On the trail of iron uptake in ancestral Cyanobacteria on early Earth.

Cyanobacteria oxygenated Earth's atmosphere ~2.4 billion years ago, during the Great Oxygenation Event (GOE), through oxygenic photosynthesis. Their high iron requirement was presumably met by high levels of Fe(II) in the anoxic Archean environment. We found that many deeply branching Cyanobacteria, including two Gloeobacter and four Pseudanabaena spp., cannot synthesize the Fe(II) specific transporter, FeoB. Phylogenetic and relaxed molecular clock analyses find evidence that FeoB and the Fe(III) transporters, cFTR1 and FutB, were present in Proterozoic, but not earlier Archaean lineages of Cyanobacteria. Furthermore Pseudanabaena sp. PCC7367, an early diverging marine, benthic strain grown under simulated Archean conditions, constitutively expressed cftr1, even after the addition of Fe(II). Our genetic profiling suggests that, prior to the GOE, ancestral Cyanobacteria may have utilized alternative metal iron transporters such as ZIP, NRAMP, or FicI, and possibly also scavenged exogenous siderophore bound Fe(III), as they only acquired the necessary Fe(II) and Fe(III) transporters during the Proterozoic. Given that Cyanobacteria arose 3.3-3.6 billion years ago, it is possible that limitations in iron uptake may have contributed to the delay in their expansion during the Archean, and hence the oxygenation of the early Earth.

Large-group one-session treatment: Feasibility and efficacy in 138 individuals with phobic fear of flying.

Recent research suggests that exposure-based large-group one-session treatments (LG-OSTs) may represent useful and efficient treatment options for different types of phobic fear. Although there are effective single session- and small group-interventions for the treatment of clinically relevant Fear of Flying (FoF), no LG-OST for this type of phobic fear has been realized so far. The present study aimed to investigate feasibility and efficacy of an LG-OST for the treatment of clinically relevant FoF. Two months after an initial diagnostics to assess FoF severity and confirm the underlying diagnoses (89% specific flight phobia; 10% agoraphobia), 138 patients attended the LG-OST consisting of psychoeducation, imparting of a breathing technique and a joint 2 ½ hour exposure flight in a chartered airplane (Airbus A320). FoF again was assessed at pre- and post-treatment as well as at 6-months follow-up with the latter again containing clinical diagnostics. Only a small decrease in FoF emerged in the pre-treatment interval. From pre-to post-treatment however, substantial reductions in FoF were observed with a large mean 'intention-to-treat' effect size of Cohen's d = 1.42 that remained stable over time (mean d = 1.44). At follow-up, 71% of the patients were rated as fully (55%) or partially remitted (16%). Also concerning the treatment of clinically relevant FoF, a LG-OST proved feasible and effective. Therefore, LG-OST can be regarded as a highly efficient and promising treatment tool which in terms of efficiency combines the advantages of one-session individual and group treatments.

Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma.

Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+), cytotoxic-T cells (CD8+), T-helper cells (CD4+), B cells (CD20+), macrophages (CD68+), mast cells (CD117+), mononuclear cells (CD11c+), plasma cells, activated-T cells (MUM1+), B cells, myeloid cells (PD1+) and neutrophilic granulocytes (myeloperoxidase+) compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells) in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition.