Vascularization of the trachea in the bottlenose dolphin: Comparison with bovine and evidence for evolutionary adaptations to diving

The rigid structure of the mammalian trachea is functional to maintain constant patency and airflow during breathing, but no gas exchange takes place through its walls. The structure of the organ in dolphins shows increased rigidity of the tracheal cartilaginous rings and the presence of vascular lacunae in the submucosa. However, no actual comparison was ever made between the size and capacity of the vascular lacunae of the dolphin trachea and the potentially homologous structures of terrestrial mammals. In the present study, the extension of the lacunae has been compared between the bottlenose dolphin and the bovine, a closely related terrestrial Cetartiodactyla. Our results indicate that the extension of the blood spaces in the submucosa of dolphins is over 12 times larger than in the corresponding structure of the bovines. Furthermore, a microscopic analysis revealed the presence of valve-like structures in the walls of the cetacean lacunae. The huge difference in size suggests that the lacunae are not merely a product of individual physiological plasticity, but may constitute a true adaptive evolutionary character, functional to life in the aquatic environment. The presence of valve-like structures may be related to the regulation of blood flow, and curtail excessive compression under baric stress at depth

Galectin genes: regulation of expression.

In this review we have summarized the more recent studies on the expression of mammalian galectins. One interesting observation that can be made is that in most of microarrays and/or differential display analysis performed in recent years one or more galectins have been picked up. From a critical evaluation of the pertinent studies the main conclusion that can be drawn is that, although it is not yet clear whether the 14 galectins identified so far have functions in common, a striking common feature of all galectins is the strong modulation of their expression during development, differentiation stages and under different physiological or pathological conditions. This suggests that the expression of different galectins is finely tuned and possibly coordinated. In spite of these observations it is rather unexpected that very few studies have been performed on the molecular mechanisms governing the activity of galectin genes

Impact of M&A on the R&D process. An empirical analysis of the role of technological and market relatedness, The

While the impact of M&A on R&D and innovation examined at the aggregate level left inconclusive evidence, we find that at the level of the R&D process both the technological and the market relatedness between the target and the acquirer are helpful dimensions to identify effects. Using information on 31 in-depth cases of individual M&A deals we show that technological relatedness between M&A partners directly affects the inputs and organizational structure of the R&D process. M&A partners that operate in the same technological fields tend to reduce their R&D effort and rationalize the R&D process after the M&A compared to firms active in complementary technological fields that merge. These firms will furthermore face less technological competition in the technology market, but risk creating a more bureaucratic R&D process with a less motivated workforce. Market relatedness between partners, while having comparable aggregate effects on the R&D process, operates on different dimensions of the R&D process. Former rivals that engage in a M&A are significantly less likely to expand into new R&D fields or leverage their technological competences across the products and markets of the new entity. Non-rival firms that join forces, in contrast, significantly increase R&D output and productivity through these activities.M&A; R&D; scale and scope; market relatedness; technological relatedness;

Targeting GLI factors to inhibit the Hedgehog pathway

Hedgehog (Hh) signaling has emerged in recent years as an attractive target for anticancer therapy because its aberrant activation is implicated in several cancers. Major progress has been made in the development of SMOOTHENED (SMO) antagonists, although they have shown several limitations due to downstream SMO pathway activation or the occurrence of drug-resistant SMO mutations. Recently, particular interest has been elicited by the identification of molecules able to hit glioma-associated oncogene (GLI) factors, the final effectors of the Hh pathway, which provide a valid tool to overcome anti-SMO resistance. Here, we review results achieved in developing GLI antagonists, explaining their mechanisms of action and highlighting their therapeutic potential. We also underline the relevance of structural details in their discovery and optimization

Toward improved simulation tools for compressible turbomachinery: assessment of Residual-Based Compact schemes for the transonic compressor NASA Rotor 37

Residual-based-compact schemes (RBC) of 2nd and 3rd-order accuracy are applied to a challenging 3D ow through a transonic compressor. The proposed schemes provide almost mesh-converged solutions in good agreement with experimental data on relatively coarse grids, which allows achieving a given accuracy level with computational cost reductions by a factor between 2 and 4 with respect to standard solvers.FP7- Projet IDIHO

The role of posterior aortopexy in the treatment of left mainstem bronchus compression

OBJECTIVES: We reviewed the role of posterior aortopexy for left mainstem bronchus compression in infants and children. METHODS: Eighteen children with respiratory symptoms were enrolled between 2005 and 2015 for surgical decompression of the left mainstem bronchus. The children were managed from diagnosis to follow-up by a dedicated tracheal team. Primary outcomes were the complete relief of symptoms or improvement with respect to preoperative clinical status. RESULTS: The median age was 4 years (0.3-15.4) and the median weight was 13.2 kg (3, 1-40). Symptoms or indications for bronchoscopy included difficult weaning from mechanical ventilation (n = 3, 17%), difficult weaning from tracheotomy (n = 4, 22%), recurrent pneumonia (n = 4, 22%), wheezing (n = 3, 17%), atelectasis (n = 1, 5.5%), bitonal cough (n = 1, 5.5%) and stridor (n = 2, 11%). Associated malformations were present in 88.7%. The diagnosis was made by bronchoscopy and computed tomography. Indication for surgery was the presence of pulsations and reduction in the diameter of the left mainstem bronchus compression of more than 70%. Surgery was performed by left posterolateral thoracotomy. Aortopexy was done under bronchoscopic control. No early or late deaths were observed, nor were reoperations necessary. Residual malacia was observed in 8 children (44%). Median follow-up was 4.1 years (0.1-7.1). At last follow-up, 17/18 (94.4%) children showed adequate airway patency. CONCLUSIONS: The intrathoracic location of the left mainstem bronchus predisposes it to compression. Vascular anomalies represent the most frequent causes. Aortopexy has been advocated as a safe and useful method to relieve the compression, and our results confirmed these findings. Management of these patients is challenging and requires a multidisciplinary team

Mucosa-Environment Interactions in the Pathogenesis of Rheumatoid Arthritis

Mucosal surfaces play a central role in the pathogenesis of rheumatoid arthritis (RA). Several risk factors, such as cigarette smoking, environmental pollution, and periodontitis interact with the host at the mucosal level, triggering immune system activation. Moreover, the alteration of microbiota homeostasis is gaining increased attention for its involvement in the disease pathogenesis, modulating the immune cell response at a local and subsequently at a systemic level. Currently, the onset of the clinical manifest arthritis is thought to be the last step of a series of pathogenic events lasting years. The positivity for anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF), in absence of symptoms, characterizes a preclinical phase of RA namely systemic autoimmune phase- which is at high risk for disease progression. Several immune abnormalities, such as local ACPA production, increased T cell polarization towards a pro-inflammatory phenotype, and innate immune cell activation can be documented in at-risk subjects. Many of these abnormalities are direct consequences of the interaction between the environment and the host, which takes place at the mucosal level. The purpose of this review is to describe the humoral and cellular immune abnormalities detected in subjects at risk of RA, highlighting their origin from the mucosa environment interaction