The mammalian LINC complex component SUN1 regulates muscle regeneration by modulating drosha activity.

Here we show that a major muscle specific isoform of the murine LINC complex protein SUN1 is required for efficient muscle regeneration. The nucleoplasmic domain of the isoform specifically binds to and inhibits Drosha, a key component of the microprocessor complex required for miRNA synthesis. Comparison of the miRNA profiles between wildtype and SUN1 null myotubes identified a cluster of miRNAs encoded by a non-translated retrotransposon-like one antisense (Rtl1as) transcript that are decreased in the WT myoblasts due to SUN1 inhibition of Drosha. One of these miRNAs miR-127 inhibits the translation of the Rtl1 sense transcript, that encodes the retrotransposon-like one protein (RTL1), which is also required for muscle regeneration and is expressed in regenerating/dystrophic muscle. The LINC complex may therefore regulate gene expression during muscle regeneration by controlling miRNA processing. This provides new insights into the molecular pathology underlying muscular dystrophies and how the LINC complex may regulate mechanosignaling

Prognostic impact of c-Rel nuclear expression and REL amplification and crosstalk between c-Rel and the p53 pathway in diffuse large B-cell lymphoma

Dysregulated NF-κB signaling is critical for lymphomagenesis. The regulation, function, and clinical relevance of c-Rel/NF-κB activation in diffuse large B-cell lymphoma (DLBCL) have not been well studied. In this study we analyzed the prognostic significance and gene-expression signature of c-Rel nuclear expression as surrogate of c-Rel activation in 460 patients with de novo DLBCL. Nuclear c-Rel expression, observed in 137 (26.3%) DLBCL patients frequently associated with extranoal origin, did not show significantly prognostic impact in the overall- or germinal center B-like-DLBCL cohort, likely due to decreased pAKT and Myc levels, up-regulation of FOXP3, FOXO3, MEG3 and other tumor suppressors coincided with c-Rel nuclear expression, as well as the complicated relationships between NF-κB members and their overlapping function. However, c-Rel nuclear expression correlated with significantly poorer survival in p63+ and BCL-2− activated B-cell-like-DLBCL, and in DLBCL patients with TP53 mutations. Multivariate analysis indicated that after adjusting clinical parameters, c-Rel positivity was a significantly adverse prognostic factor in DLBCL patients with wild type TP53. Gene expression profiling suggested dysregulations of cell cycle, metabolism, adhesion, and migration associated with c-Rel activation. In contrast, REL amplification did not correlate with c-Rel nuclear expression and patient survival, likely due to co-amplification of genes that negatively regulate NF-κB activation. These insights into the expression, prognostic impact, regulation and function of c-Rel as well as its crosstalk with the p53 pathway underscore the importance of c-Rel and have significant therapeutic implications

A Two-Stage Path Planning Algorithm Based on Rapid-Exploring Random Tree for Ships Navigating in Multi-Obstacle Water Areas Considering COLREGs

A two-stage ship path planning method is proposed, based on the Rapid-exploring Random Tree (RRT) algorithm, which is composed of global path planning and local path planning, addressing the important problem of finding an economical and safe path from start to destination for ships under dynamic environment, especially in waters with multiple obstacles and multiple target ships. The global path planning takes into consideration the ship draft and Under Keel Clearance to find navigable water using RRT, and reduces the path length and waypoints based on elliptic sampling and smoothing. In the local path planning, a dynamic collision risk detection model is constructed by introducing the Quaternion Ship Domain under a dynamic environment, and the restrictions of ship manoeuvrability and COLREGs are also involved. The simulation results show that the proposed model can find a satisfactory path within a few iterations, and keep clear of both static obstacles and dynamic ships. The research can be used to make and verify planned ship routes before sailing and to guide officers to make decisions regarding collision avoidance

Use of Hybrid Causal Logic Method for Preliminary Hazard Analysis of Maritime Autonomous Surface Ships

Funding Information: The research was supported by the Hubei Provincial Natural Science Foundation of China (2019CFA039), the Natural Science Foundation of China (No.52071247) and the innovation and entrepreneurship team import project of Shaoguan city (201208176230693). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Recently, the safety issue of maritime autonomous surface ships (MASS) has become a hot topic. Preliminary hazard analysis of MASS can assist autonomous ship design and ensure safe and reliable operation. However, since MASS technology is still at its early stage, there are not enough data for comprehensive hazard analysis. Hence, this paper attempts to combine conventional ship data and MASS experiments to conduct a preliminary hazard analysis for autonomy level III MASS using the hybrid causal logic (HCL) method. Firstly, the hazardous scenario of autonomy level III MASS is developed using the event sequence diagram (ESD). Furthermore, the fault tree (FT) method is utilized to analyze mechanical events in ESD. The events involving human factors and related to MASS in the ESD are analyzed using Bayesian Belief Network (BBN). Finally, the accident probability of autonomy level III MASS is calculated in practice through historical data and a test ship with both an autonomous and a remote navigation mode in Wuhan and Nanjing, China. Moreover, the key influence factors are found, and the accident-causing event chains are identified, thus providing a reference for MASS design and safety assessment process. This process is applied to the preliminary hazard analysis of the test ship.Peer reviewe

Thorea baiyunensis sp. nov. (Thoreales, Rhodophyta) and T. okadae, a new record from China

The freshwater red algal order Thoreales has a triphasic life history, of which the “Chantransia” phase is a small filamentous sporophyte. The “Chantransia” stage is difficult to distinguish from species in the genus Audouinella by its morphological characteristics. In this study, five “Chantransia” isolates (GX41, GX81, GD224, GD225, GD228) were collected from Guangxi Zhuang Autonomous Region and Guangdong Province in China. Based on morphological data, all five isolates were similar to A. pygmaea, whereas sequence data from the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (rbcL) gene and the 5’ region of the mitochondrial cytochrome oxidase I gene (COI-5P) determined that these specimens represented the “Chantransia” stage of two species in the genus Thorea rather than Audouinella. Phylogenetic analyses of the concatenated genes supported the proposal of a new species, T. baiyunensis, and a new geographic record of T. okadae, a species previously described only in Japan. Therefore, combined with previous records, four species of this genus are now recognized in China, including T. hispida, T. violacea, T. baiyunensis and T. okadae

Mechanical ventilation after bidirectional superior cavopulmonary anastomosis for single-ventricle physiology: a comparison of pressure support ventilation and neurally adjusted ventilatory assist

We evaluated the effects of different respiratory assist modes on cerebral blood flow (CBF) and arterial oxygenation in single-ventricle patients after bidirectional superior cavopulmonary anastomosis (BCPA). We hypothesized that preserved auto-regulation of respiration during neurally adjusted ventilatory assist (NAVA) may have potential advantages for CBF and pulmonary blood flow regulation after the BCPA procedure. We enrolled 23 patients scheduled for BCPA, who underwent pressure-controlled ventilation (PCV), pressure support ventilation (PSV), and NAVA at two assist levels for all modes in a randomized order. PCV targeting large V T (15 mL × kg(-1)) resulted in lower CBF and oxygenation compared to targeting low V T (10 mL × kg(-1)). During PSV and NAVA, ventilation assist levels were titrated to reduce EAdi from baseline by 75 % (high assist) and 50 % (low assist). High assist levels during PSV (PSVhigh) were associated with lower PaCO2, PaO2, and O2SAT, lower CBF, and higher pulsatility index compared with those during NAVAhigh. There were no differences in parameters when using low assist levels, except for slightly greater oxygenation in the NAVAlow group. Modifying assist levels during NAVA did not influence hemodynamics, cerebral perfusion, or gas exchange. Targeting the larger V T during PCV resulted in hyperventilation, did not improve oxygenation, and was accompanied by reduced CBF. Similarly, high assist levels during PSV led to mild hyperventilation, resulting in reduced CBF. NAVA's results were independent of the assist level chosen, causing normalized PaCO2, improved oxygenation, and better CBF than did any other mode, with the exception of PSV at low assist levels

Hepatitis C virus positive diffuse large B-cell lymphomas have distinct molecular features and lack BCL2 translocations

The clinical presentation of patients with hepatitis C virus (HCV)-positive diffuse large B-cell lymphoma (DLBCL) is different from their HCV-negative counterparts, but the underlying molecular and pathological characteristics are largely under investigated. The virus has a role in lymphomagenesis, as witnessed by the curative potential of antiviral therapy in HCV-related low-grade B-cell lymphomas

AKT Hyperactivation and the Potential of AKT-Targeted Therapy in Diffuse Large B-Cell Lymphoma.

Contains fulltext : 177844.pdf (Publisher’s version ) (Open Access

AKT Hyperactivation and the Potential of AKT-Targeted Therapy in Diffuse Large B-Cell Lymphoma

AKT signaling is important for proliferation and survival of tumor cells. The clinical significance of AKT activation in diffuse large B-cell lymphoma (DLBCL) is not well analyzed. Here, we assessed expression of phosphorylated AKT (p-AKT) in 522 DLBCL patients. We found that high levels of p-AKT nuclear expression, observed in 24.3% of the study cohort, were associated with significantly worse progression-free survival and Myc and Bcl-2 overexpression. However, multivariate analysis indicated that AKT hyperactivation was not an independent factor. miRNA profiling analysis demonstrated that 63 miRNAs directly or indirectly related to the phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin pathway were differentially expressed between DLBCLs with high and low p-AKT nuclear expression. We further targeted AKT signaling using a highly selective AKT inhibitor MK-2206 in 26 representative DLBCL cell lines and delineated signaling alterations using a reverse-phase protein array. MK-2206 treatment inhibited lymphoma cell viability, and MK-2206 sensitivity correlated with AKT activation status in DLBCL cells. On MK-2206 treatment, p-AKT levels and downstream targets of AKT signaling were significantly decreased, likely because of the decreased feedback repression; Rictor and phosphatidylinositol 3-kinase expression and other compensatory pathways were also induced. This study demonstrates the clinical and therapeutic implications of AKT hyperactivation in DLBCL and suggests that AKT inhibitors need to be combined with other targeted agents for DLBCL to achieve optimal clinical efficacy