K63-Linked Ubiquitination in Kinase Activation and Cancer

Ubiquitination has been demonstrated to play a pivotal role in multiple biological functions, which include cell growth, proliferation, apoptosis, DNA damage response, innate immune response, and neuronal degeneration. Although the role of ubiquitination in targeting proteins for proteasome-dependent degradation have been extensively studied and well-characterized, the critical non-proteolytic functions of ubiquitination, such as protein trafficking and kinase activation, involved in cell survival and cancer development, just start to emerge, In this review, we will summarize recent progresses in elucidating the non-proteolytic function of ubiquitination signaling in protein kinase activation and its implications in human cancers. The advancement in the understanding of the novel functions of ubiquitination in signal transduction pathways downstream of growth factor receptors may provide novel paradigms for the treatment of human cancers

Activated regulatory T cell regulates neural stem cell proliferation in the subventricular zone of normal and ischemic mouse brain through interleukin 10

Recent studies have demonstrated that the depletion of Regulatory T cells (Tregs) inhibits neural progenitor cell migration after brain ischemia. However, whether Tregs affect neural stem/progenitor cell proliferation is unclear. We explored the effect of Tregs on neurogenesis in the subventricular zone after ischemia. Tregs were isolated and activated in vitro. Adult male C57BL/6 mice underwent 60 minutes transient middle cerebral artery occlusion (tMCAO). Then Tregs (1x105) were injected into the left lateral ventricle of normal and ischemic mouse brain. Neurogenesis was determined by immunostaining. The mechanism was examined by inhibiting interleukin 10 (IL-10) and transforming growth factor (TGF-) signaling. We found that the number of BrdU+ cells in the subventricular zone was significantly increased in the activated Tregs-treated mice. Double immunostaining showed that these BrdU+ cells expressed Mash1. Blocking IL-10 reduced the number of Mash1+/BrdU+ cells, but increased the amount of GFAP+/BrdU+ cells. Here we conclude that activated Tregs enhanced neural stem cell proliferation in the subventricular zone of normal and ischemic mice; blockage of IL-10 abolished Tregs-mediated neural stem cell proliferation in vivo and in vitro. Our results suggest that activated Tregs promoted neural stem cell proliferation via IL-10, which provides a new therapeutic approach for ischemic stroke

Phylogenetic Diversity of Culturable Fungi in Heshang Cave, Central China

Caves are nutrient-limited and dark subterranean ecosystems. To date, attention has been focused on geological research of caves in China, whilst indigenous microbial diversity has been insufficiently characterized. Here, we report the fungal diversity in the pristine, oligotrophic, karst Heshang Cave, central China, using a culture-dependent method coupled with the analysis of the fungal rRNA-ITS gene sequences. A total of 194 isolates were obtained with six different media from 14 sampling sites of sediments, weathered rocks and bat guanos. Phylogenetic analysis clustered the 194 sequenced isolates into 33 genera within 15 orders of 3 phyla, Ascomycota, Basidiomycota and Zygomycota, indicating a high degree of fungal diversity in the Heshang cave. Notably, 16 out of the 36 fungal genera were also frequently observed in solution caves around the world and 23 genera were previously found in carbonate cave, indicating potential similarities among fungal communities in cave ecosystems. However, 10 genera in this study were not reported previously in any solution caves, thus expanding our knowledge about fungal diversity in cave ecosystems. Moreover, culturable fungal diversity varied from one habitat to another within the cave, being the highest in sediments, followed by weathered rocks and bat guanos as indicated by alpha-diversity indexes. At the genus level, Penicillium accounted for 40 %, 54 % and 52 % in three habitats of sediments, weathered rocks and bat guanos respectively. Trichoderma, Paecilomyces and Aspergillus accounted for 9 %, 22 % and 37 % in the above habitats, correspondingly. Despite of the dominance of Penicillium in all samples beta-diversity index indicated significant differences between each two fungal communities in the three habitats in view of both the composition and abundance. Our study is the first report on fungal communities in a natural pristine solution cave system in central China and sheds light on fungal diversity and functions in cave ecosystems

Microbial community changes along the active seepage site of one cold seep in the Red Sea

The active seepage of the marine cold seeps could be a critical process for the exchange of energy between the submerged geosphere and the sea floor environment through organic-rich fluids, potentially even affecting surrounding microbial habitats. However, few studies have investigated the associated microbial community changes. In the present study, 16S rRNA genes were pyrosequenced to decipher changes in the microbial communities from the Thuwal seepage point in the Red Sea to nearby marine sediments in the brine pool, normal marine sediments and water, and benthic microbial mats. An unexpected number of reads from unclassified groups were detected in these habitats; however, the ecological functions of these groups remain unresolved. Furthermore, ammonia-oxidizing archaeal community structures were investigated using the ammonia monooxygenase subunit A (amoA) gene. Analysis of amoA showed that planktonic marine habitats, including seeps and marine water, hosted archaeal ammonia oxidizers that differed from those in microbial mats and marine sediments, suggesting modifications of the ammonia oxidizing archaeal communities along the environmental gradient from active seepage sites to peripheral areas. Changes in the microbial community structure of ammonia oxidizing archaea in different habitats (water versus sediment) potentially correlated with changes in salinity and oxygen concentrations. Overall, the present results revealed for the first time unanticipated novel microbial groups and changes in the ammonia-oxidizing archaea in response to environmental gradients near the active seepages of a cold seep

Game theory paradigm: a new tool for investigating social dysfunction in major depressive disorders

Social dysfunction is a prominent source of distress and disability in patients with major depressive disorder (MDD) but is commonly omitted from current clinical studies, although some researchers propose an evolutionary strategy to understand these negative outcomes. Limited knowledge about the neural basis of social dysfunction in MDD results from traditional paradigms, which lack insights into social interactions. Game theoretical modelling offers a new tool for investigating social interaction impairments in neuropsychiatric disorders. This review first introduces three widely-used games from game theory and the major behavioral and neuroimaging findings obtained using these games in healthy populations. We also address the factors that modulate behaviors in games and their neural bases. We then summarize the current findings obtained by using these games in depressed patients and discuss the clinical implications of these abnormal game behaviors. Finally, we briefly discuss future prospects that may further elucidate the clinical use of a game theory paradigm in MDD

Evaluation of Clinical Outcomes of Patients with Post-Stroke Wrist and Finger Spasticity after Ultrasonography-Guided BTX-A Injection and Rehabilitation Training

Objective: Using ultrasonography (US) to guide botulinum toxin type A (BTX-A) injection in patients with post-stroke wrist and finger flexor muscle spasticity and assessing clinical outcomes after the injection and rehabilitation intervention. Methods: Twenty-three patients with wrist and finger spasticity after stroke were recruited in this study from May 2012 to May 2013. Under US guidance, the proper dose (250U) of BTX-A was injected into each spastic muscle at two injection sites. Then, conventional rehabilitation training started next day after BTX-A injection. The degree of spasticity was assessed by modified Ashworth scale (MAS) and wrist and finger motor function by active rang of movement (AROM), and Fugl-Meyer assessment (FMA) at the baseline, 1, 2, 4 and 12 weeks after BTX-A injection. Results: Significant decreases (p < 0.02) in the MAS scores of both the finger flexor muscle tone and wrist flexor muscle tone measured at 1, 2, 4, and 12 weeks after the BTX-A injection were found in comparison with the baseline scores. Compared with the baseline, the AROM values of the wrist and finger extensions and the FMA scores of the wrist and hand significantly increased (p < 0.02) at 2, 4 and 12 weeks after the BTX-A injection. Conclusions: US-guided BTX-A injection combined with rehabilitation exercise decrease spasticity of the wrist and finger flexor muscles and improve their motor function in stroke patients up to 12 weeks following BTX-A injection

A novel rat model of blast-induced traumatic brain injury simulating different damage degree: implications for morphological, neurological, and biomarker changes

In current military conflicts and civilian terrorism, blast-induced traumatic brain injury (bTBI) is the primary cause of neurotrauma. However, the effects and mechanisms of bTBI are poorly understood. Although previous researchers have made significant contributions to establishing animal models for the simulation of bTBI, the precision and controllability of blast-induced injury in animal models must be improved. Therefore, we established a novel rat model to simulate blast-wave injury to the brain. To simulate different extents of bTBI injury, the animals were divided into moderate and severe injury groups. The miniature spherical explosives (PETN) used in each group were of different sizes (2.5 mm diameter in the moderate injury group and 3.0 mm diameter in the severe injury group). A specially designed apparatus was able to precisely adjust the positions of the miniature explosives and create eight rats with bTBI simultaneously, using a single electric detonator. Neurological functions, gross pathologies, histopathological changes and the expression levels of various biomarkers were examined after the explosion. Compared with the moderate injury group, there were significantly more neurological dysfunctions, cortical contusions, intraparenchymal hemorrhages, cortical expression of S-100β, MBP, NSE, IL-8, IL-10, iNOS and HIF-1α in the severe injury group. These results demonstrate that we have created a reliable and reproducible bTBI model in rats. This model will be helpful for studying the mechanisms of bTBI and developing strategies for clinical bTBI treatment

Numerical processing efficiency improved in children using mental abacus: ERP evidence utilizing a numerical Stroop task

This study examined whether long-term abacus-based mental calculation (AMC) training improved numerical processing efficiency and at what stage of information processing the effect appeard. Thirty-three children participated in the study and were randomly assigned to two groups at primary school entry, matched for age, gender and IQ. All children went through the same curriculum except that the abacus group received a 2-hour/per week AMC training, while the control group did traditional numerical practice for a similar amount of time. After a two-year training, they were tested with a numerical Stroop task. Electroencephalographic (EEG) and event related potential (ERP) recording techniques were used to monitor the temporal dynamics during the task. Children were required to determine the numerical magnitude (NC task) or the physical size (PC task) of two numbers presented simultaneously. In the NC task, the AMC group showed faster response times but similar accuracy compared to the control group. In the PC task, the two groups exhibited the same speed and accuracy. The saliency of numerical information relative to physical information was greater in AMC group. With regards to ERP results, the AMC group displayed congruity effects both in the earlier (N1) and later (N2 and LPC (late positive component) time domain, while the control group only displayed congruity effects for LPC. In the left parietal region, LPC amplitudes were larger for the AMC than the control group. Individual differences for LPC amplitudes over left parietal area showed a positive correlation with RTs in the NC task in both congruent and neutral conditions. After controlling for the N2 amplitude, this correlation also became significant in the incongruent condition. Our results suggest that AMC training can strengthen the relationship between symbolic representation and numerical magnitude so that numerical information processing becomes quicker and automatic in AMC children

Comparative Genomic Analysis of the ICESa2603 Family ICEs and Spread of erm(B)- and tet(O)-Carrying Transferable 89K-Subtype ICEs in Swine and Bovine Isolates in China

Integrative and conjugative elements (ICEs) of the ICESa2603 family have been isolated from several species of Streptococcus spp.; however, the comparative genomic and evolutionary analyses of these particular ICEs are currently only at their initial stages. By investigating 13 ICEs of the ICESa2603 family and two ICESa2603 family-like ICEs derived from diverse hosts and locations, we have determined that ICEs comprised a backbone of 30 identical syntenic core genes and accessory genes that were restricted to the intergenic sites or the 3'-end of the non-conserved domain of core genes to maintain its function. ICESa2603 family integrase IntICESa2603 specifically recognized a 15-bp att sequence (TTATTTAAGAGTAAC) at the 3'-end of rplL, which was highly conserved in genus Streptococcus. Phylogenetic analyses suggest that extensive recombination/insertion and the occurrence of a hybrid/mosaic in the ICESa2603 family were responsible for the significant increase in ICE diversity, thereby broadening its host range. Approximately 42.5% and 38.1% of the tested Streptococcus suis and Streptococcus agalactiae clinical isolates respectively contained ICESa2603 family Type Ⅳ secretion system (T4SS) genes, and 80.5% and 62.5% of which also respectively carried intICESa2603, indicating that ICESa2603 family is widely distributed across these bacteria. Sequencing and conjugation transfer of a novel sequence type ST303 clinical S. suis isolate HB1011 demonstrated that the 89K-subtype ICESsuHB1011 retained its transferrable function, thereby conferring tetracycline and macrolide resistance

Carbon material optimized biocathode for improving microbial fuel cell performance

To improve the performance of microbial fuel cells (MFCs), the biocathode electrode material of double-chamber was optimized. Alongside the basic carbon fiber brush, three carbon materials namely graphite granules, activated carbon granules and activated carbon powder, were added to the cathode-chambers to improve power generation. The result shows that the addition of carbon materials increased the amount of available electroactive microbes on the electrode surface and thus promote oxygen reduction rate, which improved the generation performance of the MFCs. The Output current (external resistance = 1000 Ω) greatly increased after addition of the three carbon materials and maximum power densities in current stable phase increased by 47.4%, 166.1% and 33.5%, respectively. Additionally, coulombic efficiencies of the MFC increased by 16.3%, 64.3% and 20.1%, respectively. These results show that MFC when optimized with activated carbon granules show better power generation, higher chemical oxygen demands (COD) removal rate and coulombic efficiency