, we describe T-DNA insertion mutants of both of these genes. While each mutant allele shows normal growth, spds1-1 spds2-1 double-mutant seeds are abnormally shrunken and they have embryos that are arrested morphologically at the heart-torpedo transition stage. These seeds contain significantly reduced levels of spermidine and high levels of its precursor, putrescine. The embryo lethal phenotype of spds1-1 spds2-1 is complemented by the wild-type SPDS1 gene. In addition, we observed a nearly identical seed phenotype among an F2 seed population from the cross between the spds2-1 allele and SPDS1 RNA interference transgenic lines. These data provide the first genetic evidence indicating a critical role of the spermidine synthase in plant embryo development.
Concise Review: Role and Function of the Ubiquitin‐Proteasome System in Mammalian Stem and Progenitor Cells

Highly ordered degradation of cell proteins by the ubiquitin‐proteasome system, a sophisticated cellular proteolytic machinery, has been identified as a key regulatory mechanism in many eukaryotic cells. Accumulating evidence reveals that the ubiquitin‐proteasome system is involved in the regulation of fundamental processes in mammalian stem and progenitor cells of embryonic, neural, hematopoietic, and mesenchymal origin. Such processes, including development, survival, differentiation, lineage commitment, migration, and homing, are directly controlled by the ubiquitin‐proteasome system, either via proteolytic degradation of key regulatory proteins of signaling and gene expression pathways or via nonproteolytic mechanisms involving the proteasome itself or posttranslational modifications of target proteins by ubiquitin or other ubiquitin‐like modifiers. Future characterization of the precise roles and functions of the ubiquitin‐proteasome system in mammalian stem and early progenitor cells will improve our understanding of stem cell biology and may provide an experimental basis for the development of novel therapeutic strategies in regenerative medicine.
Electricity trade and cooperation in the BBIN region: lessons from global experience

ABSTRACT The acute shortage of electric power in South Asia has severely hampered regional economic growth. Cross-border electricity trade – supported by appropriate policies, institutions and grid interconnections – can be a powerful tool for improving people’s livelihoods in its Bangladesh–Bhutan–India–Nepal (BBIN) region. This paper reviews four cases of regional power trade and cooperation from four different continents – Asia, Africa, Latin America and Europe – and identifies six key elements that will be necessary for success in cross-border electricity trade in the BBIN region. It assesses the current status of these key elements in the BBIN countries and suggests areas for immediate intervention. Cooperation in the electricity sector in the region could be the building block for a larger regional cooperation in South Asia – and ultimately for regional economic integration.
Patch-based finger encoding for hand posture recogntion

This paper proposes a method for hand posture recognition based on finger characteristics. These characteristics can be classified into fully extended or bended finger which are useful for further recognition process. Each finger is encoded for five elements codeword and each element is set up from the area of finger phalanges. This system will be decided whether each finger is extended or bended. After obtaining the finger state, the combinations of bended state (0's) and extended state (1's) from five fingers define the sign pattern codeword. Hamming distance between sign pattern codeword and template codeword is applied to recognize the corresponding alphabet. The result of experimenting 360 samples from nine alphabet patterns shows that the performance evaluation is about 90.83 %.
Solutions Manual and Supplementary Materials for Econometric Analysis of Cross Section and Panel Data

This is the essential companion to Jeffrey Wooldridge's widely-used graduate text Econometric Analysis of Cross Section and Panel Data (MIT Press, 2001). Already established as a leading graduate econometrics text, the book offers an intuitive yet rigorous treatment of two methods used in econometric research, cross section and panel data techniques. The numerous end-of-chapter problems are an important component of the book, encouraging the student to use the analytical tools presented in the text. This manual contains answers to selected problems, new examples, and supplementary materials designed by the author. Users of the textbook will find the manual a necessary adjunct to the book.
An exaggerated systolic blood pressure response to exercise is associated with cardiovascular remodeling in subjects with prehypertension.

BACKGROUND Although many observers consider the cardiovascular risk associated with isolated prehypertension to be low and not worth pharmacological treating, the cardiovascular disease rate is increased among individuals within this blood pressure stratum. METHODS We performed Doppler echocardiography and submaximal bicycle ergometry in 20 nonsmoking sedentary prehypertensive subjects and 20 age- and sex-matched nonsmoking sedentary normotensive subjects, and investigated the association between the systolic blood pressure response to exercise (SBPRE) and hypertensive target organ damage. An exaggerated SBPRE (E-SBPRE) and a normal SBPRE (N-SBPRE) were diagnosed using the mean +2 standard deviations of systolic blood pressure at 100 W in normotensives. RESULTS Body mass index was similar in the two groups. Resting blood pressure and systemic vascular resistance were higher in prehypertensives. Almost half the latter had an E-SBPRE. There were no differences in age, gender, and body mass index between normotensives and prehypertensives with an E-SBPRE or a N-SBPRE. Resting blood pressure and systemic vascular resistance were similarly increased in prehypertensives with an E-SBPRE and a N-SBPRE vs normotensives. Compared with normotensives, prehypertensives with an E-SBPRE showed: (a) a significantly greater left ventricular relative wall thickness, mostly due to a smaller cavity, (b) a significantly longer left ventricular isovolumic relaxation time, and (c) a significantly greater global arterial stiffness, as estimated by the pulse pressure/left ventricular stroke volume ratio. CONCLUSIONS Our findings suggest that an E-SBPRE is frequent among prehypertensive subjects and is associated with cardiovascular remodeling, which may herald cardiovascular disease.
Genome scans reveal candidate regions involved in the adaptation to host plant in the pea aphid complex

A major goal in evolutionary biology is to uncover the genetic basis of adaptation. Divergent selection exerted on ecological traits may result in adaptive population differentiation and reproductive isolation and affect differentially the level of genetic divergence along the genome. Genome‐wide scan of large sets of individuals from multiple populations is a powerful approach to identify loci or genomic regions under ecologically divergent selection. Here, we focused on the pea aphid, a species complex of divergent host races, to explore the organization of the genomic divergence associated with host plant adaptation and ecological speciation. We analysed 390 microsatellite markers located at variable distances from predicted genes in replicate samples of sympatric populations of the pea aphid collected on alfalfa, red clover and pea, which correspond to three common host‐adapted races reported in this species complex. Using a method that accounts for the hierarchical structure of our data set, we found a set of 11 outlier loci that show higher genetic differentiation between host races than expected under the null hypothesis of neutral evolution. Two of the outliers are close to olfactory receptor genes and three other nearby genes encoding salivary proteins. The remaining outliers are located in regions with genes of unknown functions, or which functions are unlikely to be involved in interactions with the host plant. This study reveals genetic signatures of divergent selection across the genome and provides an inventory of candidate genes responsible for plant specialization in the pea aphid, thereby setting the stage for future functional studies.
Regulation of fibronectin alternative splicing during peripheral nerve repair

Wallerian degeneration following peripheral nerve injury is associated with increased production of fibronectin and other extracellular matrix molecules that are thought to enhance repair. We have shown previously that alternative splicing of the mRNA for fibronectin also changes following sciatic nerve lesions so as to reexpress forms of mRNA seen during embryogenesis. In the present study, we have examined the role of the regenerating axons in the regulation of this splicing. We have compared the patterns of fibronectin mRNA splicing seen in sciatic nerve development with that seen in cut nerves (that do not regenerate), crushed nerves (that regenerate successfully), and Schwann cells cultured in forskolin so as to mimic axonal signals. By using a reverse transcriptase polymerase chain reaction assay to examine all three regions of fibronectin mRNA splicing in a quantitative manner, we found that embryonic patterns of fibronectin mRNA splicing appear rapidly following injury and are not then altered by reestablishment of axons in the nerve. In addition, we found that forskolin has no effect on fibronectin mRNA splicing in cultured cells. We conclude that axonal signals do not regulate the pattern of fibronectin alternative splicing in peripheral nerve repair. J. Neurosci. Res. 56:323–333, 1999. © 1999 Wiley‐Liss, Inc.