In Vitro Analysis of the Thyroid Hormone Receptor in Mitochondrial Transcription

The central dogma theory relates how DNA is transcribed into messenger RNA (mRNAs) and then translated into proteins. Since the nucleus contains the majority of the DNA in cells, research related to transcription and translation focuses on these processes within the nucleus and cytosol; however, these processes are also taking place within the mitochondrial organelle. Mitochondria are most widely known for their essential role in producing energy for the cell, but the organelle also contains its own small, circular genome. Transcription of mitochondrial DNA (mtDNA) follows similar mechanisms as does transcription of nuclear DNA. During this essential process, specific mitochondrial transcription factors, such as TFAM and TFB2M, regulate the attachment of the mitochondrial RNA polymerase (POLRMT) to the promoter and initiation of transcription. With a fully functioning mitochondrial RNA polymerase, transcription is properly conducted, and transcripts can be translated to protein by the mitochondrial ribosome. Mitochondrial transcription is a major regulatory process within the organelle, and determining transcription factors involved in this control point is important for understanding mitochondrial function and many diseases relating to mitochondrial dysfunction. Numerous transcription factors are found both in the nucleus as well as in the mitochondria where their function is not well understood. One such transcription factor is the thyroid hormone receptor. Previous research suggests that when the hormone triiodothyronine (T3) is present and taken up in cells, mitochondrial transcription increases. The mechanism behind the T3 stimulation of transcription is thought to be a coordinated effect by interacting with both the mitochondrial and nuclear thyroid hormone receptor. Our aim is to analyze the level of interaction that the mitochondrial thyroid hormone receptor (mt-TRalpha1) has with the mitochondrial DNA and other core mitochondrial transcription factors in the presence and absence of the T3 hormone. With this information, we further understand another component of mitochondrial transcription that could have implications in mitochondrial dysfunction and disease

Non-immortalized human tenocyte cultures as a vehicle for understanding cellular aspects to tendinopathy

The biochemical mechanisms underlying tendinopathy are obscure. We briefly describe preliminary observations of human tenocyte behaviour in culture as a vehicle for determining the role of reactive oxygen in tendon patholog

Unconventional Josephson Effect in Hybrid Superconductor-Topological Insulator Devices

We report on transport properties of Josephson junctions in hybrid superconducting-topological insulator devices, which show two striking departures from the common Josephson junction behavior: a characteristic energy that scales inversely with the width of the junction, and a low characteristic magnetic field for suppressing supercurrent. To explain these effects, we propose a phenomenological model which expands on the existing theory for topological insulator Josephson junctions

Pet191 Is a Cytochrome c Oxidase Assembly Factor in \u3ci\u3eSaccharomyces cerevisiae\u3c/i\u3e

The twin-Cx9C motif protein Pet191 is essential for cytochrome c oxidase maturation. The motif Cys residues are functionally important and appear to be present in disulfide linkages within a large oligomeric complex associated with the mitochondrial inner membrane. The import of Pet191 differs from that of other twin-Cx9C motif class of proteins in being independent of the Mia40 pathway

Three-dimensional dental microwear in type-Maastrichtian mosasaur teeth (Reptilia, Squamata)

Mosasaurs (Squamata, Mosasauridae) were large aquatic reptiles from the Late Cretaceous that filled a range of ecological niches within marine ecosystems. The type-Maastrichtian strata (68–66 Ma) of the Netherlands and Belgium preserve remains of five species that seemed to have performed different ecological roles (carnivores, piscivores, durophages). However, many interpretations of mosasaur diet and niche partitioning are based on qualitative types of evidence that are difficult to test explicitly. Here, we apply three-dimensional dental microwear texture analysis (DMTA) to provide quantitative dietary constraints for type-Maastrichtian mosasaurs, and to assess levels of niche partitioning between taxa. DMTA indicates that these mosasaurs did not exhibit neatly defined diets or strict dietary partitioning. Instead, we identify three broad groups: (i) mosasaurs Carinodens belgicus and Plioplatecarpus marshi plotting in the space of modern reptiles that are predominantly piscivorous and/or consume harder invertebrate prey, (ii) Prognathodon saturator and Prognathodon sectorius overlapping with extant reptiles that consume larger amounts of softer invertebrate prey items, and (iii) Mosasaurus hoffmanni spanning a larger plot area in terms of dietary constraints. The clear divide between the aforementioned first two groups in texture-dietary space indicates that, despite our small sample sizes, this method shows the potential of DMTA to test hypotheses and provide quantitative constraints on mosasaur diets and ecological roles

Interplay of chiral and helical states in a Quantum Spin Hall Insulator lateral junction

We study the electronic transport across an electrostatically-gated lateral junction in a HgTe quantum well, a canonical 2D topological insulator, with and without applied magnetic field. We control carrier density inside and outside a junction region independently and hence tune the number and nature of 1D edge modes propagating in each of those regions. Outside the 2D gap, magnetic field drives the system to the quantum Hall regime, and chiral states propagate at the edge. In this regime, we observe fractional plateaus which reflect the equilibration between 1D chiral modes across the junction. As carrier density approaches zero in the central region and at moderate fields, we observe oscillations in resistance that we attribute to Fabry-Perot interference in the helical states, enabled by the broken time reversal symmetry. At higher fields, those oscillations disappear, in agreement with the expected absence of helical states when band inversion is lifted.Comment: 5 pages, 4 figures, supp. ma

Developing and assessing a new web-based tapping test for measuring distal movement in Parkinson's disease: a Distal Finger Tapping test

Disability in Parkinson's disease (PD) is measured by standardised scales including the MDS-UPDRS, which are subject to high inter and intra-rater variability and fail to capture subtle motor impairment. The BRadykinesia Akinesia INcoordination (BRAIN) test is a validated keyboard tapping test, evaluating proximal upper-limb motor impairment. Here, a new Distal Finger Tapping (DFT) test was developed to assess distal upper-limb function. Kinetic parameters of the test include kinesia score (KS20, key taps over 20 s), akinesia time (AT20, mean dwell-time on each key) and incoordination score (IS20, variance of travelling time between key taps). To develop and evaluate a new keyboard-tapping test for objective and remote distal motor function in PD patients. The DFT and BRAIN tests were assessed in 55 PD patients and 65 controls. Test scores were compared between groups and correlated with the MDS-UPDRS-III finger tapping sub-scores. Nine additional PD patients were recruited for monitoring motor fluctuations. All three parameters discriminated effectively between PD patients and controls, with KS20 performing best, yielding 79% sensitivity for 85% specificity; area under the receiver operating characteristic curve (AUC) = 0.90. A combination of DFT and BRAIN tests improved discrimination (AUC = 0.95). Among three parameters, KS20 showed a moderate correlation with the MDS-UPDRS finger-tapping sub-score (Pearson's r = - 0.40, p = 0.002). Further, the DFT test detected subtle changes in motor fluctuation states which were not reflected clearly by the MDS-UPDRS-III finger tapping sub-scores. The DFT test is an online tool for assessing distal movements in PD, with future scope for longitudinal monitoring of motor complications