A supramolecular assembly formed by influenza A virus genomic RNA segments

The influenza A virus genome consists of eight viral RNAs (vRNAs) that form viral ribonucleoproteins (vRNPs). Even though evidence supporting segment-specific packaging of vRNAs is accumulating, the mechanism ensuring selective packaging of one copy of each vRNA into the viral particles remains largely unknown. We used electron tomography to show that the eight vRNPs emerge from a common 'transition zone' located underneath the matrix layer at the budding tip of the virions, where they appear to be interconnected and often form a star-like structure. This zone appears as a platform in 3D surface rendering and is thick enough to contain all known packaging signals. In vitro, all vRNA segments are involved in a single network of intermolecular interactions. The regions involved in the strongest interactions were identified and correspond to known packaging signals. A limited set of nucleotides in the 5' region of vRNA 7 was shown to interact with vRNA 6 and to be crucial for packaging of the former vRNA. Collectively, our findings support a model in which the eight genomic RNA segments are selected and packaged as an organized supramolecular complex held together by direct base pairing of the packaging signals.     

The differential response of workers and queens of the ant Lasius niger to an environment marked by workers: Ants dislike the unknown

It is well known that ants can use cuticular hydrocarbons (CHCs) as a specific recognition cue. Most previous studies addressed the perception of CHCs occurring on the cuticle. However, the presence of CHCs in the environment (e.g., on the substrate) and the role of these compounds as a signal cue are less clear.     

A reference microsatellite kit to assess for genetic diversity of Sorghum bicolor (Poaceae)

? Premise of the study: Discrepancies in terms of genotyping data are frequently observed when comparing simple sequence repeat (SSR) data sets across genotyping technologies and laboratories. This technical concern introduces biases that hamper any synthetic studies or comparison of genetic diversity between collections. To prevent this for Sorghum bicolor, we developed a control kit of 48 SSR markers. ? Methods and Results: One hundred seventeen markers were selected along the genome to provide coverage across the length of all 10 sorghum linkage groups. They were tested for polymorphism and reproducibility across two laboratories (Centre de Cooperation Internationale en Recherche Agronomique pour le Developpement [CIRAD], France, and International Crops Research Institute for the Semi-Arid Tropics [ICRISAT], India) using two commonly used genotyping technologies (polyacrylamide gel-based technology with LI-COR sequencing machines and capillary systems with ABI sequencing apparatus) with DNA samples from a diverse set of 48 S. bicolor accessions. ? Conclusions: A kit for diversity analysis (http://sat.cirad.fr/sat/sorghum_SSR_kit/) was developed. It contains information on 48 technically robust sorghum microsatellite markers and 10 DNA controls. It can further be used to calibrate sorghum SSR genotyping data acquired with different technologies and compare those to genetic diversity references.     

Discovery and optimization of a potent and selective triazolopyridinone series of c-Met inhibitors

Deregulation of the receptor tyrosine kinase c-Met has been implicated in several human cancers and is an attractive target for small molecule drug discovery. Herein, we report the discovery of a structurally diverse series of carbon-linked quinoline triazolopyridinones, which demonstrates nanomolar inhibition of c-Met kinase activity. This novel series of inhibitors exhibits favorable pharmacokinetics as well as potent inhibition of HGF-mediated c-Met phosphorylation in a mouse liver pharmacodynamic model.     

Autophagy machinery controls nitrogen remobilization at the whole-plant level under both limiting and ample nitrate conditions in Arabidopsis

? Processes allowing the recycling of organic nitrogen and export to young leaves and seeds are important determinants of plant yield, especially when plants are nitrate-limited. Because autophagy is induced during leaf ageing and in response to nitrogen starvation, its role in nitrogen remobilization was suspected. It was recently shown that autophagy participates in the trafficking of Rubisco-containing bodies to the vacuole. ? To investigate the role of autophagy in nitrogen remobilization, several autophagy-defective (atg) Arabidopsis mutants were grown under low and high nitrate supplies and labeled with at the vegetative stage in order to determine (15) N partitioning in seeds at harvest. Because atg mutants displayed earlier and more rapid leaf senescence than wild type, we investigated whether their defects in nitrogen remobilization were related to premature leaf cell death by studying the stay-green atg5.sid2 and atg5.NahG mutants. ? Results showed that nitrogen remobilization efficiency was significantly lower in all the atg mutants irrespective of biomass defects, harvest index reduction, leaf senescence phenotypes and nitrogen conditions. ? We conclude that autophagy core machinery is needed for nitrogen remobilization and seed filling.     

Laboratory monitoring of patients treated with antihypertensive drugs and newly exposed to non steroidal anti-inflammatory drugs: a cohort study

Background

Drug-Drug Interactions between Non Steroidal Anti-Inflammatory Drugs (NSAIDs) and Angiotensin Converting Enzyme Inhibitors (ACEIs), Angiotensin Receptor Blocker (ARBs) or diuretics can lead to renal failure and hyperkalemia. Thus, monitoring of serum creatinine and potassium is recommended when a first dispensing of NSAID occur in patients treated with these drugs.

Methods

We conducted a pharmacoepidemiological retrospective cohort study using data from the French Health Insurance Reimbursement Database to evaluate the proportion of serum creatinine and potassium laboratory monitoring in patients treated with ACEI, ARB or diuretic and receiving a first dispensing of NSAID. We described the first dispensing of NSAID among 3,500 patients of a 4-year cohort (6,633 patients treated with antihypertensive drugs) and analyzed serum creatinine and potassium laboratory monitoring within the 3 weeks after the first NSAID dispensing.

Results

General Practitioners were the most frequent prescribers of NSAIDs (85.5%, 95% CI: 84.3–86.6). The more commonly prescribed NSAIDs were ibuprofen (20%), ketoprofen (15%), diclofenac (15%) and piroxicam (12%). Serum creatinine and potassium monitoring was 10.7% (95% CI: 9.5–11.8) in patients treated by ACEIs, ARBs or diuretics. Overall, monitoring was more frequently performed to women aged over 60, treated with digoxin or glucose lowering drugs, but not to patients treated with ACEIs, ARBs or diuretics. Monitoring was more frequent when NSAIDs'' prescribers were cardiologists or anesthesiologists.

Conclusion

Monitoring of serum creatinine and potassium of patients treated with ACEIs, ARBs or diuretics and receiving a first NSAID dispensing is insufficiently performed and needs to be reinforced through specific interventions.     

Agreement among health care professionals in diagnosing case Vignette-based surgical site infections

Objective

To assess agreement in diagnosing surgical site infection (SSI) among healthcare professionals involved in SSI surveillance.

Methods

Case-vignette study done in 2009 in 140 healthcare professionals from seven specialties (20 in each specialty, Anesthesiologists, Surgeons, Public health specialists, Infection control physicians, Infection control nurses, Infectious diseases specialists, Microbiologists) in 29 University and 36 non-University hospitals in France. We developed 40 case-vignettes based on cardiac and gastrointestinal surgery patients with suspected SSI. Each participant scored six randomly assigned case-vignettes before and after reading the SSI definition on an online secure relational database. The intraclass correlation coefficient (ICC) was used to assess agreement regarding SSI diagnosis on a seven-point Likert scale and the kappa coefficient to assess agreement for superficial or deep SSI on a three-point scale.

Results

Based on a consensus, SSI was present in 21 of 40 vignettes (52.5%). Intraspecialty agreement for SSI diagnosis ranged across specialties from 0.15 (95% confidence interval, 0.00–0.59) (anesthesiologists and infection control nurses) to 0.73 (0.32–0.90) (infectious diseases specialists). Reading the SSI definition improved agreement in the specialties with poor initial agreement. Intraspecialty agreement for superficial or deep SSI ranged from 0.10 (−0.19–0.38) to 0.54 (0.25–0.83) (surgeons) and increased after reading the SSI definition only among the infection control nurses from 0.10 (−0.19–0.38) to 0.41 (−0.09–0.72). Interspecialty agreement for SSI diagnosis was 0.36 (0.22–0.54) and increased to 0.47 (0.31–0.64) after reading the SSI definition.

Conclusion

Among healthcare professionals evaluating case-vignettes for possible surgical site infection, there was large disagreement in diagnosis that varied both between and within specialties.     

Short and long-term safety of the 2009 AS03-adjuvanted pandemic vaccine

Background

This study assessed the short and the long term safety of the 2009 AS03 adjuvanted monovalent pandemic vaccine through an active web-based electronic surveillance. We compared its safety profile to that of the seasonal trivalent inactivated influenza vaccine (TIV) for 2010–2011.

Methodology/Principal Findings

Health care workers (HCW) vaccinated in 2009 with the pandemic vaccine (Arepanrix ® from GSK) or HCW vaccinated in 2010 with the 2010–2011 TIV were invited to participate in a web-based active surveillance of vaccine safety. They completed two surveys the day-8 survey covered the first 7 days post-vaccination and the day-29 survey covered events occurring 8 to 28 days after vaccination. Those who reported a problem were called by a nurse to obtain details. The main outcome was the occurrence of a new health problem or the worsening of an existing health condition that resulted in a medical consultation or work absenteeism. For the pandemic vaccine, a six-month follow-up for the occurrence of serious adverse events (SAE) was conducted. Among the 6242 HCW who received the pandemic vaccine, 440 (7%) reported 468 events compared to 328 of the 7645 HCW (4.3%) who reported 339 events after the seasonal vaccine. The 2009 pandemic vaccine was associated with significantly more local reactions than the 2010–2011 seasonal vaccine (1% vs. 0.03%, p<0.001). Paresthesia was reported by 7 HCW (0.1%) after the pandemic vaccine but by none after the seasonal vaccine. For the pandemic vaccine, no clustering of SAE was found in the 6 month follow-up.

Conclusion

The 2009 pandemic vaccine seems to have a good safety profile, similar to the 2010–2011 TIV, with the exception of local reactions. This surveillance was adequately powered to identify AE associated with an excess risk ≥1 per 1000 vaccinations but is insufficient to detect rare AE.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01289418","term_id":"NCT01289418"}}NCT01289418, {"type":"clinical-trial","attrs":{"text":"NCT01318876","term_id":"NCT01318876"}}NCT01318876