Platelet-derived Growth Factor β-Receptor,Transforming Growth Factor β Type I Receptor,and CD44 Protein Modulate Each Other's Signaling and Stability

Growth factors, such as platelet-derived growth factor BB (PDGF-BB) and transforming growth factor β (TGFβ), are key regulators of cellular functions, including proliferation, migration, and differentiation. Growth factor signaling is modulated by context-dependent cross-talk between different signaling pathways. We demonstrate in this study that PDGF-BB induces phosphorylation of Smad2, a downstream mediator of the canonical TGFβ pathway, in primary dermal fibroblasts. The PDGF-BB-mediated Smad2 phosphorylation was dependent on the kinase activities of both TGFβ type I receptor (TβRI) and PDGF β-receptor (PDGFRβ), and it was prevented by inhibitory antibodies against TGFβ. Inhibition of the activity of the TβRI kinase greatly reduced the PDGF-BB-dependent migration in dermal fibroblasts. Moreover, we demonstrate that the receptors for PDGF-BB and TGFβ interact physically in primary dermal fibroblasts and that stimulation with PDGF-BB induces internalization not only of PDGFRβ but also of TβRI. In addition, silencing of PDGFRβ by siRNA decreased the stability of TβRI and delayed TGFβ-induced signaling. We further show that the hyaluronan receptor CD44 interacts with both PDGFRβ and TβRI. Depletion of CD44 by siRNA increased signaling via PDGFRβ and TβRI by stabilizing the receptor proteins. Our data suggest that cross-talk between PDGFRβ and TβRI occurs in dermal fibroblasts and that CD44 negatively modulates signaling via these receptors.     

Stereoselective and driving-force-dependent photoinduced electron-transfer reactions of zinc myoglobin with optically active N,N′-dimethylcinchoninium and N,N′-dimethylcinchonidinium ions

In order to understand the detailed mechanism of the stereoselective photoinduced electron-transfer (ET) reactions of zinc-substituted myoglobin (ZnMb) with optically active molecules by flash photolysis, we designed and prepared new optically active agents, such as N,N′-dimethylcinchoninium diiodide ([MCN]I₂) and N,N′-dimethylcinchonidinium diiodide ([MCD]I₂). The photoexcited triplet state of ZnMb, ³(ZnMb)*, was successfully quenched by [MCN]²⁺ and [MCD]²⁺ ions to form the radical pair of ZnMb cation (ZnMb^·+) and reduced [MCN]^·+ and [MCD]^·+, followed by a thermal back ET reaction to the ground state. The rate constants (k _q) for the ET quenching at 25 °C were obtained as k _q(MCN)=(1.9±0.1)×10⁶ M⁻¹ s⁻¹ and k _q(MCD)=(3.0±0.2)×10⁶ M⁻¹ s⁻¹, respectively. The ratio of k _q(MCD)/k _q(MCN)=1.6 indicates that the [MCD]²⁺ preferentially quenches ³(ZnMb)*. The second-order rate constants (k _b) for the thermal back ET reaction from [MCN]^·+ and [MCD]^·+ to ZnMb^·+ at 25 °C were k _b(MCN)=(0.79±0.04)×10⁸ M⁻¹ s⁻¹ and k _b(MCD)=(1.0±0.1)×10⁸ M⁻¹ s⁻¹, respectively, and the selectivity was k _q(MCD)/k _q(MCN)=1.3. Both quenching and thermal back ET reactions are controlled by the ET step. In the quenching reaction, the energy differences of ΔΔH ^≠(MCD–MCN) and ΔΔS ^≠(MCD–MCN) at 25 °C were obtained as −1.1 and 0 kJ mol⁻¹, respectively. On the other hand, ΔΔH ^≠(MCD–MCN)=11±2 kJ mol⁻¹ and TΔΔS ^≠(MCD–MCN)=−10±2 kJ mol⁻¹ were given in the thermal back ET reaction. The highest stereoselectivity of 1.7 for [MCD]^·+ found at low temperature (10 °C) was due to the ΔΔS ^≠ value obtained in the thermal back ET reaction. Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Formation of the thioester,N,S-diacetylcysteine,from acetaldehyde and N,N′diacetylcystine in aqueous solution with ultraviolet light

Summary The thioester, N,S-diacetylcysteine, is formed during the illumination of phosphate buffered (pH 7.0) aqueous solutions of acetaldehyde and N,N-diacetylcystine with ultraviolet light. The yield of N,S-diacetylcysteine relative to N-acetylcysteine and unidentified products progressively increases as ultraviolet light below 239 nm, 253 nm and 281 nm is cut off with optical filters. When ultraviolet light below 320 nm is removed with an optical filter, there is no detectable reaction. Illumination of 0.025 M N,N-diacetylcystine with 0.5 M and 1.0 M acetaldehyde with filtered ultraviolet light gives, respectively, 20% and 80% yields of N,S-diacetylcysteine. In the reaction with 1.0 M acetaldehyde, N-acetylcysteine forms early in the reaction and later decreases with its conversion to N,S-diacetylcysteine. The prebiotic significance of these reactions is discussed.Abbreviations Ac-Cys N-acetylcysteine - Ac-Cys(Ac) N,S-diacetylcysteine - Ac-Cys N,N-diacetylcystine     

Endless Urban Growth? On the Mismatch of Population,Household and Urban Land Area Growth and Its Effects on the Urban Debate

In European cities, the rate of population growth has declined significantly, while the number of households has increased. This increase in the number of households is associated with an increase in space for housing. To date, the effects of both a declining population and decreasing household numbers remain unclear. In this paper, we analyse the relationship between population and household number development in 188 European cities from 1990–2000 and 2000–2006 to the growth of urban land area and per capita living space. Our results support a trend toward decreasing population with simultaneously increasing household number. However, we also found cites facing both a declining population and a decreasing household number. Nevertheless, the urban land area of these “double-declining” cities has continued to spread because the increasing per capita living space counteracts a reduction in land consumption. We conclude that neither a decline in population nor in household number “automatically” solve the global problem of land consumption.     

N2 fixation,and the relative contribution of fixed N,in corals from Curaçao and Hawaii

Coral Reefs - Corals from Hawaii (Montipora capitata) and the Caribbean (brown and orange morphs of Montastraea cavernosa) have previously been shown to harbor symbiotic bacteria capable of fixing...     

Growth, Sporulation, δ-Endotoxins Synthesis, and Toxicity During Culture of Bacillus thuringiensis H14

Growth, sporulation, synthesis of δ-endotoxins, and toxicity against the larvae of Aedes aegypti and Culex pipiens were studied during fermentation of Bacillus thuringiensis H14 in a 20-L fermentor. Measurements of optical density and dielectric permittivity for biomass determination suggest a highly promising technique for on-line evaluation of sporulation. The synthesis of 65-, 25- and 130-kDa proteins started at 16, 18, and 23 h, respectively. These proteins were enriched in different ways until the end of culture (48 h). Toxicity in the course of sporulation was significantly different for the larvae of both mosquito species. Maximal activity against Ae. aegypti was obtained at the end of culture, whereas for Cx. pipiens, the sample at 38 h was the most active.     

Gαi2 Signaling Is Required for Skeletal Muscle Growth,Regeneration, and Satellite Cell Proliferation and Differentiation

We have previously shown that activation of Gαi2, an α subunit of the heterotrimeric G protein complex, induces skeletal muscle hypertrophy and myoblast differentiation. To determine whether Gαi2 is required for skeletal muscle growth or regeneration, Gαi2-null mice were analyzed. Gαi2 knockout mice display decreased lean body mass, reduced muscle size, and impaired skeletal muscle regeneration after cardiotoxin-induced injury. Short hairpin RNA (shRNA)-mediated knockdown of Gαi2 in satellite cells (SCs) leads to defective satellite cell proliferation, fusion, and differentiation ex vivo. The impaired differentiation is consistent with the observation that the myogenic regulatory factors MyoD and Myf5 are downregulated upon knockdown of Gαi2. Interestingly, the expression of microRNA 1 (miR-1), miR-27b, and miR-206, three microRNAs that have been shown to regulate SC proliferation and differentiation, is increased by a constitutively active mutant of Gαi2 [Gαi2(Q205L)] and counterregulated by Gαi2 knockdown. As for the mechanism, this study demonstrates that Gαi2(Q205L) regulates satellite cell differentiation into myotubes in a protein kinase C (PKC)- and histone deacetylase (HDAC)-dependent manner.     

Pastoral Sedentarization and Its Effects on Children’s Diet,Health, and Growth Among Rendille of Northern Kenya

Throughout the arid regions of Africa formerly mobile pastoral populations are becoming sedentary. Although pastoral sedentarization is encouraged by international development agencies and national governments as solutions to food insecurity, poor health care, and problems of governance, it has not been demonstrated that abandoning the pastoral way of life, and particularly childrens access to milk and other livestock products, is beneficial to the health and well-being of pastoral populations. This paper reports the results of a 3-year study of one pastoral and four settled Rendille communities of northern Kenya based on data from 17 repeated bimonthly surveys of childhood dietary, growth, and morbidity patterns and household level economic strata. Bivariate analysis of 5,535 measurements from 488 children from birth to 9 years revealed that age-specific height and weight measurements for the pastoral community are uniformly heavier and taller than children from the sedentary villages. Multivariate analysis using Generalized Estimating Equations methodology showed that the amount of milk consumed was always a statistically significant determinant of child weight and height growth, regardless of drought or non-drought times and breastfeeding status. Other significant determinants of child growth include morbidity and poverty, both associated with sedentary communities. These results indicate that international development assistance should not neglect improvements in livestock production and support of pastoral movements in Africas arid lands.     

Growth,ionic balance,proton excretion,and nitrate reductase activity in Alnus and Hippophaë supplied with different sources of nitrogen

Summary Pre-cultivated, nodulated and non-nodulated plants of black alder (Alnus glutinosa) and sea buckthorn (Hippophaë rhamnoides ssp.rhamnoides) were grown on different N sources, with and without acidity control. Dry matter yields were lowest when plants were supplied with only NO ₃ ^– and were much greater when NH ₄ ⁺ was supplied either alone or in combination with NO ₃ ^– as long as the external pH was controlled; the final yields of the N₂-fixing plants were relatively low, especially withH. rhamnoides. Without acidity control, yields were greatly reduced in the presence of NH ₄ ⁺ .Proton or hydroxyl-ion effluxes, calculated on the basis of plant analyses, agreed well with measured excretion values. Without pH adjustment, the total proton efflux into the external solution was greater inA. glutinosa than inH. rhamnoides.Both species, but particularlyA. glutinosa, displayed the highest nitrate reductase activity in the roots.     

Interactions of Bovine Brain Tubulin with Pyridostigmine Bromide and N,N′-Diethyl-m-Toluamide

Pyridostigmine bromide (PB), an inhibitor of acetylcholinesterase, has been used as a prophylactic for nerve gas poisoning. N,N-diethyl-m-toluamide (DEET) is the active ingredient in most insect repellents and is thought to interact synergistically with PB. Since PB can inhibit the binding of organophosphates to tubulin and since organophosphates inhibit microtubule assembly, we decided to examine the effects of PB and DEET on microtubule assembly as well as their interactions with tubulin, the subunit protein of microtubules. We found that PB binds to tubulin with an apparent K _d of about 60 M. PB also inhibits microtubule assembly in vitro, although at higher concentrations PB induces formation of tubulin aggregates of high absorbance. Like PB, DEET is a weak inhibitor of microtubule assembly and also induces formation of tubulin aggregates. Many tubulin ligands stabilize the conformation of tubulin as measured by exposure of sulfhydryl groups and hydrophobic areas and stabilization of colchicine binding. PB appears to have very little effect on tubulin conformation, and DEET appears to have no effect. Neither compound interferes with colchicine binding to tubulin. Our results raise the possibility that PB and DEET may exert some of their effects in vivo by interfering with microtubule assembly or function, although high intracellular levels of these compounds would be required.     

Age Structure and Growth of the Dusky Damselfish, Stegastes Fuscus, From Tamandaré Reefs, Pernambuco, Brazil

Age structure and growth of Stegastes fuscus were investigated during the present study. Individuals were collected monthly by divers using nets and spears in the reefs off Tamandaré, Pernambuco, Brazil. Otoliths were removed from 346 individuals and sectioned transversally to determine individual age. Otolith sections showed a clear pattern of opaque and translucent bands. Opaque bands were counted and initially attributed to the age of individual fish. To determine the periodicity of band formation, a validation experiment was performed, in which individuals (n = 8) were injected with tetracycline (50mgkg^-1) and kept in the laboratory for periods of three months to one year. Results of the validation experiment showed that one opaque band is deposited per year. The age of individuals collected from January to December 1995 ranged between 0 and 15 years. Analysis of margins of monthly collected individuals suggested that opaque bands are deposited during the dry season, between September and March. Readings of tetracycline-marked otoliths corroborated these results. The length-at-age curve yielded a growth constant (K) of 0.19y^-1. The high variability of the length-at-age data indicated high variability in individual growth. Length–frequency data were also used to obtain growth parameters. The growth constant, as determined with these data was 0.6y^-1 and differed markedly from K values determined from length-at-age data. It was concluded that length-frequency data are not suitable to determine growth of this species. The present study showed that otoliths are a reliable structure for aging S. fuscus, which showed to be a relatively long-lived and slow-growing tropical reef species.     

Streptomycetes in micro-cultures: Growth, production of secondary metabolites, and storage and retrieval in the 96–well format

Mycelium-forming Streptomyces strains were grown in one milliliter liquid micro-cultures in square deep-well microtiter plates. Growth was evaluated with respect to biomass formation and production of secondary metabolites which were found to be very similar in the micro-cultures, bioreactor, and shake flask cultivations, respectively. Despite repetitive sampling and extensive growth on the walls of the wells, no cross contamination occurred. Furthermore, we successfully employed cold storage at –20 °C of spore suspensions (in the 96–well format), directly prepared from cultures grown on agar in the microtitre plate. Cultures were retrieved by replicating aliquots from the frozen spore suspensions.     

Dioxo-, oxothio- and dithio-tungsten(VI) and tungsten(V) complexes of the ligand N,N′-Dimethyl-N,N′-bis(2-mercaptophenyl)ethylenediamine

Synthesis of complexes cis,cis-W^VOXL (X=Cl, NCS), cis,trans-W^VOXL (X=Cl, OPh, SPh) and cis,trans-W^VIE₂L (E₂=O₂, OS, S₂) of the title ligand LH₂ are reported. cis,cis-W^VOCIL crystallises in space group P2₁/c with a=13.6541(9) Å, b=7.1555(11) Å, c=18.198(2) Å, β=95.294(6)°, V=1770.4(3) ų and Z=4 while the cis,trans isomer crystallises in space group P2₁/n with a=10.361(3) Å, b=14.141(4) Å, c=12.213(5) Å, β=102.56(3)°, V=1747(2) ų and Z=4. cis,trans-W^VIS₂L crystallises in space group P2₁/n with a=10.645(2) Å, b=13.929(2) Å, c=12.189(2) Å, β=103.14(2)°, V=1760(1) ų and Z=4. A short CH₃···Cl distance of 3.067(7) Å and an acute OWCl angle of 94.1(2)° are seen in cis,cis-W^VOClL, which converts to the cis,trans form on heating in MeCN. The latter isomer features a CH₃···Cl distance of 3.38(2) Å and an OWCl angle of 105.1(8)°. Electrochemical and EPR data are reported. In particular, cis,trans-W^VIE₂L may be reduced to [W^VE₂L]^–. EPR properties of these anions and those of complexes W^VOXL are discussed in the context of W^V centres in tungsten enzymes.     

Growth, Natural Mortality, Length–weight Relationship, Maximum Length and Length-at-first-maturity of the Coelacanth Latimeria chalumnae

Based on the re-interpretation of published data, the von Bertalanffy growth function parameters of the coelacanth, Latimeria chalumnae, are estimated as L=218cm total length, s.e. 23; K=0.059 (year^–1), s.e. 0.012; t₀=–3.3 (year), s.e. 0.5, corresponding to a life span of 48 years. The length–weight relationship of the form W=a*TLb, with wet weight (W) in g and total length (TL) in cm, is estimated as a=0.0278, b=2.89, r²=0.893, n=87, range=42.5–183cm TL. Using extreme value theory, the maximum length for female coelacanths is estimated as 199cm TL (95% confidence interval=175–223cm TL) and for males as 168cm TL (95% confidence interval 155–180cm TL). Based on data from seven females with embryos or mature eggs, the length-at-first-maturity for females is estimated to be about 150cm TL, corresponding to an age of about 16 years. Based on the value of t₀=–3.3 years and on the presence of three scale rings found in a newborn coelacanth, the period of embryogenesis lasts for about three years, the longest known in vertebrates. The natural mortality rate is estimated at M=0.12. Population food consumption is found to be 1.4 times the existing biomass per year, and gross food conversion efficiency indicates that only 10% of the consumed food is utilized for somatic growth.     

βKlotho Is Required for Fibroblast Growth Factor 21 Effects on Growth and Metabolism

Fibroblast growth factor 21 (FGF21) is a fasting-induced hepatokine that has potent pharmacologic effects in mice, which include improving insulin sensitivity and blunting growth. The single-transmembrane protein βKlotho functions as a coreceptor for FGF21 in?vitro. To determine if βKlotho is required for FGF21 action in?vivo, we generated whole-body and adipose tissue-selective βKlotho-knockout mice. All of the effects of FGF21 on growth and metabolism were lost in whole-body βKlotho-knockout mice. Selective elimination of βKlotho in adipose tissue blocked the acute insulin-sensitizing effects of FGF21. Taken together, these data demonstrate that βKlotho is essential for FGF21 activity and that βKlotho in adipose tissue contributes to the beneficial metabolic actions of FGF21.     

Growth kinetics and competition — some contemporary comments

Results of competition experiments with one growth-limiting factor under idealized experimental conditions have been reported extensively, and usually provide ample support for the conclusion that complete competitors cannot coexist. However, under conditions of multiple substrate limitation and discontinuous or alternating supply of nutrients, coexistence of species is quite common. Since such patterns of nutrient supply may be expected to prevail in many natural environments the mechanisms ruling the survival and growth of bacteria under such conditions need to be understood. However, it appears that surprisingly little is known of the physiological state of individual competing species grown in mixed cultures. Unfortunately, basic information such as the actual concentration of limiting nutrients is lacking in most cases. But perhaps the recent development of new and powerful techniques to explore the physiological properties even of individual cells will further stimulate studies into the mechanisms behind the competitiveness of microbial species.     

The Weak Cytokinins N,N′-bis-(1-naphthyl)urea and N,N′-bis-(2-naphthyl)urea may Enhance Rooting in Apple and Mung Bean

The present research investigates the possibility that 2 weak urea-type cytokinins, the N,N′-bis-(1-naphthyl)urea and the N,N′-bis-(2-naphthyl)urea, enhance adventitious root formation. The rooting activity was assessed using the stem slice test, the mung bean rooting test and the rooting of apple microcuttings. The two compounds influenced the adventitious rooting process differently as regards the bioassay used. In the stem slice test, in the presence of exogenous auxin, both compounds enhanced the rooted slice percentage. In mung bean shoots, the N,N′-bis-(1-naphthyl)urea enhanced the root formation at the lowest concentration used (0.01 μM) while the N,N′-bis-(2-naphthyl)urea enhanced rooting at higher concentrations. In the rooting test of apple microcuttings the N,N′-bis-(1-naphthyl)urea and the N,N′-bis-(2-naphthyl)urea slightly enhanced only the mean root number per microcutting.