Miracle-dz/UniFAR-FTUs huggingface dataset:
MARCKS modulates radial progenitor placement, proliferation and organization in the developing cerebral cortex

The radial glial cells serve as neural progenitors and as a migratory guide for newborn neurons in the developing cerebral cortex. These functions require appropriate organization and proliferation of the polarized radial glial scaffold. Here, we demonstrate in mice that the myristoylated alanine-rich C-kinase substrate protein (MARCKS), a prominent cellular substrate for PKC, modulates radial glial placement and expansion. Loss of MARCKS results in ectopic collection of mitotically active radial progenitors away from the ventricular zone (VZ) in the upper cerebral wall. Apical restriction of key polarity complexes [CDC42, β-catenin (CTNNB1), N-cadherin (CDH2), myosin IIB (MYOIIB), aPKCζ, LGL, PAR3, pericentrin, PROM1] is lost. Furthermore, the radial glial scaffold in Marcks null cortex is compromised, with discontinuous, non-radial processes apparent throughout the cerebral wall and deformed, bulbous, unbranched end-feet at the basal ends. Further, the density of radial processes within the cerebral cortex is reduced. These deficits in radial glial development culminate in aberrant positioning of neurons and disrupted cortical lamination. Genetic rescue experiments demonstrate, surprisingly, that phosphorylation of MARCKS by PKC is not essential for the role of MARCKS in radial glial cell development. By contrast, the myristoylation domain of MARCKS needed for membrane association is essential for MARCKS function in radial glia. The membrane-associated targeting of MARCKS and the resultant polarized distribution of signaling complexes essential for apicobasal polarity may constitute a critical event in the appropriate placement, proliferation and organization of polarized radial glial scaffold in the developing cerebral cortex.
Studies on antioxidant enzymes in Canna indica plant under copper stress.

Bright red-flowered Canna indica L. plants were subjected to grow in nutrient solution supplemented with five different concentrations (0, 5, 10, 30 and 50 microM) of CuCl2 to study antioxidant defense responses of the plant. Accumulation of Cu was dose-dependent and much higher in the roots (108-191 microg g(-1) d. wt. ) than in the leaves (23.36-40.43 microg g d.wt.). Total ascorbate content did not changed in both tissues, but ascorbate redox state decreased (0.570-0.640) in Cu-treated Canna roots. In contrast, both total and reduced glutathione contents increased (387-591.9 nmol g(-1) f. wt. ) considerably in roots, accompanied with enhanced activities of dehydroascorbate reductase (153.3-160 nmol mg(-1) protein) and glutathione reductase (67-87.5 nmol mg(-1) protein). No significant change, however, was observed for monodehydroascorbate reductase activity in both tissues of the treated plant. The efficient scavenging of hydrogen peroxide was performed by normal (control level) activities of both ascorbate peroxidase and catalase in leaf and increased activity of only catalase in root, preventing its accumulation at toxic concentrations (despite high superoxide dismutase activity) and subsequent damage of membrane lipids by peroxidation. Together, these ensured normal dry weight of leaves and roots, indicating tolerance of Canna indica plant to Cu-induced oxidative stress.
Laboratory measurements of sound scattering from a buried sphere above and below the critical angle.

Laboratory measurements of low frequency (1–10 kHz) evanescent wave field scattering from a sphere buried in water-saturated sand was examined. A 60 cm stainless steel sphere was buried just below a sand–water interface and the acoustic backscattering cross section was measured for above and below critical angle geometries. The below critical angle insonification results clearly show significant levels of backscatter from the buried sphere due to evanescent wave insonification at the lower end of the spectrum (1–3.5 kHz). These measurements compare favorably with first principle estimates of the backscattered target strength and with a T-matrix-based numerical model.
Air Pollution and Distributions of Lymphocyte Immunophenotypes in Cord and Maternal Blood at Delivery

A cross-sectional study of deliveries in two districts in the Czech Republic, 1994–1996, assessed the relation between air pollution and lymphocyte immunophenotype distributions. Maternal and cord blood samples were assayed by flow cytometry within 24 hours of delivery for 303 deliveries from Teplice, a polluted district, and 215 from Prachatice, a less polluted district. Analyses focused on: CD3+ T-lymphocytes, CD3−CD19+ B-lymphocytes, and CD3−CD16+56+ natural killer (NK) lymphocytes, as well as the subsets CD3+CD4+ (“T-helper”) and CD3+CD8+ (“T cytotoxic/suppressor”) and the ratio of these two lymphocytes. We collected reproductive, occupational, and life-style information by questionnaire, and abstracted data on labor and delivery from medical records. After adjustment for numerous risk factors in multivariate linear regression models fit for each lymphocyte subset, mothers from Teplice had lower percentages of total T-cells and of CD4+ cells, and a lower ratio of CD4+:CD8+ cells. Cord bloods from Teplice had a higher percentage of NK cells and a less precise lower percentage of T-cells. Stronger differences in maternal lymphocytes were seen when analyses were limited to the central hospital in each district. Heavy air pollution may affect the immune system in pregnant women and/or fetuses, reflecting an acute and/or chronic effect, although unmeasured confounders could also play a role.
Quantitative screening of embryonic stem cell differentiation: Endoderm formation as a model

Embryonic stem (ES) cells have attracted much attention as a possible source of functional cells for regenerative medicine. Therapeutic use of ES cells requires control over the types and frequencies of cells generated during their in vitro differentiation. Due to the complexity of factors that impact upon ES cell differentiation, novel approaches for the optimization of tissue‐specific development are required. This motivates our use of factorial and composite design methods to make empirical investigations more efficient, and to reveal unexpected interactions missed by conventional dose–response analysis. Factorial experiments would benefit from the high content evaluation of a large number of test conditions, necessitating the development of a quantitative screening technology (QST) capable of reporting the absolute number and frequency of target cells. We have developed and validated such a technology for ES cell differentiation analysis using automated fluorescence microscopy, employing endoderm differentiation as a model system. To test this platform, a two‐level factorial experiment was carried out to identify major and interactive effects of glucose, insulin, retinoic acid (RA), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) on endoderm formation. RA was found to have inhibitory effects on endoderm formation, while low glucose proved beneficial. QST was demonstrated to be a powerful tool to study factors impacting endoderm‐specific ES cell differentiation, and should be applicable to the analysis of a range of ES cell–derived tissues. © 2004 Wiley Periodicals, Inc.
Mutational analysis of the cytoplasmic domain of β1,4-galactosyltransferase I: influence of phosphorylation on cell surface expression

β1,4-Galactosyltransferase I (GalT I) exists in two subcellular compartments where it performs two distinct functions. The majority of GalT I is localized in the Golgi complex where it participates in glycoprotein biosynthesis; however, a small portion of GalT I is expressed on the cell surface where it functions as a matrix receptor by binding terminal N-acetylglucosamine residues on extracellular glycoside ligands. The GalT I polypeptide occurs in two alternate forms that differ only in the length of their cytoplasmic domains. It is thought that the longer cytoplasmic domain is responsible for GalT I function as a cell surface receptor because of its ability to associate with the detergent-insoluble cytoskeleton. In this study, we demonstrate that the long GalT I cytoplasmic and transmembrane domains are capable of targeting a reporter protein to the plasma membrane, whereas the short cytoplasmic and transmembrane domains do not have this property. The surface-localized GalT I reporter protein partitions with the detergent-insoluble pool, a portion of which co-fractionates with caveolin-containing lipid rafts. Site-directed mutagenesis of the cytoplasmic domain identified a requirement for serine and threonine residues for cell surface expression and function. Replacing either the serine or threonine with aspartic acid reduces surface expression and function, whereas substitution with neutral alanine has no effect on surface expression or function. These results suggest that phosphorylation negatively regulates GalT I function as a surface receptor. Consistent with this, phosphorylation of the endogenous, full-length GalT I inhibits its stable expression on the cell surface. Thus, the 13 amino acid extension unique to the long GalT I isoform is required for GalT I expression on the cell surface, the function of which is regulated by phosphorylation.
Why Do Canadian Firms Cross‐List? The Flip Side of the Issue

We investigate the relation between managerial incentives and the decision to cross&#8208;list by comparing Canadian firms cross&#8208;listed on US stock exchanges to industry&#8208; and size&#8208;matched control firms. After controlling for firm and ownership structure characteristics, we find a positive association between substantial holdings of vested options held by CEOs prior to cross&#8208;listing and the decision to cross&#8208;list. Further, firms managed by CEOs with substantial holdings of vested options exhibit positive announcement returns and negative post&#8208;announcement long&#8208;run returns. CEOs of cross&#8208;listed firms seem to take advantage of the aforementioned market behaviour, because they abnormally exercise vested options and sell the proceeds during the year of listing only when their firms underperform during the subsequent year. In addition, there is a positive relation between substantial holdings of vested options and discretionary accruals during the year of listing, consistent with the view that CEOs manage earnings to keep stock prices at high levels. Overall, these results have significant implications for the cross&#8208;listing literature, suggesting an association between cross&#8208;listing and CEO incentives to maximize CEO private benefits.
A Short Sequence within Two Purine-Rich Enhancers Determines 5′ Splice Site Specificity

ABSTRACT Purine-rich enhancers are exon sequences that promote inclusion of alternative exons, usually via activation of weak upstream 3′ splice sites. A recently described purine-rich enhancer from the caldesmon gene has an additional activity by which it directs selection of competing 5′ splice sites within an alternative exon. In this study, we have compared the caldesmon enhancer with another purine-rich enhancer from the chicken cardiac troponin T (cTNT) gene for the ability to regulate flanking splice sites. Although similar in sequence and length, the two enhancers demonstrated strikingly different specificities towards 5′ splice site choice when placed between competing 5′ splice sites in an internal exon. The 32-nucleotide caldesmon enhancer caused effective usage of the exon-internal 5′ splice site, whereas the 30-nucleotide cTNT enhancer caused effective usage of the exon-terminal 5′ splice site. Both enhancer-mediated splicing pathways represented modulation of the default pathway in which both 5′ splice sites were utilized. Each enhancer is multipartite, consisting of two purine-rich sequences of a simple (GAR) n repeat interdigitated with two enhancer-specific sequences. The entire enhancer was necessary for maximal splice site selectivity; however, a 5- to 7-nucleotide region from the 3′ end of each enhancer dictated splice site selectivity. Mutations that interchanged this short region of the two enhancers switched specificity. The portion of the cTNT enhancer determinative for 5′ splice site selectivity was different than that shown to be maximally important for activation of a 3′ splice site, suggesting that enhancer environment can have a major impact on activity. These results are the first indication that individual purine-rich enhancers can differentiate between flanking splice sites. Furthermore, localization of the specificity of splice site choice to a short region within both enhancers indicates that subtle differences in enhancer sequence can have profound effects on the splicing pathway.
The Metabolic Response of Skeletal Muscle to Endurance Exercise Is Modified by the ACE-I/D Gene Polymorphism and Training State

The insertion/deletion polymorphism in the gene for the regulator of vascular tone, angiotensin-converting enzyme (ACE), is the prototype of a genetic influence on physical fitness and this involves an influence on capillary supply lines and dependent aerobic metabolism in skeletal muscle. The respective interaction of ACE-I/D genotype and training status on local metabolic and angiogenic reactions in exercised muscle is not known. Toward this end we characterized the metabolomic and angiogenic response in knee extensor muscle, m. vastus lateralis, in 18 untrained and 34 endurance-trained (physically active, V˙O2max > 50 mL min−1 kg−1) white British men to an exhaustive bout of one-legged cycling exercise. We hypothesized that training status and ACE-I/D genotype affect supply-related muscle characteristics of exercise performance in correspondence to ACE expression and angiotensin 2 levels. ACE-I/D genotype and training status developed an interaction effect on the cross-sectional area (CSA) of m. vastus lateralis and mean CSA of slow type fibers, which correlated with peak power output (r ≥ 0.44). Genotype × training interactions in muscle also resolved for exercise-induced alterations of 22 metabolites, 8 lipids, glycogen concentration (p = 0.016), ACE transcript levels (p = 0.037), and by trend for the pro-angiogenic factor tenascin-C post exercise (p = 0.064). Capillary density (p = 0.001), capillary-to-fiber ratio (p = 0.010), systolic blood pressure (p = 0.014), and exercise-induced alterations in the pro-angiogenic protein VEGF (p = 0.043) depended on the ACE-I/D genotype alone. Our observations indicate that variability in aerobic performance in the studied subjects was in part reflected by an ACE-I/D-genotype-modulated metabolic phenotype of a major locomotor muscle. Repeated endurance exercise appeared to override this genetic influence in skeletal muscle by altering the ACE-related metabolic response and molecular aspects of the angiogenic response to endurance exercise.
The Results of Repair of Massive Tears of the Rotator Cuff*†

Background: Massive tears of the tendons of the rotator cuff cause atrophy and fatty degeneration of the rotator cuff muscles and painful loss of function of the shoulder. Repair of massive rotator cuff tears is often followed by retears of the tendons, additional muscular degeneration, and a poor clinical outcome. The purposes of this study were to determine whether a new method of repair of rotator cuff tendons can yield a lower retear rate and a better clinical outcome than previously reported methods, to assess the muscular changes following repair of massive tears of the musculotendinous units, and to correlate findings on magnetic resonance imaging with the clinical results. Methods: Twenty-nine massive rotator cuff tears involving complete detachment of at least two tendons were repaired operatively with use of a new laboratory-tested technique in a prospective study. At least two years (average, thirty-seven months; range, twenty-four to sixty-one months) postoperatively, twenty-seven patients were evaluated clinically and with magnetic resonance imaging to determine the clinical outcome, the integrity of the repair, and the condition of the rotator cuff muscles. Results: The age and gender-adjusted Constant score improved from an average of 49 percent preoperatively to an average of 85 percent postoperatively, corresponding to a subjective shoulder value of 78 percent of that of a normal shoulder. Pain-free flexion improved from an average of 92 degrees to an average of 142 degrees, and abduction improved from an average of 82 degrees to an average of 137 degrees. Pain decreased and performance of activities of daily living improved significantly (p < 0.05). The seventeen patients who had a structurally successful repair all had an excellent clinical outcome. Muscle atrophy could not be reversed except in successfully repaired supraspinatus musculotendinous units. Fatty degeneration increased in all muscles. Conclusions: The method of repair of massive rotator cuff tears that was used in this study yielded a comparatively low retear rate and good-to-excellent clinical results; however, the repair did not result in substantial reversal of muscular atrophy and fatty degeneration. Retears occurred more often in patients who had had a shorter interval between the onset of the symptoms and the operation (p < 0.05). Patients who had a retear had improvement of the shoulder compared with the preoperative state, but they had less improvement than did those who had a successful repair.
Heritability of Dental Fear

The objective was to test a hypothesized genetic component (i.e., monozygotic being more similar compared with dizygotic twins) in dental fear/anxiety by comparing the probandwise concordance. We analyzed data based on a dichotomous measure of Dental Fear/Anxiety and a continuous measure of Dental Fear Intensity from over 2000 twins, collected when participants were 13–14 years old and once again three years later. The hypothesis was confirmed, but heritability of Dental Fear/Anxiety was estimated to be higher for girls (0.77 at time 1 and 0.55 at time 2) than for boys (0.14 and 0.0 at times 1 and 2, respectively). Heritability of Dental Fear Intensity, however, was similar for girls (0.30 and 0.40 at times 1 and 2, respectively) and boys (0.47, 0.44). Studies of the etiology of dental fear/anxiety should take genetic vulnerability into account and include molecular biology measures. Possible heritability differences between girls and boys need attention.
Social media’s impact on organizational performance and entrepreneurial orientation in organizations

Purpose Based on the system of value chain theory, the purpose of this paper is to investigate the impact of social media usage on the performance and the entrepreneurial orientation of the organizations. Design/methodology/approach A total of 174 organizations responded to the survey. Findings The result of the study showed that social media usage has a very strong positive impact on organizations’ performance, in terms of cost reduction, improved customer relations, and enhanced information accessibility. Research limitations/implications In the study, social media usage was categorized into three sub-constructs such as social media usage for marketing, social media usage for building customer relations, and social media usage for information search. This study investigated the usage of social media and its impact as a whole, considering all social media tools together. Finally, this study used a cross-sectional sample to collect data. Practical implications The result of the study benefits the managers to understand the various areas of organizational performance that can be improved by social media usage. Social implications The study also provided evidence that social media usage has strong positive influences on enhancing the entrepreneurial orientation of the organizations. Originality/value This study provides a clearer idea on the real importance of social media and its benefits. This study demonstrated the various areas of organizational performance that can be improved through social media usage.
The effect of short-term fasting on liver and skeletal muscle lipid, glucose, and energy metabolism in healthy women and men

Fasting promotes triglyceride (TG) accumulation in lean tissues of some animals, but the effect in humans is unknown. Additionally, fasting lipolysis is sexually dimorphic in humans, suggesting that lean tissue TG accumulation and metabolism may differ between women and men. This study investigated lean tissue TG content and metabolism in women and men during extended fasting. Liver and muscle TG content were measured by magnetic resonance spectroscopy during a 48-h fast in healthy men and women. Whole-body and hepatic carbohydrate, lipid, and energy metabolism were also evaluated using biochemical, calorimetric, and stable isotope tracer techniques. As expected, postabsorptive plasma fatty acids (FAs) were higher in women than in men but increased more rapidly in men with the onset of early starvation. Concurrently, sexual dimorphism was apparent in lean tissue TG accumulation during the fast, occurring in livers of men but in muscles of women. Despite differences in lean tissue TG distribution, men and women had identical fasting responses in whole-body and hepatic glucose and oxidative metabolism. In conclusion, TG accumulated in livers of men but in muscles of women during extended fasting. This sexual dimorphism was related to differential fasting plasma FA concentrations but not to whole body or hepatic utilization of this substrate.
The sensitivity of R&D investments to cash flows: comparing young and old EU and US leading innovators

ABSTRACT Using firm-level information on the world leading R&D investors and employing a system generalised method of moment estimation, this paper investigates how sensitive R&D investments are to cash-flow movements, which would be suggestive of financial constraints. The analysis confirms that over the last decade, the R&D investments of younger aged leading innovators appear to be more sensitive to cash flows compared to their older counterparts and that this holds particularly for EU younger aged leading innovators compared to their US counterparts, particularly in medium- and high-tech sectors.