In this letter, we report the preparation of a compact, functional quantum dot (QD)-DNA conjugate, where the capturing target DNA is directly and covalently coupled to the QD surface. This enables control of the separation distance between the QD donor and dye acceptor to within the range of the Förster radius. Moreover, a tri(ethylene glycol) linker is introduced to the QD surface coating to effectively eliminate the strong, nonspecific adsorption of DNA on the QD surface. As a result, this QD-DNA conjugate hybridizes specifically to its complementary DNA with a hybridization rate constant comparable to that of free DNAs in solution. We show this system is capable of specific detection of nanomolar unlabeled complimentary DNA at low DNA probe/QD copy numbers via a "signal-on" fluorescence resonance energy transfer (FRET) response.

Repetitive transcranial magnetic stimulation (rTMS) has demonstrated antidepressant efficacy but has limited evidence in depression associated with traumatic brain injury (TBI). Here, we investigate the use of rTMS targeted with individualized resting-state network mapping (RSNM) of dorsal attention network (DAN) and default mode network (DMN) in subjects with treatment-resistant depression associated with concussive or moderate TBI. The planned sample size was 50 with first interim analysis planned at 20, but only 15 were enrolled before the study was terminated for logistical reasons. Subjects were randomized to 20 sessions of bilateral rTMS (4000 left-sided excitatory pulses, 1000 right-sided inhibitory pulses) or sham. Treatment was targeted to the dorsolateral prefrontal cluster with maximal difference between DAN and DMN correlations based on resting-state functional magnetic resonance imaging with individualized RSNM. Mean improvement in the primary outcome, Montgomery-Asberg Depression Rating Scale (MADRS), was 56%-14% (n = 9) with active treatment and 27%-25% (n = 5) with sham (Cohen's d = 1.43). One subject randomized to sham withdrew before starting treatment. There were no seizures or other significant adverse events. MADRS improvement was inversely correlated with functional connectivity between the right-sided stimulation site and the subgenual anterior cingulate cortex (sgACC; r =-0.68, 95% confidence interval 0.03-0.925). Active treatment led to increased sgACC-DMN connectivity (d = 1.55) and increased sgACC anti-correlation with the left-and right-sided stimulation sites (d =-1.26 and-0.69, respectively). This pilot study provides evidence that RSNM-targeted rTMS is feasible in TBI patients with depression. Given the dearth of existing evidence-based treatments for depression in this patient population, these preliminarily encouraging results indicate that larger controlled trials are warranted.

White matter (WM) atrophy is a significant feature of Huntington disease (HD), although its aetiology and early pathological manifestations remain poorly defined. In this study, we aimed to characterize WM-related features in the transgenic YAC128 and BACHD models of HD. Using diffusion tensor magnetic resonance imaging (DT-MRI), we demonstrate that microstructural WM abnormalities occur from an early age in YAC128 mice. Similarly, electron microscopy analysis of myelinated fibres of the corpus callosum indicated that myelin sheaths are thinner in YAC128 mice as early as 1.5 months of age, well before any neuronal loss can be detected. Transcript levels of myelin-related genes in striatal and cortical tissues were significantly lower in YAC128 mice from 2 weeks of age, and these findings were replicated in differentiated primary oligodendrocytes from YAC128 mice, suggesting a possible mechanistic explanation for the observed structural deficits. Concordant with these observations, we demonstrate reduced expression of myelin-related genes at 3 months of age and WM microstructural abnormalities using DT-MRI at 12 months of age in the BACHD rats. These findings indicate that WM deficits in HD are an early phenotype associated with cell-intrinsic effects of mutant huntingtin on myelin-related transcripts in oligodendrocytes, and raise the possibility that WM abnormalities may be an early contributing factor to the pathogenesis of HD.