Balanced Shh signaling is required for proper formation and maintenance of dorsal telencephalic midline structures

<p>Abstract</p> <p>Background</p> <p>The rostral telencephalic dorsal midline is an organizing center critical for the formation of the future cortex and hippocampus. While the intersection of WNTs, BMPs, and FGFs establishes boundaries within this critical center, a direct role of Shh signaling in this region remains controversial. In this paper we show that both increased and decreased Shh signaling directly affects boundary formation within the telencephalic dorsal midline.</p> <p>Results</p> <p>Viral over-expression of Shh in the embryonic telencephalon prevents formation of the cortical hem and choroid plexus, while expanding the roof plate. In a transgenic model where cholesterol-lacking ShhN is expressed from one allele (<it>ShhN/+</it>), genes expressed in all three domains, cortical hem, choroid plexus and roof plate expand. In <it>Gli1/2 -/- </it>mutant brains, where Shh signaling is reduced, the roof plate expands, again at the expense of cortical hem and plexus. Cell autonomous activation of Shh signaling in the dorsal midline through Gdf7-driven activated Smoothened expression results in expansion of the <it>Wnt3a</it>-expressing cortical hem into the plexus domain. In addition, developmental stage determines dorsal midline responsiveness to Shh.</p> <p>Conclusions</p> <p>Together, these data demonstrate that balanced Shh signaling is critical for maintaining regional boundaries within the dorsal midline telencephalic organizing center.</p

Cortical and spinal mechanisms of task failure of sustained submaximal fatiguing contractions

In this and the subsequent companion paper, results are presented that collectively seek to delineate the contribution that supraspinal circuits have in determining the time to task failure (TTF) of sustained submaximal contractions. The purpose of this study was to compare adjustments in supraspinal and spinal excitability taken concurrently throughout the performance of two different fatigue tasks with identical mechanical demands but different TTF (i.e., force-matching and position-matching tasks). On separate visits, ten healthy volunteers performed the force-matching or position-matching task at 15% of maximum strength with the elbow flexors to task failure. Single-pulse transcranial magnetic stimulation (TMS), paired-pulse TMS, paired cortico-cervicomedullary stimulation, and brachial plexus electrical stimulation were delivered in a 6-stimuli sequence at baseline and every 2–3 minutes throughout fatigue-task performance. Contrary to expectations, the force-matching task TTF was 42% shorter (17.5±7.9 min) than the position-matching task (26.9±15.11 min; p0.05). Therefore, failure occurred after a similar mean decline in motorneuron excitability developed (p0.10) and an index of upstream excitation of the motor cortex remained constant (p>0.40). Together, these results suggest that as fatigue develops prior to task failure, the increase in corticospinal excitability observed in relationship to the decrease in spinal excitability results from a combination of decreasing intracortical inhibition with constant levels of intracortical facilitation and upstream excitability that together eventually fail to provide the input to the motor cortex necessary for descending drive to overcome the spinal cord resistance, thereby contributing to task failure

Preliminary evidence that anodal transcranial direct current stimulation enhances time to task failure of a sustained submaximal contraction.

The purpose of this study was to determine whether anodal transcranial direct current stimulation (tDCS) delivered while performing a sustained submaximal contraction would increase time to task failure (TTF) compared to sham stimulation. Healthy volunteers (n = 18) performed two fatiguing contractions at 20% of maximum strength with the elbow flexors on separate occasions. During fatigue task performance, either anodal or sham stimulation was delivered to the motor cortex for up to 20 minutes. Transcranial magnetic stimulation (TMS) was used to assess changes in cortical excitability during stimulation. There was no systematic effect of the anodal tDCS stimulation on TTF for the entire subject set (n = 18; p = 0.64). Accordingly, a posteriori subjects were divided into two tDCS-time groups: Full-Time (n = 8), where TTF occurred prior to the termination of tDCS, and Part-Time (n = 10), where TTF extended after tDCS terminated. The TTF for the Full-Time group was 31% longer with anodal tDCS compared to sham (p = 0.04), whereas TTF for the Part-Time group did not differ (p = 0.81). Therefore, the remainder of our analysis addressed the Full-Time group. With anodal tDCS, the amount of muscle fatigue was 6% greater at task failure (p = 0.05) and the amount of time the Full-Time group performed the task at an RPE between 8–10 (“very hard”) increased by 38% (p = 0.04) compared to sham. There was no difference in measures of cortical excitability between stimulation conditions (p = 0.90). That the targeted delivery of anodal tDCS during task performance both increased TTF and the amount of muscle fatigue in a subset of subjects suggests that augmenting cortical excitability with tDCS enhanced descending drive to the spinal motorpool to recruit more motor units. The results also suggest that the application of tDCS during performance of fatiguing activity has the potential to bolster the capacity to exercise under conditions required to derive benefits due to overload

Gene regulatory networks controlling temporal patterning, neurogenesis, and cell-fate specification in mammalian retina

Gene regulatory networks (GRNs), consisting of transcription factors and their target sites, control neurogenesis and cell-fate specification in the developing central nervous system. In this study, we use integrated single-cell RNA and single-cell ATAC sequencing (scATAC-seq) analysis in developing mouse and human retina to identify multiple interconnected, evolutionarily conserved GRNs composed of cell-type-specific transcription factors that both activate genes within their own network and inhibit genes in other networks. These GRNs control temporal patterning in primary progenitors, regulate transition from primary to neurogenic progenitors, and drive specification of each major retinal cell type. We confirm that NFI transcription factors selectively activate expression of genes promoting late-stage temporal identity in primary retinal progenitors and identify other transcription factors that regulate rod photoreceptor specification in postnatal retina. This study inventories cis- and trans-acting factors that control retinal development and can guide cell-based therapies aimed at replacing retinal neurons lost to disease

Atoh7-independent specification of retinal ganglion cell identity

Retinal ganglion cells (RGCs) relay visual information from the eye to the brain. RGCs are the first cell type generated during retinal neurogenesis. Loss of function of the transcription facto

Effect of Temperature Gradient on Thick Film Selective Emitter Emittance

A temperature gradient across a thick (greater than or equal to .1 mm) film selective emitter will produce a significant reduction in the spectral emittance from the no temperature gradient case. Thick film selective emitters of rare earth doped host materials such as yttrium-aluminum-garnet (YAG) are examples where temperature gradient effects are important. In this paper a model is developed for the spectral emittance assuming a linear temperature gradient across the film. Results of the model indicate that temperature gradients will result in reductions the order of 20% or more in the spectral emittance

Efficacy, effort, and cost comparisons of trapping and acetaminophen-baiting for control of brown treesnakes on Guam

Brown treesnakes (Boiga irregularis) are an invasive species to the island of Guam. Because they have extirpated the native forest avifauna on Guam and are a threat to other Pacific islands, the development of efficient and cost-effective methods to control them is desired. We compared the efficacy, cost, and effort required to remove brown treesnakes on 6-ha plots in forest scrub on Guam, using 2 methods: trapping and poison baiting. Toxic baits consisted of dead neonatal mice adulterated with 80-mg acetaminophen. To assess efficacy, we used mark-recapture methods to estimate snake abundance on plots 12 days before and 12 days after treatment. We also monitored bait-take or trap success for 20 days during treatment. From 6,304 trap-nights, we recorded 801 captures of 504 snakes on 6, 6-ha plots during a 51-day period. Snake populations on plots ranged from 41 to 107 prior to treatment. Using trapping to gauge survival of marked snakes, the 2 methods (trapping and baiting) had similar efficacies (0.05 to 0.1). Based on trapping, post-treatment population estimates ranged from 26 to 40, yielding reductions from estimated pre-treatment populations of 7 to 68% for both types of snake-removal treatments. Using post-treatment bait-take of unadulterated mice as an index of efficacy, poisoned baiting was twice as effective as trapping in diminishing snake activity. Trapped plots had post-treatment bait-take rates similar to reference plots (75%), whereas poison-baited plots had bait-take rates of 38%, suggesting that some snakes cannot be trapped and that baiting affects a wider range of the snake population. Because of the potential for baiting to impact more snakes, this method was about 1.67 times more cost effective than trapping. If baiting were to occur via aerial drop rather than via bait stations, the economic incentive for using baiting as a control strategy would be even greater. These observations will prove useful for managers making decisions about appropriate methods for control of brown treesnake populations