Pathology of Anopheles stephensi after infection with Plasmodium berghei berghei. II. Changes in amino acid contents.

Infection with Plasmodium berghei results in the disease of a relatively high percentage of mosquitoes depending on the experimental conditions. The damage caused by the parasites may be so severe that the host dies. It can also become manifest for instance in a change in the amino acid content of the mosquito homogenate. The amino acid content of mosquitoes fed on a glucose solution, normal mouse blood, or the blood of infected mice was analysed qualitatively and quantitatively over a period of 14 days. The amino acids lysine, phenylalanine, proline, threonine, and tyrosine are always found in higher concentrations in infected mosquitoes. The content of leucine (and/or isoleucine) increased from the 6th day and glutamic acid from the 9th day compared to the controls. Lower concentrations were found for alanine, aspartic acid, glycine, and serine as compared to uninfected mosquitoes. Further investigations on this subject might help to find the causes for the susceptibility or resistance of individual mosquitoes to plasmodia.     

Thermal ecology and baseline energetic requirements of a large‐bodied ectotherm suggest resilience to climate change

1. Most studies on how rising temperatures will impact terrestrial ectotherms have focused on single populations or multiple sympatric species. Addressing the thermal and energetic implications of climatic variation on multiple allopatric populations of a species will help us better understand how a species may be impacted by altered climates.
2. We used eight years of thermal and behavioral data collected from four populations of Pacific rattlesnakes (Crotalus oreganus) living in climatically distinct habitat types (inland and coastal) to determine the field‐active and laboratory‐preferred body temperatures, thermoregulatory metrics, and maintenance energetic requirements of snakes from each population.
3. Physical models showed that thermal quality was best at coastal sites, but inland snakes thermoregulated more accurately despite being in more thermally constrained environments. Projected increases of 1 and 2°C in ambient temperature result in an increase in overall thermal quality at both coastal and inland sites.
4. Population differences in modeled standard metabolic rate estimates were driven by body size and not field‐active body temperature, with inland snakes requiring 1.6× more food annually than coastal snakes.
5. All snakes thermoregulated with high accuracy, suggesting that small increases in ambient temperature are unlikely to impact the maintenance energetic requirements of individual snakes and that some species of large‐bodied reptiles may be robust to modest thermal perturbations under conservative climate change predictions.

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An apicoplast‐resident folate transporter is essential for sporogony of malaria parasites

Malaria parasites are fast replicating unicellular organisms and require substantial amounts of folate for DNA synthesis. Despite the central role of this critical co‐factor for parasite survival, only little is known about intraparasitic folate trafficking in Plasmodium. Here, we report on the expression, subcellular localisation and function of the parasite's folate transporter 2 (FT2) during life cycle progression in the murine malaria parasite Plasmodium berghei. Using live fluorescence microscopy of genetically engineered parasites, we demonstrate that FT2 localises to the apicoplast. In invasive P. berghei stages, a fraction of FT2 is also observed at the apical end. Upon genetic disruption of FT2, blood and liver infection, gametocyte production and mosquito colonisation remain unaltered. But in the Anopheles vector, FT2‐deficient parasites develop inflated oocysts with unusual pulp formation consisting of numerous single‐membrane vesicles, which ultimately fuse to form large cavities. Ultrastructural analysis suggests that this defect reflects aberrant sporoblast formation caused by abnormal vesicular traffic. Complete sporogony in FT2‐deficient oocysts is very rare, and mutant sporozoites fail to establish hepatocyte infection, resulting in a complete block of parasite transmission. Our findings reveal a previously unrecognised organellar folate transporter that exerts critical roles for pathogen maturation in the arthropod vector.     

A simple and inexpensive method for investigating microbiological,enzymatic, or inorganic catalysis using standard histology and microbiology laboratory equipment: assembly,mass transfer properties,hydrodynamic conditions and evaluation

We introduce a generic, simple, and inexpensive method for performing microbiological, enzymatic, or inorganic catalysis with solids using standard histology and microbiology laboratory equipment. Histology cassettes were used to standardize hydrodynamic conditions and to protect the catalysts and their solid supports. Histology cassettes have the following advantages: they are readily available, inexpensive, solvent and acid resistant, automatable, and the slots in the cassette walls allow liquid to circulate freely. Standard Erlenmeyer flasks were used as reaction vessels. We developed a new camera to observe the movement and position of the histology cassettes as well as the liquid in the Erlenmeyer flasks. The camera produces a stable image of the rotating liquid in the Erlenmeyer flask. This visualization method revealed that in a 250?ml Erlenmeyer flask, stable operating conditions are achieved at a shaking frequency of 300?rpm and a fill volume of 30?ml. In vessels with vertical walls, such as beakers or laboratory bottles, the movement of the histology cassette is not reproducible. Mass transfer characterization using a biological model system and the chemical sulfite-oxidation method revealed that the histology cassette does not influence gas-liquid mass transfer.     

Experimental Sepsis Impairs Humoral Memory in Mice

Patients with sepsis are often immune suppressed, and experimental mouse models of sepsis also display this feature. However, acute sepsis in mice is also characterized by a generalized B cell activation and plasma cell differentiation, resulting in a marked increase in serum antibody concentration. Its effects on humoral memory are not clearly defined. We measured the effects of experimental sepsis on long-term immunological memory for a defined antigen: we induced colon ascendens stent peritonitis (CASP) 8 weeks after 2 rounds of immunization with ovalbumin. Four weeks later, the antigen-specific bone marrow plasma cell count had doubled in immunized non-septic animals, but remained unchanged in immunized septic animals. Sepsis also caused a decrease in antigen-specific serum antibody concentration. We conclude that sepsis weakens humoral memory by impeding the antigen-specific plasma cell pool’s development, which is not complete 8 weeks after secondary immunization.     

The IKK Inhibitor Bay 11-7082 Induces Cell Death Independent from Inhibition of Activation of NFκB Transcription Factors

Multiple myeloma (MM) displays an NFκB activity-related gene expression signature and about 20% of primary MM samples harbor genetic alterations conducive to intrinsic NFκB signaling activation. The relevance of blocking the classical versus the alternative NFκB signaling pathway and the molecular execution mechanisms involved, however, are still poorly understood. Here, we comparatively tested NFκB activity abrogation through TPCA-1 (an IKK2 inhibitor), BAY 11-7082 (an IKK inhibitor poorly selective for IKK1 and IKK2), and MLN4924 (an NEDD8 activating enzyme (NAE)-inhibitor), and analyzed their anti-MM activity. Whereas TPCA-1 interfered selectively with activation of the classical NFκB pathway, the other two compounds inhibited classical and alternative NFκB signaling without significant discrimination. Noteworthy, whereas TPCA-1 and MLN4924 elicited rather mild anti-MM effects with slight to moderate cell death induction after 1 day BAY 11-7082 was uniformly highly toxic to MM cell lines and primary MM cells. Treatment with BAY 11-7082 induced rapid cell swelling and its initial effects were blocked by necrostatin-1 or the ROS scavenger BHA, but a lasting protective effect was not achieved even with additional blockade of caspases. Because MLN4924 inhibits the alternative NFκB pathway downstream of IKK1 at the level of p100 processing, the quite discordant effects between MLN4924 and BAY 11-7082 must thus be due to blockade of IKK1-mediated NFκB-independent necrosis-inhibitory functions or represent an off-target effect of BAY 11-7082. In accordance with the latter, we further observed that concomitant knockdown of IKK1 and IKK2 did not have any major short-term adverse effect on the viability of MM cells.