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Here, we report the genome assembly and annotation of two clinical isolates of Naegleria fowleri from primary amebic meningoencephalitis cases in Costa Rica in 2020 using Illumina sequencing. Each assembly comprised 37 reference-guided scaffolds, with genome sizes of approximately 28 Mbp and a GC content of 36.87%.
Background/Objectives: Microbial biotransformation of monoterpenoids is a promising approach for obtaining bioactive compounds. Rhodococcus species are attractive biocatalysts due to their metabolic versatility and ability to transform hydrophobic substrates. In this study, we investigated the catalytic potential of Rhodococcus qingshengii IEGM 267 toward carveol isomers and explored genomic features that may underlie this activity. Methods: The strain was cultivated in mineral medium supplemented with (-)-trans-carveol. Biotransformation products were analyzed by TLC and GC-MS. The draft genome was sequenced, assembled, taxonomically assigned, and annotated using standard bioinformatics tools. Results: Rhodococcus qingshengii IEGM 267 efficiently converted (-)-trans-carveol to carvone. Genome analysis confirmed the taxonomic assignment of the strain and revealed a large repertoire of oxidoreductases, including monooxygenases, hydroxylases, and dehydrogenases. Seven genes encoding cytochrome P450-dependent oxygenases were identified as candidate enzymes potentially involved in carveol oxidation. Conclusions: R. qingshengii IEGM 267 is an efficient and stereoselective biocatalyst for (-)-trans-carveol oxidation. The results of bioinformatics analysis suggest an alternative enzymatic basis for this transformation and provide a foundation for future functional characterization.
We present a comprehensive bibliography of books aimed to help physicians, other health care providers, and parents prepare children for medical contacts. Publications have been annotated and rated on the basis of use and cost. We propose that this will be a useful reference for those responsible for the health care of the pediatric population.
An annotated translation into English of Chapter 11, Book One, "On the Teeth, Which Are Also Counted as Bones," from Andreas Vesalius' De humani corporis fabrica. The translation incorporates the text of both the 1543 and 1555 editions, and verified citations of ancient sources. In this chapter, Vesalius corrects errors of Galen and demonstrates and describes for the first time the anatomy and function of the dental pulp cavity.
The term "secretome" has been defined as a set of secreted proteins (Grimmond et al. [2003] Genome Res 13:1350-1359). The term "secreted protein" encompasses all proteins exported from the cell including growth factors, extracellular proteinases, morphogens, and extracellular matrix molecules. Defining the genes encoding secreted proteins that change in expression during organogenesis, the dynamic secretome, is likely to point to key drivers of morphogenesis. Such secreted proteins are involved in the reciprocal interactions between the ureteric bud (UB) and the metanephric mesenchyme (MM) that occur during organogenesis of the metanephros. Some key metanephric secreted proteins have been identified, but many remain to be determined. In this study, microarray expression profiling of E10.5, E11.5, and E13.5 kidney and consensus bioinformatic analysis were used to define a dynamic secretome of early metanephric development. In situ hybridisation was used to confirm microarray results and clarify spatial expression patterns for these genes. Forty-one secreted factors were dynamically expressed between the E10.5 and E13.5 timeframe profiled, and 25 of these factors had not previously been implicated in kidney development. A text-based anatomical ontology was used to spatially annotate the expression pattern of these genes in cultured metanephric explants.
To facilitate genetic screens to identify and maintain recessive mutations that map to the short arm of human chromosome 1, we have utilized chromosome engineering to generate two mouse strains that carry large inversions on the distal region of mouse chromosome 4. The inversion intervals are 16 and 22 cM in size together they cover approximately half of chromosome 4. Since recombination between the wild-type and inversion chromosomes does not occur within these inversion intervals, mutant alleles of genes mapping to this region can be identified and maintained. Therefore, these inversion chromosomes work as balancer chromosomes. These inversions have the additional advantage that they are tagged with genes encoding the visible coat color markers tyrosinase and agouti, and therefore the dosage of the inversion chromosome (+/+, Inv/+, Inv/Inv) can be visually recognized. These inversion strains will be extremely useful for mutagenesis screens that focus on functional annotation of human chromosome 1p.
The E48 antigen is a successfully explored molecular marker for the diagnosis and therapy of HNSCC. The applicability of E48 as an HNSCC-associated antigen, however, is restricted due to its heterogeneous expression in 30% of tumors; and identification of additional target antigens is therefore desired. E48 belongs to the Ly-6 antigen family, comprising a group of highly homologous, low m.w., GPI-anchored surface proteins, of which some show tissue-restricted expression patterns. To identify novel human HNSCC-associated Ly-6 members with squamous cell-associated expression patterns, we performed comprehensive gene-screening consisting of BLAST searches within GenBank databases, followed by expression analysis. Using this approach, the Ly-6K gene could be annotated as a novel member of the human Ly-6 family. Expression of the human Ly-6 genes E48, Ly-6K, PSCA, GML, RIG-E, G6C and Ly-6H was prescreened by qualitative RT-PCR and subsequently analyzed by quantitative RT-PCR in normal keratinocytes, HNSCC cell lines, normal mucosa, HNSCC tumors as well as normal peripheral blood and bone marrow cells. PSCA was highly expressed in normal mucosa, but 100-fold decreased expression was seen in HNSCC. For Ly-6H, GML and G6C, no or very low expression was observed in keratinocytes and HNSCC. Expression of RIG-E was high in normal and malignant squamous cells and in peripheral blood and bone marrow cells, thus limiting its applicability as an HNSCC-associated marker. In contrast, besides the E48 gene, the Ly-6K gene also appeared to be selectively expressed in HNSCC and normal squamous cells. Moreover, expression of Ly-6K was shown in HNSCC cell lines, in which no E48 expression could be detected. These data justify further evaluation of Ly-6K as potential target antigen for the diagnosis and therapy of HNSCC.
The halophilic archaeon Halobacterium salinarum (strain R1, DSM 671) contains 2784 protein-coding genes as derived from the genome sequence. The cytosolic proteome containing 2042 proteins was separated by two-dimensional gel electrophoresis (2-DE) and systematically analyzed by a semi-automatic procedure. A reference map was established taking into account the narrow isoelectric point (pI) distribution of halophilic proteins between 3.5 and 5.5. Proteins were separated on overlapping gels covering the essential areas of pI and molecular weight. Every silver-stained spot was analyzed resulting in 661 identified proteins out of about 1800 different protein spots using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) peptide mass fingerprinting (PMF). There were 94 proteins that were found in multiple spots, indicating post-translational modification. An additional 141 soluble proteins were identified on 2-D gels not corresponding to the reference map. Thus about 40% of the cytosolic proteome was identified. In addition to the 2784 protein-coding genes, the H. salinarum genome contains more than 6000 spurious open reading frames longer than 100 codons. Proteomic information permitted an improvement in genome annotation by validating and correcting gene assignments. The correlation between theoretical pI and gel position is exceedingly good and was used as a tool to improve start codon assignments. The fraction of identified chromosomal proteins was much higher than that of those encoded on the plasmids. In combination with analysis of the GC content this observation permitted an unambiguous identification of an episomal insert of 60 kbp ("AT-rich island") in the chromosome, as well as a 70 kbp region from the chromosome that has integrated into one of the megaplasmids and carries a series of essential genes. About 63% of the chromosomally encoded proteins larger than 25 kDa were identified, proving the efficacy of 2-DE MALDI-TOF MS PMF technology. The analysis of the integral membrane proteome by tandem mass spectrometric techniques added another 141 identified proteins not identified by the 2-DE approach (see following paper).
The HUPO Brain Proteome Project is an initiative coordinating proteomics studies to characterise human and mouse brain proteomes. Proteins identified in human brain samples during the project's pilot phase were put into biological context through integration with various annotation sources followed by a bioinformatics analysis. The data set was related to the genome sequence via the genes encoding identified proteins including an assessment of splice variant identification as well as an analysis of tissue specificity of the respective transcripts. Proteins were furthermore categorised according to subcellular localisation, molecular function and biological process, grouped into protein families and mapped to biological pathways they are known to act in. Involvement in pathological conditions was examined based on association with entries in the online version of Mendelian Inheritance in Man and an interaction network was derived from curated protein-proteininteraction data. Overall a non-redundant set of 1804 proteins was identified in human brain samples. In the majority of cases splice variants could be unambiguously identified by unique peptides, including matches to several hypothetical transcripts of known as well as predicted genes.
Limitations in techniques for the elucidation of protein function have led to an increasing gap between the annotated proteins and those encoded in a genome. The functional selection and three-dimensional structural constraints of proteins in nature often relate to the retention of significant sequence similarity between proteins of similar fold and function despite poor sequence identity. We identify spatially interacting conserved regions, or motifs, within protein superfamilies that are critical for structure and/or function. A search in sequence databases using these descriptors as additional constraints is an approach to identifying putative additional members of superfamilies. Such constrained searches have been tested against proteins of known structure to demonstrate high percentage specificity (93) with a low error rate of 0.0004. This approach has been compared with other sensitive sequence search methods (e.g., PSI-BLAST, HMMsearch, and IMPALA). It has been extended to analyze the distribution of 11 superfamilies in 93 genomes, including the human genome.
Single-point mutations are one of the most frequent causes of genetic variability in both human and close species. The recent availability of different bioinformatics tools for annotating human single nucleotide polymorphisms (SNPs) has opened the possibility of using them to score SNPs from species with a biomedical interest, in particular from mice and other models of human disease. Also, this ability to predict pathogenicity of single point mutations in one species, based on data from another species, opens the possibility to predict the pathological character of single point mutations in humans using data from well-characterized model systems of human disease. This could provide a valuable alternative to the more traditional genetic population approaches. However, transferral of prediction tools may be limited by different factors, from a species bias in the training set, to a large sequence divergence between the proteomes of the training and the target species. Here we study the conditions under which prediction tools can be transferred among species, concentrating in the case of mice. We find that for the majority of the human-mouse homolog pairs, the sequence similarity is large enough to preserve the pathological character of mutations among species, in general. We then establish that prediction/annotation tools developed for one organism can be used to predict the neutral/pathological character of mutations/SNPs in the other organism.
This paper provides an annotated bibliography of over 100 articles concerning methods for analysing correlated categorical response data. Most of the papers listed here concern categorical regression models and estimation, with particular emphasis on binary responses. The papers are classified by several characteristics which group them according to common themes. The bibliography serves as a reference of methods for analysts of correlated categorical data, as well as for persons interested in methodologic work in this active area of statistical research.
Changes in the expression of genes were used to elucidate the metabolic pathways and regulatory mechanisms that respond to environmental or genetic modifications. Results from previously published chemostat datasets were merged with novel data generated in the present study. ORFs displaying significant changes in expression that correlated with those of other ORFs were analysed using GO mapping tools and supplemented by literature information. The strategy developed was used to propose annotations for ORFs of unknown function. The following ORFs were assigned functions as a result of this study: YMR090w, YGL157w, YGR243w, YLR327c, YER121w, YFR017c, YGR067c, YKL187c, YGR236c (SPG1), YMR107w (SPG4), YMR206w, YER067w, YJL103c, YNL175C (NOP13) YJL200C, YDL070C (FMP16) and YGR173W.
Distal mouse chromosome 16 (MMU16) shares conserved linkage with human chromosome 21 (HSA21), trisomy for which causes Down syndrome (DS). A 4.5-Mb physical map extending from Cbr1 to Tmprss2 on MMU16 provides a minimal tiling path of P1 artificial chromosomes (PACs) for comparative mapping and genomic sequencing. Thirty-four expressed sequences were positioned on the mouse map, including 19 that were not physically mapped previously. This region of the mouse:human comparative map shows a high degree of evolutionary conservation of gene order and content, which differs only by insertion of one gene (in mouse) and a small inversion involving two adjacent genes. "Low-pass" (2.2x) mouse sequence from a portion of the contig was ordered and oriented along 510 kb of finished HSA21 sequence. In combination with 68 kb of unique PAC end sequence, the comparison provided confirmation of genes predicted by comparative mapping, indicated gene predictions that are likely to be incorrect, and identified three candidate genes in mouse and human that were not observed in the initial HSA21 sequence annotation. This comparative map and sequence derived from it are powerful tools for identifying genes and regulatory regions, information that will in turn provide insights into the genetic mechanisms by which trisomy 21 results in DS.
Human chromosome Xp11.3-Xp11.23 encompasses the map location for a growing number of diseases with a genetic basis or genetic component. These include several eye disorders, syndromic and nonsyndromic forms of X-linked mental retardation (XLMR), X-linked neuromuscular diseases and susceptibility loci for schizophrenia, type 1 diabetes, and Graves' disease. We have constructed an approximately 2.7-Mb high-resolution physical map extending from DXS8026 to ELK1, corresponding to a genetic distance of approximately 5.5 cM. A combination of chromosome walking and sequence-tagged site (STS)-content mapping resulted in an integrated framework and transcript map, precisely positioning 10 polymorphic microsatellites (one of which is novel), 16 ESTs, and 12 known genes (RP2, PCTK1, UHX1, UBE1, RBM10, ZNF157, SYN1, ARAF1, TIMP1, PFC, ELK1, UXT). The composite map is currently anchored with 89 STSs to give an average resolution of approximately 1 STS every 30 kb. By a combination of EST database searches and in silico detection of UniGene clusters within genomic sequence generated from this template map, we have mapped several novel genes within this interval: a Na+/H+ exchanger (SLC9A7), at least two zincfinger transcription factors (KIAA0215 and Hs.68318), carbohydrate sulfotransferase-7 (CHST7), regucalcin (RGN), inactivation-escape-1 (INE1), the human ortholog of mouse neuronal protein 15.6, and four putative novel genes. Further genomic analysis enabled annotation of the sequence interval with 20 predicted pseudogenes and 21 UniGene clusters of unknown function. The combined PAC/BAC transcript map and YAC scaffold presented here clarifies previously conflicting data for markers and genes within the Xp11.3-Xp11.23 interval and provides a powerful integrated resource for functional characterization of this clonally unstable, yet gene-rich and clinically significant region of proximal Xp.
OBJECTIVE: The teaching of procedures that involve risk of pain or morbidity deserves special care. The author set out to develop a teaching program for medical students to ensure quality control of bedside diagnostic and therapeutic procedures. DESIGN: A bibliography of available videotapes and related audiovisual teaching materials on 15 common bedside procedures was assembled following requests for materials from all U.S. medical schools. Audiovisual materials from nine institutions were reviewed. SETTING: Medical schools and teaching institutions. PARTICIPANTS: Medical schools and libraries. MAIN RESULTS: Seventy-three percent (24/33) of responding schools had no visual material on the procedures. There was ten times more material on physical diagnosis than on bedside procedures. About 20 videotapes were reviewed in an annotated bibliography. Some videos contained valuable insights on how to make good teaching materials. A set of criteria for quality videotapes is listed. CONCLUSIONS: Considerable work needs to be done to develop audiovisual materials and curricula for teaching bedside procedures. Videotape is a valuable medium for introducing procedures and ensuring uniformity of technique. After reviewing all available videotapes, the author decided that videotapes should be the initial part of a multidimensional program for teaching procedures.
Recent advances in proteomics have provided impetus towards the development of robust technologies for high-throughput studies of enzymes. The term "catalomics" defines an emerging '-omics' field in which high-throughput studies of enzymes are carried out by using advanced chemical proteomics approaches. Of the various available methods, microarrays have emerged as a powerful and versatile platform to accelerate not only the functional annotation but also the substrate and inhibitor specificity (e.g. substrate and inhibitor fingerprinting, respectively) of enzymes. Herein, we review recent developments in the fabrication of various types of microarray technologies (protein-, peptide- and small-molecule-based microarrays) and their applications in high-throughput characterizations of enzymes.
The type I MADS-box genes constitute a largely unexplored subfamily of the extensively studied MADS-box gene family, well known for its role in flower development. Genes of the type I MADS-box subfamily possess the characteristic MADS box but are distinguished from type II MADS-box genes by the absence of the keratin-like box. In this in silico study, we have structurally annotated all 47 members of the type I MADS-box gene family in Arabidopsis thaliana and exerted a thorough analysis of the C-terminal regions of the translated proteins. On the basis of conserved motifs in the C-terminal region, we could classify the gene family into three main groups, two of which could be further subdivided. Phylogenetic trees were inferred to study the evolutionary relationships within this large MADS-box gene subfamily. These suggest for plant type I genes a dynamic of evolution that is significantly different from the mode of both animal type I (SRF) and plant type II (MIKC-type) gene phylogeny. The presence of conserved motifs in the majority of these genes, the identification of Oryza sativa MADS-box type I homologues, and the detection of expressed sequence tags for Arabidopsis thaliana and other plant type I genes suggest that these genes are indeed of functional importance to plants. It is therefore even more intriguing that, from an experimental point of view, almost nothing is known about the function of these MADS-box type I genes.