Effect of pneumococcal conjugate vaccination on serotype-specific carriage and invasive disease in England: a cross-sectional study

Background

We investigated the effect of the 7-valent pneumococcal conjugate vaccine (PCV7) programme in England on serotype-specific carriage and invasive disease to help understand its role in serotype replacement and predict the impact of higher valency vaccines.

Methods and Findings

Nasopharyngeal swabs were taken from children <5 y old and family members (n = 400) 2 y after introduction of PCV7 into routine immunization programs. Proportions carrying Streptococcus pneumoniae and serotype distribution among carried isolates were compared with a similar population prior to PCV7 introduction. Serotype-specific case∶carrier ratios (CCRs) were estimated using national data on invasive disease. In vaccinated children and their contacts vaccine-type (VT) carriage decreased, but was offset by an increase in non-VT carriage, with no significant overall change in carriage prevalence, odds ratio 1.06 (95% confidence interval 0.76–1.49). The lower CCRs of the replacing serotypes resulted in a net reduction in invasive disease in children. The additional serotypes covered by higher valency vaccines had low carriage but high disease prevalence. Serotype 11C emerged as predominant in carriage but caused no invasive disease whereas 8, 12F, and 22F emerged in disease but had very low carriage prevalence.

Conclusion

Because the additional serotypes included in PCV10/13 have high CCRs but low carriage prevalence, vaccinating against them is likely to significantly reduce invasive disease with less risk of serotype replacement. However, a few serotypes with high CCRs could mitigate the benefits of higher valency vaccines. Assessment of the effect of PCV on carriage as well as invasive disease should be part of enhanced surveillance activities for PCVs. Please see later in the article for the Editors'' Summary     

Evaluation of coseasonality of influenza and invasive pneumococcal disease: results from prospective surveillance

Background

The wintertime co-occurrence of peaks in influenza and invasive pneumococcal disease (IPD) is well documented, but how and whether wintertime peaks caused by these two pathogens are causally related is still uncertain. We aimed to investigate the relationship between influenza infection and IPD in Ontario, Canada, using several complementary methodological tools.

Methods and Findings

We evaluated a total number of 38,501 positive influenza tests in Central Ontario and 6,191 episodes of IPD in the Toronto/Peel area, Ontario, Canada, between 1 January 1995 and 3 October 2009, reported through population-based surveillance. We assessed the relationship between the seasonal wave forms for influenza and IPD using fast Fourier transforms in order to examine the relationship between these two pathogens over yearly timescales. We also used three complementary statistical methods (time-series methods, negative binomial regression, and case-crossover methods) to evaluate the short-term effect of influenza dynamics on pneumococcal risk. Annual periodicity with wintertime peaks could be demonstrated for IPD, whereas periodicity for influenza was less regular. As for long-term effects, phase and amplitude terms of pneumococcal and influenza seasonal sine waves were not correlated and meta-analysis confirmed significant heterogeneity of influenza, but not pneumococcal phase terms. In contrast, influenza was shown to Granger-cause pneumococcal disease. A short-term association between IPD and influenza could be demonstrated for 1-week lags in both case-crossover (odds ratio [95% confidence interval] for one case of IPD per 100 influenza cases  = 1.10 [1.02–1.18]) and negative binomial regression analysis (incidence rate ratio [95% confidence interval] for one case of IPD per 100 influenza cases  = 1.09 [1.05–1.14]).

Conclusions

Our data support the hypothesis that influenza influences bacterial disease incidence by enhancing short-term risk of invasion in colonized individuals. The absence of correlation between seasonal waveforms, on the other hand, suggests that bacterial disease transmission is affected to a lesser extent. Please see later in the article for the Editors'' Summary     

Impact of capsular switch on invasive pneumococcal disease incidence in a vaccinated population

Background

Despite the dramatic decline in the incidence of invasive pneumococcal disease (IPD) observed since the introduction of conjugate vaccination, it is feared that several factors may undermine the future effectiveness of the vaccines. In particular, pathogenic pneumococci may switch their capsular types and evade vaccine-conferred immunity.

Methodology/Principal Findings

Here, we first review the literature and summarize the available epidemiological data on capsular switch for S. pneumoniae. We estimate the weekly probability that a persistently carried strain may switch its capsule from four studies, totalling 516 children and 6 years of follow-up, at 1.5×10⁻³/week [4.6×10⁻⁵–4.8×10⁻³/week]. There is not enough power to assess an increase in this frequency in vaccinated individuals. Then, we use a mathematical model of pneumococcal transmission to quantify the impact of capsular switch on the incidence of IPD in a vaccinated population. In this model, we investigate a wide range of values for the frequency of vaccine-selected capsular switch. Predictions show that, with vaccine-independent switching only, IPD incidence in children should be down by 48% 5 years after the introduction of the vaccine with high coverage. Introducing vaccine-selected capsular switch at a frequency up to 0.01/week shows little effect on this decrease; yearly, at most 3 excess cases of IPD per 10⁶ children might occur due to switched pneumococcal strains.

Conclusions

Based on all available data and model predictions, the existence of capsular switch by itself should not impact significantly the efficacy of pneumococcal conjugate vaccination on IPD incidence. This optimistic result should be tempered by the fact that the selective pressure induced by the vaccine is currently increasing along with vaccine coverage worldwide; continued surveillance of pneumococcal populations remains of the utmost importance, in particular during clinical trials of the new conjugate vaccines.     

6A型肺炎球菌结合物分子大小对小鼠免疫原性的影响

目的 比较不同分子大小的6A型肺炎球菌(serotype 6A Streptococcus Pneumoniae )结合物和佐剂吸附在小鼠体内免疫原性的影响。方法 通过乙酸水解降低6A型荚膜多糖的相对分子质量制备成水解物,水解物经1-氰基-4-二甲胺基吡啶四氟硼酸盐(CDAP)活化并与破伤风类毒素己二酸酰肼衍生物TT AH 结合,制备成结合物。用Sepharose 4 Fast Flow 纯化结合物,并根据化学检测结果将结合物分为 K D 0.0~0.2、 K D 0.2~0.4、 K D 0.4~0.6等3个组分,每个组分分别以磷酸铝佐剂吸附,将吸附前后的各个组分按照每针次每只小鼠0.2 μg分别免疫小鼠,并采用ELISA检测结合物在小鼠体内的抗体水平。结果 3种不同相对分子质量吸附前后的结合物在小鼠体内均能产生较高水平的抗体,各组2、3针之间具有明显的加强效应。在吸附组和未吸附组中,3种不同分子大小的结合物在小鼠体内产生抗体水平无明显差异。各组分佐剂吸附后的结合物血清抗体滴度高于未吸附组,但这种差异无统计学意义( P > 0.05)。结论 结合物的分子大小对小鼠体内抗体水平的产生没有明显影响;磷酸铝佐剂吸附对于不同分子大小的结合物在小鼠体内的免疫原性有一定的增强效应,但这种增强效应差异无统计学意义。     

Cellular pathophysiology of cystic kidney disease: insight into future therapies.

Polycystic kidney disease (PKD) is a developmental kidney disorder which can be inherited as either an autosomal dominant trait, with an incidence of 1:50 to 1:1000, or as an autosomal recessive trait with an incidence of 1:6,000 to 1:40,000. Three different genes have now been cloned that are associated with mutations that cause PKD. Two of these are linked to the most common forms of the dominant disease while the third is associated with the orpk mouse model of recessive polycystic kidney disease. Advances in understanding the molecular genetics of PKD have been paralleled by new insights into the cellular pathophysiology of cyst formation and progressive enlargement. Current data suggest that a number of PKD proteins may interact in a complex, which when disrupted by mutations in PKD genes may lead to altered epithelial proliferative activity, secretion, and cell matrix biology. The identification of a unique cystic epithelial phenotype presents new opportunities for targeted therapies. These include targeted gene therapy, gene complementation, and specific immunological or pharmacological interruption of growth factor pathways.     

Carotenoids and Alzheimer's disease: an insight into therapeutic role of retinoids in animal models

Carotenoids play a pivotal role in prevention of many degenerative diseases mediated by oxidative stress including neurodegenerative diseases like Alzheimer’s Disease (AD). The involvement of retinoids in physiology, AD pathology and their therapeutic role in vitro and in vivo has been extensively studied. This review focuses on the role of carotenoids like retinoic acid (RA), all trans retinoic acid (ATRA), lycopene and β-carotene in prevention of AD symptoms primarily through inhibition of amyloid beta (Aβ) formation, deposition and fibril formation either by reducing the levels of p35 or inhibiting corresponding enzymes. The role of antioxidant micronutrients in prevention or delaying of AD symptoms has been included. This study emphasizes the dietary supplementation of carotenoids to combat AD and warrants further studies on animal models to unravel their mechanism of neuroprotection.     

Studying synthetic lethal interactions in the zebrafish system: insight into disease genes and mechanisms

The post-genomic era is marked by a pressing need to functionally characterize genes through understanding gene-gene interactions, as well as interactions between biological pathways. Exploiting a phenomenon known as synthetic lethality, in which simultaneous loss of two interacting genes leads to loss of viability, aids in the investigation of these interactions. Although synthetic lethal screening is a powerful technique that has been used with great success in many model organisms, including Saccharomyces cerevisiae, Drosophila melanogaster and Caenorhabditis elegans, this approach has not yet been applied in the zebrafish, Danio rerio. Recently, the zebrafish has emerged as a valuable system to model many human disease conditions; thus, the ability to conduct synthetic lethal screening using zebrafish should help to uncover many unknown disease-gene interactions. In this article, we discuss the concept of synthetic lethality and provide examples of its use in other model systems. We further discuss experimental approaches by which the concept of synthetic lethality can be applied to the zebrafish to understand the functions of specific genes.     

Colon tumor mutations and epigenetic changes associated with genetic polymorphism: insight into disease pathways

Variation in genes associated with serum levels of proteins may be useful for examining specific disease pathways. Using data from a large study of colon cancer, we examine genetic variants in insulin, inflammation, estrogen, metabolizing enzymes, and energy homeostasis genes to explore associations with microsatellite instability (MSI), CpG Island methylator phenotype (CIMP), mutations of p53 in exons 5 through 8, and mutations in codons 12 and 13 of Ki-ras. Insulin-related genes were associated with CIMP-positive and MSI tumors, with the strongest associations among aspirin users. The Fok1 vitamin D receptor (VDR) polymorphism was associated with CIMP-positive/Ki-ras-mutated tumors; the Poly A and CDX2 VDR polymorphisms were associated only with Ki-ras-mutated tumors. NAT2 was associated with CIMP-positive/Ki-ras-mutated tumors but not with MSI tumors. The TCF7L2 rs7903146 polymorphism was associated with p53 mutated tumors. Most associations varied by recent aspirin/NSAID use: IL6 rs1800796 and rs1800795 polymorphisms were associated inversely with tumor mutations in the presence of aspirin/NSAIDs; POMC significantly reduced risk of Ki-ras-mutated tumors when aspirin/NSAIDs were not used; the TCF7L2 rs7903146 was associated with reduced risk of Ki-ras-mutated tumors in the presence of aspirin and increased risk in the absence of aspirin. These data, although exploratory, identify specific tumor subsets that may be associated with specific exposures/polymorphism combinations. The important modifying effects of aspirin/NSAIDs on associations with genetic polymorphisms reinforce the underlying role of inflammation in the etiology of colon cancer.     

Expression of Shigella dysenteriae serotype 1 O-antigenic polysaccharide by Shigella flexneri aroD vaccine candidates and different S. flexneri serotypes.

The potential utility of Shigella flexneri aroD vaccine candidates for the development of bi- or multivalent vaccines has been explored by the introduction of the genetic determinants rfp and rfb for heterologous O antigen polysaccharide from Shigella dysenteriae serotype 1. The serotype Y vaccine strain SFL124 expressed the heterologous antigen qualitatively and quantitatively well, qualitatively in the sense of the O antigen polysaccharide being correctly linked to the S. flexneri lipopolysaccharide R3 core oligosaccharide and quantitatively in the sense that typical yields were obtained, with ratios of homologous to heterologous O antigen being 4:1 for one construct and 1:1 for another. Moreover, both polysaccharide chains were shown to be linked to position O-4 of the subterminal D-glucose residue of the R3 core. In contrast to the hybrid serotype Y SFL124 derivatives, analogous derivatives of serotype 2a vaccine strain SFL1070 did not elaborate a complete heterologous O antigen. Such derivatives, and analogous derivatives of rough, O antigen-negative mutants of SFL1070, formed instead a hybrid lipopolysaccharide molecule consisting of the S. flexneri lipid A R3 core with a single repeat unit of the S. dysenteriae type 1 O antigen. Introduction of the determinants for the S. dysenteriae type 1 O antigen into a second serotype 2a strain and into strains representing other serotypes of S. flexneri, revealed the following for the expression of the heterologous O antigen: serotypes 1a, 1b, 2a, and 5a did not produce the heterologous O antigen, whereas serotypes 2b, 3a, 3b, 4a, 4b, 5b, and X did.     

One-carbon metabolism and Alzheimer's disease: focus on epigenetics

Alzheimer's disease (AD) represents the most common form of dementia in the elderly, characterized by progressive loss of memory and cognitive capacity severe enough to interfere with daily functioning and the quality of life. Rare, fully penetrant mutations in three genes (APP, PSEN1 and PSEN2) are responsible for familial forms of the disease. However, more than 90% of AD is sporadic, likely resulting from complex interactions between genetic and environmental factors. Increasing evidence supports a role for epigenetic modifications in AD pathogenesis. Folate metabolism, also known as one-carbon metabolism, is required for the production of S-adenosylmethionine (SAM), which is the major DNA methylating agent. AD individuals are characterized by decreased plasma folate values, as well as increased plasma homocysteine (Hcy) levels, and there is indication of impaired SAM levels in AD brains. Polymorphisms of genes participating in one-carbon metabolism have been associated with AD risk and/or with increased Hcy levels in AD individuals. Studies in rodents suggest that early life exposure to neurotoxicants or dietary restriction of folate and other B vitamins result in epigenetic modifications of AD related genes in the animal brains. Similarly, studies performed on human neuronal cell cultures revealed that folate and other B vitamins deprivation from the media resulted in epigenetic modification of the PSEN1 gene. There is also evidence of epigenetic modifications in the DNA extracted from blood and brains of AD subjects. Here I review one-carbon metabolism in AD, with emphasis on possible epigenetic consequences.     

New insight into lysosomal protein storage disease: Delayed catabolism of ATP synthase subunit c in batten disease

Subunit c is normally present as an inner mitochondrial membrane component of the Fo sector of the ATP synthase complex, but in the late infantile form of neuronal ceroid lipofuscinosis (NCL) it was also found in lysosomes in high concentrations. Mechanism for specific accumulation of subunit c in lysosomes is not known. The rate of degradation of subunit c as measured by pulsechase and immunoprecipitation showed a marked delay of degradation in patients fibroblasts with late infantile form of NCL. There were no significant differences between control cells and cells with disease in the degradation of cytochrome oxidase subunit IV, an inner membrane protein of mitochondria. Measurement of labeled subunit c in mitochondrial and lysosomal fractions showed that the accumulation of labeled subunit c in the mitochondrial fraction can be detected before lysosomal appearance of radioactive subunit c, suggesting that subunit c accumulated as a consequence of abnormal catabolism in the mitochondrion and is transferred to lysosomes, through an autophagic process. There were no large differences of various lysosomal protease activities between control and patient cells. In patient cells sucrose loading caused a marked shift of lysosomal density, but did not a shift of subunit c containing storage body. The biosynthetic rate of subunit c and mRNA levels for P1 and P2 genes that code for it were almost the same in both control and patient cells. These findings suggest that a specific failure in the degradation of subunit c after its normal inclusion in mitochondria and its consequent accumulation in lysosomes.Special issue dedicated to Dr. Leon S. Wolfe.     

Dissecting the genetics of complex inheritance: linkage disequilibrium mapping provides insight into Crohn disease

Family studies for Crohn disease (CD) report extensive linkage on chromosome 16q and pinpoint NOD2 as a possible causative locus. However, linkage is also observed in families that do not bear the most frequent NOD2 causative mutations, but no other signals on 16q have been found so far in published genome-wide association studies. Our aim is to identify this missing genetic contribution. We apply a powerful genetic mapping approach to the Wellcome Trust Case-Control Consortium and the National Institute of Diabetes and Digestive and Kidney Diseases genome-wide association data on CD. This method takes into account the underlying structure of linkage disequilibrium (LD) by using genetic distances from LD maps and provides a location for the causal agent. We find genetic heterogeneity within the NOD2 locus and also show an independent and unsuspected involvement of the neighboring gene, CYLD. We find associations with the IRF8 region and the region containing CDH1 and CDH3, as well as substantial phenotypic and genetic heterogeneity for CD itself. The genes are known to be involved in inflammation and immune dysregulation. These findings provide insight into the genetics of CD and suggest promising directions for understanding disease heterogeneity. The application of this method thus paves the way for understanding complex inheritance in general, leading to the dissection of different pathways and ultimately, personalized treatment.     

Behaviourally and genetically distinct populations of an invasive ant provide insight into invasion history and impacts on a tropical ant community

Populations of invasive species often exhibit a high degree of spatial and temporal variability in abundance and hence their effects on resident communities. Here, we examine behavioural, genetic and environmental factors that influence variation in populations of the yellow crazy ant, Anoplolepis gracilipes, on the remote Nukunonu Atoll of Tokelau, Pacific Ocean. Behavioural assays revealed high levels of aggression between two groups of yellow crazy ants from different islands, and genetic analysis confirmed the presence of two distinct populations with unique mitochondrial (mt)DNA haplotypes, designated A and D. The two populations likely resulted from two separate invasion events. The populations exhibited significant differences in abundance of A. gracilipes, with a mean sevenfold difference in relative abundance between the two main haplotypes. The higher density haplotype D population coexisted with 50% fewer other ant species and altered ant community composition. Vegetation composition was also significantly different on islands harbouring the two populations. The results suggest genetic differences could play a role in the spatial and temporal variation in the effect of the yellow crazy ant on a small oceanic atoll. We could not differentiate between genetic effects and effects of vegetation. However, our results indicate that spatial variability in behaviour and impacts within populations of invasive species could be in part due to genetic differences, and play a substantial role in influencing the outcome of biological invasions.     

Serum proteome analysis of vivax malaria: An insight into the disease pathogenesis and host immune response

Vivax malaria is the most widely distributed human malaria resulting in 80-300 million clinical cases every year. It causes severe infection and mortality but is generally regarded as a benign disease and has not been investigated in detail. The present study aimed to perform human serum proteome analysis in a malaria endemic area in India to identify potential serum biomarkers for vivax malaria and understand host response. The proteomic analysis was performed on 16 age and gender matched subjects (vivax patients and control) in duplicate. Protein extraction protocols were optimized for large coverage of the serum proteome and to obtain high-resolution data. Identification of 67 differentially expressed and statistically significant (Student's t-test; p<0.05) protein spots was established by MALDI-TOF/TOF mass spectrometry. Many of the identified proteins such as apolipoprotein A and E, serum amyloid A and P, haptoglobin, ceruloplasmin, and hemopexin are interesting from a diagnostic point of view and could further be studied as potential serum biomarkers. The differentially expressed serum proteins in vivax malaria identified in this study were subjected to functional pathway analysis using multiple software, including Ingenuity Pathway Analysis (IPA), Protein ANalysis THrough Evolutionary Relationships (PANTHER) and Database for Annotation, Visualization and Integrated Discovery (DAVID) functional annotation tool for better understanding of the biological context of the identified proteins, their involvement in various physiological pathways and association with disease pathogenesis. Functional pathway analysis of the differentially expressed proteins suggested the modulation of multiple vital physiological pathways, including acute phase response signaling, complement and coagulation cascades, hemostasis and vitamin D metabolism pathway due to this parasitic infection. This article is part of a Special Issue entitled: Proteomics: The clinical link.     

Proteomics and personalized medicine: a focus on kidney disease

ABSTRACT

Introduction: Inter-individual variability in response to drug treatment has induced an increased demand for decisions via personalize medicine. Also, the contribution of proteomics to the era of personalized medicine would seem to be vital in improving therapeutic outcomes.

Areas covered: We review validated biomarkers discovered by proteomics techniques and their use in personalized medicine with the focus on kidney diseases. We discuss this topic with a special emphasis on recent publications and relevant initiatives and depict some limitations that remain for personalized medicine.

Expert opinion: The development of highly accurate biomarkers is essential for optimizing the management of kidney diseases. Various biomarkers of kidney diseases have been identified using proteomic techniques. However, only a few of these biomarkers showed the potential to be used in clinical practice concerning personalized medicine. Therefore, it becomes evident that the combination of multiple biomarkers confers higher accuracy and the ability to depict complex pathophysiological conditions, a prerequisite for personalized treatment. CKD273, a multimarker panel for early CKD detection may serve as a first example for personalized medicine in nephrology. Based on this successful example, proteomics is expected to develop into the key technology to guide personalized intervention.     

Effect of trehalose on W7FW14F apomyoglobin and insulin fibrillization: new insight into inhibition activity

Trehalose, a disaccharide present in many nonmammalian species, protects cells against various environmental stresses. Trehalose has recently been shown to decrease aggregate formation and toxicity in cell models and to alleviate amyloid-induced diseases. The aim of our study was to use two amyloid-forming proteins, i.e., W7FW14F apomyoglobin and insulin, as model systems to elucidate the molecular mechanism by which trehalose affects the amyloid aggregation process and to investigate further its therapeutic potential. Protein aggregation was examined by far-UV circular dichroism, UV absorption, thioflavin T fluorescence, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, atomic force microscopy, and Fourier transform infrared spectroscopy. Cell viability was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. We found that trehalose does not inhibit protein aggregation but acts at different stages of the fibrillization process depending on the protein model used. In fact, trehalose dose-dependently inhibited fibril formation in the W7FW14F apomyoglobin model and increased the lag phase in the insulin model. In both cases, trehalose caused accumulation of toxic oligomeric species. The results suggest that trehalose may favor or inhibit the formation of "on-pathway" or "off-pathway" oligomeric intermediates depending on the nature of the aggregating protein.     

Copper dysfunction in Alzheimer's disease: from meta-analysis of biochemical studies to new insight into genetics

The involvement of body copper metabolism in the development of Alzheimer's disease (AD) - the most common form of dementia - is a deeply investigated issue in recent years. Copper is essential for life, but in excess it can be toxic. Recently, it has been hypothesized that copper toxicity may be a contributory factor in the etiology of the neurodegenerative disease AD. Studies on copper evaluation in AD vs. healthy controls collected in the latest 30 years and merged in a meta-analysis demonstrate that serum copper is slightly increased in AD. A specific form of copper, the copper non-bound to ceruloplasmin, or 'free' copper, seems to best characterize this increase in copper in AD patients. Clinical studies from us and other groups have demonstrated that free copper is associated with the typical deficits of AD, incipient AD and mild cognitive impairment, and specific cerebrospinal markers. Moreover, very recent data addressing molecular processes underlying copper dysfunction in AD have indicated that genetic variations of K832R and R952K Single Nucleotide Polymorphisms (SNPs) of the Wilson's disease gene ATP7B are associated also with sporadic AD. Specifically, ATP7B encodes for the protein ATPase 7B which controls free copper status in the body, and both R allele in K832R and K allele in R952K ATP7B SNPs are associated with an increased risk of having AD. Even though copper dysfunction cannot be assumed as a determinant of the disease, its causative, rather than associated, role in AD pathology as risk factor can be claimed.     

Effects of an invasive forest pathogen on abundance of ticks and their vertebrate hosts in a California Lyme disease focus

Invasive species, including pathogens, can have important effects on local ecosystems, including indirect consequences on native species. This study focuses on the effects of an invasive plant pathogen on a vertebrate community and Ixodes pacificus, the vector of the Lyme disease pathogen (Borrelia burgdorferi) in California. Phytophthora ramorum, the causative agent of sudden oak death, is a non-native pathogen killing trees in California and Oregon. We conducted a multi-year study using a gradient of SOD-caused disturbance to assess the impact on the dusky-footed woodrat (Neotoma fuscipes) and the deer mouse (Peromyscus maniculatus), two reservoir hosts of B. burgdorferi, as well as the impact on the Columbian black-tailed deer (Odocoileus hemionus columbianus) and the western fence lizard (Sceloporus occidentalis), both of which are important hosts for I. pacificus but are not pathogen reservoirs. Abundances of P. maniculatus and S. occidentalis were positively correlated with greater SOD disturbance, whereas N. fuscipes abundance was negatively correlated. We did not find a change in space use by O. hemionus. Our data show that SOD has a positive impact on the density of nymphal ticks, which is expected to increase the risk of human exposure to Lyme disease all else being equal. A positive correlation between SOD disturbance and the density of nymphal ticks was expected given increased abundances of two important hosts: deer mice and western fence lizards. However, further research is needed to integrate the direct effects of SOD on ticks, for example via altered abiotic conditions with host-mediated indirect effects.     

Effect of serum on the plasma membrane fluidity of hybridomas: an insight into its shear protective mechanism.

We have previously shown that decreasing the concentration of fetal bovine serum (FBS) increased the fragility of a mouse hybridoma (HB-32) during agitated batch cultivation and that increasing the plasma membrane fluidity (PMF) increased the shear sensitivity during exposure to laminar flow. In this study, the effect of FBS concentration on the PMF of HB-32 was investigated. PMF was evaluated by steady-state fluorescence anisotropy (rs) of 1-[4-(trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene. Increasing serum concentration increased the rs of hybridomas, indicating a decrease in their PMF. The effect of cholesterol modulation on the PMF and shear sensitivity was also evaluated. Hybridomas were exposed to turbulent fluid shear after modification of PMF by cholesterol modulation. Direct cholesterol enrichment of the plasma membranes caused a decrease in the PMF and shear sensitivity, while cholesterol depletion caused an increase in PMF and shear sensitivity. Low- and high-density lipoprotein supplementation to cultures in serum-free or complete medium decreased their shear sensitivity. Lipoprotein supplementation to serum-free cultures decreased the PMF. Altogether, these results suggest that the protective mechanism of serum against hydrodynamic damage relies, at least partially, on its ability to decrease the PMF of hybridomas possibly through the transfer of cholesterol from the serum lipoproteins into the plasma membrane.