Ethylene-mediated nitric oxide depletion pre-adapts plants to hypoxia stress

Timely perception of adverse environmental changes is critical for survival. Dynamic changes in gases are important cues for plants to sense environmental perturbations, such as submergence. In Arabidopsis thaliana, changes in oxygen and nitric oxide (NO) control the stability of ERFVII transcription factors. ERFVII proteolysis is regulated by the N-degron pathway and mediates adaptation to flooding-induced hypoxia. However, how plants detect and transduce early submergence signals remains elusive. Here we show that plants can rapidly detect submergence through passive ethylene entrapment and use this signal to pre-adapt to impending hypoxia. Ethylene can enhance ERFVII stability prior to hypoxia by increasing the NO-scavenger PHYTOGLOBIN1. This ethylene-mediated NO depletion and consequent ERFVII accumulation pre-adapts plants to survive subsequent hypoxia. Our results reveal the biological link between three gaseous signals for the regulation of flooding survival and identifies key regulatory targets for early stress perception that could be pivotal for developing flood-tolerant crops

Ethylene augments root hypoxia tolerance via growth cessation and reactive oxygen species amelioration

Flooded plants experience impaired gas diffusion underwater, leading to oxygen deprivation (hypoxia). The volatile plant hormone ethylene is rapidly trapped in submerged plant cells and is instrumental for enhanced hypoxia acclimation. However, the precise mechanisms underpinning ethylene-enhanced hypoxia survival remain unclear. We studied the effect of ethylene pre-treatment on hypoxia survival of Arabidopsis (Arabidopsis thaliana) primary root tips. Both hypoxia itself and re-oxygenation following hypoxia are highly damaging to root tip cells, and ethylene pre-treatments reduced this damage. Ethylene pre-treatment alone altered the abundance of transcripts and proteins involved in hypoxia responses, root growth, translation, and reactive oxygen species (ROS) homeostasis. Through imaging and manipulating ROS abundance in planta, we demonstrated that ethylene limited excessive ROS formation during hypoxia and subsequent re-oxygenation and improved oxidative stress survival in a PHYTOGLOBIN1-dependent manner. In addition, we showed that root growth cessation via ethylene and auxin occurred rapidly and that this quiescence behavior contributed to enhanced hypoxia tolerance. Collectively, our results show that the early flooding signal ethylene modulates a variety of processes that all contribute to hypoxia survival

Kleur bekennen?: Evaluatie van het Etnisch Cultureel Minderhedenbeleid

In februari 2005 heeft de Inspecteur Generaal der Krijgsmacht (IGK) van de Minister van Defensie (MinDef) het verzoek ontvangen om in 2005 in de vorm van een IGK-thema aandacht te besteden aan het onderwerp “Diversiteit in de krijgsmacht”. Diversiteit in het personeelsbestand van defensie komt tot uiting in verschillen in etniciteit, sekse, sociale klasse, leeftijd, seksuele geaardheid, rang, opleiding, religie etcetera. Met veel van deze verschillen, zoals opleiding en rang, zijn medewerkers binnen de defensieorganisatie in de loop der tijd vertrouwd geraakt. Op die aspecten is de diversiteit van het personeel dan ook nauwelijks meer structureel problematisch en zijn deze verschillen ingebed in de structuur en cultuur van de organisatie. Bij defensie geldt een dergelijke “vanzelfsprekendheid” nog niet ten aanzien van de verschillen op de aspecten gender, etniciteit en seksuele geaardheid, ook al zijn er in de afgelopen jaren reeds veranderingen en verbetering op dit gebied bereikt. Zo zijn, onder andere naar aanleiding van verzoeken van de Minister aan de IGK, in het recente verleden onderzoeken gedaan naar diversiteit op het gebied van seksuele geaardheid (Van Stoppelenberg en Veenstra, 1999), gender (IGK, 2002) en ongewenst gedrag in het algemeen (KPMG, 2004). Vooral op het gebeid van seksuele geaardheid en gender, hebben deze onderzoeken geleid tot concrete beleidsmaatregelen ter verbetering van de situatie van vrouwen en homoseksuelen binnen de defensieorganisatie. In het algemeen streeft defensie ernaar om een diversiteitbeleid te voeren, dat begint met de opname en acceptatie van vrouwen, etnisch culturele minderheden (ECM’n) en homoseksuelen en zich verder uitstrekt tot de kwaliteitsbenutting van alle diverse groepen binnen de defensieorganisatie. Maar is er binnen defensie in dezelfde periode ook aandacht besteed aan diversiteit met betrekking tot de etnisch culturele dimensie? De noodzaak voor defensie om hieraan aandacht te besteden vloeit voort uit actuele en toekomstige maatschappelijke ontwikkelingen en het streven van defensie om zoveel mogelijk een afspiegeling te zijn van de samenleving. In de eerste plaats zijn er ontwikkelingen die een verandering in het klimaat ten opzichte van ECM’n in Nederland hebben veroorzaakt, zoals de aanslag op het WTC in New York, de aanslagen in Madrid, London en op Bali en de moord op Theo van Gogh, en die een verhoogde aandacht voor de positie van deze groepen legitimeren binnen de defensieorganisatie (Olivas-Lujan, Harzing en McCoy, 2004; Richardson, Bosch en Moelker, 2006;). In de tweede plaats is er sprake van een explosieve groei van ECM’n in Nederland van vooral Turkse, Marokkaanse, Antilliaanse en Arubaanse afkomst (CBS, 2004). Dit zijn juist de groepen die voor de defensieorganisatie interessant zijn met het oog op het toekomstig arbeidspotentieel (Ministerie van Defensie, 2004). Toch blijkt tot nu toe dat vooral de werving van dat potentieel achter blijft bij de verwachtingen of zelfs terugloopt, ondanks doelgroepgerichte maatregelen als de Afkoopregeling Turkse Dienstplicht (Ministerie van Defensie, 2004; Richardson, Bosch en Moelker, verwacht in 2005). In de derde plaats is voor de taakuitoefening in het kader van vredesoperaties in NAVO- of VN verband etnisch culturele diversiteit in het eigen personeelsbestand van belang. Internationalisering en globalisering van dergelijke operaties hebben er immers toe bijgedragen dat personeel in hogere en lagere echelons van defensie steeds vaker in divers samengestelde teams moeten functioneren en intensief samenwerken met lokale bevolking en NGO's (Cockburn & Zarkov, 2002). Op basis van het bovenstaande en met het oog op toekomstige ontwikkelingen heeft de Minister van Defensie de IGK gevraagd in 2005 onderzoek te doen naar de beleidsontwikkelingen omtrent en de positie van ECM’n binnen de defensieorganisatie. In deze rapportage worden de resultaten van dit onderzoek beschreven. Allereerst wordt in hoofdstuk 2 aandacht besteed aan de onderzoeksopzet. Vervolgens worden de beleidsontwikkelingen op centraal niveau in de periode van 2000-2005 beschreven in hoofdstuk 3. In hoofdstuk 4 wordt de implementatie en uitvoering van dat centrale beleid bij de verschillende defensieonderdelen beschreven. Hoofdstuk 5 is volledig gewijd aan de resultaten van het onderzoek naar het actueel diversiteitsklimaat binnen de defensieorganisatie. Hoofdstuk 6 bevat een discussie over de resultaten en hoofdstuk 7 de conclusies van het onderzoek. De conclusies van dit onderzoek zijn in het jaarverslag van de IGK omgezet in een aantal aanbevelingen voor toekomstig beleid over ECM’n binnen defensie

Retrograde intramedullary nailing for humeral midshaft fractures: a retrospective cohort study

Aim: This study evaluates the patient-reported functional outcome, clinical functional outcome and frequency of complications of simple oblique and transverse humeral midshaft fractures treated with a retrograde expert humeral nail.Methods: A retrospective cohort study of humeral midshaft fractures (AO 12-A2, 12-A3) treated with retrograde nailing between January 2010 and February 2018 in a level II trauma center was performed. Patients’ perception of functional outcome was measured using the Disabilities of the Arm, Shoulder and Hand (DASH) scores.Results: Thirteen patients with a median age of 20-years were treated with a retrograde nail. The median DASH score, administered 29 months (IQR 74) after surgery, was 7.9 (IQR 15.9). There were no perioperative fractures and the frequency of complications was 8%, being one nonunion.Conclusions: Retrograde nailing for humeral midshaft fractures is a safe technique, with excellent patient reported and clinical functional outcome. No iatrogenic perioperative fractures occurred, and had a low complication frequency. We recommend the retrograde technique, if surgical fixation of humeral midshaft fractures is needed, especially in younger patients for who rotator cuff associated injuries will have a major impact on quality of life

Tuning surface charges of peptide nanofibers for induction of antigen-specific immune tolerance: an introductory study

Induction of antigen-specific immune tolerance has emerged as the next frontier in treating autoimmune disorders, including atherosclerosis and graft-vs-host reactions during transplantation. Nanostructures are under investigation as a platform for the coordinated delivery of critical components, i.e., the antigen epitope combined with tolerogenic agents, to the target immune cells and subsequently induce tolerance. In the present study, the utility of supramolecular peptide nanofibers to induce antigen-specific immune tolerance was explored. To study the influence of surface charges of the nanofibers towards the extent of the induced immune response, the flanking charge residues at both ends of the amphipathic fibrillization peptide sequences were varied. Dexamethasone, an immunosuppressive glucocorticoid drug, and the ovalbumin-derived OVA323-339 peptide that binds to I-A(d) MHC Class II were covalently linked at either end of the peptide sequences. It was shown that the functional extensions did not alter the structural integrity of the supramolecular nanofibers. Furthermore, the surface charges of the nanofibers were modulated by the inclusion of charged residues. Dendritic cell culture assays suggested that nanofiber of less negative ζ-potential can augment the antigen-specific tolerogenic response. Our findings illustrate a molecular approach to calibrate the tolerogenic response induced by peptide nanofibers, which pave the way for better design of future tolerogenic immunotherapies

Tuning surface charges of peptide nanofibers for induction of antigen-specific immune tolerance: an introductory study

Induction of antigen-specific immune tolerance has emerged as the next frontier in treating autoimmune disorders, including atherosclerosis and graft-vs-host reactions during transplantation. Nanostructures are under investigation as a platform for the coordinated delivery of critical components, i.e., the antigen epitope combined with tolerogenic agents, to the target immune cells and subsequently induce tolerance. In the present study, the utility of supramolecular peptide nanofibers to induce antigen-specific immune tolerance was explored. To study the influence of surface charges of the nanofibers towards the extent of the induced immune response, the flanking charge residues at both ends of the amphipathic fibrillization peptide sequences were varied. Dexamethasone, an immunosuppressive glucocorticoid drug, and the ovalbumin-derived OVA323-339 peptide that binds to I-A(d) MHC Class II were covalently linked at either end of the peptide sequences. It was shown that the functional extensions did not alter the structural integrity of the supramolecular nanofibers. Furthermore, the surface charges of the nanofibers were modulated by the inclusion of charged residues. Dendritic cell culture assays suggested that nanofiber of less negative ζ-potential can augment the antigen-specific tolerogenic response. Our findings illustrate a molecular approach to calibrate the tolerogenic response induced by peptide nanofibers, which pave the way for better design of future tolerogenic immunotherapies

Benchmarking daily adaptation using fully automated radiotherapy treatment plan optimization for rectal cancer

Background/purpose: In daily plan adaptation the radiotherapy treatment plan is adjusted just prior to delivery. A simple approach is taking the planning objectives of the reference plan and directly applying these in re-optimization. Here we present a tested method to verify whether daily adaptation without tweaking of the objectives can maintain the plan quality throughout treatment. Materials/methods: For fifteen rectal cancer patients, automated treatment planning was used to generate plans mimicking manual reference plans on the planning scans. For 74 fraction scans (4–5 per patient) an automated plan and a daily adapted plan were generated, where the latter re-optimizes the reference plan objectives without any tweaking. To evaluate the robustness of the daily adaptation, the adapted plans were compared to the autoplanning plans. Results: Median differences between the autoplanning plans on the planning scans and the reference plans were between −1 and 0.2 Gy. The largest interquartile range (1 Gy) was seen for the Lumbar Skin D2%. For the daily scans the PTV D2% and D98% differences between autoplanning and adapted plans were within ±0.7 Gy, with mean differences within ±0.3 Gy. Positive differences indicate higher values were obtained using autoplanning. For the Bowelarea + Bladder and the Lumbar Skin the D2% and Dmean differences were all within ±2.6 Gy, with mean differences between −0.9 and 0.1 Gy. Conclusion: Automated treatment planning can be used to benchmark daily adaptation techniques. The investigated adaptation workflow can robustly perform high quality adaptations without daily adjusting of the patient-specific planning objectives for rectal cancer radiotherapy

A life-history allele of large effect shortens developmental time in a wild insect population

Developmental time is a key life-history trait with large effects on Darwinian fitness. In many insects, developmental time is currently under strong selection to minimize ecological mismatches in seasonal timing induced by climate change. The genetic basis of responses to such selection, however, is poorly understood. To address this problem, we set up a long-term evolve-and-resequence experiment in the beetle Tribolium castaneum and selected replicate, outbred populations for fast or slow embryonic development. The response to this selection was substantial and embryonic developmental timing of the selection lines started to diverge during dorsal closure. Pooled whole-genome resequencing, gene expression analysis and an RNAi screen pinpoint a 222 bp deletion containing binding sites for Broad and Tramtrack upstream of the ecdysone degrading enzyme Cyp18a1 as a main target of selection. Using CRISPR/Cas9 to reconstruct this allele in the homogenous genetic background of a laboratory strain, we unravel how this single deletion advances the embryonic ecdysone peak inducing dorsal closure and show that this allele accelerates larval development but causes a trade-off with fecundity. Our study uncovers a life-history allele of large effect and reveals the evolvability of developmental time in a natural insect population.</p

A life-history allele of large effect shortens developmental time in a wild insect population

Developmental time is a key life-history trait with large effects on Darwinian fitness. In many insects, developmental time is currently under strong selection to minimize ecological mismatches in seasonal timing induced by climate change. The genetic basis of responses to such selection, however, is poorly understood. To address this problem, we set up a long-term evolve-and-resequence experiment in the beetle Tribolium castaneum and selected replicate, outbred populations for fast or slow embryonic development. The response to this selection was substantial and embryonic developmental timing of the selection lines started to diverge during dorsal closure. Pooled whole-genome resequencing, gene expression analysis and an RNAi screen pinpoint a 222 bp deletion containing binding sites for Broad and Tramtrack upstream of the ecdysone degrading enzyme Cyp18a1 as a main target of selection. Using CRISPR/Cas9 to reconstruct this allele in the homogenous genetic background of a laboratory strain, we unravel how this single deletion advances the embryonic ecdysone peak inducing dorsal closure and show that this allele accelerates larval development but causes a trade-off with fecundity. Our study uncovers a life-history allele of large effect and reveals the evolvability of developmental time in a natural insect population.</p

Tuning surface charges of peptide nanofibers for induction of antigen-specific immune tolerance: an introductory study

Induction of antigen-specific immune tolerance has emerged as the next frontier in treating autoimmune disorders, including atherosclerosis and graft-vs-host reactions during transplantation. Nanostructures are under investigation as a platform for the coordinated delivery of critical components, i.e., the antigen epitope combined with tolerogenic agents, to the target immune cells and subsequently induce tolerance. In the present study, the utility of supramolecular peptide nanofibers to induce antigen-specific immune tolerance was explored. To study the influence of surface charges of the nanofibers towards the extent of the induced immune response, the flanking charge residues at both ends of the amphipathic fibrillization peptide sequences were varied. Dexamethasone, an immunosuppressive glucocorticoid drug, and the ovalbumin-derived OVA323-339 peptide that binds to I-A(d) MHC Class II were covalently linked at either end of the peptide sequences. It was shown that the functional extensions did not alter the structural integrity of the supramolecular nanofibers. Furthermore, the surface charges of the nanofibers were modulated by the inclusion of charged residues. Dendritic cell culture assays suggested that nanofiber of less negative ζ-potential can augment the antigen-specific tolerogenic response. Our findings illustrate a molecular approach to calibrate the tolerogenic response induced by peptide nanofibers, which pave the way for better design of future tolerogenic immunotherapies