Akklimatisierung und Anpassung an Eisenmangelbedingungen in den marinen Kieselalgen Phaeodactylum tricornutum und Thalassiosira oceanica

In the open ocean phytoplankton growth is widely limited by the availability of iron, an essential element of the photosynthetic electron transport system. Survival under these conditions requires sophisti-cated strategies to maintain growth, e.g. lowering iron requirements and enhancing cellular iron affinity. In this work we used genomic and transcriptomic data to unravel acclimation (transcriptomics) and adaptation (genomics) to low-iron conditions in the two diatoms Thalassiosira oceanica and Phaeodactylum tricornutum, who both are highly tolerant to iron limitation. The acclimation response to low ambient iron concentrations is very similar in the two diatoms. Both undergo an extensive cellular retrenchment, best visible from chloroplast reduction and from the concomitant pigment loss that imposes a chlorotic phenotype on the cells. Growth rates are very low with a high degree of photosynthetic energy dissipation. The differential regulation of the genes for ferre-doxin (PETF) and flavodoxin (FLDA) and for class II and class I fructose-bisphosphate aldolases (FBA) indicates that cellular iron requirements are lowered by replacing abundant iron-rich proteins with iron-free substitutes. Genetically fixed features of T. oceanica and P. tricornutum that may represent beneficial adaptations to low-iron are the small cell sizes found for these species and the possession of class I FBA genes not present in the coastal diatom species Thalassiosira pseudonana. As adaptations specific to T. oceanica we observe the constitutive expres-sion of the plastocyanin gene (PCY) that encodes for a substitute of iron-containing cytochrome c6. The ferredoxin gene (PETF) has been transferred from the chloroplast to the nuclear genome in this species, facilitating its co-regulation with the flavodoxin gene (FLDA). The acclimation of diatoms to low-iron resembles the processes running off in green plants and algae upon low-iron stress. Thus, the response to low-iron represents an ancient cellular mechanism com-mon to most, if not all photosynthetic groups. Genetic adaptation to a persistent shortage of iron such as in the open ocean likely occurs by exploring strategies to optionally or permanently replace abundant iron-rich proteins by iron-free substitutes, thereby approximating the cellular iron requirements to a lowest possible level. The adaptive significance of substitution strategies is strengthened by their absence in coastal diatoms like T. pseudonana which is adapted to iron-rich coastal waters and is highly sensitive to low ambient iron concen-trations.Im offenen Ozean ist das Phytoplankton-Wachstum häufig limitiert durch die Verfügbarkeit von Eisen, einem wesentlichen Bestandteil der photosynthetischen Elektronen-Transportkette. Damit Wachstum und Vermehrung aufrechterhalten werden können, muss der zelluläre Eisenbedarf gesenkt bzw. das Binde- und Aufnahmevermögens für Eisen erhöht werden. In der vorliegenden Arbeit werden Genom- und Transkriptomdaten genutzt, um Akklimatisierung (Transkriptomics) sowie Adaptation (Genomics) der Kieselalgen Thalassiosira oceanica und Phaeodactylum tricornutum an eisenarme Bedingungen zu unter-suchen. Beide Spezies sind sehr tolerant gegenüber Eisenmangel. Die Akklimatisierung an eisenarme Bedingungen verläuft in beiden Spezies sehr ähnlich. Die gesamte Zell-Biomasse wird stark reduziert, erkennbar an der Reduktion der Chloroplasten und dem damit einher-gehenden Pigmentverlust, welcher der Zelle einen ausgeblichenen, chlorotischen Phänotyp verleiht. Wachstumsraten sind extrem niedrig bei gleichzeitig hohem Anteil photosynthetisch nichtverwertbarer Lichtenergie, die ungenutzt abgeleitet wird. Die differentielle Regu-lation der Gene für Ferredoxin (PETF) und Flavodoxin (FLDA) sowie von Genen für Klasse II und Klasse I Fructosebisphosphataldolasen (FBA) weist darauf hin, daß der zelluläre Eisenbedarf gesenkt wird, indem eisenreiche durch eisenfreie Proteine ersetzt werden. Genetisch manifestierte Merkmale von T. oceanica und P. tricornu-tum, welche vorteilhafte Adaptationen an Eisenmangelbedingungen darstellen könnten, sind sowohl die geringen Zellgrößen beider Arten, als auch der Besitz von Klasse I FBA-Genen, welche nicht in der küstennah beheimateten Art Thalassiosira pseudonana vorkommen. Als für T. oceanica spezifische Adaptationen beobachten wir die konsti-tutive Expression des Plastocyanin-Gens (PCY), das ein Substitut für das eisenhaltige Cytochrom c6 kodiert. Das Ferredoxin-Gen (PETF) wurde in dieser Spezies vom Chloroplasten- zum Kerngenom verlagert, was seine Koregulation mit dem Flavodoxin-Gen (FLDA) erleichert. Die Akklimatisierung von Kieselalgen an Eisenmangelbedingungen ähnelt den Reaktionen von grünen Pflanzen und Algen auf Eisenstress und repräsentiert einen evolutionär alten Mechanismus, der den mei-sten, wenn nicht allen, photosynthetischen Organismen gemein ist. Genetische Adaptation an dauerhaften Eisenmangel, wie er im offenen Ozean vorherrscht, geschieht wahrscheinlich vorwiegend durch fortgesetztes Ausloten neuer Möglichkeiten, wie eisenreiche durch eisenarme Proteine ersetzt werden können, um somit den zellulären Eisenbedarf auf ein Minimum zu reduzieren. Die mögliche Bedeutung solcher Ersetzungsstrategien für evolutionäre Anpassung an Eisen-mangel wird unterstrichen durch deren Fehlen in Küsten-Spezies wie T. pseudonana, die an eisenreiche Standorte angepasst ist

Acclimation and adaptation to low-iron conditions in the marine diatoms Phaeodactylum tricornutum and Thalassiosira oceanica

In the open ocean phytoplankton growth is widely limited by the availability of iron, an essential element of the photosynthetic electron transport system. Survival under these conditions requires sophisti-cated strategies to maintain growth, e.g. lowering iron requirements and enhancing cellular iron affinity. In this work we used genomic and transcriptomic data to unravel acclimation (transcriptomics) and adaptation (genomics) to low-iron conditions in the two diatoms Thalassiosira oceanica and Phaeodactylum tricornutum, who both are highly tolerant to iron limitation. The acclimation response to low ambient iron concentrations is very similar in the two diatoms. Both undergo an extensive cellular retrenchment, best visible from chloroplast reduction and from the concomitant pigment loss that imposes a chlorotic phenotype on the cells. Growth rates are very low with a high degree of photosynthetic energy dissipation. The differential regulation of the genes for ferre-doxin (PETF) and flavodoxin (FLDA) and for class II and class I fructose-bisphosphate aldolases (FBA) indicates that cellular iron requirements are lowered by replacing abundant iron-rich proteins with iron-free substitutes. Genetically fixed features of T. oceanica and P. tricornutum that may represent beneficial adaptations to low-iron are the small cell sizes found for these species and the possession of class I FBA genes not present in the coastal diatom species Thalassiosira pseudonana. As adaptations specific to T. oceanica we observe the constitutive expres-sion of the plastocyanin gene (PCY) that encodes for a substitute of iron-containing cytochrome c6. The ferredoxin gene (PETF) has been transferred from the chloroplast to the nuclear genome in this species, facilitating its co-regulation with the flavodoxin gene (FLDA). The acclimation of diatoms to low-iron resembles the processes running off in green plants and algae upon low-iron stress. Thus, the response to low-iron represents an ancient cellular mechanism com-mon to most, if not all photosynthetic groups. Genetic adaptation to a persistent shortage of iron such as in the open ocean likely occurs by exploring strategies to optionally or permanently replace abundant iron-rich proteins by iron-free substitutes, thereby approximating the cellular iron requirements to a lowest possible level. The adaptive significance of substitution strategies is strengthened by their absence in coastal diatoms like T. pseudonana which is adapted to iron-rich coastal waters and is highly sensitive to low ambient iron concen-trations

Magnetotransport in 2D electron systems with a Rashba spin-orbit interaction

The beating pattern of Shubnikov-de Haas oscillations in 2D electron system in the presence of a Rashba zero-field spin splitting is reproduced. It is shown, taking into account the Zeeman splitting, that the explicit formulae for the node position well describes the experimental data. The spin-orbit interaction strength obtained is found to be magnetic field independent in an agreement with the basic assumptions of the Rashba model.Comment: 4 pages, 2 figure

Huntingtin–HAP40 complex is a novel Rab5 effector that regulates early endosome motility and is up-regulated in Huntington's disease

The molecular mechanisms underlying the targeting of Huntingtin (Htt) to endosomes and its multifaceted role in endocytosis are poorly understood. In this study, we have identified Htt-associated protein 40 (HAP40) as a novel effector of the small guanosine triphosphatase Rab5, a key regulator of endocytosis. HAP40 mediates the recruitment of Htt by Rab5 onto early endosomes. HAP40 overexpression caused a drastic reduction of early endosomal motility through their displacement from microtubules and preferential association with actin filaments. Remarkably, endogenous HAP40 was up-regulated in fibroblasts and brain tissue from human patients affected by Huntington's disease (HD) as well as in STHdhQ111 striatal cells established from a HD mouse model. These cells consistently displayed altered endosome motility and endocytic activity, which was restored by the ablation of HAP40. In revealing an unexpected link between Rab5, HAP40, and Htt, we uncovered a new mechanism regulating cytoskeleton-dependent endosome dynamics and its dysfunction under pathological conditions

Manipulation of spin dephasing in InAs quantum wires

The spin dephasing due to the Rashba spin-orbit coupling, especially its dependence on the direction of the electric field is studied in InAs quantum wire. We find that the spin dephasing is strongly affected by the angle of Rashba effective magnetic field and the applied magnetic field. The nonlinearity in spin dephasing time versus the direction of the electric field shows a potential evenue to manipulate the spin lifetime in spintronic device. Moreover, we figure out a quantity that can well represent the inhomogeneous broadening of the system which may help us to understand the many-body spin dephasing due to the Rashba effect.Comment: 4 pages, 3 figure

Testing the validity of the Danish urban myth that alcohol can be absorbed through feet: open labelled self experimental study

Objective To determine the validity of the Danish urban myth that it is possible to get drunk by submerging feet in alcohol

Recent transfer of an iron-regulated gene from the plastid to the nuclear genome in an oceanic diatom adapted to chronic iron limitation

Background Although the importance and widespread occurrence of iron limitation in the contemporary ocean is well documented, we still know relatively little about genetic adaptation of phytoplankton to these environments. Compared to its coastal relative Thalassiosira pseudonana, the oceanic diatom Thalassiosira oceanica is highly tolerant to iron limitation. The adaptation to low-iron conditions in T. oceanica has been attributed to a decrease in the photosynthetic components that are rich in iron. Genomic information on T. oceanica may shed light on the genetic basis of the physiological differences between the two species. Results The complete 141790 bp sequence of the T. oceanica chloroplast genome [GenBank: GU323224], assembled from massively parallel pyrosequencing (454) shotgun reads, revealed that the petF gene encoding for ferredoxin, which is localized in the chloroplast genome in T. pseudonana and other diatoms, has been transferred to the nucleus in T. oceanica. The iron-sulfur protein ferredoxin, a key element of the chloroplast electron transport chain, can be replaced by the iron-free flavodoxin under iron-limited growth conditions thereby contributing to a reduction in the cellular iron requirements. From a comparison to the genomic context of the T. pseudonana petF gene, the T. oceanica ortholog can be traced back to its chloroplast origin. The coding potential of the T. oceanica chloroplast genome is comparable to that of T. pseudonana and Phaeodactylum tricornutum, though a novel expressed ORF appears in the genomic region that has been subjected to rearrangements linked to the petF gene transfer event. Conclusions The transfer of the petF from the cp to the nuclear genome in T. oceanica represents a major difference between the two closely related species. The ability of T. oceanica to tolerate iron limitation suggests that the transfer of petF from the chloroplast to the nuclear genome might have contributed to the ecological success of this species

Glucocorticoid-induced diabetes in patients with metastatic spinal cord compression

Background: The risk of developing diabetes mellitus (DM) during treatment with high-dose glucocorticoids is unknown and monitoring of glucose is random in many settings. Objective: To determine incidence of and risk factors for induction of DM during high-dose glucocorticoid therapy of metastatic spinal cord compression (MSCC) in patients referred to radiotherapy. Furthermore, to describe the time course of development of DM. Subjects and methods: 140 patients were recruited (131 were included in the analysis) with MSCC receiving high-dose glucocorticoid ≥100 mg prednisolone per day were included in a prospective, observational cohort study. The primary endpoint was development of DM defined by two or more plasma glucose values ≥11.1 mmol/L. Plasma glucose was monitored on a daily basis for 12 days during radiotherapy. Results: Fifty-six of the patients (43%; 95% CI 35–52%) were diagnosed with DM based on plasma glucose measurements during the study period. Sixteen patients, 12% (95% CI 6–18%), were treated with insulin. At multivariate analysis, only high baseline HbA1c predicted the development of insulin-treated DM. An HbA1c-value <39 mmol/mol was associated with a negative predictive value of 96% for not developing DM needing treatment with insulin. The diagnosis of diabetes with need for insulin treatment was made within 7 days in 14 of the 16 (88%; 95% CI 72–100%) patients. Conclusion: The risk of developing DM during treatment with high-dose glucocorticoids in patients with MSCC referred to radiotherapy is high in the first treatment week. Only referral HbA1c predicts the development of DM

A multicenter experience using adipose-derived mesenchymal stem cell therapy for cats with chronic, non-responsive gingivostomatitis.

BackgroundThe ability of mesenchymal stem cells (MSCs) to modulate immune responses inspired a series of clinical trials addressing oral mucosal inflammation. We previously reported on the safety and efficacy of fresh, allogeneic and autologous, adipose-derived mesenchymal stem cells (ASCs) to treat feline gingivostomatitis (FCGS), an oral mucosal inflammatory disease that shares similarities with human oral lichen planus.MethodsTo meet clinical demand and goals for future commercialization, we determined the feasibility of shipping fresh ASCs to distant clinics and extended our pilot studies to expand safety and efficacy data for shipped and non-shipped ASCs in a cohort of 18 FCGS cats enrolled locally and at a few different locations within the USA.ResultsWe found that ASCs retained their viability, phenotype, and function after shipment. ASCs administered systemically resulted in a 72% positive response rate, identical to that noted in our previous studies. Cats that responded to ASC therapy had a significant decrease in circulating globulin concentration and histological evidence of decreased CD3+ T cells and CD20+ B cells in the oral mucosa. Responder cats also had significantly decreased percentages of CD8lo cells in blood prior to and at 3 months post-ASC therapy. CD8lo cells may serve as a potential "predictor" for response to systemic ASC therapy.ConclusionFresh feline ASCs can be successfully shipped and administered to cats with FCGS. ASCs modulate the immune response and demonstrate efficacy for chronic oral mucosal inflammatory lesions that are characterized by CD8+ T cell inflammation and T cell activation. FCGS is a potentially useful naturally occurring large animal model of human oral inflammatory diseases