International Journal of Biological Sciences
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ISSN 1449-2288

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International Journal of Medical Sciences

Editor-in-Chief: Chuxia Deng, Mammalian Genetics Section, NIDDK, NIH
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In Celebration of Dr. Mario R. Capecchi's Nobel Prize: This year, the Nobel Prize in Physiology or Medicine goes to Drs. Mario R. Capecchi, Martin J. Evans and Oliver Smithies for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem (ES) cells. This technology, commonly referred to as gene targeting or knockout, is based on homologous recombination between DNA sequences residing in the chromosome and newly introduced DNA to mutate any genes of interesting in mouse genome. ...more

The winners of 2005 Most Cited Paper Award were Ashley C. Bibby and David W. Litchfield, who were issued a certificate together with a cash prize. For 2006 Most Cited Paper Award (to be announced on Dec. 31, 2008), top cited papers are:new

  1. The Inhibition and Treatment of Breast Cancer with Poly (ADP-ribose) Polymerase (PARP-1) Inhibitors
    JA De Soto, X Wang, Y Tominaga, et al
    Cited by 15
  2. Metaphylogeny of 82 gene families sheds a new light on chordate evolution
    A Vienne, P Pontarotti
    Cited by 15
  3. Hox genes are not always Colinear
    AS Monteiro, DEK Ferrier
    Cited by 12

Details ...

Protein phosphatase 1a (PP1a) regulates phosphorylation of BRCA1, which contains a PP1-binding motif 898KVTF901. In this study, Yu et al. showed that mutation of the PP1-binding motif in BRCA1 affected recruitment of Rad51 to sites of DNA damage, and impaired the DNA repair function of BRCA1. Consistent with these findings, knockdown of PP1a in BRCA1-proficient cells by small interfering RNA significantly reduced Rad51 focus formation induced by DNA damage. Further analysis indicated that mutation of the PP1-binding motif compromised BRCA1 activities in homologous recombination. Altogether, these data implicate that interaction with PP1a is important for BRCA1 function in DNA damage repair.
Cellular longevity is a complex process relevant to age-related diseases including but not limited to chronic illness such as diabetes and metabolic syndromes. Members of Sirtuin and FOXO families have been shown to play a role in the genetic regulation of longevity, yet their relationship remains elusive. In this study, Jacobs et al. showed at the first time that FOXO3a is a mitochondrial protein and it forms a physical interaction with SIRT3 in the mitochondria. They demonstrated that overexpression of a wild-type SIRT3 gene in HCT116 cells increases FOXO3a DNA-binding activity and FOXO3a dependent gene expression. Biochemical analysis of HCT116 cells over expressing the deacetylation mutant, as compared to wild- type SIRT3 gene, demonstrated an overall oxidized intracellular environment, as monitored by increase in intracellular superoxide and oxidized glutathione levels. Thus both SIRT3 and FOXO3a are located in the mitochondrial and comprise a potential mitochondrial signaling cascade response pathway.
Signal transducer and activator of transcription (STAT) proteins are known to play critical roles as transcription factors for regulating cell proliferation and survival. Recent studies have identified other roles, including association at focal adhesions and cell-cell junctions that may contribute to cell motility. Of the six different STATs reported, STAT3 has been a focus of interest in cardiac research, since cardiac-restricted STAT3 knockout in mice has been shown to result in several detrimental effects, including increased sensitivity to injury, decreased LV capillary formation, increased fibrosis, and decreased contractile function. Tyrosine phosphorylation of STAT3, mediated by members of the nonreceptor tyrosine kinase (NTK) family, in particular JAK2, is required for its transcriptional activation. In this context, previous studies show that a member of the recently identified TEC family of NTKs, BMX, mediates STAT3 phosphorylation in several mammalian cells and contributes to arteriogenesis and angiogenesis in several tissues. In the present study, we show a novel finding in pressure-overloaded myocardium where activation and cellular redistribution of STAT3 are linked to integrin-mediated BMX activation.
It is hypothesized that cancer stem cells arise either from normal stem cells or from progenitor cells that have gained the ability to self-renew. In this study, Vassilopoulos et al. tested this hypothesis and they found that BRCA1 mutant cancer cells contain a subpopulation of CD24+CD29+ or CD24+CD49f+ cells that exhibit increased proliferation and colony forming ability in vitro, and enhanced tumor-forming ability in vivo. These CD24+CD29+ cells could form tubular structures reminiscent of the mammary ductal tree when grown in three-dimensional cultures, implying that these cancer initiating cells maintain some of the characteristics of the normal stem cells. These data provide evidence that breast cancer stem cells originate from normal stem cells and advance our understanding of BRCA1-associated tumorigenesis with possible implications for future cancer treatment. ... more
Hepatitis B is a common and serious infectious disease in China. Approximately half of the HBV carriers get infected via mother-to- infant transmission. While multiple factors determine the susceptibility to intrauterine HBV infection, Xu et al. (p.111) demonstrated that high frequency of HLA-DRB1*07 increases the susceptibility of the infants to intrauterine HBV infection (OR=6.66, P=0.004). This finding is fundamental for developing new strategies of prophylactic and therapeutic approaches. In a related study, Jia et al. (p.103) successfully screened human antibody Fab fragment against HBsAg; improved the affinity of the Fab by chain shuffling and constructed its dsFv form by PCR-based point mutagenesis method. The dsFv maintains the specificity of the Fab. An expected loss of binding affinity is well compensated by the improved stability of dsFv both in vitro and in vivo. These series of studies have provided direct molecular evidence for the susceptibility to intrauterine HBV infection and offered a novel technique for the production of dsFv against HBsAg for its potential clinic use in disease prevention and therapy.

Several reports have shown that urotensin 2 (UTS2) and its receptor (UTS2R) are involved in glucose metabolism and insulin resistance, which lead to development of type 2 diabetes mellitus (T2DM) in humans. In the present study, we annotated both bovine UTS2 and UTS2R genes and identified 5 single nucleotide polymorphisms (SNPs) for the former gene and 14 mutations for the latter gene. Four mutations were genotyped on a Wagyu x Limousin reference population, including 6 F1 bulls, 113 F1 dams and ~250 F2 progeny. Among 12 phenotypes related to fat deposition and fatty acid composition, we observed that the UTS2 gene was significantly associated with the amount of skeletal saturated fatty acids, while its receptor (UTS2R) gene had significant effects on amounts of saturated and monounsaturated fatty acids, Δ9 desaturase activity for converting 16:0 into 16:1, muscle fat (marbling) score and Longissimus Dorsi muscle area. ...more

Inorganic polyphosphate [poly(P)] is a biopolymer existing in almost all cells and tissues, although its biological functions in higher eukaryotes have not been completely elucidated. In this study, Kawazoe, et al investigated the effect of poly(P) on the cell differentiation of human stem cells via FGF signaling systems. Human dental pulp cells (HDPCs) isolated from human dental pulp show the characteristics of multipotent mesenchymal stem cells (MSCs). HDPCs secreted FGFs and the proliferation of HDPCs was enhanced by treatment with poly(P). Cell surface receptor-bound FGF-2 was stably maintained for more than 40 hours in the presence of poly(P). The phosphorylation of ERK1/2 was also enhanced by poly(P). Microarray analysis showed that expression of matrix metalloproteinase-1 (MMP1), osteopontin (OPN), osteocalcin (OC) and osteoprotegerin was induced in both HDOCs and MSCs cells by poly(P). ...more

IJBS issue coverA peer-reviewed journal publishes articles of significance in all areas of biological sciences in the forms of original research papers, reviews and short research communications.

Recent articles:

Post-Weaning Protein Malnutrition in the Rat Produces Short and Long Term Metabolic Impairment, in Contrast to Earlier and Later Periods
María del Carmen Miñana-Solis, Carolina Escobar
Int. J. Biol. Sci. 2008, 4: 422-432
[Abstract] [Full text] [PDF]

cDNA, genomic sequence and overexpression of crystallin alpha-B Gene (CRYAB) of the Giant Panda
Yi-ling Hou, Wan-ru Hou, Zheng-long Ren, Yan-zhe Hao, Tian Zhang
Int. J. Biol. Sci. 2008, 4: 415-421
[Abstract] [Full text] [PDF]

Genome Assembly Anchored QTL Map of Bovine Chromosome 14
Tito A. Wibowo, Charles T. Gaskins, Ruth C. Newberry, Gary H. Thorgaard, Jennifer J. Michal, Zhihua Jiang
Int. J. Biol. Sci. 2008, 4: 406-414
[Abstract] [Full text] [PDF]

Comparing methods of detection and quantitation of RNA editing of rat glycine receptor alpha3P185L
Aya Nakae, Tatsuya Tanaka, Keiko Miyake, Makiko Hase, Takashi Mashimo
Int. J. Biol. Sci. 2008, 4: 397-405
[Abstract] [Full text] [PDF] [PubMed] [PMC]

LGI1 and LGI4 bind to ADAM22, ADAM23 and ADAM11
Koji Sagane, Yasushi Ishihama, Hachiro Sugimoto
Int. J. Biol. Sci. 2008, 4: 387-396
[Abstract] [Full text] [PDF] [PubMed] [PMC]

Production & Characterization of a Unique Dextran from an Indigenous Leuconostoc mesenteroides CMG713
Farwa Sarwat, Shah Ali Ul Qader, Afsheen Aman, Nuzhat Ahmed
Int. J. Biol. Sci. 2008, 4: 379-386
[Abstract] [Full text] [PDF] [PubMed] [PMC]

Biological and functional analysis of statistically significant pathways deregulated in colon cancer by using gene expression profiles
Angela Distaso, Luca Abatangelo, Rosalia Maglietta, Teresa Maria Creanza, Ada Piepoli, Massimo Carella, Annarita D'Addabbo, Nicola Ancona
Int. J. Biol. Sci. 2008, 4: 368-378
[Abstract] [Full text] [PDF] [PubMed] [PMC]

Association of Insertion/Deletion Polymorphism of Alpha-Adrenoceptor Gene in Essential Hypertension with or without Type 2 Diabetes Mellitus in Malaysian Subjects
R. Vasudevan, Patimah Ismail, Johnson Stanslas, Norashikin Shamsudin, Aisyah binti Ali
Int. J. Biol. Sci. 2008, 4: 362-367
[Abstract] [Full text] [PDF] [PubMed] [PMC]

A PP1-binding motif present in BRCA1 plays a role in its DNA repair function
Young-Mi Yu, Serena M. Pace, Susan R. Allen, Chu-Xia Deng, Lih-Ching Hsu
Int. J. Biol. Sci. 2008, 4: 352-361
[Abstract] [Full text] [PDF] [PubMed] [PMC]

Significant associations of stearoyl-CoA desaturase (SCD1) gene with fat deposition and composition in skeletal muscle
Zhihua Jiang, Jennifer J. Michal, David J. Tobey, Tyler F. Daniels, Daniel C. Rule, Michael D. MacNeil
Int. J. Biol. Sci. 2008, 4: 345-351
[Abstract] [Full text] [PDF] [PubMed] [PMC]

Inducible SOS Response System of DNA Repair and Mutagenesis in Escherichia coli
Celina Janion
Int. J. Biol. Sci. 2008, 4: 338-344
[Abstract] [Full text] [PDF] [PubMed] [PMC]

Antifungal Potential of Extracellular Metabolites Produced by Streptomyces hygroscopicus against Phytopathogenic Fungi
Benjaphorn Prapagdee, Chutima Kuekulvong, Skorn Mongkolsuk
Int. J. Biol. Sci. 2008, 4: 330-337
[Abstract] [Full text] [PDF] [PubMed] [PMC]

Unveiling the Bmp13 Enigma: Redundant Morphogen or Crucial Regulator?
Lisa A Williams, Divya Bhargav, Ashish D Diwan
Int. J. Biol. Sci. 2008, 4: 318-329
[Abstract] [Full text] [PDF] [PubMed] [PMC]

A combined computational-experimental analyses of selected metabolic enzymes in Pseudomonas species
Deepak Perumal, Chu Sing Lim, Vincent T.K. Chow, Kishore R. Sakharkar, Meena K. Sakharkar
Int. J. Biol. Sci. 2008, 4: 309-317
[Abstract] [Full text] [PDF] [PubMed] [PMC]

Effect of exercise training on calpain systems in lean and obese Zucker rats
Yao-Yuan Hsieh, Chi-Chen Chang, Kung-Hao Hsu, Fuu-Jen Tsai, Chih-Ping Chen, Horng-Der Tsai
Int. J. Biol. Sci. 2008, 4: 300-308
[Abstract] [Full text] [PDF] [PubMed] [PMC]

SIRT3 interacts with the daf-16 homolog FOXO3a in the Mitochondria, as well as increases FOXO3a Dependent Gene expression
Kristi Muldoon Jacobs, J. Daniel Pennington, Kheem S. Bisht, Nukhet Aykin-Burns, Hyun-Seok Kim, Mark Mishra, Lunching Sun, Phuongmai Nguyen, Bong-Hyun Ahn, Jaime Leclerc, Chu-Xia Deng, Douglas R. Spitz, David Gius
Int. J. Biol. Sci. 2008, 4: 291-299
[Abstract] [Full text] [PDF] [PubMed] [PMC]

Advances in Susceptibility Genetics of Intervertebral Degenerative Disc Disease
Yin'gang Zhang, Zhengming Sun, Jiangtao Liu, Xiong Guo
Int. J. Biol. Sci. 2008, 4: 283-290
[Abstract] [Full text] [PDF] [PubMed] [PMC]

Discovery of four natural clones in a crayfish species Procambarus clarkii
G. H. Yue, G. L. Wang, B. Q. Zhu, C. M. Wang, Z .Y. Zhu, L. C. Lo
Int. J. Biol. Sci. 2008, 4: 279-282
[Abstract] [Full text] [PDF] [PubMed] [PMC]

Preconditioning of Carbon Monoxide Releasing Molecule-derived CO Attenuates LPS-induced Activation of HUVEC
Bingwei Sun, Xiangqian Zou, Yueling Chen, Ping Zhang, Gengsheng Shi
Int. J. Biol. Sci. 2008, 4: 270-278
[Abstract] [Full text] [PDF] [PubMed] [PMC]

Aberrant c-erbB2 expression in cell clusters overlying focally disrupted breast myoepithelial cell layers: a trigger or sign for emergence of more aggressive cell clones?
Xichen Zhang, Shahreyar Shar Hashemi, Morvarid Yousefi, Jinsong Ni, Qiuyue Wang, Ling Gao, Pengtao Gong, Chunling Gao, Joy Sheng, Jeffrey Mason, Yan-gao Man
Int. J. Biol. Sci. 2008, 4: 259-269
[Abstract] [Full text] [PDF] [PubMed] [PMC]

Bad seeds produce bad crops: a single stage-process of prostate tumor invasion
Yan-gao Man, William A. Gardner
Int. J. Biol. Sci. 2008, 4: 246-258
[Abstract] [Full text] [PDF] [PubMed] [PMC]

In reply to Zou et al. “New amyloid plaques or a game of hide-and-seek?”
Bradley Hyman
Int. J. Biol. Sci. 2008, 4: 245-245
[Abstract] [Full text] [PDF] [PubMed] [PMC]

PPAR gamma agonist normalizes glomerular filtration rate, tissue levels of homocysteine, and attenuates endothelial-myocyte uncoupling in alloxan induced diabetic mice
Walter E. Rodriguez, Utpal Sen, Neetu Tyagi, Munish Kumar, Gene Carneal, Deep Aggrawal, Justin Newsome, Suresh C. Tyagi
Int. J. Biol. Sci. 2008, 4: 236-244
[Abstract] [Full text] [PDF] [PubMed] [PMC]

Dysregulated Mitochondrial Genes and Networks with Drug Targets in Postmortem Brain of Patients with Posttraumatic Stress Disorder (PTSD) Revealed by Human Mitochondria-Focused cDNA Microarrays
Yan A. Su, Jun Wu, Lei Zhang, Qiuyang Zhang, David M. Su, Ping He, Bi-Dar Wang, He Li, Maree J. Webster, Traumatic Stress Brain Study Group, Owen M. Rennert, Robert J. Ursano
Int. J. Biol. Sci. 2008, 4: 223-235
[Abstract] [Full text] [PDF] [PubMed] [PMC]

Qualification and application of an ELISA for the determination of Tamm Horsfall Protein (THP) in human urine and its use for screening of Kidney Stone Disease
Wai-Hoe Lau, Wing-Seng Leong, Zhari Ismail, Lay-Harn Gam
Int. J. Biol. Sci. 2008, 4: 215-222
[Abstract] [Full text] [PDF] [PubMed] [PMC]

Relatively high levels of serum adiponectin in obese women, a potential indicator of anti-inflammatory dysfunction: Relation to sex hormone-binding globulin
Altan Onat, Gülay Hergenç, Dursun Dursunoğlu, Zekeriya Küçükdurmaz, Serkan Bulur, Günay Can
Int. J. Biol. Sci. 2008, 4: 208-214
[Abstract] [Full text] [PDF] [PubMed] [PMC]

Generation and Validation of a Mouse Line with a Floxed SRC-3/AIB1 Allele for Conditional Knockout
Zhaoliang Liu, Lan Liao, Suoling Zhou, Jianming Xu
Int. J. Biol. Sci. 2008, 4: 202-207
[Abstract] [Full text] [PDF] [PubMed] [PMC]

New amyloid plaques or a game of hide-and-seek?
Kun Zou, Tomoji Maeda, Makoto Michikawa, Hiroto Komano
Int. J. Biol. Sci. 2008, 4: 200-201
[Abstract] [Full text] [PDF] [PubMed] [PMC]

STAT3 Activation in Pressure-Overloaded Feline Myocardium: Role for Integrins and the Tyrosine Kinase BMX
Christopher D. Willey, Arun P. Palanisamy, Rebecca K. Johnston, Santhosh K. Mani, Hirokazu Shiraishi, William J. Tuxworth, Michael R. Zile, Sundaravadivel Balasubramanian, Dhandapani Kuppuswamy
Int. J. Biol. Sci. 2008, 4: 184-199
[Abstract] [Full text] [PDF] [PubMed] [PMC]

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