Statins suppress cell-to-cell propagation of α-synuclein by lowering cholesterol.

Cell-to-cell propagation of protein aggregates has been implicated in the progression of neurodegenerative diseases. However, the underlying mechanism and modulators of this process are not fully understood. Here, we screened a small-molecule library in a search for agents that suppress the propagation of α-synuclein and mutant huntingtin (mHtt).

Modeling α-Synuclein Propagation with Preformed Fibril Injections.

The aggregation of α-synuclein (α-syn) has been implicated in the pathogenesis of many neurodegenerative disorders, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Postmortem analyses of α-syn pathology, especially that of PD, have suggested that aggregates progressively spread from a few discrete locations to wider brain regions. The neuron-to-neuron propagation of α-syn has been suggested to be the underlying mechanism by which aggregates spread throughout the brain.

BMP-SHH signaling network controls epithelial stem cell fate via regulation of its niche in the developing tooth.

During embryogenesis, ectodermal stem cells adopt different fates and form diverse ectodermal organs, such as teeth, hair follicles, mammary glands, and salivary glands. Interestingly, these ectodermal organs differ in their tissue homeostasis, which leads to differential abilities for continuous growth postnatally. Mouse molars lose the ability to grow continuously, whereas incisors retain this ability.

Integration of comprehensive 3D microCT and signaling analysis reveals differential regulatory mechanisms of craniofacial bone development.

Growth factor signaling regulates tissue-tissue interactions to control organogenesis and tissue homeostasis. Specifically, transforming growth factor beta (TGFβ) signaling plays a crucial role in the development of cranial neural crest (CNC) cell-derived bone, and loss of Tgfbr2 in CNC cells results in craniofacial skeletal malformations. Our recent studies indicate that non-canonical TGFβ signaling is activated whereas canonical TGFβ signaling is compromised in the absence of Tgfbr2 (in Tgfbr2(fl/fl);Wnt1-Cre mice).

Humeral shaft fracture treatment in the elite throwing athlete: a unique application of flexible intramedullary nailing.

Humeral shaft stress fractures are being increasingly recognized as injuries that can significantly impact throwing mechanics if residual malalignment exists. While minimally displaced and angulated injuries are treated nonoperatively in a fracture brace, the management of significantly displaced humeral shaft fractures in the throwing athlete is less clear. Currently described techniques such as open reduction and internal fixation with plate osteosynthesis and rigid antegrade/retrograde locked intramedullary nailing have significant morbidity due to soft tissue dissection and damage.

Reagentless ultrasensitive specific DNA array detection based on responsive polymeric biochips.

Self-assembled molecular structures immobilized on solid substrates and composed of fluorophore-tagged oligonucleotide probes and an optical polymeric transducer were investigated for the trace level detection of DNA target molecules. Rapid and efficient energy transfer between the polymeric transducer and fluorophores within the molecular aggregates leads to a massive intrinsic amplification of the fluorescence signal and to the label-free detection of as little as 300 DNA molecules, with the specificity required for the detection of single-nucleotide mismatches. This capacity for attomolar detection levels while the sensing structures are attached onto solid supports could lead to the development of biochip platforms for fast and simple PCR-free multitarget DNA detection.

Detection of target DNA using fluorescent cationic polymer and peptide nucleic acid probes on solid support.

Background: Nucleic acids detection using microarrays requires labelling of target nucleic acids with fluorophores or other reporter molecules prior to hybridization.

Results: Using surface-bound peptide nucleic acids (PNA) probes and soluble fluorescent cationic polythiophenes, we show a simple and sensitive electrostatic approach to detect and identify unlabelled target nucleic acid on microarray.

Conclusion: This simple methodology opens exciting possibilities for applied genetic analysis for the diagnosis of infections, identification of genetic mutations, and forensic inquiries.

Optical sensors based on hybrid DNA/conjugated polymer complexes.

Single-stranded DNA (ss-DNA) can specifically bind to various targets, including a complementary ss-DNA, ions, proteins, drugs, and so forth. When binding takes place, the oligonucleotide probe often undergoes a conformational transition. This conformational change of the negatively charged ss-DNA can be detected by using a water-soluble, cationic polythiophene derivative, which transduces the complex formation into an optical (colorimetric or fluorometric) signal without any labeling of the probe or the target.

Fluorescent polymeric transducer for the rapid, simple, and specific detection of nucleic acids at the zeptomole level.

We report the specific detection of a few hundred molecules of genetic material using a fluorescent polythiophene biosensor. Such recognition is based on simple electrostatic interactions between a cationic polymeric optical transducer and the negatively charged nucleic acid target and can be done in less than 1 h, simply and affordably, and without any chemical reaction. This simple system is versatile enough to detect nucleic acids of various lengths, including a segment from the RNA genome of the Influenza virus.

Optical sensors based on hybrid aptamer/conjugated polymer complexes.

Single-stranded DNA (aptamer) can specifically bind potassium ions or human alpha-thrombin. When binding takes place, the aptamer undergoes a conformational transition from an unfolded to a folded structure. This conformational change of the negatively charged oligonucleotide can be detected by adding a water-soluble, cationic polythiophene derivative, which transduces the new complex formation into an optical (colorimetric or fluorometric) signal without any labeling of the probe or of the target.