Miracle-dz/UniFAR-FTUs huggingface dataset:
Calmodulin‐myosin light chain kinase inhibition changes fibroblast‐populated collagen lattice contraction, cell migration, focal adhesion formation, and wound contraction

Wound healing requires fibroblast migration, synthesis of new extracellular matrix, and organization of that matrix, all of which depend upon myosin ATPase activation and subsequent cytoplasmic actin‐myosin contraction. Myosin ATPase activity is optimized by phosphorylation of myosin light chain at serine 19. Several different signaling pathways can perform that phosphorylation, the focus here is calcium saturated calmodulin dependent ‐myosin light chain kinase (CaM‐MLCK). It is proposed that CaM‐MLCK phosphorylation of myosin light chain and subsequent myosin ATPase activation affects granulation tissue fibroblast behavior and contributes to wound contraction. Myosin ATPase activity generates actin‐myosin contraction within fibroblasts. Myosin ATPase activity is involved in ATP‐induced cell contraction, the generation of focal adhesions, fibroblast migration, fibroblast populated collagen lattice (FPCL) contraction, and wound contraction. The MLCK inhibitors ML‐9 and ML‐7 inhibited ATP‐induced cell contraction, fibroblast migration, FA formation, and FPCL contraction. The calmodulin inhibitors W7 and fluphenazine blocked rat open wound contraction. In addition, fluphenazine delayed re‐epithelialization. These findings support the idea that fibroblast CaM‐MLCK activity is essential for tissue repair. We speculate that inhibition of CaM‐MLCK may reduce or prevent detrimental fibrotic contracture.
Comparison of DMRT3 genotypes among American Saddlebred horses with reference to gait.

Horse owners choose whether or not to train American Saddlebred horses (ASHs) to perform the 4-beat gaits called rack and slow gait. The rack and slow gait are similar to ambling gaits shown to be associated with variation in the DMRT3 gene in other breeds but are trained rather than naturally occurring gaits. A premature stop codon in the DMRT3 gene (DMRT3_Ser301STOP) caused by the Ch23:g.22999655C>A SNP has an effect on the pattern of locomotion in horses and allows for the pacing gait and strong association with performance of ambling gaits in diverse breeds. We used horse show records to identify ASHs trained to perform as 5-gaited horses and compared them to other Saddlebreds for the prevalence of the A allele of the Ch23:g.22999655C>A SNP of DMRT3. Genomic DNA was typed using a PCR-RFLP technique for 5-gaited ASHs (n = 55), 3-gaited or harness ASHs (n = 64) and ASHs not shown (n = 128). We did not observe differences in the frequencies of the Ch23:g.22999655C>A SNP of DMRT3 when comparing 5-gaited ASHs to other ASHs (P > 0.22). These results suggest that DMRT3 alleles do not affect the choice of breeders to train and show ASHs as 5-gaited horses.
Cannabinoid-induced chemotaxis in bovine corneal epithelial cells.

PURPOSE Cannabinoid CB1 receptors are found in abundance in the vertebrate eye, with most tissue types expressing this receptor. However, the function of CB1 receptors in corneal epithelial cells (CECs) is poorly understood. Interestingly, the corneas of CB1 knockout mice heal more slowly after injury via a mechanism proposed to involve protein kinase B (Akt) activation, chemokinesis, and cell proliferation. The current study examined the role of cannabinoids in CEC migration in greater detail. METHODS We determined the role of CB1 receptors in corneal healing. We examined the consequences of their activation on migration and proliferation in bovine CECs (bCECs). We additionally examined the mRNA profile of cannabinoid-related genes and CB1 protein expression as well as CB1 signaling in bovine CECs. RESULTS We now report that activation of CB1 with physiologically relevant concentrations of the synthetic agonist WIN55212-2 (WIN) induces bCEC migration via chemotaxis, an effect fully blocked by the CB1 receptor antagonist SR141716. The endogenous agonist 2-arachidonoylglycerol (2-AG) also enhances migration. Separately, mRNA for most cannabinoid-related proteins are present in bovine corneal epithelium and cultured bCECs. Notably absent are CB2 receptors and the 2-AG synthesizing enzyme diglycerol lipase-α (DAGLα). The signaling profile of CB1 activation is complex, with inactivation of mitogen-activated protein kinase (MAPK). Lastly, CB1 activation does not induce bCEC proliferation, but may instead antagonize EGF-induced proliferation. CONCLUSIONS In summary, we find that CB1-based signaling machinery is present in bovine cornea and that activation of this system induces chemotaxis.
Is crossed laterality associated with academic achievement and intelligence? A systematic review and meta-analysis

Over the last century, sporadic research has suggested that people whose hand, eye, foot, or ear dominances are not consistently right- or left-sided are at special risk of suffering academic difficulties. This phenomenon is known as crossed laterality. Although the bulk of this research dates from 1960’s and 1970’s, crossed laterality is becoming increasingly popular in the area of school education, driving the creation of several interventions aimed at restoring or consolidating lateral dominance. However, the available evidence is fragmentary. To determine the impact of crossed laterality on academic achievement and intelligence, we conducted a systematic review and meta-analysis of articles published since 1900. The inclusion criteria for the review required that studies used one or more lateral preference tasks for at least two specific parts of the body; they included a valid measure of crossed laterality; they measured the impact of crossed laterality on academic achievement or intelligence; and they included participants between 3 and 17 years old. The final sample included 26 articles that covered a total population of 3578 children aged 5 to 12. Taken collectively, the results of these studies do not support the claim that there is a reliable association between crossed laterality and either academic achievement or intelligence. Along with this, we detected important shortcomings in the literature, such as considerable heterogeneity among the variables used to measure laterality and among the tasks utilized to measure the outcomes. The educational implications of these results are discussed.
Sending RNAs into the Future: RNA Localization and Germ Cell Fate

RNA localization is a cellular mechanism used to localize proteins to subcellular domains and to control protein synthesis regionally. In oocytes, RNA localization has profound implications for development, setting up local concentrations of regulatory proteins that will establish regional fates in the future embryo. One such fate is that of the germ cell lineage. In a diverse number of organisms, including Drosophila and Xenopus, the germ cell lineage is determined by the inheritance of germ plasm assembled during oogenesis. This process requires the recruitment of specific RNAs, many now identified, to the germ plasm. Complex signals located in the 3' UTR direct RNAs to their destinations. These signals are sites for protein binding and assembly into particles competent to localize. Three different mechanisms have been described that operate during oogenesis or embryogenesis to localize RNAs in the germ plasm: motor driven transport, differential stability, and entrapment. Each of these localization mechanisms must be coordinated with translation and anchoring mechanisms to achieve functional germ plasms. Here we review what is known about these processes in germ cells, but the cellular mechanisms that select and transport RNAs are likely to be conserved among somatic cells as well. IUBMB Life, 56: 19‐27, 2004
Application of Fluorescent Amplified Fragment Length Polymorphism for Comparison of Human and Animal Isolates of Yersinia enterocolitica

ABSTRACT An amplified fragment length polymorphism (AFLP) method, developed to genotype Yersinia enterocolitica, has been used to investigate 70 representative strains isolated from humans, pigs, sheep, and cattle in the United Kingdom. AFLP primarily distinguished Y. enterocolitica strains according to their biotype, with strains dividing into two distinct clusters: cluster A, comprising largely the putatively pathogenic biotypes (BT2 to -4), and cluster B, comprising the putatively nonpathogenic biotype 1A strains and a single BT1B isolate. Within these two clusters, subclusters formed largely on the basis of serotype. However, AFLP profiles also allowed differentiation of strains within these serotype-related subclusters, indicating the high discriminatory power of the technique for Y. enterocolitica. Investigation of the relationship between strain AFLP profile and host confirmed that pigs are, and provides further proof that sheep may be, potential sources of human infection with putatively pathogenic strains. However, the results suggest that some strains causing human disease do not come from veterinary sources identifiable at this time. The distribution of some BT1A isolates within cluster A raises questions about the relationship between virulence potential and biotype.
Structure and function of small airways in smokers: relationship between air trapping at CT and airway inflammation.

PURPOSE To use quantitative computed tomography (CT) to compare lung attenuation with both inflammatory infiltration and in vitro reactivity of peripheral airways in smokers scheduled to undergo lung resection for localized pulmonary lesions. MATERIALS AND METHODS Attenuation was measured in nine ex-smokers, 13 current smokers, and eight nonsmoking control subjects by using CT with respiratory gating and a contour-tracing algorithm. After lung resection in smokers, peripheral bronchi were dissected and studied in terms of both inflammation (by using immunohistochemistry to examine glycolmethacrylate-embedded specimens) and mechanical activity (by using an isolated organ bath system). Comparisons between groups were made by using analysis of variance and subsequent unpaired t tests. Correlations were evaluated by using the Pearson coefficient and stepwise multiple regression analysis. RESULTS The difference between inspiratory and expiratory attenuation was significantly higher in control subjects (-128 HU +/- 11 [SD]) than in ex-smokers (-77 HU +/- 10; P =.004) or current smokers (-67 HU +/- 11; P =.001). Cells infiltrating the smooth muscle increased with the decrease in expiratory attenuation (r = -0.46; P =.03) and the increase in inspiratory versus expiratory attenuation (r = 0.66; P =.001). Mast cell and neutrophil infiltration of smooth muscle was the most important factor in this relationship. Cellular infiltration of the smooth muscle increased with the decrease of in vitro relaxation response to salbutamol. CONCLUSION In smokers, air trapping is correlated with inflammatory infiltration of the smooth muscle layer of small airways.
Quantitative Sensitivity Analysis of Surface Attached Optical Fiber Strain Sensor

Optical fiber strain sensors, in particular, the fiber Bragg grating (FBG) type, are widely applied in different applications. The most common installation method is surface-attached. In principle, the optical fiber strain sensor with adequate sampling and signal processing techniques is usually more accurate than electrical resistive strain gauge. However, the strain of the surface of structure may not transfer to the sensing element perfectly. The ratio between the measured and actual strain can be correlated by a strain transfer factor (STF). However, it depends on the material and geometrical properties of the optical fiber and adhesive. It is noneconomical and impractical to measure the STF for every installed sensor. It is desirable to identify the most of the sensitive parameters on the variation of the STF so that the quality control and assurance procedure can be performed more efficiently. In this paper, a quantitative global sensitivity analysis, called extended Fourier amplitude sensitivity test will be performed to compute the first-order and total sensitivity indexes based on a well-established semi-analytical/empirical mechanical model of three material and five geometrical parameters of both integral and optical FBG type optical fiber strain sensor with two different kinds of polymeric coating under three types of strain field in 16 different configurations. From the detail analysis, the most of the sensitive parameters on the STF are bond length, the thickness of adhesive beneath the optical fiber and the deviation of grating position, which are related to workmanship instead of the material properties of the optical fiber and adhesive.
Treatment options in distraction osteogenesis therapy using a new bidirectional distractor system.

PURPOSE The purpose of this retrospective study was to compare a bidirectional distraction system with a unidirectional system with regard to bone height attained and the need for secondary graft procedures. MATERIALS AND METHODS Unidirectional and bidirectional distractor devices were used for vertical augmentation of the maxilla and mandible in 2 separate groups of patients (n = 10 and n = 11, respectively). Clinical and radiographic outcome data were collected at postoperative follow-up examinations for up to 2.5 years. The height of the augmented alveolar ridge and the sagittal location of the bone fragment were measured on panoramic radiographs or lateral cephalograms. These data were analyzed with 1-way analysis of variance. Nonparametric data, such as treatment complications, were analyzed with the Fisher exact test. The dental implant survival data were evaluated with a Kaplan-Meier survival analysis. RESULTS The difference in vertical bone gain observed between unidirectional and bidirectional groups (5.3 +/- 1.8 mm vs 6.1 +/- 2.3 mm) was not statistically significant. In the unidirectional group, additional autogenous bone grafting was required in 6 cases, while grafting was required in only 2 cases in the bidirectional group. This difference was due to the more precise control of the distraction process associated with the bidirectional distractor; however, it was not a statistically significant difference. Postaugmentation, 59 implants were placed in the augmented sites. These implants exhibited primary stability and were restored with good functional and esthetic results. CONCLUSIONS The need for additional grafting procedures may be reduced in cases where the distraction vector is optimized, as generally seen with bidirectional distractor use.
CpG island methylation of tumor-related promoters occurs preferentially in undifferentiated carcinoma.

OBJECTIVE To understand the role of epigenetic inactivation of tumor-related genes in the pathogenesis of thyroid cancer, we investigated the methylation profile of distinct thyroid neoplasms. DESIGN We analyzed the methylation pattern of 17 gene promoters in nine thyroid cancer cell lines and in 38 primary thyroid carcinomas (13 papillary thyroid carcinoma [PTC], 10 follicular thyroid carcinoma [FTC], 9 undifferentiated thyroid carcinoma [UTC], 6 medullary thyroid carcinoma [MTC]), 12 goiters, and 10 follicular adenomas (FA) by methylation- specific polymerase chain reaction (PCR). Epigenetic inactivation was validated by expression analysis. MAIN OUTCOME Twelve of these genes (RASSF1A, p16(INK4A), TSHR, MGMT, DAPK, ERalpha, ERbeta, RARbeta, PTEN, CD26, SLC5A8, and UCHL1) were frequently methylated in UTC (15%-86%) and thyroid cancer cell lines (25%-100%). In the more aggressive UTC, the mean methylation index (MI = 0.44) was the highest compared to other thyroid alterations PTC (MI = 0.29, p = 0.123), FTC (MI = 0.15, p = 0.005), MTC (MI = 0.13; p = 0.017), FA (MI = 0.27; p = 0.075) and goiters (MI = 0.23; p = 0.024). Methylation of TSHR, MGMT, UCHL1, and p16 occurred preferentially in UTC and this inactivation was reverted by a demethylating agent. CONCLUSIONS Our results show that hypermethylation of several tumor-related gene promoters is a frequent event in UTC. The hypermethylation status may be reversed by DNA demethylating agents. Their clinical value remains to be investigated.
Androgens positively regulate follicle-stimulating hormone beta-subunit mRNA levels in rat pituitary cells.

We have shown previously that androgens negatively regulate LH alpha and beta-subunit mRNA levels, but have little or no effect on FSH beta mRNA levels in rats in vivo. In contrast, estrogen negatively regulates all three gonadotropin subunit mRNA levels in vivo. We have examined the effects of these sex steroids on gonadotropin subunit synthesis directly at the level of the pituitary gland by using cultured rat pituitary cells. Adult female and male rat pituitaries were dissected, dispersed enzymatically, and maintained in culture for 2 days. At that time, cells were treated for varying lengths of time with either medium alone or sex-steroid hormone treatments (estradiol or testosterone). Dose-response and time-course experiments were performed. Cells were then harvested and total RNA was extracted. Gonadotropin subunit mRNA levels were assessed by blot hybridization techniques. Sex-steroid hormones were added to achieve final concentrations ranging from 10(-12) to 10(-6) M for dose response experiments and 10(-8) M for time-course experiments. Testosterone treatment (10(-8) M) increased FSH beta mRNA levels 3-fold in females (P less than 0.01) and males (P less than 0.05), but had no effect on alpha or LH beta mRNA levels in either sex. Dose-related increases in FSH beta mRNA levels with increasing concentrations of testosterone were observed in both female and male pituitary cell cultures. Time-course studies revealed that the testosterone-stimulated increases in FSH beta mRNA levels are statistically significant by 12 h and 6 h after hormone addition in female and male cultures, respectively. (ABSTRACT TRUNCATED AT 250 WORDS)
Robo-3–mediated repulsive interactions guide R8 axons during Drosophila visual system development

The formation of neuronal connections requires the precise guidance of developing axons toward their targets. In the Drosophila visual system, photoreceptor neurons (R cells) project from the eye into the brain. These cells are grouped into some 750 clusters comprised of eight photoreceptors or R cells each. R cells fall into three classes: R1 to R6, R7, and R8. Posterior R8 cells are the first to project axons into the brain. How these axons select a specific pathway is not known. Here, we used a microarray-based approach to identify genes expressed in R8 neurons as they extend into the brain. We found that Roundabout-3 (Robo3), an axon-guidance receptor, is expressed specifically and transiently in R8 growth cones. In wild-type animals, posterior-most R8 axons extend along a border of glial cells demarcated by the expression of Slit, the secreted ligand of Robo3. In contrast, robo3 mutant R8 axons extend across this border and fasciculate inappropriately with other axon tracts. We demonstrate that either Robo1 or Robo2 rescues the robo3 mutant phenotype when each is knocked into the endogenous robo3 locus separately, indicating that R8 does not require a function unique to the Robo3 paralog. However, persistent expression of Robo3 in R8 disrupts the layer-specific targeting of R8 growth cones. Thus, the transient cell-specific expression of Robo3 plays a crucial role in establishing neural circuits in the Drosophila visual system by selectively regulating pathway choice for posterior-most R8 growth cones.
Carbon pool densities and a first estimate of the total carbon pool in the Mongolian forest‐steppe

The boreal forest biome represents one of the most important terrestrial carbon stores, which gave reason to intensive research on carbon stock densities. However, such an analysis does not yet exist for the southernmost Eurosiberian boreal forests in Inner Asia. Most of these forests are located in the Mongolian forest‐steppe, which is largely dominated by Larix sibirica. We quantified the carbon stock density and total carbon pool of Mongolia's boreal forests and adjacent grasslands and draw conclusions on possible future change. Mean aboveground carbon stock density in the interior of L. sibirica forests was 66 Mg C ha−1, which is in the upper range of values reported from boreal forests and probably due to the comparably long growing season. The density of soil organic carbon (SOC, 108 Mg C ha−1) and total belowground carbon density (149 Mg C ha−1) are at the lower end of the range known from boreal forests, which might be the result of higher soil temperatures and a thinner permafrost layer than in the central and northern boreal forest belt. Land use effects are especially relevant at forest edges, where mean carbon stock density was 188 Mg C ha−1, compared with 215 Mg C ha−1 in the forest interior. Carbon stock density in grasslands was 144 Mg C ha−1. Analysis of satellite imagery of the highly fragmented forest area in the forest‐steppe zone showed that Mongolia's total boreal forest area is currently 73 818 km2, and 22% of this area refers to forest edges (defined as the first 30 m from the edge). The total forest carbon pool of Mongolia was estimated at ~ 1.5−1.7 Pg C, a value which is likely to decrease in future with increasing deforestation and fire frequency, and global warming.
Role of cholesterol in amyloid cascade: cholesterol‐dependent modulation of tau phosphorylation and mitochondrial function

Apolipoprotein E (apoE) alleles are important genetic risk factors for Alzheimer's disease (AD), with the ɛ4 allele increasing and the ɛ2 allele decreasing the risk of developing AD. ApoE is the major apolipoprotein that modulates cholesterol transport in the central nervous system, cholesterol being an essential component of membranes for maintaining their structure and functions. Epidemiological studies have suggested a link between serum cholesterol levels and AD development and the potential therapeutic effectiveness of statins for AD; and furthermore, biological studies have shown that amyloid β‐protein (Aβ) secretion is modulated by cellular cholesterol level. However, other lines of evidence show controversial results. In addition to the role of cholesterol in Aβ generation, different interactions of cholesterol with Aβ and its role in AD pathogenesis have been shown, i.e. Aβ affects cholesterol dynamics in neurons, and altered cholesterol metabolism in turn leads to neurodegeneration with abnormally phosphorylated tau (tauopathy). In this review, the reciprocal interactions between cholesterol and Aβ, and the role of cholesterol in tauopathy are discussed. The isoform‐specific involvement of apoE in this cascade, in which high‐density lipoprotein‐like particles are generated and supplied to neurons to maintain cholesterol homeostasis, is also discussed.