Epigenetic modification in 4T1 mouse breast cancer model by artificial light at night and melatonin – the role of DNA-methyltransferase

Currently, one of the most disputed hypotheses regarding breast cancer (BC) development is exposure to short wavelength artificial light at night (ALAN) as multiple studies suggest a possible link between them. This link is suggested to be mediated by nocturnal melatonin suppression that plays an integral role in circadian regulations including cell division. The objective of the research was to evaluate effects of 1 × 30 min/midnight ALAN (134 µ Wcm^?2, 460 nm) with or without nocturnal melatonin supplement on tumor development and epigenetic responses in 4T1 tumor-bearing BALB/c mice. Mice were monitored for body mass (W_b) and tumor volume for 3 weeks and thereafter urine samples were collected at regular intervals for determining daily rhythms of 6-sulfatoxymelatonin (6-SMT). Finally, mice were sacrificed and the tumor, lungs, liver, and spleen were excised for analyzing the total activity of DNA methyltransferases (DNMT) and global DNA methylation (GDM) levels. Mice exposed to ALAN significantly reduced 6-SMT levels and increased W_b, tumor volume, and lung metastasis compared with controls. These effects were diminished by melatonin. The DNMT activity and GDM levels showed tissue-specific response. The enzymatic activity and GDM levels were lower in tumor and liver and higher in spleen and lungs under ALAN compared with controls. Our results suggest that ALAN disrupts the melatonin rhythm and potentially leading to increased BC burden by affecting DNMT activity and GDM levels. These data may also be applicable to early detection and management of BC by monitoring melatonin and GDM levels as early biomarker of ALAN circadian disruption.     

FastStor: improving the performance of a large scale hybrid storage system via caching and prefetching

Storing enormous amount of data on hybrid storage systems has become a widely accepted solution for today’s production level applications in order to trade off the performance and cost. However, how to improve the performance of large scale storage systems with hybrid components (e.g. solid state disks, hard drives and tapes) and complicated user behaviors is not fully explored. In this paper, we conduct an in-depth case study (we call it FastStor) on designing a high performance hybrid storage system to support one of the world’s largest satellite images distribution systems operated by the U.S. Geological Survey (USGS) Earth Resources Observation and Science (EROS) center. We demonstrate how to combine conventional caching policies with innovative current popularity oriented and user-specific prefetching algorithms to improve the performance of the EROS system. We evaluate the effectiveness of our proposed solution using over 5 million real world user download requests provided by EROS. Our experimental results show that using the Least Recently Used (LRU) caching policy alone, we are able to achieve an overall 64 % or 70 % hit ratio on a 100 TB or 200 TB FTP server farm composed of Solid State Disks (SSDs) respectively. The hit ratio can be further improved to 70 % (for 100 TB SSDs) and 76 % (for 200 TB SSDs) if intelligent prefetching algorithms are used together with LRU.     

IDENTIFYING COEVOLUTIONARY PATTERNS IN HUMAN LEUKOCYTE ANTIGEN (HLA) MOLECULES

The antigenic peptide, major histocompatibility complex molecule (MHC; also called human leukocyte antigen, HLA), coreceptor CD8, or CD4 and T‐cell receptor (TCR) function as a complex to initiate effectors’ mechanisms of the immune system. The tight functional and physical interaction among these molecules may have involved strong coevolution links among domains within and between proteins. Despite the importance of unraveling such dependencies to understand the arms race of host–pathogen interaction, no previous studies have aimed at achieving such an objective. Here, we perform an exhaustive coevolution analysis and show that indeed such dependencies are strongly shaping the evolution and probably the function of these molecules. We identify intramolecular coevolution in HLA class I and II at domains important for their immune activity. Most of the amino acid sites identified to be coevolving in HLAI have been also detected to undergo positive Darwinian selection highlighting therefore their adaptive value. We also identify coevolution among antigen‐binding pockets (P1‐P9) and among these and TCR‐binding sites. Conversely to HLAI, coevolution is weaker in HLAII. Our results support that such coevolutionary patterns are due to selective pressures of host–pathogen coevolution and cooperative binding of TCRs, antigenic peptides, and CD8/CD4 to HLAI and HLAII.     

The foot-and-mouth disease RNA virus as a model in experimental phylogenetics.

Phylogenetic reconstruction methods are subject to two types of limitations: our knowledge about the true history of organisms and the gross simplification implied in the numerical simulation models of the relationships between them. In such a situation, experimental phylogenetics provides a way to assess the accuracy of the phylogenetic reconstruction methods. Nonetheless, this capacity is only feasible for organisms in which replication and mutation rates are high enough to provide valuable data. On the other hand, experimental phylogenetics also provides insights on the main evolutionary processes acting on viral variability under different population dynamics. Our study with the foot-and-mouth disease virus (FMDV) strongly suggests that the phylogenetic reconstruction methods can infer erroneous phylogenies due to nucleotide convergences between isolates belonging to different experimental lineages. We also point out that the diverse evolutionary mechanisms acting in different experimental dynamics generate alterations and change the frequencies of genetic variants, which can lead to the misinterpretation of the real evolutionary history.