We report a method to detect label-free oligonucleotide targets. The conformation of surface-tethered probe nucleic acids is modulated by alternating electric fields, which cause the molecules to extend away from or fold onto the biased surface. Binding (hybridization) of targets to the single-stranded probes results in a pronounced enhancement of the layer-height modulation amplitude, monitored optically in real time. The method features an exceptional detection limit of <3 ؋ 10 8 bound targets per cm 2 sensor area. Single base-pair mismatches in the sequences of DNA complements may readily be identified; moreover, binding kinetics and binding affinities can be determined with high accuracy. When driving the DNA to oscillate at frequencies in the kHz regime, distinct switching kinetics are revealed for single-and double-stranded DNA. Molecular dynamics are used to identify the binding state of molecules according to their characteristic kinetic fingerprints by using a chip-compatible detection format.fluorescence ͉ sensor ͉ SNP ͉ affinity ͉ energy transfer
Evidence is mounting that the novel corona virus SARS-CoV2 inflicts neurological symptoms in a subgroup of COVID-19 patients. While plenty of theories on the route of neuroinvasion have been proposed, little histological evidence has been presented supporting any of these hypotheses. Therefore, we carried out immunostainings for ACE2 and TMPRSS2, two proteinases crucial for the entry of SARS-CoV2 into host cells, in the human enteric nervous system (ENS), as well as in the choroid plexus of the lateral ventricles. Both of these sites are important, yet often neglected entry gates to the nervous system. We found that ACE2 and TMPRSS2 are expressed by enteric neurons and glial cells of the small and large intestine, as well as choroid plexus epithelial cells, indicating that these cells meet the molecular requirements for viral entry. Together, our results are fundamental histological evidence substantiating current theories of neuroinvasion by SARS-CoV2.
There is no standard in hematopoietic stem cell transplantations (HSCT) for pre-transplant screening of psychosocial risk factors, e.g., regarding immunosuppressant non-adherence. The aim of this prospective study is to explore the predictive value of the pretransplant psychosocial screening instrument Transplant Evaluation Rating Scale (TERS) for mortality in a 3-year follow-up. Between 2012 and 2017 61 patients were included and classified as low (TERS = 26.5–29) and increased-risk group (TERS = 29.5–79.5). Both groups were compared regarding mortality until 36 months after transplantation and secondary outcomes [Medication Experience Scale for Immunosuppressants (MESI); incidence/grade of GvHD]. The increased-risk group (n = 28) showed significantly worse cumulative survival in the outpatient setting (from 3 months to 3 years after HSCT) [Log Rank (Mantel Cox) P = 0.029] compared to low-risk group (n = 29) but there was no significant result for the interval immediately after HSCT until 3 years afterwards. Pre-transplant screening with TERS contributes to prediction of survival after HSCT. The reason remains unclear, since TERS did not correlate with GvHD or MESI. The negative result regarding the interval immediately after HSCT until 3 years could be caused by the intensive in-patient setting with mortality which is explained rather by biological reasons than by non-adherence.
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