Diaphragmatic ultrasound can help evaluate pulmonary dysfunction in patients with stroke.

Objective: Pulmonary dysfunction after stroke is increasingly gaining attention from clinical and rehabilitation specialists. However, owing to cognitive and motor dysfunction in patients with stroke, determining the pulmonary function of these patients remains challenging. The present study aimed to devise a simple method for an early evaluation of pulmonary dysfunction in patients with stroke. Methods: Overall, 41 patients with stroke in the recovery period (stroke group) and 22 matched healthy controls (control group) were included in the study. We first collected data regarding baseline characteristics for all participants. Furthermore, the participants with stroke were examined using additional scales, such as the National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer assessment scale (FMA), and modified Barthel Index (MBI). Subsequently, we examined the participants with simple pulmonary function detection and diaphragm ultrasound (B-mode). Ultrasound indices calculated were as follows: the thickness of the diaphragm under the position of functional residual capacity (TdiFRC), the thickness of the diaphragm under the position of forced vital capacity (TdiFVC), thickness fraction, and diaphragmatic mobility. Finally, we compared and analyzed all data to identify group differences, the correlation between pulmonary function and diaphragmatic ultrasound indices, and the correlation between pulmonary function and assessment scale scores in patients with stroke, respectively. Results: Compared with the control group, patients in the stroke group exhibited lower values for indices of pulmonary and diaphragmatic function (p < 0.001), except for TdiFRC (p > 0.05). The majority of the patients with stroke had restrictive ventilatory dysfunction, as indicated by a significantly higher incidence ratio (36 in 41 patients) than that in the control group (0 in 22 patients) (p < 0.001). Moreover, significant correlations were found between pulmonary function and diaphragmatic ultrasound indices (p < 0.05), with the strongest correlation between TdiFVC and pulmonary indices. In the stroke group, pulmonary function indices were negatively correlated with the NIHSS scores (p < 0.001) and positively correlated with the FMA scores (p < 0.001). No (p > 0.05) or weak (p < 0.05) correlation was found between pulmonary function indices and the MBI scores. Conclusion: We found that patients with stroke had pulmonary dysfunction even in the recovery period. Diaphragmatic ultrasound can be used as a simple and effective tool for detecting pulmonary dysfunction in patients with stroke, with TdiFVC being the most effective index.

Intermittent theta burst stimulation vs. high-frequency repetitive transcranial magnetic stimulation for post-stroke cognitive impairment: Protocol of a pilot randomized controlled double-blind trial.

Introduction: Intermittent theta burst stimulation (iTBS), a novel mode of transcranial magnetic stimulation (TMS), has curative effects on patients with post-stroke cognitive impairment (PSCI). However, whether iTBS will be more applicable in clinical use than conventional high-frequency repetitive transcranial magnetic stimulation (rTMS) is unknown. Our study aims to compare the difference in effect between iTBS and rTMS in treating PSCI based on a randomized controlled trial, as well as to determine its safety and tolerability, and to further explore the underlying neural mechanism. Methods: The study protocol is designed as a single-center, double-blind, randomized controlled trial. Forty patients with PSCI will be randomly assigned to two different TMS groups, one with iTBS and the other with 5 Hz rTMS. Neuropsychological evaluation, activities of daily living, and resting electroencephalography will be conducted before treatment, immediately post-treatment, and 1 month after iTBS/rTMS stimulation. The primary outcome is the change in the Montreal Cognitive Assessment Beijing Version (MoCA-BJ) score from baseline to the end of the intervention (D11). The secondary outcomes comprise changes in resting electroencephalogram (EEG) indexes from baseline to the end of the intervention (D11) as well as the Auditory Verbal Learning Test, the symbol digit modality test, the Digital Span Test findings, and the MoCA-BJ scores from baseline to endpoint (W6). Discussion: In this study, the effects of iTBS and rTMS will be evaluated using cognitive function scales in patients with PSCI as well as data from resting EEG, which allows for an in-depth exploration of underlying neural oscillations. In the future, these results may contribute to the application of iTBS for cognitive rehabilitation of patients with PSCI.

Deregulation of PRDM5 promotes cell proliferation by regulating JAK/STAT signaling pathway through SOCS1 in human lung adenocarcinoma.

BACKGROUND: PRDM5 is considered a tumor suppressor in several types of solid tumors and is involved in multiple cellular processes. However, target genes regulated by PRDM5 in lung cancer and its potential mechanism are poorly defined. METHODS: Survival analysis was conducted using Kaplan-Meier estimates based on the online databases. RNA-sequencing and bioinformatics analysis were performed to identify the differentially expressed genes in PRDM5-overexpressed A549 cells. RESULTS: We observed deregulated PRDM5 in several lung adenocarcinoma cell lines and its association with a poor prognosis. PRDM5 overexpression inhibited the proliferation of lung adenocarcinoma cells in vitro and suppressed tumor growth in a xenograft model. PRDM5 upregulated the promoter activity of SOCS1, which then inhibited the phosphorylation of JAK2 and STAT3. CONCLUSIONS: Our study suggests that the low expression of PRDM5 promotes the proliferation of lung adenocarcinoma cells by downregulating SOCS1 and then upregulating the JAK2/STAT3 signaling pathway.

Effects of Cerium Doping on the Mechanical Properties and Energy-Releasing Behavior of High-Entropy Alloys.

Energetic structural materials play an important role in improving the damage performance of future weapons. To improve the energy-releasing behavior, Al0.5NbZrTi1.5Ta0.8Cex high-entropy alloys were prepared by vacuum-arc melting. The results showed the presence of BCC and FCC phases in the alloy with dendritic-morphology-element segregation and there were significant dislocations in the alloys. The current study focused on the effects of cerium content on the dynamic compressive mechanical and energetic characteristics. Cerium doping enhanced the energy-releasing characteristics of high-entropy alloys. The severity of the reaction increased with the increase in the cerium content, while the dynamic compressive strength generally decreased with the increase in cerium content. The Al0.5NbZrTi1.5Ta0.8Ce0.25 showed excellent mechanical and energy-releasing characteristics. The ballistic experiments indicated that Al0.5NbZrTi1.5Ta0.8Ce0.25 can penetrate 6-millimeter A3 plates and ignite the cotton behind the target at a velocity of 729 m/s, making it an ideal energetic structural material.

Personality and brain contribute to academic achievements of medical students.

There are many factors that influence the academic achievements of medical students, but how personality and brain modulate the academic achievements of medical students remains unclear. The study collected the personality, brain imaging, and academic data from 448 medical students at Tianjin Medical University with admission time between 2008 and 2017. Four types of academic achievements, including behavioral and social sciences, clinical sciences and skills, basic biomedical sciences, and scientific methods, were assessed by the academic records of 58 courses. Personality was evaluated by Tridimensional Personality Questionnaire and Neuroticism Extraversion Openness Personality Inventory. Brain structural and functional properties, including gray matter volume, spontaneous brain activity and functional connectivity, were computed based on magnetic resonance imaging (MRI). Linear regression was used to evaluate the associations between personality and academic achievements. A voxel-wise correlation was used to identify areas of the brain where structural and functional properties were associated with academic achievements. Mediation analysis was used to test whether brain properties and personality independently contribute to academic achievements. Our results showed that novelty seeking (NS) was negatively correlated, and conscientiousness was positively correlated with all types of academic achievements. Brain functional properties showed negatively correlated with academic achievement in basic biomedical sciences. However, we did not find any mediation effect of the brain functional properties on the association between personality (NS and conscientiousness) and academic achievement in basic biomedical sciences, nor mediation effect of the personality (NS and conscientiousness) on the association between brain functional properties and academic achievement in basic biomedical sciences. These findings suggest that specific personality (NS and conscientiousness) and brain functional properties independently contribute to academic achievements in basic biomedical sciences, and that modulation of these properties may benefit academic achievements among medical students.

Ignition and Combustion Characteristic of B·Mg Alloy Powders.

Boron and its alloys have been explored a lot and it is expected that they can replace pure aluminum powder in the energetic formulation of active materials. MgB2 compounds were prepared and characterized by a combination of mechanical alloying and heat treatment. The ignition and combustion of boron-magnesium alloys were studied with the ignition wire method and laser ignition infrared temperature measurement. The results show that MgB2 has good ignition characteristics with maximum ignition temperatures obtained by the two various methods of 1292 K and 1293 K, respectively. Compared with boron, the ignition temperature of MgB2 is greatly reduced after alloying. The ignition reaction of MgB2 mainly occurs on the surface and the ignition process has two stages. In the initial stage of ignition, the large flame morphology and combustion state are close to the combustion with gaseous Mg, whereas the subsequent combustion process is close to the combustion process of B. Compared with boron, the ignition temperature of MgB2 is greatly reduced which suggests that MgB2 may be used in gunpowder, propellant, explosives, and pyrotechnics due to its improved ignition performance.

Nuclear receptor coactivator 4-mediated ferritinophagy contributes to cerebral ischemia-induced ferroptosis in ischemic stroke.

Ischemic stroke poses a significant health risk due to its high rate of disability and mortality. To address this problem, several therapeutic approaches have been proposed, including interruption targeting programmed cell death (PCD). Ferroptosis is a newly defined PCD characterized by iron-dependent accumulation of lipid peroxidation, and is becoming a promising target for treating numerous diseases. To explore the underlying mechanisms of the initiation and execution of ferroptosis in ischemic stroke, we established stroke models in vivo and in vitro simulating ischemia/reperfusion (I/R) neuronal injury. Different from previous reports on stroke, we tested ferroptosis by measuring the levels of core proteins, such as ACSL4, 15-LOX2, Ferritin and GPX4. In addition, I/R injury induces excessive degradation of ferritin via the autophagy pathway and subsequent increase of free iron in neurons. This phenomenon has recently been termed ferritinophagy and reported to be regulated by nuclear receptor coactivator 4 (NCOA4) in some cell lines. Increased NCOA4 in cytoplasm was detected in our study and then silenced by shRNA to investigate its function. Both in vivo and in vitro, NCOA4 deletion notably abrogated ferritinophagy caused by I/R injury and thus inhibited ferroptosis. Furthermore, we found that NCOA4 was upregulated by ubiquitin specific peptidase 14 (USP14) via a deubiquitination process in damaged neurons, and we found evidence of pharmacological inhibition of USP14 effectively reducing NCOA4 levels to protect neurons from ferritinophagy-mediated ferroptosis. These findings suggest a novel and effective target for treating ischemic stroke.

Length Dependent Folding Kinetics of Alanine-Based Helical Peptides from Optimal Dimensionality Reduction.

We present a computer simulation study of helix folding in alanine homopeptides (ALA)n of length n = 5, 8, 15, and 21 residues. Based on multi-microsecond molecular dynamics simulations at room temperature, we found helix populations and relaxation times increasing from about 6% and ~2 ns for ALA5 to about 60% and ~500 ns for ALA21, and folding free energies decreasing linearly with the increasing number of residues. The helix folding was analyzed with the Optimal Dimensionality Reduction method, yielding coarse-grained kinetic models that provided a detailed representation of the folding process. The shorter peptides, ALA5 and ALA8, tended to convert directly from coil to helix, while ALA15 and ALA21 traveled through several intermediates. Coarse-grained aggregate states representing the helix, coil, and intermediates were heterogeneous, encompassing multiple peptide conformations. The folding involved multiple pathways and interesting intermediate states were present on the folding paths, with partially formed helices, turns, and compact coils. Statistically, helix initiation was favored at both termini, and the helix was most stable in the central region. Importantly, we found the presence of underlying universal local dynamics in helical peptides with correlated transitions for neighboring hydrogen bonds. Overall, the structural and dynamical parameters extracted from the trajectories are in good agreement with experimental observables, providing microscopic insights into the complex helix folding kinetics.

Integrative analysis regarding the correlation between GAS2 family genes and human glioma prognosis.

BACKGROUND: Emerging oncogenes were reportedly linked to the complicated subtypes and pathogenesis of clinical gliomas. Herein, we first comprehensively explored the potential correlation between growth-arrest-specific two family genes (GAS2, GAS2L1, GAS2L2, GAS2L3) and gliomas by bioinformatics analysis and cellular experiments. METHODS: Based on the available datasets of TCGA (The Cancer Genome Atlas), CGGA (Chinese Glioma Genome Atlas), and Oncomine databases, we performed a series of analyses, such as gene expression, survival prognosis, DNA methylation, immune infiltration, and partner enrichment. We also utilized two glioma cell lines to conduct the colony formation and wound-healing assay. RESULTS: GAS2L3 gene was highly expressed in glioma tissues compared to normal brain tissues (p < 0.05). We further observed the relationship between the high expressed GAS2L3 and poor clinical prognosis of brain low-grade glioma (LGG) cases in our Cox proportional hazard model (hazard ratio [HR] = 0.1715, p < 0.001). Moreover, DNA hypomethylation status of GAS2L3 was correlated with the high expression of GAS2L3 in LGG tissues and the poor clinical prognosis of primary glioma cases (p < 0.05). We also found that the high expression of GAS2L3 was associated with the infiltration level of immune cells, especially the T cells (p < 0.0001). Functional enrichment analysis of GAS2L3-correlated genes and interaction partners further indicated that GAS2L3 might take part in the occurrence of glioma by influencing a series of biological behaviors, such as cell division, cytoskeleton binding, and cell adhesion. Additionally, our cellular experiment data suggested that a highly expressed GAS2L3 gene contributes to the enhanced proliferation and migration of glioma cells. CONCLUSION: This study first analyzed the potential role of GAS2 family genes, especially GAS2L3, in the clinical prognosis and possible functional mechanisms of glioma, which gives a novel insight into the relationship between GAS2L3 and LGG.

Migration of fish bones into abdominal para-aortic tissue from the duodenum after leading to duodenal perforation: a case report.

BACKGROUND: Migration of fish bones into abdominal para-aortic tissue after penetrating the junction of 3rd and 4th part of duodenum is incredibly rare. CASE PRESENTATION: A 68-year-old man was admitted to our hospital with persistent colic in the lower abdomen after eating fish two weeks ago. Abdominal computed tomography (CT) scan showed High density streaks along the anterior and lower edges of the 3rd part of duodenum with peripheral exudation and localized peritonitis. Esophagogastroduodenoscopy didn't find foreign bodies and perforations in the digestive tract. Laparoscopic surgery and intraoperative endoscopy were made to detect foreign bodies and perforation site was found. After transition to open surgery, the fish bone was found in abdominal para-aortic tissue and removed without complications. Postoperative recovery is smooth, and the patient resumed normal diet and was discharged. CONCLUSIONS: It is difficult to choose a treatment plan for foreign bodies at the 3rd part of the duodenum, because it is difficult to judge the damage caused by the foreign body to the intestine and the positional relationship with the surrounding important organs. Conservative treatment or surgical treatment both have huge risks. The handling of this situation will extremely test the psychology, physical strength and professional experience of the surgeon.

Oncoprotein SND1 hijacks nascent MHC-I heavy chain to ER-associated degradation, leading to impaired CD8+ T cell response in tumor.

SND1 is highly expressed in various cancers. Here, we identify oncoprotein SND1 as a previously unidentified endoplasmic reticulum (ER) membrane-associated protein. The amino-terminal peptide of SND1 predominantly associates with SEC61A, which anchors on ER membrane. The SN domain of SND1 catches and guides the nascent synthesized heavy chain (HC) of MHC-I to ER-associated degradation (ERAD), hindering the normal assembly of MHC-I in the ER lumen. In mice model bearing tumors, especially in transgenic OT-I mice, deletion of SND1 promotes the presentation of MHC-I in both B16F10 and MC38 cells, and the infiltration of CD8+ T cells is notably increased in tumor tissue. It was further confirmed that SND1 impaired tumor antigen presentation to cytotoxic CD8+ T cells both in vivo and in vitro. These findings reveal SND1 as a novel ER-associated protein facilitating immune evasion of tumor cells through redirecting HC to ERAD pathway that consequently interrupts antigen presentation.

A pan-cancer analysis of the oncogenic role of staphylococcal nuclease domain-containing protein 1 (SND1) in human tumors.

Although emerging cell- or animal-based evidence supports the relationship between SND1 and cancers, no pan-cancer analysis is available. We thus first explored the potential oncogenic roles of SND1 across thirty-three tumors based on the datasets of TCGA (The cancer genome atlas) and GEO (Gene expression omnibus). SND1 is highly expressed in most cancers, and distinct associations exist between SND1 expression and prognosis of tumor patients. We observed an enhanced phosphorylation level of S426 in several tumors, such as breast cancer or lung adenocarcinoma. SND1 expression was associated with the CD8+T-cell infiltration level in colon adenocarcinoma and melanoma, and cancer-associated fibroblast infiltration was observed in other tumors, such as bladder urothelial carcinoma or testicular germ cell tumors. Moreover, protein processing- and RNA metabolism-associated functions were involved in the functional mechanisms of SND1. Our first pan-cancer study offers a relatively comprehensive understanding of the oncogenic roles of SND1 across different tumors.

[Spatial and Temporal Distribution Characteristics and the Retention Effects of Nutrients in Xiangjiaba Reservoir].

After the construction of the Xiangjiaba Dam, the hydrodynamic conditions, nutrient distributions, and transport conditions of the Jinsha River were changed. Here, the nutrient distribution characteristics and retention effects of Xiangjiaba Reservoir were investigated according to the results of water quality monitoring from 2015 to 2016. Spatial and temporal variations in TN, TP, SiO32-Si, and other nutrients, and retention flux and retention rate were analyzed. The results showed that the nutrient mass concentration of TN, TP, and SiO32--Si was 0.905 mg·L-1, 0.034 mg·L-1, and 7.98 mg·L-1, respectively. The distribution of TN was affected by point sources and the concentration of TN was large in urban areas. This distribution of TP was mainly granular and the mass concentrations decreased along the river path. The mass concentration of SiO32--Si did not significantly vary over time and space. Furthermore, Xiangjiaba Reservoir had a persistent effect on nutrient salts; the average annual retention of TN, TP, and SiO32--Si was 2.30×104 t·a-1, 0.146×104 t·a-1, and -2.4×104 t·a-1, respectively. During different seasons, the retention of TN and SiO32--Si varied between positive or negative; however, TP appeared to be consistent. The average monthly retention efficiency of TN, TP, and SiO32--Si was 17.5%, 32.8%, and -2.14%, respectively. Overall, retention efficiencies were higher during the dry season than that wet season, and phosphorus retention was most pronounced. The retention of TN in the reservoir may be related to denitrification and the input of external load; the flux of SiO32--Si was mainly affected by runoff; and the particle morphology of phosphorus, as well as reservoir period, were the main factors affecting TP retention. There were no clear correlations between nutrient retention and the mass concentrations of TN and SiO32--Si, but the nutrient retention effect of Xiangjiaba Reservoir reduced TP concentrations along the river path and increased TP concentration with vertical depth.

Genetic relationship between IL-10 gene polymorphisms and the risk of clinical atopic dermatitis.

BACKGROUND: We retrieved different reports containing different genetic effects of - 1082 A/G, - 819 T/C, and - 592 A/C polymorphisms within the IL-10 (interleukin-10) gene on the susceptibility to clinical atopic dermatitis. METHODS: Herein, we conducted a meta-analysis to comprehensively assess such a genetic relationship after collecting the available published evidence. STATA 12.0 software was used for the statistical analysis under the allelic, homozygotic, heterozygotic, dominant, recessive and carrier genetic models. RESULTS: By retrieving and screening database literature, a total of 16 eligible case-control studies were finally selected. For the IL-10 -1082 A/G polymorphism, we did not detect a significant difference between atopic dermatitis cases and population-based controls in the overall meta-analysis under the genetic models of allele G vs. A (P = 0.540), GG vs. AA (P = 0.853), AG vs AA (P = 0.265), AG + GG vs AA (P = 0.221), GG vs AA+AG (P = 0.540) and carrier G vs. A (P = 0.643). Moreover, a statistically non-significant association was observed in the most subgroup meta-analyses by the factors of ethnicity, country and Hardy-Weinberg equilibrium. Likewise, the negative results were detected for the synthetic analysis of IL-10 -819 T/C and - 592 C/A polymorphisms. CONCLUSION: The current evidence does not support a strong genetic relationship between IL-10 -1082 A/G, - 819 T/C and - 592 A/C polymorphisms and the susceptibility to atopic dermatitis.

Correction: Elongation Factor Tu and Heat Shock Protein 70 Are Membrane-Associated Proteins from Mycoplasma ovipneumoniae Capable of Inducing Strong Immune Response in Mice.

[This corrects the article DOI: 10.1371/journal.pone.0161170.].

Aggregation of SND1 in Stress Granules is Associated with the Microtubule Cytoskeleton During Heat Shock Stimulus.

Stress granules (SGs) are dynamic dense structures in the cytoplasm that form in response to a variety of environmental stress stimuli. Staphylococcal nuclease and Tudor domain containing 1 (SND1) is a type of RNA-binding protein and has been identified as a transcriptional co-activator. Our previous studies have shown that SND1 is a component of the stress granule, which forms under stress conditions. Here, we observed that SND1 granules were often surrounded by ɑ-tubulin-microtubules in 45°C-treated HeLa cells at 15 min or colocalized with microtubules at 30 or 45 min. Furthermore, Nocodazole-mediated microtubule depolymerization could significantly affect the efficient recruitment of SND1 proteins to the SGs during heat shock stress. In addition, the 45°C heat shock mediated the enhancement of eIF2α phosphorylation, which was not affected by treatment with Nocodazole, an agent that disrupts the cytoskeleton. The intact microtubule cytoskeletal tracks are important for the efficient assembly of SND1 granules under heat shock stress and may facilitate SND1 shuttling between cytoplasmic RNA foci. Anat Rec, 300:2192-2199, 2017. © 2017 The Authors The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

Elongation Factor Tu and Heat Shock Protein 70 Are Membrane-Associated Proteins from Mycoplasma ovipneumoniae Capable of Inducing Strong Immune Response in Mice.

Chronic non-progressive pneumonia, a disease that has become a worldwide epidemic has caused considerable loss to sheep industry. Mycoplasma ovipneumoniae (M. ovipneumoniae) is the causative agent of interstitial pneumonia in sheep, goat and bighorn. We here have identified by immunogold and immunoblotting that elongation factor Tu (EF-Tu) and heat shock protein 70 (HSP 70) are membrane-associated proteins on M. ovipneumonaiea. We have evaluated the humoral and cellular immune responses in vivo by immunizing BALB/c mice with both purified recombinant proteins rEF-Tu and rHSP70. The sera of both rEF-Tu and rHSP70 treated BALB/c mice demonstrated increased levels of IgG, IFN-γ, TNF-α, IL-12(p70), IL-4, IL-5 and IL-6. In addition, ELISPOT assay showed significant increase in IFN-γ+ secreting lymphocytes in the rHSP70 group when compared to other groups. Collectively our study reveals that rHSP70 induces a significantly better cellular immune response in mice, and may act as a Th1 cytokine-like adjuvant in immune response induction. Finally, growth inhibition test (GIT) of M. ovipneumoniae strain Y98 showed that sera from rHSP70 or rEF-Tu-immunized mice inhibited in vitro growth of M. ovipneumoniae. Our data strongly suggest that EF-Tu and HSP70 of M. ovipneumoniae are membrane-associated proteins capable of inducing antibody production, and cytokine secretion. Therefore, these two proteins may be potential candidates for vaccine development against M. ovipneumoniae infection in sheep.

Histone H3k9 and H3k27 Acetylation Regulates IL-4/STAT6-Mediated Igε Transcription in B Lymphocytes.

IL-4 activates STAT6 and causes the subsequent up-regulation of Ig heavy chain germline Igε via chromatin remodeling involved in B lymphocytes development. STAT6 acts as a molecular switch to regulate the higher-order chromatin remodeling via dynamically orchestrating co-activators (CBP/Tudor-SN) and co-repressors (HDAC1/PSF). Here, we demonstrated that STAT6/Tudor-SN/PSF form a complex, balancing the acetylation and deacetylation states to co-regulate IL-4/STAT6 gene transcription. In addition, we confirmed that IL-4 treatment increased the HATs activity in Ramos cells. As "active" markers, the expression of H3K9ac and H3K27ac increased after treatment with IL-4. However, transcriptional repressors such as H3K9me3 and H3K27me3 decreased in response to IL-4 stimulation. Moreover, IL-4 treatment enhanced H3 acetylation at the Igε promoter regions. Our results revealed that the Igε gene transcription is regulated by histone modifications in the IL-4/STAT6 pathway. The study will provide novel insights into the pathogenesis of allergic diseases.

Poly(A)(+) mRNA-binding protein Tudor-SN regulates stress granules aggregation dynamics.

Stress granules (SGs) and processing bodies (PBs) comprise the main types of cytoplasmic RNA foci during stress. Our previous data indicate that knockdown of human Tudor staphylococcal nuclease (Tudor-SN) affects the aggregation of SGs. However, the precise molecular mechanism has not been determined fully. In the present study, we demonstrate that Tudor-SN binds and colocalizes with many core components of SGs, such as poly(A)(+) mRNA binding protein 1, T-cell internal antigen-1-related protein and poly(A)(+) mRNA, and SG/PB sharing proteins Argonaute 1/2, but not PB core proteins, such as decapping enzyme 1 a/b, confirming that Tudor-SN is an SG-specific protein. We also demonstrate that the Tudor-SN granule actively communicates with the nuclear and cytosolic pool under stress conditions. Tudor-SN can regulate the aggregation dynamics of poly(A)(+) mRNA-containing SGs and selectively stabilize the SG-associated mRNA during cellular stress.

Tudor staphylococcal nuclease (Tudor-SN), a novel regulator facilitating G1/S phase transition, acting as a co-activator of E2F-1 in cell cycle regulation.

Tudor staphylococcal nuclease (Tudor-SN) is a multifunctional protein implicated in a variety of cellular processes. In the present study, we identified Tudor-SN as a novel regulator in cell cycle. Tudor-SN was abundant in proliferating cells whereas barely expressed in terminally differentiated cells. Functional analysis indicated that ectopic overexpression of Tudor-SN promoted the G1/S transition, whereas knockdown of Tudor-SN caused G1 arrest. Moreover, the live-cell time-lapse experiment demonstrated that the cell cycle of MEF(-/-) (knock-out of Tudor-SN in mouse embryonic fibroblasts) was prolonged compared with wild-type MEF(+/+). We noticed that Tudor-SN was constantly expressed in every cell cycle phase, but was highly phosphorylated in the G1/S border. Further study revealed that Tudor-SN was a potential substrate of Cdk2/4/6, supportively, we found the physical interaction of endogenous Tudor-SN with Cdk4/6 in G1 and the G1/S border, and with Cdk2 in the G1/S border and S phase. In addition, roscovitine (Cdk1/2/5 inhibitor) or CINK4 (Cdk4/6 inhibitor) could inhibit the phosphorylation of Tudor-SN, whereas ectopic overexpression of Cdk2/4/6 increased the Tudor-SN phosphorylation. The underlying molecular mechanisms indicated that Tudor-SN could physically interact with E2F-1 in vivo, and could enhance the physical association of E2F-1 with GCN5 (a cofactor of E2F-1, which possesses histone acetyltransferase activity), and promote the binding ability of E2F-1 to the promoter region of its target genes CYCLIN A and E2F-1, and as a result, facilitate the gene transcriptional activation. Taken together, Tudor-SN is identified as a novel co-activator of E2F-1, which could facilitate E2F-1-mediated gene transcriptional activation of target genes, which play essential roles in G1/S transition.