124-Color Super-resolution Imaging by Engineering DNA-PAINT Blinking Kinetics

Optical super-resolution techniques reach unprecedented spatial resolution down to a few nanometers. However, efficient multiplexing strategies for the simultaneous detection of hundreds of molecular species are still elusive. Here, we introduce an entirely new approach to multiplexed super-resolution microscopy by designing the blinking behavior of targets with engineered binding frequency and duration in DNA-PAINT. We assay this kinetic barcoding approach in silico and in vitro using DNA origami structures, show the applicability for multiplexed RNA and protein detection in cells, and finally experimentally demonstrate 124-plex super-resolution imaging within minutes.We thank Martin Spitaler and the imaging facility of the MPI of Biochemistry for confocal imaging support

Die sinodale verband van die Nederduitse Gereformeerde Kerk in die Vrystaat: enkele tendense by die ontstaan daarvan in 1864-1865

In the Reformed tradition the basic documents of a church, apart from the Bible on which it should be based, are its confessions of faith and its church order. These documents show tendencies which indicate the orientation point and belief of such a church. If one investigates the way in which the Dutch Reformed Church in the Free State approached its confessions and church order at the church conference in 1864 where it was founded, and at its first Synod in 1865, three points emerge. Firstly this Synod was historically close to the Dutch Reformed Church in the Cape; secondly it was Reformed in its government, but mixed it with elements of collegialism; and thirdly it was focused on the Orange Free State, the country in which it originated. Elements of the same approach can still be seen in this synod today. It still wants to be Reformed; it still has a stability and tendency not to be radical — it very often stays in calm waters — and it can be convinced of the merit of an issue if it can be shown that it corresponds to the Scriptures and the confessions. Apart from that, there are indications that it clearly sees itself as a synod in the Free State Province.Acta Theologica Vol. 1 2007: pp. 121-13

Condensation cyclization reactions of electron deficient aromatics. 4: Tricyclic nitropropene nitronates from the reaction of phloroglucinol and cycloalkanones with sym-trinitrobenzene

Interesting similarities have been shown between the reactions of sym-trinitrobenzene with cycloalkanones, and with phloroglucinol. Previously unsuspected common intermediates have been shown to intervene. The structurally similar products in each case are tricyclic nitropropene nitronates. Protonation of these yields the corresponding nitronic acids in certain instances

Molecular Basis for poly(A) RNP Architecture and Recognition by the Pan2-Pan3 Deadenylase

The stability of eukaryotic mRNAs is dependent on a ribonucleoprotein (RNP) complex of poly(A)-binding proteins (PABPC1/Pab1) organized on the poly(A) tail. This poly(A) RNP not only protects mRNAs from premature degradation but also stimulates the Pan2-Pan3 deadenylase complex to catalyze the first step of poly(A) tail shortening. We reconstituted this process in vitro using recombinant proteins and show that Pan2-Pan3 associates with and degrades poly(A) RNPs containing two or more Pab1 molecules. The cryo-EM structure of Pan2-Pan3 in complex with a poly(A) RNP composed of 90 adenosines and three Pab1 protomers shows how the oligomerization interfaces of Pab1 are recognized by conserved features of the deadenylase and thread the poly(A) RNA substrate into the nuclease active site. The structure reveals the basis for the periodic repeating architecture at the 3' end of cytoplasmic mRNAs. This illustrates mechanistically how RNA-bound Pab1 oligomers act as rulers for poly(A) tail length over the mRNAs' lifetime.We would like to thank ... the MPIB cryo-EM, and core facilities ..

Advanced superconducting magnets investigation

Mathematical models for steady state behavior of composite superconductors and experimental verification using magnet coi

Identification of depression in a rural general practice

Major depression is underdiagnosed by general practitioners, but the reasons for this are not clear. This study aimed to establish the prevalence of major depression and coexisting generalised anxiety disorder in a rural general practice in the Orange Free State. It also assessed the predictive value of a screening questionnaire for use by general practitioners. The two practitioners evaluated 858 patients over a 4-week period. Those who met the screening criteria, together with a random sample of 60 patients who did not, were re-evaluated by a registrar in psychiatry who was unaware of the findings of his colleagues. Of the patients studied, 134 (15,6%) had major depression; 59 of these (44,0%) also had coexisting generalised anxiety disorder. The general practitioners had . correctly diagnosed major depression in 32 patients (3,7%) before the study started. The screening questionnaire had a 42% chance of correctly identifying a patient with depression and a 97% chance of correctly identifying a patient who did not have major depression. Both practitioners were equally capable at identifying major depression. The study confirmed both the high prevalence of depression in a rural general practice and its low identification rate. It also showed the advantage of using a screening questionnaire to alert practitioners to the possibility of depression in their patients