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

Patterning of ventral telencephalon requires positive function of Gli transcription factors

AbstractThe ability of neuroepithelial cells to generate a diverse array of neurons is influenced by locally secreted signals. In the spinal cord, Sonic Hedgehog (Shh) is known to induce distinct cell fates in a concentration-dependent manner by regulating the activities of the three Gli transcription factors in neural precursors. However, whether Gli-mediated Shh signaling is also required to induce different cell types in the ventral telencephalon has been controversial. In particular, loss of Shh has little effect on dorsoventral patterning of the telencephalon when Gli3 is also removed. Furthermore, no ventral telencephalic phenotypes have been found in individual Gli mutants. To address this issue, we first characterized Shh-responding ventral telencephalic progenitors between E9.5 and E12.5 and found that they produce neurons migrating to different layers of the cortex. We also discovered a loss of Nkx2.1 and Nkx6.2 expression in two subgroups of progenitors in embryos lacking major Gli activators. Finally, we analyzed the telencephalic phenotypes of embryos lacking all Gli genes and found that the ventral telencephalon was highly disorganized with intermingling of distinct neuronal cell types. Together, these studies unravel a role for Gli transcription factors in mediating Shh signaling to control specification, differentiation and positioning of ventral telencephalic neurons

MOVELETS: A DICTIONARY OF MOVEMENT

Recent technological advances provide researchers a way of gathering real-time information on an individual’s movement through the use of wearable devices that record acceleration. In this paper, we propose a method for identifying activity types, like walking, standing, and resting, from acceleration data. Our approach decomposes movements into short components called “movelets”, and builds a reference for each activity type. Unknown activities are predicted by matching new movelets to the reference. We apply our method to data collected from a single, three-axis accelerometer and focus on activities of interest in studying physical function in elderly populations. An important technical advantage of our methods is that they allow identification of short activities, such as taking two or three steps and then stopping, as well as low frequency rare activities, such as sitting on a chair. Based on our results we provide simple and actionable recommendations for the design and implementation of large epidemiological studies that could collect accelerometry data for the purpose of predicting the time series of activities and connecting it to health outcomes

Evidential Uncertainty Quantification: A Variance-Based Perspective

Uncertainty quantification of deep neural networks has become an active field of research and plays a crucial role in various downstream tasks such as active learning. Recent advances in evidential deep learning shed light on the direct quantification of aleatoric and epistemic uncertainties with a single forward pass of the model. Most traditional approaches adopt an entropy-based method to derive evidential uncertainty in classification, quantifying uncertainty at the sample level. However, the variance-based method that has been widely applied in regression problems is seldom used in the classification setting. In this work, we adapt the variance-based approach from regression to classification, quantifying classification uncertainty at the class level. The variance decomposition technique in regression is extended to class covariance decomposition in classification based on the law of total covariance, and the class correlation is also derived from the covariance. Experiments on cross-domain datasets are conducted to illustrate that the variance-based approach not only results in similar accuracy as the entropy-based one in active domain adaptation but also brings information about class-wise uncertainties as well as between-class correlations. The code is available at https://github.com/KerryDRX/EvidentialADA. This alternative means of evidential uncertainty quantification will give researchers more options when class uncertainties and correlations are important in their applications.Comment: IEEE/CVF Winter Conference on Applications of Computer Vision (WACV) 202

E+ E- -> Tau+ Tau- at the Threshold and Beyond

The excitation curve for the $\tau^+ \, \tau^-$ production in electron positron annihilation near the threshold is revisited with the aim of updating and extending a previous work. We find that the corrections of the relative magnitude $O(\alpha)$ near the threshold are significantly contributed by the radiative modification of the Coulomb interaction between the $\tau$ leptons. The interpolation between the Coulomb effects at the threshold and the relativistic effects at higher energies is considered and the resulting formula is argued to have relative accuracy up to, but not including, terms of the order of $\alpha^2$ at any velocity of the $\tau$ leptons.Comment: 7 pages, 1 figure (LaTeX, figure appended in PostScript), UMN-TH-1232/93, TPI-MINN-93/61-

Multi-Task Pseudo-Label Learning for Non-Intrusive Speech Quality Assessment Model

This study introduces multi-task pseudo-label (MPL) learning for a non-intrusive speech quality assessment model. MPL consists of two stages which are obtaining pseudo-label scores from a pretrained model and performing multi-task learning. The 3QUEST metrics, namely Speech-MOS (S-MOS), Noise-MOS (N-MOS), and General-MOS (G-MOS) are selected as the primary ground-truth labels. Additionally, the pretrained MOSA-Net model is utilized to estimate three pseudo-labels: perceptual evaluation of speech quality (PESQ), short-time objective intelligibility (STOI), and speech distortion index (SDI). Multi-task learning stage of MPL is then employed to train the MTQ-Net model (multi-target speech quality assessment network). The model is optimized by incorporating Loss supervision (derived from the difference between the estimated score and the real ground-truth labels) and Loss semi-supervision (derived from the difference between the estimated score and pseudo-labels), where Huber loss is employed to calculate the loss function. Experimental results first demonstrate the advantages of MPL compared to training the model from scratch and using knowledge transfer mechanisms. Secondly, the benefits of Huber Loss in improving the prediction model of MTQ-Net are verified. Finally, the MTQ-Net with the MPL approach exhibits higher overall prediction capabilities when compared to other SSL-based speech assessment models

A Simple Explanation for DAMA with Moderate Channeling

We consider the possibility that the DAMA signal arises from channeled events in simple models where the dark matter interaction with nuclei is suppressed at small momenta. As with the standard WIMP, these models have two parameters (the dark matter mass and the size of the cross-section), without the need to introduce an additional energy threshold type of parameter. We find that they can be consistent with channeling fractions as low as about ~ 15%, so long as at least ~70% of the nuclear recoil energy for channeled events is deposited electronically. Given that there are reasons not to expect very large channeling fractions, these scenarios make the channeling explanation of DAMA much more compelling.Comment: 6 pages, 2 figure

The Pichia pastoris transmembrane protein GT1 is a glycerol transporter and relieves the repression of glycerol on AOX1 expression

Promoter of alcohol oxidase I (PAOX1) is the most efficient promoter involved in the regulation of recombinant protein expression in Pichia pastoris (P. pastoris). PAOX1 is tightly repressed by the presence of glycerol in the culture medium; thus, glycerol must be exhausted before methanol can be taken up by P. pastoris and the expression of the heterologous protein can be induced. In this study, a candidate glycerol transporter (GT1, GeneID: 8197545) was identified, and its role was confirmed by further studies (e.g. bioinformatics analysis, heterologous complementation in Schizosaccharomyces pombe (S. pombe)). When GT1 is co-expressed with enhanced green fluorescent protein (EGFP), it localizes to the membrane and S. pombe carrying gt1 but not the wild-type strain can grow on medium containing glycerol as the sole carbon source. The present study is the first to report that AOX1 in the X-33gt1 mutant can achieve constitutive expression in medium containing glycerol; thus, knocking down gt1 can eliminate the glycerol repression of PAOX1 in P. pastoris. These results suggest that the glycerol transporter may participate in the process of PAOX1 inhibition in glycerol medium