Niemann–Pick type C cells show cholesterol dependent decrease of APP expression at the cell surface and its increased processing through the β-secretase pathway

The link between cholesterol and Alzheimer's disease has recently been revealed in Niemann–Pick type C disease. We found that NPC1^?/? cells show decreased expression of APP at the cell surface and increased processing of APP through the β-secretase pathway resulting in increased C99, sAPPβ and intracellular Aβ40 levels. This effect is dependent on increased cholesterol levels, since cholesterol depletion reversed cell surface APP expression and lowered Aβ/C99 levels in NPC1^?/? cells to the levels observed in wt cells. Finding that overexpression of C99, a direct γ-secretase substrate, does not lead to increased intracellular Aβ levels in NPC1^?/? cells vs. CHOwt suggests that the effect on intracellular Aβ upon cholesterol accumulation in NPC1^?/? cells is not due to increased APP cleavage by γ-secretase. Our results indicate that cholesterol may modulate APP processing indirectly by modulating APP expression at the cell surface and thus its cleavage by β-secretase.     

Association of glutathione S-transferase polymorphisms (GSTM1 and GSTT1) with primary open-angle glaucoma: An evidence-based meta-analysis

Studies investigating the associations between glutathione S-transferase (GST) genetic polymorphisms and primary open-angle glaucoma (POAG) have reported controversial results. Therefore, a meta-analysis was performed to clarify the effects of GSTM1 and GSTT1 polymorphisms on POAG risk. Published literatures from PubMed, EMBASE, ISI Web of Science and CBM databases were retrieved. All studies evaluating the association between GSTM1/GSTT1 polymorphisms and POAG were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed- or random-effects model. Eleven studies on GSTM1 (1339 cases and 1412 controls) and seven studies on GSTT1 (958 cases, 1003 controls) were included. Overall analysis showed that the association between GSTM1 and GSTT1 null genotype and POAG risk is not statistically significant. Subgroup analyses showed that the null genotype of GSTM1 increased the risk of POAG in Asians. In GSTM1–GSTT1 interaction analysis, individuals with dual null genotype were associated with a significantly increased risk of POAG when compared with the dual present genotype. In conclusion, the present meta-analysis suggested that GSTM1 null genotypes are associated with increased POAG risk in Asian populations but not in Caucasian and mixed populations. Dual null genotype of GSTM1/GSTT1 is associated with increased risk of POAG. Given the limited sample size, the finding on GST polymorphisms needs further investigation.     

The effect of aerobic exercise on the expression of genes in skeletal muscles of trained and untrained men

It is well recognized that PGC-1α protein is a key regulator of mitochondrial biogenesis. Mechanical and metabolic perturbations in a skeletal muscle during and after aerobic exercise lead to an increased expression of PGC-1α gene. This increased expression of PGC-1α gene after exercise depends on the relative workload intensity and does not depend on the fitness level. The goal of this study was to compare mRNA expression of PGC-1α, TFAM, and TFB2M regulators of mitochondrial biogenesis and FOXO1 and Atrogin-1 proteolysis-related genes in a skeletal muscle of untrained and trained men after aerobic exercise with the same relative workload. This study showed that PGC-1α gene expression after exercise was the same in the two groups, but the expression of TFAM and TFB2M genes was higher in untrained muscles than in trained ones. In contrast, the expression of FOXO1 and Atrogin-1 genes increased only in the muscles of trained men.     

Warming and Nitrogen Addition Alter Photosynthetic Pigments,Sugars and Nutrients in a Temperate Meadow Ecosystem

Global warming and nitrogen (N) deposition have an important influence on terrestrial ecosystems; however, the influence of warming and N deposition on plant photosynthetic products and nutrient cycling in plants is not well understood. We examined the effects of 3 years of warming and N addition on the plant photosynthetic products, foliar chemistry and stoichiometric ratios of two dominant species, i.e., Leymus chinensis and Phragmites communis, in a temperate meadow in northeastern China. Warming significantly increased the chlorophyll content and soluble sugars in L. chinensis but had no impact on the carotenoid and fructose contents. N addition caused a significant increase in the carotenoid and fructose contents. Warming and N addition had little impact on the photosynthetic products of P. communis. Warming caused significant decreases in the N and phosphorus (P) concentrations and significantly increased the carbon (C):P and N:P ratios of L. chinensis, but not the C concentration or the C:N ratio. N addition significantly increased the N concentration, C:P and N:P ratios, but significantly reduced the C:N ratio of L. chinensis. Warming significantly increased P. communis C and P concentrations, and the C:N and C:P ratios, whereas N addition increased the C, N and P concentrations but had no impact on the stoichiometric variables. This study suggests that both warming and N addition have direct impacts on plant photosynthates and elemental stoichiometry, which may play a vital role in plant-mediated biogeochemical cycling in temperate meadow ecosystems.     

Effect of increased pCO2 on phytoplankton–virus interactions

Atmospheric carbon dioxide (CO₂) has increased since the pre-industrial period and is predicted to continue to increase throughout the twenty-first century. The ocean is a sink for atmospheric CO₂ and increased CO₂ concentration will change the carbonate equilibrium of seawater and result in lower carbonate ion concentration and lower pH. This may affect the entire marine biota but in particular calcifying organisms. In this study we investigated the effect of increased CO₂ on the virus host interaction of Emiliania huxleyi as a calcifying organism and of Phaeocystis poucheti as a non- calcifying organism. Both algae were grown in laboratory controlled conditions under past (280 ppmv), present (350 ppmv) and future (700 ppmv) CO₂ concentrations with and without added virus. Increased CO₂ had a negative effect on the growth rate of P. pouchetii, but not of E. huxleyi. No impact was found on viral lysis of P. pouchetii while increased burst size and slightly delayed lysis was observed for E. huxleyi with increased CO₂. We conclude that this short time study could not confirm earlier reports and our hypothesis of a negative effect of high CO₂ on E. huxleyi growth and E. huxleyi virus production.     

Rep1p negatively regulating MDR1 efflux pump involved in drug resistance in Candida albicans

Overexpression of MDR1 efflux pump is a major mechanism contributing to drug resistance in Candida albicans, the most common human fungal pathogen. To elucidate the regulatory pathway of drug resistance, we have identified a negative regulator of MDR1 and named it Regulator of Efflux Pump 1 (REP1). Overexpression of REP1 in Saccharomyces cerevisiae increased susceptibility to fluconazole. Furthermore, null mutations on REP1 decreased the susceptibility to antifungal drugs in C. albicans resulting from increased expression of MDR1 mRNA. Hence, Rep1p is involved in drug resistance by negatively regulating MDR1 in C. albicans.     

Effects of nutritional input and diesel contamination on soil enzyme activities and microbial communities in antarctic soils

Pollution of Antarctic soils may be attributable to increased nutritional input and diesel contamination via anthropogenic activities. To investigate the effect of these environmental changes on the Antarctic terrestrial ecosystem, soil enzyme activities and microbial communities in 3 types of Antarctic soils were evaluated. The activities of alkaline phosphomonoesterase and dehydrogenase were dramatically increased, whereas the activities of β-glucosidase, urease, arylsulfatase, and fluorescein diacetate hydrolysis were negligible. Alkaline phosphomonoesterase and dehydrogenase activities in the 3 types of soils increased 3- to 10-fold in response to nutritional input, but did not increase in the presence of diesel contamination. Consistent with the enzymatic activity data, increased copy numbers of the phoA gene, encoding an alkaline phosphomonoesterase, and the 16S rRNA gene were verified using quantitative real-time polymerase chain reaction. Interestingly, dehydrogenase activity and 16S rRNA gene copy number increased slightly after 30 days, even under diesel contamination, probably because of adaptation of the bacterial population. Intact Antarctic soils showed a predominance of Actinobacteria phylum (mostly Pseudonorcarida species) and other phyla such as Proteobacteria, Chloroflexi, Planctomycetes, Firmicutes, and Verrucomicrobia were present in successively lower proportions. Nutrient addition might act as a selective pressure on the bacterial community, resulting in the prevalence of Actinobacteria phylum (mostly Arthrobacter species). Soils contaminated by diesel showed a predominance of Proteobacteria phylum (mostly Phyllobacterium species), and other phyla such as Actinobacteria, Bacteroidetes, Planctomycetes, and Gemmatimonadetes were present in successively lower proportions. Our data reveal that nutritional input has a dramatic impact on bacterial communities in Antarctic soils and that diesel contamination is likely toxic to enzymes in this population.     

Wetting properties of fungi mycelium alter soil infiltration and soil water repellency in a γ-sterilized wettable and repellent soil

Soil water repellency (SWR) has a drastic impact on soil quality resulting in reduced infiltration, increased runoff, increased leaching, reduced plant growth, and increased soil erosion. One of the causes of SWR is hydrophobic fungal structures and exudates that change the soil–water relationship. The objective of this study was to determine whether SWR and infiltration could be manipulated through inoculation with fungi. The effect of fungi on SWR was investigated through inoculation of three fungal strains (hydrophilic – Fusarium proliferatum, chrono-amphiphilic – Trichoderma harzianum, and hydrophobic – Alternaria sp.) on a water repellent soil (WR-soil) and a wettable soil (W-soil). The change in SWR and infiltration was assessed by the water repellency index and cumulative infiltration respectively. F. proliferatum decreased the SWR on WR-soil and slightly increased SWR in W-soil, while Alternaria sp. increased SWR in both the W-soil and the WR-soil. Conversely T. harzianum increased the SWR in the W-soil and decreased the SWR in the WR-soil. All strains showed a decrease in infiltration in W-soil, while only the F. proliferatum and T. harzianum strain showed improvement in infiltration in the WR-soil. The ability of fungi to alter the SWR and enmesh soil particles results in changes to the infiltration dynamics in soil.     

Recombinant expression of glpK and glpD genes improves the accumulation of shikimic acid in E. coli grown on glycerol

Shikimic acid (SA) is an industrially important chiral compound used in diverse commercial applications, and the insufficient supply by isolation from plants and expensive chemical synthesis of SA has increased the importance of developing strategies for SA synthesis. In our previous studies, glycerol was observed to be an effective carbon source for SA accumulation in E. coli DHPYAAS-T7, where the PTS operon (ptsHIcrr) and aroL and aroK genes were inactivated, and the tktA, glk, aroE, aroF ^fbr , and aroB genes were overexpressed. For further investigation of the effects of glycerol aerobic fermentation on SA accumulation in E. coli BL21(DE3), the glpD, glpK genes and tktA, glk, aroE, aroF ^fbr , aroB genes were overexpressed simultaneously. The results indicated that SA production was increased 5.6-fold, while the yield was increased 5.3-fold over that of parental strain in shake flasks. It is demonstrated that the aerobic fermentation of glycerol associated with glpD and glpK gene overexpression increased glycerol flux, resulting in higher SA accumulation in E. coli BL21(DE3)-P-DK.     

Intertidal zonation of prosobranch gastropods: Analysis of densities of four co-existing species

The densities of populations of Nerita atramentosa Reeve, Austrocochlea constricta Lamarck, Bembiciuin nanum (Lamarck), and Cellana tramoserica (Sowerby) were recorded in 0.25 m² quadrats on landward and seaward halves of a sheltered and a moderately exposed rock platform from June 1972 to June 1973. The data have been subjected to variance and multiple regression analysis. Differences between densities of each species on the two shores and in the two areas of each shore are discussed with respect to the regressions on littoral height. Densities of Nerita on the sheltered shore, Austrocochlea and Bembicium on both shores, and Cellana, on the exposed shore, increased with height. The density of Cellana on the sheltered shore decreased as height increased. The density differences in the landward and seaward areas on the two shores were attributable to the effect of height for Nerita and Austrocochlea. Height was the major variable affecting the density of these two species on the sheltered shore. Bembicium and Cellana densities on both shores, and Austrocochlea density on the exposed shore, are not primarily determined by height.On the sheltered shore, Nerita and Cellana increased in density with increasing cover of water in rock pools. On the exposed shore, Bembicium and Cellana became sparser with increasing water cover. Bembicium on both shores increased in density with increasing cover of the alga Peyssonelia, as did Cellana on the exposed shore. Cellana and Austrocochlea tended to increase in density with Nerita on the sheltered shore. Cellana tended to be sparse where Bembicium was dense on the exposed shore. The biological effects of substrata and other species on the densities of each species remain unexplained.Significant time effects were found for variations in the densities of Nerita and Cellana on the sheltered shore and of Austrocochlea and Cellana on the exposed shore. The seasonal change in density of Nerita was parabolic with a minimum in summer, and is consistent with the known period of recruitment of this species. The lack of significant time effects on density of Austrocochlea on the sheltered shore is consistent with the known continuous recruitment of this species. The declining density of Austrocochlea on the moderately exposed shore was found, by size-frequency analysis, to be due to reduced recruitment compared with surrounding shores. The density of Cellana on both shores showed seasonal changes, with a maximum in summer, which is consistent with the known period of recruitment in Cellana. The lack of seasonal changes in density of Bembicium is briefly discussed.This type of multifactor analysis identifies biological interactions affecting variation in density of these species. It also corroborates the results of other ecological investigations and determines the relative importance of a variety of physical and biological factors in the distribution of density of intertidal gastropods.     

Genome-Wide Gene Expression Analysis of Bordetella pertussis Isolates Associated with a Resurgence in Pertussis: Elucidation of Factors Involved in the Increased Fitness of Epidemic Strains

Bordetella pertussis (B. pertussis) is the causative agent of whooping cough, which is a highly contagious disease in the human respiratory tract. Despite vaccination since the 1950s, pertussis remains the most prevalent vaccine-preventable disease in developed countries. A recent resurgence pertussis is associated with the expansion of B. pertussis strains with a novel allele for the pertussis toxin (ptx) promoter ptxP3 in place of resident ptxP1 strains. The recent expansion of ptxP3 strains suggests that these strains carry mutations that have increased their fitness. Compared to the ptxP1 strains, ptxP3 strains produce more Ptx, which results in increased virulence and immune suppression. In this study, we investigated the contribution of gene expression changes of various genes on the increased fitness of the ptxP3 strains. Using genome-wide gene expression profiling, we show that several virulence genes had higher expression levels in the ptxP3 strains compared to the ptxP1 strains. We provide the first evidence that wildtype ptxP3 strains are better colonizers in an intranasal mouse infection model. This study shows that the ptxP3 mutation and the genetic background of ptxP3 strains affect fitness by contributing to the ability to colonize in a mouse infection model. These results show that the genetic background of ptxP3 strains with a higher expression of virulence genes contribute to increased fitness.     

Species-specific effects of elevated CO2 on resource allocation in Plantago maritima and Armeria maritima

We investigated the effects of increased atmospheric CO₂ on the biomass, photosynthesis, protein and phenolic concentrations and content of Plantago maritima and Armeria maritima. This enabled us to test the protein competition model (PCM) for predicting C allocation to phenolics. Three contrasting responses to elevated CO₂ (600 μmol CO₂ mol⁻¹) between the two study species were observed. (1) In P. maritima, plant biomass increased and the maximum carboxylation rate of Rubisco (V_c,max) was decreased. However, in A. maritima, shoot biomass decreased and the V_c,max of Rubisco was unchanged. (2) The total phenolic content increased in P. maritima but decreased in A. maritima. (3) Protein concentrations and content decreased in P. maritima and root protein concentrations and content increased in A. maritima. We conclude that C and N allocation to phenolics and proteins is species- and organ-specific and the PCM predictions were correct when phenolics and proteins were expressed on a per plant content basis.     

Evidence of a Genetic Basis for Differences in Parasitization Success between Strains of Avetianella longoi (Siscaro)

When the cerambycid, Phoracantha recurva, invaded California in the mid 1990’s a parasitoid wasp was imported from its native range in Australia as part of a biological control program. The wasp was later identified to be Avetianella longoi, which had already been released years earlier to control the congener longhorned beetle, Phoracantha semipunctata. Despite being recognized as the same species, the two wasps exhibited differential success on P. recurva eggs, indicating the presence of two separate strains. Here we determine if the differentiating factor between the two strains of A. longoi is a heritable genetic trait. All four pairings between the two strains were conducted, resulting in two homogenous and two heterogeneous crosses. All crosses except one produced viable F1 female offspring. F1 females were allowed to oviposit on P. recurva eggs and the survival of their offspring was compared to determine if survival can be affected by paternal contributions. The result was that the offspring of females with fathers from the second introduced strain showed significantly increased survival compared to F1 females with parents from the first introduced strain. This increased survival demonstrated that there is a heritable dominant trait that is associated with increased survival on P. recurva host eggs.     

Influence of increased nutrient availability on biogenic volatile organic compound (BVOC) emissions and leaf anatomy of subarctic dwarf shrubs under climate warming and increased cloudiness

Background and AimsClimate change is subjecting subarctic ecosystems to elevated temperature, increased nutrient availability and reduced light availability (due to increasing cloud cover). This may affect subarctic vegetation by altering the emissions of biogenic volatile organic compounds (BVOCs) and leaf anatomy. We investigated the effects of increased nutrient availability on BVOC emissions and leaf anatomy of three subarctic dwarf shrub species, Empetrum hermaphroditum, Cassiope tetragona and Betula nana, and if increased nutrient availability modifies the responses to warming and shading.MethodsMeasurements of BVOCs were performed in situ in long-term field experiments in the Subarctic using a dynamic enclosure system and collection of BVOCs into adsorbent cartridges analysed by gas chromatography–mass spectrometry. Leaf anatomy was studied using light microscopy and scanning electron microscopy.Key ResultsIncreased nutrient availability increased monoterpene emission rates and altered the emission profile of B. nana, and increased sesquiterpene and oxygenated monoterpene emissions of C. tetragona. Increased nutrient availability increased leaf tissue thicknesses of B. nana and C. tetragona, while it caused thinner epidermis and the highest fraction of functional (intact) glandular trichomes for E. hermaphroditum. Increased nutrient availability and warming synergistically increased mesophyll intercellular space of B. nana and glandular trichome density of C. tetragona, while treatments combining increased nutrient availability and shading had an opposite effect in C. tetragona.ConclusionsIncreased nutrient availability may enhance the protection capacity against biotic and abiotic stresses (especially heat and drought) in subarctic shrubs under future warming conditions as opposed to increased cloudiness, which could lead to decreased resistance. The study emphasizes the importance of changes in nutrient availability in the Subarctic, which can interact with climate warming and increased cloudiness effects.     

长期N添加对典型草原几个物种叶片性状的影响

通过一个连续4 a(2003—2006年)N添加的野外控制试验(0、1、2、4、8、16、32、64 g/m2等8个水平),探讨了N供给改变对内蒙古典型草原几个常见物种叶片性状的影响。结果表明,沿施N水平,冷蒿(Artemisia frigida)、星毛委陵菜(Potentillaacaulis)和砂韭(Allium bidentatum)比叶面积(SLA)呈指数增加,而克氏针茅(Stipa krylovii)和糙隐子草(Cleistogenes squarrosa)SLA无明显变化规律;5个物种绿叶N浓度和枯叶N浓度均呈增加趋势,而绿叶P浓度和枯叶P浓度的变化趋势呈明显的物种差异性。物种间,冷蒿具有较高的SLA和叶片养分浓度,克氏针茅具有较低的SLA和叶片养分浓度。以上结果表明,N供给增加降低了植物保持N的能力,对植物P保持能力的影响随物种不同而异,反映了植物P策略对N供给改变的弹性适应。因此,大气N沉降增加改变着植物N和P利用策略,进而影响着植被-土壤系统N和P循环,而其物种差异性将对群落结构产生深远影响。     

The effect of relative humidity on photoresponse in sympatric species of Drosophila: Long-term exposure to desiccating environments

The photoresponse of isofemale strains of the sympatric species Drosophila immigrans and Drosophila tripunctata were compared at relative humidities of 95, 50 and 5% during an 8-h period. The onset of a change in photobehaviour due to the stress of desiccation was calculated for each strain for the three relative humidities. The two species could be distinguished on the basis of their light responses under the three desiccating conditions. With increased desiccation there was an increased positive response to light after the behavioural shift. The effect was greater and more uniform in D. tripunctata, which is a fungus feeder, than in D. immigrans, possibly because D. tripunctata occupies a narrower niche than D. immigran. The species were observed to have higher activity levels as they desiccated. It is postulated that the increased positive light responses with increased relative humidity are attributable to both desiccation and starvation. The time of onset of the shift in photobehaviour is dependent on the relative humidity.     

Maternal dietary omega-3 fatty acid intake increases resolvin and protectin levels in the rat placenta

Placental inflammation is associated with several pregnancy disorders. Inflammation is limited by anti-inflammatory and proresolving mechanisms, the latter partly mediated by resolvins and protectins derived from omega-3 polyunsaturated fatty acids (n-3PUFA). We examined effects of dietary n-3PUFAs on levels of resolvins, protectins, and lipoxygenase (ALOX) enzymes in the rat placenta. Rats consumed standard (Std) or high n-3PUFA (Hn3) diets from day 1 of pregnancy; tissues were collected on day 17 or 22 (term = day 23). Maternal Hn3 diet increased resolvin and protectin precursors, 18R/S-HEPE (P < 0.001), and 17R/S-HDHA (P < 0.01) at both days. Resolvins (17R-RvD1 and RvD1) increased at day 22 (P < 0.001) after Hn3 consumption, coincident with higher Alox15b and Alox5 mRNA expression, while RvD2 increased at both days (P < 0.05). Protectins, PD1, and 10S,17S-DiHDHA increased over late gestation (P < 0.001), coincident with higher Alox15 mRNA expression (P < 0.001) and further increased with Hn3 diet (P < 0.05). Maternal systemic and placental proinflammatory mediators were not suppressed by Hn3 diet; systemic IL1β, placental Il1β, and Il6 mRNA expression increased marginally with Hn3 at day 22 (P < 0.001), while Ptgs1 (Cox1) expression increased both days (P < 0.05). Our data indicate that maternal n-3PUFA supplementation enhances expression of enzymes in the n-3PUFA metabolic pathway and increases placental levels of resolvins and protectins.     

Melanoma cell-derived factors stimulate hyaluronan synthesis in dermal fibroblasts by upregulating HAS2 through PDGFR-PI3K-AKT and p38 signaling

In many cancers hyaluronan content is increased, either by tumor cells or the surrounding stromal cells and this increased hyaluronan content correlates with unfavorable clinical prognosis. In the present work, we studied the effects of melanoma cell (aggressive melanoma cell line C8161)-derived factors on fibroblast hyaluronan synthesis, intracellular signaling, MMP expression and invasion. Treatment of the fibroblast cultures with melanoma cell conditioned medium (CM) caused accumulation of hyaluronan in the culture medium and formation of thick pericellular hyaluronan coat and hyaluronan cables. The expression of Has2 was increased approximately 20-fold by the C8161 melanoma cell CM, while Has1 and Has3 were increased twofold. Knock-down of Has2 expression with siRNA showed that Has2 was responsible for the increased hyaluronan synthesis induced by the melanoma cell CM. To find out the signaling routes, which led to Has2 upregulation, the phosphorylation profiles of 46 kinases were screened with phosphokinase array kit. Melanoma cell CM treatment strongly induced a rapid phosphorylation of p38, JNK, AKT, CREB, HSP27, STAT3 and cJUN. Treatment of the fibroblasts with specific inhibitors of PI3K, AKT and p38 reduced the melanoma cell CM-induced hyaluronan secretion, while the inhibitor of PDGFR totally blocked it. In addition, siRNA for PDGFRα/β inhibited Has2 upregulation in melanoma cell CM-treated fibroblasts. In parallel with the increased hyaluronan synthesis the melanoma cell CM-treated fibroblasts showed spindle shape, numerous long cell protrusions, enhanced MMP expression and increased invasion into collagen-Cultrex matrix. siRNA blocking of Has2 or PDGFRα/β expression reversed the stimulatory effect of melanoma cell CM on fibroblast invasion. PDGF secreted by melanoma cells thus mediated fibroblasts activation, with HAS2 upregulation as a major factor in the fibroblast response. This effect on stromal matrix is suggested to favor tumor growth.