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		Discovery notes Functional insight into Maelstrom in the germline piRNA pathway: a unique domain homologous to the DnaQ-H 3'–5' exonuclease, its lineage-specific expansion/loss and evolutionarily active site switch Dapeng Zhang, Huiling Xiong, Jufang Shan, Xuhua Xia, Vance L Trudeau Biology Direct 2008, 3:48 (25 November 2008) Abstract \| Full text \| PDF \| PubMed \| Editor’s summary The evolutionary relationship between MAEL and DnaQ-H domains provides insight into the germline piRNA pathway and suggests a novel evolutionary mode for protein function change.
		Hypothesis On the brink between extinction and persistence Cino Pertoldi, Lars A Bach, Volker Loeschcke Biology Direct 2008, 3:47 (19 November 2008) Abstract \| Full text \| PDF \| PubMed \| Editor’s summary The pattern of how populations fluctuate in size over time can be used to separate domains of extinction and persistence by means of an analytical model.
		Hypothesis Exon definition as a potential negative force against intron losses in evolution Deng-Ke Niu Biology Direct 2008, 3:46 (13 November 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| Editor’s summary If the splicing of pre-mRNAs is initiated by exon definition, an exon larger than a particular size may cause splicing errors . Intron loss that results in oversized exons may thus be deleterious and selected against.
		Discovery notes Unraveling the biochemistry and provenance of pupylation: a prokaryotic analog of ubiquitination Lakshminarayan M Iyer, AM Burroughs, L Aravind Biology Direct 2008, 3:45 (3 November 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central
		Discovery notes Synaptic enrichment of microRNAs in adult mouse forebrain is related to structural features of their precursors Neil R Smalheiser Biology Direct 2008, 3:44 (29 October 2008) Abstract \| Full text \| PDF \| PubMed
		Research Did RNA editing in plant organellar genomes originate under natural selection or through genetic drift? Richard W Jobson, Yin-Long Qiu Biology Direct 2008, 3:43 (21 October 2008) Abstract \| Full text \| PDF \| PubMed
		Hypothesis A new model defines the minimal set of polymorphism in HLA-DQ and -DR that determines susceptibility and resistance to autoimmune diabetes Christian S Parry, Bernard R Brooks Biology Direct 2008, 3:42 (14 October 2008) Abstract \| Full text \| PDF \| PubMed \| Editor’s summary Two polar residues underlie the strong linkage between MHC class II molecules and type 1 diabetes through an electrostatic grip on the peptide resulting in slow dissociation kinetics and altered cytokine expression.
		Discovery notes Transduplication resulted in the incorporation of two protein-coding sequences into the Turmoil-1 transposable element of C. elegans Noa Sela, Adi Stern, Wojciech Makalowski, Tal Pupko, Gil Ast Biology Direct 2008, 3:41 (8 October 2008) Abstract \| Full text \| PDF \| PubMed
		Research Comparable contributions of structural-functional constraints and expression level to the rate of protein sequence evolution Maxim Y Wolf, Yuri I Wolf, Eugene V Koonin Biology Direct 2008, 3:40 (7 October 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central
		Discovery notes A new family of polymerases related to superfamily A DNA polymerases and T7-like DNA-dependent RNA polymerases Lakshminarayan M Iyer, Saraswathi Abhiman, L Aravind Biology Direct 2008, 3:39 (4 October 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central
		Research CAIcal: A combined set of tools to assess codon usage adaptation Pere Puigbò, Ignacio G Bravo, Santiago Garcia-Vallve Biology Direct 2008, 3:38 (16 September 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| Editor’s summary The analysis of codon usage has been widely used for estimation of gene expressivity or gene adaptation, and may also be helpful for refining genome annotation.
		Hypothesis An extension of the coevolution theory of the origin of the genetic code Massimo Di Giulio Biology Direct 2008, 3:37 (5 September 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| Editor’s summary A modification of the coevolution theory of the origin of the genetic code suggesting that the biosynthetic pathways of amino acids imprinted the genetic code organization early on.
		Research Same-strand overlapping genes in bacteria: compositional determinants of phase bias Niv Sabath, Dan Graur, Giddy Landan Biology Direct 2008, 3:36 (21 August 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| Editor’s summary The relative frequencies of same-strand phase-1 and phase-2 overlapping genes are determined by neutral compositional factors rather than selection.
		Research A nitty-gritty aspect of correlation and network inference from gene expression data Lev B Klebanov, Andrei Yakovlev Biology Direct 2008, 3:35 (20 August 2008) Abstract \| Full text \| PDF \| PubMed \| Editor’s summary Modern microarray technology produces signals aggregated over a random number of individual cells, causing a distortion of correlation structure, the magnitude of which is quantitatively accessed from real data.
		Research Critical role for BIM in T cell receptor restimulation-induced death Andrew L Snow, João B Oliveira, Lixin Zheng, Janet K Dale, Thomas A Fleisher, Michael J Lenardo Biology Direct 2008, 3:34 (20 August 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| Editor’s summary Rapid BIM induction following restimulation of activated T cells is critical for T cell receptor-induced apoptosis, demonstrating FAS- and BIM-dependent death of effector T cells are not mutually exclusive pathways.
		Research The evolution of strand preference in simulated RNA replicators with strand displacement: Implications for the origin of transcription Nobuto Takeuchi, Laura Salazar, Anthony M Poole, Paulien Hogeweg Biology Direct 2008, 3:33 (11 August 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| Editor’s summary Finite diffusion is shown to enable the evolution of a transcription-like pattern in a simple RNA-based replicator system with strand displacement
		Discovery notes A highly conserved family of inactivated archaeal B family DNA polymerases Igor B Rogozin, Kira S Makarova, Youri I Pavlov, Eugene V Koonin Biology Direct 2008, 3:32 (6 August 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central
		Research Origin of the nucleus and Ran-dependent transport to safeguard ribosome biogenesis in a chimeric cell Gáspár Jékely Biology Direct 2008, 3:31 (24 July 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| F1000 Biology \| Editor’s summary Nuclear compartmentalization in eukaryotes evolved via the coevolution of Ran and karyopherin dependent transport, nuclear membranes and nuclear pore complexes in order to reduce the number of chimeric ribosomes which formed after the acquisition of the protomitochondrium.
		Discovery notes Accumulation of GC donor splice signals in mammals Alexander Churbanov, Stephen Winters-Hilt, Eugene V Koonin, Igor B Rogozin Biology Direct 2008, 3:30 (9 July 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| Editor’s summary Reconstruction of the evolution of donor splice sites in mammals reveals accumulation of minor GC sites that could contribute to the evolution of alternative splicing.
		Research The Last Universal Common Ancestor: emergence, constitution and genetic legacy of an elusive forerunner Nicolas Glansdorff, Ying Xu, Bernard Labedan Biology Direct 2008, 3:29 (9 July 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| Editor’s summary The Last Universal Common Ancestor developed in a protoeukaryotic, promiscuous and genetically redundant community of cells with a broad, moderate thermal profile and an RNA genome enclosed in a protonucleus.
		Research A family of GFP-like proteins with different spectral properties in lancelet Branchiostoma floridae Diana Baumann, Malcolm Cook, Limei Ma, Arcady Mushegian, Erik Sanders, Joel Schwartz, C Ron Yu Biology Direct 2008, 3:28 (3 July 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central
		Research Detection of co-eluted peptides using database search methods Gelio Alves, Aleksey Y Ogurtsov, Siwei Kwok, Wells W Wu, Guanghui Wang, Rong-Fong Shen, Yi-Kuo Yu Biology Direct 2008, 3:27 (2 July 2008) Abstract \| Full text \| PDF \| PubMed \| Editor’s summary The "one peptide per spectrum" dogma cannot hold true due to limited chromatographic separation resulting in mass spectra containing co-eluted peptides with high probability; this issue is numerically investigated.
		Research Complete genome sequence of the extremely acidophilic methanotroph isolate V4, Methylacidiphilum infernorum, a representative of the bacterial phylum Verrucomicrobia Shaobin Hou, Kira S Makarova, Jimmy HW Saw, Pavel Senin, Benjamin V Ly, Zhemin Zhou, Yan Ren, Jianmei Wang, Michael Y Galperin, Marina V Omelchenko, Yuri I Wolf, Natalya Yutin, Eugene V Koonin, Matthew B Stott, Bruce W Mountain, Michelle A Crowe, Angela V Smirnova, Peter F Dunfield, Lu Feng, Lei Wang, Maqsudul Alam Biology Direct 2008, 3:26 (1 July 2008) Abstract \| Full text \| PDF \| PubMed \| Editor’s summary Genome sequence of a methanotrophic member of the bacterial phylum Verrucomicrobia reveals adaptations to the methane utilization under acidic conditions and supports grouping Planctomycetes, Verrucomicrobia and Chlamydiae into a superphylum
		Research Genetic characterization of Hawaiian isolates of Plasmodium relictum reveals mixed-genotype infections Susan I Jarvi, Margaret EM Farias, Carter T Atkinson Biology Direct 2008, 3:25 (25 June 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| Editor’s summary High clonal diversity of introduced avian malaria in native Hawaiian forest birds adds complexity to this disease system with potential impacts on transmission, host-pathogen interactions and virulence.
		Research In silico regulatory analysis for exploring human disease progression Dustin T Holloway, Mark Kon, Charles DeLisi Biology Direct 2008, 3:24 (18 June 2008) Abstract \| Full text \| PDF \| PubMed \| 1 comment \| Editor’s summary Machine learning methods are employed to predict targets of transcription factors in the human genome and further provide possible insights on Wt1 and its role in Wilms Tumor.

	All
		Discovery notes Functional insight into Maelstrom in the germline piRNA pathway: a unique domain homologous to the DnaQ-H 3'–5' exonuclease, its lineage-specific expansion/loss and evolutionarily active site switch Dapeng Zhang, Huiling Xiong, Jufang Shan, Xuhua Xia, Vance L Trudeau Biology Direct 2008, 3:48 (25 November 2008) Abstract \| Full text \| PDF \| PubMed \| Editor’s summary The evolutionary relationship between MAEL and DnaQ-H domains provides insight into the germline piRNA pathway and suggests a novel evolutionary mode for protein function change.
		Hypothesis On the brink between extinction and persistence Cino Pertoldi, Lars A Bach, Volker Loeschcke Biology Direct 2008, 3:47 (19 November 2008) Abstract \| Full text \| PDF \| PubMed \| Editor’s summary The pattern of how populations fluctuate in size over time can be used to separate domains of extinction and persistence by means of an analytical model.
		Hypothesis Exon definition as a potential negative force against intron losses in evolution Deng-Ke Niu Biology Direct 2008, 3:46 (13 November 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| Editor’s summary If the splicing of pre-mRNAs is initiated by exon definition, an exon larger than a particular size may cause splicing errors . Intron loss that results in oversized exons may thus be deleterious and selected against.
		Discovery notes Unraveling the biochemistry and provenance of pupylation: a prokaryotic analog of ubiquitination Lakshminarayan M Iyer, AM Burroughs, L Aravind Biology Direct 2008, 3:45 (3 November 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central
		Discovery notes Synaptic enrichment of microRNAs in adult mouse forebrain is related to structural features of their precursors Neil R Smalheiser Biology Direct 2008, 3:44 (29 October 2008) Abstract \| Full text \| PDF \| PubMed
		Research Did RNA editing in plant organellar genomes originate under natural selection or through genetic drift? Richard W Jobson, Yin-Long Qiu Biology Direct 2008, 3:43 (21 October 2008) Abstract \| Full text \| PDF \| PubMed
		Hypothesis A new model defines the minimal set of polymorphism in HLA-DQ and -DR that determines susceptibility and resistance to autoimmune diabetes Christian S Parry, Bernard R Brooks Biology Direct 2008, 3:42 (14 October 2008) Abstract \| Full text \| PDF \| PubMed \| Editor’s summary Two polar residues underlie the strong linkage between MHC class II molecules and type 1 diabetes through an electrostatic grip on the peptide resulting in slow dissociation kinetics and altered cytokine expression.
		Discovery notes Transduplication resulted in the incorporation of two protein-coding sequences into the Turmoil-1 transposable element of C. elegans Noa Sela, Adi Stern, Wojciech Makalowski, Tal Pupko, Gil Ast Biology Direct 2008, 3:41 (8 October 2008) Abstract \| Full text \| PDF \| PubMed
		Research Comparable contributions of structural-functional constraints and expression level to the rate of protein sequence evolution Maxim Y Wolf, Yuri I Wolf, Eugene V Koonin Biology Direct 2008, 3:40 (7 October 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central
		Discovery notes A new family of polymerases related to superfamily A DNA polymerases and T7-like DNA-dependent RNA polymerases Lakshminarayan M Iyer, Saraswathi Abhiman, L Aravind Biology Direct 2008, 3:39 (4 October 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central
		Research CAIcal: A combined set of tools to assess codon usage adaptation Pere Puigbò, Ignacio G Bravo, Santiago Garcia-Vallve Biology Direct 2008, 3:38 (16 September 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| Editor’s summary The analysis of codon usage has been widely used for estimation of gene expressivity or gene adaptation, and may also be helpful for refining genome annotation.
		Hypothesis An extension of the coevolution theory of the origin of the genetic code Massimo Di Giulio Biology Direct 2008, 3:37 (5 September 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| Editor’s summary A modification of the coevolution theory of the origin of the genetic code suggesting that the biosynthetic pathways of amino acids imprinted the genetic code organization early on.
		Research Same-strand overlapping genes in bacteria: compositional determinants of phase bias Niv Sabath, Dan Graur, Giddy Landan Biology Direct 2008, 3:36 (21 August 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| Editor’s summary The relative frequencies of same-strand phase-1 and phase-2 overlapping genes are determined by neutral compositional factors rather than selection.
		Research A nitty-gritty aspect of correlation and network inference from gene expression data Lev B Klebanov, Andrei Yakovlev Biology Direct 2008, 3:35 (20 August 2008) Abstract \| Full text \| PDF \| PubMed \| Editor’s summary Modern microarray technology produces signals aggregated over a random number of individual cells, causing a distortion of correlation structure, the magnitude of which is quantitatively accessed from real data.
		Research Critical role for BIM in T cell receptor restimulation-induced death Andrew L Snow, João B Oliveira, Lixin Zheng, Janet K Dale, Thomas A Fleisher, Michael J Lenardo Biology Direct 2008, 3:34 (20 August 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| Editor’s summary Rapid BIM induction following restimulation of activated T cells is critical for T cell receptor-induced apoptosis, demonstrating FAS- and BIM-dependent death of effector T cells are not mutually exclusive pathways.
		Research The evolution of strand preference in simulated RNA replicators with strand displacement: Implications for the origin of transcription Nobuto Takeuchi, Laura Salazar, Anthony M Poole, Paulien Hogeweg Biology Direct 2008, 3:33 (11 August 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| Editor’s summary Finite diffusion is shown to enable the evolution of a transcription-like pattern in a simple RNA-based replicator system with strand displacement
		Discovery notes A highly conserved family of inactivated archaeal B family DNA polymerases Igor B Rogozin, Kira S Makarova, Youri I Pavlov, Eugene V Koonin Biology Direct 2008, 3:32 (6 August 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central
		Research Origin of the nucleus and Ran-dependent transport to safeguard ribosome biogenesis in a chimeric cell Gáspár Jékely Biology Direct 2008, 3:31 (24 July 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| F1000 Biology \| Editor’s summary Nuclear compartmentalization in eukaryotes evolved via the coevolution of Ran and karyopherin dependent transport, nuclear membranes and nuclear pore complexes in order to reduce the number of chimeric ribosomes which formed after the acquisition of the protomitochondrium.
		Discovery notes Accumulation of GC donor splice signals in mammals Alexander Churbanov, Stephen Winters-Hilt, Eugene V Koonin, Igor B Rogozin Biology Direct 2008, 3:30 (9 July 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| Editor’s summary Reconstruction of the evolution of donor splice sites in mammals reveals accumulation of minor GC sites that could contribute to the evolution of alternative splicing.
		Research The Last Universal Common Ancestor: emergence, constitution and genetic legacy of an elusive forerunner Nicolas Glansdorff, Ying Xu, Bernard Labedan Biology Direct 2008, 3:29 (9 July 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| Editor’s summary The Last Universal Common Ancestor developed in a protoeukaryotic, promiscuous and genetically redundant community of cells with a broad, moderate thermal profile and an RNA genome enclosed in a protonucleus.
		Research A family of GFP-like proteins with different spectral properties in lancelet Branchiostoma floridae Diana Baumann, Malcolm Cook, Limei Ma, Arcady Mushegian, Erik Sanders, Joel Schwartz, C Ron Yu Biology Direct 2008, 3:28 (3 July 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central
		Research Detection of co-eluted peptides using database search methods Gelio Alves, Aleksey Y Ogurtsov, Siwei Kwok, Wells W Wu, Guanghui Wang, Rong-Fong Shen, Yi-Kuo Yu Biology Direct 2008, 3:27 (2 July 2008) Abstract \| Full text \| PDF \| PubMed \| Editor’s summary The "one peptide per spectrum" dogma cannot hold true due to limited chromatographic separation resulting in mass spectra containing co-eluted peptides with high probability; this issue is numerically investigated.
		Research Complete genome sequence of the extremely acidophilic methanotroph isolate V4, Methylacidiphilum infernorum, a representative of the bacterial phylum Verrucomicrobia Shaobin Hou, Kira S Makarova, Jimmy HW Saw, Pavel Senin, Benjamin V Ly, Zhemin Zhou, Yan Ren, Jianmei Wang, Michael Y Galperin, Marina V Omelchenko, Yuri I Wolf, Natalya Yutin, Eugene V Koonin, Matthew B Stott, Bruce W Mountain, Michelle A Crowe, Angela V Smirnova, Peter F Dunfield, Lu Feng, Lei Wang, Maqsudul Alam Biology Direct 2008, 3:26 (1 July 2008) Abstract \| Full text \| PDF \| PubMed \| Editor’s summary Genome sequence of a methanotrophic member of the bacterial phylum Verrucomicrobia reveals adaptations to the methane utilization under acidic conditions and supports grouping Planctomycetes, Verrucomicrobia and Chlamydiae into a superphylum
		Research Genetic characterization of Hawaiian isolates of Plasmodium relictum reveals mixed-genotype infections Susan I Jarvi, Margaret EM Farias, Carter T Atkinson Biology Direct 2008, 3:25 (25 June 2008) Abstract \| Full text \| PDF \| PubMed \| Cited on BioMed Central \| Editor’s summary High clonal diversity of introduced avian malaria in native Hawaiian forest birds adds complexity to this disease system with potential impacts on transmission, host-pathogen interactions and virulence.
		Research In silico regulatory analysis for exploring human disease progression Dustin T Holloway, Mark Kon, Charles DeLisi Biology Direct 2008, 3:24 (18 June 2008) Abstract \| Full text \| PDF \| PubMed \| 1 comment \| Editor’s summary Machine learning methods are employed to predict targets of transcription factors in the human genome and further provide possible insights on Wt1 and its role in Wilms Tumor.