ALBERT

Description: Maintenance of genome stability is carried out by a suite of DNA repair pathways that ensure the repair of damaged DNA and faithful replication of the genome. Of particular importance are the repair pathways, which respond to DNA double-strand breaks (DSBs), and how the efficiency of repair is influenced by...

Description: A critical phenomenon is an intrinsic feature of traffic dynamics, during which transition between isolated local flows and global flows occurs. However, very little attention has been given to the question of how the local flows in the roads are organized collectively into a global city flow. Here we characterize...

Description: Understanding the genetic structure of human populations has important implications for the design and interpretation of disease mapping studies and reconstructing human evolutionary history. To date, inferences of human population structure have primarily been made with common variants. However, recent large-scale resequencing studies have shown an abundance of rare variation in humans, which may be particularly useful for making inferences of fine-scale population structure. To this end, we used an information theory framework and extensive coalescent simulations to rigorously quantify the informativeness of rare and common variation to detect signatures of fine-scale population structure. We show that rare variation affords unique insights into patterns of recent population structure. Furthermore, to empirically assess our theoretical findings, we analyzed high-coverage exome sequences in 6,515 European and African American individuals. As predicted, rare variants are more informative than common polymorphisms in revealing a distinct cluster of European–American individuals, and subsequent analyses demonstrate that these individuals are likely of Ashkenazi Jewish ancestry. Our results provide new insights into the population structure using rare variation, which will be an important factor to account for in rare variant association studies.

Description: The ‘Human Immunodeficiency Virus Type 1 (HIV-1), Human Interaction Database’, available through the National Library of Medicine at http://www.ncbi.nlm.nih.gov/genome/viruses/retroviruses/hiv-1/interactions , serves the scientific community exploring the discovery of novel HIV vaccine candidates and therapeutic targets. Each HIV-1 human protein interaction can be retrieved without restriction by web-based downloads and ftp protocols and includes: Reference Sequence (RefSeq) protein accession numbers, National Center for Biotechnology Information Gene identification numbers, brief descriptions of the interactions, searchable keywords for interactions and PubMed identification numbers (PMIDs) of journal articles describing the interactions. In addition to specific HIV-1 protein–human protein interactions, included are interaction effects upon HIV-1 replication resulting when individual human gene expression is blocked using siRNA. A total of 3142 human genes are described participating in 12 786 protein–protein interactions, along with 1316 replication interactions described for each of 1250 human genes identified using small interfering RNA (siRNA). Together the data identifies 4006 human genes involved in 14 102 interactions. With the inclusion of siRNA interactions we introduce a redesigned web interface to enhance viewing, filtering and downloading of the combined data set.

Description: Much evidence show that over-expression of epidermal growth factor receptor (EGFR) plays an important role in regulating carcinogenesis. Genetic variations in 3' untranslated region (3'UTR) of gene have been reported to affect gene expression by interfering with microRNAs (miRNAs), which are thought to function as either tumour suppressors or oncogenes by binding to their target mRNA. In this study, we investigated the association between the EGFR 3'UTR 774T〉C polymorphism and bladder cancer risk. We used the TaqMan technology to genotype this genetic variant in a hospital-based case–control study of 908 bladder cancer patients and 1239 controls in a Chinese population. We found that the 774CC genotype was associated with a statistically significantly increased risk of bladder cancer [adjusted odds ratio = 1.29, 95% confidence interval = 1.05–1.58], compared with the 774TT/TC genotype, and this increased risk was more pronounced among subgroups of age 〉 65 years, non-smokers and patients’ tumour invasive stage. Furthermore, luciferase assays in T24 cell showed that EGFR 3'UTR 774 T to C substitution could increase the expression of EGFR, which was consistent with the association study finding. Additionally, we also provide evidence that 774T〉C polymorphism increasing EGFR expression was not regulated by hsa-miR-214 binding. These findings suggested that EGFR 3'UTR 774T〉C polymorphism may contribute to susceptibility to bladder cancer.

Description: CCAAT/enhancer binding protein beta protects muscle satellite cells from apoptosis after injury and in cancer cachexia Cell Death and Disease 7, e2109 (February 2016). doi:10.1038/cddis.2016.4 Authors: F Marchildon, D Fu, N Lala-Tabbert & N Wiper-Bergeron

Description: Human serum albumin (HSA) is widely used in clinical and cell culture applications. Conventional production of HSA from human blood is limited by the availability of blood donation and the high risk of viral transmission from donors. Here, we report the production of Oryza sativa recombinant HSA (OsrHSA) from transgenic rice seeds. The level of OsrHSA reached 10.58% of the total soluble protein of the rice grain. Large-scale production of OsrHSA generated protein with a purity 〉99% and a productivity rate of 2.75 g/kg brown rice. Physical and biochemical characterization of OsrHSA revealed it to be equivalent to plasma-derived HSA (pHSA). The efficiency of OsrHSA in promoting cell growth and treating liver cirrhosis in rats was similar to that of pHSA. Furthermore, OsrHSA displays similar in vitro and in vivo immunogenicity as pHSA. Our results suggest that a rice seed bioreactor produces cost-effective recombinant HSA that is safe and can help to satisfy an increasing worldwide demand for human serum albumin.

Description: Author(s): D. Fu, A. X. Levander, R. Zhang, J. W. Ager, III, and J. Wu We report an effect that occurs in semiconductors where internal electrical fields interact with a temperature gradient. Steady current vortices and a magnetic field develop in the system, even without external carrier injection. The effect is electrodynamic, energy dissipative, and fundamentally di... [Phys. Rev. B 84, 045205] Published Fri Jul 08, 2011

Description: The axoneme forms the essential and conserved core of cilia and flagella. We have used cryo-electron tomography of Chlamydomonas and sea urchin flagella to answer long-standing questions and to provide information about the structure of axonemal doublet microtubules (DMTs). Solving an ongoing controversy, we show that B-tubules of DMTs contain exactly 10 protofilaments (PFs) and that the inner junction (IJ) and outer junction between the A- and B-tubules are fundamentally different. The outer junction, crucial for the initiation of doublet formation, appears to be formed by close interactions between the tubulin subunits of three PFs with unusual tubulin interfaces; other investigators have reported that this junction is weakened by mutations affecting posttranslational modifications of tubulin. The IJ consists of an axially periodic ladder-like structure connecting tubulin PFs of the A- and B-tubules. The recently discovered microtubule inner proteins (MIPs) on the inside of the A- and B-tubules are more complex than previously thought. They are composed of alternating small and large subunits with periodicities of 16 and/or 48 nm. MIP3 forms arches connecting B-tubule PFs, contrary to an earlier report that MIP3 forms the IJ. Finally, the “beak” structures within the B-tubules of Chlamydomonas DMT1, DMT5, and DMT6 are clearly composed of a longitudinal band of proteins repeating with a periodicity of 16 nm. These findings, discussed in relation to genetic and biochemical data, provide a critical foundation for future work on the molecular assembly and stability of the axoneme, as well as its function in motility and sensory transduction.

Description: The hydrothermal fluids responsible for gold mineralization at the Ballarat East gold deposit (the second largest orogenic gold deposit in the western Lachlan orogen) are thought to have links to a variety of processes, including metamorphism, sedimentation, and/or magmatism. In the current study, noble gases and halogens have been used as fluid tracers to reevaluate the origin and evolution of the gold-related fluids at the Ballarat East deposit. Gold-bearing quartz and carbonate veins from the Ballarat East contain low salinity (~4 wt % NaCl equiv) aqueous (H2O) and mixed H2O-CO2 fluid inclusions. These fluid inclusions have variable molar Br/Cl values of between 1.2 x 10-3 and 2.9 x 10-3 and I/Cl values between 150 x 10-6 and 500 x 10-6, and Br is strongly correlated with I, defining a mixing line with a Br/I ratio of 5.6. The fluid inclusions have 40Ar/36Ar ratios ranging from 322 (close to the atmospheric 40Ar/36Ar ratio of ~296) up to a maximum of 4503. 40Ar is strongly correlated with Cl and defines a mixing line with a 40ArE/Cl ratio of 4.6 x 10-4 (40ArE denotes excess 40Ar). The fluid inclusions contain 5.1 to 32 ppm 40ArE (by mass) and exhibit minimum 36Ar concentrations ranging from 3.1 to 11 ppb, which exceed air-saturated water (ASW) levels by several parts per billion (ASW = 1.3-2.7 ppb). Fluid inclusion 84Kr/36Ar and 130Xe/36Ar values are uniformly enriched in Kr and Xe relative to air, but exhibit limited variation. These data provide strong evidence for the involvement of two noble gas and halogen reservoirs. This data is compatible with a deeply sourced fluid, possibly originating by devolatilization of altered volcanic rocks (e.g., basalts) that acquired additional noble gases and organic Br plus I by interaction with sedimentary rocks, including organic-rich shales that are found beneath and surrounding the deposit. The data are also consistent with mixing deeply sourced metamorphic fluids with sedimentary formation waters; however, both interpretations favor the involvement of metamorphic fluids and sedimentary components and highlight the significance of fluid-rock interaction as controls on fluid compositions in Victorian deposits. The data are compatible with genetic models for orogenic gold in which gold mineralization was initiated by metamorphic devolatilization in the lower crust, and was linked to Lachlan orogenesis at ca. 440 Ma.