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2005 (1),

  CELL BIOLOGY: Proteins That Promote Long Life    Stuart K. Kim
The mysteries of what causes aging and how to extend life span are being tackled by applying evolving technologies to model organisms. The tiny roundworm Caenorhabditis elegans has been a powerhouse in this arena. A key breakthrough occurred in 1993, when worms with a mutation in the daf-2 gene were observed to lead active and healthy lives twice as long as that of normal worms... - - -Edited on Aug. 3, 2007.
Science 3 August 2007   Full Text|

  Cancer: Broken genes in solid tumours    Matthew Meyerson
Mutations that cause portions of two genes to fuse together and form a hybrid gene are frequent in blood-related cancers. New findings implicate one such fusion gene in the most common type of lung cancer. - - -Edited on Aug. 3, 2007.
Nature 448, 545-546 (2007)   Full Text|

  Genomic biology: The epigenomic era opens    Stephen B. Baylin & Kornel E. Schuebel
Readout of information from the genome depends on intricate regulation of how DNA is packaged by proteins. The great endeavour to reveal how this packaging operates pan-genomically is now under way. - - -Edited on Aug. 3, 2007.
Nature 448, 548-549 (2007)   Full Text|

  MEDICINE: The Yin-Yang of Sirtuins    Andrew Dillin and Jeffery W. Kelly
The gene encoding SIRT1, a sirtuin histone deacetylase, is widely recognized for its link to aging. SIRT1 activity increases when conditions favor longevity, such as a restricted calorie intake or treatment with the polyphenol resveratrol... SIRT2 is a cytoplasmic nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that is prominently expressed in the brain.... - - -Edited on July 27, 2007.
Nature 448, 445-451 (26 July 2007)   Full Text|

  Non-transcriptional control of DNA replication by c-Myc    Nature Editors
A new, transcription-independent function for c-Myc is identified. It is found that c-Myc can bind factors involved in DNA replication, thereby causing DNA damage and affecting cell proliferation. This process may also contribute to oncogenesis. - - -Edited on July 26, 2007.
Nature 448, 445-451 (26 July 2007)   Full Text|

 Stem cells: The magic brew    Janet Rossant
Researchers have engineered embryonic stem-like cells from normal mouse skin cells. If this method can be translated to humans, patient-specific stem cells could be made without the use of donated eggs or embryos. - - -Edited on July 19, 2007.
Nature 448, 260-262 (19 July 2007)    Full Text|

  Stem cells: The magic brew
Janet Rossant   Researchers have engineered embryonic stem-like cells from normal mouse skin cells. If this method can be translated to humans, patient-specific stem cells could be made without the use of donated eggs or embryos.- - - Edited on July 19, 2007.
Nature 448, 260-262 (19 July 2007)    Full text |

  MOLECULAR BIOLOGY:How and When the Genome Sticks Together
Erwan Watrin and Jan-Michael Peters   Before a eukaryotic cell divides, it generates a copy of its genome by DNA replication. As a result, each chromosome in a postreplicative cell contains two identical DNA molecules, the sister chromatids. These DNA molecules are physically connected to each other, a phenomenon known as sister-chromatid cohesion. Cohesion is essential for the symmetrical segregation of chromosomes during cell division. Two papers in this issue, by Ström et al. on page 242 and Ünal et al. on page 245, show that cohesion can be established in response to DNA damage independently of DNA replication. This overturns a long-held belief that cohesion is strictly coupled to DNA synthesis. The papers also imply that DNA damage may have a broader impact than previously thought, triggering genomewide protection of chromosome integrity.- - - Edited on July 13, 2007.
Science 13 July 2007: Vol. 317. no. 5835, pp. 209 - 210    Full text |

  RNA Polymerase II: Just Stopping By
Matthew C. Lorincz1 & Dirk Schübeler   In this issue of Cell, Guenther et al. (2007) analyze the presence of chromatin marks and RNA polymerase at transcription start sites in the human genome. Their results reveal that many “inactive” genes harbor histone marks associated with active transcription at their 5ĀĆ ends and that although these genes initiate transcription, they do not generate full-length transcripts.- - - Edited on July 13, 2007.
Cell Vol. 130, Issue 1, 13 July 2007, Pages 16-18    Full text |

  Hard to swallow: Hard to swallow
Nature Editor   Researchers, practitioners and drug companies around the world are engaged in a complex, tentative dance over the best way to tap into the unknown potential of traditional Chinese medicine. The scientific community and the drug industry both tend to be sniffy about 'traditional' cures; yet there is a strong sense that millennia of practice in China — much of it barely documented — is likely to have yielded at least some treatments that work- - - Edited on July 12, 2007.
Nature 448, 105-106 (12 July 2007)    Full text |

  Traditional medicine: A culture in the balance
Jane Qiu   Traditional Chinese medicine and Western science face almost irreconcilable differences. Can systems biology bring them together? - - - Edited on July 12, 2007.
Nature 448, 105-106 (12 July 2007)    Full text |

  The X Factor: Skewing X Inactivation towards Cancer
René H. Medema and Boudewijn M.Th. Burgering   Increased expression of the epidermal growth factor receptor HER-2/ErbB2 is frequently observed in breast cancer and is targeted by the anticancer drug Herceptin. Now, Zuo et al. (2007) reveal that an X-linked gene encoding the transcription factor FOXP3 is a breast cancer tumor suppressor that represses expression of HER2/ErbB2. - - - Edited on June 29, 2007.
Cell Volume 129, Issue 7, 29 June 2007, Pages 1253-1254    Full text |

  HOTAIR Lifts Noncoding RNAs to New Levels
Caroline J. Woo and Robert E. Kingston   It is not clear to what extent noncoding RNAs regulate the homeobox (HOX) genes that encode key regulators of development in the embryo. In this issue, Rinn et al. (2007) characterize noncoding RNAs that regulate HOX genes and discover one, HOTAIR, that unexpectedly regulates a HOX gene cluster on a different chromosome than the HOX cluster that encodes it. - - - Edited on June 29. 2007.
Cell Volume 129, Issue 7, 29 June 2007, Pages 1257-1259.    Full text |

  It's a Small RNA World, After All
Matthew W. Vaughn and Rob Martienssen   Small RNAs (sRNAs) can regulate transcript and protein abundance. Previously, they have been identified using traditional cloning approaches, which has limited how many could be characterized. Now, the Meyers and Green laboratories have used massively parallel signature sequencing technology to find over 1.5 million sRNAs in Arabidopsis thaliana. These new sRNAs reveal a greater-than-expected potential role for sRNAs in gene regulation, preferential expression or usage of sRNAs in flowers, and the prospect of targeted sRNA-mediated regulation of pseudogenes. In addition, new plant microRNAs have been identified, some of which may be unique to Arabidopsis. - - -
Science 2 September 2005: 1525-1526.    Full text | PDF

  Cancer immunology: Cat and mouse games
Cornelis J. M. Melief   The immune system is intimately involved in how tumours develop. But how do tumours avoid being killed by immune responses? It seems that in some instances they can lull immune cells into a false sense of security.. - - -
Nature 437, 41-42 (1 September 2005)    Full text | PDF

  Chimp genome: Branching out
Carina Dennis   The chimp was a great start. But the genomes of our other primate relatives will help to reveal a whole lot more, says Carina Dennis. - - -
Nature 437, 17-19 (1 September 2005)    Full text | PDF

  Cancer: Two in one
Anton Berns   As cancer develops, at least two cell processes are disrupted — cell growth is promoted, and cell death inhibited. It seems that mutated versions of the notorious cancer-promoting protein MYC can accomplish both at once. - - -
Nature 436, 787-789 (11 August 2005)    Full text | PDF

  Cancer: Crime and punishment
Norman E. Sharpless and Ronald A. DePinho   Cellular senescence stops the growth of cells. This process, first glimpsed in cell culture, is now confirmed by in vivo evidence as a vital mechanism that constrains the malignant progression of many tumours. - - -
Nature 436, 636-637 (4 August 2005)    Full text | PDF

  Cancer: One step at a time
David Mooney   Traditional chemotherapy kills tumour cells directly; some newer drugs work instead by cutting the tumour's blood supply. An innovative approach combines these strategies sequentially to pack a double whammy. - - -
Nature 436, 468-469 (28 July 2005)    Full text | PDF

  GENOMICS: Tackling the Cancer Genome
Jocelyn Kaiser   Genome sequencers and cancer experts hope a pilot project at the National Institutes of Health to find genetic glitches in tumors will build support for a complete catalog of human cancer genes. - - -
Science, Vol 309, 29 July 2005    Full text | PDF

  Stem-cell therapies: The first wave
Catherine Zandonella   Treatments that use stem cells to replace damaged or diseased tissues are thought to lie many years away. But the cells might find other clinical applications in the near future, says Catherine Zandonella. - - -
Nature June 16 2005    Full text | PDF

  Cancer genomics: Small RNAs with big impacts
Paul S. Meltzer   Although they are tiny, microRNAs can have large-scale effects because they regulate a variety of genes. These minuscule molecules are now definitively linked to the development of cancer. - - -
Nature June 9 2005    Full text | PDF

  Stem cells: The road not taken
Hanno Hock and Stuart H. Orkin   Developmental 'road maps' chart the steps from simple cells to mature, specialized cells. A newly discovered variety of blood-cell progenitor doesn't fit into the accepted blood map, but should that map be redrawn? - - -
Nature June 2 2005    Full text | PDF

  Developmental biology: Asymmetrical threat averted
Eran Hornstein and Clifford J. Tabin   The somites are embryonic elements that give rise to the muscles, skeleton and some skin layers of the trunk. They form in a symmetrical fashion, but to do so they must be shielded from asymmetrical cues. - - -
Nature May12 2005    Full text | PDF

  CELL BIOLOGY: Wnt Signaling Glows with RNAi
Eric R. Fearon and Ken M. Cadigan   Cellular signaling pathways such as the Wnt/Wingless pathway have traditionally been pieced together one step at a time. In a Perspective, Fearon and Cadigan discuss a new high-throughput screen in fruit fly cells that blocks the activity of nearly all fruit fly genes, one by one (DasGupta et al.). This study reveals 238 components of the Wnt/ Wingless pathway, including several proteins not previously known to operate in this pathway. - - -
Science May 6, 2005    Full text | PDF

  MOLECULAR BIOLOGY: Human RNA Slows Down a Primate Retrovirus
Jennifer Couzin   A multiyear search has led a 30-something molecular biologist and his colleagues to a new way that human cells fend off viruses. A similar defense system, called RNA silencing because short RNA molecules shut down specific genes, is known to protect plants and insects from viruses, but until now a similar immune mechanism hadn't been detected in mammalian cells. - - -
Science April 22, 2005    Full text | PDF

  Medicine: Aborting the birth of cancer
ASHOK R. VENKITARAMAN   Can cells sense and stop uncontrolled division driven by cancer-promoting stimuli? Perhaps so, given evidence that aberrant division can trigger the cellular response to DNA damage -blocking growth-at early stages in human cancer. - - -
Nature April 14, 2005    Full text | PDF

 Evolutionary biology: Why sex is good
ROLF F. HOEKSTRA
According to a proposal put forward many years ago, sexual reproduction makes natural selection more effective because it increases genetic variation. Experiments now verify that idea — at least in yeast.
Nature Mar 31, 2005    Full Text

 Genomics: Frontiers of gene function
SEAN M. O'ROURKE AND BRUCE BOWERMAN
The technique of RNA interference continues to pay dividends. The latest application of the method to the nematode worm adds detail to the list of genes known to function in the early stages of development.
Nature Mar. 24, 2005    Full Text

 The DNA sequence of the human X chromosome 
MARK T. ROSS, et al.    Summary | Full Text

 X-inactivation profile reveals extensive variability in X-linked gene _expression in females 
LAURA CARREL AND HUNTINGTON F. WILLARD   First paragraph | Full Text

 Genome biology: She moves in mysterious ways 
CHRIS GUNTER
The human X chromosome is a study in contradictions. The detailed sequence of the X, and a survey of inactivated genes in females, help to illuminate this unique 'evolutionary space'.    Full Text

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Chipping away at the Embryonic Stem Cell Network
Stuart H. Orkin
Critical transcription factors, notably OCT4, SOX2, and NANOG, are necessary to maintain self-renewal and pluripotency, two properties characteristic of embryonic stem (ES) cells. By analyzing the genome-wide localization of these factors at promoter regions in human ES cells, Boyer et al., 2005 demonstrate frequent promoter cooccupancy at numerous target genes. As they discuss in this issue of Cell, their findings indicate the presence of a complex network of autoregulatory and feedforward loops in human ES cells...
Cell, Vol 122, 828-830, 23 September 2005   | Full Text | PDF |

A Skeleton of the Human Protein Interactome
Ata Ghavidel, Gerard Cagney, and Andrew Emili
In this issue of Cell, Wanker and colleagues (Stelzl et al., 2005) present a large-scale two-hybrid map of more than 3000 putative human protein-protein interactions. These new data will serve as an important source of information regarding individual protein partners and offer preliminary insight into the global molecular organization of human cells...
Cell, Vol 122, 830-832, 23 September 2005   | Full Text | PDF |

The Continuing Saga of p53— More Sleepless Nights Ahead
Carol Prives and James J. Manfredi
Despite previous assumptions that the tumor suppressor protein p53 exists primarily and functionally as a single species, recent papers document the existence and unexpected properties of numerous p53 isoforms in cells. The complexity of p53 continues to unfold...
Molecular Cell, Vol 19, 719-721, 16 September 2005   | Full Text | PDF |

Regulation of LSD1 Histone Demethylase Activity by Its Associated Factors
Yu-Jiang Shi, Caitlin Matson, ... , Tadashi Baba, and Yang Shi
LSD1 is a recently identified human lysine (K)-specific histone demethylase. LSD1 is associated with HDAC1/2; CoREST, a SANT domain-containing corepressor; and BHC80, a PHD domain-containing protein, among others. We show that CoREST endows LSD1 with the ability to demethylate nucleosomal substrates and that it protects LSD1 from proteasomal degradation in vivo. We find hyperacetylated nucleosomes less susceptible to CoREST/LSD1-mediated demethylation, suggesting that hypoacetylated nucleosomes may be the preferred physiological substrates. This raises the possibility that histone deacetylases and LSD1 may collaborate to generate a repressive chromatin environment. Consistent with this model, TSA treatment results in derepression of LSD1 target genes. While CoREST positively regulates LSD1 function, BHC80 inhibits CoREST/LSD1-mediated demethylation in vitro and may therefore confer negative regulation. Taken together, these findings suggest that LSD1-mediated histone demethylation is regulated dynamically in vivo. This is expected to have profound effects on gene expression under both physiological and pathological conditions...
Molecular Cell, 16 September 2005, Pages 857-864   | Full Text | PDF |

SUMO Modification Is Involved in the Maintenance of Heterochromatin Stability in Fission Yeast
Jin A Shin, Eun Shik Choi, ... , Sang Dai Park, and Yeun Kyu Jang
Several studies have suggested that SUMO may participate in the regulation of heterochromatin, but direct evidence is lacking. Here, we present a direct link between sumoylation and heterochromatin stability. SUMO deletion impaired silencing at heterochromatic regions and induced histone H3 Lys4 methylation, a hallmark of active chromatin in fission yeast. Our findings showed that the SUMO-conjugating enzyme Hus5/Ubc9 interacted with the conserved heterochromatin proteins Swi6, Chp2 (a paralog of Swi6), and Clr4 (H3 Lys9 methyltransferase). Moreover, chromatin immunoprecipitation (ChIP) revealed that Hus5 was highly enriched in heterochromatic regions in a heterochromatin-dependent manner, suggesting a direct role of Hus5 in heterochromatin formation. We also found that Swi6, Chp2, and Clr4 themselves can be sumoylated in vivo and defective sumoylation of Swi6 or Chp2 compromised silencing. These results indicate that Hus5 associates with heterochromatin through interactions with heterochromatin proteins and modifies substrates whose sumoylations are required for heterochromatin stability, including heterochromatin proteins themselves....
Molecular Cell, Vol 19, 817-828, 16 September 2005   | Full Text | PDF |

Taking LSD1 to a New High
Joanna Wysocka, Thomas A. Milne, and C. David Allis
Histone modifications mediate changes in gene expression by altering the underlying chromatin structure or by serving as a binding platform to recruit other proteins. One such modification, histone methylation, was thought to be irreversible until last year when Shi and coworkers broke new ground with their discovery of a lysine-specific histone demethylase (LSD1). They showed that LSD1, a nuclear amine oxidase homolog, is a bona fide histone H3 lysine 4 demethylase (Shi et al., 2004). Now, a new study from Shi et al., 2005 published in a recent issue of Molecular Cell, together with two studies recently published by Metzger et al., 2005 and Lee et al., 2005 in Nature, reveal that LSD1’s specificity and activity is in fact regulated by associated protein cofactors....
Cell, Vol 122, 654-658, 9 September 2005   | Full Text | PDF |

Nuclear Reprogramming by Human Embryonic Stem Cells
M. Azim Surani
Embryonic stem cells have two unique properties. They are capable of indefinite self-renewal and, being pluripotent, they can differentiate into all possible cell types, including germ cells. A new study by Cowan et al., 2005 published in Science shows that human embryonic stem cells are able to reprogram the nuclei of fully differentiated human somatic cells, apparently conferring on them a pluripotent state...
Cell, Vol 122, 653-654, 9 September 2005   | Full Text | PDF |

PUMA Couples the Nuclear and Cytoplasmic Proapoptotic Function of p53
Jerry E. Chipuk, Lisa Bouchier-Hayes, Tomomi Kuwana, Donald D. Newmeyer, and Douglas R. Green
The Trp53 tumor suppressor gene product (p53) functions in the nucleus to regulate proapoptotic genes, whereas cytoplasmic p53 directly activates proapoptotic Bcl-2 proteins to permeabilize mitochondria and initiate apoptosis. Here, we demonstrate that a tripartite nexus between Bcl-xL, cytoplasmic p53, and PUMA coordinates these distinct p53 functions. After genotoxic stress, Bcl-xL sequestered cytoplasmic p53. Nuclear p53 caused expression of PUMA, which then displaced p53 from Bcl-xL, allowing p53 to induce mitochondrial permeabilization. Mutant Bcl-xL that bound p53, but not PUMA, rendered cells resistant to p53-induced apoptosis irrespective of PUMA expression. Thus, PUMA couples the nuclear and cytoplasmic proapoptotic functions of p53...
Science, Vol 309, Issue 5741, 1732-1735 , 9 September 2005   | Full Text | PDF |

From Birth to Death: The Complex Lives of Eukaryotic mRNAs
Melissa J. Moore
Recent work indicates that the posttranscriptional control of eukaryotic gene expression is much more elaborate and extensive than previously thought, with essentially every step of messenger RNA (mRNA) metabolism being subject to regulation in an mRNA-specific manner. Thus, a comprehensive understanding of eukaryotic gene expression requires an appreciation for how the lives of mRNAs are influenced by a wide array of diverse regulatory mechanisms...
Science 2 September 2005: 1514-1518.   | Full Text | PDF |

The Functional Genomics of Noncoding RNA
John S. Mattick
Large numbers of noncoding RNA transcripts (ncRNAs) are being revealed by complementary DNA cloning and genome tiling array studies in animals. The big and as yet largely unanswered question is whether these transcripts are relevant. A paper by Willingham et al. shows the way forward by developing a strategy for large-scale functional screening of ncRNAs, involving small interfering RNA knockdowns in cell-based screens, which identified a previously unidentified ncRNA repressor of the transcription factor NFAT. It appears likely that ncRNAs constitute a critical hidden layer of gene regulation in complex organisms, the understanding of which requires new approaches in functional genomics...
Science 2 September 2005: 1527-1528.   | Full Text | PDF |

Fewer Genes, More Noncoding RNA
Jean-Michel Claverie
Recent studies showing that most "messenger" RNAs do not encode proteins finally explain the long-standing discrepancy between the small number of protein-coding genes found in vertebrate genomes and the much larger and ever-increasing number of polyadenylated transcripts identified by tag-sampling or microarray-based methods. Exploring the role and diversity of these numerous noncoding RNAs now constitutes a main challenge in transcription research....
Science 2 September 2005: 1529-1530.   | Full Text | PDF |

GRADUATE SCHOOLS in USA:Drop in Foreign Applications Slows
Yudhijit Bhattacharjee
Science 18 March 2005: 1706. [Summary] [Full Text] [PDF]  

 

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