The RNA Polymerase II Core Promoter in Drosophila.

Transcription by RNA polymerase II initiates at the core promoter, which is sometimes referred to as the "gateway to transcription." Here, we describe the properties of the RNA polymerase II core promoter in Drosophila The core promoter is at a strategic position in the expression of genes, as it is the site of convergence of the signals that lead to transcriptional activation. Importantly, core promoters are diverse in terms of their structure and function. They are composed of various combinations of sequence motifs such as the TATA box, initiator (Inr), and downstream core promoter element (DPE). Different types of core promoters are transcribed via distinct mechanisms. Moreover, some transcriptional enhancers exhibit specificity for particular types of core promoters. These findings indicate that the core promoter is a central component of the transcriptional apparatus that regulates gene expression

Meeting Minutes

Meeting regarding reorganization, course catalog, staffing plan, fund raising, honorary degrees, graduate assistants, multiple baccalaureates and cohort tracker

Surround inhibition in the human motor system

Human dexterity is unique within the animal kingdom. The human hand, the final product of long evolutionary process is the most fascinating and refined motor systems in nature. This thesis approaches the neural control of finger movements through the scope of surround inhibition, a neural process well described in the sensory system and recently associated with the motor system. Individuation of finger movements was explored by means of electromyography (EMG) and transcranial magnetic stimulation (TMS) during a brief flexion of the index finger. A thorough description of the motor evoked potentials and EMG activity in three intrinsic hand muscles is provided initially (Chapter 4). The role of cerebellum as a modulator of moto-cortical output was explored during the same movement and was found to modulate the motor output in a non- muscle specific manner (Chapter 5). In Chapter 6, brain plasticity, a fundamental neural process was probed by means of peripheral nerve stimulation with electrical and mechanical tools in a successful attempt to modulate the strength of surround inhibition in the motor cortex. Finally, data from patients suffering from dystonia is presented and compared with previously published literature (Chapter 7). Lack of significant differences between the dystonia and healthy groups raised questions about the credibility of the proposal that dystonia is disease model for loss of inhibition in the motor system. The thesis calls for a reappraisal of our approach to the role of SI in the motor system and in particular in the pathophysiology of movement disorders such as dystonia

Towards longitudinal data analytics in Parkinson's Disease

The CloudUPDRS app has been developed as a Class I med- ical device to assess the severity of motor symptoms for Parkinson’s Disease using a fully automated data capture and signal analysis pro- cess based on the standard Unified Parkinson’s Disease Rating Scale. In this paper we report on the design and development of the signal pro- cessing and longitudinal data analytics microservices developed to carry out these assessments and to forecast the long-term development of the disease. We also report on early findings from the application of these techniques in the wild with a cohort of early adopters

Molecular basis of RNA polymerase III transcription repression by Maf1

RNA polymerase III (Pol III) transcribes short RNAs required for cell growth. Under stress conditions, the conserved protein Maf1 rapidly represses Pol III transcription. We report the crystal structure of Maf1 and cryo-electron microscopic structures of Pol III, an active Pol III-DNA-RNA complex, and a repressive Pol III-Maf1 complex. Binding of DNA and RNA causes ordering of the Pol III-specific subcomplex C82/34/31 that is required for transcription initiation. Maf1 binds the Pol III clamp and rearranges C82/34/31 at the rim of the active center cleft. This impairs recruitment of Pol III to a complex of promoter DNA with the initiation factors Brf1 and TBP and thus prevents closed complex formation. Maf1 does however not impair binding of a DNA-RNA scaffold and RNA synthesis. These results explain how Maf1 specifically represses transcription initiation from Pol III promoters and indicate that Maf1 also prevents reinitiation by binding Pol III during transcription elongation

The tardigrade damage suppressor protein binds to nucleosomes and protects DNA from hydroxyl radicals.

Tardigrades, also known as water bears, are animals that can survive extreme conditions. The tardigrade Ramazzottius varieornatus contains a unique nuclear protein termed Dsup, for damage suppressor, which can increase the resistance of human cells to DNA damage under conditions, such as ionizing radiation or hydrogen peroxide treatment, that generate hydroxyl radicals. Here we find that R. varieornatus Dsup is a nucleosome-binding protein that protects chromatin from hydroxyl radicals. Moreover, a Dsup ortholog from the tardigrade Hypsibius exemplaris similarly binds to nucleosomes and protects DNA from hydroxyl radicals. Strikingly, a conserved region in Dsup proteins exhibits sequence similarity to the nucleosome-binding domain of vertebrate HMGN proteins and is functionally important for nucleosome binding and hydroxyl radical protection. These findings suggest that Dsup promotes the survival of tardigrades under diverse conditions by a direct mechanism that involves binding to nucleosomes and protecting chromosomal DNA from hydroxyl radicals

The tardigrade damage suppressor protein binds to nucleosomes and protects DNA from hydroxyl radicals.

Tardigrades, also known as water bears, are animals that can survive extreme conditions. The tardigrade Ramazzottius varieornatus contains a unique nuclear protein termed Dsup, for damage suppressor, which can increase the resistance of human cells to DNA damage under conditions, such as ionizing radiation or hydrogen peroxide treatment, that generate hydroxyl radicals. Here we find that R. varieornatus Dsup is a nucleosome-binding protein that protects chromatin from hydroxyl radicals. Moreover, a Dsup ortholog from the tardigrade Hypsibius exemplaris similarly binds to nucleosomes and protects DNA from hydroxyl radicals. Strikingly, a conserved region in Dsup proteins exhibits sequence similarity to the nucleosome-binding domain of vertebrate HMGN proteins and is functionally important for nucleosome binding and hydroxyl radical protection. These findings suggest that Dsup promotes the survival of tardigrades under diverse conditions by a direct mechanism that involves binding to nucleosomes and protecting chromosomal DNA from hydroxyl radicals

Photoluminescence enhancement of ZnO via coupling with surface plasmons on Al thin films

We present that the ultra-violet emission of ZnO can be enhanced, as much as six-times its integral intensity, using an Al thin interlayer film between the Si substrate and ZnO thin film and a postfabrication laser annealing process. The laser annealing is a cold process that preserves the chemical state and integrity of the underlying aluminum layer, while it is essential for the improvement of the ZnO performance as a light emitter and leads to enhanced emission in the visible and in the ultraviolet spectral ranges. In all cases, the metal interlayer enhances the intensity of the emitted light, either through coupling of the surface plasmon that is excited at the Al/ZnO interface, in the case of light-emitting ZnO in the ultraviolet region, or by the increased back reflection from the Al layer, in the case of the visible emission. In order to evaluate the process and develop a solid understanding of the relevant physical phenomena, we investigated the effects of various metals as interlayers (Al, Ag, and Au), the metal interlayer thickness, and the incorporation of a dielectric spacer layer between Al and ZnO. Based on these experiments, Al emerged as the undisputable best choice of metal interlayers because of its compatibility with the laser annealing process, as well as due to its high optical reflectivity at 380 and 248 nm, which leads to the effective coupling with surface plasmons at the Al/ZnO interfaces at 380 nm and the secondary annealing of ZnO by the back-reflected 248 nm laser beam