Riberamstrup9430

Photosynthetic organisms are frequently exposed to excess light conditions and hence to photo-oxidative stress. To counteract photo-oxidative damage, land plants and most algae make use of non- photochemical quenching (NPQ) of excess light energy, in particular the rapidly inducible and relaxing qE-mechanism. In vascular plants, the constitutively active PsbS protein is the key regulator of qE. In the green algae C. reinhardtii, however, qE activation is only possible after initial high-light (HL) acclimation for several hours and requires the synthesis of LHCSR proteins which act as qE regulators. The precise function of PsbS, which is transiently expressed during HL acclimation in C. reinhardtii, is still unclear. Here, we investigated the impact of different PsbS amounts on HL acclimation characteristics of C. reinhardtii cells. We demonstrate that lower PsbS amounts negatively affect HL acclimation at different levels, including NPQ capacity, electron transport characteristics, antenna organization and morphological changes, resulting in an overall increased HL sensitivity and lower vitality of cells. Contrarily, higher PsbS amounts do not result in a higher NPQ capacity, but nevertheless provide higher fitness and tolerance towards HL stress. Strikingly, constitutively expressed PsbS protein was found to be degraded during HL acclimation. We propose that PsbS is transiently required during HL acclimation for the reorganization of thylakoid membranes and/or antenna proteins along with the activation of NPQ and adjustment of electron transfer characteristics, and that degradation of PsbS is essential in the fully HL acclimated state. Phycobilisomes (PBs) absorb light and supply downstream photosynthetic processes with excitation energy in many cyanobacteria and algae. In response to a sudden increase in light intensity, excess excitation energy is photoprotectively dissipated in PBs by means of the orange carotenoid protein (OCP)-related mechanism or via a light-activated intrinsic decay channel. Recently, we have identified that both mechanisms are associated with far-red emission states. Here, we investigate the far-red states involved with the light-induced intrinsic mechanism by exploring the energy landscape and electro-optical properties of the pigments in PBs. While Stark spectroscopy showed that the far-red states in PBs exhibit a strong charge-transfer (CT) character at cryogenic temperatures, single molecule spectroscopy revealed that CT states should also be present at room temperature. Owing to the strong environmental sensitivity of CT states, the knowledge gained from this study may contribute to the design of a new generation of fluorescence markers. BACKGROUND AND AIMS Cholangiocarcinoma (CCA), a deadly malignancy of the bile ducts, can be classified on the basis of its anatomical location into either intrahepatic (iCCA) or extrahepatic (eCCA), each with different pathogenesis and clinical management. There is marginal understanding of the molecular landscape of eCCA and no targeted therapy with clinical efficacy has been approved. We aimed to provide a molecular classification of eCCA and identify potential targets for molecular therapies. METHODS An integrative genomic analysis of an international multi-center cohort of 189 eCCA cases was conducted. Genomic analysis included whole-genome expression, targeted DNA-sequencing and immunohistochemistry. Molecular findings were validated in an external set of 181 biliary tract tumors from ICGC. Selleckchem 2,3-Butanedione-2-monoxime RESULTS KRAS (36.7%), TP53 (34.7%), ARID1A (14%) and SMAD4 (10.7%) were the most prevalent mutations, with ∼25% of tumors having a putative actionable genomic alteration according to OncoKB. Transcriptome-based unsupervised clustering helped us define four molecular classes of eCCA. Tumors classified within the Metabolic class (19%) showed a hepatocyte-like phenotype with activation of the transcription factor HNF4A and enrichment in gene signatures related to bile acid metabolism. The Proliferation class (23%), more common in patients with distal CCA, was characterized by enrichment of MYC targets, ERBB2 mutations / amplifications and mTOR signaling activation. The Mesenchymal class (47%) was defined by signatures of epithelial-mesenchymal transition, aberrant TGF-β signaling and poor overall survival. Finally, tumors in the Immune class (11%) had a higher lymphocyte infiltration, overexpression of PD-1/PD-L1 and molecular features associated with a better response to immune checkpoint inhibitors. CONCLUSION An integrative molecular characterization identified distinct subclasses of eCCA. Genomic traits of each class provide the rationale for exploring patient stratification and novel therapeutic approaches. V.OBJECTIVE To treat mild to moderate apical compartment prolapse while preserving the uterus, our extraperitoneal uterosacral ligament hysteropexy repair technique was developed. Hysterectomy for prolapse accounted for 13% of all benign hysterectomies, which is the third most common reason [1]. Although concomitant hysterectomy risks at time of prolapse surgery are not well defined, risks associated with hysterectomy have been well described in the literature. Additionally, it is well known that anterior compartment prolapse often has an apical component [2]. Benefits of hysteropexy in prolapse surgery consistently cited in the literature include reduced surgical time, blood loss and morbidity [3]. A study by Frick et al, reported more than 60% of women would decline a concomitant hysterectomy if offered an equally efficacious surgical option [4]. Our primary aim was to achieve anatomical success as defined as apical POP-Q less than or equal to Stage 1, resolution of subjective bulge and no re-operation for recurrent prolapse. METHODS We performed a retrospective case series of extraperitoneal uterosacral ligament hysteropexy (EPUSLH) procedures from 2017 to 2019. RESULTS In our case series, the objective cure rate (POP-Q apical prolapse stage ≤ 1) and the subjective cure rate at 5 months follow up was 100%, refer to table 1. The mean length lost in total vaginal length compared to baseline was 0.5 cm, refer to table 2. Mean surgical time for EPUSLH with combined procedures was 110 minutes. The mean EBL was 101 mL. CONCLUSION EPUSLH demonstrated good short-term success with a low rate of complications in this small cohort. Being a tertiary referral center with many patients traveling long distances or internationally has limited follow-up. Although larger numbers and long-term follow-up are needed to better understand the success of this procedure, the early results are encouraging that this technique could be a simple alternative hysteropexy method.