TGF beta type II receptor signaling controls Schwann cell death and proliferation in developing nerves

During development, Schwann cell numbers are precisely adjusted to match the number of axons. It is essentially unknown which growth factors or receptors carry out this important control in vivo. Here, we tested whether the type II transforming growth factor (TGF)beta receptor has a role in this process. We generated a conditional knock-out mouse in which the type II TGF beta receptor is specifically ablated only in Schwann cells. Inactivation of the receptor, evident at least from embryonic day 18, resulted in suppressed Schwann cell death in normally developing and injured nerves. Notably, the mutants also showed a strong reduction in Schwann cell proliferation. Consequently, Schwann cell numbers in wild-type and mutant nerves remained similar. Lack of TGF beta signaling did not appear to affect other processes in which TGF beta had been implicated previously, including myelination and response of adult nerves to injury. This is the first in vivo evidence for a growth factor receptor involved in promoting Schwann cell division during development and the first genetic evidence for a receptor that controls normal developmental Schwann cell death

Unfavorable biological behavior and treatment response of neuroendocrine ovarian metastases of midgut neuroendocrine tumors

Neuroendocrine ovarian metastases (NOM) predominantly derive from midgut neuroendocrine tumors (NETs) and develop in about 25% of women with advanced stage of this malignancy. Little is known of the growth rate and treatment response of NOM. We therefore evaluated the efficacy of different management options for patients with NOM, including peptide receptor radionuclide therapy (PRRT), somatostatin analogues (SSAs) and oophorectomy. Records were screened for patients with well-differentiated NOM of midgut origin that presented in our NET referral center between 1991 and 2022. Progression-free survival (PFS) and tumor growth rate (TGR) of ovarian and extra-ovarian metastases were determined using RECIST (response evaluation criteria in solid tumors) 1.1. In 12 available patients undergoing PRRT, NOM were associated with a shorter PFS than extra-ovarian metastases (P = 0.003). While PRRT induced a similar decrease in TGR for ovarian and extra-ovarian lesions in nine patients with available data (-2.3 vs -1.4, P &gt; 0.05), only the TGR of NOM remained positive after PRRT. In 16 patients treated with SSAs, the TGR of NOM was almost three times that of extra-ovarian lesions during treatment (2.2 vs 0.8, P = 0.011). Oophorectomy was performed in 46 of the 61 included patients and was significantly associated with a prolonged OS (115 vs 38 months, P &lt; 0.001). This association persisted after propensity score matching and correction for tumor grade and simultaneous tumor debulking. In conclusion, NOM have a higher TGR compared to extra-ovarian metastases, resulting in a shorter PFS after PRRT. Bilateral salpingo-oophorectomy should be considered for postmenopausal women with NOM undergoing surgery for metastatic midgut NETs.</p

Surfactants tailored by the class Actinobacteria

Globally the change towards the establishment of a bio-based economy has resulted in an increased need for bio-based applications. This, in turn, has served as a driving force for the discovery and application of novel biosurfactants. The class Actinobacteria represents a vast group of microorganisms with the ability to produce a diverse range of secondary metabolites, including surfactants. Understanding the extensive nature of the biosurfactants produced by actinobacterial strains can assist in finding novel biosurfactants with new potential applications. This review therefore presents a comprehensive overview of the knowledge available on actinobacterial surfactants, the chemical structures that have been completely or partly elucidated, as well as the identity of the biosurfactant-producing strains. Producer strains of not yet elucidated compounds are discussed, as well as the original habitats of all the producer strains, which seems to indicate that biosurfactant production is environmentally driven. Methodology applied in the isolation, purification and structural elucidation of the different types of surface active compounds, as well as surfactant activity tests, are also discussed. Overall, actinobacterial surfactants can be summarized to include the dominantly occurring trehalose-comprising surfactants, other non-trehalose containing glycolipids, lipopeptides and the more rare actinobacterial surfactants. The lack of structural information on a large proportion of actinobacterial surfactants should be considered as a driving force to further explore the abundance and diversity of these compounds. This would allow for a better understanding of actinobacterial surface active compounds and their potential for biotechnological application

European regulatory agenices should employ full time statisticians

No abstract available