Phylogenetic diversity of endolithic bacteria in Bole granite rock in Xinjiang

The endolithic environment is a ubiquitous microbial habitat for microorganisms, such as lichens, Cyanobacteria and fungi, and it provides mineral nutrients and growth surfaces. In extremely environments, such as hot and cold desert, endolithic communities are often the main form of life. More recently, endolithic microbial communities have been observed inhabiting a variety of rock types ranging from hard granite to porous rocks such as basalt, dolomite, limestone, sandstone and granites. Regardless of geographic location and rock type, each of these habitats is characterized by a subsurface microclimate that prevents endolithic microorganisms growth. Photosynthesis-based endolithic microbial communities commonly inhabit the outer millimeters to centimeters of rocks exposed to the surface. The ability to fix carbon dioxide and in some cases atmospheric dinitrogen, gives the Cyanobacteria a clear competitive advantage over heterotrophic bacteria, so it is been called the main primary producer. Light quality and intensity appear to be the main determinant of the maximum depth to which growth occurs in endolithic phototrophic communities. Valleys of Fantastic Rocks in Bole is close to Alashankou Port of Xinjiang which belongs to extreme continental climate. In order to investigate the structure, composition and diversity of endolithic bacterial community in exposed granitic porphyry in the Valleys of Fantastic Rocks, environmental DNA was directly extracted from granite rock, the 16S rRNA genes were amplified from the total DNA by PCR with bacterial-specific primers, and an endolithic bacterial clone library was constructed. Positive clones were randomly selected from the library and identified by Restriction Fragment Length Polymorphism (RFLP). The unique rRNA types clones were sequenced, analysised and then constructed phylogenetic tree. In total, 129 positive clones were screened and grouped into 46 operational taxonomic unites (OTUs). The clone coverage C value was 89.15%, indicating that most of the estimated endolithic bacterial diversity was sampled. BLAST analysis indicated that 46 OTUs were divided into seven phyla (Acidobacteria, Actinobacteria, Bacteroidetes, Chloroflexi, Cyanobacteria, Planctomycetes, Proteobacteria) and five unknown groups. Cyanobacteria (43%), especially the Gp I, form the functional basis for an endolithic bacteria community which contain a wide spectrum species of chemotrophic bacteria (33%) with mainly Actinobacteria, α-Proteobacteria, Acidobacteria. Additionally, most clones that derived from the endolithic bacteria clone library showed high similarity to the sequence deposited in GenBank database with 97%–99%. Besides, 35% of the clones showed less than 97% of sequence similarity, of which 12% sequences were affiliated to genus Rubrobacter. The results suggested that endolithic bacteria in Valleys of Fantastic Rocks in Xinjiang were highly diverse in species richness, and maybe have a diversity of potential novel species and lineages.     

Transarterial Chemoembolization in Combination with Local Therapies for Hepatocellular Carcinoma: A Meta-Analysis

Background

In previous randomized trials, transarterial chemoembolization (TACE) has shown an improvement of survival rate in hepatocellular carcinoma (HCC) when combined with radiofrequency ablation (RFA), percutaneous ethanol injection (PEI) or other therapies. The aim of this meta-analysis was to evaluate the effectiveness of combination therapy of TACE with RFA, PEI, radiotherapy (RT), three-dimensional conformal radiation therapy (3D-CRT) or High-Intensity Focused Ultrasound (HIFU).

Methods

Randomized or nonrandomized studies comparing TACE combined with RFA, PEI, RT, 3D-CRT or HIFU with TACE alone for HCC were included. Meta-analysis was performed using a fix-effects model in RCTs and a random-effects model among the observational studies.

Results

10 randomized trials and 18 observational studies matched the selection criteria, including 2497 patients (682 in RCTs, 1815 in non-RCTs). Meta-analysis of RCTs showed that the combination of TACE and PEI ((RR)_{1 -}year=1.10, 95%CI=0.99-1.22, p=0.073; (RR)_{3 -}year=2.32, 95%CI=1.52-3.53, p<0.001), TACE+RT ((RR)_{1 -}year=1.37, 95%CI=1.11-1.70, p=0.004; (RR)_{3 -}year=2.32, 95%CI=1.44-3.75, p=0.001) were associated with higher survival rates. The results of observational studies were in good consistency with that of RCTs. Furthermore, TACE plus 3D-CRT ((RR)_{1 -}year=1.22, 95%CI=1.06-1.41, p=0.005; (RR)_{3 -}year=2.05, 95%CI=1.48-2.84, p<0.001) and TACE plus HIFU ((RR)_{1 -}year=1.16, 95%CI=1.01-1.33, p=0.033; (RR)_{3 -}year=1.66, 95%CI=1.12-2.45, p=0.011) have introduced marked survival benefit when pooling results from observational studies.

Conclusions

This meta-analysis demonstrated that TACE combined with local treatments, especially PEI, HIFU or 3D-CRT could improve the overall survival status than performing TACE alone. Importantly, these results need to be validated in further high-quality clinical trials.     

CISA: Contig Integrator for Sequence Assembly of Bacterial Genomes

A plethora of algorithmic assemblers have been proposed for the de novo assembly of genomes, however, no individual assembler guarantees the optimal assembly for diverse species. Optimizing various parameters in an assembler is often performed in order to generate the most optimal assembly. However, few efforts have been pursued to take advantage of multiple assemblies to yield an assembly of high accuracy. In this study, we employ various state-of-the-art assemblers to generate different sets of contigs for bacterial genomes. A tool, named CISA, has been developed to integrate the assemblies into a hybrid set of contigs, resulting in assemblies of superior contiguity and accuracy, compared with the assemblies generated by the state-of-the-art assemblers and the hybrid assemblies merged by existing tools. This tool is implemented in Python and requires MUMmer and BLAST+ to be installed on the local machine. The source code of CISA and examples of its use are available at http://sb.nhri.org.tw/CISA/.     

SPLUNC1 Regulates Cell Progression and Apoptosis through the miR-141-PTEN/p27 Pathway,but Is Hindered by LMP1

Little is known about the role of the host defensive protein short palate, lung and nasal epithelium clone 1 (SPLUNC1) in the carcinogenesis of nasopharyngeal carcinoma (NPC). Here we report that SPLUNC1 plays a role at a very early stage of NPC carcinogenesis. SPLUNC1 regulates NPC cell proliferation, differentiation and apoptosis through miR-141, which in turn regulates PTEN and p27 expression. This signaling axis is negatively regulated by the EBV-coded gene LMP1. Therefore we propose that SPLUNC1 suppresses NPC tumor formation and its inhibition by LMP1 provides a route for NPC tumorigenesis.     

Homologous Muscle Contraction during Unilateral Movement Does Not Show a Dominant Effect on Leg Representation of the Ipsilateral Primary Motor Cortex

Co-activation of homo- and heterotopic representations in the primary motor cortex (M1) ipsilateral to a unilateral motor task has been observed in neuroimaging studies. Further analysis showed that the ipsilateral M1 is involved in motor execution along with the contralateral M1 in humans. Additionally, transcranial magnetic stimulation (TMS) studies have revealed that the size of the co-activation in the ipsilateral M1 has a muscle-dominant effect in the upper limbs, with a prominent decline of inhibition within the ipsilateral M1 occurring when a homologous muscle contracts. However, the homologous muscle-dominant effect in the ipsilateral M1 is less clear in the lower limbs. The present study investigates the response of corticospinal output and intracortical inhibition in the leg representation of the ipsilateral M1 during a unilateral motor task, with homo- or heterogeneous muscles. We assessed functional changes within the ipsilateral M1 and in corticospinal outputs associated with different contracting muscles in 15 right-handed healthy subjects. Motor tasks were performed with the right-side limb, including movements of the upper and lower limbs. TMS paradigms were measured, consisting of short-interval intracortical inhibition (SICI) and recruitment curves (RCs) of motor evoked potentials (MEPs) in the right M1, and responses were recorded from the left rectus femoris (RF) and left tibialis anterior (TA) muscles. TMS results showed that significant declines in SICI and prominent increases in MEPs of the left TA and left RF during unilateral movements. Cortical activations were associated with the muscles contracting during the movements. The present data demonstrate that activation of the ipsilateral M1 on leg representation could be increased during unilateral movement. However, no homologous muscle-dominant effect was evident in the leg muscles. The results may reflect that functional coupling of bilateral leg muscles is a reciprocal movement.     

Lysine-Specific Demethylase 1 in Breast Cancer Cells Contributes to the Production of Endogenous Formaldehyde in the Metastatic Bone Cancer Pain Model of Rats

Background

Bone cancer pain seriously affects the quality of life of cancer patients. Our previous study found that endogenous formaldehyde was produced by cancer cells metastasized into bone marrows and played an important role in bone cancer pain. However, the mechanism of production of this endogenous formaldehyde by metastatic cancer cells was unknown in bone cancer pain rats. Lysine-specific demethylase 1 (LSD1) is one of the major enzymes catalyzing the production of formaldehyde. The expression of LSD1 and the concentration of formaldehyde were up-regulated in many high-risk tumors.

Objective

This study aimed to investigate whether LSD1 in metastasized MRMT-1 breast cancer cells in bone marrows participated in the production of endogenous formaldehyde in bone cancer pain rats.

Methodology/Principal Findings

Concentration of the endogenous formaldehyde was measured by high performance liquid chromatography (HPLC). Endogenous formaldehyde dramatically increased in cultured MRMT-1 breast cancer cells in vitro, in bone marrows and sera of bone cancer pain rats, in tumor tissues and sera of MRMT-1 subcutaneous vaccination model rats in vivo. Formaldehyde at a concentration as low as the above measured (3 mM) induced pain behaviors in normal rats. The expression of LSD1 which mainly located in nuclei of cancer cells significantly increased in bone marrows of bone cancer pain rats from 14 d to 21 d after inoculation. Furthermore, inhibition of LSD1 decreased the production of formaldehyde in MRMT-1 cells in vitro. Intraperitoneal injection of LSD1 inhibitor pargyline from 3 d to 14 d after inoculation of MRMT-1 cancer cells reduced bone cancer pain behaviors.

Conclusion

Our data in the present study, combing our previous report, suggested that in the endogenous formaldehyde-induced pain in bone cancer pain rats, LSD1 in metastasized cancer cells contributed to the production of the endogenous formaldehyde.     

Targeting Wild-Type and Mutationally Activated FGFR4 in Rhabdomyosarcoma with the Inhibitor Ponatinib (AP24534)

Rhabdomyosarcoma (RMS) is the most common childhood soft tissue sarcoma. Despite advances in modern therapy, patients with relapsed or metastatic disease have a very poor clinical prognosis. Fibroblast Growth Factor Receptor 4 (FGFR4) is a cell surface tyrosine kinase receptor that is involved in normal myogenesis and muscle regeneration, but not commonly expressed in differentiated muscle tissues. Amplification and mutational activation of FGFR4 has been reported in RMS and promotes tumor progression. Therefore, FGFR4 is a tractable therapeutic target for patients with RMS. In this study, we used a chimeric Ba/F3 TEL-FGFR4 construct to test five tyrosine kinase inhibitors reported to specifically inhibit FGFRs in the nanomolar range. We found ponatinib (AP24534) to be the most potent FGFR4 inhibitor with an IC₅₀ in the nanomolar range. Ponatinib inhibited the growth of RMS cells expressing wild-type or mutated FGFR4 through increased apoptosis. Phosphorylation of wild-type and mutated FGFR4 as well as its downstream target STAT3 was also suppressed by ponatinib. Finally, ponatinib treatment inhibited tumor growth in a RMS mouse model expressing mutated FGFR4. Therefore, our data suggests that ponatinib is a potentially effective therapeutic agent for RMS tumors that are driven by a dysregulated FGFR4 signaling pathway.     

Msb1 Interacts with Cdc42, Boi1, and Boi2 and May Coordinate Cdc42 and Rho1 Functions during Early Stage of Bud Development in Budding Yeast

Msb1 is not essential for growth in the budding yeast Saccharomyces cerevisiae since msb1Δ cells do not display obvious phenotypes. Genetic studies suggest that Msb1 positively regulates Cdc42 function during bud development, since high-copy MSB1 suppressed the growth defect of temperature-sensitive cdc24 and cdc42 mutants at restrictive temperature, while deletion of MSB1 showed synthetic lethality with cdc24, bem1, and bem2 mutations. However, the mechanism of how Msb1 regulates Cdc42 function remains poorly understood. Here, we show that Msb1 localizes to sites of polarized growth during bud development and interacts with Cdc42 in the cells. In addition, Msb1 interacts with Boi1 and Boi2, two scaffold proteins that also interact with Cdc42 and Bem1. These findings suggest that Msb1 may positively regulate Cdc42 function by interacting with Cdc42, Boi1, and Boi2, which may promote the efficient assembly of Cdc42, Cdc24, and other proteins into a functional complex. We also show that Msb1 interacts with Rho1 in the cells and Msb1 overproduction inhibits the growth of rho1-104 and rho1-3 but not rho1-2 cells. The growth inhibition appears to result from the down-regulation of Rho1 function in glucan synthesis, specifically during early stage of bud development. These results suggest that Msb1 may coordinate Cdc42 and Rho1 functions during early stage of bud development by promoting Cdc42 function and inhibiting Rho1 function. Msb1 overproduction also affects cell morphology, septin organization, and causes increased, aberrant deposition of 1,3-β-glucan and chitin at the mother-bud neck. However, the stimulation of glucan synthesis mainly occurs during late, but not early, stage of bud development.