The second year has been completed

Among many other things, the last European Respiratory Society (ERS) International Congress in Munich brought changes to the ERS Junior Members Committee (JMC). The 3-year term of JMC representatives has seen Indre Butiene, who initiated the Committee 3 years ago, finish her tenure as chair, with Anders Bjerg, respiratory epidemiologist from Gothenburg, Sweden, being elected as her replacement. Indre’s departure has also led to the election of a new representative to the ERS Education Council. We congratulate Agnes Boots from the Netherlands on her election to this important position! Also, here in Breathe, the Doing Science series has been taken over by Georgia Hardavella, UK, whose ideas will take this practical educational series to new levels in 2015. The Hot Topics section is now coordinated by Neil Saad, UK, one of many Juniors outside the JMC who have volunteered for different JMC activities

Structure-based functional inference of hypothetical proteins from Mycoplasma hyopneumoniae

Enzootic pneumonia caused by Mycoplasma hyopneumoniae is a major constraint to efficient pork production throughout the world. This pathogen has a small genome with 716 coding sequences, of which 418 are homologous to proteins with known functions. However, almost 42% of the 716 coding sequences are annotated as hypothetical proteins. Alternative methodologies such as threading and comparative modeling can be used to predict structures and functions of such hypothetical proteins. Often, these alternative methods can answer questions about the properties of a model system faster than experiments. In this study, we predicted the structures of seven proteins annotated as hypothetical in M. hyopneumoniae, using the structure-based approaches mentioned above. Three proteins were predicted to be involved in metabolic processes, two proteins in transcription and two proteins where no function could be assigned. However, the modeled structures of the last two proteins suggested experimental designs to identify their functions. Our findings are important in diminishing the gap between the lack of annotation of important metabolic pathways and the great number of hypothetical proteins in the M. hyopneumoniae genome

Thymomectomy plus total thymectomy versus simple thymomectomy for early-stage thymoma without myasthenia gravis: A European Society of Thoracic Surgeons Thymic Working Group Study

OBJECTIVES: Resection of thymic tumours including the removal of both the tumour and the thymus gland (thymothymectomy; TT) is the procedure of choice and is recommended in most relevant articles in the literature. Nevertheless, in recent years, some authors have suggested that resection of the tumour (simple thymomectomy; ST) may suffice from an oncological standpoint in patients with early-stage thymoma who do not have myasthenia gravis (MG) (non-MG). The goal of our study was to compare the short-and long-term outcomes of ST versus TT in non-MG early-stage thymomas using the European Society of Thoracic Surgeons thymic database. METHODS: A total of 498 non-MG patients with pathological stage I thymoma were included in the study. TT was performed in 466 (93.6%) of 498 patients who had surgery with curative intent; ST was done in 32 (6.4%). The completeness of resection, the rate of complications, the 30-day mortality, the overall recurrence and the freedom from recurrence were compared. We performed crude and propensity score-adjusted comparisons by surgical approach (ST vs TT). RESULTS: TT showed the same rate of postoperative complications, 30-day mortality and postoperative length of stay as ST. The 5-year overall survival rate was 89% in the TT group and 55% in the ST group. The 5-year freedom from recurrence was 96% in the TT group and 79% in the ST group. CONCLUSION: Patients with early-stage thymoma without MG who have a TT show significantly better freedom from recurrence than those who have an ST, without an increase in postoperative morbidity rate

Distinct in vitro binding properties of the anti-CD20 small modular immunopharmaceutical 2LM20-4 result in profound and sustained in vivo potency in cynomolgus monkeys

Objectives. To characterize the in vitro binding and effector function properties of CD20-directed small modular immunopharmaceutical (SMIP) 2LM20-4, and to compare its in vivo B-cell depletion activity with the mutated 2LM20-4 P331S [no in vitro complement-dependent cytotoxicity (CDC)] and rituximab in cynomolgus monkeys

Dissection of mammalian orthoreovirus µ2 reveals a self-associative domain required for binding to microtubules but not to factory matrix protein µNS

Mammalian orthoreovirus protein μ2 is a component of the viral core particle. Its activities include RNA binding and hydrolysis of the γ-phosphate from NTPs and RNA 5´-termini, suggesting roles as a cofactor for the viral RNA-dependent RNA polymerase, λ3, first enzyme in 5´-capping of viral plus-strand RNAs, and/or prohibitory of RNA-5´-triphosphate-activated antiviral signaling. Within infected cells, μ2 also contributes to viral factories, cytoplasmic structures in which genome replication and particle assembly occur. By associating with both microtubules (MTs) and viral factory matrix protein μNS, μ2 can anchor the factories to MTs, the full effects of which remain unknown. In this study, a protease-hypersensitive region allowed μ2 to be dissected into two large fragments corresponding to residues 1–282 and 283–736. Fusions with enhanced green fluorescent protein revealed that these amino- and carboxyl-terminal regions of μ2 associate in cells with either MTs or μNS, respectively. More exhaustive deletion analysis defined μ2 residues 1–325 as the minimal contiguous region that associates with MTs in the absence of the self-associating tag. A region involved in μ2 self-association was mapped to residues 283–325, and self-association involving this region was essential for MT-association as well. Likewise, we mapped that μNS-binding site in μ2 relates to residues 290–453 which is independent of μ2 self-association. These findings suggest that μ2 monomers or oligomers can bind to MTs and μNS, but that self-association involving μ2 residues 283–325 is specifically relevant for MT-association during viral factories formation

Treatment of BXSB-Yaa mice with IL-21R-Fc fusion protein minimally attenuates systemic lupus erythematosus.

Interleukin-21 (IL-21) is a pleiotropic cytokine whose function is only now being unraveled. Abundant evidence indicates that activated CD4 T cells are the primary, if not the only, source of IL-21. While it is clear that IL-21 is actively transcribed by naive activated T cells, recent studies have shown that IL-21 potentially promotes a developmental shift of naive T cells toward the Th2 phenotype. BXSB-Yaa mice develop an autoimmune syndrome similar to systemic lupus erythematosus (SLE), affecting males earlier than females on account of the presence of the Yaa (Y-linked autoimmune acceleration) locus. Previous results indicate the elevation of IL-21 expression by BXSB-Yaa mice at an age when the early characteristics of autoimmune processes first become evident. We set out to determine whether IL-21 was necessary for disease progression in BXSB-Yaa mice. Mice were treated for 24 weeks with soluble IL-21R-Fc in order to therapeutically neutralize the IL-21 present. The results overall suggest a biphasic effect of IL-21, negatively influencing survival early on and positively influencing survival at later stages. We propose that IL-21 exerts a pleiotropic effect in which it promotes the protective effects of CD8+ suppressor cells in the early disease phase and then promotes the humoral components of SLE in the later disease stages. This experiment provides preliminary evidence for a role of IL-21 in modulating the severity of SLE in BXSB-Yaa mice

Br. J. Cancer

BACKGROUND: We evaluated KRAS (mKRAS (mutant KRAS)) and BRAF (mBRAF (mutant BRAF)) mutations to determine their prognostic potential in assessing patients with colorectal cancer (CRC) for lung metastasectomy. METHODS: Data were reviewed from 180 patients with a diagnosis of CRC who underwent a lung metastasectomy between January 1998 and December 2011. RESULTS: Molecular analysis revealed mKRAS in 93 patients (51.7%), mBRAF in 19 patients (10.6%). In univariate analyses, overall survival (OS) was influenced by thoracic nodal status (median OS: 98 months for pN-, 27 months for pN+, P<0.0001), multiple thoracic metastases (75 months vs 101 months, P=0.008) or a history of liver metastases (94 months vs 101 months, P=0.04). mBRAF had a significantly worse OS than mKRAS and wild type (WT) (P<0.0001). The 5-year OS was 0% for mBRAF, 44% for mKRAS and 100% for WT, with corresponding median OS of 15, 55 and 98 months, respectively (P<0.0001). In multivariate analysis, WT BRAF (HR: 0.005 (95% CI: 0.001-0.02), P<0.0001) and WT KRAS (HR: 0.04 (95% CI: 0.02-0.1), P<0.0001) had a significant impact on OS. CONCLUSIONS: mKRAS and mBRAF seem to be prognostic factors in patients with CRC who undergo lung metastasectomy. Further studies are necessary