Explore the vast range of titles available.

Microtubules control different aspects of cell polarization. In cells with a radial microtubule system, a pivotal role in setting up asymmetry is attributed to the relative positioning of the centrosome and the nucleus. Here, we show that centrosome loss had no effect on the ability of endothelial cells to polarize and move in 2D and 3D environments. In contrast, non-centrosomal microtubules stabilized by the microtubule minus-end-binding protein CAMSAP2 were required for directional migration on 2D substrates and for the establishment of polarized cell morphology in soft 3D matrices. CAMSAP2 was also important for persistent endothelial cell sprouting during in vivo zebrafish vessel development. In the absence of CAMSAP2, cell polarization in 3D could be partly rescued by centrosome depletion, indicating that in these conditions the centrosome inhibited cell polarity. We propose that CAMSAP2-protected non-centrosomal microtubules are needed for establishing cell asymmetry by enabling microtubule enrichment in a single-cell protrusion. Networks of blood vessels grow like trees. Sprouts appear on existing vessels, stretching out to form new branches in a process called angiogenesis. The cells responsible are the same cells that line the finished vessels. These “endothelial cells” start the process by reorganizing themselves to face the direction of the new sprout, changing shape to become asymmetrical, and then they begin to migrate. Beneath the surface, a network of protein scaffolding supports each migrating cell. The scaffolding includes tube-like fibers called microtubules that extend towards the cell membrane and organize the inside of the cell. Destroying microtubules damages blood vessel formation, but their exact role remains unclear. A structure called the centrosome can organize microtubules within cells. The centrosome was generally believed to act like a compass, pointing in the direction that the cell will move. Microtubules can anchor to the centrosome, and this structure is thought to play an important role in cell migration. Yet, many microtubules organize without it; these microtubules instead are organized by a compartment of the cell called the Golgi apparatus and are stabilized by a protein named CAMSAP2. Martin et al. now report that removing the cells’ centrosomes did not affect cell migration, but getting rid of CAMSAP2 did. Analysis of cell shape and movement in cells grown in the laboratory and in living animals revealed that cells cannot become asymmetrical, or “polarize”, and migrate without CAMSAP2. In a two-dimensional wound-healing assay, a sheet of cells originally grown from the vessels of a human umbilical cord was scratched, and a microscope was then used to record the cell’s movement as they repaired the injury. Normally, the cells on either side move in a straight line using their microtubules, and though the process was not affected in cells without centrosomes, it was in those without CAMSAP2. Even more striking results were seen in three-dimensional assays. When the same blood vessel cells from human umbilical cords are grown as spheres inside collagen gels, they form sprouts as they would in the body. Without CAMSAP2, the cells could not organize their microtubules and they were unable to elongate in one direction and form stable sprouts. Lastly, depleting CAMSAP2 also prevented the normal formation of blood vessels in zebrafish embryos. Taken together, these findings change our understanding of how microtubules affect cell movement and how important the centrosome is for this process. Further work could have an impact on human health, not least in cancer research. Tumors need a good blood supply to grow, so understanding how to block blood vessel formation could lead to new treatments. Microtubules are already a target for cancer therapy, so future work could help to optimize the use of existing drugs.

The major microtubule-organizing center (MTOC) in animal cells, the centrosome, comprises a pair of centrioles surrounded by pericentriolar material (PCM), which nucleates and anchors microtubules. Centrosome assembly depends on PCM binding to centrioles, PCM self-association and dynein-mediated PCM transport, but the self-assembly properties of PCM components in interphase cells are poorly understood. Here, we used experiments and modeling to study centriole-independent features of interphase PCM assembly. We showed that when centrioles are lost due to PLK4 depletion or inhibition, dynein-based transport and self-clustering of PCM proteins are sufficient to form a single compact MTOC, which generates a dense radial microtubule array. Interphase self-assembly of PCM components depends on γ-tubulin, pericentrin, CDK5RAP2 and ninein, but not NEDD1, CEP152, or CEP192. Formation of a compact acentriolar MTOC is inhibited by AKAP450-dependent PCM recruitment to the Golgi or by randomly organized CAMSAP2-stabilized microtubules, which keep PCM mobile and prevent its coalescence. Linking of CAMSAP2 to a minus-end-directed motor leads to the formation of an MTOC, but MTOC compaction requires cooperation with pericentrin-containing self-clustering PCM. Our data reveal that interphase PCM contains a set of components that can self-assemble into a compact structure and organize microtubules, but PCM self-organization is sensitive to motor- and microtubule-based rearrangement.

Down syndrome is one of the most common genetic disorders. The distinctive facial features of Down syndrome provide an opportunity for automatic identification. Recent studies showed that facial recognition technologies have the capability to identify genetic disorders. However, there is a paucity of studies on the automatic identification of Down syndrome with facial recognition technologies, especially using deep convolutional neural networks. Here, we developed a Down syndrome identification method utilizing facial images and deep convolutional neural networks, which quantified the binary classification problem of distinguishing subjects with Down syndrome from healthy subjects based on unconstrained two-dimensional images. The network was trained in two main steps: First, we formed a general facial recognition network using a large-scale face identity database (10,562 subjects) and then trained (70%) and tested (30%) a dataset of 148 Down syndrome and 257 healthy images curated through public databases. In the final testing, the deep convolutional neural network achieved 95.87% accuracy, 93.18% recall, and 97.40% specificity in Down syndrome identification. Our findings indicate that the deep convolutional neural network has the potential to support the fast, accurate, and fully automatic identification of Down syndrome and could add considerable value to the future of precision medicine.

Postsecondary institutions worldwide generally provide career development courses or similar courses to better prepare undergraduate students for healthy and quality future careers. Understanding whether these career development courses positively affect students’ career-related outcomes is crucial. Utilizing survey data collected from a large research university located in the eastern part of China, we found that students who have taken at least one career course exhibited career awareness and career planning abilities that were 0.096 and 0.147 units higher, respectively, than those of students who have not taken career courses, with other variables held constant. More specifically, an additional career course was statistically significantly associated with a 0.099, 0.084, and 0.175 unit increase in students’ career awareness, job search self-efficacy, and career planning ability, respectively. A student’s college major and annual family income seemed to be good predictors for a student’s career awareness, job search self-efficacy, and career-planning ability. Furthermore, the more career courses that a student took, the higher the career awareness, job search self-efficacy, and career planning ability that the student had. With these findings in mind, our study recommends postsecondary stakeholders to leverage such courses to help students better prepare for a healthy and quality career development.

Deep brain stimulation (DBS) has shown a remarkably high effectiveness for Parkinson's disease (PD). In many PD patients during DBS surgery, the therapeutic effects of the stimulation test are estimated by assessing changes in bradykinesia as the stimulation voltage is increased. In this study, we evaluated the potential of the leap motion controller (LMC) to quantify the motor component of bradykinesia in PD during DBS surgery, as this could make the intraoperative assessment of bradykinesia more accurate. Seven participants with idiopathic PD receiving chronic bilateral subthalamic nucleus deep brain stimulation (DBS) therapy were recruited. The motor tasks of finger tapping (FT), hand opening and closing (OC), and hand pronation and supination (PS) were selected pre- and intraoperatively in accordance with the Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale. During the test, participants performed these tasks in sequence while being simultaneously monitored by the LMC and two professional clinicians. Key kinematic parameters differed between the preoperative and intraoperative conditions. We suggest that the average velocity (V¯) and average amplitude (A¯) of PS isolate the bradykinetic feature from that movement to provide a measure of the intraoperative state of the motor system. The LMC achieved promising results in evaluating PD patients’ hand and finger bradykinesia during DBS surgery.

Introduction. Postural instability is commonly observed in Parkinson’s disease, leading to an increasing risk of falling and worsening as the disease progresses. We found that limit of stability can be applied to reflect the dynamic evolution of postural instability in patients with Parkinson's disease. Methods. Forty-three patients (9 of Hoehn and Yahr stage I, 12 of stage II, 14 of stage III, and 8 of stage IV) met the criteria for the diagnosis of idiopathic Parkinson’s disease and could stand independently for at least 10 minutes. Twelve healthy controls with no sign of parkinsonism were also recruited. Postural instability was assessed by posturography in different directions (forward, backward, right, left, forward-right, forward-left, backward-right, and backward-left). This study trial was registered with the Chinese Clinical Trial Registry (no. ChiCTR1900022715). Results. All participants were able to complete the limit of stability tasks without any complications. Patients in stages II to IV exhibited smaller end point excursion and slower time to complete than controls, suggesting an impaired limit of stability. The patients in stage II exhibited a remarkable decline in most directions compared to controls, except for right and left, and forward and backward decline occurred the earliest. For patients in stage III, right was the only direction with no significant difference from controls. In stage IV patients, the limit of stability declined significantly in all directions (p<0.05). Conclusions. The postural abnormalities of Parkinson’s disease can occur at early stages, and the pattern of decline is more severe in the forward-backward direction. This trial is registered with ChiCTR1900022715.

China’s college graduates are experiencing extreme employment pressure, especially under the effects brought about by COVID-19. This study examines whether career-related psychological factors jointly affect college students’ career decision-making self-efficacy (CDMSE) to achieve sustainable career development. Leveraging self-administrated survey data with 703 undergraduate students, we find that career awareness, job search self-efficacy (JSSE), and career planning ability positively relate to CDMSE. We also find that career awareness positively correlates with JSSE and career planning ability. In addition, the results support that perceived career reality positively relates to JSSE and career planning ability. However, no evidence indicates the positive relationship between perceived career reality and CDMSE. Furthermore, mediation tests confirm that JSSE and career planning ability partially mediate the relationship between career awareness and CDMSE. Practical implications, limitations, and future directions are also discussed.

Vetiveria zizanioides is ideal in maintaining soil and water, and is widely used for remediation of soil contaminated by heavy metals. However, it is affected by high-temperature stress. In this study, Vetiveria zizanioides plants were sprayed with 6-BA and ABA in a growth chamber 1 d before heat stress treatment, then the plants were subjected to high-temperature conditions. Relative water content, relative electrical conductivity, contents of ascorbic acid (AsA) and reduced glutathione (GSH) as the antioxidative substances, and content of malondiadehyde (MDA) were determined. Also, the antioxidative enzyme activities and the osmoprotectants levels were detected. Diaminobenzidine (DAB) staining of leaves and roots in Vetiveria zizanioides was observed for determination of hydrogen peroxide accumulation. The results showed that relative water content was decreased, relative electrical conductivity and MDA content were increased by the heat stress treatment. Under high-temperature conditions, relative water content was increased and relative electrical conductivity was decreased by 6-BA and ABA treatments. At the middle and the late stages of the heat stress treatment, activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), and the contents of ASA and GSH in leaves of the 6-BA-treated and ABA-treated plants were significantly higher, whereas the MDA content was significantly lower than those in the high-temperature controls. Hydrogen peroxide accumulation levels in the 6-BA-treated and ABA-treated leaves and roots were lower than in the high-temperature controls. Contents of soluble sugar, sucrose, and glucose in the 6-BA-treated and ABA-treated leaves were significantly higher than those in the high-temperature controls. Proline content in the 6-BA-treated and ABA-treated leaves was stable. The results suggested that the enhancement of the heat resistance by 6-BA and ABA treatments was correlated with the activation of the antioxidant system, as well as the sugar-based osmoprotectant.

MicroRNA (miR)-mediated mRNA and multiple signaling pathway dysregulations have been extensively implicated in several cancer types, including gliomas. Although previous studies have reported that miR-301a acts as an oncogene, the underlying mechanisms of miR-301a in the initiation and progression of glioma remain unknown. The present study aimed to investigate the involvement of miR-301a-mediated signaling pathway dysregulation in glioma. The results identified that miR-301a was significantly upregulated in gliomas and was associated with a poor prognosis based on The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. Moreover, zinc and ring finger 3 (ZNRF3) exerted a critical role in the miR-301a-mediated effects on the malignant phenotype, such as by affecting proliferation and apoptosis. Mechanistically, the TOP/FOP luciferase assay, western blotting and immunofluorescence results demonstrated that miR-301a knockdown inhibited the wnt/β-catenin signaling pathway, at least partially via ZNRF3, while ZNRF3 was a direct functional target of miR-301a, as indicated by luciferase reporter assay and western blot analysis. Furthermore, ZNRF3 could in turn repress miR-301a expression, which was dependent on the wnt pathway. Collectively, the present study identified a novel miR-301a/ZNRF3/wnt/β-catenin signaling feedback loop that serves critical roles in glioma tumorigenesis, and that may represent a potential therapeutic target.

Objectives: Deep-brain stimulation (DBS) has been used for the treatment of medically refractory dystonia with excellent results. In this study, we compared in detail the therapeutic advantages of two DBS targets for generalized isolated dystonia. Methods: In this retrospective study, we recruited 29 patients with generalized isolated dystonia who had undergone DBS treatment targeting either the globus pallidus interna (GPi) or the subthalamic nucleus (STN) in the Department of Functional Neurosurgery at Tiantan Hospital, Beijing, China, between January 2016 and December 2021. The movement and disability subscales of the Burke–Fahn–Marsden dystonia rating scale (BFMDRS) were used to assess the severity of their dystonic symptoms and their activities of daily living, respectively. SF-36 was used to evaluate the patients’ health-related quality of life. Results: The percentage improvement in the BFMDRS-M score at 6 months relative to the baseline score was clearly higher in the STN group (63.91%) than in the GPi group (38.36%). At the 3-, 6-, and 12-month follow-ups, the percentage improvement in arm symptoms was significantly higher after DBS of the STN (70.64%, 80.66%, and 76.89%, respectively) than after stimulation of the GPi (36.75%, 34.21%, and 38.47%, respectively). At 12 months after surgery, patient quality of life had improved on all SF-36 subscales in both groups. Conclusions: STN-DBS may have more advantages than GPi-DBS in patients with obvious arm dystonia. STN-DBS had a better clinical effect than GPi-DBS within 6 months after surgery.