天然抗感染分子-细菌透性增加蛋白

革兰氏阴性菌细胞外壁中的脂多糖结构即内毒素,经常是引发脓毒症、菌血症等系统性炎症反应的"元凶"。近十余年的研究发现,细菌透性增加蛋白（bactericidal/permeability-increasing protein,BPI）具有特有的中和内毒素和拮抗革兰氏阴性菌的能力, 是一种抗感染的天然的分子靶。大量的临床研究结果已经显示其用药的有效性和安全性。近几年来国外生物药业公司正努力将重组人BPI推向市场。     

Responses of CAM species to increasing atmospheric CO2 concentrations

Crassulacean acid metabolism (CAM) species show an average increase in biomass productivity of 35% in response to a doubled atmospheric CO₂ concentration. Daily net CO₂ uptake is similarly enhanced, reflecting in part an increase in chlorenchyma thickness and accompanied by an even greater increase in water‐use efficiency. The responses of net CO₂ uptake in CAM species to increasing atmospheric CO₂ concentrations are similar to those for C₃ species and much greater than those for C₄ species. Increases in net daily CO₂ uptake by CAM plants under elevated atmospheric CO₂ concentrations reflect increases in both Rubisco‐mediated daytime CO₂ uptake and phosphoenolpyruvate carboxylase (PEPCase)‐mediated night‐time CO₂ uptake, the latter resulting in increased nocturnal malate accumulation. Chlorophyll contents and the activities of Rubisco and PEPCase decrease under elevated atmospheric CO₂, but the activated percentage for Rubisco increases and the K_M(HCO₃ ^? ) for PEPCase decreases, resulting in more efficient photosynthesis. Increases in root:shoot ratios and the formation of additional photosynthetic organs, together with increases in sucrose‐Pi synthase and starch synthase activity in these organs under elevated atmospheric CO₂ concentrations, decrease the potential feedback inhibition of photosynthesis. Longer‐term studies for several CAM species show no downward acclimatization of photosynthesis in response to elevated atmospheric CO₂ concentrations. With increasing temperature and drought duration, the percentage enhancement of daily net CO₂ uptake caused by elevated atmospheric CO₂ concentrations increases. Thus net CO₂ uptake, productivity, and the potential area for cultivation of CAM species will be enhanced by the increasing atmospheric CO₂ concentrations and the increasing temperatures associated with global climate change.     

Baicalin prevents Candida albicans infections via increasing its apoptosis rate

Background

These experiments were employed to explore the mechanisms underlying baicalin action on Candida albicans.

Methodology and principal findings

We detected the baicalin inhibition effects on three isotope-labeled precursors of ³H-UdR, ³H-TdR and ³H-leucine incorporation into C. albicans using the isotope incorporation technology. The activities of Succinate Dehydrogenase (SDH), cytochrome oxidase (CCO) and Ca²⁺–Mg²⁺ ATPase, cytosolic Ca²⁺ concentration, the cell cycle and apoptosis, as well as the ultrastructure of C.albicans were also tested. We found that baicalin inhibited ³H-UdR, ³H-TdR and ³H-leucine incorporation into C.albicans (P < 0.005). The activities of the SDH and Ca²⁺–Mg²⁺ ATPase of C.albicans in baicalin groups were lower than those in control group (P < 0.05). Ca²⁺ concentrations of C. albicans in baicalin groups were much higher than those in control group (P < 0.05). The ratio of C.albicans at the G0/G1 stage increased in baicalin groups in dose dependent manner (P < 0.01). There were a significant differences in the apoptosis rate of C.albicans between baicalin and control groups (P < 0.01). After 12–48 h incubation with baicalin (1 mg/ml), C. albicans shown to be markedly damaged under transmission electron micrographs.

Innovation and significance

Baicalin can increase the apoptosis rate of C. albicans. These effects of Baicalin may involved in its inhibiting the activities of the SDH and Ca²⁺–Mg²⁺ ATPase, increasing cytosolic Ca²⁺ content and damaging the ultrastructure of C. albicans.     

Interactions between increasing CO2 concentration and temperature on plant growth

The global environment is changing with increasing temperature and atmospheric carbon dioxide concentration, [CO₂]. Because these two factors are concomitant, and the global [CO₂] rise will affect all biomes across the full global range of temperatures, it is essential to review the theory and observations on effects of temperature and [CO₂] interactions on plant carbon balance, growth, development, biomass accumulation and yield. Although there are sound theoretical reasons for expecting a larger stimulation of net CO₂ assimilation rates by increased [CO₂] at higher temperatures, this does not necessarily mean that the pattern of biomass and yield responses to increasing [CO₂] and temperature is determined by this response. This paper reviews the interactions between the effects of [CO₂] and temperature on plants. There is little unequivocal evidence for large differences in response to [CO₂] at different temperatures, as studies are confounded by the different responses of species adapted and acclimated to different temperatures, and the interspecific differences in growth form and development pattern. We conclude by stressing the importance of initiation and expansion of meristems and organs and the balance between assimilate supply and sink activity in determining the growth response to increasing [CO₂] and temperature.     

Modelling forest response to increasing CO2 concentration under nutrient-limited conditions

The growth rates of woody plants depend on both the rate of photosynthetic carbon gain and the availability of essential nutrients. Instantaneous carbon gain is known to increase in response to increasing atmospheric CO₂ concentration, but it is uncertain whether this will translate into increased growth in the longer term under nutrient-limited conditions. An analytical model to address this question was developed by Comins & McMurtrie (1993, Ecological Applications 3, 666–681). Their model was further tested and analysed. Manipulation of various assumptions in the model revealed its key assumptions and allowed a more confident prediction of expected growth responses to CO₂ enrichment under nutrient-limited conditions. The analysis indicated that conclusions about the CO₂ sensitivity of production were strongly influenced by assumptions about the relationship between foliar and heartwood nitrogen concentrations. With heartwood nitrogen concentration proportional to foliar nitrogen concentration, the model predicted a strong response of plant productivity to increasing CO₂ concentration, whereas with heartwood nitrogen concentration set constant, the model predicted only a very slight growth response to changing CO₂ concentration. On the other hand, predictions were only slightly affected by: (1) assumptions about the extent of nitrogen retranslocation out of senescing roots and foliage or wood during heartwood formation; (2) the effects of nitrogen status on specific leaf area or (3) leaf longevity; (4) carbon allocation between different plant parts; or (5) changes in the N:C ratio of organic matter sequestered in the passive pool of soil organic matter. Modification of the effect of foliar nitrogen concentration on the light utilization coefficient had only a small effect on the CO₂ sensitivity for pines. However, this conclusion was strongly dependent on the chosen relationship between single-leaf photosynthesis and leaf nitrogen concentration. Overall, the analysis suggested that trees growing under nitrogen-limited conditions can respond to increasing atmospheric CO₂ concentration with considerable increases in growth.     

A novel function of transcription factor alpha-Pal/NRF-1: increasing neurite outgrowth

Alpha-Pal/NRF-1 is a critical regulator of the promoter of human IAP/CD47 gene, a gene related to memory formation in rodents. However, its function in neurons was unknown. We found that stable or transient expression of full-length alpha-Pal/NRF-1 in human neuroblastoma IMR-32 cells significantly induced neurite outgrowth and increased the length of neurites both in medium containing 10% fetal bovine serum and in serum-free medium. In contrast, the dominant-negative mutant of alpha-Pal/NRF-1 inhibited the induction and extension of neurites. Ectopic expression of full-length alpha-Pal/NRF-1 also increased the induction of neurite outgrowth in primary mouse cortical neurons. The IAP antisense cDNA significantly inhibited the increase of neurite outgrowth by alpha-Pal/NRF-1. These findings indicate that a novel function of alpha-Pal/NRF-1 is to regulate neuronal differentiation, and that this function is mediated partly via its downstream IAP gene.     

Female red squirrels fit Williams' hypothesis of increasing reproductive effort with increasing age

Williams predicted that reproductive effort should increase as individuals age and their reproductive value declines. This simple prediction has proven difficult to test because conventional measures of energy expenditure on reproduction may not be a true reflection of reproductive effort. We investigated age-specific variation in female reproductive effort in a stable population of North American red squirrels where energy expenditure on reproduction is likely to reflect actual reproductive effort. We used seven measures of reproductive effort spanning conception to offspring weaning. We found that females completed growth by age 3 and that reproductive value decreased after this age likely because of reproductive and survival senescence. We therefore, predicted that reproductive effort would increase from age 3 onwards. The probability of breeding, litter mass at weaning, and likelihood of territory bequeathal were all lower for 1- and 2-year-old females than for females older than 3 years, the age at which growth is completed. That growing females are faced with additional energetic requirements might account for their lower allocation to reproduction as compared with older females. The probability of attempting a second reproduction within the same breeding season and the propensity to bequeath the territory to juveniles increased from 3 years of age onwards, indicating an increase in reproductive effort with age. We think this increase in reproductive effort is an adaptive response of females to declining reproductive values when ageing, thereby supporting Williams' prediction.     

Insulin/IGF-I receptor hybrids: a mechanism for increasing receptor diversity.

Insulin and IGF-I receptors are homologous disulfide linked alpha 2 beta 2 tetramers. These tetramers are formed biosynthetically when proreceptors containing alpha and beta subunits in a single uninterrupted linear peptide form disulfide linked homodimers and are subsequently proteolytically cleaved at the alpha-beta junctions. Cells expressing both receptors also express hybrid receptors that contain one insulin receptor alpha and beta subunit, and one IGF-I receptor alpha and beta subunit. These presumably form by the association of mixed proreceptors. Hybrid receptors greatly expand the possible repertoire of cellular responses to hormonal stimulation. Although not yet examined in detail, both the hormone binding and the signaling properties of the hybrid receptor appear to be different from that of either insulin or IGF-I receptor. Regulatory mechanisms that involve either insulin or IGF-I receptor, at the level of expression or subsequently, could alter the expression or function of the hybrid receptor or the other receptor. Similarly, pathology in one receptor could affect both the hybrid and other receptor, or perhaps be partially compensated for by a hybrid receptor. The magnitude of these effects could vary greatly in different tissues depending upon the relative level of expression of the different receptor forms. These postulated responses might explain some of the complex heterogeneity and linkage of these receptors that have been observed previously.     

Effect of increasing zinc sulphate concentration during in vitro maturation of bovine oocytes

The objective was to investigate the effects of supplementary zinc (Zn) during in vitro maturation (IVM) of bovine oocytes. The DNA damage in cumulus cells was low with supplemental Zn concentrations of 1.1 and 1.5 μg/mL in the IVM medium (mean ± SEM index of DNA damage was 67.52 ± 9.32, 68.52 ±13.34, 33.80 ± 4.89, and 34.65 ± 7.92 for supplementation with 0, 0.7, 1.1, and 1.5 μg/mL Zn, respectively; P < 0.01). Total glutathione concentrations did not differ following Zn supplementation of 1.1 and 1.5 μg/mL (3.7 ± 0.4 vs. 4.0 ± 0.5 pmol, respectively, in oocytes; and in cumulus cells, 0.5 ± 0.04 nmol/10⁶ cells, combined for both treatments), but were greater (P < 0.01) than supplementation with 0.7 μg/mL (1.8 ± 0.5 pmol in oocytes and 0.2 ± 0.02 nmol/10⁶ cumulus cells). Cleavage rate increased (P < 0.05) when Zn was added to the IVM medium at any concentration (67.16 ± 1.17, 73.15 ± 1.15, 74.05 ± 1.23, and 72.76 ± 0.74 for 0, 0.7, 1.1, and 1.5 μg/mL Zn). For these concentrations, subsequent embryo development to the blastocyst stage was 17.83 ± 2.15, 21.95 ± 0.95, 27.65 ± 1.61, and 30.33 ± 2.78%, highest (P < 0.01) in oocytes matured with 1.5 μg/mL Zn. There was an increase (P < 0.05) in mean cell number per blastocyst obtained from oocytes matured with 1.1 and 1.5 μg/mL Zn relative to 0 Zn (IVM alone) and 0.7 μg/mL Zn. In conclusion, Zn during oocytes maturation significantly affected intracellular GSH content and DNA integrity of cumulus cells, and improved preimplantational embryo development. We inferred that optimal embryo development to the blastocyst stage was partially dependent on the presence of adequate Zn concentrations.     

HGF/scatter factor selectively promotes cell invasion by increasing integrin avidity.

Hepatocyte growth factor/scatter factor (HGF/SF) controls a genetic program known as 'invasive growth', which involves as critical steps cell adhesion, migration, and trespassing of basement membranes. We show here that in MDA-MB-231 carcinoma cells, these steps are elicited by HGF/SF but not by epidermal growth factor (EGF). Neither factor substantially alters the production or activity of extracellular matrix proteases. HGF/SF, but not EGF, selectively promotes cell adhesion on laminins 1 and 5, fibronectin, and vitronectin through a PI3-K-dependent mechanism. Increased adhesion is followed by enhanced invasiveness through isolated matrix proteins as well as through reconstituted basement membranes. Inhibition assays using function-blocking antibodies show that this phenomenon is mediated by multiple integrins including beta1, beta3, beta4, and beta5. HGF/SF triggers clustering of all these integrins at actin-rich adhesive sites and lamellipodia but does not quantitatively modify their membrane expression. These data suggest that HGF/SF promotes cell adhesion and invasiveness by increasing the avidity of integrins for their specific ligands.     

Modeled microgravity stimulates osteoclastogenesis and bone resorption by increasing osteoblast RANKL/OPG ratio

Mechanical unloading causes detrimental effects on the skeleton, but the underlying mechanisms are still unclear. We investigated the effect of microgravity on osteoblast ability to regulate osteoclastogenesis. Mouse osteoblast primary cultures were grown for 24 h at unit gravity or under simulated microgravity, using the NASA-developed Rotating Wall Vessel bioreactor. Conditioned media (CM) from osteoblasts subjected to microgravity increased osteoclastogenesis and bone resorption in mouse bone marrow cultures. In these osteoblasts, the RANKL/OPG ratio was higher relative to 1g. Consistently, treatment with high concentrations of OPG-inhibited osteoclastogenesis and bone resorption in the presence of CM arising from osteoblasts cultured under microgravity. Microgravity failed to affect osteoblast differentiation and function in the time frame of the experiment, as we found no effect on alkaline phosphatase mRNA and activity, nor on Runx2, osteocalcin, osteopontin, and collagen1A2 mRNA expression. In contrast, microgravity induced a time dependent increase of ERK-1/2 phosphorylation, while phospho-p38 and phospho-JNK remained unchanged. Apoptosis, revealed by bis-benzimide staining, was similar among the various gravity conditions, while it was increased under microgravity after treatment with the MEK-1/2 inhibitor, PD98059, suggesting a protection role by ERK-1/2 against cell death. In conclusion, microgravity is capable to indirectly stimulate osteoclast formation and activity by regulating osteoblast secretion of crucial regulatory factors such as RANKL and OPG. We hypothesize that this mechanism could contribute to bone loss in individuals subjected to weightlessness and other unloading conditions.     

Metabolic engineering of Corynebacterium glutamicum for increasing the production of l-ornithine by increasing NADPH availability

The experiments presented here were based on the conclusions of our previous proteomic analysis. Increasing the availability of glutamate by overexpression of the genes encoding enzymes in the l-ornithine biosynthesis pathway upstream of glutamate and disruption of speE, which encodes spermidine synthase, improved l-ornithine production by Corynebacterium glutamicum. Production of l-ornithine requires 2 moles of NADPH per mole of l-ornithine. Thus, the effect of NADPH availability on l-ornithine production was also investigated. Expression of Clostridium acetobutylicum gapC, which encodes NADP-dependent glyceraldehyde-3-phosphate dehydrogenase, and Bacillus subtilis rocG, which encodes NAD-dependent glutamate dehydrogenase, led to an increase of l-ornithine concentration caused by greater availability of NADPH. Quantitative real-time PCR analysis demonstrates that the increased levels of NADPH resulted from the expression of the gapC or rocG gene rather than that of genes (gnd, icd, and ppnK) involved in NADPH biosynthesis. The resulting strain, C. glutamicum ΔAPRE::rocG, produced 14.84 g l^?1 of l-ornithine. This strategy of overexpression of gapC and rocG will be useful for improving production of target compounds using NADPH as reducing equivalent within their synthetic pathways.     

Adipose stromal/stem cells assist fat transplantation reducing necrosis and increasing graft performance

Autologous fat transfer (AFT) is a procedure for adipose tissue (AT) repair after trauma, burns, post-tumor resections and lipodystrophies still negatively impacted by the lack of graft persistence. The reasons behind this poor outcome are unclear and seem to involve damages in either harvested/transplanted mature adipocytes or on their mesenchymal progenitors, namely adipose stromal/stem cells (ASC), and due to post-transplant AT apoptosis and involution. A rabbit subcutaneous AT regeneration model was here developed to first evaluate graft quality at different times after implant focusing on related parameters, such as necrosis and vasculogenesis. Standard AFT was compared with a strategy where purified autologous ASC, combined with hyaluronic acid (HA), assisted AFT. Five million of autologous ex vivo isolated CD29+, CD90+, CD49e+ ASC, loaded into HA, enriched 1 ml of AT generating an early significant protective effect in reducing AFT necrosis and increasing vasculogenesis with a preservation of transplanted AT architecture. This beneficial impact of ASC assisted AFT was then confirmed at three months with a robust lipopreservation and no signs of cellular transformation. By a novel ASC assisted AFT approach we ensure a reduction in early cell death favoring an enduring graft performance possibly for a more stable benefit in patients.     

喷施多效唑提高麻疯树幼苗耐盐性的生理机制

研究了600 mg?L-1 PP333喷施对200 mmol?L-1 NaCl胁迫处理下麻疯树幼苗干重、含水量、叶片细胞超微结构、光合作用、叶片渗透调节能力、叶片丙二醛含量和叶片抗氧化能力的影响。结果表明：600 mg?L-1 PP333喷施处理能显著提高200 mmol?L-1 NaCl胁迫下植株的干重、根冠比和叶片含水量,同时显著降低叶片电解质外渗率（ELP）,降低叶片细胞超微结构的伤害程度,显著提高了其叶绿素含量、净光合速率、渗透调节能力、SOD酶活性和CAT酶活性,显著降低了MDA含量和POD酶活性。可见,PP333喷施能显著提高麻疯树幼苗对盐渍的适应,主要因为其提高了植株的抗氧化能力、光合作用、渗透调节能力。     

The increasing importance of Acanthamoeba infections

Free-living amebae belonging to the genus Acanthamoeba are the causative agents of granulomatous amebic encephalitis, a chronic progressive disease of the central nervous system, and of amebic keratitis, a chronic eye infection. Granulomatous amebic encephalitis occurs more frequently in immunocompromised patients while keratitis occurs in healthy individuals. The recent increased incidence in Acanthamoeba infections is due in part to infection in patients with acquired immune deficiency syndrome, while that for keratitis is due to the increased use of contact lenses. Understanding the mechanism of host resistance to Acanthamoeba is essential since the amebae are resistant to many therapeutic agents. Studies in our laboratory as well as from others have demonstrated that macrophages from immunocompetent animals are important effector cells against Acanthamoeba. We have demonstrated also that microglial cells, resident macrophages of the brain, elicit cytokines in response to A. castellanii. Neonatal rat cortical microglia from Sprague-Dawley rats co-cultured with A. castellanii produced mRNA for the inflammatory cytokines, interleukin 1alpha, interleukin 1beta, and tumor necrosis factor alpha. In addition, scanning and transmission electron microscopy revealed that microglia ingested and destroyed A. castellanii in vitro. These results implicate macrophages as playing an effector role against Acanthamoeba and suggest immune modulation as a potential alternative therapeutic mode of treatment for these infections.     

The increasing importance of Vermamoeba vermiformis

Vermamoeba vermiformis are one of the most prevalent free-living amoebae. These amoebae are ubiquitous and also thermotolerant. Of concern, V. vermiformis have been found in hospital water networks. Furthermore, associations between V. vermiformis and pathogenic bacteria have been reported, such as Legionella pneumophila. Moreover, V. vermiformis are well known to host viruses, bacteria, and other microorganisms and cases of keratitis due to V. vermiformis in conjunction with other amoebae have been reported. Despite the preceding, the medical importance of V. vermiformis is still an ongoing discussion and its genome has been only recently sequenced. Herein, we present a review of the current understanding of the biology and pathogenesis pertaining to V. vermiformis, as well as its’ role as an etiological agent and trojan horse. An approach known as theranostics which combines both diagnosis and therapy could be utilized to eradicate and diagnose keratitis cases caused by such amoebae. Given the rise in global warming, it is imperative to investigate these rarely studied amoebae and to understand their importance in human health.