Nonsense Mediated Decay Inhibition under NaCl stress in Arabidopsis thaliana

Nonsense mediated decay (NMD) ist ein mRNA-Kontrollmechanismus in Eukaryoten, der eine Vielzahl von Transkripten reguliert. Daher hat er auch einen großen, direkten Einfluss auf die Expression vieler Gene. NMD spielt eine zentrale Rolle in der Pflanzenentwicklung und ist Teil von vielen Stressantworten. Salzstress ist eine große Bedrohung für Nutzpflanzen weltweit, und hat außerdem einen Einfluss auf NMD. Um die zugrundeliegenden Mechanismen der durch Salzstress vermittelten Beeinträchtigung des NMD näher zu untersuchen, wurde zuerst eine zuverlässige Methode zur Messung des RNA Abbaus etabliert. Mittels dieser Messmethode konnte gezeigt werden, dass die Salzstress-vermittelte Inhibition des NMD Dosis abhängig ist, sowie spezifisch auf den Mechanismus des NMD wirkt, und nicht von einer allgemeinen Beeinflussung der RNA Abbauprozessen her rührt. Die Salzstress vermittelte NMD Inhibition scheint spezifisch für NaCl zu sein, da andere Salze wie z.B. KCl keinen vergleichbaren Effekt zeigen. Zudem weisen einige Transkripte zentraler NMD Komponenten NMD auslösende Charakteristika auf, was uns dazu veranlasste, NMD vermittelte Rückkopplungseffekte an diesen Transkripten zu untersuchen. Mittels der von uns etablierten Methode zur Erfassung von RNA Abbauprozessen sowie verschiedenen NMD defizienten Mutanten gelang es uns zu zeigen, dass tatsächlich einige dieser Transkripte selbst einer Regulation durch NMD unterliegen. Die in NMD Mutanten auftretende Stabilisierung dieser Transkripte wurde unter Salzstress noch verstärkt. Dies weist daraufhin, dass die noch teilweise Erhaltene NMD Funktion der Mutanten durch applizierten Salzstress weiter verringert werden kann. Im Bestreben übergeordnete, regulatorische Prozesse zu identifizieren, wurde festgestellt, dass Abszisinsäure (ABA) weder ausreicht, noch benötigt wird für Salzstress abhängige NMD Inhibition. Die untergeordneten SNF1-RELATED KINASES 2 (SnRK2s) ist ebenfalls unbeteiligt, was anhand von Analysen der Klasse I und III SnRK2 Mutanten gezeigt werden konnte. SnRK2s und das davon phosphorylierte VARICOSE (VCS) wurden überprüft, da andere Studien eine Rolle in die Regulation von mRNA Stabilität während Salzstress zeigten. Die Reduktion der VCS Expression in VCS amiRNA Linien zeigte eine Inhibition von NMD regulierten Transkripten unter Kontrollbedingungen, jedoch keinen signifikanten Effekt unter Salzstress im Vergleich zum Wildtyp (WT). Des Weiteren weist NMD eine enge Verbindung zu Translationsprozessen auf. Die Applikation des Translations-Elongations Inhibitors Cycloheximid hat die Akkumulation von NMD regulierten Transkripten zur Folge. Dies legt nahe, dass eine NMD Inhibition die Beeinträchtigung der Translations-Elongation zur Folge hat. Dennoch konnte durch die Applikation von Chlorsulfuron, einem Induktor der Phosphorylierung des EUKARYOTISCHEN INITIATIONSFAKTORS 2 a (eIF2a), kein Effekt auf den Abbau von NMD regulierten Transkripten festgestellt werden. Ein Effekt war ebenfalls nicht detektierbar in gcn2 (general control nondepressible 2 ) Linien. GCN2 vermittelt in-vivo die eIF2a phosphorylierung. Auch andere Stressfaktoren wie z.B. Hitzestress wurden untersucht. Bei 30 _C konnte ein beschleunigter Abbau von regulierten Transkripten festgestellt werden, bei 38 _C hingegen eine Stabilisierung derselben. Ausgehend von jüngster Literatur, könnte dies von der Bildung von Hitzestress-Körperchen (Heat stress-granules) bei 34 _C herrühren. Unter Kontrollbedingungen scheinen Pflanzen mit mutierten Decapping Komponenten, die mit UP-FRAMESHIFT PROTEIN 1 (UPF1) interagieren, und des Weiteren Bestandteile von P-bodies und Stress-Körperchen (Stress granules) sind, NMD regulierte Transkripte beeinflussen. Unter Salzstress zeigen diese jedoch nur minimale Änderungen in Ihrer Expression im Vergleich zum WT. Basierend auf der schnellen und reversiblen (De-) Stabilisierung von NMD regulierten Transkripte, sind sehr wahrscheinlich Phosphorylierungsprozesse in die NaCl vermittelte NMD Inhibition involviert. Das Stabilisierungsmuster von NMD Transkripten unter Salzstress kann sowohl durch die Stimulation von cytosolischem Ca2+ Influx, als auch durch externe H2O2 Applikation nachgeahmt werden. Eine mittels Paraquat Behandlung ausgelöste Reaktive Sauerstoffspezies (ROS) Akkumulation in den Chloroplasten hingegen zeigte keinen Einfluss. Die SALT OVERLY SENSITIVE (SOS) Mutanten sos1-1 und sos2-2 zeigen eine Hyperstabilisierung von NMD regulierten Transkripten, sos3-1 jedoch zeigen keinen Effekt. In einem Phos-Tag Gel konnte SUPPRESSOR WITH MORPHOLOGICAL DEFECTS IN GENITALIA 7 (SMG7) in sos2-2 Pflanzen nicht nachgewiesen werden. Auf dem entsprechenden Western-Blot war der Nachweis möglich, was die Folge einer suboptimalen Extraktion des phosphoryliertem SMG7 sein könnte. Zusammen mit den Daten der Ca2+ und der H2O2 Experimente, sowie von neuesten Publikationen, schlage ich einen Mechanismus vor, in welchem SMG7 Ca2+ abhängig phosphoryliert wird, was wiederum unter anderem durch apoplastisches H2O2 im Rahmen einer Salzstress Antwort ausgelöst wird. Ausgehend von diesem Modell wird mittels des Phosphorylierungsstatus von SMG7 die NMD Effizienz moduliert, was wiederum eine dosis-abhängige Feinjustierung der Transkriptkontrolle in der Zelle erlaubt

Aqueous Extract from Hibiscus sabdariffa Linnaeus Ameliorate Diabetic Nephropathy via Regulating Oxidative Status and Akt/Bad/14-3-3γ in an Experimental Animal Model

Several studies point out that oxidative stress maybe a major culprit in diabetic nephropathy. Aqueous extract of Hibiscus sabdariffa L. (HSE) has been demonstrated as having beneficial effects on anti-oxidation and lipid-lowering in experimental studies. This study aimed at investigating the effects of Hibiscus sabdariffa L. on diabetic nephropathy in streptozotocin induced type 1 diabetic rats. Our results show that HSE is capable of reducing lipid peroxidation, increasing catalase and glutathione activities significantly in diabetic kidney, and decreasing the plasma levels of triglyceride, low-density lipoprotein (LDL) and increasing high-density lipoprotein (HDL) value. In histological examination, HSE improves hyperglycemia-caused osmotic diuresis in renal proximal convoluted tubules (defined as hydropic change) in diabetic rats. The study also reveals that up-regulation of Akt/Bad/14-3-3γ and NF-κB-mediated transcription might be involved. In conclusion, our results show that HSE possesses the potential effects to ameliorate diabetic nephropathy via improving oxidative status and regulating Akt/Bad/14-3-3γ signaling

Esophageal Food Impaction: A Homemade Suction Tube Attached to Esophagogastroduodenoscopy for Food Bolus Removal

The most common esophageal foreign body in adults is impacted food bolus. Polypectomy snares, Dormia baskets, retrieval nets, rat-tooth forceps, alligator forceps or polyp graspers are usually used to remove it. Here, we report the case of a 78-year-old woman whose esophagogastroduodenoscopy (EGD) showed a firm goose liver impacted tightly in the lower esophagus; all of the above-mentioned retrieval instruments could not remove it. We used a homemade device by attaching a modified nasogastric tube to an EGD and successfully removed the goose liver by suction under endoscopic visualization. The method is very effective to remove firm and tightly impacted materials in a narrow lumen. When the usual retrieval instruments fail, a homemade suction tube attached to an EGD is an alternative

InfiniCity: Infinite-Scale City Synthesis

Toward infinite-scale 3D city synthesis, we propose a novel framework, InfiniCity, which constructs and renders an unconstrainedly large and 3D-grounded environment from random noises. InfiniCity decomposes the seemingly impractical task into three feasible modules, taking advantage of both 2D and 3D data. First, an infinite-pixel image synthesis module generates arbitrary-scale 2D maps from the bird's-eye view. Next, an octree-based voxel completion module lifts the generated 2D map to 3D octrees. Finally, a voxel-based neural rendering module texturizes the voxels and renders 2D images. InfiniCity can thus synthesize arbitrary-scale and traversable 3D city environments, and allow flexible and interactive editing from users. We quantitatively and qualitatively demonstrate the efficacy of the proposed framework. Project page: https://hubert0527.github.io/infinicity

ATIVS: analytical tool for influenza virus surveillance

The WHO Global Influenza Surveillance Network has routinely performed genetic and antigenic analyses of human influenza viruses to monitor influenza activity. Although these analyses provide supporting data for the selection of vaccine strains, it seems desirable to have user-friendly tools to visualize the antigenic evolution of influenza viruses for the purpose of surveillance. To meet this need, we have developed a web server, ATIVS (Analytical Tool for Influenza Virus Surveillance), for analyzing serological data of all influenza viruses and hemagglutinin sequence data of human influenza A/H3N2 viruses so as to generate antigenic maps for influenza surveillance and vaccine strain selection. Functionalities are described and examples are provided to illustrate its usefulness and performance. The ATIVS web server is available at http://influenza.nhri.org.tw/ATIVS/

Type I IL-1 Receptor (IL-1RI) as Potential New Therapeutic Target for Bronchial Asthma

The IL-1R/TLR family has been receiving considerable attention as potential regulators of inflammation through their ability to act as either activators or suppressors of inflammation. Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness, allergic inflammation, elevated serum total, allergen-specific IgE levels, and increased Th2 cytokine production. The discovery that the IL-1RI–IL-1 and ST2–IL-33 pathways are crucial for allergic inflammation has raised interest in these receptors as potential targets for developing new therapeutic strategies for bronchial asthma. This paper discusses the current use of neutralizing mAb or soluble receptor constructs to deplete cytokines, the use of neutralizing mAb or recombinant receptor antagonists to block cytokine receptors, and gene therapy from experimental studies in asthma. Targeting IL-1RI–IL-1 as well as ST2–IL-33 pathways may promise a disease-modifying approach in the future

Composite type A thymoma and diffuse large B-cell lymphoma

AbstractThe concurrent occurrence of thymoma and diffuse large B-cell lymphoma in the thymus has not been previously reported. We describe a 74-year-old man who presented with general weakness, neck lymphadenopathy, night sweats, and body weight loss. A right anterior mediastinal mass was found on computed tomography of the chest. The immunohistochemical stains AE1/AE3, CD20, CD3, and MUM-1 confirmed the different components of the mediastinal tumor. A heavy-chain gene clonality assay and light-chain gene clonality assay confirmed the B-cell clonality of the mediastinal tumor and neck lymph node. The patient had received a complete course of chemotherapy, and the result of positron emission tomography–computed tomography showed complete remission. The pathologic report of this mass revealed composite type A thymoma and diffuse large B-cell lymphoma. If concurrent or composite thymoma and lymphoma are suspected, a thorough examination of the thymoma with a combination of ancillary studies is recommended to rule out the possibility of concurrent lymphoma

The Volcanic Earthquake Swarm of October 20, 2009 in the Tatun Area of Northern Taiwan

On October 20, 2009, a series of felt earthquakes with local magnitudes ranging from 2.8 - 3.2 occurred in the Tatun volcanic area off the northern tip of Taiwan. Although there was no damage caused by those earthquakes, many residents in the Taipei metropolitan area, particularly for people who live near the Yangminshan National Park, felt strong ground shaking. In order to know what the possible mechanisms were that generated those earthquakes, we carefully examined seismic data recorded by a dense seismic array in the Tatun volcanic area. During the period between October 18 and 22, 2009 we detected at least 202 micro-earthquakes. Most of the earthquakes were relocated using the double-difference method and were clustered in the shallow crust beneath the Dayoukeng area, which is the strongest fumarole in the Tatun volcanic area. Among these earthquakes, 72 focal mechanisms were determined by polarizing the first P-wave motion. Most earthquakes belonged to normal faulting. An extremely high b-value of 2.17 was obtained from those earthquakes. Based on the seismic variations in both the temporary and spatial distribution as well as an extremely high b-value, we conclude that the earthquake sequence on October 20, 2009 was a typically seismic swarm associated with possible active volcanism in the Tatun volcanic area

Knockdown of PsbO leads to induction of HydA and production of photobiological H2 in the green alga Chlorella sp. DT

Green algae are able to convert solar energy to H2 via the photosynthetic electron transport pathway under certain conditions. Algal hydrogenase (HydA, encoded by HYDA) is in charge of catalyzing the reaction: 2H+ + 2e− ↔ H2 but usually inhibited by O2, a byproduct of photosynthesis. The aim of this study was to knockdown PsbO (encoded by psbO), a subunit concerned with O2 evolution, so that it would lead to HydA induction. The alga, Chlorella sp. DT, was then transformed with short interference RNA antisense-psbO (siRNA-psbO) fragments. The algal mutants were selected by checking for the existence of siRNA-psbO fragments in their genomes and the low amount of PsbO proteins. The HYDA transcription and the HydA expression were observed in the PsbO-knockdown mutants. Under semi-aerobic condition, PsbO-knockdown mutants could photobiologically produce H2 which increased by as much as 10-fold in comparison to the wild type

Juvenile Dermatomyositis: A 20-year Retrospective Analysis of Treatment and Clinical Outcomes

BackgroundJuvenile dermatomyositis is a rare childhood multisystem autoimmune disease involving primarily the skin and muscles, and it may lead to long-term disability. This study aimed to describe the clinical course of juvenile dermatomyositis and determine if any early clinical or laboratory features could predict outcome.MethodsMedical charts of patients aged ≤18 years and diagnosed with juvenile dermatomyositis (according to the criteria of Bohan and Peter) at the Pediatric Department, National Taiwan University Hospital, between 1989 and 2009 were reviewed. The endpoints for disease assessment were complete clinical response and complete clinical remission. Cox's proportional hazards model was fitted to identify important predictors of complete clinical remission.ResultsA total of 39 patients with juvenile dermatomyositis were reviewed. Two-thirds were females, and the mean age at disease onset was 81.97 ± 46.63 months. The most common initial presentations were Gottron's papule (82.1%) and muscle weakness (82.1%). After excluding one patient with an incomplete record, the remaining 31 patients who had muscle weakness were analyzed; among them, 22 (70.97%) achieved complete clinical response, but only six (19.4%) achieved complete clinical remission. Multivariate analysis showed that female sex, negative Gowers' sign at disease onset, and positive photosensitivity at disease onset were favorable factors to achieve complete clinical remission. Moreover, covariate-adjusted survival curves were drawn for making predictions of complete clinical remission. Only 13 (33.33%) patients were symptom free at the end of follow up, whereas the other 26 suffered from different kinds of complications. None of them developed malignancy, but two (5.13%) patients died during the follow-up period.ConclusionFactors such as male sex and Gowers' sign were unlikely to favor the achievement of complete clinical remission in juvenile dermatomyositis. Certain complications cannot be avoided, and thus more effective treatments and monitoring strategies are needed for better control of juvenile dermatomyositis