Three-dimensional aromaticity in an antiaromatic cyclophane

Understanding of interactions among molecules is essential to elucidate the binding of pharmaceuticals on receptors, the mechanism of protein folding and self-assembling of organic molecules. While interactions between two aromatic molecules have been examined extensively, little is known about the interactions between two antiaromatic molecules. Theoretical investigations have predicted that antiaromatic molecules should be stabilized when they stack with each other by attractive intermolecular interactions. Here, we report the synthesis of a cyclophane, in which two antiaromatic porphyrin moieties adopt a stacked face-to-face geometry with a distance shorter than the sum of the van der Waals radii of the atoms involved. The aromaticity in this cyclophane has been examined experimentally and theoretically. This cyclophane exhibits three-dimensional spatial current channels between the two subunits, which corroborates the existence of attractive interactions between two antiaromatic π-systems

Medical Safety and Device Reliability of Active Transcutaneous Middle Ear and Bone Conducting Implants: A Long-Term Multi-Centre Observational Study

Active bone-conducting hearing devices (aBCHD; e.g., MEDEL Bonebridge® (BB)) and active middle ear implants (aMEI; e.g., MEDEL Vibrant Soundbridge® (VSB)) use radio frequency transmission to send information from an external microphone and sound processor to an internally implanted transducer. These devices potentially have an advantage over devices with percutaneous links because the skin is closed over the implantable components, which should reduce the risk of skin problems and infection. On the other hand, surgical procedures are more complex, with a greater risk of damage due to surgery. The objectives of this research were to quantify the reliability and long-term survival of MEDEL VSB and BB devices, determine the adverse and serious adverse device-related complications, and consider associated causes. A multi-center observational retrospective and prospective study was conducted at eleven auditory implant centers in the United Kingdom. Data was collected using a surgical questionnaire and audiological reports. Data were obtained from patient notes or from prospective cases that had a minimum follow-up of one year post-implant. Consecutive patient records were reviewed. Datasets from 109 BB and 163 VSB were reviewed. Of these, 205 were retrospective case note reviews, and 67 were prospective cases. The mean follow-up was 4 and 6 years, respectively, for BB and VSB. Kaplan–Meier Survival analyses indicated that the BB survival was 97% and 93.3% at 1 and 5 years, respectively, and the VSB was 92.1% and 87% at the same time points. This is a large cohort study for the field and has indicated that BB and VSB are safe interventions. Care should be taken to monitor magnet strength in the first few months. For the majority of device-related effects, there was no apparent association with etiology. However, an interesting pattern emerged for individuals who exhibited an inflammatory response, e.g., adhesions or device extrusion, and those with a history of chronic suppurative otitis media. This should be considered in future work and is not surprising given that many VSB recipients have a complicated hearing history, often associated with otitis media

Unraveling the stepwise maturation of the yeast telomerase including a Cse1 and Mtr10 mediated quality control checkpoint

Telomerases elongate the ends of chromosomes required for cell immortality through their reverse transcriptase activity. By using the model organism Saccharomyces cerevisiae we defined the order in which the holoenzyme matures. First, a longer precursor of the telomerase RNA, TLC1 is transcribed and exported into the cytoplasm, where it associates with the protecting Sm-ring, the Est and the Pop proteins. This partly matured telomerase is re-imported into the nucleus via Mtr10 and a novel TLC1 -import factor, the karyopherin Cse1. Remarkably, while mutations in all known transport factors result in short telomere ends, mutation in CSE1 leads to the amplification of Y′ elements in the terminal chromosome regions and thus elongated telomere ends. Cse1 does not only support TLC1 import, but also the Sm-ring stabilization on the RNA enableling Mtr10 contact and nuclear import. Thus, Sm-ring formation and import factor contact resembles a quality control step in the maturation process of the telomerase. The re-imported immature TLC1 is finally trimmed into the 1158 nucleotides long mature form via the nuclear exosome. TMG-capping of TLC1 finalizes maturation, leading to mature telomerase.Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659Georg-August-Universität Göttingen (1018

dsRNA formation leads to preferential nuclear export and gene expression

Abstract When mRNAs have been transcribed and processed in the nucleus, they are exported to the cytoplasm for translation. This export is mediated by the export receptor heterodimer Mex67–Mtr2 in the yeast Saccharomyces cerevisiae (TAP–p15 in humans) 1,2 . Interestingly, many long non-coding RNAs (lncRNAs) also leave the nucleus but it is currently unclear why they move to the cytoplasm 3 . Here we show that antisense RNAs (asRNAs) accelerate mRNA export by annealing with their sense counterparts through the helicase Dbp2. These double-stranded RNAs (dsRNAs) dominate export compared with single-stranded RNAs (ssRNAs) because they have a higher capacity and affinity for the export receptor Mex67. In this way, asRNAs boost gene expression, which is beneficial for cells. This is particularly important when the expression program changes. Consequently, the degradation of dsRNA, or the prevention of its formation, is toxic for cells. This mechanism illuminates the general cellular occurrence of asRNAs and explains their nuclear export

When to use broader internalising and externalising subscales instead of the hypothesised five subscales on the Strengths and Difficulties Questionnaire (SDQ): data from British parents, teachers and children.

The Strengths and Difficulties Questionnaire (SDQ) is a widely used child mental health questionnaire with five hypothesised subscales. There is theoretical and preliminary empirical support for combining the SDQ's hypothesised emotional and peer subscales into an 'internalizing' subscale and the hypothesised behavioral and hyperactivity subscales into an 'externalizing' subscale (alongside the fifth prosocial subscale). We examine this using parent, teacher and youth SDQ data from a representative sample of 5-16 year olds in Britain (N = 18,222). Factor analyses generally supported second-order internalizing and externalizing factors, and the internalizing and externalizing subscales showed good convergent and discriminant validity across informants and with respect to clinical disorder. By contrast, discriminant validity was poorer between the emotional and peer subscales and between the behavioral, hyperactivity and prosocial subscales. This applied particularly to children with low scores on those subscales. We conclude that there are advantages to using the broader internalizing and externalizing SDQ subscales for analyses in low-risk samples, while retaining all five subscales when screening for disorder