Contralateral seventh cervical nerve transfer for central spastic arm paralysis: a systematic review and meta-analysis

ObjectivesThe specific benefits of a contralateral cervical 7 nerve transplant in people with spastic paralysis of the upper extremity caused by cerebral nerve injury are unclear. To evaluate the efficacy and safety of contralateral C7 nerve transfer for central spastic paralysis of the upper extremity, we conducted a comprehensive literature search and meta-analysis.Materials and methodsPRISMA guidelines were used to search the databases for papers comparing the efficacy of contralateral cervical 7 nerve transfer vs. rehabilitation treatment from January 2010 to August 2022. The finishing indications were expressed using SMD ± mean. A meta-analysis was used to assess the recovery of motor function in the paralyzed upper extremity.ResultsThe meta-analysis included three publications. One of the publications offers information about RCTs and non-RCTs. A total of 384 paralyzed patients were included, including 192 who underwent CC7 transfer and 192 who received rehabilitation. Results from all patients were combined and revealed that patients who had CC7 transfer may have regained greater motor function in the Fugl-Meyer score (SMD 3.52, 95% CI = 3.19–3.84, p < 0.00001) and had superior improvement in range of motion compared to the rehabilitation group (SMD 2.88, 95% CI = 2.47–3.29, p < 0.00001). In addition, the spasticity in the paralyzed upper extremity significantly improved in patients with CC7 transfer (SMD −1.42, 95% CI = −1.60 to −1.25, p < 0.00001).ConclusionOur findings suggested that a contralateral C7 nerve transfer, which has no additional adverse effects on the healthy upper limb, is a preferable method to restore motor function

Deadenylation is prerequisite for P-body formation and mRNA decay in mammalian cells

Deadenylation is the major step triggering mammalian mRNA decay. One consequence of deadenylation is the formation of nontranslatable messenger RNA (mRNA) protein complexes (messenger ribonucleoproteins [mRNPs]). Nontranslatable mRNPs may accumulate in P-bodies, which contain factors involved in translation repression, decapping, and 5′-to-3′ degradation. We demonstrate that deadenylation is required for mammalian P-body formation and mRNA decay. We identify Pan2, Pan3, and Caf1 deadenylases as new P-body components and show that Pan3 helps recruit Pan2, Ccr4, and Caf1 to P-bodies. Pan3 knockdown causes a reduction of P-bodies and has differential effects on mRNA decay. Knocking down Caf1 or overexpressing a Caf1 catalytically inactive mutant impairs deadenylation and mRNA decay. P-bodies are not detected when deadenylation is blocked and are restored when the blockage is released. When deadenylation is impaired, P-body formation is not restorable, even when mRNAs exit the translating pool. These results support a dynamic interplay among deadenylation, mRNP remodeling, and P-body formation in selective decay of mammalian mRNA

Stability Mechanism and Control Factors on Equipment Removal Area under “Goaf-Roof-Coal” Structure

One of the main difficulties in longwall mining (LM) is the movement of mining equipment from one panel to the next panel during mining process. The shields of the LM face may be damaged by the collapse of the roof in shallow coal seam under the “Goaf-Roof-Coal” (GRC) structure, especially when moving the shields from the current panel to the next panel. In order to solve this problem, the stability mechanism and its control factors during the LM equipment removal were investigated by using comprehensive methods including theoretical analysis, numerical simulation, and field validation based on the working conditions of Panel 31102 in Liangshuijing Coal Mine. The numerical simulations demonstrate that four different failure zones, shear failure zone, tension failure zone, partly elastic zone, and plastic failure zone, appear around the area due to the position of rock and the arrangements of the supports. The shear failure zone, which is controlled by shield working resistance and roof supporting strength, is the main cause of the failure in the removal area. To minimize the shear failure zone, several measures such as optimizing the end position for LM face, decreasing the width of removal area, and increasing the amount of cable support were taken to ensure the stability of surrounding rock in removal area, which have successfully controlled the damage of roof and equipment in Panel 31102. The field observation confirms that the proposed stability mechanism and control measures are effective under GRC structure

Optimal Layout Methods for Deep Chamber to Separate Coal and Gangue Based on the Weak Stratum Horizon

Aiming at the optimal layout of a deep chamber for coal–gangue separation (DCCS) based on the weak stratum horizon, an in-depth study was carried out by combining field investigations, model tests, and numerical simulations. Firstly, the main structural characteristics of DCCS were summarized. Then, the deformation and failure law for rocks surrounding DCCS were revealed under different horizons in the weak stratum. Finally, the optimal layout methods of DCCS based on the thickness and horizon in the weak stratum were determined in different in situ stresses, using the proposed comprehensive evaluation method for surrounding-rock stability. The results show that if the thickness of the weak stratum was small, the side near the roof of DCCS should be arranged along the weak stratum when the lateral pressure coefficient was λ λ > 1. The side near the floor of DCCS was arranged along the weak stratum when 0.6 ≤ λ ≤ 1 and the surrounding-rock stability was the best. If the thickness of the weak stratum was large, the side of DCCS should be arranged along the weak stratum when λ λ > 1. The floor of DCCS was arranged along the weak stratum when 0.6 ≤ λ ≤ 1, which was most favorable for the surrounding-rock control. The research results have important guiding significance for the spatial layout and support design of DCCS

Functional dissection of hnRNP D suggests that nuclear import is required before hnRNP D can modulate mRNA turnover in the cytoplasm

Many shuttling proteins not only function in the nucleus but also control mRNA fates in the cytoplasm. We test whether a link exists between their nuclear association with mRNPs and their cytoplasmic functions using the p37 isoform of hnRNP D, which inhibits the rapid cytoplasmic mRNA decay in NIH3T3 cells. We showed that p37 shuttles between nucleus and cytoplasm, and narrowed down the nuclear import signal to a 50-amino-acid C-terminal domain. A p37 mutant missing this domain, still capable of associating with target mRNAs in vitro, was confined to the cytoplasm, where it was unable to block cytoplasmic mRNA turnover. Introducing heterologous shuttling domains to this mutant, thereby restoring its ability to enter the nucleus, concomitantly restored its cytoplasmic function. Association of p37 with its target mRNAs can only be detected when it can enter the nucleus. Our results suggest that nuclear import of hnRNP D is a prerequisite for it to exert its cytoplasmic function. This study provides a useful model system to elucidate the mechanisms by which “nuclear history” affects cytoplasmic mRNA fates

Presentation_2_Contralateral seventh cervical nerve transfer for central spastic arm paralysis: a systematic review and meta-analysis.pdf

ObjectivesThe specific benefits of a contralateral cervical 7 nerve transplant in people with spastic paralysis of the upper extremity caused by cerebral nerve injury are unclear. To evaluate the efficacy and safety of contralateral C7 nerve transfer for central spastic paralysis of the upper extremity, we conducted a comprehensive literature search and meta-analysis.Materials and methodsPRISMA guidelines were used to search the databases for papers comparing the efficacy of contralateral cervical 7 nerve transfer vs. rehabilitation treatment from January 2010 to August 2022. The finishing indications were expressed using SMD ± mean. A meta-analysis was used to assess the recovery of motor function in the paralyzed upper extremity.ResultsThe meta-analysis included three publications. One of the publications offers information about RCTs and non-RCTs. A total of 384 paralyzed patients were included, including 192 who underwent CC7 transfer and 192 who received rehabilitation. Results from all patients were combined and revealed that patients who had CC7 transfer may have regained greater motor function in the Fugl-Meyer score (SMD 3.52, 95% CI = 3.19–3.84, p ConclusionOur findings suggested that a contralateral C7 nerve transfer, which has no additional adverse effects on the healthy upper limb, is a preferable method to restore motor function.</p

Presentation_1_Contralateral seventh cervical nerve transfer for central spastic arm paralysis: a systematic review and meta-analysis.pdf

ObjectivesThe specific benefits of a contralateral cervical 7 nerve transplant in people with spastic paralysis of the upper extremity caused by cerebral nerve injury are unclear. To evaluate the efficacy and safety of contralateral C7 nerve transfer for central spastic paralysis of the upper extremity, we conducted a comprehensive literature search and meta-analysis.Materials and methodsPRISMA guidelines were used to search the databases for papers comparing the efficacy of contralateral cervical 7 nerve transfer vs. rehabilitation treatment from January 2010 to August 2022. The finishing indications were expressed using SMD ± mean. A meta-analysis was used to assess the recovery of motor function in the paralyzed upper extremity.ResultsThe meta-analysis included three publications. One of the publications offers information about RCTs and non-RCTs. A total of 384 paralyzed patients were included, including 192 who underwent CC7 transfer and 192 who received rehabilitation. Results from all patients were combined and revealed that patients who had CC7 transfer may have regained greater motor function in the Fugl-Meyer score (SMD 3.52, 95% CI = 3.19–3.84, p ConclusionOur findings suggested that a contralateral C7 nerve transfer, which has no additional adverse effects on the healthy upper limb, is a preferable method to restore motor function.</p

Versatile applications of transcriptional pulsing to study mRNA turnover in mammalian cells

Development of transcriptional pulsing approaches using the c-fos and Tet-off promoter systems greatly facilitated studies of mRNA turnover in mammalian cells. However, optimal protocols for these approaches vary for different cell types and/or physiological conditions, limiting their widespread application. In this study, we have further optimized transcriptional pulsing systems for different cell lines and developed new protocols to facilitate investigation of various aspects of mRNA turnover. We apply the Tet-off transcriptional pulsing strategy to investigate ARE-mediated mRNA decay in human erythroleukemic K562 cells arrested at various phases of the cell cycle by pharmacological inhibitors. This application facilitates studies of the role of mRNA stability in control of cell-cycle dependent gene expression. To advance the investigation of factors involved in mRNA turnover and its regulation, we have also incorporated recently developed transfection and siRNA reagents into the transcriptional pulsing approach. Using these protocols, siRNA and DNA plasmids can be effectively cotransfected into mouse NIH3T3 cells to obtain high knockdown efficiency. Moreover, we have established a tTA-harboring stable line using human bronchial epithelial BEAS-2B cells and applied the transcriptional pulsing approach to monitor mRNA deadenylation and decay kinetics in this cell system. This broadens the application of the transcriptional pulsing system to investigate the regulation of mRNA turnover related to allergic inflammation. Critical factors that need to be considered when employing these approaches are characterized and discussed

Human TOB, an Antiproliferative Transcription Factor, Is a Poly(A)-Binding Protein-Dependent Positive Regulator of Cytoplasmic mRNA Deadenylation▿ †

In mammalian cells, mRNA decay begins with deadenylation, which involves two consecutive phases mediated by the PAN2-PAN3 and the CCR4-CAF1 complexes, respectively. The regulation of the critical deadenylation step and its relationship with RNA-processing bodies (P-bodies), which are thought to be a site where poly(A)-shortened mRNAs get degraded, are poorly understood. Using the Tet-Off transcriptional pulsing approach to investigate mRNA decay in mouse NIH 3T3 fibroblasts, we found that TOB, an antiproliferative transcription factor, enhances mRNA deadenylation in vivo. Results from glutathione S-transferase pull-down and coimmunoprecipitation experiments indicate that TOB can simultaneously interact with the poly(A) nuclease complex CCR4-CAF1 and the cytoplasmic poly(A)-binding protein, PABPC1. Combining these findings with those from mutagenesis studies, we further identified the protein motifs on TOB and PABPC1 that are necessary for their interaction and found that interaction with PABPC1 is necessary for TOB's deadenylation-enhancing effect. Moreover, our immunofluorescence microscopy results revealed that TOB colocalizes with P-bodies, suggesting a role of TOB in linking deadenylation to the P-bodies. Our findings reveal a new mechanism by which the fate of mammalian mRNA is modulated at the deadenylation step by a protein that recruits poly(A) nuclease(s) to the 3′ poly(A) tail-PABP complex