Fibroblast growth factor‐2/platelet‐derived growth factor enhances atherosclerotic plaque stability

Increased immature neovessels contribute to plaque growth and instability. Here, we investigated a method to establish functional and stable neovessel networks to increase plaque stability. Rabbits underwent aortic balloon injury and were divided into six groups: sham, vector and lentiviral transfection with vascular endothelial growth factor‐A (VEGF)‐A, fibroblast growth factor (FGF)‐2, platelet‐derived growth factor (PDGF)‐BB and FGF‐2 + PDGF‐BB. Lentivirus was percutaneously injected into the media‐adventitia of the abdominal aorta by intravascular ultrasound guidance, and plaque‐rupture rate, plaque‐vulnerability index and plaque neovessel density at the injection site were evaluated. Confocal microscopy, Prussian Blue assay, Evans Blue, immunofluorescence and transmission electron microscopy were used to assess neovessel function and pericyte coverage. To evaluate the effect of FGF‐2/PDGF‐BB on pericyte migration, we used the mesenchymal progenitor cell line 10T1/2 as an in vitro model. VEGF‐A‐ and FGF‐2‐overexpression increased the number of immature neovessels, which caused intraplaque haemorrhage and inflammatory cell infiltration, eventually resulting in the plaque vulnerability; however, FGF‐2/PDGF‐BB induced mature and functional neovessels, through increased neovessel pericyte coverage. Additionally, in vitro analysis of 10T1/2 cells revealed that FGF‐2/PDGF‐BB induced epsin‐2 expression and enhanced the VEGF receptor‐2 degradation, which negatively regulated pericyte function consistent with the in vivo data. These results showed that the combination of FGF‐2 and PDGF‐BB promoted the function and maturation of plaque neovessels, thereby representing a novel potential treatment strategy for vulnerable plaques.     

Fungal growth during rice tapé fermentation

Fungal growth was quantified during Indonesian rice tapé fermentation using an agar-film technique following sample homogenization for 1 min at 25000 rev/min. After 72 h fermentation, mould hyphal length was 0·68 km/g, yeast hyphal length 2·1 km/g and the numbers of mould chlamydospores and single yeast cells were 14 times 10⁵/g and 5·1 times 10⁷/g respectively. The estimated fungal biomass in rice tapé after 72 h was 25 mg/g dry weight with 62% of this being mould hyphae, 24% mould chlamydospores, 13% yeast hyphae and 1% yeast cells.     

Modelling avian growth with the Unified‐Richards: as exemplified by wader‐chick growth

Postnatal growth in birds is traditionally modelled by fitting three‐parameter models, namely the logistic, the Gompertz, or the von Bertalanffy models. The purpose of this paper is to address the utility of the Unified‐Richards (U‐Richards) model. We draw attention to two forms of the U‐Richards and lay down a set of recommendations for the analysis of bird growth, in order to make this model and the methods more accessible. We examine the behaviour of the four parameters in each model form and the four derived measurements, and we show that all are easy to interpret, and that each parameter controls a single curve characteristic. The two parameters that control the inflection point, enable us to compare its placement in two dimensions, 1) inflection value (mass or length at inflection) and 2) inflection time (time since hatching), between data sets (e.g. between biometrics or between species). We also show how the parameter controlling growth rate directly presents us with the relative growth rate at inflection, and we demonstrate how one can compare growth rates across data sets. The three traditional models, where the inflection value is fixed (to a specific percentage of the upper asymptote), provide incompatible growth‐rate coefficients. One of the two forms of the U‐Richards model makes it possible to fix not only the upper asymptote (adult value), but also the intersection with the y‐axis (hatching value). Fitting the new model forms to data validates the usefulness of interpreting the inflection placement in addition to the growth rate. It also illustrated the advantages and limitations of constraining the upper asymptote (adult value) and the y‐axis intersection (hatching value) to fixed values. We show that the U‐Richards model can successfully replace some of the commonly used growth models, and we advocate replacing these with the U‐Richards when modelling bird growth.     

Slowdown of growth controls cellular differentiation

How can changes in growth rate affect the regulatory networks behavior and the outcomes of cellular differentiation? We address this question by focusing on starvation response in sporulating Bacillus subtilis. We show that the activity of sporulation master regulator Spo0A increases with decreasing cellular growth rate. Using a mathematical model of the phosphorelay—the network controlling Spo0A—we predict that this increase in Spo0A activity can be explained by the phosphorelay protein accumulation and lengthening of the period between chromosomal replication events caused by growth slowdown. As a result, only cells growing slower than a certain rate reach threshold Spo0A activity necessary for sporulation. This growth threshold model accurately predicts cell fates and explains the distribution of sporulation deferral times. We confirm our predictions experimentally and show that the concentration rather than activity of phosphorelay proteins is affected by the growth slowdown. We conclude that sensing the growth rates enables cells to indirectly detect starvation without the need for evaluating specific stress signals.     

The effect of growth regulators on the growth and pigmentation of "Baccara" rose flowers

"Baccara" rose buds were treated with various growth regulatorsduring late stages of bud development. The effect of these substanceson growth and pigmentation were determined. Growth regulatorswere applied by spray or injection or as a lanolin paste, alsoin the nutrient media on which petals were cultured in vitro.Injection of GA into the base of the receptacle caused elongationof the bud whereas IAA, K, ABA, AMO-1618, CCC, and SADH hadlittle or no effect. CCC and MeCl-F did not reduce the elongationcaused by GA. GA treatments also enhanced flower weight andpetal pigmentation and MeCl-F decreased the gibberellin effecton pigmentation. GA treatments of intact flowers and excisedpetals cultured in vitro, were only effective at low temperatures. Gibberellin treatments increased the size of petals, the receptacleand the pedicel only if applied directly to the receptacle.Treatments at lower positions on the flowering shoot eitherhad no effect at all, or caused elongation of only the receptacle. Endogenous gibberellin levels are higher in the receptacle thanin petals or in the pedicel. Injection of GA into the receptaclesignificantly increased gibberellin activity in all flower partswhereas injection into the flowering-shoot base increased gibberellinactivity only in the receptacle. The possibility is discussed that GA, which is exogenously supplieddirectly to the receptacle, enhances flower dimensions and pigmentationby drawing photosynthates to the flower as a consequence ofintensification of the sink. (Received August 17, 1973; )     

Pursuing a ‘turning point’ in growth cone research

Growth cones are highly motile structures found at the leading edge of developing and regenerating nerve processes. Their role in axonal pathfinding has been well established and many guidance cues that influence growth cone behavior have now been identified. Many studies are now providing insights into the transduction and integration of signals in the growth cone, though a full understanding of growth cone behavior still eludes us. This review focuses on recent studies adding to the growing body of literature on growth cone behavior, focusing particularly on the level of autonomy the growth cone possesses and the role of local protein synthesis.     

Sex-related growth and secondary compounds in Juniperus oxycedrus macrocarpa

Gender-related differences in growth and concentration of secondary metabolites have been documented in dioecious plants. Males usually grow faster than females, whilst females allocate more resources to reproduction and chemical defences than males, hence their growth is reduced. This hypothesis was tested on prickly juniper (Juniperus oxycedrus macrocarpa), a Mediterranean evergreen tree. The results showed that males grew faster than females but also had higher concentrations of both phenolics and terpenoids. However, neither phenolic nor terpenoid concentrations were correlated with growth in either sex, nor with a “reproductive effort” index in female trees. No browsing occurred on any of the trees sampled. Contrary to predictions, this study suggests that allocation of resources to reproduction in plants may reduce the resources available to both growth and secondary compounds. This might be particularly pronounced in plants with “expensive” fruits, such as prickly juniper, characterised by relatively large, long-lived fruits.     

Heterochrony and post‐natal growth in mammals – an examination of growth plates in limbs

Mammals display a broad spectrum of limb specializations coupled with different locomotor strategies and habitat occupation. This anatomical diversity reflects different patterns of development and growth, including the timing of epiphyseal growth plate closure in the long bones of the skeleton. We investigated the sequence of union in 15 growth plates in the limbs of about 400 specimens, representing 58 mammalian species: 34 placentals, 23 marsupials and one monotreme. We found a common general pattern of growth plate closure sequence, but one that is universal neither between species nor in higher‐order taxa. Locomotor habitat has no detectable correlation with the growth plate closure sequence, but observed patterns indicate that growth plate closure sequence is determined more strongly through phylogenetic factors. For example, the girdle elements (acetabulum and coracoid process) always ossify first in marsupials, whereas the distal humerus is fused before the girdle elements in some placentals. We also found that heterochronic shifts (changes in timing) in the growth plate closure sequence of marsupials occur with a higher rate than in placentals. This presents a contrast with the more limited variation in timing and morphospace occupation typical for marsupial development. Moreover, unlike placentals, marsupials maintain many epiphyses separated throughout life. However, as complete union of all epiphyseal growth plates is recorded in monotremes, the marsupial condition might represent the derived state.     

Induction of growth phase-specific autolysis in <Emphasis Type="Italic">Bacillus subtilis</Emphasis> 168 by growth inhibitors

Growth phase-specific autolysis of Bacillus subtilis by inhibitors of membrane permeability, inhibitors of macromolecule biosynthesis, inhibitors of cell wall biosynthesis and detergents were tested and characterized in glucose limited liquid medium. The minimum autolysin induction concentration (MAIC) of test compounds, which was at least l/20th lower than the conventional autolysis induction concentration, induced autolysis only for cells at the glucose exhaustion point (diauxic point) of the growth phase, while it was not induced for cells at pre- and post-diauxic points. Inhibitors of macromolecule synthesis that are not known for inducing autolysis, such as chloramphenicol, rifampicin, nalidixic acid, and detergents, also induced specific autolysis. Two types of autolysis corresponding to the concentrations of compounds are distinguished: concentration-sensitive and concentration-insensitive types.     

Influences of the environment on the endocrine and paracrine fish growth hormone–insulin‐like growth factor‐I system

Insulin‐like growth factor‐I (IGF‐I) is a key component of the complex system that regulates differentiation, development, growth and reproduction of fishes. The IGF‐I gene is mainly expressed in the liver that represents the principal source of endocrine IGF‐I but also in numerous other organs where the hormone most probably acts in an autocrine–paracrine manner. The primary stimulus for synthesis and release of IGF‐I is growth hormone (GH) from the anterior pituitary. Thus, in analogy to mammals, it is usual to speak of a fish ‘GH–IGF‐I axis'. The GH–IGF‐I system is affected by changes in the environment and probably represents a target of endocrine disrupting compounds (EDC) that impair many physiological processes in fishes. Thus, the review deals with the influences of changes in different environmental factors, such as food availability, temperature, photoperiod, season, salinity and EDCs, on GH gene expression in pituitary, IGF‐I gene expression in liver and extrahepatic sites and the physiological effects resulting from the evoked alterations in endocrine and local IGF‐I. Environmental influences certainly interact with each other but for convenience of the reader they will be dealt with in separate sections. Current trends in GH–IGF‐I research are analysed and future focuses are suggested at the end of the sections.     

Effects of sugars and growth regulators on <Emphasis Type="Italic">in vitro</Emphasis> growth of <Emphasis Type="Italic">Dactylorhiza</Emphasis> species

The influence of sugars and growth regulators on shoot and root growth of Dactylorhiza species was studied under in vitro conditions. The seedling development was stimulated with the application of glucose and sucrose at concentration of 10 g dm⁻³ each. The improvement of shoot growth rate and shoot length was enhanced by cytokinins N ⁶-(2-isopentenyl)adenine or N ⁶-benzyladenine and their combination with auxin indolebutyric acid (IBA). The root growth rate and root length of seedlings increased in the presence of IBA and α-naphthaleneacetic acid. Individual Dactylorhiza species showed statistically significant differences in shoot and root development depending on sugar and growth regulator combinations.     

Hepatoma‐derived growth factor promotes growth and metastasis of hepatocellular carcinoma cells

We aimed to elucidate the effects of hepatoma‐derived growth factor (HDGF) on growth and metastasis of hepatocellular carcinoma (HCC) cells. Tissue microarrays with 236 HCC specimens and 18 extrahepatic metastases were utilized to detect the HDGF expression by immunohistochemistry. Meanwhile, HDGF expressions in HCC cell lines with different metastatic potentials were examined using immunofluorescence staining, real‐time PCR and western blotting. After HDGF silencing, the growth and metastatic potentials of HCC cells were evaluated by soft agar assay, invasion assay, together with tumorigenicity assay in nude mice. The gelatin zymography was performed by detecting MMP‐2 and MMP‐9 levels. Additionally, western blotting was conducted to determine the levels of total and phosphorylated ERK1/2, JNK, p38 and Akt. The results showed that HDGF was overexpressed in HCC metastasis tumour, and the expression increased with the differentiation degree of tumours (Grade I 44.0%, Grade II 48.4% and Grade III 65.6%). Consistently, HDGF levels were positively associated with the metastatic capability of HCC cells (MHCC97L < MHCC97H < HCCLM3). The growth and metastasis were suppressed by HDGF‐siRNA. Gelatinolytic activities were enhanced in the three metastatic HCC cell lines, but had no significant difference among them. The tumourigenicity and metastatic capability of HCCLM3 cells in nude mice were inhibited after silencing HDGF. Meanwhile, HDGF‐siRNA specifically suppressed the total and phosphorylated protein levels of ERK1/2, while not JNK, p38 and Akt. In conclusion, HDGF was overexpressed in HCC patients and cells, and HDGF might be closely correlated with HCC metastasis via regulating ERK signalling pathway. Copyright © 2016 John Wiley & Sons, Ltd.     

miR‐134 inhibits non‐small cell lung cancer growth by targeting the epidermal growth factor receptor

The epidermal growth factor receptor (EGFR) is frequently activated in a wide range of solid tumours and represents an important therapeutic target. MicroRNAs (miRNAs) have recently been recognized as a rational and potential modality for anti‐EGFR therapies. However, more EGFR‐targeting miRNAs need to be explored. In this study, we identified a novel EGFR‐targeting miRNA, miRNA‐134 (miR‐134), in non‐small‐cell lung cancer (NSCLC) cell lines. Luciferase assays confirmed that EGFR is a direct target of miR‐134. In addition, the overexpression of miR‐134 inhibited EGFR‐related signaling and suppressed NSCLC cells proliferation by inducing cell cycle arrest and/or apoptosis, suggesting that miR‐134 functions as a tumour suppressor in NSCLC. Further mechanistic investigation including RNAi and rescue experiments suggested that the down‐regulation of EGFR by miR‐134 partially contributes to the antiproliferative role of miR‐134. Last, in vivo experiments demonstrated that miR‐134 suppressed tumour growth of A549 xenograft in nude mice. Taken together, our findings suggest that miR‐134 inhibits non‐small cell lung cancer growth by targeting the EGFR.