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Biology subjects

Franke, M.

Publications and source records attributed to Franke, M..

3 recordsLinked to original sources

A Truly Injectable Neural Stimulation Electrode Made From an In-Body Curing Polymer/Metal Composite

Implanted neural stimulation and recording devices hold vast potential to treat a variety of neurological conditions, but the invasiveness, complexity, and cost of the implantation procedure greatly reduce access to an otherwise promising therapeutic approach. To address this need, we have developed a novel electrode that begins as an uncured, flowable pre-polymer that can be injected around a neuroanatomical target to minimize surgical manipulation. Referred to as the Injectrode, the electrode conforms to target structures forming an electrically conductive interface which is orders of magnitude less stiff than conventional neuromodulation electrodes. To validate the Injectrode, we performed detailed electrochemical and microscopy characterization of its material properties and validated the feasibility of using it to electrically stimulate the nervous system in rats and swine. The silicone-metal-particle composite performed very similarly to pure wire of the same metal (silver) in all measures, including exhibiting a favorable cathodic charge storage capacity (CSCC) and charge injection limits compared to the clinical LivaNova stimulation electrode and silver wire electrodes. By virtue of being simpler than traditional electrode designs, less invasive, and more cost-effective, the Injectrode has the potential to increase the adoption of neuromodulation therapies for existing and new indications.

bioengineering

Functional dissection of TADs reveals non-essential and instructive roles in regulating gene expression

The genome is organized in megabase-sized three-dimensional units, called Topologically Associated Domains (TADs), that are separated by boundaries. TADs bring distant cis-regulatory elements into proximity, a process dependent on the cooperative action of cohesin and the DNA binding factor CTCF. Surprisingly, genome-wide depletion of CTCF has little effect on transcription, yet structural variations affecting TADs have been shown to cause gene misexpression and congenital disease. Here, we investigate TAD function in vivo in mice by systematically editing components of TAD organization at the Sox9/Kcnj locus. We find that TADs are formed by a redundant system of CTCF sites requiring the removal of all major sites within the TAD and at the boundary for two neighboring TADs to fuse. TAD fusion resulted in leakage of regulatory activity from the Sox9 to the Kcnj TAD, but no major changes in gene expression. This indicates that TAD structures provide robustness and precision, but are not essential for developmental gene regulation. Gene misexpression and resulting disease phenotypes, however, were attained by re-directing regulatory activity through inversions and/or the re-positioning of boundaries. Thus, efficient re-wiring of enhancer promoter interaction and aberrant disease causing gene activation is not induced by a mere loss of insulation but requires the re-direction of contacts.

genetics

Mycobacterium tuberculosis detection from oral swabs with Xpert MTB/RIF ULTRA: A pilot study

ObjectiveDiagnostic testing for tuberculosis depends on microbiological detection of Mycobacterium tuberculosis (Mtb) in sputum. For patients unable to expectorate sputum, such as children and individuals living with HIV, this poses barriers to rapid diagnosis and treatment initiation. Therefore, this study aimed to use oral swabs have as alternative sample type for Mtb detection via molecular testing. ResultsIn a pilot study, we aimed to evaluate sensitivity of Mtb detection via oral swabs using Xpert MTB/RIF ULTRA. We enrolled 63 TB cases and controls from Lima, Peru, and detected Mtb from oral swabs with a sensitivity of 45% (95% confidence interval (CI): 29%-63%) and specificity of 100% (95% CI: 84%-100%) using liquid culture of sputum as reference test. Our current protocol will need optimization, but these results support future exploration of the use of oral swabs for Mtb detection.

microbiology