The insect vector Cacopsylla picta vertically transmits the bacterium ‘Candidatus Phytoplasma mali’ to its progeny

The phloem-sucking psyllid Cacopsylla picta plays an important role in transmitting the bacterium ‘Candidatus Phytoplasma mali’, the agent associated with apple proliferation disease. The psyllid can ingest ‘Ca. Phytoplasma mali’ from infected apple trees and spread the bacterium by subsequently feeding on uninfected trees. Until now, this has been the most important method of ‘Ca. Phytoplasma mali’ transmission. The aim of this study was to investigate whether infected C. picta are able to transmit ‘Ca. Phytoplasma mali’ directly to their progeny. This method of transmission would allow the bacteria to bypass a time-consuming reproductive cycle in the host plant. Furthermore, this would cause a high number of infected F1 individuals in the vector population. To address this question, eggs, nymphs and adults derived from infected overwintering adults of C. picta were reared on non-infected apple saplings and subsequently tested for the presence of ‘Ca. Phytoplasma mali’. In this study it was shown for the first time that infected C. picta individuals transmit ‘Ca. Phytoplasma mali’ to their eggs, nymphs and F1 adults, thus providing the basis for a more detailed understanding of ‘Ca. Phytoplasma mali’ transmission by C. pict

Characterizing the gamma-ray long-term variability of PKS 2155-304 with H.E.S.S. and Fermi-LAT

Studying the temporal variability of BL Lac objects at the highest energies provides unique insights into the extreme physical processes occurring in relativistic jets and in the vicinity of super-massive black holes. To this end, the long-term variability of the BL Lac object PKS 2155-304 is analyzed in the high (HE, 100 MeV 200 GeV) gamma-ray domain. Over the course of ~9 yr of H.E.S.S observations the VHE light curve in the quiescent state is consistent with a log-normal behavior. The VHE variability in this state is well described by flicker noise (power-spectral-density index {\ss}_VHE = 1.10 +0.10 -0.13) on time scales larger than one day. An analysis of 5.5 yr of HE Fermi LAT data gives consistent results ({\ss}_HE = 1.20 +0.21 -0.23, on time scales larger than 10 days) compatible with the VHE findings. The HE and VHE power spectral densities show a scale invariance across the probed time ranges. A direct linear correlation between the VHE and HE fluxes could neither be excluded nor firmly established. These long-term-variability properties are discussed and compared to the red noise behavior ({\ss} ~ 2) seen on shorter time scales during VHE-flaring states. The difference in power spectral noise behavior at VHE energies during quiescent and flaring states provides evidence that these states are influenced by different physical processes, while the compatibility of the HE and VHE long-term results is suggestive of a common physical link as it might be introduced by an underlying jet-disk connection.Comment: 11 pages, 16 figure

Characterization of the binding sites of the anticancer ruthenium(III) complexes KP1019 and KP1339 on human serum albumin via competition studies

Indazolium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (KP1019) and its Na+ analogue (KP1339) are two of the most prominent non-platinum antitumor metal complexes currently undergoing clinical trials. After intravenous administration, they are known to bind to human serum albumin (HSA) in a noncovalent manner. To elucidate their HSA binding sites, displacement reactions with the established site markers warfarin and dansylglycine as well as bilirubin were monitored by spectrofluorimetry, ultrafiltration-UV-vis spectrophotometry, and/or capillary zone electrophoresis. Conditional stability constants for the binding of KP1019 and KP1339 to sites I and II of HSA were determined, indicating that both Ru(III) compounds bind to both sites with moderately strong affinity (log K (1)' = 5.3-5.8). No preference for either binding site was found, and similar results were obtained for both metal complexes, demonstrating low influence of the counter ion on the binding event

The lateral septum mediates kinship behavior in the rat

Kinship behavior in rodents has been documented in the laboratory setting but the neural mechanisms that mediate kinship behavior are not known. Here, the authors show that the lateral septum has a key role in organizing mammalian kinship behavior

Cys34-cysteinylated human serum albumin is a sensitive plasma marker in oxidative stress-related chronic diseases

The degree of oxidized cysteine (Cys) 34 in human serum albumin (HSA), as determined by high performance liquid chromatography (HPLC), is correlated with oxidative stress related pathological conditions. In order to further characterize the oxidation of Cys34-HSA at the molecular level and to develop a suitable analytical method for a rapid and sensitive clinical laboratory analysis, the use of electrospray ionization time-of-flight mass spectrometer (ESI-TOFMS) was evaluated. A marked increase in the cysteinylation of Cys34 occurs in chronic liver and kidney diseases and diabetes mellitus. A significant positive correlation was observed between the Cys-Cys34-HSA fraction of plasma samples obtained from 229 patients, as determined by ESI-TOFMS, and the degree of oxidized Cys34-HSA determined by HPLC. The Cys-Cys34-HSA fraction was significantly increased with the progression of liver cirrhosis, and was reduced by branched chain amino acids (BCAA) treatment. The changes in the Cys-Cys34-HSA fraction were significantly correlated with the alternations of the plasma levels of advanced oxidized protein products, an oxidative stress marker for proteins. The binding ability of endogenous substances (bilirubin and tryptophan) and drugs (warfarin and diazepam) to HSA purified from chronic liver disease patients were significantly suppressed but significantly improved by BCAA supplementation. Interestingly, the changes in this physiological function of HSA in chronic liver disease were correlated with the Cys-Cys34-HSA fraction. In conclusion, ESI-TOFMS is a suitable high throughput method for the rapid and sensitive quantification of Cys-Cys34-HSA in a large number of samples for evaluating oxidative stress related chronic disease progression or in response to a treatment

Steroids in kidney transplant patients

Any evaluation of steroids in kidney transplantation is hampered by individual variability in metabolism, the lack of clinically available steroid blood levels, and overall little attention to steroid exposure. Many feel that steroids were an essential part of chronic immunosuppression in past decades but may no longer be necessary in low-risk populations when our newer and more potent drugs are used. Potential differences in long-term outcome will be unapparent in short-term antibody induction studies in low-risk patients, particularly with low on steroid doses, as may have happened in the recent, well-done Astellas trial. In many studies, the evidence for the superiority of mycophenolate (MMF) and tacrolimus (TAC) was not as strong as the evidence for the benefit of steroids in the Canadian cyclosporine study. As the practice of steroid withdrawal has increased, we have not seen the improvement in long-term graft survival that many expected with our newer agents. Steroids have immunosuppressive effects even in doses that are low by historic standards, and side effects may not justify their abandonment

Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure

Background & Aims Acute-on-chronic liver failure (ACLF) is characterized by severe systemic inflammation, multi-organ failure and high mortality rates. Its treatment is an urgent unmet need. DIALIVE is a novel liver dialysis device that aims to exchange dysfunctional albumin and remove damage- and pathogen-associated molecular patterns. This first-in-man randomized-controlled trial was performed with the primary aim of assessing the safety of DIALIVE in patients with ACLF, with secondary aims of evaluating its clinical effects, device performance and effect on pathophysiologically relevant biomarkers. Methods Thirty-two patients with alcohol-related ACLF were included. Patients were treated with DIALIVE for up to 5 days and end points were assessed at Day 10. Safety was assessed in all patients (n = 32). The secondary aims were assessed in a pre-specified subgroup that had at least three treatment sessions with DIALIVE (n = 30). Results There were no significant differences in 28-day mortality or occurrence of serious adverse events between the groups. Significant reduction in the severity of endotoxemia and improvement in albumin function was observed in the DIALIVE group, which translated into a significant reduction in the CLIF-C (Chronic Liver Failure consortium) organ failure (p = 0.018) and CLIF-C ACLF scores (p = 0.042) at Day 10. Time to resolution of ACLF was significantly faster in DIALIVE group (p = 0.036). Biomarkers of systemic inflammation such as IL-8 (p = 0.006), cell death [cytokeratin-18: M30 (p = 0.005) and M65 (p = 0.029)], endothelial function [asymmetric dimethylarginine (p = 0.002)] and, ligands for Toll-like receptor 4 (p = 0.030) and inflammasome (p = 0.002) improved significantly in the DIALIVE group. Conclusions These data indicate that DIALIVE appears to be safe and impacts positively on prognostic scores and pathophysiologically relevant biomarkers in patients with ACLF. Larger, adequately powered studies are warranted to further confirm its safety and efficacy. Impact and implications This is the first-in-man clinical trial which tested DIALIVE, a novel liver dialysis device for the treatment of cirrhosis and acute-on-chronic liver failure, a condition associated with severe inflammation, organ failures and a high risk of death. The study met the primary endpoint, confirming the safety of the DIALIVE system. Additionally, DIALIVE reduced inflammation and improved clinical parameters. However, it did not reduce mortality in this small study and further larger clinical trials are required to re-confirm its safety and to evaluate efficacy. Clinical trial number NCT03065699