Pseudogenization of the tumor-growth promoter angiogenin in a leaf-eating monkey

Physiological functions of human genes may be studied by gene-knockout experiments in model organisms such as the mouse. This strategy relies on the existence of one-to-one gene orthology between the human and mouse. When lineage-specific gene duplication occurs and paralogous genes share a certain degree of functional redundancy, knockout mice may not provide accurate functional information on human genes. Angiogenin is a small protein that stimulates blood-vessel growth and promotes tumor development. Humans and related primates only have one angiogenin gene, while mice have three paralogous genes. This makes it difficult to generate angiogenin-knockout mice and even more difficult to interpret the genotype-phenotype relation from such animals should they be generated. We here show that in the douc langur (Pygathrix nemaeus), an Asian leaf-eating colobine monkey, the single-copy angiogenin gene has a one-nucleotide deletion in the sixth codon of the mature peptide, generating a premature stop codon. This nucleotide deletion is found in five unrelated individuals sequenced, and therefore is likely to have been fixed in the species. Five colobine species that are closely related to the douc langur have intact angiogenin genes, suggesting that the pseudogenization event was recent and unique to the douc langur lineage. This natural knockout experiment suggests that primate angiogenin is dispensable even in the wild. Further physiological studies of douc largurs may offer additional information on the role of this cancer-related gene in normal physiology of primates, including humans. Our findings also provide a strong case for the importance of evolutionary analysis in biomedical studies of gene functions. (C) 2003 Elsevier Science B.V. All rights reserved.

D77, one benzoic acid derivative, functions as a novel anti-HIV-1 inhibitor targeting the interaction between integrase and cellular LEDGF/p75

Integration of viral-DNA into host chromosome mediated by the viral protein HIV-1 integrase (IN) is an essential step in the HIV-1 life cycle. In this process, Lens epithelium-derived growth factor (LEDGF/p75) is discovered to function as a cellular co-fa

Measurements of triggering and transient growth in a model lean-premixed gas turbine combustor

Instability triggering and transient growth of thermoacoustic oscillations were experimentally investigated in combination with linear/nonlinear flame transfer function (FTF) methodology in a model lean-premixed gas turbine combustor operated with CH 4 and air at atmospheric pressure. A fully premixed flame with 10kW thermal power and an equivalence ratio of 0.60 was chosen for detailed characterization of the nonlinear transient behaviors. Flame transfer functions were experimentally determined by simultaneous measurements of inlet velocity fluctuations and heat release rate oscillations using a constant temperature anemometer and OH */CH * chemiluminescence emissions, respectively. The phase-resolved variation of the local flame structure at a limit cycle was measured by planar laser-induced fluorescence of OH. Simultaneous measurements of inlet velocity, OH */CH * emission, and acoustic pressure were performed to investigate the temporal evolution of the system from a stable to a limit cycle operation. This measurement allows us to describe an unsteady instability triggering event in terms of several distinct stages: (i) initiation of a small perturbation, (ii) exponential amplification, (iii) saturation, (iv) nonlinear evolution of the perturbations towards a new unstable periodic state, (v) quasi-steady low-amplitude periodic oscillation, and (vi) fully-developed high-amplitude limit cycle oscillation. Phase-plane portraits of instantaneous inlet velocity and heat release rate clearly show the presence of two different attractors. Depending on its initial position in phase space at infinitesimally small amplitude, the system evolves towards either a high-amplitude oscillatory state or a low-amplitude oscillatory state. This transient phenomenon was analyzed using frequency- and amplitude-dependent damping mechanisms, and compared to subcritical and supercritical bifurcation theories. The results presented in this paper experimentally demonstrate the hypothesis proposed by Preetham et al. based on analytical and computational solutions of the nonlinear G-equation [J. Propul. Power 24 (2008) 1390-1402]. Good quantitative agreement was obtained between measurements and predictions in terms of the conditions for the onset of triggering and the amplitude of triggered combustion instabilities. © 2011 The Combustion Institute.

Lyapunov functions for stable cascades and applications to global stabilization

This paper generalizes recent Lyapunov constructions for a cascade of two nonlinear systems, one of which is stable rather than asymptotically stable. A new cross-term construction in the Lyapunov function allows us to replace earlier growth conditions by a necessary boundedness condition. This method is instrumental in the global stabilization of feedforward systems, and new stabilization results are derived from the generalized construction.

Growth of GaSb layers on GaAs (001) substrate by molecular beam epitaxy

GaSb 1 mu m-thick layers were grown by molecular beam epitaxy on GaAs (001). The effects of the growth conditions on the crystalline quality, surface morphology, electrical properties and optical properties were studied by double crystalline x-ray diffraction, atomic force microscopy, Hall measurement and photoluminescence spectroscopy, respectively. It was found that the surface roughness and hole mobility are highly dependent on the antimony-to-gallium flux ratios and growth temperatures. The crystalline quality, electrical properties and optical properties of GaSb layers were also studied as functions of growth rate, and it was found that a suitably low growth rate is beneficial for the crystalline quality and electrical and optical properties. Better crystal quality GaSb layers with a minimum root mean square surface roughness of 0.1 nm and good optical properties were obtained at a growth rate of 0.25 mu m h(-1).

The dependence of GexSi1-x epitaxial growth on GeH4 flow using chemical vapour deposition

GexSi1-x epilayers were grown at 700-900 degrees C by atmospheric pressure chemical vapour deposition. GexSi1-x, Si and Ge growth rates as functions of GeH4 flow are considered separately to investigate how the growth of the epilayers is enhanced. Arrhenius plots of Si and Ge incorporation in the GexSi1-x growth show the activation energies associated with the growth rates are about 1.2 eV for silicon and 0.4 eV for germanium, indicating that Si growth is limited by surface kinetics and Ge growth is limited by mass transport. A model based on this idea is proposed and used to simulate the growth of GexSi1-x. The calculation and experiment are in good agreement. Growth rate and film composition increase monotonically with growth pressure; both observations are explained by the model.

Effects of the “all-fish” GH (growth hormone) transgene expression on resistance to Ichthyophthirius multifiliis infections in common carp, Cyprinus carpio L.

A study was undertaken on the susceptibility of the F-4 generation of "all-fish" growth hormone transgenic carp, Cyprinus carpio L, against Ichthyophthirius multifiliis infections. When 1-year old, transgenic carp, with non-transgenic carp and non-manipulated carp (controls) were split into three batches, and experimental infections were performed throughout the 3-month period. All 72 fish were successfully infected. It was shown that there was a significant difference (P<0.01) on infection level between transgenics and non-transgenics, and transgenics and controls. It possibly resulted from transgenics that had stronger non-specific immune functions. In addition, fish surface area affected significantly infection level (P<0.001). Carp with larger surface area harboured more parasites for each type of fish, but transgenic with larger surface area than non-transgenics and controls (P<0.01), loaded fewer parasites than others. Besides, the time of infection also greatly influenced (P<0.001) infection level. Results showed that there was a significant decline in parasite infectivity through October to November (P<0.001). It was likely to suggest that there existed senescence resulted in failure of any I. multifiliis isolate maintenance. Significant difference in infectivity between isolate G from grass carp and isolate H from gold fish suggested that different parasite strains may exist. (C) 2009 Elsevier B.V. All rights reserved.

Growth characters and photosynthetic capacity of Gracilaria lemaneiformis as a biofilter in a shellfish farming area in Sanggou Bay, China

Experiments on growth characters and ecological functions of the macroalgae Gracilaria lemaneiformis, collected from south China, were conducted in polyculture areas of kelp and filter-feeding bivalve in Sanggou Bay in Weihai City, Shandong, in north China from May 2002 to May 2003. The results of 116 days cultivation showed that the average wet weight of alga increased 89 times from 0.1 to 8.9 kg rope(-1), with an average specific growth rate ( based on wet weight) of 3.95% per day. The most favorable water layer for its growth was 1.0 - 1.8 m below the surface in July and August, with an average specific growth rate of 8.2% per day in 30-day experiments. Photosynthetic activity changed seasonally, with an average of 7.3 mg O-2 g dw(-1) h(-1). The maximum rate (14.4 mg O-2 g dw(-1) h(-1)) was recorded in July, or 19.3 mg CO2 g dw(-1) h(-1), while the minimum (0.40 mg CO2 g dw(-1) h(-1)) was in April. This study indicated that the culture of G. lemaneiformis is an effective way to improve water quality where scallops are cultivated intensively.

The rpf gene of Micrococcus luteus encodes an essential secreted growth factor

Galina V. Mukamolova, Obolbek A. Turapov, Konstantin Kazarian, Miroslav Telkov, Arseny S. Kaprelyants, Douglas B. Kell and Michael Young (2002). The rpf gene of Micrococcus luteus encodes an essential secreted growth factor. Molecular Microbiology, 46 (3), 611-621. Sponsorship: BBSRC / Russian Foundation for Basic Research (grant 00-04-48691)/ WHO Global Programme for Vaccines and Immunization / Wellcome Trust RAE2008

Effector functions of heparin-binding hemagglutinin-specific CD8+ T lymphocytes in latent human tuberculosis.

BACKGROUND: Most individuals infected with Mycobacterium tuberculosis do not develop tuberculosis (TB) and can be regarded as being protected by an appropriate immune response to the infection. The characterization of the immune responses of individuals with latent TB may thus be helpful in the definition of correlates of protection and the development of new vaccine strategies. The highly protective antigen heparin-binding hemagglutinin (HBHA) induces strong interferon (IFN)- gamma responses during latent, but not active, TB. Because of the recently recognized importance of CD8(+) T lymphocytes in anti-TB immunity, we characterized the CD8(+) T lymphocyte responses to HBHA in subjects with latent TB. RESULTS: HBHA-specific CD8(+) T lymphocytes expressed memory cell markers and synthesized HBHA-specific IFN- gamma .They also restricted mycobacterial growth and expressed cytotoxicity by a granule-dependent mechanism. This activity was associated with the intracellular expression of HBHA-induced perforin. Surprisingly, the perforin-producing CD8(+) T lymphocytes were distinct from the IFN- gamma -producing CD8(+) T lymphocytes. CONCLUSION: During latent TB, the HBHA-specific CD8(+) T lymphocyte population expresses all 3 effector functions associated with CD8(+) T lymphocyte-mediated protective immune mechanisms, which supports the notion that HBHA may be protective in humans and suggests that markers of HBHA-specific CD8(+) T lymphocyte responses may be useful in the monitoring of protection.

Ocean acidification with (de)eutrophication will alter future phytoplankton growth and succession.

Human activity causes ocean acidification (OA) though the dissolution of anthropogenically generated CO2 into seawater, and eutrophication through the addition of inorganic nutrients. Eutrophication increases the phytoplankton biomass that can be supported during a bloom, and the resultant uptake of dissolved inorganic carbon during photosynthesis increases water-column pH (bloom-induced basification). This increased pH can adversely affect plankton growth. With OA, basification commences at a lower pH. Using experimental analyses of the growth of three contrasting phytoplankton under different pH scenarios, coupled with mathematical models describing growth and death as functions of pH and nutrient status, we show how different conditions of pH modify the scope for competitive interactions between phytoplankton species. We then use the models previously configured against experimental data to explore how the commencement of bloom-induced basification at lower pH with OA, and operating against a background of changing patterns in nutrient loads, may modify phytoplankton growth and competition. We conclude that OA and changed nutrient supply into shelf seas with eutrophication or de-eutrophication (the latter owing to pollution control) has clear scope to alter phytoplankton succession, thus affecting future trophic dynamics and impacting both biogeochemical cycling and fisheries.

Mouse Uterine Natural Killer Cell Functions During Early Pregnancy

Early pregnancy is characterized by complex interactions between blood vessels, leukocytes, and conceptus-derived trophoblasts within the gestational uterus. Uterine Natural Killer (uNK) cells become the most abundant leukocyte during decidualization and produce a wide array of angiogenic factors, yet little is known regarding their early pregnancy functions. To characterize the role(s) of uNK cells, whole mount in situ immunohistochemistry of live early implant sites was performed. A timecourse examination of murine early pregnancy (virgin, and gd4.5-9.5) implantation sites was performed. Comparison of Gd6.5, 8.5 and 9.5 implant sites from BALB/c+/+ controls (BALB/c) and BALB/c-Rag2-/-Il2rg-/- (alymphoid) identified anomalies that result from the absence of lymphocytes. In alymphoid decidua basalis, mesometrial angiogenesis was widespread but pruning of nascent vessels within alymphoid decidua basalis was deficient. As early gestation progressed, vessels of alymphoid decidua basalis showed no evidence for remodeling. Alymphoid implantation sites showed ~24h delay in uterine lumen closure and embryonic development. To determine if uNK cells would normalize the anomalies observed in alymphoid implantation sites, adoptive cell transfer of NK+ B- T- marrow to alymphoid mice was performed. All of the above anomalies were reversed by adoptive transfer of NK+B-T- marrow. My results suggest that uNK cells support vascular growth and development which ensures the decidua can support the growing conceptus early in pregnancy prior to formation and function of the placenta. Human decidual NK cells may fill similar roles and be important targets for strategies designed to correct intra-uterine growth restriction.

Dynamics of Gompertzian tumour growth under environmental fluctuations

We investigate the effect of correlated additive and multiplicative Gaussian white noise oil the Gompertzian growth of tumours. Our results are obtained by Solving numerically the time-dependent Fokker-Planck equation (FPE) associated with the stochastic dynamics. In Our numerical approach we have adopted B-spline functions as a truncated basis to expand the approximated eigenfunctions. The eigenfunctions and eigenvalues obtained using this method are used to derive approximate solutions of the dynamics under Study. We perform simulations to analyze various aspects, of the probability distribution. of the tumour cell populations in the transient- and steady-state regimes. More precisely, we are concerned mainly with the behaviour of the relaxation time (tau) to the steady-state distribution as a function of (i) of the correlation strength (lambda) between the additive noise and the multiplicative noise and (ii) as a function of the multiplicative noise intensity (D) and additive noise intensity (alpha). It is observed that both the correlation strength and the intensities of additive and multiplicative noise, affect the relaxation time.

A quorum-quenching approach to investigate the conservation of quorum-sensing-regulated functions within the Burkholderia cepacia complex

Taxonomic studies of the past few years have shown that the Burkholderia cepacia complex, a heterogeneous group of B. cepacia-like organisms, consists of at least nine species. B. cepacia complex strains are ubiquitously distributed in nature and have been used for biocontrol, bioremediation, and plant growth promotion purposes. At the same time, B. cepacia complex strains have emerged as important opportunistic pathogens of humans, particularly those with cystic fibrosis. All B. cepacia complex species investigated thus far use quorum-sensing (QS) systems that rely on N-acylhomoserine lactone (AHL) signal molecules to express certain functions, including the production of extracellular proteases, swarming motility, biofilm formation, and pathogenicity, in a population-density-dependent manner. In this study we constructed a broad-host-range plasmid that allowed the heterologous expression of the Bacillus sp. strain 240B1 AiiA lactonase, which hydrolyzes the lactone ring of various AHL signal molecules, in all described B. cepacia complex species. We show that expression of AiiA abolished or greatly reduced the accumulation of AHL molecules in the culture supernatants of all tested B. cepacia complex strains. Phenotypic characterization of wild-type and transgenic strains revealed that protease production, swarming motility, biofilm formation, and Caenorhabditis elegans killing efficiency was regulated by AHL in the large majority of strains investigated.