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Morphological studies of skeletal muscle tissue provide insights into the architecture of muscle fibers, the surrounding cells, and the extracellular matrix (ECM). However, a spatial proteomics analysis of the skeletal muscle including the muscle-tendon transition zone is lacking. Here, we prepare cryotome muscle sections of the mouse soleus muscle and measure each slice using short liquid chromatography-mass spectrometry (LC-MS) gradients. We generate 3,000 high-resolution protein profiles that serve as the basis for a network analysis to reveal the complex architecture of the muscle-tendon junction. Among the protein profiles that increase from muscle to tendon, we find proteins related to neuronal activity, fatty acid biosynthesis, and the renin-angiotensin system (RAS). Blocking the RAS in cultured mouse tenocytes using losartan reduces the ECM synthesis. Overall, our analysis of thin cryotome sections provides a spatial proteome of skeletal muscle and reveals that the RAS acts as an additional regulator of the matrix within muscle-tendon junctions. [Display omitted] • High-resolution spatial proteomic profiles (3,000+) localized muscle-tendon junction zone • Distance-based networks reveal that myotendinous junction is complex and highly connected • Longitudinal profiles highlight de novo fatty acid synthesis and renin-angiotensin system • This indicates modulation of matrix formation in the muscle-tendon junction and tendon Schmidt et al. generated high-resolution protein profiles of skeletal muscles using thin cryosections and sensitive mass spectrometry to identify the molecular architecture of the muscle-tendon transition zone. This analysis reveals that the myotendinous junction is a highly complex connected area, including metabolic activities related to fatty acid synthesis and TGF-β signaling. [ABSTRACT FROM AUTHOR]

Thermochemical conversion of CO 2 in biomass gasification is a promising technology for utilizing CO 2 as a feedstock to produce a CO-rich gas. Simultaneous decomposition reactions of biomass and various gas-solid and gas-gas reactions form the product gas in this process. The overlap in sub-processes makes it challenging to assess the conversion of feedstock CO 2 with common methods like mass balancing. This work introduces stable carbon isotope ratio analysis (δ13C) to identify the sourcing of carbonaceous product gas components and determine the conversion of CO 2. This methodology is applied to evaluate experiments conducted for one hour of continuous operation in a lab-scale fluidized bed gasifier. Softwood pellets and wood char are used as fuel, with Olivine as a bed material, a target heating temperature of 1000 °C and atmospheric pressure. Product gas with more than 80 vol% CO was generated when wood char was used as fuel. Stable carbon isotope measurements show that CO 2 is converted at 48–93% in this process, underpinning the position of biomass CO 2 gasification as carbon capture and utilization technology. These results were up to 25% higher than suggested by mass balancing, with higher discrepancies at lower CO 2 conversions when using softwood as fuel. Therefore, stable carbon isotope ratio measurement can be a valuable tool for improving the process understanding of biomass CO 2 gasification. The results can be used for carbon accounting and the technical development of gasifiers with high CO 2 utilization efficiency. [Display omitted] • Carbon from CO 2 and fuel was differentiated by stable carbon isotope analysis. • Up to 93% of feedstock CO 2 was converted to CO by gasification with biomass. • The product gas is rich in carbon monoxide with a reduction potential of up to 14. • Up to 50% of carbon monoxide in product gas comes from CO 2 utilization. • This method can be used for carbon accounting or process development. [ABSTRACT FROM AUTHOR]

• Emerging connection between the nucleolar stress response and autophagy. • Involvement of the ubiquitin-proteasome system (UPS) and autophagy in ribosome biogenesis and protein homeostasis. • Impaired ribosome biogenesis induces nucleolar stress and p53 activation. • Autophagy activation in response to nucleolar stress as a cytoprotective mechanism. The nucleolus functions as the cellular hub for the initiation and early steps of ribosome biogenesis. Ribosomes are key components of the translation machinery and, accordingly, their abundance needs to be adjusted to the cellular energy status. Further, to ensure translational fidelity, the integrity and quality of ribosomes needs to be monitored under conditions of cellular stress. Stressful insults, such as nutrient, genotoxic or proteotoxic stress, interfere with ribosome biogenesis and activate a cellular response referred to as nucleolar stress. This nucleolar stress response typically affects nucleolar integrity and is intricately linked to the activation of protein quality control pathways, including (i) the ubiquitin proteasome system (UPS) and (ii) the autophagy machinery, to restore cellular proteostasis. Here we will review some key features of the nucleolar stress response with a particular focus on the role of the UPS and autophagy in this process. [ABSTRACT FROM AUTHOR]

The nucleolar scaffold protein NPM1 is a multifunctional regulator of cellular homeostasis, genome integrity, and stress response. NPM1 mutations, known as NPM1c variants promoting its aberrant cytoplasmic localization, are the most frequent genetic alterations in acute myeloid leukemia (AML). A hallmark of AML cells is their dependency on elevated autophagic flux. Here, we show that NPM1 and NPM1c induce the autophagy-lysosome pathway by activating the master transcription factor TFEB, thereby coordinating the expression of lysosomal proteins and autophagy regulators. Importantly, both NPM1 and NPM1c bind to autophagy modifiers of the GABARAP subfamily through an atypical binding module preserved within its N terminus. The propensity of NPM1c to induce autophagy depends on this module, likely indicating that NPM1c exerts its pro-autophagic activity by direct engagement with GABARAPL1. Our data report a non-canonical binding mode of GABARAP family members that drives the pro-autophagic potential of NPM1c, potentially enabling therapeutic options. [Display omitted] • NPM1/NPM1c induce the autophagy-lysosome pathway by activating the master regulator TFEB • NPM1/NPM1c bind to GABARAP proteins via an atypical module in their N-terminal regions • The pro-autophagic activity of NPM1c depends on this GABARAP binding module Mende and co-workers report that NPM1 and NPM1c induce the autophagy-lysosome pathway by activating the master transcription factor TFEB. They identify an atypical GABARAP binding module in the N-terminal region of NPM1 and the AML-associated oncogenic mutant NPM1c and show that the pro-autophagic activity of NPM1c depends on this module. [ABSTRACT FROM AUTHOR]

Background: Pain is a frequent problem faced by emergency medical services (EMS) in pre-hospital settings. This large observational study aims to assess the prevalence of sufficiently provided analgesia and to analyze the efficacy of different analgesics. Moreover, we evaluated if quality of analgesia changed with an emergency physician on scene or depended on paramedics' gender.Methods: This is a retrospective analysis of all pre-hospital medical charts from adults and adolescents treated by the municipal EMS Schutz & Rettung Zürich over a period of 4 years from 2013 to 2016. Inclusion criteria were age ≥16 years, initial GCS > 13, NACA score ≥I and ≤V, an initial numeric rating scale (NRS) ≥ I and a documented NRS at hospital admission. 20,978 out of 142,484 missions fulfilled the inclusion criteria and therefore underwent further investigation. Descriptive, univariate and multivariate analyses were applied.Results: Initial NRS on scene was on average 5.2 ± 3.0. Mean NRS reduction after treatment was 2.2 ± 2.5 leading to a NRS at hospital admission of 3.0 ± 1.9. This resulted in sufficient analgesia for 77% of included patients. Among analgesics, the highest odds ratio for sufficient analgesia was observed for ketamine (OR 4.7, 95%CI 2.2-10.4, p < 0.001) followed by fentanyl (OR 1.4, 95%CI 1.1-1.7, p = 0.004). Female paramedics provided better analgesia (OR 1.2, 95%CI 1.1-1.2; p < 0.001). Patient's sex had no influence on analgesia. In patients with a NACA score > 2, the presence of an emergency physician on scene improved the quality of analgesia significantly.Conclusions: Pre-hospital analgesia is mostly adequate, especially when done with ketamine or fentanyl. Female paramedics provided better analgesia and in selected patients, an emergency physician on scene improved quality of analgesia in critical patients. [ABSTRACT FROM AUTHOR]

In addition to the climate crisis's looming dangers, Europe was recently affected by profoundly volatile energy markets, entailing soaring inflation and political uncertainty. Power-to-Liquid processes have the potential to curb global warming by valorizing CO 2 to produce synthetic fuels and platform chemicals while simultaneously substituting fossil energy imports. The impact of the CO 2 source, i.e., cement production, biogas upgrading and solid biomass combustion, on Power-to-Liquid plants was evaluated by implementing the designed configuration, including CO 2 capture, solid-oxide electrolyzer, Fischer-Tropsch synthesis and steam reforming, in IPSEpro, a stationary equation-based process simulation tool. Maximum Power-to-Liquid efficiency of 63.8% and maximum carbon efficiency of 88.6% were obtained by exploiting CO 2 emitted by a biogas upgrading unit. Solid-oxide electrolyzers ranging from 23 MW el. (biogas) to 504 MW el. (cement) are required to process CO 2 streams from 4.5 to 100 t/h. In addition, the mass and energy balances of the three considered configurations were determined and embedded in a process flow diagram. The presented study aims to facilitate future decisions concerning carbon capture and utilization policy by assessing the CO 2 source's influence on Power-to-Liquid plants' key performance indicators. Furthermore, the underlying work supports a sustainable realization of Power-to-Liquid plants by offering a framework for exploiting CO 2 sources. [Display omitted] • A simulation study of a Power-to-Liquid plant producing FT products is presented. • Models of a solid-oxide electrolyzer, CO 2 capture and a steam reformer were established. • The CO 2 source's influence on the plant's key performance indicators was evaluated. • Power-to-Liquid efficiencies ranged from 54.7% to 63.8%. • The obtained carbon efficiencies ranged from 68.4% to 88.6%. [ABSTRACT FROM AUTHOR]

Background The mediator complex consists of 33 subunits and plays a central role in transcription. Studies have already described the involvement of individual subunits, especially in carcinogenesis. With regard to the subunit MED30, this has, so far, only been confirmed in gastric and breast carcinoma. The role of MED30 in urological tumours is unknown. Materials and methods First, a database analysis using cBioPortal was performed for the mRNA expression and survival analysis of MED30 in clear cell renal cell carcinoma (ccRCC) and papillary RCC (pRCC). The immunohistochemical analysis (IHC) against MED30 was performed on tissue microarrays (TMA), with benign, ccRCC, pRCC samples, and ccRCC-metastases. Intensity evaluation was performed using the IRS (Immunoreactive Score). The ccRCC cell lines ACHN and A-498 were used for the functional investigation of proliferation, migration, and invasion after the knockdown of MED30 by siRNA. Results In a database analysis by cBioPortal, it was shown that mRNA overexpression of MED30 in the pRCC was significantly associated with a poorer overall survival and progression-free survival. In the IHC, pRCC showed the highest level of MED30 expression, unfortunately without significant results in the survival analysis. The knockdown of MED30 resulted in a significant decrease in proliferation, migration, and invasion in ccRCC. Conclusion In summary, MED30 seems to be involved in the progression of the RCC. [ABSTRACT FROM AUTHOR]

Objective Cardiopulmonary bypass (CPB) surgery commonly threatens the heart and remote organs with ischemia-reperfusion injury. Transient episodes of ischemia to nonvital tissue, known as remote ischemic preconditioning (RIPC), is thought to help local and remote vital organs to withstand subsequent ischemic insults. Design Prospective, randomized, double-blinded control trial. Setting Tertiary referral academic teaching hospital. Participants Thirty patients undergoing elective CPB surgery Intervention RIPC was achieved via three 5-minute cycles of upper limb ischemia using a blood pressure cuff or control (sham cuff). Measurements and Main Results Primary outcome was the occurrence of intestinal injury, as measured by an increase in intestinal fatty acid binding protein (I-FABP). Secondary outcomes included incidence of gastrointestinal complications and duration of intensive care unit (ICU) stay. RIPC did not affect serum IFABP levels at the end of surgery and on the first postoperative day (p = 0.697 and p = 0.461, respectively). For all patients, mean I-FABP levels significantly increased at the end of surgery and decreased to under baseline levels on the first postoperative day (from a mean [± standard deviation] baseline value of 764 ± 492 pg/mL to 2,002 ± 974 pg/mL and decreased to 568 ± 319 pg/mL, p < 0.001). All patients remained clinically absent of gastrointestinal complications until hospital discharge. Duration of ICU stay was not correlated with I-FABP levels at the end of surgery. Neither duration of CPB nor duration of aortic clamping significantly correlated with postoperative I-FABP levels. Conclusions These findings suggest that RIPC does not affect intestinal injury in patients undergoing CPB surgery. In patients undergoing cardiac surgery, intestinal injury appears to be moderate and transient without any clinical relevant complication. [ABSTRACT FROM AUTHOR]

Summary Post-translational modification of proteins with ubiquitin-like SUMO modifiers is a tightly regulated and highly dynamic process. The SENP family of SUMO-specific isopeptidases comprises six cysteine proteases. They are instrumental in counterbalancing SUMO conjugation, but their regulation is not well understood. We demonstrate that in hypoxic cell extracts, the catalytic activity of SENP family members, in particular SENP1 and SENP3, is inhibited in a rapid and fully reversible process. Comparative mass spectrometry from normoxic and hypoxic cells defines a subset of hypoxia-induced SUMO1 targets, including SUMO ligases RanBP2 and PIAS2, glucose transporter 1, and transcriptional regulators. Among the most strongly induced targets, we identified the transcriptional co-repressor BHLHE40, which controls hypoxic gene expression programs. We provide evidence that SUMOylation of BHLHE40 is reversed by SENP1 and contributes to transcriptional repression of the metabolic master regulator gene PGC-1α. We propose a pathway that connects oxygen-controlled SENP activity to hypoxic reprogramming of metabolism. [ABSTRACT FROM AUTHOR]

Abstract: Objective:: The purpose of this study was to assess the ability of four different either solid or fluid barriers to reduce adhesions in an established model of gynecological surgery. Study design:: 50 Chinchilla rabbits underwent bilateral deperitonealization and devascularization of the uterine horns (DUH). Afterwards solid membranes of either hyaluronic acid-carboxymethylcellulose (HA-CMC) or lactide-caprolactone-copolymer (LCC) were placed around the injured uterine horns or fluids (icodextrin (ID) or phospholipids (PL)) were intraperitonealy administered. The control group went without protection. After 10 days, adhesions were measured by planimetry. Results:: Phospholipids (median 49.8mm2) significantly reduced adhesion areas in comparison to all other groups: surgical controls (median 230.6mm2), HA-CMC (median 194.9mm2), LCC (median 327.1mm2), and icodextrin (median 242.1mm2). Conclusions:: These results prove the efficacy of phospholipids to reduce primary adhesion formation in the Chinchilla double uterine horn model compared to HA-CMC, LCC and icodextrin. Future clinical studies are recommended. [Copyright &y& Elsevier]

In 2012 a small terminal deletion in the short arm of chromosome 10 in the region 10p15.3 was reported as a novel microdeletion syndrome. By now 21 patients, including a single familial case, have been reported. Characteristic findings comprise variable cognitive impairment or developmental delay, disorder of speech development, as well as various dysmorphic signs. We here report on a new patient, an eight year old girl, with a microdeletion syndrome 10p15.3. She is a foster child showing intellectual deficits, disorder of speech development, behavioral problems, congenital heart defect, and several dysmorphic signs. The same microdeletion was subsequently found in the six year old maternal half-sister, showing very similar developmental and cognitive issues, including major speech impairment. The mother has not obtained a school degree. She was described as being a dissocial person with severe alcohol abuse and showing minor cognitive disability. Thus inheritance of the microdeletion from a probably symptomatic mother can be assumed. The patients presented here add up to the as yet small number of reported cases of microdeletion 10p15.3 and thereby might help to establish a more comprehensive clinical spectrum of this rather newly discovered syndrome. [ABSTRACT FROM AUTHOR]