Preliminary report on permineralized Senftenbergia from the Chester Series of Illinois

Specimens of Senftenbergia from the Chester Series of Illinois include ones having both external features diagnostic of the genus, and internal anatomy. The anatomy of the frond does not support the generally held view that Senftenbergia is related at the family level to the modern schizaeaceous ferns. Both the form of the vascular system and the presence of peripheral loops are characters that the genus shares with the coenopterid ferns Ankyropteris and Clepsydropsis, but are unlike any of the Schizaeaceae.     

Rapid demineralization in acidic buffers

Summary The demineralization of routine histological specimens in buffers of weakly ionized organic acids, unbuffered formic acid, and EDTA was investigated. The rate of demineralization was measured by a chemical method and from radiographs. Lactate-containing buffers and buffers of formic acid with its potassium salt were more rapid in effect than any other agent. Acidic buffers and unbuffered formic acid produced rapid diffuse demineralization with secondary precipitation of calcium salts. Preservation of dental enamel in such buffers resulted from the significantly slower rate of enamel demineralization than that for bone and dentine. In rapid demineralizing agents the secondary salts were quickly redissolved while in slow buffers these salts persisted. Multivalent ions such as citrate and maleate slowed the rate of demineralization, and a citrate-containing buffer was the slowest of all the agents tested. Demineralization in EDTA exhibited a different pattern with the establishment of a well-defined front of demineralization without apparent reprecipitation. EDTA attacked enamel, bone and dentine at the same rate. An attempt was made to relate the observed rates of demineralization to current theories of the demineralization process.Supported by the British Medical Research Council     

Extracellular phenol oxidase patterns during depolymerization of low-rank coal by three basidiomycetes

The activity of ligninolytic phenol oxidases from three white rot fungi, Pycnoporus cinnabarinus Polyporus ciliatus, and an unidentified basidiomycete, during the reaction with low-rank coal were studied. Even though, each fungus displayed a unique phenol oxidase pattern all three strains decolorized and depolymerized the substrate demonstrating that alternative extracellular enzyme systems and their respective cofactors are capable of degrading low-rank coal.     

Neuroblastoma signalling models unveil combination therapies targeting feedback-mediated resistance

Very high risk neuroblastoma is characterised by increased MAPK signalling, and targeting MAPK signalling is a promising therapeutic strategy. We used a deeply characterised panel of neuroblastoma cell lines and found that the sensitivity to MEK inhibitors varied drastically between these cell lines. By generating quantitative perturbation data and mathematical modelling, we determined potential resistance mechanisms. We found that negative feedbacks within MAPK signalling and via the IGF receptor mediate re-activation of MAPK signalling upon treatment in resistant cell lines. By using cell-line specific models, we predict that combinations of MEK inhibitors with RAF or IGFR inhibitors can overcome resistance, and tested these predictions experimentally. In addition, phospho-proteomic profiling confirmed the cell-specific feedback effects and synergy of MEK and IGFR targeted treatment. Our study shows that a quantitative understanding of signalling and feedback mechanisms facilitated by models can help to develop and optimise therapeutic strategies. Our findings should be considered for the planning of future clinical trials introducing MEKi in the treatment of neuroblastoma.     

Rubicon-deficiency sensitizes mice to mixed lineage kinase domain-like (MLKL)-mediated kidney ischemia-reperfusion injury

The cytosolic protein rubicon (RUBCN) has been implicated in the removal of necrotic debris and autoimmunity. However, the role of RUBCN in models of acute kidney injury (AKI), a condition that typically involves necrotic kidney tubules, was not investigated. Here, we demonstrate that RUBCN-deficient mice are hypersensitive to renal damage induced by ischemia-reperfusion injury (IRI) and cisplatin-induced AKI. Combined deficiency of RUBCN and mixed lineage kinase domain-like (MLKL) partially reversed the sensitivity in the IRI model suggesting that the absence of RUBCN sensitizes to necroptosis in that model. Necroptosis is known to contribute to TNFα-induced severe inflammatory response syndrome (SIRS), but we detected no statistically significant difference in overall survival following injection of TNFα in RUBCN-deficient mice. We additionally generated RUBCN-deficient mice which lack gasdermin D (GSDMD), the terminal mediator of pyroptosis, but no reversal of the AKI phenotype was observed. Finally, and in contrast to the previous understanding of the role of RUBCN, we did not find a significant autoimmune phenotype in RUBCN-deficient mice, but detected chronic kidney injury (CKD) in aged RUBCN-deficient mice of both sexes. In summary, our data indicate that RUBCN-deficient mice are hypersensitive to kidney injury.Subject terms: Cell death, Kidney diseases     

Rapid and Non-Enzymatic In Vitro Retrieval of Tumour Cells from Surgical Specimens

The study of tumourigenesis commonly involves the use of established cell lines or single cell suspensions of primary tumours. Standard methods for the generation of short-term tumour cell cultures include the disintegration of tissue based on enzymatic and mechanical stress. Here, we describe a simple and rapid method for the preparation of single cells from primary carcinomas, which is independent of enzymatic treatment and feeder cells. Tumour biopsies are processed to 1 mm³ cubes termed explants, which are cultured 1–3 days on agarose-coated well plates in specified medium. Through incisions generated in the explants, single cells are retrieved and collected from the culture supernatant and can be used for further analysis including in vitro and in vivo studies. Collected cells retain tumour-forming capacity in xenotransplantation assays, mimic the phenotype of the primary tumour, and facilitate the generation of cell lines.     

Learning viewpoint invariant object representations using a temporal coherence principle

Invariant object recognition is arguably one of the major challenges for contemporary machine vision systems. In contrast, the mammalian visual system performs this task virtually effortlessly. How can we exploit our knowledge on the biological system to improve artificial systems? Our understanding of the mammalian early visual system has been augmented by the discovery that general coding principles could explain many aspects of neuronal response properties. How can such schemes be transferred to system level performance? In the present study we train cells on a particular variant of the general principle of temporal coherence, the “stability” objective. These cells are trained on unlabeled real-world images without a teaching signal. We show that after training, the cells form a representation that is largely independent of the viewpoint from which the stimulus is looked at. This finding includes generalization to previously unseen viewpoints. The achieved representation is better suited for view-point invariant object classification than the cells’ input patterns. This property to facilitate view-point invariant classification is maintained even if training and classification take place in the presence of an – also unlabeled – distractor object. In summary, here we show that unsupervised learning using a general coding principle facilitates the classification of real-world objects, that are not segmented from the background and undergo complex, non-isomorphic, transformations.     

Homo- and heterodimerization of APP family members promotes intercellular adhesion

The amyloid precursor protein (APP) plays a central role in Alzheimer's disease, but its physiological function and that of its mammalian paralogs, the amyloid precursor-like proteins 1 and 2 (APLPs), is still poorly understood. APP has been proposed to form dimers, a process that could promote cell adhesion via trans-dimerization. We investigated the dimerization and cell adhesion properties of APP/APLPs and provide evidence that all three paralogs are capable of forming homo- and heterocomplexes. Moreover, we show that trans-interaction of APP family proteins promotes cell-cell adhesion in a homo- and heterotypic fashion and that endogenous APLP2 is required for cell-cell adhesion in mouse embryonic fibroblasts. We further demonstrate interaction of all the three APP family members in mouse brain, genetic interdependence, and molecular interaction of APP and APLPs in synaptically enriched membrane compartments. Together, our results provide evidence that homo- and heterocomplexes of APP/APLPs promote trans-cellular adhesion in vivo.     

A novel extracellular esterase from Bacillus subtilis and its conversion to a monoacylglycerol hydrolase.

A novel gene lipB, which encodes an extracellular lipolytic enzyme, was identified in the Bacillus subtilis genomic DNA sequence. We have cloned and overexpressed lipB in B. subtilis and Escherichia coli and have also purified the enzyme from a B. subtilis culture supernatant to electrophoretic homogeneity. Four different lipase assays were used to determine its catalytic activity: pH-stat, spectrophotometry, fluorimetry and the monomolecular film technique. LipB preferentially hydrolysed triacylglycerol-esters and p-nitrophenyl-esters of fatty acids with short chain lengths of 相似文献