Surrogate markers of protective immunity to malaria in humans are needed to rationalize malaria vaccine discovery and development. In an effort to identify such markers, and thereby provide a clue to ...the complex equation malaria vaccine development is facing, we investigated the relationship between protection acquired through exposure in the field with naturally occurring immune responses (i.e., induced by the parasite) to molecules that are considered as valuable vaccine candidates.
We analyzed, under comparative conditions, the antibody responses of each of six isotypes to five leading malaria vaccine candidates in relation to protection acquired by exposure to natural challenges in 217 of the 247 inhabitants of the African village of Dielmo, Senegal (96 children and 121 older adolescents and adults). The status of susceptibility or resistance to malaria was determined by active case detection performed daily by medical doctors over 6 y from a unique follow-up study of this village. Of the 30 immune responses measured, only one, antibodies of the IgG3 isotype directed to merozoite surface protein 3 (MSP3), was strongly associated with clinical protection against malaria in all age groups, i.e., independently of age. This immunological parameter had a higher statistical significance than the sickle cell trait, the strongest factor of protection known against Plasmodium falciparum. A single determination of antibody was significantly associated with the clinical outcome over six consecutive years in children submitted to massive natural parasite challenges by mosquitoes (over three parasite inoculations per week). Finally, the target epitopes of these antibodies were found to be fully conserved.
Since anti-MSP3 IgG3 antibodies can naturally develop along with protection against P. falciparum infection in young children, our results provide the encouraging indication that these antibodies should be possible to elicit by vaccination early in life. Since these antibodies have been found to achieve parasite killing under in vitro and in vivo conditions, and since they can be readily elicited by immunisation in naïve volunteers, our immunoepidemiological findings support the further development of MSP3-based vaccine formulations.
We present a simple method to estimate the isoelectric point (pI) of Tomato Bushy Stunt particles. We demonstrate that the combination of agarose gels with different pH buffers can be used to ...electrophorese the virus particles and their migration patterns can be compared. This method allows us to estimate the pI of the virus particles (wild type, wt, and genetically modified particles) and to monitor the effect of the pI of modified peptide side chains of the viral capsid subunit on the pI of the whole virus particle.
Parasitoids are an important mortality factor for insects. Susceptibility to parasitoids should thus be under strong negative selection. Nevertheless, ample genetic variation for susceptibility to ...parasitoids is commonly observed in natural populations, suggesting that trade-offs may constrain the evolution of reduced susceptibility. This can be studied by assessing genetic variation for susceptibility and its covariation with other components of fitness. In a set of 17 clones of the peach potato aphid, Myzus persicae, for which good estimates of heritable variation for life-history traits were available, we found significant clonal variation for susceptibility to two of their common parasitoids: Aphidius colemani and Diaeretiella rapae. One clone, the only one harbouring a facultative endosymbiotic bacterium, Regiella insecticola, was entirely resistant to both parasitoids. Susceptibilities to the two parasitoids exhibited a positive genetic correlation close to unity, implying a general mechanism of defence. However, the susceptibility to parasitoids was uncorrelated to the clones' fecundity or rate of increase, providing no evidence for costs of the ability to resist parasitoids.
Background
Anastomotic leakage (AL) is a severe complication following colorectal surgery. C-reactive protein (CRP) is considered to be an indicator of postoperative complications.
Materials and ...methods
Between August 2002 and August 2005 342 colorectal resections with primary anastomosis were performed at the Department of General and Vascular Surgery. Johann Wolfgang Goethe-University Frankfurt. For this retrospective study serum CRP was measured daily until postoperative day 7, and in cases of AL it was excluded from statistical analysis beginning with the day on which the AL was diagnosed.
Results
Twenty-six of 342 (7.6%) patients developed AL at a mean of 8.7 days postoperatively. The in-hospital mortality was 3.5% for all patients and was significantly higher in the AL group (11.5 versus 2.8%). The CRP level in the two groups showed a peak on day 2.5 and day 2.2, respectively. In case of postoperative AL the CRP level did not show a marked decline during the next few days. Compared to the cases where AL did not develop, there was a significantly higher increase in CRP from the preoperative level to the levels measured on postoperative day 3, 5, 6 and 7. Higher CRP levels were observed in patients experiencing pneumonia or urinary tract infection, but the decrease of CRP values was not as slow as in cases of AL.
Conclusions
This study shows serum CRP level to be a relevant marker in detecting postoperative complications in colorectal surgery. Prolonged elevation and a missing decline in CRP level precede the occurrence of AL.
► C57BL/6 (B6) mice are commonly considered insensitive to convulsants. ► However, B6 substrains and sublines markedly differ in sensitivity to pilocarpine. ► B6J (JAX) mice have the lowest ...sensitivity, while a subline of B6NCrl is very sensitive. ► Further breeding of these B6NCrl mice results in a highly sensitive F3 generation. ► We have started to use these mice for identifying genetic determinants of seizure susceptibility.
C57BL/6 (B6) is the most widely used inbred mouse strain, but its use in epilepsy research is compromised by low sensitivity to various convulsants, including pilocarpine. We recently identified a subline of B6NCrl mice in a barrier (#8) of a German vendor (Charles River) that was much more sensitive to status epilepticus (SE) induction than B6NCrl mice from four other barriers of the same vendor and other B6 substrains. Breeding experiments indicated that the observed differences have a genetic basis, thus offering a unique opportunity to identify the genes and pathways involved and contributing to a better understanding of the underlying molecular mechanisms of seizure susceptibility. Since the pilocarpine-sensitive B6 subline (B6NCrl#8) is not further available from the breeder, we decided to generate a new highly pilocarpine-sensitive B6NCrl subline by crossing female B6NCrl#8 mice with male F1 hybrids. Further sister–brother mating of the resulting F2 generation generated a highly susceptible F3 generation. Similar to B6NCrl#8 mice, mice from the F3 generation were significantly more susceptible to SE induction than any other B6 substrain, including B6J (JAX) mice, which were particularly insensitive to seizure induction. In contrast to the marked inter-subline differences in susceptibility to induction of SE, B6 sublines did not differ in the long-term consequences of SE, i.e., development of spontaneous seizures and neurodegeneration in the hippocampus, although hippocampal damage was much less severe than previously reported for other mouse strains. We have started to search for genetic loci underlying the high seizure susceptibility of B6NCrl#8 and filial generations obtained by cross-breeding with this B6 subline. Further characterization of the genetic variations underlying high susceptibility to convulsants such as pilocarpine will facilitate our understanding of the pathomechanisms involved in the evolution of single seizures to a self-sustained SE and provide new opportunities for interventions.
Bacterial cell appendix formation supports cell‐cell interaction, cell adhesion and cell movement. Additionally, in bioelectrochemical systems (BES), cell appendages have been shown to participate in ...extracellular electron transfer. In this work, the cell appendix formation of Clostridium acetobutylicum in biofilms of a BES are imaged and compared with conventional biofilms. Under all observed conditions, the cells possess filamentous appendages with a higher number and density in the BES. Differences in the amount of extracellular polymeric substance in the biofilms of the electrodes lead to the conclusion that the cathode can be used as electron donor and the anode as electron acceptor by C. acetobutylicum. When using conductive atomic force microscopy, a current response of about 15 nA is found for the cell appendages from the BES. This is the first report of conductivity for clostridial cell appendices and represents the basis for further studies on their role for biofilm formation and electron transfer.
Out of the cell: This study illustrates that Clostridium acetobutylicum forms cell appendages under all studied conditions with a denser network in biofilms of bioelectrochemical systems compared to conventional cultivations. A current response of about 15 nA of the cell appendices is measured with conductive atomic force microscopy. Moreover, an increased extracellular polymeric substance (EPS) formation in the biofilm of the cathode is observed compared to the anode, which encourages further studies about the electron transfer between C. acetobutylicum and electrodes acting as electron acceptors and donors.
The Janzen-Connell model states that plant-specific natural enemies may have a disproportionately large negative effect on progeny close to maternal trees. The majority of experimental and ...theoretical studies addressing the Janzen-Connell model have explored how it can explain existing patterns of species diversity in tropical mainland areas. Very few studies have investigated how the model's predictions apply to isolated oceanic islands, or to the conservation management of endangered plants. Here, we provide the first experimental investigation of the predictions of the Janzen-Connell model on an oceanic island, in a conservation context. In addition, we experimentally evaluate the use of ecological analogue animals to resurrect the functional component of extinct frugivores that could have dispersed seeds away from maternal trees.
In Mauritius, we investigated seed germination and seedling survival patterns of the critically endangered endemic plant Syzygium mamillatum (Myrtaceae) in relation to proximity to maternal trees. We found strong negative effects of proximity to maternal trees on growth and survival of seedlings. We successfully used giant Aldabran tortoises as ecological analogues for extinct Mauritian frugivores. Effects of gut-passage were negative at the seed germination stage, but seedlings from gut-passed seeds grew taller, had more leaves, and suffered less damage from natural enemies than any of the other seedlings.
We provide the first experimental evidence of a distance-dependent Janzen-Connell effect on an oceanic island. Our results potentially have serious implications for the conservation management of rare plant species on oceanic islands, which harbour a disproportionately large fraction of the world's endemic and endangered plants. Furthermore, in contrast to recent controversy about the use of non-indigenous extant megafauna for re-wilding projects in North America and elsewhere, we argue that Mauritius and other oceanic islands are ideal study systems in which to empirically explore the use of ecological analogue species in restoration ecology.
Bacterial nanocellulose (BNC) is a promising material for the use in medical implants. BNC does not induce unwanted reactions in vivo, is long term stable and possesses unique mechanical properties. ...However, to make the most of these features, BNC must be carefully processed. Details of the cultivation and post-synthetic methods offer various ways to control the properties of BNC. The focus of this work is put on drying of the BNC. Different unconstrained drying methods (climate chamber at 23°C, oven at 100°C, freeze-drying) and constrained drying under excertion of uniaxial pressure at various temperatures have been investigated. The reduction of the high water content of native BNC ( 98%) causes a thickness reduction of the samples. For oven or climate chamber drying a thickness reduction of 98% is observed, while freeze-drying widely preserves the nano- or micro-structure of the fibrous material and leads to a thickness reduction of only 13%. During drying or pressing at high temperature (100°C), i.e. by evaporation of the water, intermolecular hydrogen bonds are formed and interconnect the individual fibres and strands. Consequently mechanical stiffening is observed in tensile tests at small strains. After drying, a densified cellulose nano-fibre network is observed by scanning electron microscopy. Due to the irreversibility of drying by evaporation, the water content and water retention capacity of BNC are not recovered by rehydration. Applying uniaxial pressure before drying further enhances the irreversible reinforcement of the fibre network, while this is not the case when pressing the samples after drying. The presented results show that the properties of BNC can be widely controlled by post-processing steps. Thus, taylor-made BNC can be produced for biomedical applications.
Cellular metabolism is a tightly controlled process in which the cell adapts fluxes through metabolic pathways in response to changes in nutrient supply. Among the transcription factors that regulate ...gene expression and thereby cause changes in cellular metabolism is the basic leucine-zipper (bZIP) transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα). Protein lysine acetylation is a key post-translational modification (PTM) that integrates cellular metabolic cues with other physiological processes. Here, we show that C/EBPα is acetylated by the lysine acetyl transferase (KAT) p300 and deacetylated by the lysine deacetylase (KDAC) sirtuin1 (SIRT1). SIRT1 is activated in times of energy demand by high levels of nicotinamide adenine dinucleotide (NAD+) and controls mitochondrial biogenesis and function. A hypoacetylated mutant of C/EBPα induces the transcription of mitochondrial genes and results in increased mitochondrial respiration. Our study identifies C/EBPα as a key mediator of SIRT1-controlled adaption of energy homeostasis to changes in nutrient supply.
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•p300 acetylates C/EBPα on several lysines•SIRT1 deacetylates C/EBPα•Hypoacetylated C/EBPα increases mitochondrial function•C/EBPα is a mediator of SIRT1-controlled energy homeostasis
Zaini et al. show that the transcription factor C/EBPα is acetylated by p300 and deacetylated by the lysine deacetylase SIRT1. Hypoacetylated C/EBPα induces the transcription of mitochondrial genes and results in increased mitochondrial respiration. C/EBPα is a key mediator of SIRT1-controlled adaption of energy homeostasis to changes in nutrient supply.
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