Graphs with second largest eigenvalue less than 1/21/2

We characterize the simple connected graphs with the second largest eigenvalue less than 1/2, which consists of 13 classes of specific graphs. These 13 classes hint that $c_{2}\in [1/2, \sqrt{2+\sqrt{5}}]$, where $c_2$ is the minimum real number $c$ for which every real number greater than $c$ is a limit point in the set of the second largest eigenvalues of the simple connected graphs. We leave it as a problem.Comment: 36 pages, 2 table

Arsenite binds to the RING finger domains of RNF20-RNF40 histone E3 ubiquitin ligase and inhibits DNA double-strand break repair.

Arsenic is a widespread environmental contaminant. However, the exact molecular mechanisms underlying the carcinogenic effects of arsenic remain incompletely understood. Core histones can be ubiquitinated by RING finger E3 ubiquitin ligases, among which the RNF20-RNF40 heterodimer catalyzes the ubiquitination of histone H2B at lysine 120. This ubiquitination event is important for the formation of open and biochemically accessible chromatin fiber that is conducive for DNA repair. Herein, we found that arsenite could bind directly to the RING finger domains of RNF20 and RNF40 in vitro and in cells, and treatment with arsenite resulted in substantially impaired H2B ubiquitination in multiple cell lines. Exposure to arsenite also diminished the recruitment of BRCA1 and RAD51 to laser-induced DNA double-strand break (DSB) sites, compromised DNA DSB repair in human cells, and rendered cells sensitive toward a radiomimetic agent, neocarzinostatin. Together, the results from the present study revealed, for the first time, that arsenite may exert its carcinogenic effect by targeting cysteine residues in the RING finger domains of histone E3 ubiquitin ligase, thereby altering histone epigenetic mark and compromising DNA DSB repair. Our results also suggest arsenite as a general inhibitor for RING finger E3 ubiquitin ligases

Detecting and phenotyping of aneuploid circulating tumor cells in patients with various malignancies

Circulating tumor cells (CTCs) have been exclusively studied and served to assess the clinical outcomes of treatments and progression of cancer. Most CTC data have mainly been derived from distinct cohorts or selected tumor types. In the present study, a total of 594 blood samples from 479 cases with 19 different carcinomas and 30 healthy samples were collected and analyzed by Subtraction enrichment method combined with immunostaining-fluorescence in situ hybridization (iFISH). Non-hematopoietic cells with aneuploid chromosome 8 (more than 2 copies) were regarded as positive CTCs. The results showed that none of CTCs was found in all 30 healthy samples. The overall positive rate of CTCs was 89.0% in diagnosed cancer patients (ranging from 75.0% to 100.0%). Average number of 11, 5, 8 and 4 CTCs per 7.5 mL was observed in lung cancer, liver cancer, renal cancer and colorectal cancer, respectively. Among 19 different carcinomas, the total number of CTCs, tetraploid chromosome 8, polyploid chromosome 8, CTM (Circulating tumor microemboli) and large CTCs in patients with stage Ⅲ and Ⅳ were statistically higher than patients with stage Ⅰ and Ⅱ (P < 0.05). Furthermore, EpCAM expression was more frequently found in most CTCs than vimentin expression, confirming that these CTCs were of epithelial origin. In addition, small and large CTCs were also classified, and the expression of vimentin was mostly observed in small CTCs and CTM. Our results revealed that there are higher numbers of CTCs, tetraploid, polyploid and large CTCs in patients with stage Ⅲ and Ⅳ, indicating that the quantification of chromosome ploidy performed by SE-iFISH for CTCs might be a useful tool to predict and evaluate therapeutic efficacy as well as to monitoring disease progression

Ubiquitination in Scleroderma Fibrosis and Its Treatment

Scleroderma (systemic sclerosis, SSc) is a highly heterogeneous rheumatic disease, and uncontrolled fibrosis in visceral organs is the major cause of death in patients. The transforming growth factor-β (TGF-β) and WNT/β-catenin signaling pathways, along with signal transducer and activator of transcription 3 (STAT3), play crucial roles in this fibrotic process. Currently, no therapy is available that effectively arrests or reverses the progression of fibrosis in patients with SSc. Ubiquitination is an important post-translational modification that controls many critical cellular functions. Dysregulated ubiquitination events have been observed in patients with systemic lupus erythematosus, rheumatoid arthritis and fibrotic diseases. Inhibitors targeting the ubiquitination pathway have considerable potential for the treatment of rheumatic diseases. However, very few studies have examined the role and mechanism of ubiquitination in patients with SSc. In this review, we will summarize the molecular mechanisms of ubiquitination in patients with SSc and explore the potential targets for treatment

Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres

Photoacoustic tomography (PAT) also referred to as optoacoustic tomography (OAT) is a hybrid imaging modality that employs nonionizing optical radiation and ultrasonic detection. Here, we describe the application of a new class of optical contrast agents based on mesoscopic hollow gold nanospheres (HAuNS) to PAT. HAuNS are ∼40 nm in diameter with a hollow interior and consist of a thin gold wall. They display strong resonance absorption tuned to the near-infrared (NIR) range, with an absorption peak at 800 nm, whose photoacoustic efficiency is significantly greater than that of blood. Following surface conjugation with thiolated poly(ethylene glycol), the pegylated HAuNS (PEG-HAuNS) had distribution and elimination half-lives of 1.38 ± 0.38 and 71.82 ± 30.46 h, respectively. Compared with PAT images based on the intrinsic optical contrast in nude mice, the PAT images acquired within 2 h after intravenous administration of PEG-HAuNS showed the brain vasculature with greater clarity and detail. The image depicted brain blood vessels as small as ∼100 μm in diameter using PEG-HAuNS as contrast agents. Preliminary results showed no acute toxicity to the liver, spleen, or kidneys in mice following a single imaging dose of PEG-HAuNS. Our results indicate that PEG-HAuNS are promising contrast agents for PAT, with high spatial resolution and enhanced sensitivity

Use acupuncture to relieve perimenopausal syndrome: study protocol of a randomized controlled trial

Law Number 11 / 2008 on Information and Electronic Transaction (UU ITE) is the regulation concerning on criminal law in addition to the Criminal Code (KUHP). UU ITE is commonly regarded additional regulation of the Criminal Code as a special law (lex specialis) in which Penal Code is deemed as lex generalis. It is based on the principle of lex specialis derogate legi generalis. This article uses legal research to review the decision of District Court in Bandung Number 1033/PID.B/2014/PN.BDG where it comprises legislation and cases. It concludes that the judge is not frugal in applying the principle lex specialis derogat legi generalis in the consideration. This is associated with the indictment of public prosecutor which only prejudges with article 303 paragraph (1) to 2. In contrast, the indictment which does not meet the requirement of a careful, clear, and complete description asserts to become void by law. Keywords: Online Gambling, Criminal Principle, Indictmen

Comparative transcriptome profiling provides insights into plant salt tolerance in seashore paspalum (\u3ci\u3ePaspalum vaginatum\u3c/i\u3e)

Background Seashore paspalum (Paspalum vaginatum), a halophytic warm-seasoned perennial grass, is tolerant of many environmental stresses, especially salt stress. To investigate molecular mechanisms underlying salinity tolerance in seashore paspalum, physiological characteristics and global transcription profiles of highly (Supreme) and moderately (Parish) salinity-tolerant cultivars under normal and salt stressed conditions were analyzed. Results Physiological characterization comparing highly (Supreme) and moderately (Parish) salinity-tolerant cultivars revealed that Supreme’s higher salinity tolerance is associated with higher Na+ and Ca2+ accumulation under normal conditions and further increase of Na+ under salt-treated conditions (400 mM NaCl), possibly by vacuolar sequestration. Moreover, K+ retention under salt treatment occurs in both cultivars, suggesting that it may be a conserved mechanism for prevention of Na+ toxicity. We sequenced the transcriptome of the two cultivars under both normal and salt-treated conditions (400 mM NaCl) using RNA-seq. De novo assembly of about 153 million high-quality reads and identification of Open Reading Frames (ORFs) uncovered a total of 82,608 non-redundant unigenes, of which 3250 genes were identified as transcription factors (TFs). Gene Ontology (GO) annotation revealed the presence of genes involved in diverse cellular processes in seashore paspalum’s transcriptome. Differential expression analysis identified a total of 828 and 2222 genes that are responsive to high salinity for Supreme and Parish, respectively. “Oxidation-reduction process” and “nucleic acid binding” are significantly enriched GOs among differentially expressed genes in both cultivars under salt treatment. Interestingly, compared to Parish, a number of salt stress induced transcription factors are enriched and show higher abundance in Supreme under normal conditions, possibly due to enhanced Ca2+ signaling transduction out of Na+ accumulation, which may be another contributor to Supreme’s higher salinity tolerance. Conclusion Physiological and transcriptome analyses of seashore paspalum reveal major molecular underpinnings contributing to plant response to salt stress in this halophytic warm-seasoned perennial grass. The data obtained provide valuable molecular resources for functional studies and developing strategies to engineer plant salinity tolerance

Act1, a Negative Regulator in CD40- and BAFF-Mediated B Cell Survival

AbstractTNF receptor (TNFR) superfamily members, CD40, and BAFFR play critical roles in B cell survival and differentiation. Genetic deficiency in a novel adaptor molecule, Act1, for CD40 and BAFF results in a dramatic increase in peripheral B cells, which culminates in lymphadenopathy and splenomegaly, hypergammaglobulinemia, and autoantibodies. While the B cell-specific Act1 knockout mice displayed a similar phenotype with less severity, the pathology of the Act1-deficient mice was mostly blocked in CD40-Act1 and BAFF-Act1 double knockout mice. CD40- and BAFF-mediated survival is significantly increased in Act1-deficent B cells, with stronger IκB phosphorylation, processing of NF-κB2 (p100/p52), and activation of JNK, ERK, and p38 pathways, indicating that Act1 negatively regulates CD40- and BAFF-mediated signaling events. These findings demonstrate that Act1 plays an important role in the homeostasis of B cells by attenuating CD40 and BAFFR signaling

Bacillus thuringiensis Suppresses the Humoral Immune System to Overcome Defense Mechanism of Plutella xylostella

Background:Plutella xylostella has become a notorious pest of cruciferous crops all over the world. Delta-endotoxins of Bacillus thuringiensis are widely used insecticidal proteins for controlling P. xylostella. However, the interaction mechanism of B. thuringiensis with the immune system of P. xylostella, at the genomic level, is still unclear. This study explored the immune response of P. xylostella to B. thuringiensis, at different time intervals, 6 h, 12 h, 18 h, 24 h, and 36 h, by using RNA-Sequencing (RNA-Seq) and RT-qPCR.Results: In total, 167 immunity-related genes were identified and placed into different families, including pattern recognition receptors (PRRs), signal modulators, immune pathways (Toll, IMD, and JAK/STAT), and immune effectors. It is worth mentioning that the analyses of the differentially expressed immunity-related genes revealed that most of the differentially expressed genes (DEGs) (87, 56, 76, 67, and 73 genes) were downregulated in P. xylostella following B. thuringiensis oral infection at 6 h, 12 h, 18 h, 24 h, and 36 h. Interestingly, our RNA-Seq analysis also revealed reduced expression of antimicrobial peptides, that play a vital role in the humoral immune system of P. xylostella.Conclusion: This study demonstrates that B. thuringiensis plays a novel role in controlling P. xylostella, by suppressing the immune system