Effects of Selective Deafferentation on the Discharge Characteristics of Medial Rectus Motoneurons

Medial rectus motoneurons receive two main pontine inputs: abducens internuclear neurons, whose axons course through the medial longitudinal fasciculus (MLF), and neurons in the lateral vestibular nucleus, whose axons project through the ascending tract of Deiters (ATD). Abducens internuclear neurons are responsible for conjugate gaze in the horizontal plane, whereas ATD neurons provide medial rectus motoneurons with a vestibular input comprising mainly head velocity. To reveal the relative contribution of each input to the oculomotor physiology, single-unit recordings from medial rectus motoneurons were obtained in the control situation and after selective deafferentation from cats with unilateral transection of either the MLF or the ATD. Both MLF and ATD transection produced similar short-term alterations in medial rectus motoneuron firing pattern, which were more drastic in MLF of animals. However, long-term recordings revealed important differences between the two types of lesion. Thus, while the effects of the MLF section were permanent, 2 months after ATD lesioning all motoneuronal firing parameters were similar to the control. These findings indicated a more relevant role of the MLF pathway in driving motoneuronal firing and evidenced compensatory mechanisms following the ATD lesion. Confocal immunocytochemistry revealed that MLF transection produced also a higher loss of synaptic boutons, mainly at the dendritic level. Moreover, 2 months after ATD transection, we observed an increase in synaptic coverage around motoneuron cell bodies compared with short-term data, which is indicative of a synaptogenic compensatory mechanism of the abducens internuclear pathway that could lead to the observed firing and morphological recovery. SIGNIFICANCE STATEMENT Eye movements rely on multiple neuronal circuits for appropriate performance. The abducens internuclear pathway through the medial longitudinal fascicle (MLF) and the vestibular neurons through the ascending tract of Deiters (ATD) are a dual system that supports the firing of medial rectus motoneurons. We report the effect of sectioning the MLF or the ATD pathway on the firing of medial rectus motoneurons, as well as the plastic mechanisms by which one input compensates for the lack of the other. This work shows that while the effects of MLF transection are permanent, the ATD section produces transitory effects. A mechanism based on axonal sprouting and occupancy of the vacant synaptic space due to deafferentation is the base for the mechanism of compensation on the medial rectus motoneuron

LiDARs detected signal and Target distance estimation: measurement errors from Target reflectance and multiple echos

The use of LiDARs in automotive is increasingly widespread. In order to operate in a critical environment such as that of mobility, these systems must offer increasingly high performance. In particular, the ability to estimate the position of objects regardless of their reflectance and presence of diffusing backgrounds is a very sought-after feature by manufacturers. In commercial systems various strategies are used to make the measurement as insensitive as possible to these effects, however, it is not possible to fully compensate for the measurement errors caused by them. In this paper, we propose two simple experimental setups to verify the presence of these measurement errors in two scenarios. Moreover, we report the performance of a commercial LiDAR (MRS 6000 by Sick) using certified reflectance standards (Spectralon (R) Diffuse Reflectance Standards, by Labsphere). For this LiDAR, the results obtained show that a logarithmic variation of the reflectance of the target of 1.26-log at a target distance 2.4 m provides incompatible measurements. Furthermore, the presence of a background at a distance shorter than 11 cm, 12 cm and 13 cm respectively with 50 %, 75 % and 99 % reflectance also provides incompatible measurements for a target distance of 1.3 m from the LiDAR

Comparison of VLP-16 and MRS-1000 LiDAR systems with absolute interferometer

Nowadays, LiDARs hold a relevant place in providing the environmental sensing required by most ADAS. Promoted by such increasing demand, many new manufacturers are emerging and, new LiDARs are continuously made available on the market. If, on the one hand, the availability of LiDARs with increasing performance and reducing cost has brought significant benefits also promoting the spread of such measuring systems in other areas such as industrial controls and agriculture, on the other, it has made it more difficult to extricate in the immense set of LiDARs present on the market today. In response to this growing need for standards and methods capable of comparing the various LiDARs, many international standards and scientific publications are being produced on the subject. In this paper, we continue our work on LiDARs characterization, focusing our attention on comparing the performances of two of the must popular systems - namely, the MRS 1000 by Sick and the VLP 16 by Velodyne. Starting from the analysis of the warm-up time and stability, such a comparison focused on analyzing the axial error of both systems. Such errors have been estimated by exploiting a custom rail system and an absolute interferometer. The obtained results revealed warm-up times of a few tens of minutes and maximum absolute axial errors of a few centimeters in the range [1.5,21] m

Analysis, Quantification, and Discussion of the Approximations Introduced by Pulsed 3-D LiDARs

Light detection and rangings (LiDARs) are considered essential for the environmental sensing required by most advanced driver assistance system (ADAS), including autonomous driving. This has led to significant investments resulted in the availability of countless measuring systems that are increasingly performing and less expensive. Nevertheless, the extremely high speed of light still leads to a nonnegligible quantization error in the direct time-of-flight (ToF) measure at the base of pulsed LiDARs-the leading technology for automotive applications. Hence, pulsed 3-D LiDARs analyze the surrounding by approximating and deforming it on concentric spheres whose radii are quantized with a quantization step that, for most commercial systems, is on the order of some centimeters. The deformation and error introduced by such quantization can thus he significant. In this study, we point out the approximations and assumptions intrinsic to 3-D LiDARs and propose a measurement procedure that, through the analysis of the fine variations of the target position, allows an accurate investigation of the axial resolution and error-probably among the few limitations still affecting this technology. To the best of our knowledge, this is the first study focused on the detailed analysis of the quantization error in 3-D LiDARs. The proposed method has been tested on one of the most popular 3-D LiDARs, namely the MRS 6000 by Sick. The obtained results revealed for the MRS 6000 a quantization step of about 6 cm (ToF quantization of about 0.4 ns) and an axial error normally distributed with experimental standard deviation of about 30 mm

Nowcasting COVID-19 incidence indicators during the Italian first outbreak

A novel parametric regression model is proposed to fit incidence data typically collected during epidemics. The proposal is motivated by real-time monitoring and short-term forecasting of the main epidemiological indicators within the first outbreak of COVID-19 in Italy. Accurate short-term predictions, including the potential effect of exogenous or external variables are provided. This ensures to accurately predict important characteristics of the epidemic (e.g., peak time and height), allowing for a better allocation of health resources over time. Parameter estimation is carried out in a maximum likelihood framework. All computational details required to reproduce the approach and replicate the results are provided

Ruthenium-Catalyzed Decarboxylative Rearrangement of 4-Alkenyl-isoxazol-5-ones to Pyrrole Derivatives

Easily accessible isoxazol-5(4H)-ones are useful precursors of heterocycles. In this context, we report the ruthenium-catalyzed transformation of 4-alkenyl-substituted isoxazol-5-ones to afford 1H-pyrrole derivatives. The operative conditions were proven to be effective also on cyclohexane-fused isoxazolones giving 4,5,6,7-tetrahydroindoles. The reactions, which allow for access to tri-and tetra-substituted pyrroles in moderate to high yields, occur through decarboxylative ring-opening/ring-closure involving C-H functionalization of the alkenyl moiety

Aberrant splicing and expression of the non muscle myosin heavy-chain gene MYH14 in DM1 muscle tissues

Myotonic dystrophy type 1 (DM1) is a complex multisystemic disorder caused by an expansion of a CTG repeat located at the 3' untranslated region (UTR) of DMPK on chromosome 19q13.3. Aberrant messenger RNA (mRNA) splicing of several genes has been reported to explain some of the symptoms of DM1 including insulin resistance, muscle wasting and myotonia. In this paper we analyzed the expression of the MYH14 mRNA and protein in the muscle of DM1 patients (n=12) with different expansion lengths and normal subjects (n=7). The MYH14 gene is located on chromosome 19q13.3 and encodes for one of the heavy chains of the so called class II "nonmuscle" myosins (NMHCII). MYH14 has two alternative spliced isoforms: the inserted isoform (NMHCII-C1) which includes 8 amino acids located in the globular head of the protein, not encoded by the non inserted isoform (NMHCII-C0). Results showed a splicing unbalance of the MYH14 gene in DM1 muscle, with a prevalent expression of the NMHCII-C0 isoform more marked in DM1 patients harboring large CTG expansions. Minigene assay indicated that levels of the MBNL1 protein positively regulates the inclusion of the MYH14 exon 6. Quantitative analysis of the MYH14 expression revealed a significant reduction in the DM1 muscle samples, both at mRNA and protein level. No differences were found between DM1 and controls in the skeletal muscle localization of MYH14, obtained through immunofluorescence analysis. In line with the thesis of an "RNA gain of function" hypothesis described for the CTG mutation, we conclude that the alterations of the MYH14 gene may contribute to the DM1 molecular pathogenesis

Cyclin D1 Restrains Oncogene-Induced Autophagy by Regulating the AMPK-LKB1 Signaling Axis.

Autophagy activated after DNA damage or other stresses mitigates cellular damage by removing damaged proteins, lipids, and organelles. Activation of the master metabolic kinase AMPK enhances autophagy. Here we report that cyclin D1 restrains autophagy by modulating the activation of AMPK. In cell models of human breast cancer or in a cyclin D1-deficient model, we observed a cyclin D1-mediated reduction in AMPK activation. Mechanistic investigations showed that cyclin D1 inhibited mitochondrial function, promoted glycolysis, and reduced activation of AMPK (pT172), possibly through a mechanism that involves cyclin D1-Cdk4/Cdk6 phosphorylation of LKB1. Our findings suggest how AMPK activation by cyclin D1 may couple cell proliferation to energy homeostasis

Kinase-independent role of cyclin D1 in chromosomal instability and mammary tumorigenesis

Cyclin D1 is an important molecular driver of human breast cancer but better understanding of its oncogenic mechanisms is needed, especially to enhance efforts in targeted therapeutics. Currently, pharmaceutical initiatives to inhibit cyclin D1 are focused on the catalytic component since the transforming capacity is thought to reside in the cyclin D1/CDK activity. We initiated the following study to directly test the oncogenic potential of catalytically inactive cyclin D1 in an in vivo mouse model that is relevant to breast cancer. Herein, transduction of cyclin D1(-/-) mouse embryonic fibroblasts (MEFs) with the kinase dead KE mutant of cyclin D1 led to aneuploidy, abnormalities in mitotic spindle formation, autosome amplification, and chromosomal instability (CIN) by gene expression profiling. Acute transgenic expression of either cyclin D1(WT) or cyclin D1(KE) in the mammary gland was sufficient to induce a high CIN score within 7 days. Sustained expression of cyclin D1(KE) induced mammary adenocarcinoma with similar kinetics to that of the wild-type cyclin D1. ChIP-Seq studies demonstrated recruitment of cyclin D1(WT) and cyclin D1(KE) to the genes governing CIN. We conclude that the CDK-activating function of cyclin D1 is not necessary to induce either chromosomal instability or mammary tumorigenesis