Ube2j2 ubiquitinates hydroxylated amino acids on ER-associated degradation substrates

An E2–E3 complex can ubiquitinate substrates via either an isopeptide bond (to a lysine) or an ester bond (to a serine or threonine) and preferentially uses the latter to induce ERAD

De invloed van orthografie op verleden tijdsvorming door zwakke lezers

In dit onderzoek werden morfofonologische vaardigheden van normale en zwakke lezers vergeleken. Specifiek werd de invloed van orthografie op de vervoeging van de verleden tijd bekeken bij 8- tot 11-jarige normale en zwakke lezers. Deze groepen lezers kregen bestaande werkwoorden en pseudo-werkwoorden gepresenteerd in de infiniefvorm (bijvoorbeeld blaffen of taven), waarna hen gevraagd werd de verleden tijdsvorm te produceren. Er is onderzocht of kinderen de juiste vorm van het suffix (-te of -de) selecteerden, op basis van de stemhebbendheid van de mediale obstruent. Ook is onderzocht of kinderen gevoelig waren voor de relatie tussen klinkerlengte en stemhebbendheid in het Nederlands, door pseudo-woorden aan te bieden die verschillen in de mate waarin ze het Nederlandse patroon volgen. Tot slot werd bekeken of auditieve presentatie van de werkwoorden mét het bijbehorende schriftbeeld (waarbij dus ook letters als ‘f’ of ‘v’ zichtbaar waren) leidde tot meer correcte verleden tijdsvormen dan alleen auditieve presentatie van de werkwoorden. De resultaten laten geen verschillen zien tussen de normale en zwakke lezers in het aantal correct vervoegde werkwoorden. Beide groepen zijn beter in staat correcte verleden tijden te maken van bestaande dan van pseudo-werkwoorden. Daarnaast zijn beide groepen gevoelig voor subtiele fonotactische patronen: kinderen maken meer correcte verleden tijdsvormen als de pseudo-werkwoorden het Nederlandse patroon volgen. Ook maakten beide groepen meer fouten met stemloze dan stemhebbende mediale obstruenten (zoals in blaffen - *blafde). De normale lezers presteerden echter beter in de vervoeging van bestaande werkwoorden wanneer het schriftbeeld werd toegevoegd, in tegenstelling tot de zwakke lezers die hier niet van profiteerden. Deze resultaten laten zien dat de (morfo-)fonologie van de zwakke lezers (op deze leeftijd en taak) niet verschilt van de normale lezers, maar dat ze minder gebruik kunnen maken van de orthografie. Dit wijst erop dat niet de fonologische verwerving als zodanig aangetast is bij slechte lezers in deze leeftijdsgroep, maar dat de integratie tussen (morfo-)fonologie en orthografie anders verloopt

Optimized Longitudinal Monitoring of Stem Cell Grafts in Mouse Brain Using a Novel Bioluminescent/Near Infrared Fluorescent Fusion Reporter

Biodistribution and fate of transplanted stem cells via longitudinal monitoring has been successfully achieved in the last decade using optical imaging

Whose national emergency? Caboolture and Kirribili? or Milikapiti and Mutitjulu?

Keynote Address - Ms Marion Scrymgour MLA Member for Arafura, Northern Territory Government. Other Speakers - Professor Gavin Brown AO FAA, Vice-Chancellor and Principal, University of Sydney; Mr Neville Perkins OAM, Master of Ceremonies; Mr Charles Madden, Welcome to country; Ms Michelle Blanchard, Acting Director, Koori Centre; Mr Nicholas Beeton, Ms Kerry Wallace-Massone, Ms Jade Swan Prize winners, Dr Charles Perkins AO Annual Memorial Prize

Off-Label Prescription of Genetically Modified Organism Medicines in Europe:Emerging Conflicts of Interest?

Recently, the first human medicine containing a genetically modified organism (GMO medicine) was authorized for use in the European market. Just as any medicinal product, the market authorization for a GMO medicine contains a precise description of the therapeutic use for which the medicinal product is intended. Within this use, the application of the GMO medicine is permitted, without the need for the institution to obtain a specific permit. In practice, however, medicinal products are also frequently prescribed for treatment outside the registered therapeutic use, a practice that is referred to as "off-label use." While off-label use of conventional medicines is permitted and has been very useful, the off-label use of GMO medicines is not covered in the European Union (EU) legislation or guidelines and falls under each member state's national environmental legislation. This implies that in the Netherlands and most other EU member states, an environmental permit will be required for any institution that uses the GMO medicine outside the registered application(s). In the Netherlands, this permit is identical to the permits required for the execution of clinical trials involving nonregistered GMOs. The application procedure for such permit is time-consuming. This process can therefore limit the therapeutic options for medical professionals. As a consequence, desired treatment regimens could be withheld for certain patient (groups). To make future off-label use of GMO medicines permissible in a way that is acceptable for all stakeholders, regulators should adopt a proactive attitude and formulate transparent legislative procedures for this. Only then the field can maintain the public acceptance of GMO medicines, while maintaining the freedom to operate of medical professionals

Conversion of Mature Human β-Cells Into Glucagon-Producing α-Cells

Conversion of one terminally differentiated cell type into another (or transdifferentiation) usually requires the forced expression of key transcription factors. We examined the plasticity of human insulin-producing β-cells in a model of islet cell aggregate formation. Here, we show that primary human β-cells can undergo a conversion into glucagon-producing α-cells without introduction of any genetic modification. The process occurs within days as revealed by lentivirus-mediated β-cell lineage tracing. Converted cells are indistinguishable from native α-cells based on ultrastructural morphology and maintain their α-cell phenotype after transplantation in vivo. Transition of β-cells into α-cells occurs after β-cell degranulation and is characterized by the presence of β-cell–specific transcription factors Pdx1 and Nkx6.1 in glucagon+ cells. Finally, we show that lentivirus-mediated knockdown of Arx, a determinant of the α-cell lineage, inhibits the conversion. Our findings reveal an unknown plasticity of human adult endocrine cells that can be modulated. This endocrine cell plasticity could have implications for islet development, (patho)physiology, and regeneration

Synthesis and in vitro evaluation of a multifunctional and surface-switchable nanoemulsion platform

We present a multifunctional nanoparticle platform that has targeting moieties shielded by a matrix metalloproteinase-2 (MMP2) cleavable PEG coating. Upon incubation with MMP2 this surface-switchable coating is removed and the targeting ligands become available for binding. The concept was evaluated in vitro using biotin and αvβ3-integrin-specific RGD-peptide functionalized nanoparticles.National Heart, Lung, and Blood InstituteNational Institutes of Health (U.S.) (Program of Excellence in Nanotechnology (PEN) Award Contract HHSN268201000045C