Diagnostics and prognostic evaluation in renal cell tumors: the German S3 guidelines recommendations

The German guidelines on renal cell carcinoma (RCC) have been developed at highest level of evidence based on systematic literature review. In this paper, we are presenting the current recommendations on diagnostics including preoperative imaging and imaging for stage evaluation as well as histopathological classification. The role of tumor biopsy is further discussed. In addition, different prognostic scores and the status of biomarkers in RCC are critically evaluated

A stable backbone for the fungi

Fungi are abundant in the biosphere. They have fascinated mankind as far as written history goes and have considerably influenced our culture. In biotechnology, cell biology, genetics, and life sciences in general fungi constitute relevant model organisms. Once the phylogenetic relationships of fungi are stably resolved individual results from fungal research can be combined into a holistic picture of biology. However, and despite recent progress, the backbone of the fungal phylogeny is not yet fully resolved. Especially the early evolutionary history of fungi and the order or below-order relationships within the ascomycetes remain uncertain. Here we present the first phylogenomic study for a eukaryotic kingdom that merges all publicly available fungal genomes and expressed sequence tags (EST) to build a data set comprising 128 genes and 146 taxa. The resulting tree provides a stable phylogenetic backbone for the fungi. Moreover, we present the first formal supertree based on 161 fungal taxa and 128 gene trees. The combined evidences from the trees support the deep-level stability of the fungal groups towards a comprehensive natural system of the fungi. They indicate that the classification of the fungi, especially their alliance with the Microsporidia, requires careful revision. Our analysis is also an inventory of present day sequence information for the fungi. It provides insights into which phylogenenetic conclusions can and which cannot be drawn from the current data and may serve as a guide to direct further sequencing initiatives. Together with a comprehensive animal phylogeny, we provide the second of three pillars to understand the evolution of the multicellular eukaryotic kingdoms, fungi, metazoa, and plants, in the past 1.6 billion years

Synthesis of Silver Nanowires with Reduced Diameters Using Benzoin-Derived Radicals to Make Transparent Conductors with High Transparency and Low Haze.

Reducing the diameter of silver nanowires has been proven to be an effective way to improve their optoelectronic performance by lessening light attenuation. The state-of-the-art silver nanowires are typically around 20 nm in diameter. Herein we report a modified polyol synthesis of silver nanowires with average diameters as thin as 13 nm and aspect ratios up to 3000. The success of this synthesis is based on the employment of benzoin-derived radicals in the polyol approach and does not require high-pressure conditions. The strong reducing power of radicals allows the reduction of silver precursors to occur at relatively low temperatures, wherein the lateral growth of silver nanowires is restrained because of efficient surface passivation. The optoelectronic performance of as-prepared 13 nm silver nanowires presents a sheet resistance of 28 Ω sq-1 at a transmittance of 95% with a haze factor of ∼1.2%, comparable to that of commercial indium tin oxide (ITO)

TonB-dependent transporters and their occurrence in cyanobacteria

Background Different iron transport systems evolved in Gram-negative bacteria during evolution. Most of the transport systems depend on outer membrane localized TonB-dependent transporters (TBDTs), a periplasma-facing TonB protein and a plasma membrane localized machinery (ExbBD). So far, iron chelators (siderophores), oligosaccharides and polypeptides have been identified as substrates of TBDTs. For iron transport, three uptake systems are defined: the lactoferrin/transferrin binding proteins, the porphyrin-dependent transporters and the siderophore-dependent transporters. However, for cyanobacteria almost nothing is known about possible TonB-dependent uptake systems for iron or other substrates. Results We have screened all publicly available eubacterial genomes for sequences representing (putative) TBDTs. Based on sequence similarity, we identified 195 clusters, where elements of one cluster may possibly recognize similar substrates. For Anabaena sp. PCC 7120 we identified 22 genes as putative TBDTs covering almost all known TBDT subclasses. This is a high number of TBDTs compared to other cyanobacteria. The expression of the 22 putative TBDTs individually depends on the presence of iron, copper or nitrogen. Conclusions We exemplified on TBDTs the power of CLANS-based classification, which demonstrates its importance for future application in systems biology. In addition, the tentative substrate assignment based on characterized proteins will stimulate the research of TBDTs in different species. For cyanobacteria, the atypical dependence of TBDT gene expression on different nutrition points to a yet unknown regulatory mechanism. In addition, we were able to clarify a hypothesis of the absence of TonB in cyanobacteria by the identification of according sequences

Mathematiklehrkräfte und -fortbildende reflektieren die Nutzung eines Chatbots zur Vorbereitung einer schulpraktischen Erprobung innovativer Lernumgebungen

Dieser Beitrag stellt die qualitative Evaluation eines Chatbots als innovatives Fortbildungsmaterial zur Unterstützung schulpraktischer Erprobungen – also Phasen situierten Lernens von Lehrkräften – in den Mittelpunkt. Dazu werden überblicksartig die Hintergründe, der bisherige Entwicklungsprozess, der methodische Rahmen sowie erste Ergebnisse der Evaluation dargestellt

A Consistent Phylogenetic Backbone for the Fungi

The kingdom of fungi provides model organisms for biotechnology, cell biology, genetics, and life sciences in general. Only when their phylogenetic relationships are stably resolved, can individual results from fungal research be integrated into a holistic picture of biology. However, and despite recent progress, many deep relationships within the fungi remain unclear. Here, we present the first phylogenomic study of an entire eukaryotic kingdom that uses a consistency criterion to strengthen phylogenetic conclusions. We reason that branches (splits) recovered with independent data and different tree reconstruction methods are likely to reflect true evolutionary relationships. Two complementary phylogenomic data sets based on 99 fungal genomes and 109 fungal expressed sequence tag (EST) sets analyzed with four different tree reconstruction methods shed light from different angles on the fungal tree of life. Eleven additional data sets address specifically the phylogenetic position of Blastocladiomycota, Ustilaginomycotina, and Dothideomycetes, respectively. The combined evidence from the resulting trees supports the deep-level stability of the fungal groups toward a comprehensive natural system of the fungi. In addition, our analysis reveals methodologically interesting aspects. Enrichment for EST encoded data—a common practice in phylogenomic analyses—introduces a strong bias toward slowly evolving and functionally correlated genes. Consequently, the generalization of phylogenomic data sets as collections of randomly selected genes cannot be taken for granted. A thorough characterization of the data to assess possible influences on the tree reconstruction should therefore become a standard in phylogenomic analyses

Complement activation via the lectin and alternative pathway in patients with severe COVID-19

Complement plays an important role in the direct defense to pathogens, but can also activate immune cells and the release of pro-inflammatory cytokines. However, in critically ill patients with COVID-19 the immune system is inadequately activated leading to severe acute respiratory syndrome (SARS) and acute kidney injury, which is associated with higher mortality. Therefore, we characterized local complement deposition as a sign of activation in both lungs and kidneys from patients with severe COVID-19. Using immunohistochemistry we investigated deposition of complement factors C1q, MASP-2, factor D (CFD), C3c, C3d and C5b-9 as well as myeloperoxidase (MPO) positive neutrophils and SARS-CoV-2 virus particles in lungs and kidneys from 38 patients who died from COVID-19. In addition, tissue damage was analyzed using semi-quantitative scores followed by correlation with complement deposition. Autopsy material from non-COVID patients who died from cardiovascular causes, cerebral hemorrhage and pulmonary embolism served as control (n=8). Lung injury in samples from COVID-19 patients was significantly more pronounced compared to controls with formation of hyaline membranes, thrombi and edema. In addition, in the kidney tubular injury was higher in these patients and correlated with lung injury (r=0.361*). In autopsy samples SARS-CoV-2 spike protein was detected in 22% of the lungs of COVID-19 patients but was lacking in kidneys. Complement activation was significantly stronger in lung samples from patients with COVID-19 via the lectin and alternative pathway as indicated by deposition of MASP-2, CFD, C3d and C5b9. Deposits in the lung were predominantly detected along the alveolar septa, the hyaline membranes and in the alveolar lumina. In the kidney, complement was significantly more deposited in patients with COVID-19 in peritubular capillaries and tubular basement membranes. Renal COVID-19-induced complement activation occurred via the lectin pathway, while activation of the alternative pathway was similar in both groups. Furthermore, MPO-positive neutrophils were found in significantly higher numbers in lungs and kidneys of COVID-19 patients and correlated with local MASP-2 deposition. In conclusion, in patients who died from SARS-CoV-2 infection complement was activated in both lungs and kidneys indicating that complement might be involved in systemic worsening of the inflammatory response. Complement inhibition might thus be a promising treatment option to prevent deregulated activation and subsequent collateral tissue injury in COVID-19

Bisphosphonate-associated osteonecrosis of the jaw is linked to suppressed TGFβ1-signaling and increased Galectin-3 expression: A histological study on biopsies

Background Bisphosphonate associated osteonecrosis of the jaw (BRONJ) implies an impairment in oral hard- and soft tissue repair. An understanding of the signal transduction alterations involved can inform therapeutic strategies. Transforming growth factor β1 (TGFβ1) is a critical regulator of tissue repair; galectin-3 mediates tissue differentiation and specifically modulates periodontopathic bacterial infection. The aim of this study was to compare the expression of TGFβ1-related signaling molecules and Galectin-3 in BRONJ-affected and healthy mucosal tissues. To discriminate between BRONJ-specific impairments in TGFβ1 signaling and secondary inflammatory changes, the results were compared to the expression of TGFβ1 and Galectin-3 in mucosal tissues with osteoradionecrosis. Methods Oral mucosal tissue samples with histologically-confirmed BRONJ (n = 20), osteoradionecrosis (n = 20), and no lesions (normal, n = 20) were processed for immunohistochemistry. Automated staining with an alkaline phosphatase-anti-alkaline phosphatase kit was used to detect TGFβ1, Smad-2/3, Smad-7, and Galectin-3. We semiquantitatively assessed the ratio of stained cells/total number of cells (labeling index, Bonferroni-adjustment). Results TGFβ1 and Smad-2/3 were significantly decreased (p < 0.032 and p(0.028, respectively) in the BRONJ samples and significantly increased (p < 0.04 and p <0.043, respectively) in the osteoradionecrosis samples compared to normal tissue. Smad-7 was significantly increased (p < 0.031) in the BRONJ group and significantly decreased (p < 0.026) in the osteoradionecrosis group. Galectin-3 staining was significantly (p < 0.025) increased in both the BRONJ and the osteoradionecrosis (p < 0.038) groups compared to the normal tissue group. However, Galectin-3 expression was significantly higher in the BRONJ samples than in the osteoradionecrosis samples (p < 0.044). Conclusion Our results showed that disrupted TGFβ1 signaling was associated with delayed periodontal repair in BRONJ samples. The findings also indicated that impairments in TGFβ1-signaling were different in BRONJ compared to osteoradionecrosis. BRONJ appeared to be associated with increased terminal osseous differentiation and decreased soft tissue proliferation. The increase in Galectin-3 reflected the increase in osseous differentiation of mucoperiosteal progenitors, and this might explain the inflammatory anergy observed in BRONJ-affected soft tissues. The results substantiated the clinical success of treating BRONJ with sequestrectomy, followed by strict mucosa closure. BRONJ can be further elucidated by investigating the specific intraoral osteoimmunologic status

Perinatal mortality in German dairy cattle: Unveiling the importance of cow-level risk factors and their interactions using a multifaceted modelling approach

Perinatal mortality (PM) is a common issue on dairy farms, leading to calf losses and increased farming costs. The current knowledge about PM in dairy cattle is, however, limited and previous studies lack comparability. The topic has also primarily been studied in Holstein-Friesian cows and closely related breeds, while other dairy breeds have been largely ignored. Different data collection techniques, definitions of PM, studied variables and statistical approaches further limit the comparability and interpretation of previous studies. This article aims to investigate the factors contributing to PM in two underexplored breeds, Simmental (SIM) and Brown Swiss (BS), while comparing them to German Holstein on German farms, and to employ various modelling techniques to enhance comparability to other studies, and to determine if different statistical methods yield consistent results. A total of 133,942 calving records from 131,657 cows on 721 German farms were analyzed. Amongst these, the proportion of PM (defined as stillbirth or death up to 48 hours of age) was 6.1%. Univariable and multivariable mixed-effects logistic regressions, random forest and multimodel inference via brute-force model selection approaches were used to evaluate risk factors on the individual animal level. Although the balanced random forest did not incorporate the random effect, it yielded results similar to those of the mixed-effect model. The brute-force approach surpassed the widely adopted backwards variable selection method and represented a combination of strengths: it accounted for the random effect similar to mixed-effects regression and generated a variable importance plot similar to random forest. The difficulty of calving, breed and parity of the cow were found to be the most important factors, followed by farm size and season. Additionally, four significant interactions amongst predictors were identified: breed—calving ease, breed—season, parity—season and calving ease—farm size. The combination of factors, such as secondiparous SIM breed on small farms and experiencing easy calving in summer, showed the lowest probability of PM. Conversely, primiparous GH cows on large farms with difficult calving in winter exhibited the highest probability of PM. In order to reduce PM, appropriate management of dystocia, optimal heifer management and a wider use of SIM in dairy production are possible ways forward. It is also important that future studies are conducted to identify farm-specific contributors to higher PM on large farms