Corrigendum to "Chaperone-Mediated Autophagy Markers LAMP2A and HSC70 Are Independent Adverse Prognostic Markers in Primary Resected Squamous Cell Carcinomas of the Lung".

[This corrects the article DOI: 10.1155/2020/8506572.]

Transurethral injection of autologous muscle precursor cells for treatment of female stress urinary incontinence: a prospective phase I clinical trial

INTRODUCTION AND HYPOTHESIS The purpose was to investigate the safety and feasibility of transurethral injections of autologous muscle precursor cells (MPCs) into the external urinary sphincter (EUS) to treat stress urinary incontinence (SUI) in female patients. METHODS Prospective and randomised phase I clinical trial. Standardised 1-h pad test, International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), urodynamic study, and MRI of the pelvis were performed at baseline and 6 months after treatment. MPCs gained through open muscle biopsy were transported to a GMP facility for processing and cell expansion. The final product was injected into the EUS via a transurethral ultrasound-guided route. Primary outcomes were defined as any adverse events (AEs) during follow-up. Secondary outcomes were functional, questionnaire, and radiological results. RESULTS Ten female patients with SUI grades I-II were included in the study and 9 received treatment. Out of 8 AEs, 3 (37.5%) were potentially related to treatment and treated conservatively: 1 urinary tract infection healed with antibiotics treatment, 1 dysuria and 1 discomfort at biopsy site. Functional urethral length under stress was 25 mm at baseline compared with 30 mm at 6 months' follow-up (p=0.009). ICIQ-UI-SF scores improved from 7 points at baseline to 4 points at follow-up (p=0.035). MRI of the pelvis revealed no evidence of tumour or necrosis, whereas the diameter of the EUS muscle increased from 1.8 mm at baseline to 1.9 mm at follow-up (p=0.009). CONCLUSION Transurethral injections of autologous MPCs into the EUS for treatment of SUI in female patients can be regarded as safe and feasible. Only a minimal number of expected and easily treatable AEs were documented

Biodiversity-stability relationships strengthen over time in a long-term grassland experiment.

Numerous studies have demonstrated that biodiversity drives ecosystem functioning, yet how biodiversity loss alters ecosystems functioning and stability in the long-term lacks experimental evidence. We report temporal effects of species richness on community productivity, stability, species asynchrony, and complementarity, and how the relationships among them change over 17 years in a grassland biodiversity experiment. Productivity declined more rapidly in less diverse communities resulting in temporally strengthening positive effects of richness on productivity, complementarity, and stability. In later years asynchrony played a more important role in increasing community stability as the negative effect of richness on population stability diminished. Only during later years did species complementarity relate to species asynchrony. These results show that species complementarity and asynchrony can take more than a decade to develop strong stabilizing effects on ecosystem functioning in diverse plant communities. Thus, the mechanisms stabilizing ecosystem functioning change with community age

Biodiversity–stability relationships strengthen over time in a long-term grassland experiment

Numerous studies have demonstrated that biodiversity drives ecosystem functioning, yet how biodiversity loss alters ecosystems functioning and stability in the long-term lacks experimental evidence. We report temporal effects of species richness on community productivity, stability, species asynchrony, and complementarity, and how the relationships among them change over 17 years in a grassland biodiversity experiment. Productivity declined more rapidly in less diverse communities resulting in temporally strengthening positive effects of richness on productivity, complementarity, and stability. In later years asynchrony played a more important role in increasing community stability as the negative effect of richness on population stability diminished. Only during later years did species complementarity relate to species asynchrony. These results show that species complementarity and asynchrony can take more than a decade to develop strong stabilizing effects on ecosystem functioning in diverse plant communities. Thus, the mechanisms stabilizing ecosystem functioning change with community age

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Levels of the Autophagy-Related 5 Protein Affect Progression and Metastasis of Pancreatic Tumors in Mice

[Background and Aims]: Cells in pancreatic ductal adenocarcinoma (PDAC) undergo autophagy, but its effects vary with tumor stage and genetic factors. We investigated the consequences of varying levels of the autophagy related 5 (Atg5) protein on pancreatic tumor formation and progression. [Methods]: We generated mice that express oncogenic Kras in primary pancreatic cancer cells and have homozygous disruption of Atg5 (A5;Kras) or heterozygous disruption of Atg5 (A5+/–;Kras), and compared them with mice with only oncogenic Kras (controls). Pancreata were analyzed by histology and immunohistochemistry. Primary tumor cells were isolated and used to perform transcriptome, metabolome, intracellular calcium, extracellular cathepsin activity, and cell migration and invasion analyses. The cells were injected into wild-type littermates, and orthotopic tumor growth and metastasis were monitored. Atg5 was knocked down in pancreatic cancer cell lines using small hairpin RNAs; cell migration and invasion were measured, and cells were injected into wild-type littermates. PDAC samples were obtained from independent cohorts of patients and protein levels were measured on immunoblot and immunohistochemistry; we tested the correlation of protein levels with metastasis and patient survival times. [Results]: A5+/–;Kras mice, with reduced Atg5 levels, developed more tumors and metastases, than control mice, whereas A5;Kras mice did not develop any tumors. Cultured A5+/–;Kras primary tumor cells were resistant to induction and inhibition of autophagy, had altered mitochondrial morphology, compromised mitochondrial function, changes in intracellular Ca2+ oscillations, and increased activity of extracellular cathepsin L and D. The tumors that formed in A5+/–;Kras mice contained greater numbers of type 2 macrophages than control mice, and primary A5+/–;Kras tumor cells had up-regulated expression of cytokines that regulate macrophage chemoattraction and differentiation into M2 macrophage. Knockdown of Atg5 in pancreatic cancer cell lines increased their migratory and invasive capabilities, and formation of metastases following injection into mice. In human PDAC samples, lower levels of ATG5 associated with tumor metastasis and shorter survival time. [Conclusions]: In mice that express oncogenic Kras in pancreatic cells, heterozygous disruption of Atg5 and reduced protein levels promotes tumor development, whereas homozygous disruption of Atg5 blocks tumorigenesis. Therapeutic strategies to alter autophagy in PDAC should consider the effects of ATG5 levels to avoid the expansion of resistant and highly aggressive cells.This study was supported in part by the Mildred-Scheel-Professur der Deutschen Krebshilfe 111464, DFG AL 1174/6-1 to H.A., DFG DI 2299/1-1 to K.N.D., DFG SFB1321 (S01) to K.S. and W.W., and the German Federal Ministry of Education and Research to the German Center for Diabetes Research (DZD e.V.) to J.A

Designing organometallic compounds for catalysis and therapy

Bioorganometallic chemistry is a rapidly developing area of research. In recent years organometallic compounds have provided a rich platform for the design of effective catalysts, e.g. for olefin metathesis and transfer hydrogenation. Electronic and steric effects are used to control both the thermodynamics and kinetics of ligand substitution and redox reactions of metal ions, especially Ru II. Can similar features be incorporated into the design of targeted organometallic drugs? Such complexes offer potential for novel mechanisms of drug action through incorporation of outer-sphere recognition of targets and controlled activation features based on ligand substitution as well as metal- and ligand-based redox processes. We focus here on η 6-arene, η 5-cyclopentadienyl sandwich and half-sandwich complexes of Fe II, Ru II, Os II and Ir III with promising activity towards cancer, malaria, and other conditions. © 2012 The Royal Society of Chemistry

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Steam gasification of sewage sludge for synthesis processes

The paper presents measurement results of a gasification test run. Municipal sewage sludge from a digestion tower is gasified in an advanced dual fluidized bed reactor system. Steam is used as gasification agent and an olivine-limestone mixture as bed material. The fuel analysis shows a very high ash content and a low heating value of the dried sewage sludge. In addition, a significant amount of nitrogen in the fuel is present, leading to a high ammonia content in the product gas.Sintering effects caused by the high ash content do not occur. Thus, a gasification process without limitation is achieved. The fuel input is located in the lower gasification reactor operating as bubbling fluidized bed, whereas the upper gasification reactor is designed as a column of turbulent fluidized zones for tar cracking. The results show an efficient in-situ tar reduction. With a look on the product gas composition a comparatively high carbon dioxide and a low carbon monoxide content is surprising. It is obvious that an iron oxide reduction of the initial fuel ash occur in the gasification reactor. In addition, it is assumed that the significant iron content in the fuel ash also leads to a transport of oxygen from the combustion reactor to the gasification reactor. Thus, carbon monoxide and hydrogen are oxidized in the gasification reactor by the circulating iron-rich ash particles (chemical looping effect).FFG - Österr. Forschungsförderungs- gesellschaft mbH4351

Attributing the variability of eddy‐covariance CO 2 flux measurements across temporal scales using geostatistical regression for a mixed northern hardwood forest

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95220/1/gbc1702.pd