Effect of Regional Brain Activity Following Repeat Transcranial Magnetic Stimulation in SCA3: A Secondary Analysis of a Randomized Clinical Trial.

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuroregulatory technique used to treat neurodegenerative diseases, holds promise for spinocerebellar ataxia type 3 (SCA3) treatment, although its efficacy and mechanisms remain unclear. This study aims to observe the short-term impact of cerebellar rTMS on motor function in SCA3 patients and utilize resting-state functional magnetic resonance imaging (RS-fMRI) to assess potential therapeutic mechanisms. Twenty-two SCA3 patients were randomly assigned to receive actual rTMS (AC group, n = 11, three men and eight women; age 32-55 years) or sham rTMS (SH group, n = 11, three men and eight women; age 26-58 years). Both groups underwent cerebellar rTMS or sham rTMS daily for 15 days. The primary outcome measured was the ICARS scores and parameters for regional brain activity. Compared to baseline, ICARS scores decreased more significantly in the AC group than in the SH group after the 15-day intervention. Imaging indicators revealed increased Amplitude of Low Frequency Fluctuation (ALFF) values in the posterior cerebellar lobe and cerebellar tonsil following AC stimulation. This study suggests that rTMS enhances motor functions in SCA3 patients by modulating the excitability of specific brain regions and associated pathways, reinforcing the potential clinical utility of rTMS in SCA3 treatment. The Chinese Clinical Trial Registry identifier is ChiCTR1800020133.

Functional imaging of brain organoids using high-density microelectrode arrays.

Abstract: Studies have provided evidence that human cerebral organoids (hCOs) recapitulate fundamental milestones of early brain development, but many important questions regarding their functionality and electrophysiological properties persist. High-density microelectrode arrays (HD-MEAs) represent an attractive analysis platform to perform functional studies of neuronal networks at the cellular and network scale. Here, we use HD-MEAs to derive large-scale electrophysiological recordings from sliced hCOs. We record the activity of hCO slices over several weeks and probe observed neuronal dynamics pharmacologically. Moreover, we present results on how the obtained recordings can be spike-sorted and subsequently studied across scales. For example, we show how to track single neurons across several days on the HD-MEA and how to infer axonal action potential velocities. We also infer putative functional connectivity from hCO recordings. The introduced methodology will contribute to a better understanding of developing neuronal networks in brain organoids and provide new means for their functional characterization. Impact statement: Human cerebral organoids (hCOs) represent an attractive in vitro model system to study key physiological mechanisms underlying early neuronal network formation in tissue with healthy or disease-related genetic backgrounds. Despite remarkable advances in the generation of brain organoids, knowledge on the functionality of their neuronal circuits is still scarce. Here, we used complementary metal-oxide-semiconductor (CMOS)-based high-density microelectrode arrays (HD-MEAs) to perform large-scale recordings from sliced hCOs over several weeks and quantified their activity across scales. Using single-cell and network metrics, we were able to probe aspects of hCO neurophysiology that are more difficult to obtain with other techniques, such as patch clamping (lower yield) and calcium imaging (lower temporal resolution). These metrics included, for example, extracellular action potential (AP) waveform features and axonal AP velocity at the cellular level, as well as functional connectivity at the network level. Analysis was enabled by the large sensing area and the high spatiotemporal resolution provided by HD-MEAs, which allowed recordings from hundreds of neurons and spike sorting of their activity. Our results demonstrate that HD-MEAs provide a multi-purpose platform for the functional characterization of hCOs, which will be key in improving our understanding of this model system and assessing its relevance for translational research. Supplementary Information: The online version contains supplementary material available at 10.1557/s43577-022-00282-w.

High-performance unbiased Ge metal-semiconductor-metal photodetector covered with asymmetric HfSe2 contact geometries.

A Ge metal-semiconductor-metal photodetector covered with asymmetric HfSe2 contact geometries has been proposed to realize high-performance unbiased photodetection at 1550 nm. At -1 V bias, the responsivity of this device shows a 71% improvement compared to the device without HfSe2. Moreover, the responsivity and detectivity of this device at zero bias can reach to 71.2 mA/W and 3.27×1010 Jones, respectively. Furthermore, the fall time of this device is 2.2 µs and 53% shorter than the device without HfSe2. This work provides a feasible way to develop unbiased Ge-based photodetectors in the near-IR communications band.

Structural Covariance of the Ipsilesional Primary Motor Cortex in Subcortical Stroke Patients with Motor Deficits.

The analysis of structural covariance has emerged as a powerful tool to explore the morphometric correlations among broadly distributed brain regions. However, little is known about the interactions between the damaged primary motor cortex (M1) and other brain regions in stroke patients with motor deficits. This study is aimed at investigating the structural covariance pattern of the ipsilesional M1 in chronic subcortical stroke patients with motor deficits. High-resolution T1-weighted brain images were acquired from 58 chronic subcortical stroke patients with motor deficits (29 with left-sided lesions and 29 with right-sided lesions) and 50 healthy controls. Structural covariance patterns were identified by a seed-based structural covariance method based on gray matter (GM) volume. Group comparisons between stroke patients (left-sided or right-sided groups) and healthy controls were determined by a permutation test. The association between alterations in the regional GM volume and motor recovery after stroke was investigated by a multivariate regression approach. Structural covariance analysis revealed an extensive increase in the structural interactions between the ipsilesional M1 and other brain regions in stroke patients, involving not only motor-related brain regions but also non-motor-related brain regions. We also identified a slightly different pattern of structural covariance between the left-sided stroke group and the right-sided stroke group, thus indicating a lesion-side effect of cortical reorganization after stroke. Moreover, alterations in the GM volume of structural covariance brain regions were significantly correlated to the motor function scores in stroke patients. These findings indicated that the structural covariance patterns of the ipsilesional M1 in chronic subcortical stroke patients were induced by motor-related plasticity. Our findings may help us to better understand the neurobiological mechanisms of motor impairment and recovery in patients with subcortical stroke from different perspectives.

Improved Generation of Human Induced Pluripotent Stem Cell-Derived Cardiac Pacemaker Cells Using Novel Differentiation Protocols.

Current protocols for the differentiation of human-induced pluripotent stem cells (hiPSC) into cardiomyocytes only generate a small amount of cardiac pacemaker cells. In previous work, we reported the generation of high amounts of cardiac pacemaker cells by co-culturing hiPSC with mouse visceral endoderm-like (END2) cells. However, potential medical applications of cardiac pacemaker cells generated according to this protocol, comprise an incalculable xenogeneic risk. We thus aimed to establish novel protocols maintaining the differentiation efficiency of the END2 cell-based protocol, yet eliminating the use of END2 cells. Three protocols were based on the activation and inhibition of the Wingless/Integrated (Wnt) signaling pathway, supplemented either with retinoic acid and the Wnt activator CHIR99021 (protocol B) or with the NODAL inhibitor SB431542 (protocol C) or with a combination of all three components (protocol D). An additional fourth protocol (protocol E) was used, which was originally developed by the manufacturer STEMCELL Technologies for the differentiation of hiPSC or hESC into atrial cardiomyocytes. All protocols (B, C, D, E) were compared to the END2 cell-based protocol A, serving as reference, in terms of their ability to differentiate hiPSC into cardiac pacemaker cells. Our analysis revealed that protocol E induced upregulation of 12 out of 15 cardiac pacemaker-specific genes. For comparison, reference protocol A upregulated 11, while protocols B, C and D upregulated 9, 10 and 8 cardiac pacemaker-specific genes, respectively. Cells differentiated according to protocol E displayed intense fluorescence signals of cardiac pacemaker-specific markers and showed excellent rate responsiveness to adrenergic and cholinergic stimulation. In conclusion, we characterized four novel and END2 cell-independent protocols for the differentiation of hiPSC into cardiac pacemaker cells, of which protocol E was the most efficient.

Filterless radio-over-fiber system that generates 80 and 160 GHz millimeter waves based on two MZMs.

In this paper, we propose a radio-over-fiber system with no filters and generate 80 and 160 GHz millimeter (mm) waves via two Mach-Zehnder modulators (MZMs). The two MZMs, biased at the maximum transmission point, are used to suppress odd-order sidebands. By controlling the phase difference between the RF driving signal of the two MZMs, the $\pm({4}{n - 2})$-order is canceled. By adjusting the optical attenuator and phase shifter, the 0-order sideband is canceled, so only the $\pm 4{n}$-order sidebands are left. The simulation results show that using a 10 GHz RF signal to drive the MZMs, we obtain an 80 GHz mm wave signal with a 36.59 dB optical sideband suppression ratio (OSSR), a 30.27 dB radio frequency sideband suppression ratio (RFSSR), and a 160 GHz mm wave signal with a 30.34 dB OSSR and 24.77 dB RFSSR. The results are consistent with the theoretical analysis. Because no optical filter is employed and only two MZMs are used, the system exhibits a simple structure, good performance and is low cost.

Improved Mask R-CNN for Aircraft Detection in Remote Sensing Images.

In recent years, remote sensing images has become one of the most popular directions in image processing. A small feature gap exists between satellite and natural images. Therefore, deep learning algorithms could be applied to recognize remote sensing images. We propose an improved Mask R-CNN model, called SCMask R-CNN, to enhance the detection effect in the high-resolution remote sensing images which contain the dense targets and complex background. Our model can perform object recognition and segmentation in parallel. This model uses a modified SC-conv based on the ResNet101 backbone network to obtain more discriminative feature information and adds a set of dilated convolutions with a specific size to improve the instance segmentation effect. We construct WFA-1400 based on the DOTA dataset because of the shortage of remote sensing mask datasets. We compare the improved algorithm with other state-of-the-art algorithms. The object detection AP50 and AP increased by 1-2% and 1%, respectively, objectively proving the effectiveness and the feasibility of the improved model.

Research on Airplane and Ship Detection of Aerial Remote Sensing Images Based on Convolutional Neural Network.

The wide range, complex background, and small target size of aerial remote sensing images results in the low detection accuracy of remote sensing target detection algorithms. Traditional detection algorithms have low accuracy and slow speed, making it difficult to achieve the precise positioning of small targets. This paper proposes an improved algorithm based on You Only Look Once (YOLO)-v3 for target detection of remote sensing images. Due to the difficulty in obtaining the datasets, research on small targets for complex images, such as airplanes and ships, is the focus of research. To make up for the problem of insufficient data, we screen specific types of training samples from the DOTA (Dataset of Object Detection in Aerial Images) dataset and select small targets in two different complex backgrounds of airplanes and ships to jointly evaluate the optimization degree of the improved network. We compare the improved algorithm with other state-of-the-art target detection algorithms. The results show that the performance indexes of both datasets are ameliorated by 1-3%, effectively verifying the superiority of the improved algorithm.

Arbitrary multiple beam forming by two cascaded liquid crystal optical phased arrays.

A new method for non-mechanical laser beam splitting and steering is demonstrated. Two cascaded liquid crystal optical phased arrays (LC-OPAs) controllably modulate the amplitude and phase of an incident laser beam to realize the near-field wavefronts of multiple simultaneous beams with arbitrary directions. Diffraction between the two arrays is avoided by precise 4-f imaging from one LC-OPA to the other (array resolution 1×1920). In the method of cascaded amplitude and phase (CAP) devices, numerical simulation results show the characteristics of amplitude and phase modulation profiles, as well as the far-field intensity patterns. Both the numerical and experimental results clearly demonstrate the capabilities of fast multi-beam forming with high efficiency (>85%, 4 beams) and accuracy (deviation <90µrad).

Effects of epigallocatechin-3-gallate on bovine oocytes matured in vitro.

OBJECTIVE: Epigallocatechin-3-gallate (EGCG) is a major ingredient of catechin polyphenols and is considered one of the most promising bioactive compounds in green tea because of its strong antioxidant properties. However, the protective role of EGCG in bovine oocyte in vitro maturation (IVM) has not been investigated. Therefore, we aimed to study the effects of EGCG on IVM of bovine oocytes. METHODS: Bovine oocytes were treated with different concentrations of EGCG (0, 25, 50, 100, and 200 µM), and the nuclear and cytoplasmic maturation, cumulus cell expansion, intracellular reactive oxygen species (ROS) levels, total antioxidant capacity, the early apoptosis and the developmental competence of in vitro fertilized embryos were measured. The mRNA abundances of antioxidant genes (nuclear factor erythriod-2 related factor 2 [NRF2], superoxide dismutase 1 [SOD1], catalase [CAT], and glutathione peroxidase 4 [GPX4]) in matured bovine oocytes were also quantified. RESULTS: Nuclear maturation which is characterized by first polar body extrusion, and cytoplasmic maturation characterized by peripheral and cortical distribution of cortical granules and homogeneous mitochondrial distribution were significantly improved in the 50 µM EGCG-treated group compared with the control group. Adding 50 µM EGCG to the maturation medium significantly increased the cumulus cell expansion index and upregulated the mRNA levels of cumulus cell expansion-related genes (hyaluronan synthase 2, tumor necrosis factor alpha induced protein 6, pentraxin 3, and prostaglandin 2). Both the intracellular ROS level and the early apoptotic rate of matured oocytes were significantly decreased in the 50 µM EGCG group, and the total antioxidant ability was markedly enhanced. Additionally, both the cleavage and blastocyst rates were significantly higher in the 50 µM EGCG-treated oocytes after in vitro fertilization than in the control oocytes. The mRNA abundance of NRF2, SOD1, CAT, and GPX4 were significantly increased in the 50 µM EGCG-treated oocytes. CONCLUSION: In conclusion, 50 µM EGCG can improve the bovine oocyte maturation, and the protective role of EGCG may be correlated with its antioxidative property.

Protective effects of melatonin on bovine sperm characteristics and subsequent in vitro embryo development.

We aimed to investigate the effect of melatonin on bovine frozen-thawed semen and its impact on fertilization outcome. Plasma membrane integrity, mitochondrial activity, acrosome integrity, and levels of intracellular reactive oxygen species (ROS) were measured in spermatozoa treated with different concentrations of melatonin. Melatonin-treated spermatozoa were then used for in vitro fertilization, followed by analysis of subsequent embryo development and the expression of apoptosis- and antioxidant-related genes. The results revealed that 10-5 and 10-3 M melatonin led to higher plasma membrane integrity, mitochondrial activity, and acrosome integrity, and significantly decreased intracellular ROS levels (P < 0.05). The blastocyst development rate of in vitro-produced bovine embryos originating from 10-3 M melatonin-treated spermatozoa was significantly higher, while the incidence of apoptotic nuclei in blastocysts was markedly lower than for embryos from any other group (P < 0.05). CASP3 and BAX mRNA abundance were significantly reduced whereas BCL2, XIAP, and CAT transcript abundance were significantly increased in embryos produced from spermatozoa treated with 10-3 M melatonin; GPX4 expression, however, was comparable in all treatment groups. Thus, 10-3 M melatonin can improve the quality of bovine frozen-thawed semen. These beneficial effects appear to influence preimplantation embryos, given the correlation with its anti-apoptotic and anti-oxidative properties. Mol. Reprod. Dev. 83: 993-1002, 2016 © 2016 Wiley Periodicals, Inc.

A clinical comparative study of anatomic parameters before and after total hip replacement on congenital dysplasia.

[Purpose] To study preoperative and postoperative hip circumference data of various types of congenital dysplasia of the hip treated with total hip replacement, including the femoral offset, femoral neck length, height, and hip abductor arm parameters. [Subjects and Methods] This study included seventy-eight cases of congenital dysplasia of the hip (I-III type). Furthermore, four parameters were measured, including the preoperative and postoperative femoral offset. Statistical data analysis was performed using the SPSS 13.0 software. [Results] The femoral offset was 33.3 ± 8.4 mm (preoperative) and 39.1 ± 7.1 mm (postoperative). The femoral head height was 59.5 ± 8.7 mm (preoperative) and 68.8 ± 11.0 mm (postoperative). The femoral neck length was 50.8 ± 10.8 mm (preoperative) and 61.5 ± 10.4 mm (postoperative). The hip abductor arm was 54.3 ± 9.6 mm (preoperative) 64.7 ± 10.1 mm (postoperative). The preoperative and postoperative parameters showed statistical differences. Furthermore, no significant differences were evidenced when comparing the postoperative hip parameters with the normal data parameters. [Conclusion] Total hip replacement on congenital dysplasia of the hip could lead to the rebuilt of an almost normal physiological anatomy for each hip case (type I-III).

[Causes of failure after total knee arthroplasty].

OBJECTIVE: To identify the causes of failure after total knee arthroplasty (TKA). METHODS: Retrospective reviews were conducted for the causes of failures of 181 TKA patients between January 2007 and December 2013. RESULTS: Among the causes of failures after primary TKA, infection was the major cause of failure (53%, 96/181) followed by aseptic loosening (16%, 29/181), arthrofibrosis (10%, 18/181), instability (6.6%, 12/181), extensor mechanism problem (5%, 9/181), wear (4.4%, 8/181), periprosthetic fracture (2.8%, 5/181) and others (2.2%, 4/181). And 64.1% occurred in the first two years, 19.9% occurred between 2 and 5 years and 16.0% occurred after 5 years after operation. Up to 84.0% occurred in 5 years. CONCLUSION: The top three causes of failures after primary TKA at our center are infection, aseptic loosening and arthrofibrosis.

A Comprehensive Study of NF3-Based Selective Etching Processes: Application to the Fabrication of Vertically Stacked Horizontal Gate-All-around Si Nanosheet Transistors.

In this paper, we demonstrate a comprehensive study of NF3-based selective etching processes for inner spacer formation and for channel release, enabling stacked horizontal gate-all-around Si nanosheet transistor architectures. A cyclic etching process consisting of an oxidation treatment step and an etching step is proposed and used for SiGe selective etching. The cyclic etching process exhibits a slower etching rate and higher etching selectivity compared to the direct etching process. The cycle etching process consisting of Recipe 1, which has a SiGe etching rate of 0.98 nm/cycle, is used for the cavity etch. The process achieved good interlayer uniformity of cavity depth (cavity depth ≤ 5 ± 0.3 nm), while also obtaining a near-ideal rectangular SiGe etch front shape (inner spacer shape = 0.84) and little Si loss (0.44 nm@ each side). The cycle etching process consisting of Recipe 4 with extremely high etching selectivity is used for channel release. The process realizes the channel release of nanosheets with a multi-width from 30 nm to 80 nm with little Si loss. In addition, a selective isotropic etching process using NF3/O2/Ar gas mixture is used to etch back the SiN film. The impact of the O2/NF3 ratio on the etching selectivity of SiN to Si and the surface roughness of SiN after etching is investigated. With the introduction of O2 into NF3/Ar discharge, the selectivity increases sharply, but when the ratio of O2/NF3 is up to 1.0, the selectivity tends to a constant value and the surface roughness of SiN increases rapidly. The optimal parameter is O2/NF3 = 0.5, resulting in a selectivity of 5.4 and a roughness of 0.19 nm.

Bioadhesive and electroactive hydrogels for flexible bioelectronics and supercapacitors enabled by a redox-active core-shell PEDOT@PZIF-71 system.

Stretchable and conductive hydrogels are rapidly emerging as new generation candidates for wearable devices. However, the poor electroactivity and bioadhesiveness of traditional conductive hydrogels has limited their applications. Herein, a mussel-inspired strategy is proposed to prepare a specific core-shell redox-active system, consisting of a polydopamine (PDA) modified zeolitic imidazolate framework 71 (ZIF-71) core, and a poly 3,4-ethylenedioxythiopene (PEDOT) shell. Owing to the abundant catechol groups, PEDOT can be assembled on the surface of ZIF-71 to create a redox-active system. The core-shell nanoparticles could act as a redox-active nanofiller to develop a conductive polyacrylamide (PAM) hydrogel with energy-storage properties. The core-shell PEDOT@PZIF-71 system provides a mussel-inspired environment in the hydrogel matrix and endows the hydrogel with stretchability and adhesiveness. The hydrogel can be applied as a functional electrode for both bioelectronics and supercapacitors. Moreover, this hydrogel exhibits favorable biocompatibility and can be implanted in vivo for biosignal measurement without causing inflammation. This redox-active core-shell PEDOT@PZIF-71 system provides a promising strategy for the design of hydrogel-based wearable electronic devices.

Exploring a novel seven-gene marker and mitochondrial gene TMEM38A for predicting cervical cancer radiotherapy sensitivity using machine learning algorithms.

Background: Radiotherapy plays a crucial role in the management of Cervical cancer (CC), as the development of resistance by cancer cells to radiotherapeutic interventions is a significant factor contributing to treatment failure in patients. However, the specific mechanisms that contribute to this resistance remain unclear. Currently, molecular targeted therapy, including mitochondrial genes, has emerged as a new approach in treating different types of cancers, gaining significant attention as an area of research in addressing the challenge of radiotherapy resistance in cancer. Methods: The present study employed a rigorous screening methodology within the TCGA database to identify a cohort of patients diagnosed with CC who had received radiotherapy treatment. The control group consisted of individuals who demonstrated disease stability or progression after undergoing radiotherapy. In contrast, the treatment group consisted of patients who experienced complete or partial remission following radiotherapy. Following this, we identified and examined the differentially expressed genes (DEGs) in the two cohorts. Subsequently, we conducted additional analyses to refine the set of excluded DEGs by employing the least absolute shrinkage and selection operator regression and random forest techniques. Additionally, a comprehensive analysis was conducted in order to evaluate the potential correlation between the expression of core genes and the extent of immune cell infiltration in patients diagnosed with CC. The mitochondrial-associated genes were obtained from the MITOCARTA 3.0. Finally, the verification of increased expression of the mitochondrial gene TMEM38A in individuals with CC exhibiting sensitivity to radiotherapy was conducted using reverse transcription quantitative polymerase chain reaction and immunohistochemistry assays. Results: This process ultimately led to the identification of 7 crucial genes, viz., GJA3, TMEM38A, ID4, CDHR1, SLC10A4, KCNG1, and HMGCS2, which were strongly associated with radiotherapy sensitivity. The enrichment analysis has unveiled a significant association between these 7 crucial genes and prominent signaling pathways, such as the p53 signaling pathway, KRAS signaling pathway, and PI3K/AKT/MTOR pathway. By utilizing these 7 core genes, an unsupervised clustering analysis was conducted on patients with CC, resulting in the categorization of patients into three distinct molecular subtypes. In addition, a predictive model for the sensitivity of CC radiotherapy was developed using a neural network approach, utilizing the expression levels of these 7 core genes. Moreover, the CellMiner database was utilized to predict drugs that are closely linked to these 7 core genes, which could potentially act as crucial agents in overcoming radiotherapy resistance in CC. Conclusion: To summarize, the genes GJA3, TMEM38A, ID4, CDHR1, SLC10A4, KCNG1, and HMGCS2 were found to be closely correlated with the sensitivity of CC to radiotherapy. Notably, TMEM38A, a mitochondrial gene, exhibited the highest degree of correlation, indicating its potential as a crucial biomarker for the modulation of radiotherapy sensitivity in CC.

A Novel Atomic-Level Post-Etch-Surface-Reinforcement Process for High-Performance p-GaN Gate HEMTs Fabrication.

A novel atomic-level post-etch-surface-reinforcement (PESR) process is developed to recover the p-GaN etching induced damage region for high performance p-GaN gate HEMTs fabrication. This process is composed of a self-limited surface modification step with O2 plasma, following by an oxide removal step with BCl3 plasma. With PESR process, the AlGaN surface morphology after p-GaN etching was comparable to the as-epitaxial level by AFM characterization, and the AlGaN lattice crystallization was also recovered which was measured in a confocal Raman system. The electrical measurement further confirmed the significant improvement of AlGaN surface quality, with one-order of magnitude lower surface leakage in a metal-semiconductor (MS) Schottky-diode and 6 times lower interface density of states (Dit) in a MIS C-V characterization. The XPS analysis of Al2O3/AlGaN showed that the p-GaN etching induced F-byproduct and Ga-oxide was well removed and suppressed by PESR process. Finally, the developed PESR process was successfully integrated in p-GaN gate HEMTs fabrication, and the device performance was significantly enhanced with ~20% lower of on-resistance and ~25% less of current collapse at Vds,Q bias of 40 V, showing great potential of leverage p-GaN gate HEMTs reliability.

Non-Buffer Epi-AlGaN/GaN on SiC for High-Performance Depletion-Mode MIS-HEMTs Fabrication.

A systematic study of epi-AlGaN/GaN on a SiC substrate was conducted through a comprehensive analysis of material properties and device performance. In this novel epitaxial design, an AlGaN/GaN channel layer was grown directly on the AlN nucleation layer, without the conventional doped thick buffer layer. Compared to the conventional epi-structures on the SiC and Si substrates, the non-buffer epi-AlGaN/GaN structure had a better crystalline quality and surface morphology, with reliable control of growth stress. Hall measurements showed that the novel structure exhibited comparable transport properties to the conventional epi-structure on the SiC substrate, regardless of the buffer layer. Furthermore, almost unchanged carrier distribution from room temperature to 150 °C indicated excellent two-dimensional electron gas (2DEG) confinement due to the pulling effect of the conduction band from the nucleation layer as a back-barrier. High-performance depletion-mode MIS-HEMTs were demonstrated with on-resistance of 5.84 Ω·mm and an output current of 1002 mA/mm. The dynamic characteristics showed a much smaller decrease in the saturation current (only ~7%), with a quiescent drain bias of 40 V, which was strong evidence of less electron trapping owing to the high-quality non-buffer AlGaN/GaN epitaxial growth.

CSPP1 stabilizes growing microtubule ends and damaged lattices from the luminal side.

Microtubules are dynamic cytoskeletal polymers, and their organization and stability are tightly regulated by numerous cellular factors. While regulatory proteins controlling the formation of interphase microtubule arrays and mitotic spindles have been extensively studied, the biochemical mechanisms responsible for generating stable microtubule cores of centrioles and cilia are poorly understood. Here, we used in vitro reconstitution assays to investigate microtubule-stabilizing properties of CSPP1, a centrosome and cilia-associated protein mutated in the neurodevelopmental ciliopathy Joubert syndrome. We found that CSPP1 preferentially binds to polymerizing microtubule ends that grow slowly or undergo growth perturbations and, in this way, resembles microtubule-stabilizing compounds such as taxanes. Fluorescence microscopy and cryo-electron tomography showed that CSPP1 is deposited in the microtubule lumen and inhibits microtubule growth and shortening through two separate domains. CSPP1 also specifically recognizes and stabilizes damaged microtubule lattices. These data help to explain how CSPP1 regulates the elongation and stability of ciliary axonemes and other microtubule-based structures.

Altered brain white matter structural motor network in spinocerebellar ataxia type 3.

OBJECTIVES: Spinocerebellar ataxia type 3 is a disorder within the brain network. However, the relationship between the brain network and disease severity is still unclear. This study aims to investigate changes in the white matter (WM) structural motor network, both in preclinical and ataxic stages, and its relationship with disease severity. METHODS: For this study, 20 ataxic, 20 preclinical SCA3 patients, and 20 healthy controls were recruited and received MRI scans. Disease severity was quantified using the SARA and ICARS scores. The WM motor structural network was created using probabilistic fiber tracking and was analyzed using graph theory and network-based statistics at global, nodal, and edge levels. In addition, the correlations between network topological measures and disease duration or clinical scores were analyzed. RESULTS: Preclinical patients showed increasing assortativity of the motor network, altered subnetwork including 12 edges of 11 nodes, and 5 brain regions presenting reduced nodal strength. In ataxic patients assortativity of the motor network also increased, but global efficiency, global strength, and transitivity decreased. Ataxic patients showed a wider altered subnetwork and a higher number of reduced nodal strengths. A negative correlation between the transitivity of the motor network and SARA and ICARS scores was observed in ataxic patients. INTERPRETATION: Changes to the WM motor network in SCA3 start before ataxia onset, and WM motor network involvement increases with disease progression. Global network topological measures of the WM motor network appear to be a promising image biomarker for disease severity. This study provides new insights into the pathophysiology of disease in SCA3/MJD.