Novel Rickettsiella Bacterium in the Leafhopper Orosius albicinctus (Hemiptera: Cicadellidae)

Bacteria in the genus Rickettsiella (Coxiellaceae), which are mainly known as arthropod pathogens, are emerging as excellent models to study transitions between mutualism and pathogenicity. The current report characterizes a novel Rickettsiella found in the leafhopper Orosius albicinctus (Hemiptera: Cicadellidae), a major vector of phytoplasma diseases in Europe and Asia. Denaturing gradient gel electrophoresis (DGGE) and pyrosequencing were used to survey the main symbionts of O. albicinctus, revealing the obligate symbionts Sulcia and Nasuia, and the facultative symbionts Arsenophonus and Wolbachia, in addition to Rickettsiella. The leafhopper Rickettsiella is allied with bacteria found in ticks. Screening O. albicinctus from the field showed that Rickettsiella is highly prevalent, with over 60% of individuals infected. A stable Rickettsiella infection was maintained in a leafhopper laboratory colony for at least 10 generations, and fluorescence microscopy localized bacteria to accessory glands of the female reproductive tract, suggesting that the bacterium is vertically transmitted. Future studies will be needed to examine how Rickettsiella affects host fitess and its ability to vector phytopathogens.     

Preparation of Chloramphenicol/Amino Acid Combinations Exhibiting Enhanced Dissolution Rates and Reduced Drug-Induced Oxidative Stress

Chloramphenicol is an old antibiotic agent that is re-emerging as a valuable alternative for the treatment of multidrug-resistant pathogens. However, it exhibits suboptimal biopharmaceutical properties and toxicity profiles. In this work, chloramphenicol was combined with essential amino acids (arginine, cysteine, glycine, and leucine) with the aim of improving its dissolution rate and reduce its toxicity towards leukocytes. The chloramphenicol/amino acid solid samples were prepared by freeze-drying method and characterized in the solid state by using Fourier transform infrared spectroscopy, powder X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and solid-state nuclear magnetic resonance. The dissolution properties, antimicrobial activity, reactive oxygen species production, and stability of the different samples were studied. The dissolution rate of all combinations was significantly increased in comparison to that of the pure active pharmaceutical ingredient. Additionally, oxidative stress production in human leukocytes caused by chloramphenicol was decreased in the chloramphenicol/amino acid combinations, while the antimicrobial activity of the antibiotic was maintained. The CAP:Leu binary combination resulted in the most outstanding solid system makes it suitable candidate for the development of pharmaceutical formulations of this antimicrobial agent with an improved safety profile.     

Rickettsia 'in' and 'out': two different localization patterns of a bacterial symbiont in the same insect species

Intracellular symbionts of arthropods have diverse influences on their hosts, and their functions generally appear to be associated with their localization within the host. The effect of localization pattern on the role of a particular symbiont cannot normally be tested since the localization pattern within hosts is generally invariant. However, in Israel, the secondary symbiont Rickettsia is unusual in that it presents two distinct localization patterns throughout development and adulthood in its whitefly host, Bemisia tabaci (B biotype). In the "scattered" pattern, Rickettsia is localized throughout the whitefly hemocoel, excluding the bacteriocytes, where the obligate symbiont Portiera aleyrodidarum and some other secondary symbionts are housed. In the "confined" pattern, Rickettsia is restricted to the bacteriocytes. We examined the effects of these patterns on Rickettsia densities, association with other symbionts (Portiera and Hamiltonella defensa inside the bacteriocytes) and on the potential for horizontal transmission to the parasitoid wasp, Eretmocerus mundus, while the wasp larvae are developing within the whitefly nymph. Sequences of four Rickettsia genes were found to be identical for both localization patterns, suggesting that they are closely related strains. However, real-time PCR analysis showed very different dynamics for the two localization types. On the first day post-adult emergence, Rickettsia densities were 21 times higher in the "confined" pattern vs. "scattered" pattern whiteflies. During adulthood, Rickettsia increased in density in the "scattered" pattern whiteflies until it reached the "confined" pattern Rickettsia density on day 21. No correlation between Rickettsia densities and Hamiltonella or Portiera densities were found for either localization pattern. Using FISH technique, we found Rickettsia in the gut of the parasitoid wasps only when they developed on whiteflies with the "scattered" pattern. The results suggest that the localization pattern of a symbiont may influence its dynamics within the host.     

Dynamics of thyroid diseases and thyroid‐axis gland masses

Thyroid disorders are common and often require lifelong hormone replacement. Treating thyroid disorders involves a fascinating and troublesome delay, in which it takes many weeks for serum thyroid‐stimulating hormone (TSH) concentration to normalize after thyroid hormones return to normal. This delay challenges attempts to stabilize thyroid hormones in millions of patients. Despite its importance, the physiological mechanism for the delay is unclear. Here, we present data on hormone delays from Israeli medical records spanning 46 million life‐years and develop a mathematical model for dynamic compensation in the thyroid axis, which explains the delays. The delays are due to a feedback mechanism in which peripheral thyroid hormones and TSH control the growth of the thyroid and pituitary glands; enlarged or atrophied glands take many weeks to recover upon treatment due to the slow turnover of the tissues. The model explains why thyroid disorders such as Hashimoto''s thyroiditis and Graves'' disease have both subclinical and clinical states and explains the complex inverse relation between TSH and thyroid hormones. The present model may guide approaches to dynamically adjust the treatment of thyroid disorders.     

Does immune function influence population fluctuations and level of parasitism in the cyclic geometrid moth?

Populations of the autumnal moth, Epirrita autumnata, exhibit cycles with high amplitudes in northernmost Europe, culminating in devastating outbreak densities at favourable sites. Parasitism by hymenopteran parasitoids has been hypothesised to operate with a delayed density dependence capable of producing the observed dynamics. It has also been hypothesised that insects in crowded conditions invest greatly in their immunity as a counter-measure to increased risk of parasitism and pathogen infections. Furthermore, inducible plant defences consequent to grazing by herbivorous insects may be linked to the performance of parasitoids and pathogens through increased immunocompetence of the herbivore feeding on the foliage, in which the defence induction has taken place. At ten sampling sites, we quantified larval abundance, outbreak status and percentage larval parasitism during an extended peak phase of a population cycle. These population level covariates, together with an individual pupal mass, were used to explain differences in the immune defence, measured as an encapsulation reaction to artificial antigen. We also conducted a field study for an investigation of the susceptibility of autumnal moth pupae to naturally occurring pupal parasitoids. We did not find obvious differences between the encapsulation rate of autumnal moths originating from the sites with different past and current larval densities and risks for parasitism. The best ranked statistical models included pupal mass and outbreak status as explanatory variables, although both showed only slight effects on the encapsulation rate. The host resistance test revealed positive relationships between the encapsulation rate, body size and percentage parasitism of the exposed pupae, indicating that pupal parasitoids chose, and/or survived better, in large host individuals irrespective of their encapsulation ability. Thus, our results do not provide support for the hypothesis that variation in the immune function drives or modulates population cycles of autumnal moths. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Selective protein exit from yeast endoplasmic reticulum in absence of functional COPII coat component Sec13p

Sec13p has been thought to be an essential component of the COPII coat, required for exit of proteins from the yeast endoplasmic reticulum (ER). We show herein that normal function of Sec13p was not required for ER exit of the Hsp150 glycoprotein. Hsp150 was secreted to the medium under restrictive conditions in a sec13-1 mutant. The COPII components Sec23p and Sec31p and the GTP/GDP exchange factor Sec12p were required in functional form for secretion of Hsp150. Hsp150 leaves the ER in the absence of retrograde COPI traffic, and the responsible determinant is a peptide repeated 11 times in the middle of the Hsp150 sequence. Herein, we localized the sorting determinant for Sec13p-independent ER exit to the C-terminal domain. Sec13p-dependent invertase left the ER in the absence of normal Sec13p function, when fused to the C-terminal domain of Hsp150, demonstrating that this domain contained an active mediator of Sec13p-independent secretion. Thus, Hsp150 harbors two different signatures that regulate its ER exit. Our data show that transport vesicles lacking functional Sec13p can carry out ER-to-Golgi transport, but select only specific cargo protein(s) for ER exit.     

Germline stem cell arrest inhibits the collapse of somatic proteostasis early in Caenorhabditis elegans adulthood

All cells rely on highly conserved protein folding and clearance pathways to detect and resolve protein damage and to maintain protein homeostasis (proteostasis). Because age is associated with an imbalance in proteostasis, there is a need to understand how protein folding is regulated in a multicellular organism that undergoes aging. We have observed that the ability of Caenorhabditis elegans to maintain proteostasis declines sharply following the onset of oocyte biomass production, suggesting that a restricted protein folding capacity may be linked to the onset of reproduction. To test this hypothesis, we monitored the effects of different sterile mutations on the maintenance of proteostasis in the soma of C. elegans. We found that germline stem cell (GSC) arrest rescued protein quality control, resulting in maintenance of robust proteostasis in different somatic tissues of adult animals. We further demonstrated that GSC‐dependent modulation of proteostasis requires several different signaling pathways, including hsf‐1 and daf‐16/kri‐1/tcer‐1, daf‐12, daf‐9, daf‐36, nhr‐80, and pha‐4 that differentially modulate somatic quality control functions, such that each signaling pathway affects different aspects of proteostasis and cannot functionally complement the other pathways. We propose that the effect of GSCs on the collapse of proteostasis at the transition to adulthood is due to a switch mechanism that links GSC status with maintenance of somatic proteostasis via regulation of the expression and function of different quality control machineries and cellular stress responses that progressively lead to a decline in the maintenance of proteostasis in adulthood, thereby linking reproduction to the maintenance of the soma.     

Senescent cells and the incidence of age‐related diseases

Age‐related diseases such as cancer, cardiovascular disease, kidney failure, and osteoarthritis have universal features: Their incidence rises exponentially with age with a slope of 6–8% per year and decreases at very old ages. There is no conceptual model which explains these features in so many diverse diseases in terms of a single shared biological factor. Here, we develop such a model, and test it using a nationwide medical record dataset on the incidence of nearly 1000 diseases over 50 million life‐years, which we provide as a resource. The model explains incidence using the accumulation of senescent cells, damaged cells that cause inflammation and reduce regeneration, whose level rise stochastically with age. The exponential rise and late drop in incidence are captured by two parameters for each disease: the susceptible fraction of the population and the threshold concentration of senescent cells that causes disease onset. We propose a physiological mechanism for the threshold concentration for several disease classes, including an etiology for diseases of unknown origin such as idiopathic pulmonary fibrosis and osteoarthritis. The model can be used to design optimal treatments that remove senescent cells, suggeting that treatment starting at old age can sharply reduce the incidence of all age‐related diseases, and thus increase the healthspan.