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Reviewer acknowledgement
Koonin, Eugene V
Landweber, Laura F
Lipman, David
Biology Direct
Contributing reviewers
The editors of Biology Direct would like to thank all the reviewers who have contributed to the journal in Volume 9 (2014).
Related Articles
Dynamics of social network structure for Alzheimer and Lymphoma scientific communities
Barbash, Shahar
Biology Direct
It is generally assumed that sociology affects scientific progress but specific examples of this assumption are hard to find. We examined this hypothesis by comparing the social network structure and its dynamics over the last 16 years, for two common human diseases; Alzheimer's disease, for which there has been very little therapeutic progress, and Lymphoma, were there has been significant therapeutic progress. We found that the Alzheimer's research community is more interlinked ('dense') and more 'cliquish' than that of Lymphoma and suggest that this could affect its scientific progress.
This article was reviewed by Vladimir Kuznetsov and Anthony Almudevar
Alzheimer's disease; Lymphoma; Social network
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Whole-genome assembly of Akkermansia muciniphila sequenced directly from human stool
Caputo, Aurélia
Dubourg, Grégory
Croce, Olivier
Gupta, Sushim
Robert, Catherine
Papazian, Laurent
Rolain, Jean-Marc
Raoult, Didier
Biology Direct
Alterations in gut microbiota composition under antibiotic pressure have been widely studied, revealing a restricted diversity of gut flora, including colonization by organisms such as Enterococci, while their impact on bacterial load is variable. High-level colonization by Akkermansia muciniphila, ranging from 39% to 84% of the total bacterial population, has been recently reported in two patients being treated with broad-spectrum antibiotics, although attempts to cultivate this microorganism have been unsuccessful.
Here, we propose an original approach of genome sequencing for Akkermansia muciniphila directly from the stool sample collected from one of these patients. We performed and assembly using metagenomic data obtained from the stool sample. We used a mapping method consisting of aligning metagenomic sequencing reads against the reference genome of the Akkermansia muciniphila MucT strain, and a De novo assembly to support this mapping method. We obtained draft genome of the Akkermansia muciniphila strain Urmite with only 56 gaps. The absence of particular metabolic requirement as possible explanation of our inability to culture this microorganism, suggests that the bacterium was dead before the inoculation of the stool sample. Additional antibiotic resistance genes were found following comparison with the reference genome, providing some clues pertaining to its survival and colonization in the gut of a patient treated with broad-spectrum antimicrobial agents. However, no gene coding for imipenem resistance was detected, although this antibiotic was a part of the patient's antibiotic regimen.
This work highlights the potential of metagenomics to facilitate the assembly of genomes directly from human stool.
This article was reviewed by Eric Bapteste, William Martin and Vivek Anantharaman.
Electronic supplementary material
The online version of this article (doi:10.1186/s13062-015-0041-1) contains supplementary material, which is available to authorized users.
Akkermansia muciniphila; Genome; Gut microbiota; Metagenomics; Antibiotics
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"Off-Spotter": very fast and exhaustive enumeration of genomic lookalikes for designing CRISPR/Cas guide RNAs
Pliatsika, Venetia
Rigoutsos, Isidore
Biology Direct
CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated nucleases) is a powerful component of the prokaryotic immune system that has been adapted for targeted genetic engineering in higher organisms. A key element of CRISPR/Cas is the "guide" RNA (gRNA) that is ~20 nucleotides (nts) in length and designed to be complementary to the intended target site. An integral requirement of the CRISPR/Cas system is that the target site be followed by a protospacer adjacent motif (PAM). Care needs to be exercised during gRNA design to avoid unintended ("off-target") interactions.
We designed and implemented the Off-Spotter algorithm to assist with the design of optimal gRNAs. When presented with a candidate gRNA sequence and a PAM, Off-Spotter quickly and exhaustively identifies all genomic sites that satisfy the PAM constraint and are identical or nearly-identical to the provided gRNA. Off-Spotter achieves its extreme performance through purely algorithmic means and not through hardware accelerators such as graphical processing units (GPUs). Off-Spotter also allows the user to identify on-the-fly how many and which nucleotides of the gRNA comprise the "seed". Off-Spotter's output includes a histogram showing the number of potential off-targets as a function of the number of mismatches. The output also includes for each potential off-target the site's genomic location, a human genome browser hyperlink to the corresponding location, genomic annotation in the vicinity of the off-target, GC content, etc.
Off-Spotter is very fast and flexible and can help in the design of optimal gRNAs by providing several PAM choices, a run-time definition of the seed and of the allowed number of mismatches, and a flexible output interface that allows sorting of the results, optional viewing/hiding of columns, etc. A key element of Off-Spotter is that it does not have a rigid definition of the seed: instead, the user can declare both the seed's location and extent on-the-fly. We expect that this flexibility in combination with Off-Spotter's speed and richly annotated output will enable experimenters to interactively and quickly explore different scenarios and gRNA possibilities.
This article was reviewed by Dr Eugene Koonin and Dr Frank Eisenhaber.
Electronic supplementary material
The online version of this article (doi:10.1186/s13062-015-0035-z) contains supplementary material, which is available to authorized users.
CRISPR; Off-targets; Cas endonucleases; Cas9; Guide RNAs; gRNAs; Indexing; Hashing
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The microbiome mutiny hypothesis: can our microbiome turn against us when we are old or seriously ill?
Rózsa, Lajos
Apari, Péter
Müller, Viktor
Biology Direct
The symbiotic organisms of the healthy microbiome tend to be harmless or even beneficial for the host; however, some symbionts are able to adjust their virulence in response to external stimuli. Evolutionary theory suggests that optimal virulence might increase if the mortality of the host (from unrelated causes) increases.
Presentation of the hypothesis
We hypothesize that microorganisms of the human microbiome may be capable of a coordinated phenotypic switch to higher virulence ("microbiome mutiny") in old or seriously ill people, to optimize their transmission under the conditions of increased background mortality. This proposed virulence shift might contribute to the death of old or seriously ill people even in the absence of apparent disease.
Testing the hypothesis
Testable predictions of the hypothesis include increased expression of virulence factors in isolates of the same species of the microbiome obtained from ailing/old versus healthy/young individuals, and the existence of microbial mechanisms to assess the general condition (background mortality) of the host. Such tests are going to be important to distinguish the cases of "microbiome mutiny" from the situation where opportunistic infections or increased effective virulence arise from relaxed immune control in ailing or old individuals in the absence of changes in the symbionts/pathogens.
Implications of the hypothesis
Elucidating this potential mechanism might open up new possibilities for the clinical management of age related health issues and critical injuries or disease. Targeted prophylaxis against the microbes capable of virulence shifts could break the harmful feedback loop between deteriorating health and the "mutiny" of the microbiome.
This article was reviewed by Eugene V Koonin, Neil Greenspan and Michael Gilchrist.
Evolutionary medicine; Facultative virulence; Microbiome; Host-pathogen communication; Pathogenesis
Related Articles
Genome-wide association study for posthitis in the free-living population of European bison (Bison bonasus)
Oleński, Kamil
Tokarska, Małgorzata
Hering, Dorota Maria
Puckowska, Paulina
Ruść, Anna
Pertoldi, Cino
Kamiński, Stanisław
Biology Direct
About 5–6% of the European bison (Bison bonasus) males are affected by posthitis (necrotic inflammation of the prepuce) and die in the wild forest. Despite many years of study, pathogenesis of this disease has not yet been determined. The main aim of the study was to find SNP markers significantly associated with the incidence of posthitis and mine the genome for candidate genes potentially involved in the development of the disease.
It was shown that relatively small number of SNPs effects reached genome-wide significance after false discovery rate (FDR) correction. Among 25 significant markers, the highest effects were found for two SNPs (rs110456748 and rs136792896) located at the distance of 23846 bp and 37742 bp, respectively, from OR10A3 gene (olfactory receptor genes), known to be involved in atopic dermatitis in humans. It was also observed that five other significant SNP markers were located in the proximity of candidate genes involved in severe diseases of skin tissue and cancer/tumour development of epithelial or testicular germ cells, which suggest their potential participation in the posthitis. The 25 investigated SNPs showed marked differences in allelic and genotypic frequencies between the healthy and affected bison groups.
The 2 Mb region of the BTA15 chromosome is involved in genetic background of posthitis and should be closer examined to find causal mutations helpful in better understanding of the disease ethology and to control its incidence in the future.
This article was reviewed by Prof. Lev Klebanov and Dr. Fyodor Kondrashov.
Bison; Posthitis; GWAS; Illumina BovineHD 777K
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A new ensemble coevolution system for detecting HIV-1 protein coevolution
Li, Guangdi
Theys, Kristof
Verheyen, Jens
Pineda-Peña, Andrea-Clemencia
Khouri, Ricardo
Piampongsant, Supinya
Eusébio, Mónica
Ramon, Jan
Vandamme, Anne-Mieke
Biology Direct
A key challenge in the field of HIV-1 protein evolution is the identification of coevolving amino acids at the molecular level. In the past decades, many sequence-based methods have been designed to detect position-specific coevolution within and between different proteins. However, an ensemble coevolution system that integrates different methods to improve the detection of HIV-1 protein coevolution has not been developed.
We integrated 27 sequence-based prediction methods published between 2004 and 2013 into an ensemble coevolution system. This system allowed combinations of different sequence-based methods for coevolution predictions. Using HIV-1 protein structures and experimental data, we evaluated the performance of individual and combined sequence-based methods in the prediction of HIV-1 intra- and inter-protein coevolution. We showed that sequence-based methods clustered according to their methodology, and a combination of four methods outperformed any of the 27 individual methods. This four-method combination estimated that HIV-1 intra-protein coevolving positions were mainly located in functional domains and physically contacted with each other in the protein tertiary structures. In the analysis of HIV-1 inter-protein coevolving positions between Gag and protease, protease drug resistance positions near the active site mostly coevolved with Gag cleavage positions (V128, S373-T375, A431, F448-P453) and Gag C-terminal positions (S489-Q500) under selective pressure of protease inhibitors.
This study presents a new ensemble coevolution system which detects position-specific coevolution using combinations of 27 different sequence-based methods. Our findings highlight key coevolving residues within HIV-1 structural proteins and between Gag and protease, shedding light on HIV-1 intra- and inter-protein coevolution.
This article was reviewed by Dr. Zoltán Gáspári.
Electronic supplementary material
The online version of this article (doi:10.1186/s13062-014-0031-8) contains supplementary material, which is available to authorized users.
HIV-1; Protein coevolution; Gag; Protease; Ensemble coevolution system; Sequence-based method
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Once upon a time the cell membranes: 175 years of cell boundary research
Lombard, Jonathan
Biology Direct
All modern cells are bounded by cell membranes best described by the fluid mosaic model. This statement is so widely accepted by biologists that little attention is generally given to the theoretical importance of cell membranes in describing the cell. This has not always been the case. When the Cell Theory was first formulated in the XIXth century, almost nothing was known about the cell membranes. It was not until well into the XXth century that the existence of the plasma membrane was broadly accepted and, even then, the fluid mosaic model did not prevail until the 1970s. How were the cell boundaries considered between the articulation of the Cell Theory around 1839 and the formulation of the fluid mosaic model that has described the cell membranes since 1972? In this review I will summarize the major historical discoveries and theories that tackled the existence and structure of membranes and I will analyze how these theories impacted the understanding of the cell. Apart from its purely historical relevance, this account can provide a starting point for considering the theoretical significance of membranes to the definition of the cell and could have implications for research on early life.
This article was reviewed by Dr. Étienne Joly, Dr. Eugene V. Koonin and Dr. Armen Mulkidjanian.
Cell membrane discovery; Cell membrane structure; Cell Theory; History of Science; Cell definition; Origins of life; Early evolution; Cenancestor
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The fundamental tradeoff in genomes and proteomes of prokaryotes established by the genetic code, codon entropy, and physics of nucleic acids and proteins
Goncearenco, Alexander
Berezovsky, Igor N
Biology Direct
Mutations in nucleotide sequences provide a foundation for genetic variability, and selection is the driving force of the evolution and molecular adaptation. Despite considerable progress in the understanding of selective forces and their compositional determinants, the very nature of underlying mutational biases remains unclear.
We explore here a fundamental tradeoff, which analytically describes mutual adjustment of the nucleotide and amino acid compositions and its possible effect on the mutational biases. The tradeoff is determined by the interplay between the genetic code, optimization of the codon entropy, and demands on the structure and stability of nucleic acids and proteins.
The tradeoff is the unifying property of all prokaryotes regardless of the differences in their phylogenies, life styles, and extreme environments. It underlies mutational biases characteristic for genomes with different nucleotide and amino acid compositions, providing foundation for evolution and adaptation.
This article was reviewed by Eugene Koonin, Michael Gromiha, and Alexander Schleiffer.
Electronic supplementary material
The online version of this article (doi:10.1186/s13062-014-0029-2) contains supplementary material, which is available to authorized users.
Fundamental tradeoff; Genomes; Proteomes; Prokaryotes; Nucleic acids; Proteins; Structure; Stability; Evolution; Adaptation
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Genome-scale identification and characterization of moonlighting proteins
Khan, Ishita
Chen, Yuqian
Dong, Tiange
Hong, Xioawei
Takeuchi, Rikiya
Mori, Hirotada
Kihara, Daisuke
Biology Direct
Moonlighting proteins perform two or more cellular functions, which are selected based on various contexts including the cell type they are expressed, their oligomerization status, and the binding of different ligands at different sites. To understand overall landscape of their functional diversity, it is important to establish methods that can identify moonlighting proteins in a systematic fashion. Here, we have developed a computational framework to find moonlighting proteins on a genome scale and identified multiple proteomic characteristics of these proteins.
First, we analyzed Gene Ontology (GO) annotations of known moonlighting proteins. We found that the GO annotations of moonlighting proteins can be clustered into multiple groups reflecting their diverse functions. Then, by considering the observed GO term separations, we identified 33 novel moonlighting proteins in Escherichia coli and confirmed them by literature review. Next, we analyzed moonlighting proteins in terms of protein-protein interaction, gene expression, phylogenetic profile, and genetic interaction networks. We found that moonlighting proteins physically interact with a higher number of distinct functional classes of proteins than non-moonlighting ones and also found that most of the physically interacting partners of moonlighting proteins share the latter's primary functions. Interestingly, we also found that moonlighting proteins tend to interact with other moonlighting proteins. In terms of gene expression and phylogenetically related proteins, a weak trend was observed that moonlighting proteins interact with more functionally diverse proteins. Structural characteristics of moonlighting proteins, i.e. intrinsic disordered regions and ligand binding sites were also investigated.
Additional functions of moonlighting proteins are difficult to identify by experiments and these proteins also pose a significant challenge for computational function annotation. Our method enables identification of novel moonlighting proteins from current functional annotations in public databases. Moreover, we showed that potential moonlighting proteins without sufficient functional annotations can be identified by analyzing available omics-scale data. Our findings open up new possibilities for investigating the multi-functional nature of proteins at the systems level and for exploring the complex functional interplay of proteins in a cell.
This article was reviewed by Michael Galperin, Eugine Koonin, and Nick Grishin.
Electronic supplementary material
The online version of this article (doi:10.1186/s13062-014-0030-9) contains supplementary material, which is available to authorized users.
Moonlighting protein; Multitasking; Function annotation; Genome; Omics data
Related Articles
Mammalian Argonaute-DNA binding?
Smalheiser, Neil R
Gomes, Octavio L A
Biology Direct
When a field shares the consensus that a particular phenomenon does NOT occur, this may reflect extensive experimental investigations with negative outcomes, or may represent the "common sense" position based on current knowledge and established ways of thinking. The current consensus of the RNA field is that eukaryotic Argonaute (Ago) proteins employ RNA guides and target other RNAs. The alternative -- that eukaryotic Ago has biologically important interactions with DNA in vivo – has not been seriously considered, in part because the only role contemplated for DNA was as a guide strand, and in part because it did not seem plausible that any natural source of suitable DNAs exists in eukaryotic cells. However, eukaryotic Argonaute domains bind DNA in the test tube, and several articles report that small inhibitory double-stranded DNAs do have the ability to silence target RNAs in a sequence-dependent (though poorly characterized) manner. A search of the literature identified potential DNA binding partners for Ago, including (among others) single-stranded DNAs residing in extracellular vesicles, and cytoplasmic satellite-repeat DNA fragments that are associated with the plasma membrane and transcribed by Pol II. It is interesting to note that both cytoplasmic and extracellular vesicle DNA are expressed at greatly elevated levels in cancer cells relative to normal cells. In such a pathological scenario, if not under normal conditions, there may be appreciable binding of Ago to DNA despite its lower affinity compared to RNA. If so, DNA might displace Ago from binding to its normal partners (miRNAs, siRNAs and other short ncRNAs), disrupting tightly controlled post-transcriptional gene silencing processes that are vital to correct functioning of a normal cell. The possible contribution to cancer pathogenesis is a strong motivator for further investigation of Ago-DNA binding. More generally, this case underscores the need for better informatics tools to allow investigators to analyze the state of a given scientific question at a high-level and to identify possible new research directions.
Reviewers: This article was reviewed by Eugene Koonin, Kira S. Makarova, Alexander Maxwell Burroughs (nominated by L Aravind), and Isidore Rigoutsos.
Open peer review: Reviewed by Eugene Koonin, Kira S. Makarova, Alexander Maxwell Burroughs (nominated by L Aravind), and Isidore Rigoutsos. For the full reviews, please go to the Reviewers' comments section.
Consensus; Hypothesis assessment; Scientific discovery; DNA interference; Cytoplasmic DNA; RNA interference
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Molecular complementarity between simple, universal molecules and ions limited phenotype space in the precursors of cells
Norris, Vic
Reusch, Rosetta N
Igarashi, Kazuei
Root-Bernstein, Robert
Biology Direct
Fundamental problems faced by the protocells and their modern descendants include how to go from one phenotypic state to another; escape from a basin of attraction in the space of phenotypes; reconcile conflicting growth and survival strategies (and thereby live on 'the scales of equilibria'); and create a coherent, reproducible phenotype from a multitude of constituents.
Presentation of the hypothesis
The solutions to these problems are likely to be found with the organic and inorganic molecules and inorganic ions that constituted protocells, which we term SUMIs for Simple Universal Molecules and Ions. These SUMIs probably included polyphosphate (PolyP) as a source of energy and of phosphate; poly-(R)-3-hydroxybutyrate (PHB) as a source of carbon and as a transporter in association with PolyP; polyamines as a source of nitrogen; lipids as precursors of membranes; as well as peptides, nucleic acids, and calcium. Here, we explore the hypothesis that the direct interactions between PHB, PolyP, polyamines and lipids – modulated by calcium – played a central role in solving the fundamental problems faced by early and modern cells.
Testing the hypothesis
We review evidence that SUMIs (1) were abundant and available to protocells; (2) are widespread in modern cells; (3) interact with one another and other cellular constituents to create structures with new functions surprisingly similar to those of proteins and RNA; (4) are essential to creating coherent phenotypes in modern bacteria. SUMIs are therefore natural candidates for reducing the immensity of phenotype space and making the transition from a "primordial soup" to living cells.
Implications of the hypothesis
We discuss the relevance of the SUMIs and their interactions to the ideas of molecular complementarity, composomes (molecular aggregates with hereditary properties based on molecular complementarity), and a prebiotic ecology of co-evolving populations of composomes. In particular, we propose that SUMIs might limit the initial phenotype space of composomes in a coherent way. As examples, we propose that acidocalcisomes arose from interactions and self-selection among SUMIs and that the phosphorylation of proteins in modern cells had its origin in the covalent modification of proteins by PHB.
This article was reviewed by Doron Lancet and Kepa Ruiz-Mirazo.
Origin of life; Protein kinase; Hyperstructure; Network; Cation; Polymer; Complementarity; DNA; RNA
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Microbes on the edge of Occam's razor
Starokadomskyy, Petro
Biology Direct
Our body harbors hundreds of microbial species and contains many more bacterial than human cells. These microbes are not passive riders but rather a vital component of the organism. The human microbiota affects our health in multiple ways, both positively and negatively. One of the new attractive directions in microbiome biology is the "microbiome-brain axis". Several groups of researchers have described the ability of the gut microbiota to communicate with the brain and thus modulate human behavior. These limited experimental data became the foundation of the "biomeme hypothesis" of possible microbial origin of some religious rituals that has recently appeared in Biology Direct. Here I propose a critical analysis of this hypothesis. I conclude that there is no evidence of the microbial origin of religious practices but there are strong indications of their psychological and social roots.
This article was reviewed by Eugene Koonin, Neil R Smalheiser, Etienne Joly.
Microbes; Religious rituals; Microbiome-brain axis; Biomeme hypothesis; Popper; Falsifiability; Occam's razor
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Cooperation and selfishness both occur during molecular evolution
Penny, David
Biology Direct
Perhaps the 'selfish' aspect of evolution has been over-emphasised, and organisms considered as basically selfish. However, at the macromolecular level of genes and proteins the cooperative aspect of evolution is more obvious and balances this self-centred aspect. Thousands of proteins must function together in an integrated manner to use and to produce the many molecules necessary for a functioning cell. The macromolecules have no idea whether they are functioning cooperatively or competitively with other genes and gene products (such as proteins). The cell is a giant cooperative system of thousands of genes/proteins that function together, even if it has to simultaneously resist 'parasites'. There are extensive examples of cooperative behavior among genes and proteins in both functioning cells and in the origin of life, so this cooperative nature, along with selfishness, must be considered part of normal evolution. The principles also apply to very large numbers of examples of 'positive interactions' between organisms, including both eukaryotes and akaryotes (prokaryotes). This does not negate in any way the 'selfishness' of genes – but macromolecules have no idea when they are helping, or hindering, other groups of macromolecules. We need to assert more strongly that genes, and gene products, function together as a cooperative unit.
Reviewers: This article was reviewed by Prof. Bill Martin (Düsseldorf), Dr. Nicolas Galtier (Montpellier) and Dr. Anthony Poole (Christchurch).
Cooperation; Molecular evolution; Molecular level; Origin of life; Natural selection
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Chordopoxvirus protein F12 implicated in enveloped virion morphogenesis is an inactivated DNA polymerase
Yutin, Natalya
Faure, Guilhem
Koonin, Eugene V
Mushegian, Arcady R
Biology Direct
Through the course of their evolution, viruses with large genomes have acquired numerous host genes, most of which perform function in virus reproduction in a manner that is related to their original activities in the cells, but some are exapted for new roles. Here we report the unexpected finding that protein F12, which is conserved among the chordopoxviruses and is implicated in the morphogenesis of enveloped intracellular virions, is a derived DNA polymerase, possibly of bacteriophage origin, in which the polymerase domain and probably the exonuclease domain have been inactivated. Thus, F12 appears to present a rare example of a drastic, exaptive functional change in virus evolution.
Reviewers: This article was reviewed by Frank Eisenhaber and Juergen Brosius. For complete reviews, go the Reviewers' Reports section.
DNA polymerase; Exaptation; Poxviruses; Evolution of viruses
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Putative roles of purinergic signaling in human immunodeficiency virus-1 infection
Pacheco, Paulo AF
Faria, Robson X
Ferreira, Leonardo GB
Paixão, Izabel CNP
Biology Direct
This article was reviewed by Neil S. Greenspan and Rachel Gerstein.
Nucleotides and nucleosides act as potent extracellular messengers via the activation of the family of cell-surface receptors termed purinergic receptors. These receptors are categorized into P1 and P2 receptors (P2Rs). P2Rs are further classified into two distinct families, P2X receptors (P2XRs) and P2Y receptors (P2YRs). These receptors display broad tissue distribution throughout the body and are involved in several biological events. Immune cells express various P2Rs, and purinergic signaling mechanisms have been shown to play key roles in the regulation of many aspects of immune responses. Researchers have elucidated the involvement of these receptors in the host response to infections. The evidences indicate a dual function of these receptors, depending on the microorganism and the cellular model involved. Three recent reports have examined the relationship between the level of extracellular ATP, the mechanisms underlying purinergic receptors participating in the infection mechanism of HIV-1 in the cell. Although preliminary, these results indicate that purinergic receptors are putative pharmacological targets that should be further explored in future studies.
P2X7R; HIV-1 infection; Antagonists; Pharmacological targets
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A new rhesus macaque assembly and annotation for next-generation sequencing analyses
Zimin, Aleksey V
Cornish, Adam S
Maudhoo, Mnirnal D
Gibbs, Robert M
Zhang, Xiongfei
Pandey, Sanjit
Meehan, Daniel T
Wipfler, Kristin
Bosinger, Steven E
Johnson, Zachary P
Tharp, Gregory K
Marçais, Guillaume
Roberts, Michael
Ferguson, Betsy
Fox, Howard S
Treangen, Todd
Salzberg, Steven L
Yorke, James A
Norgren,, Robert B
Biology Direct
The rhesus macaque (Macaca mulatta) is a key species for advancing biomedical research. Like all draft mammalian genomes, the draft rhesus assembly (rheMac2) has gaps, sequencing errors and misassemblies that have prevented automated annotation pipelines from functioning correctly. Another rhesus macaque assembly, CR_1.0, is also available but is substantially more fragmented than rheMac2 with smaller contigs and scaffolds. Annotations for these two assemblies are limited in completeness and accuracy. High quality assembly and annotation files are required for a wide range of studies including expression, genetic and evolutionary analyses.
We report a new de novo assembly of the rhesus macaque genome (MacaM) that incorporates both the original Sanger sequences used to assemble rheMac2 and new Illumina sequences from the same animal. MacaM has a weighted average (N50) contig size of 64 kilobases, more than twice the size of the rheMac2 assembly and almost five times the size of the CR_1.0 assembly. The MacaM chromosome assembly incorporates information from previously unutilized mapping data and preliminary annotation of scaffolds. Independent assessment of the assemblies using Ion Torrent read alignments indicates that MacaM is more complete and accurate than rheMac2 and CR_1.0. We assembled messenger RNA sequences from several rhesus tissues into transcripts which allowed us to identify a total of 11,712 complete proteins representing 9,524 distinct genes. Using a combination of our assembled rhesus macaque transcripts and human transcripts, we annotated 18,757 transcripts and 16,050 genes with complete coding sequences in the MacaM assembly. Further, we demonstrate that the new annotations provide greatly improved accuracy as compared to the current annotations of rheMac2. Finally, we show that the MacaM genome provides an accurate resource for alignment of reads produced by RNA sequence expression studies.
The MacaM assembly and annotation files provide a substantially more complete and accurate representation of the rhesus macaque genome than rheMac2 or CR_1.0 and will serve as an important resource for investigators conducting next-generation sequencing studies with nonhuman primates.
This article was reviewed by Dr. Lutz Walter, Dr. Soojin Yi and Dr. Kateryna Makova.
Macaca mulatta; Rhesus macaque; Genome; Assembly; Annotation; Transcriptome; Next-generation sequencing
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Mycobacteriophage-drived diversification of Mycobacterium abscessus
Sassi, Mohamed
Gouret, Philippe
Chabrol, Olivier
Pontarotti, Pierre
Drancourt, Michel
Biology Direct
Mycobacterium abscessus is an emerging opportunistic pathogen which diversity was acknowledged by the recent description of two subspecies accommodating M. abscessus, Mycobacterium bolletii and Mycobacterium massiliense isolates.
Here, genome analysis found 1–8 prophage regions in 47/48 M. abscessus genomes ranging from small prophage-like elements to complete prophages. A total of 20,304 viral and phage proteins clustered into 853 orthologous groups. Phylogenomic and phylogenetic analyses based on prophage region homology found three main clusters corresponding to M. abscessus, M. bolletii and M. massiliense. Analysing 135 annotated Tape Measure Proteins found thirteen clusters and four singletons, suggesting that at least 17 mycobacteriophages had infected M. abscessus during its evolution. The evolutionary history of phages differed from that of their mycobacterial hosts. In particular, 33 phage-related proteins have been horizontally transferred within M. abscessus genomes. They comprise of an integrase, specific mycobacteriophage proteins, hypothetical proteins and DNA replication and metabolism proteins. Gene exchanges, loss and gains which occurred in M. abscessus genomes have been driven by several mycobacteriophages.
This analysis of phage-mycobacterium co-evolution suggests that mycobacteriophages are playing a key-role in the on-going diversification of M. abscessus.
This article was reviewed by Eric Bapteste, Patrick Forterre and Eugene Koonin.
Mycobacterium abscessus; Mycobacterium bolletii; Mycobacterium massiliense; Prophages; Mycobacteriophages
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Parallel universes of Black Six biology
Kraev, Alexander
Biology Direct
Creation of lethal and synthetic lethal mutations in an experimental organism is a cornerstone of genetic dissection of gene function, and is related to the concept of an essential gene. Common inbred mouse strains carry background mutations, which can act as genetic modifiers, interfering with the assignment of gene essentiality. The inbred strain C57BL/6J, commonly known as "Black Six", stands out, as it carries a spontaneous homozygous deletion in the nicotinamide nucleotide transhydrogenase (Nnt) gene [GenBank: AH009385.2], resulting in impairment of steroidogenic mitochondria of the adrenal gland, and a multitude of indirect modifier effects, coming from alteration of glucocorticoid-regulated processes. Over time, the popular strain has been used, by means of gene targeting technology, to assign "essential" and "redundant" qualifiers to numerous genes, thus creating an internally consistent "parallel universe" of knowledge. It is unrealistic to suggest phasing-out of this strain, given the scope of shared resources built around it, however, continuing on the road of "strain-unawareness" will result in profound waste of effort, particularly where translational research is concerned. The review analyzes the historical roots of this phenomenon and proposes that building of "parallel universes" should be urgently made visible to a critical reader by obligatory use of unambiguous and persistent tags in publications and databases, such as hypertext links, pointing to a vendor's strain description web page, or to a digital object identifier (d.o.i.) of the original publication, so that any research done exclusively in C57BL/6J, could be easily identified.
This article was reviewed by Dr. Neil Smalheiser and Dr. Miguel Andrade-Navarro.
Mouse; Inbred strain; C57BL/6J; Synthetic lethality; Gene interaction; Essential gene; Nicotinamide nucleotide transhydrogenase; Mitochondria; Glucocorticoid hormone; Adrenal gland
Related Articles
Translational selection in human: more pronounced in housekeeping genes
Ma, Lina
Cui, Peng
Zhu, Jiang
Zhang, Zhihua
Zhang, Zhang
Biology Direct
Translational selection is a ubiquitous and significant mechanism to regulate protein expression in prokaryotes and unicellular eukaryotes. Recent evidence has shown that translational selection is weakly operative in highly expressed genes in human and other vertebrates. However, it remains unclear whether translational selection acts differentially on human genes depending on their expression patterns.
Here we report that human housekeeping (HK) genes that are strictly defined as genes that are expressed ubiquitously and consistently in most or all tissues, are under stronger translational selection.
These observations clearly show that translational selection is also closely associated with expression pattern. Our results suggest that human HK genes are more efficiently and/or accurately translated into proteins, which will inevitably open up a new understanding of HK genes and the regulation of gene expression.
This article was reviewed by Yuan Yuan, Baylor College of Medicine; Han Liang, University of Texas MD Anderson Cancer Center (nominated by Dr Laura Landweber) Eugene Koonin, NCBI, NLM, NIH, United States of America Sandor Pongor, International Centre for Genetic Engineering and biotechnology (ICGEB), Italy.
Translational selection; Codon usage bias; Expression regulation; Housekeeping gene; Tissue-specific gene
Related Articles
Impairment of translation in neurons as a putative causative factor for autism
Poliakov, Eugenia
Koonin, Eugene V
Rogozin, Igor B
Biology Direct
A dramatic increase in the prevalence of autism and Autistic Spectrum Disorders (ASD) has been observed over the last two decades in USA, Europe and Asia. Given the accumulating data on the possible role of translation in the etiology of ASD, we analyzed potential effects of rare synonymous substitutions associated with ASD on mRNA stability, splicing enhancers and silencers, and codon usage.
Presentation of the hypothesis
We hypothesize that subtle impairment of translation, resulting in dosage imbalance of neuron-specific proteins, contributes to the etiology of ASD synergistically with environmental neurotoxins.
Testing the hypothesis
A statistically significant shift from optimal to suboptimal codons caused by rare synonymous substitutions associated with ASD was detected whereas no effect on other analyzed characteristics of transcripts was identified. This result suggests that the impact of rare codons on the translation of genes involved in neuron development, even if slight in magnitude, could contribute to the pathogenesis of ASD in the presence of an aggressive chemical background. This hypothesis could be tested by further analysis of ASD-associated mutations, direct biochemical characterization of their effects, and assessment of in vivo effects on animal models.
Implications of the hypothesis
It seems likely that the synergistic action of environmental hazards with genetic variations that in themselves have limited or no deleterious effects but are potentiated by the environmental factors is a general principle that underlies the alarming increase in the ASD prevalence.
This article was reviewed by Andrey Rzhetsky, Neil R. Smalheiser, and Shamil R. Sunyaev.
Synonymous mutations; Single nucleotide polymorphism; Codon usage; Splicing enhancer; Splicing silencer; mRNA secondary structure; Transcription factor binding; Neurotoxin
Related Articles
Exploring the stability of long intergenic non-coding RNA in K562 cells by comparative studies of RNA-Seq datasets
Wang, Lei
Zhou, Dequan
Tu, Jing
Wang, Yan
Lu, Zuhong
Biology Direct
The stability of long intergenic non-coding RNAs (lincRNAs) that possess tissue/cell-specific expression, might be closely related to their physiological functions. However, the mechanism associated with stability of lincRNA remains elusive. In this study, we try to study the stability of lincRNA in K562 cells, an important model cell, through comparing two K562 transcriptomes which are obtained from ENCODE Consortium and our sequenced RNA-Seq dataset (PH) respectively.
By lincRNAs analysis pipeline, 1804 high-confidence lincRNAs involving 1564 annotated lincRNAs and 240 putative novel lincRNAs were identified in PH, and 1587 high-confidence lincRNAs including 1429 annotated lincRNAs and 158 putative novel lincRNAs in ENCODE. There are 1009 unique lincRNAs in PH, 792 unique lincRNAs were in ENCODE, and 795 overlapping lincRNAs in both datasets. The analysis of differences in minimum free energy distribution and lincRNA half-life showed that a large proportion of overlapping lincRNAs were more stable than the unique lincRNAs. Most lincRNAs were more unstable than protein-coding RNAs through comparing their minimum free energy.
Identification of overlapping and unique lincRNAs can be helpful to classify the stability of lincRNAs. Our results suggest that overlapping lincRNAs (relatively stable linRNAs) and unique lincRNAs (relatively unstable lincRNAs) might be involved in different cellular processes.
This article has been reviewed by Prof. Oliviero Carugo, Dr. Alistair Forrest and Prof. Manju Bansal.
RNA Sequencing (RNA-Seq); Long intergenic non-coding RNAs (lincRNAs); K562; RNA stability
Related Articles
Midichlorians - the biomeme hypothesis: is there a microbial component to religious rituals?
Panchin, Alexander Y
Tuzhikov, Alexander I
Panchin, Yuri V
Biology Direct
Cutting edge research of human microbiome diversity has led to the development of the microbiome-gut-brain axis concept, based on the idea that gut microbes may have an impact on the behavior of their human hosts. Many examples of behavior-altering parasites are known to affect members of the animal kingdom. Some prominent examples include Ophiocordyceps unilateralis (fungi), Toxoplasma gondii (protista), Wolbachia (bacteria), Glyptapanteles sp. (arthropoda), Spinochordodes tellinii (nematomorpha) and Dicrocoelium dendriticum (flat worm). These organisms belong to a very diverse set of taxonomic groups suggesting that the phenomena of parasitic host control might be more common in nature than currently established and possibly overlooked in humans.
Presentation of the hypothesis
Some microorganisms would gain an evolutionary advantage by encouraging human hosts to perform certain rituals that favor microbial transmission. We hypothesize that certain aspects of religious behavior observed in the human society could be influenced by microbial host control and that the transmission of some religious rituals could be regarded as the simultaneous transmission of both ideas (memes) and parasitic organisms.
Testing the hypothesis
We predict that next-generation microbiome sequencing of samples obtained from gut or brain tissues of control subjects and subjects with a history of voluntary active participation in certain religious rituals that promote microbial transmission will lead to the discovery of microbes, whose presence has a consistent and positive association with religious behavior. Our hypothesis also predicts a decline of participation in religious rituals in societies with improved sanitation.
Implications of the hypothesis
If proven true, our hypothesis may provide insights on the origin and pervasiveness of certain religious practices and provide an alternative explanation for recently published positive associations between parasite-stress and religiosity. The discovery of novel microorganisms that affect host behavior may improve our understanding of neurobiology and neurochemistry, while the diversity of such organisms may be of interest to evolutionary biologists and religious scholars.
This article was reviewed by Prof. Dan Graur, Dr. Rob Knight and Dr. Eugene Koonin
Microbiome; Religion; Brain; Metagenome; Midichlorians; Biomeme; Behavior; Rituals
Related Articles
Pseudo-chaotic oscillations in CRISPR-virus coevolution predicted by bifurcation analysis
Berezovskaya, Faina S
Wolf, Yuri I
Koonin, Eugene V
Karev, Georgy P
Biology Direct
The CRISPR-Cas systems of adaptive antivirus immunity are present in most archaea and many bacteria, and provide resistance to specific viruses or plasmids by inserting fragments of foreign DNA into the host genome and then utilizing transcripts of these spacers to inactivate the cognate foreign genome. The recent development of powerful genome engineering tools on the basis of CRISPR-Cas has sharply increased the interest in the diversity and evolution of these systems. Comparative genomic data indicate that during evolution of prokaryotes CRISPR-Cas loci are lost and acquired via horizontal gene transfer at high rates. Mathematical modeling and initial experimental studies of CRISPR-carrying microbes and viruses reveal complex coevolutionary dynamics.
We performed a bifurcation analysis of models of coevolution of viruses and microbial host that possess CRISPR-Cas hereditary adaptive immunity systems. The analyzed Malthusian and logistic models display complex, and in particular, quasi-chaotic oscillation regimes that have not been previously observed experimentally or in agent-based models of the CRISPR-mediated immunity. The key factors for the appearance of the quasi-chaotic oscillations are the non-linear dependence of the host immunity on the virus load and the partitioning of the hosts into the immune and susceptible populations, so that the system consists of three components.
Bifurcation analysis of CRISPR-host coevolution model predicts complex regimes including quasi-chaotic oscillations. The quasi-chaotic regimes of virus-host coevolution are likely to be biologically relevant given the evolutionary instability of the CRISPR-Cas loci revealed by comparative genomics. The results of this analysis might have implications beyond the CRISPR-Cas systems, i.e. could describe the behavior of any adaptive immunity system with a heritable component, be it genetic or epigenetic. These predictions are experimentally testable.
Reviewers' reports
This manuscript was reviewed by Sandor Pongor, Sergei Maslov and Marek Kimmel. For the complete reports, go to the Reviewers' Reports section.
Related Articles
Selecting biologically informative genes in co-expression networks with a centrality score
Azuaje, Francisco J
Biology Direct
Measures of node centrality in biological networks are useful to detect genes with critical functional roles. In gene co-expression networks, highly connected genes (i.e., candidate hubs) have been associated with key disease-related pathways. Although different approaches to estimating gene centrality are available, their potential biological relevance in gene co-expression networks deserves further investigation. Moreover, standard measures of gene centrality focus on binary interaction networks, which may not always be suitable in the context of co-expression networks. Here, I also investigate a method that identifies potential biologically meaningful genes based on a weighted connectivity score and indicators of statistical relevance.
The method enables a characterization of the strength and diversity of co-expression associations in the network. It outperformed standard centrality measures by highlighting more biologically informative genes in different gene co-expression networks and biological research domains. As part of the illustration of the gene selection potential of this approach, I present an application case in zebrafish heart regeneration. The proposed technique predicted genes that are significantly implicated in cellular processes required for tissue regeneration after injury.
A method for selecting biologically informative genes from gene co-expression networks is provided, together with free open software.
This article was reviewed by Anthony Almudevar, Maciej M Kańduła (nominated by David P Kreil) and Christine Wells.
Network hubs; Weighted networks; Gene co-expression networks; Centrality scores; Zebrafish; Heart regeneration; Cancer; Microarrays; RNA-Seq
Related Articles
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text: Share It MainStoriesMy golden girl My golden girl Brigid Klein | Jun 26, 2014 | North America: Virginia My daughter Elizabeth had a tough decision to make when selected to participate in USA Games as part of Team Virginia – walk in her high school graduation ceremony or go for the gold in New Jersey. We told her the choice was hers. I am so glad she chose to go for gold and she got it in 100 backstroke! It was a spectacular week in New Jersey – thanks Special Olympics! About Me:Proud parent of a Special Olympic athelete Read More Stories Making a Difference in India and NepalDavid HircockThank You, Special Olympics LouisianaJude and Paula BernardAgreement in Italy Will Boost Inclusion and RespectMaureen RabbittBelgium Athlete Addresses Experts at European ForumMartha Jo BraycichMy Coaches Were There For MeCarla SimonBond Between Student and Coach Transforms Life of Special Olympics Swimmer at YMCACarolyn GessnerIn Malta, a Proud Mother Shares Her StoryNatasha MicallefAn "Awesome" Secret: The Universal Power of Unified SportsDavid EvangelistaA Unified Gathering Like No OtherNoha Gaballa"We all need to work together and respect each other to be successful"Maureen RabbittMore Schools in the UK want to Play UnifiedMaureen RabbittDo You Have A Story to Share?Share Your Story More Stories

subset: commoncrawl


text:
Sakaguchi also mentioned that Final Fantasy XI will probably have a player-driven storyline, and will be a lot like Ultima Online in its ability to allow gamers from all around the world to log on and get into the game.
As for Final Fantasy X, Sakaguchi-san explained that the game's production is finished and is awaiting a release in Japan, though US gamers will have to wait until early next year for their copies.
The full interview is at Gamespot.com
Tales from the Borderlands July 31 • 9:00am PDT/12:00pm EDT
Sword Coast Legends Aug 7 • 9:00am PDT/12:00pm EDT
Breath of Fire IV Continues! Every Monday • 5:00pm PDT/8:00pm EDT
Star Wars: KotOR Continues! Coming soon...


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GNOME 3.21.4 Desktop Arrives for Testing As GUADEC Conference Approaches
Frederic Peters has been happy to inform Softpedia about the availability of the fourth development release for the upcoming GNOME 3.22 "Karlsruhe" desktop environment for GNU/Linux operating systems.
Ubuntu Budgie Remix 16.04.1 Released with Full-Disk Encryption, Snap Support
David Mohammed has been extremely happy to inform Softpedia about the availability of the Ubuntu Budgie Remix 16.04.1 operating system, as part of the recent Ubuntu 16.04.1 LTS (Xenial Xerus) release.
Bodhi 4.0.0 Alpha Release
Not only is our first 4.0.0 alpha release here – but it is here relatively on schedule. If all goes according to plan we will have something stamped as stable before September hits. I would just like to be clear that this is far from a polished / finished product. I would encourage anyone wanting to write a review to wait to do so until our stable release. If you are not someone who is interested in helping find issues please wait as well.
Games for GNU/Linux


text:
RATINGS: 799 WEIGHTED AVG: 3.1/5 SEASONAL: Special EST. CALORIES: 120 ABV: 4%
Designed as a flavorful session beer, Oarsman Ale uses a classic German brewing technique to impart a light, refreshing tartness. Oarsman Ale grew out of a desire to explore the tradition of session beers, trading intensity for finesse while still creating a worthwhile experience for the taster. The grain bill includes a healthy portion of wheat, while light hopping lend citrus & herbal notes to the aroma. Fermented with Bells house ale yeast, Oarsman comes in at 4.0% alcohol by volume. Rather than being the dominant flavor note, the tartness in Oarsman takes on more of a palate-cleansing role, making it perfect with meals or purely on its own.
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text:
Susan Dunn is a professor of arts and humanities at Williams College and the author of the forthcoming book "1940: FDR, Willkie, Lindbergh, Hitler — The Election Amid the Storm."
"YOU know, he is a very good fellow," the president said to his labor secretary after meeting in the White House with the election rival he had just trounced. "He has lots of talent. I want to use him somehow. I want to offer him an important post in the government. Can you think of one?"
No, those weren't President Obama's words after meeting Mitt Romney for lunch at the White House on Thursday. They were Franklin D. Roosevelt's about Wendell Willkie, whom Roosevelt defeated in the 1940 election. And the sentiment led to a legendary partnership.
Mr. Obama has extended conciliatory words to Mr. Romney, but where will it lead? Will this president welcome the counsel and assistance of a man who, for months, pounded his philosophy and policies? Can the defeated candidate see past his pain and withstand predictable criticism from divisive figures in his own party to cooperate with Mr. Obama?
With the country on the brink of the "fiscal cliff" and yearning for longer-term unity, the two men's coming together might be an excellent outcome. And each would have a ready role model in the partnership that blossomed seven decades ago....


text:
To Arms; To Arms - The I-Cubs Are Coming!
I had a nice chat before Jeff Samardzija's return engagement in Des Moines Saturday night with I-Cub pitching coach Mike Mason. We talked about Jose Ascanio's pitch counts, Samardzija's repertoire, the organization's pitcher pecking order and the effect, if any, of yo-yoing between the bullpen in Chicago and the rotation in Des Moines on young arms and minds.
Ascanio was the first order of business. It took him until his 6th start to record a win, despite a 1.01 ERA, because his pitch count leash was still so short. After a high-water mark of 81 two starts ago, he'd been pulled after 76 last time out even though he fanned the side in the 4th and 5th, his last two innings of work. Why wasn't he allowed to come out for the 6th?
"He was still closing in winter ball," Mason noted. "When the decision was made in camp to start him this year, the plan was to give him a couple starts at each pitch count level - 60, 70, 80 - as he went along and see how he handled it. The other day we figured why trot him out for the 6th just to pull him after half a dozen more pitches."
Mason had lots more to say about Ascanio before Chad Fox's elbow came undone again later that same night in Milwaukee. I asked him if the organization saw Jose as a pleasant surprise at this point.
"Pleasant is a huge understatement. He's done way better than expected," he grinned. "All along the thought was that the [Chicago] Cubs' 6th starter would come from the organization, but nobody thought 'Hosie' was the guy. Well, he's the 6th starter now. He's passed Atkins."
What about Samardzija? Passed him too?
"Ascanio is a four pitch guy. He throws a curve, a slider and a change-up that's his best offspeed pitch," Mason said. "Jeff and I are talking about him working to develop a curveball to go with his fastball and split." Apparently Samardzija's change-up isn't the complement yet to his high-nineties heat that Ascanio's is to his.
"'Hosie' used to start with Atlanta through Double A," Mason recounted. "Then he went to relief, but he's been throwing multiple pitches longer than Jeff. Jeff's attitude coming back here is great and he understands what he's got to work on."
Later that night of course, Mason's ranking of the trio of proteges in his care was borne out when Ascanio was summoned to the big leagues in the wake of Fox's latest, and maybe last, breakdown.
Yesterday Atkins responded to his snub with probably his best start of the year in pitching the team to a 9-2 win over Memphis. After a rocky start he settled down to last seven innings, the last six of them scoreless.
I asked Mason about Jeff Stevens, who appears to be the best early dividend of the DeRosa trade, although he won't be filling in at 3rd for Aramis Ramirez as DeRosa could capably have done. Stevens still has a non-existent ERA, having allowed only four hits in 14 innings. Batters are 4-45 against him for a BAA of .088, 3rd best right now in professional baseball among pitchers who've thrown at least 10 innings.
"Jeff's been very good, but he's young and he knows he wouldn't get by in the big leagues with essentially one pitch like he is here right now," said Mason. "Down the line if the bullpen keeps struggling in Chicago, I suppose they might give him a shot, but right now there's probably guys ahead of him." Mason named Kevin Hart as one of those, despite his uneven pattern so far this spring.
What about guys like Ascanio and Samardzija ping-ponging between short relief and starting?
"That's a bigger issue in terms of mental preparation than physical." according to Mason. "And even the physical part might be more with the legs than the arm because you just don't run as much if you're in the pen as you do if you're starting every five days. You have to have a different approach with your legs and your head as much as your arm if you know you might pitch any day you come to the ballpark."
I asked Mason if he mostly carries out orders from above or if he has latitude in how he works with his pitchers at the Triple A level.
"I talk with Larry [Rothschild] all the time, and he might say, like with Jeff [Samardzija], 'he's gotta develop secondary pitches,' but it's up to me what pitches we work on. That's why Jeff and I are talkin' about maybe workin' on a curveball for him. They give me assignments, but it's up to me how I work on them." he explained.
Given the ongoing bullpen turmoil in Chicago it doesn't appear Mason's workload will let up any time soon.
OTHERWISE: Greg Reinhard will start in today's noon matinee in the wake of Ascanio's call-up. In 18 innings out of the bullpen he's compiled a 0.49 ERA with 26 strikeouts and only five BB's...the PCL American North is a nice parallel to the NL Central with Iowa [16-13], Memphis [17-11] and Nashville [17-14] jockeying in the standings like their counterparts in Chicago, St. Louis and Milwaukee...Jake Fox has been day-to-day since catching some broken bat shrapnel on Friday night and taking a few stitches to close a leg wound. He's expected back in the lineup today...catcher Chris Robinson is not only hitting .394, he's also swiped five bases! For what it's worth, he's only nabbed 2/15 stealing against him...couldn't help but notice that the redhead is till red hot. Matt Murton is hitting .411 at Colorado Springs. Sometimes we take our stats with a grain of salt in the PCL...MW
Re: To Arms; To Arms - The I-Cubs Are Coming!
Good report from AAA Mike!
Javier Lopez was just DFAed by the Red Sox, he has struggled this year, but has been money for the last three. I wonder if the Cubs will take a look at him.
Re: To Arms; To Arms - The I-Cubs Are Coming!
Iowa Mike, love the AAA Report! Way to get the inside scoop.
Isn't Stevens a little old to be a one-pitch pitcher? Obviously he's got a good fastball with excellent movement to survive just on that.
It's good to get scoop behind the numbers; we hunger to know if the great starts by Ascanio, Stevens, and Reinhard are due to real improvement, or just small sample size
Re: To Arms; To Arms - The I-Cubs Are Coming!
Really excellent stuff, Mike. Thanks.
I thought my BA Prospects handbook said Stevens had 2 pitches. Any more info on what his 2nd pitch is supposed to be, and if they're scrapping it and looking for a different one?
Re: To Arms; To Arms - The I-Cubs Are Coming!
Thanks, Mike!
Re: To Arms; To Arms - The I-Cubs Are Coming!
according to this 2008 scouting report stevens has 4 pitches including a fb between 92-95 and a "whiffle ball" slider: http://www.indiansprospectinsider.com/2008/01/jeff...
excellent piece Mike, thanks for the info...
Stevens best pitch seemed to be his curve/slider when I saw him briefly in spring training...Wilken says he's basically a 2-pitch pitcher.
He added that Stevens is primarily a two-pitch pitcher.
"In the last two years, we've seen semblance, a fiddling around with the changeup but not a lot," Wilken said. "It's been basically fastball, curveball. At times, he seems to dabble in a pitch that you might want to call a slurve-slider, but the curveball is his pitch and he's got power to it. Whereas I think he had more of a slurve-slider before, he's kind of tightened it up and throws it pretty hard velocity-wise.
"It's anywhere from 82 to 86 (mph), and a lot of people say, 'Well, that can't be a curveball.' Yeah, it can, but some people, even though it's got a curveball break, will refuse to call it one because of the hardness of the velocity. Stan, who is
Re: Thanks...
Ridiculous! I hope I get to see him pitch, if for no other reason to see this 82 MPH curve. Cue up comparisons to Ben Sheet's curveball.
Re: To Arms; To Arms - The I-Cubs Are Coming!
I hope the Cubs get serious about the bullpen. The Cubs need to win some close and come-from-behind games and they can't do that if the bullpen is giving up runs like they're Mexico.
I have no idea what that means, but it sounds raunchy and borderline xenophobic, so I thought it was cool. Yay me.
F'real though... and let's hope we're seeing the start of Bradley's bat warming up, because he's going to have to step it up with our big bats gone (Zambrano & Ramirez). Go Cubs!
Re: To Arms; To Arms - The I-Cubs Are Coming!
Neal Cotts = Montezuma's Revenge?
Re: To Arms; To Arms - The I-Cubs Are Coming!
Yeah, Bradley has the signs of coming out of his year long slump (6 for his last 20 - .300), but the Cubs will need more than even his hot bat to keep pace. With no ARam and Lee MIA, Soriano, K-Fuk, Bradley and Soto are going to need to carry the load. There is just not much room for error with the healthy players on the roster right now.
Re: To Arms; To Arms - The I-Cubs Are Coming!
Mike --
Nice job! Very well done.
Re: To Arms; To Arms - The I-Cubs Are Coming!
Mike W: 23-year old RHRP Blake Parker (2006 16th round pick out of U. of Arkansas) has been moved up from AA Tennessee and will be replacing Jose Ascanio on the I-Cubs roster.
Once a power-hitting C-3B-1B-DH, Parker was converted to pitcher at Fitch Park just about exactly two years ago, and he has developed into a fine righty reliever. At the time he made the move to pitcher, he was the EXST Cubs clean-up hitter and #1 run-producer, but one of the Cubs pitching coaches (I believe it was Tom Pratt) saw Parker fooling around throwing off the mound after an EXST game, and the very next day Parker was a pitcher and he hasn't looked back. I remember the other guys at EXST at that time were shocked to see their former clean-up hitter suddenly throwing off the mound, but obviously the Cubs knew what they were doing.
It's interesting that the Cubs have decided to slide Gregory Reinhard into the starting rotation (at least temporarily), since Jesse Estrada was in the I-Cubs starting rotation right up until the end of minor league camp, while Reinhard was primed to work out of the pen.
Reinhard pitched great in minor league camp, getting good results throwing his fastball-slider-splitter combo (while junking his old slider & straight change), and I'll bet his not getting an NRI to ST (getting squeezed out by Esmailin Caridad, Rocky Roquet, J. R. Mathes, and Brian Schlitter) hurts Reinhard's chances to get a call-up now because Piniella & Rothschild haven't seen him throw, and familiarity from Spring Training does make a difference when the brain-trust decides who gets called up to the big club, especially early in the season. But Reinhard should get a shot before too long. He is a definite big league relief prospect, especially if he can throw strikes with his slider and get swings & misses with his splitter.
Reinhard is eligible for the Rule 5 Draft post-2009, so he will get added to the Cubs 40-man roster sometime this year. It's only a matter of when.
Same goes for LHRP John Gaub, presently at AA Tennessee. Gaub has a mid-90's fastball/power-slider combo that works great against LH hitters, and so he would project as a LOOGY in the big leagues. Unfortunately, guys like Gaub aren't used that way in the minors (they usually just pitch innings, regardless of who the hitters are), so Gaub hasn't had a chance (yet) to be used the way he will eventually be used in the big leagues. But with his history of shoulder problems that goes back to his college days, facing one or two hitters per outing would seem to be the perfect mission for him, since his shoulder doesn't bounce back right away when he throws too many pitches per outing.
If the Cubs want to give Gaub a shot as a LOOGY for a week or two at some point and then find that they need to option him back to the minors, it wouldn't have a negative impact on Gaub's option years because (as of now) he is eligible for four minor league options (he has completed only one "full season" through the 2008 season).
Re: To Arms; To Arms - The I-Cubs Are Coming!
Don't tell Lou that Blake Parker used to be a clean-up hitter. If he finds out he might be the #2 PH off the bench after Z. :)
Re: To Arms; To Arms - The I-Cubs Are Coming!
Thanks for input, Phil. The Reinhard's newfound success is associated with replacing a change with a splitter, and an inferior slider with a revised slider, that helps to explain his success.
I'd assumed he was a minor-league roster filler who happened to have a good month; your comments suggesting that he's definitely a big-league prospect are very encouraging.
Usually I associate slider/splitter guys as groundball pitchers. That is definitely not his profile, he's been a strong flyball pitcher both this year and last.
Wrigley Field
An article on ESPN.com about Wrigley Field. Not bad, or at least as bad as one would expect from ESPN. Al Yellon gets some pub.
Looks like the trend of kids being named Addison Clark is growing pretty good now. I named one of my twin girls born in December: Addison Clark Scott.
Re: To Arms; To Arms - The I-Cubs Are Coming!
Really interesting stuff, Mike, thanks. A question and some comments.
Q: Did Reinhard's name come up at all? With 1 run and 26K/5BB in 18 innings, those are some notable numbers. (Especially for a guy who's never been that good previously.) Did Mason mention him, or give any indication whether he's a prospect or not?
Some comments on things that surprised me:
1. The notes that Ascanio is a 4-pitch guy. He's been criticized for being too fastball-reliant in past.
2. The comment that Stevens is a 1-pitch guy and is behind hart on the foodchain. Given that Hart has allowed 11 earned runs in 13 innings (less innings than Stevens), that seems rather puzzling. Hart's didn't all come in one game, either; he's been scored on in each of his last three games and in 6 of 12 appearances. I know he can throw fast, but clearly whatever he's throwing for his 2nd-etc. pitches isn't doing much either. As for Stevens, your point is well taken, maybe Stevens is too stubborn to do what he's told and is just succeeding on his fastball, and until he mixes in a second pitch Mason won't support him. I wouldn't have a problem with that. My guess is that Stevens is probably fighting with his breaking ball. He's walked 7 guys in 14 innings, that doesn't seem like the profile for a guy who's all fastball. More like a scenario where a guy is struggling with his breaking pitch, but having success with his fastball, so for now he's really relying on the fastball. Disappointing feedback, whatever. Either it means that mason is a goofball, or else that Stevens has problems . We've seen plenty of Hart and we know Hart has command/location/deception problems; so if Mason views Stevens as an even lesser prospect than Hart, it follows that we probably shouldn't be too excited about Stevens either.
3. The other surprise is the Samardz comment. In past they always talked about him refining his slider, and working on his change. And of course he has the splitter. Talk about teaching him a curve, in addition to needing to come up with a 2nd pitch, that suggests that they are really giving up on his slider. Curves are normally much harder to control than sliders, of course. So I admit I'm not very encouraged that apparently the slider and change look so hopeless and they are starting over with the curve.
Re: To Arms; To Arms - The I-Cubs Are Coming!
I don't understand the Orgin-I-zations insistance on Samjay being a Starter?
Clearly he throws hard and his slider has its moments. Put the kid in the bullpen and let him try to be the best short reliever he can be.
The odds of him learning 2 new MLB quality pitches at age 24 seem alot longer, than the odds that the Cubs coaches end up ruining his arm/confidence and turning him into Chadd Blasko.
Re: To Arms; To Arms - The I-Cubs Are Coming!
Yes, curves are harder to control than sliders, but unless you're Carlos Marmol, Brad Lidge, or Felix Hernandez, they're also harder to hit if you are able to control it.
His slider isn't very good. It's just not. It's got no vertical movement on it whatsoever more often than not.
I imagine he's played around with a curve at some juncture, he probably just wasn't really happy with the results. Maybe if he can get one of the minor league coaches to work with him on it, it'll come around for him. I think it would suit him nicely to have a nice 80-82 power curve to go with the splitty, honestly.
Re: To Arms; To Arms - The I-Cubs Are Coming!
Good points. Certainly true that curves are harder to hit, and that his slider has been quite bad. During the brief period where he was good last year, was his slider working then? Or was that totally fastball/splitter?
If he could come up with a good curve, obviously that would be great.
I guess I'm thinking that if he hasn't made any progress in 4 years with the easier slider, how likely is it that he'll end up with a servicable curve within 4 years, much less four months?
And where is he going to practice it? Last year he'd been fairly lousy for a couple of years, then one good month and Hendry called him up. This year he was fairly lousy all spring, but two effective outings at Iowa and Hendry called him up. I guess I'm thinking that if you're going to come up with a curve that you'll trust and be able to throw for strikes effectively in the majors, that takes some time. Not sure he'll get that time.
Re: To Arms; To Arms - The I-Cubs Are Coming!
I don't recall him ever throwing a good slider. But he can move that fastball around. Throws the straight 4 seamer. Seen a 2 seamer that runs in to righties and maybe even a few cutters that run away. He's obviously got the splitfinger to go with it.
As far as learning new pitches goes, you've obviously got your bullpen sessions on your side day to iron that stuff out. You've just got to get it to serviceable down there before you pull it out in a game. Work the grip out, work the different arm angle out, and work the timing out with your wrist and elbow on the release and then you can start throwing it to hitters. I'd say it'd be a couple more appearances before we see him use a curve in a game, if that's what they're going to do.
Remember that every type of pitch is different. Your grip, mechanics, and even something like finger length all impact different types of pitches in a different way. Just because he can't throw a good slider doesn't mean he can't throw a different pitch well. Just because he's battled with trying to learn a GOOD slider doesn't mean he won't learn a good curve, either. It also doesn't mean that it'll take him 4 years to do it.
On the other hand, he may not ever learn a good curve, and he may not ever learn a good 3rd pitch to go with his asssortment of fastballs. We won't know until he tries.
Re: To Arms; To Arms - The I-Cubs Are Coming!
Cubs minor league roster moves: RHRP Blake Parker and 3B-1B Kyle Reynolds move up to Iowa from Tennessee, and RHRP David Cales (Daytona's closer) and 1B Russ Canzler move up to Tennessee from Daytona. Cales is the third Cubs pitcher selected in the 2008 June draft to get promoted to AA (Jay Jackson and Casey Coleman are the other two).
And no word yet on whether Daytona outfielders Tyler Colvin and/or Tony Campana (both sustained concussions in an outfield collision Saturday and were removed via ambulance to a local hospital) will be going on the DL. Campana was apparently knocked unconcious. Colvin (November 2008 TJS) has started playing outfield at Daytona and will likely get a promotion to Tennessee before too long, presuming he has no lasting ill effects from the concussion.
Thanks Phil...I am very excited about Cales
He is a native Chicagoan and played high school ball at Mt. Carmel, where a close friend of mine coaches. Coach stated that Cales slider is incredible and, while he has coached a first round draft pick and multiple players drafted in the early rounds, he expects Cales to be the first to reach the majors (Cales was drafted in about the 20th round, I believe). He has been dominant so far this year and it is great he is moving up (even if only temporarily) to AA ball.
Re: To Arms; To Arms - The I-Cubs Are Coming!
Thanks for the info, Phil. The Campana/Colvin collision sounds brutal. I hope they are ok.
And...Kyle Reynolds to AAA? Has batting line is deadly (after a terrible season last year at AA). Is he being sent up there specifically to work with Von Joshua?
And I am excited about Cales, am glad he's moving up.
Re: To Arms; To Arms - The I-Cubs Are Coming!
If Reynolds is solid at third, that may explain the promotion.
After all, is any of the following adept at playing third-- Fontenot, Miles, Scales, Freel, K. Hill?
You can't replace Aramis's bat, but a defensive upgrade would be nice.
Re: To Arms; To Arms - The I-Cubs Are Coming!
Outstanding, Mike. Neither the S-T nor the Trib has even scratched the surface of what you've addressed in such depth here.
Mason's comment that Ascanio "has passed Atkins" is remarkably frank. Mason will probably have to be schooled in the art of equivocation if he gets a job at the Major League level.
Again, wonderful post.
Re: To Arms; To Arms - The I-Cubs Are Coming!
Great article, Mike! Keep cornering those coach/management types.
Re: To Arms; To Arms - The I-Cubs Are Coming!
"if for no other reason to see this 82 MPH curve. Cue up comparisons to Ben Sheet's curveball"
How about the infamous "Eephus" pitch? Always loved when Bill Lee served that one up.
Re: To Arms; To Arms - The I-Cubs Are Coming!
"Matt Murton is hitting .411 at Colorado Springs. Sometimes we take our stats with a grain of salt in the PCL..."
Murton's up with the Rockies now.
Re: To Arms; To Arms - The I-Cubs Are Coming!
I still say the dude can hit. But he's like 50 now, right?
Lee avoids the DL
The Cubs say they got good news on Sunday's MRI of first baseman Derrek Lee's neck. Lee is said to be significantly improved and that he did not need an injection. Lee has a bulging disc, which is causing the neck to spasm. The MRI confirmed nothing worse, according to the Cubs, who added Lee was in no danger of serious problems.
Re: Lee avoids the DL
Is this good news or bad news? I'm not comfortable with Hoffpauir getting knocked out of the lineup till the league figures him out.
Re: To Arms; To Arms - The I-Cubs Are Coming!
On other blogs I've been sort of ranting about the demise of newspapers and "where are those RSS news feeds gonna come from and who's gonna research and pay for finding out when city hall is corrupt and tell us the governor is a low life squeem boy??" blah blah.
But this fucking site is my main source of Cubs news. Not just for the flash so and so got traded that you get in the comments but for the detail in Wellman's, The Doctor's, and AZ Phil's reports.
Unbelievable shit, dudes.
Re: To Arms; To Arms - The I-Cubs Are Coming!
"Unbelievable shit, dudes."
Recent comments
trevor clifton (high-A) could be interesting in a couple seasons...could even become a high/middle rotation guy. he's got a lot of pluses in his pitching except control.
eric leal's (high-A) progression through the minors should be worth watching even if only projects to be an mid/end-rotation starter.
we also gotta keep a long-distance eye on guys like jose paulino (ss-A) and preston morrison (A).
As Johnny Bach used to say when it was time for the MJ Bulls to crank up the defensive pressure: "Release the Dobermans!", and Jordan, Pippen, Rodman and Harper would just suffocate the other team.
I'd love to add Carl Jr. to that group - he's got the stuff.
Historically, the Moneyball guys have been great at identifying productive hitters. Not so much with pitchers.
Wow - Pierce Johnson with an ERA of 8.01 in 42IP!
What a stud prospect! Must be pitching with a pierced johnson.
Looks like Ryan Williams is the only legit prospect there. That is sad...
Well it would seem that's all they need now. "Stropy" can have his moments, but he's been more consistent post-asg.
Take THAT, Cardinals -- you beat Fernandez, we beat Sale.
I really like Lackey as a 6-inning pitcher.
Three amigos? Because the Dominican, the Venezuelan, and the Cuban?
Maybe the three-headed dragon?
Who says Contreras can't frame? Stone cold robbery of Eaton with that called third strike for the first out in the eighth
Three amigos time?
he should hit more of those. that would be an ideal outcome. /moneyballs
Russell with 19 RBI in July so far. Grand Slams help.
...and Familia with back-to-back blown saves. Blows a one-run lead vs. Rockies today, gets his 2nd consecutive loss.
I am OK with the Mets missing the playoffs and suffering crushing losses at home --- just want them to beat St. Louis.
He played with fire twice agains the Cubs -- unfortunately, the Cubs couldn't stop swinging.
How about Kyle Farnsworth? I know he was consistently upper 90s.
If he puts up Soriano numbers I will be ecstatic
I think Javy is learning--but he's learning to make contact, not learning to lay off pitches out of the zone. A quick glance at his plate discipline numbers on Fangraphs shows that his contact rate is up, especially his contact rate out of the zone, but his swing rate is up too, especially his swing rate out of the zone.
I definitely saw ballpark radar guns go up to 102 on Kerry Wood back when he was still a starter, but who knows how accurate they were.


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Utah Jazz instant analysis: Gordon Hayward was the best player on the court in big win over Miami
Tom Smart, Deseret News
LeBron James is considered by many the best player in the NBA. Down the stretch Monday, though, Gordon Hayward was the best player on the court. Behind the third-year swingman's clutch play, the Utah Jazz clung on to a tenuous lead to defeat the NBA champion Miami Heat, 104-97.
A determined Utah team came out and imposed its will on the Heat. It grabbed an early edge and slowly but surely built it up to a 15-point halftime lead. At one point, the Jazz were up by 21 points. Miami made a furious, defense-driven comeback, cutting the Jazz's advantage down to two points late in the game. Ultimately, however, the Jazz made the plays they needed on both ends to hold on to the win.
Al Jefferson once against led the Utah attack, scoring 23 points. James did his thing, scoring 32 points of his own.
Hayward's Heroics: It is evident that Hayward is and will continue to be one of Utah's cornerstones. As the Jazz near the halfway point of this long NBA season, Hayward's continual improvement has proved integral for the now 21-19 team.
Hayward had a smooth stretch in the first half where he quickly put 10 points up on the board. But it was his second-half dramatics that stood out. During a particularly potent Miami run, Hayward smoothly canned a 3-pointer that temporarily stemmed the tide. But no shot was bigger than his step-back jumper with 40 seconds remaining, the shot that proved to be the dagger in Miami's side. And while he nailed some big, tough jumpers, Hayward was defensively able to stick with Miami guard Ray Allen down the stretch.
Odds n' Ends:
-- Utah's bench was a major factor for the Jazz, especially in an animated and spirited first half. The Jazz's bench players struggled in the fourth quarter, as they were pitted against many of Miami's starters. When it was said and done, though, they bested their counterparts by scoring 45 to the Heat's 26.
-- Eight of the 11 Utah players who saw court time registered two or more assists.
-- Miami actually had more assists (25) than rebounds (23).
-- In an odd exchange, a front-row fan and Miami star Dwyane Wade seemingly exchanged some words, with the former eventually being escorted out of the game.
-- The Heat had six players reach double-digit scoring, albeit in a losing cause.
David Smith provides instant analysis for Deseret News' Utah Jazz coverage. He works for LDS Philanthropies and also blogs for the Utah Jazz 360 website. He can be reached at firstname.lastname@example.com or on Twitter at davidjsmith1232.
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The Ernie Farm Train features Ernie from Sesame Street riding around in a train with images of animals on the side. Ernie is the conductor, and he's transporting a pig in a rail car. Kids can hear more than 30 sound effects, songs, and Ernie phrases when they push down on Ernie's head. This toy is compatible with the Elmo Junction 2-in-1 Car & Train Set, which is sold separately.
This is a cute toy for kids who love animals and Sesame Street. Little ones will love rolling the Ernie Farm Train all around and imagining all sorts of farm adventures.
The Ernie Farm Train is for Sesame Street fans ages 18 months–4 years.
Two AAA batteries are included for the in-store try-me purposes. It's recommended that you replace them before you play for best results. The toy also comes packaged in try-me mode, so make sure you flip the switch from "try-me" to "on" to activate the toy's full features.
2 AAA batteries required
LeapFrog Scout's Count & Colors Band
from LeapFrog
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from Hasbro
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from Hasbro
Nano Junior
from Hexbug
Cuddle Bots Betty Bumble Bee
from Hexbug
Bob the Builder Mash and Mold Construction Site
from Fisher-Price
The Lion Guard Deluxe Figure Set
from Just Play
Melody the Musical Turtle
from LeapFrog
Fridge Numbers Magnetic Number Set
from LeapFrog
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from Little Passports


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This item sold on December 12, 2012.
Excluding the watch face, all materials are from recycled bridal materials. The watch hardware measures 1 and 1/2'' by 1''. This is a wrap around watch that measures 22'' in total length. I HIGHLY encourage you to use a tape measure to wrap around your wrist to make sure this will fit your properly. The trick with finding your correct strap length is to measure the circumference of your wrist, multiply that by three, and add three inches. For example: My wrist is 6" X 3= 18+ 3+=21" This style of watch is so wonderful because it seems to meld to your arm. I am not a fan of the watch, but if you have to keep your eye on the time, also keep in on peaceful abiding, hope in your dreams, and love in your heart. Please convo me if you need a custom size made!
Green Recycled leather Wrap Watch
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