A note on modular forms and generalized anomaly cancellation formulas

By studying modular invariance properties of some characteristic forms, we prove some new anomaly cancellation formulas which generalize the Han-Zhang and Han-Liu-Zhang anomaly cancellation formula

Deciphering hierarchical organization of topologically associated domains through change-point testing.

BACKGROUND: The nucleus of eukaryotic cells spatially packages chromosomes into a hierarchical and distinct segregation that plays critical roles in maintaining transcription regulation. High-throughput methods of chromosome conformation capture, such as Hi-C, have revealed topologically associating domains (TADs) that are defined by biased chromatin interactions within them. RESULTS: We introduce a novel method, HiCKey, to decipher hierarchical TAD structures in Hi-C data and compare them across samples. We first derive a generalized likelihood-ratio (GLR) test for detecting change-points in an interaction matrix that follows a negative binomial distribution or general mixture distribution. We then employ several optimal search strategies to decipher hierarchical TADs with p values calculated by the GLR test. Large-scale validations of simulation data show that HiCKey has good precision in recalling known TADs and is robust against random collisions of chromatin interactions. By applying HiCKey to Hi-C data of seven human cell lines, we identified multiple layers of TAD organization among them, but the vast majority had no more than four layers. In particular, we found that TAD boundaries are significantly enriched in active chromosomal regions compared to repressed regions. CONCLUSIONS: HiCKey is optimized for processing large matrices constructed from high-resolution Hi-C experiments. The method and theoretical result of the GLR test provide a general framework for significance testing of similar experimental chromatin interaction data that may not fully follow negative binomial distributions but rather more general mixture distributions

Sulforaphane induces adipocyte browning and promotes glucose and lipid utilization

Scope: Obesity is closely related to the imbalance of white adipose tissue storing excess calories, and brown adipose tissue dissipating energy to produce heat in mammals. Recent studies revealed that acquisition of brown characteristics by white adipocytes, termed “browning,” may positively contribute to cellular bioenergetics and metabolism homeostasis. The goal was to investigate the putative effects of natural antioxidant sulforaphane (1-isothiocyanate-4-methyl-sulfonyl butane; SFN) on browning of white adipocytes. Methods and Results: 3T3-L1 mature white adipocytes were treated with SFN for 48 h, and then the mitochondrial content, function, and energy utilization were assessed. SFN was found to induce 3T3-L1 adipocytes browning based on the increased mitochondrial content and activity of respiratory chain enzymes, whereas the mechanism involved the upregulation of nuclear factor E2-related factor 2/ sirtuin1/ peroxisome proliferator-activated receptor gamma coactivator 1 alpha signaling. SFN enhanced uncoupling protein 1 expression, a marker for brown adipocyte, leading to the decrease in cellular ATP. SFN also enhanced glucose uptake and oxidative utilization, lipolysis and fatty acid oxidation in 3T3-L1 adipocytes. Conclusion: SFN-induced browning of white adipocytes enhanced the utilization of cellular fuel, and the application of SFN is a promising strategy to combat obesity and obesity-related metabolic disorder

Quantum transport through a double Aharonov-Bohm-interferometer in the presence of Andreev reflection

Quantum transport through a double Aharonov-Bohm-interferometer in the presence of Andreev reflection is investigated in terms of the nonequilibrium Green function method with which the reflection current is obtained. Tunable Andreev reflection probabilities depending on the interdot coupling strength and magnetic flux as well are analysised in detail. It is found that the oscillation period of the reflection probability with respect to the magnetic flux for the double interferometer depends linearly on the ratio of two parts magnetic fluxes n, i.e. 2(n+1)pi, while that of a single interferometer is 2pi. The coupling strength not only affects the height and the linewidth of Andreev reflection current peaks vs gate votage but also shifts the peak positions. It is furthermore demonstrated that the Andreev reflection current peaks can be tuned by the magnetic fluxes.Comment: 13 pages, 12 figur

Bacterial conjugated linoleic acid production and their applications

peer-reviewedConjugated linoleic acid (CLA) has been shown to exert various potential physiological properties including anti-carcinogenic, anti-obesity, anti-cardiovascular and anti-diabetic activities, and consequently has been considered as a promising food supplement. Bacterial biosynthesis of CLA is an attractive approach for commercial production due to its high isomer-selectivity and convenient purification process. Many bacterial species have been reported to convert free linoleic acid (LA) to CLA, hitherto only the precise CLA-producing mechanisms in Propionibacterium acnes and Lactobacillus plantarum have been illustrated completely, prompting the development of recombinant technology used in CLA production. The purpose of the article is to review the bacterial CLA producers as well as the recent progress on describing the mechanism of microbial CLA-production. Furthermore, the advances and potential in the heterologous expression of CLA genetic determinants will be presented

BET Bromodomain Inhibition Triggers Apoptosis of NF1-Associated Malignant Peripheral Nerve Sheath Tumors through Bim Induction

SummaryMalignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive sarcomas that develop sporadically or in neurofibromatosis type 1 (NF1) patients. There is no effective treatment for MPNSTs and they are typically fatal. To gain insights into MPNST pathogenesis, we utilized an MPNST mouse model that allowed us to study the evolution of these tumors at the transcriptome level. Strikingly, in MPNSTs we found upregulation of a chromatin regulator, Brd4, and show that BRD4 inhibition profoundly suppresses both growth and tumorigenesis. Our findings reveal roles for BET bromodomains in MPNST development and report a mechanism by which bromodomain inhibition induces apoptosis through induction of proapoptotic Bim, which may represent a paradigm shift in therapy for MPNST patients. Moreover, these findings indicate epigenetic mechanisms underlying the balance of anti- and proapoptotic molecules and that bromodomain inhibition can shift this balance in favor of cancer cell apoptosis

PTEN loss mediated Akt activation promotes prostate tumor growth and metastasis via CXCL12/CXCR4 signaling

Abstract Introduction The chemokine CXCL12, also known as SDF-1, and its receptor, CXCR4, are overexpressed in prostate cancers and in animal models of prostate-specific PTEN deletion, but their regulation is poorly understood. Loss of the tumor suppressor PTEN (phosphatase and tensin homolog) is frequently observed in cancer, resulting in the deregulation of cell survival, growth, and proliferation. We hypothesize that loss of PTEN and subsequent activation of Akt, frequent occurrences in prostate cancer, regulate the CXCL12/CXCR4 signaling axis in tumor growth and bone metastasis. Methods Murine prostate epithelial cells from PTEN+/+, PTEN +/− , and PTEN−/− (prostate specific knockdown) mice as well as human prostate cancer cell lines C4-2B, PC3, and DU145 were used in gene expression and invasion studies with Akt inhibition. Additionally, HA-tagged Akt1 was overexpressed in DU145, and tumor growth in subcutaneous and intra-tibia bone metastasis models were analyzed. Results Loss of PTEN resulted in increased expression of CXCR4 and CXCL12 and Akt inhibition reversed expression and cellular invasion. These results suggest that loss of PTEN may play a key role in the regulation of this chemokine activity in prostate cancer. Overexpression of Akt1 in DU145 resulted in increased CXCR4 expression, as well as increased proliferation and cell cycle progression. Subcutaneous injection of these cells also resulted in increased tumor growth as compared to neo controls. Akt1 overexpression reversed the osteosclerotic phenotype associated with DU145 cells to an osteolytic phenotype and enhanced intra-osseous tumor growth. Conclusions These results suggest the basis for activation of CXCL12 signaling through CXCR4 in prostate cancer driven by the loss of PTEN and subsequent activation of Akt. Akt1-associated CXCL12/CXCR4 signaling promotes tumor growth, suggesting that Akt inhibitors may potentially be employed as anticancer agents to target expansion of PC bone metastases

Mining bifidobacteria from the neonatal gastrointestinal tract for conjugated linolenic acid production

peer-reviewedConjugated linolenic acid (CLNA) is a family of isomers of linolenic acid with a number of healthassociated benefits, which has been attracting great interest. Microbial CLNA producers are potentially an alternative source of CLNA for human nutrition. In present study, 16 neonate feces were collected and used for Bifidobacteria isolation, from which 25 bifidobacteria isolates were obtained. The bifidobacteria isolates were identified using 16s rDNA sequencing as Bifidobacterium adolescentis, B. breve, B. longum and B. pseudocatenulatum. These isolates were further investigated for their ability to produce CLNA using linolenic acid as substrate via GC-MS. The results showed most of the isolates could convert free linolenic acid into c9,t11,c15-CLNA and t9,t11,c15-CLNA at different levels. B. pseudocatenulatum was the most effective CLNA producer, which converted 86.91% of linolenic acid to c9,t11,c15-CLNA and 3.59% of to t9,t11,c15-CLNA isomer and the isolate exhibited to accumulate CLNA during 72 h culturing in which most CLNA isomers were in the supernatant fluid. The results indicated that utilization of this isolate for CLNA production will eliminate the purification process.National Natural Science Foundation of Chin