bluuebunny/crossref_metadata_2025 huggingface dataset:
The mycobacterial mutasome: composition and recruitment in live cells
Authors: Gessner Sophia , Martin Zela , Reiche Michael A. , Santos Joana A. , Dhar Neeraj , Dinkele Ryan , De Wet Timothy , Ramudzuli Atondaho , Anoosheh Saber , Lang Dirk M. , Aaron Jesse , Chew Teng-Leong , Herrmann Jennifer , Müller Rolf , McKinney John D. , Woodgate Roger , Mizrahi Valerie , Lamers Meindert H. , Warner Digby F.
Published: November 2021

A DNA damage-inducible mutagenic gene cassette has been implicated in the emergence of drug resistance in Mycobacterium tuberculosis during anti-tuberculosis (TB) chemotherapy. However, the molecular composition and operation of the encoded “mycobacterial mutasome” – minimally comprising DnaE2 polymerase and ImuA′ and ImuB accessory proteins – remain elusive. Following exposure of mycobacteria to DNA damaging agents, we observe that DnaE2 and ImuB co-localize with the DNA polymerase III β subunit (β clamp) in distinct intracellular foci. Notably, genetic inactivation of the mutasome in an imuBAAAAGG mutant containing a disrupted β clamp-binding motif abolishes ImuB-β clamp focus formation, a phenotype recapitulated pharmacologically by treating bacilli with griselimycin and in biochemical assays in which this β clamp-binding antibiotic collapses pre-formed ImuB-β clamp complexes. These observations establish the essentiality of the ImuB-β clamp interaction for mutagenic DNA repair in mycobacteria, identifying the mutasome as target for adjunctive therapeutics designed to protect anti-TB drugs against emerging resistance.
Continuous decision to wait for a future reward is guided by fronto-hippocampal anticipatory dynamics
Authors: Shintaki Reiko , Tanaka Daiki , Suzuki Shinsuke , Yoshimoto Takaaki , Sadato Norihiro , Chikazoe Junichi , Jimura Koji
Published: November 2021

Deciding whether to wait for a future reward is crucial for acquiring rewards in an uncertain world and involves anticipating future reward attainment. While seeking for a reward in natural environments, behavioral agents constantly face a trade-off between staying in their current environment or leaving it. It remains unclear, however, how humans make continuous decisions in such situations. Here we show that anticipatory brain activity in the anterior prefrontal cortex (aPFC) and hippocampus underpins continuous stay-leave decision making. Human participants awaited for real liquid rewards available after tens of seconds, and continuous decision was tracked by monitoring dynamic patterns of brain activity. Participants stopped waiting more frequently and sooner after they experienced longer delays and received smaller rewards. When dynamic activity reflecting the anticipation of a future reward was enhanced in the aPFC, participants remained in their current environment, but when this activity diminished, they left the environment for a new one. The anticipatory activity in the aPFC and hippocampus was associated with distinct decision strategies; aPFC activity was enhanced in participants adopting a leave strategy, whereas those remaining stationary showed enhanced activity in the hippocampus. Our results suggest that fronto-hippocampal anticipatory dynamics underlie continuous decision making while anticipating a future reward.
Proteomic analysis of rice leaves following treatment of Xanthomonas oryzae pv. oryzae secreted cell wall degrading enzyme
Authors: Kumar Anirudh , Malukani Kamal Kumar , Pamidimukkala Ramya , Patel Hitendra Kumar , Sonti Ramesh V
Published: November 2021

Bacterial Blight (BB) disease caused by Xanthomonas oryzae pv. oryzae (Xoo), is one of the most devastating diseases in various rice cultivating countries. Xoo secretes a mixture of plant cell wall degrading enzymes (CWDEs) such as cellulases, lipases, xylanases, and proteases to degrade different components of the plant cell wall. LipA; a lipase/esterase, is one such Xoo secreted CWDE and is an important virulence factor of Xoo. Treatment of rice tissue with purified LipA induces immune responses. In this study, a LC-MS based proteomics study was performed to identify the differentially expressed proteins (DEPs) in rice following LipA treatment. A total of 212 proteins were identified in control and 201 proteins in LipA treated samples. There were 151 proteins common between control and treatment. Fold change analysis of these common proteins through SIEVE identified 26 upregulated and 49 downregulated proteins by at least ≥1.5 fold in the LipA treated sample. Pathway analysis indicated that many proteins related to redox regulation, photosynthesis, and translation are differentially expressed after LipA treatment. We also observed that some of the differentially expressed proteins contain translation regulatory elements that may regulate translation after LipA treatment. The comparison of proteomics data with previously performed transcriptome analysis indicated that different sets of genes and pathways are altered in both the analyses.
Estimating the Repeat Structure and Length of DNA Sequences Using ℓ-Tuples
Authors: Li Xiaoman , Waterman Michael S.
Published: November 2021

In shotgun sequencing projects, the genome or BAC length is not always known. We approach estimating genome length by first estimating the repeat structure of the genome or BAC, sometimes of interest in its own right, on the basis of a set of random reads from a genome project. Moreover, we can find the consensus for repeat families before assembly. Our methods are based on the ℓ-tuple content of the reads.
Effects of Recombination Rate and Gene Density on Transposable Element Distributions in Arabidopsis thaliana
Authors: Wright Stephen I. , Agrawal Newton , Bureau Thomas E.
Published: November 2021

Transposable elements (TEs) comprise a major component of eukaryotic genomes, and exhibit striking deviations from random distribution across the genomes studied, including humans, flies, nematodes, and plants. Although considerable progress has been made in documenting these patterns, the causes are subject to debate. Here, we use the genome sequence of Arabidopsis thaliana to test for the importance of competing models of natural selection against TE insertions. We show that, despite TE accumulation near the centromeres, recombination does not generally correlate with TE abundance, suggesting that selection against ectopic recombination does not influence TE distribution in A. thaliana. In contrast, a consistent negative correlation between gene density and TE abundance, and a strong under-representation of TE insertions in introns suggest that selection against TE disruption of gene expression is playing a more important role in A. thaliana. High rates of self-fertilization may reduce the importance of recombination rate in genome structuring in inbreeding organisms such as A. thaliana and Caenorhabditis elegans.
Two Functional Copies of the DGCR6 Gene Are Present on Human Chromosome 22q11 Due to a Duplication of an Ancestral Locus
Authors: Edelmann Lisa , Stankiewicz Pavel , Spiteri Elizabeth , Pandita Raj K. , Shaffer Lisa , Lupski James , Morrow Bernice E.
Published: November 2021

The DGCR6 (DiGeorge critical region) gene encodes a putative protein with sequence similarity to gonadal(gdl), a Drosophila melanogaster gene of unknown function. We mapped the DGCR6 gene to chromosome 22q11 within a low copy repeat, termed sc11.1a, and identified a second copy of the gene, DGCR6L, within the duplicate locus, termed sc11.1b. Both sc11.1 repeats are deleted in most persons with velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS), and they map immediately adjacent and internal to the low copy repeats, termed LCR22, that mediate the deletions associated with VCFS/DGS. We sequenced genomic clones from both loci and determined that the putative initiator methionine is located further upstream than originally described, but in a position similar to the mouse and chicken orthologs.DGCR6L encodes a highly homologous, functional copy ofDGCR6, with some base changes rendering amino acid differences. Expression studies of the two genes indicate that both genes are widely expressed in fetal and adult tissues. Evolutionary studies using FISH mapping in several different species of ape combined with sequence analysis of DGCR6 in a number of different primate species indicate that the duplication is at least 12 million years old and may date back to before the divergence of Catarrhines from Platyrrhines, 35 mya. These data suggest that there has been selective evolutionary pressure toward the functional maintenance of both paralogs. Interestingly, a full-length HERV-K provirus integrated into the sc11.1a locus after the divergence of chimpanzees and humans.
Phylogeny of the Serpin Superfamily: Implications of Patterns of Amino Acid Conservation for Structure and Function
Authors: Irving James A. , Pike Robert N. , Lesk Arthur M. , Whisstock James C.
Published: November 2021

We present a comprehensive alignment and phylogenetic analysis of the serpins, a superfamily of proteins with known members in higher animals, nematodes, insects, plants, and viruses. We analyze, compare, and classify 219 proteins representative of eight major and eight minor subfamilies, using a novel technique of consensus analysis. Patterns of sequence conservation characterize the family as a whole, with a clear relationship to the mechanism of function. Variations of these patterns within phylogenetically distinct groups can be correlated with the divergence of structure and function. The goals of this work are to provide a carefully curated alignment of serpin sequences, to describe patterns of conservation and divergence, and to derive a phylogenetic tree expressing the relationships among the members of this family. We extend earlier studies by Huber and Carrell as well as by Marshall, after whose publication the serpin family has grown functionally, taxonomically, and structurally. We used gene and protein sequence data, crystal structures, and chromosomal location where available. The results illuminate structure–function relationships in serpins, suggesting roles for conserved residues in the mechanism of conformational change. The phylogeny provides a rational evolutionary framework to classify serpins and enables identification of conserved amino acids. Patterns of conservation also provide an initial point of comparison for genes identified by the various genome projects. New homologs emerging from sequencing projects can either take their place within the current classification or, if necessary, extend it.
High-Throughput Genotyping with Single Nucleotide Polymorphisms
Authors: Ranade Koustubh , Chang Mau-Song , Ting Chih-Tai , Pei Dee , Hsiao Chin-Fu , Olivier Michael , Pesich Robert , Hebert Joan , Chen Yii-Der I. , Dzau Victor J. , Curb David , Olshen Richard , Risch Neil , Cox David R. , Botstein David
Published: November 2021

To make large-scale association studies a reality, automated high-throughput methods for genotyping with single-nucleotide polymorphisms (SNPs) are needed. We describe PCR conditions that permit the use of the TaqMan or 5′ nuclease allelic discrimination assay for typing large numbers of individuals with any SNP and computational methods that allow genotypes to be assigned automatically. To demonstrate the utility of these methods, we typed >1600 individuals for a G-to-T transversion that results in a glutamate-to-aspartate substitution at position 298 in the endothelial nitric oxide synthase gene, and a G/C polymorphism (newly identified in our laboratory) in intron 8 of the 11–β hydroxylase gene. The genotyping method is accurate—we estimate an error rate of fewer than 1 in 2000 genotypes, rapid—with five 96-well PCR machines, one fluorescent reader, and no automated pipetting, over one thousand genotypes can be generated by one person in one day, and flexible—a new SNP can be tested for association in less than one week. Indeed, large-scale genotyping has been accomplished for 23 other SNPs in 13 different genes using this method. In addition, we identified three “pseudo-SNPs” (WIAF1161, WIAF2566, and WIAF335) that are probably a result of duplication.
Whole Proteome pI Values Correlate with Subcellular Localizations of Proteins for Organisms within the Three Domains of Life
Authors: Schwartz Russell , Ting Claire S. , King Jonathan
Published: November 2021

Isoelectric point (pI) values have long been a standard measure for distinguishing between proteins. This article analyzes distributions of pI values estimated computationally for all predicted ORFs in a selection of fully sequenced genomes. Histograms of pI values confirm the bimodality that has been observed previously for bacterial and archaeal genomes (Van Bogelen et al. 1999) and reveal a trimodality in eukaryotic genomes. A similar analysis on subsets of a nonredundant protein sequence database generated from the full database by selecting on subcellular localization shows that sequences annotated as corresponding to cytosolic and integral membrane proteins have pI distributions that appear to correspond with the two observed modes of bacteria and archaea. Furthermore, nuclear proteins have a broader distribution that may account for the third mode observed in eukaryotes. On the basis of this association between pI and subcellular localization, we conclude that the bimodal character of whole proteome pI values in bacteria and archaea and the trimodal character in eukaryotes are likely to be general properties of proteomes and are associated with the need for different pI values depending on subcellular localization. Our analyses also suggest that the proportions of proteomes consisting of membrane-associated proteins may be currently underestimated.
Characterization of Clustered MHC-Linked Olfactory Receptor Genes in Human and Mouse
Authors: Younger Ruth M. , Amadou Claire , Bethel Graeme , Ehlers Anke , Lindahl Kirsten Fischer , Forbes Simon , Horton Roger , Milne Sarah , Mungall Andrew J. , Trowsdale John , Volz Armin , Ziegler Andreas , Beck Stephan
Published: November 2021

Olfactory receptor (OR) loci frequently cluster and are present on most human chromosomes. They are members of the seven transmembrane receptor (7-TM) superfamily and, as such, are part of one of the largest mammalian multigene families, with an estimated copy number of up to 1000 ORs per haploid genome. As their name implies, ORs are known to be involved in the perception of odors and possibly also in other, nonolfaction-related, functions. Here, we report the characterization of ORs that are part of the MHC-linked OR clusters in human and mouse (partial sequence only). These clusters are of particular interest because of their possible involvement in olfaction-driven mate selection. In total, we describe 50 novel OR loci (36 human, 14 murine), making the human MHC-linked cluster the largest sequenced OR cluster in any organism so far. Comparative and phylogenetic analyses confirm the cluster to be MHC-linked but divergent in both species and allow the identification of at least one ortholog that will be useful for future regulatory and functional studies. Quantitative feature analysis shows clear evidence of duplications of blocks of OR genes and reveals the entire cluster to have a genomic environment that is very different from its neighboring regions. Based on in silico transcript analysis, we also present evidence of extensive long-distance splicing in the 5′-untranslated regions and, for the first time, of alternative splicing within the single coding exon of ORs. Taken together with our previous finding that ORs are also polymorphic, the presented data indicate that the expression, function, and evolution of these interesting genes might be more complex than previously thought.

[The sequence data described in this paper have been submitted to the EMBL nucleotide data library under accession nos.Z84475, Z98744, Z98745, AL021807, AL021808, AL022723, AL022727,AL031893, AL035402, AL035542, AL050328, AL050339, AL078630, AL096770,AL121944, AL133160, and AL133267.]
A Method For Parallel, Automated, Thermal Cycling of Submicroliter Samples
Authors: Nakane Jonathan , Broemeling David , Donaldson Roger , Marziali Andre , Willis Thomas D. , O'Keefe Matthew , Davis Ronald W.
Published: November 2021

A large fraction of the cost of DNA sequencing and other DNA-analysis processes results from the reagent costs incurred during cycle sequencing or PCR. In particular, the high cost of the enzymes and dyes used in these processes often results in thermal cycling costs exceeding $0.50 per sample. In the case of high-throughput DNA sequencing, this is a significant and unnecessary expense. Improved detection efficiency of new sequencing instrumentation allows the reaction volumes for cycle sequencing to be scaled down to one-tenth of presently used volumes, resulting in at least a 10-fold decrease in the cost of this process. However, commercially available thermal cyclers and automated reaction setup devices have inherent design limitations which make handling volumes of <1 μL extremely difficult. In this paper, we describe a method for thermal cycling aimed at reliable, automated cycling of submicroliter reaction volumes.
A Comparative Map of the Zebrafish Genome
Authors: Woods Ian G. , Kelly Peter D. , Chu Felicia , Ngo-Hazelett Phuong , Yan Yi-Lin , Huang Hui , Postlethwait John H. , Talbot William S.
Published: November 2021

Zebrafish mutations define the functions of hundreds of essential genes in the vertebrate genome. To accelerate the molecular analysis of zebrafish mutations and to facilitate comparisons among the genomes of zebrafish and other vertebrates, we used a homozygous diploid meiotic mapping panel to localize polymorphisms in 691 previously unmapped genes and expressed sequence tags (ESTs). Together with earlier efforts, this work raises the total number of markers scored in the mapping panel to 2119, including 1503 genes and ESTs and 616 previously characterized simple-sequence length polymorphisms. Sequence analysis of zebrafish genes mapped in this study and in prior work identified putative human orthologs for 804 zebrafish genes and ESTs. Map comparisons revealed 139 new conserved syntenies, in which two or more genes are on the same chromosome in zebrafish and human. Although some conserved syntenies are quite large, there were changes in gene order within conserved groups, apparently reflecting the relatively frequent occurrence of inversions and other intrachromosomal rearrangements since the divergence of teleost and tetrapod ancestors. Comparative mapping also shows that there is not a one-to-one correspondence between zebrafish and human chromosomes. Mapping of duplicate gene pairs identified segments of 20 linkage groups that may have arisen during a genome duplication that occurred early in the evolution of teleosts after the divergence of teleost and mammalian ancestors. This comparative map will accelerate the molecular analysis of zebrafish mutations and enhance the understanding of the evolution of the vertebrate genome.
Lineage-Specific Gene Expansions in Bacterial and Archaeal Genomes
Authors: Jordan I. King , Makarova Kira S. , Spouge John L. , Wolf Yuri I. , Koonin Eugene V.
Published: November 2021

Gene duplication is an important mechanistic antecedent to the evolution of new genes and novel biochemical functions. In an attempt to assess the contribution of gene duplication to genome evolution in archaea and bacteria, clusters of related genes that appear to have expanded subsequent to the diversification of the major prokaryotic lineages (lineage-specific expansions) were analyzed. Analysis of 21 completely sequenced prokaryotic genomes shows that lineage-specific expansions comprise a substantial fraction (∼5%–33%) of their coding capacities. A positive correlation exists between the fraction of the genes taken up by lineage-specific expansions and the total number of genes in a genome. Consistent with the notion that lineage-specific expansions are made up of relatively recently duplicated genes, >90% of the detected clusters consists of only two to four genes. The more common smaller clusters tend to include genes with higher pairwise similarity (as reflected by average score density) than larger clusters. Regardless of size, cluster members tend to be located more closely on bacterial chromosomes than expected by chance, which could reflect a history of tandem gene duplication. In addition to the small clusters, almost all genomes also contain rare large clusters of size ≥20. Several examples of the potential adaptive significance of these large clusters are explored. The presence or absence of clusters and their related genes was used as the basis for the construction of a similarity graph for completely sequenced prokaryotic genomes. The topology of the resulting graph seems to reflect a combined effect of common ancestry, horizontal transfer, and lineage-specific gene loss.
AAA+: A Class of Chaperone-Like ATPases Associated with the Assembly, Operation, and Disassembly of Protein Complexes
Authors: Neuwald Andrew F. , Aravind L. , Spouge John L. , Koonin Eugene V.
Published: November 2021

Using a combination of computer methods for iterative database searches and multiple sequence alignment, we show that protein sequences related to the AAA family of ATPases are far more prevalent than reported previously. Among these are regulatory components of Lon and Clp proteases, proteins involved in DNA replication, recombination, and restriction (including subunits of the origin recognition complex, replication factor C proteins, MCM DNA-licensing factors and the bacterial DnaA, RuvB, and McrB proteins), prokaryotic NtrC-related transcription regulators, the Bacillus sporulation protein SpoVJ, Mg2+, and Co2+ chelatases, theHalobacterium GvpN gas vesicle synthesis protein, dynein motor proteins, TorsinA, and Rubisco activase. Alignment of these sequences, in light of the structures of the clamp loader δ′ subunit ofEscherichia coli DNA polymerase III and the hexamerization component of N-ethylmaleimide-sensitive fusion protein, provides structural and mechanistic insights into these proteins, collectively designated the AAA+ class. Whole-genome analysis indicates that this class is ancient and has undergone considerable functional divergence prior to the emergence of the major divisions of life. These proteins often perform chaperone-like functions that assist in the assembly, operation, or disassembly of protein complexes. The hexameric architecture often associated with this class can provide a hole through which DNA or RNA can be thread; this may be important for assembly or remodeling of DNA–protein complexes.
Mapping ESTs by Fiber–FISH
Authors: Horelli-Kuitunen Nina , Aaltonen Johanna , Yaspo Marie-Laure , Eeva Mervi , Wessman Maija , Peltonen Leena , Palotie Aarno
Published: November 2021

A visual transcript map of six genes was constructed on the chromosome 21q22.3 by high resolution fluorescence in situ hybridization (FISH). Expressed sequence tags (ESTs) from six genes—PWP2, KNP1, AIRE, C21orf3,SMT3A, and C21orf1—were successfully localized by fiber–FISH by use of sensitive tyramide-based detection. The sizes of the ESTs varied between 315 to 956 bp and most of them map within the 3′-untranslated region. The ESTs were assigned to and subsequently ordered within cosmid, PAC, and BAC clones hybridized on DNA fibers. Physical distances between ESTs and known markers were determined. Our results demonstrate the feasibility and accuracy of visual mapping EST sequences in relation to known markers. The main advantage of this approach is that it can be applied to finely map any of the database ESTs for positional cloning efforts. The sensitivity, specificity, and reproducibility of this high-resolution EST mapping technique is evaluated.
Identification and Characterization of a Homozygous Deletion Found in Ovarian Ascites by Representational Difference Analysis
Authors: Watson J.E. Vivienne , Gabra Hani , Taylor Karen J. , Rabiasz Genevieve J. , Morrison Harris , Perry Paul , Smyth John F. , Porteous David J.
Published: November 2021

We have performed representational difference analysis (RDA) on DNA from tumor cells and normal fibroblasts isolated from the ascites of a patient with ovarian cancer. Five of six products of the RDA were homozygously deleted from the tumor DNA. One of these products has been characterized and identifies a homozygous deletion of ∼6.9 Mb at chromosome 9p21 in the original ovarian tumor material. This deletion encompasses CDKN2A (p16), CDKN2B (p15), and IFN-α. PCR analysis of other tumor cell lines using the novel STS based on the RDA product has shown it to lie between IFN-α and p16, and to identify the distal extent of a homozygous deletion in another ovarian cancer cell line. These data provide further evidence for a tumor suppressor locus distinct from, but mapping close to, p16 on 9p21. Cytogenetic analysis using comparative genomic hybridization (CGH) performed on the same primary tumor confirmed a loss of material from chromosome 9p. However, the CGH technique had neither the resolution nor the sensitivity to define a subregion of homozygous loss.

[The GenBank accession no. for this sequence is AF113912.]
Analysis of Sequence-Tagged-Connector Strategies for DNA Sequencing
Authors: Siegel Andrew F. , Trask Barbara , Roach Jared C. , Mahairas Gregory G. , Hood Leroy , van den Engh Ger
Published: November 2021

The BAC-end sequencing, or sequence-tagged-connector (STC), approach to genome sequencing involves sequencing the ends of BAC inserts to scatter sequence tags (STCs) randomly across the genome. Once any BAC or other large segment of DNA is sequenced to completion by conventional shotgun approaches, these STC tags can be used to identify a minimum tiling path of BAC clones overlapping the nucleation sequence for sequence extension. Here, we explore the properties of STC-sequencing strategies within a mathematical model of a random target with homologous repeats and imperfect sequencing technology to understand the consequences of varying various parameters on the incidence of problem clones and the cost of the sequencing project. Problem clones are defined as clones for which either (A) there is no identifiable overlapping STC to extend the sequence in a particular direction or (B) the identified STC with minimum overlap comes from a nonoverlapping clone, either owing to random false matches or repeat-family homology. Based on the minimum overlap, we estimate the number of clones to be entirely sequenced and, then, using cost estimates, identify the decision rule (the degree of sequence similarity required before a match is declared between an STC and a clone) to minimize overall sequencing cost. A method to optimize the overlap decision rule is highly desirable, because both the total cost and the number of problem clones are shown to be highly sensitive to this choice. For a target of 3 Gb containing ∼800 Mb of repeats with 85%–90% identity, we expect <10 problem clones with 15 times coverage by 150-kb clones. We derive the optimal redundancy and insert sizes of clone libraries for sequencing genomes of various sizes, from microbial to human. We estimate that establishing the resource of STCs as a means of identifying minimally overlapping clones represents only 1%–3% of the total cost of sequencing the human genome, and, up to a point of diminishing returns, a larger STC resource is associated with a smaller total sequencing cost.
Comparative Mapping of the Region of Human Chromosome 7 Deleted in Williams Syndrome
Authors: DeSilva Udaya , Massa Hillary , Trask Barbara J. , Green Eric D.
Published: November 2021

Williams syndrome (WS) is a complex developmental disorder resulting from the deletion of a large (∼1.5–2 Mb) segment of human chromosome 7q11.23. Physical mapping studies have revealed that this deleted region, which contains a number of known genes, is flanked by several large, nearly identical blocks of DNA. The presence of such highly related DNA segments in close physical proximity to one another has hampered efforts to elucidate the precise long-range organization of this segment of chromosome 7. To gain insight about the structure and evolutionary origins of this important and complex genomic region, we have constructed a fully contiguous bacterial artificial chromosome (BAC) and P1-derived artificial chromosome (PAC) contig map encompassing the corresponding region on mouse chromosome 5. In contrast to the difficulties encountered in constructing a clone-based physical map of the human WS region, the BAC/PAC-based map of the mouse WS region was straightforward to construct, with no evidence of large duplicated segments, such as those encountered in the human WS region. To confirm this difference, representative human and mouse BACs were used as probes for performing fluorescence in situ hybridization (FISH) to metaphase and interphase chromosomes. Human BACs derived from the nonunique portion of the WS region hybridized to multiple, closely spaced regions on human chromosome 7q11.23. In contrast, corresponding mouse BACs hybridized to a single site on mouse chromosome 5. Furthermore, FISH analysis revealed the presence of duplicated segments within the WS region of various nonhuman primates (chimpanzee, gorilla, orangutan, and gibbon). Hybridization was also noted at the genomic locations corresponding to human chromosome 7p22 and 7q22 in human, chimpanzee, and gorilla, but not in the other animal species examined. Together, these results indicate that the WS region is associated with large, duplicated blocks of DNA on human chromosome 7q11.23 as well as the corresponding genomic regions of other nonhuman primates. However, such duplications are not present in the mouse.
An Automated Sample Preparation System for Large-Scale DNA Sequencing
Authors: Marziali Andre , Willis Thomas D. , Federspiel Nancy A. , Davis Ronald W.
Published: November 2021

Recent advances in DNA sequencing technologies, both in the form of high lane-density gels and automated capillary systems, will lead to an increased requirement for sample preparation systems that operate at low cost and high throughput. As part of the development of a fully automated sequencing system, we have developed an automated subsystem capable of producing 10,000 sequence-ready ssDNA templates per day from libraries of M13 plaques at a cost of $0.29 per sample. This Front End has been in high throughput operation since June, 1997 and has produced > 400,000 high-quality DNA templates.
Fluorescence Polarization in Homogeneous Nucleic Acid Analysis
Authors: Chen Xiangning , Levine Leanna , Kwok Pui-Yan
Published: November 2021

A new method for DNA diagnostics based on template-directed primer extension and detection by fluorescence polarization is described. In this method, amplified genomic DNA containing a polymorphic locus is incubated with oligonucleotide primers (designed to hybridize to the DNA template adjacent to the polymorphic site) in the presence of allele-specific dye-labeled dideoxyribonucleoside triphosphates and a commercially available modified Taq DNA polymerase. The primer is extended by the dye-terminator specific for the allele present on the template, increasing ∼10-fold the molecular weight of the fluorophore. At the end of the reaction, the fluorescence polarization of the two dye-terminators in the reaction mixture are analyzed directly without separation or purification. This homogeneous DNA diagnostic method is shown to be highly sensitive and specific and is suitable for automated genotyping of large number of samples.

[The data shown in Figure 3 are available as an online supplement at http://www.genome.org.]
Linkage Disequilibrium and Physical Mapping of Pas1 in Mice
Authors: Manenti Giacomo , Stafford Amanda , De Gregorio Laura , Gariboldi Manuela , Falvella F. Stefania , Avner Philip , Dragani Tommaso A.
Published: November 2021

By using linkage disequilibrium (LD) analysis in 21 strains of known susceptibility to lung cancer and by assembling a YAC contig, we mapped to a ∼1.5-Mb region on distal mouse chromosome 6 the Pas1locus, the major determinant of lung cancer predisposition in mice. Our results, on the basis of haplotype and phenetic analysis, suggest that the Pas1s susceptibility allele is shared by several mouse-inbred strains of independent origin, which show either high or intermediate predisposition to lung tumorigenesis. Therefore, the Pas1s allele is probably derived from an ancestral mouse rather than from independent mutations of the same gene. We showed the feasibility of LD in common inbred strains for the fine mapping of disease loci, and provided the biological basis and the reagents for the cloning of the Pas1 gene.
Detection and Assignment of Mutations and Minihaplotypes in Human DNA Using Peptide Mass Signature Genotyping (PMSG): Application to the Human RDS/Peripherin Gene
Authors: Telmer Cheryl A. , Retchless Adam R. , Kinsey Ashley D. , Conley Yvette , Rigatti Brian , Gorin Michael B. , Jarvik Jonathan W.
Published: November 2021

Peptide mass-signature genotyping (PMSG) is a scanning genotyping method that identifies mutations and polymorphisms by translating the sequence of interest in more than one reading frame and measuring the masses of the resulting peptides by mass spectrometry. PMSG was applied to the RDS/peripherin gene of 16 individuals from a family exhibiting autosomal dominant macular degeneration. The method revealed an A→T transversion in the 5′ splice site of intron 2 that is the likely cause of the disease. It also revealed four different minihaplotypes in exon 3 that represent particular combinations of SNPs at four different locations. This study demonstrates the utility of PMSG for identifying and characterizing point mutations and local minihaplotypes that are not readily analyzed by other approaches.
Can the results of quantum refinement be improved with a continuum-solvation model?
Authors: Bergmann Justin , Oksanen Esko , Ryde Ulf
Published: November 2021

Quantum refinement has repeatedly been shown to be a powerful approach to interpret and improve macromolecular crystal structures, allowing for the discrimination between different interpretations of the structure, regarding the protonation states or the nature of bound ligands, for example. In this method, the empirical restraints, used to supplement the crystallographic raw data in standard crystallographic refinement, are replaced by more accurate quantum mechanical (QM) calculations for a small, but interesting, part of the structure. Previous studies have shown that the results of quantum refinement can be improved if the charge of the QM system is reduced by adding neutralizing groups. However, this significantly increases the computation time for the refinement. In this study, we show that a similar improvement can be obtained if the original highly charged QM system is instead immersed in a continuum solvent in the QM calculations. The best results are typically obtained with a high dielectric constant (ɛ). The continuum solvent improves real-space Z values, electron-density difference maps and strain energies, and it normally does not affect the discriminatory power of the calculations between different chemical interpretations of the structure. However, for structures with a low charge in the QM system or with a low crystallographic resolution (>2 Å), no improvement of the structures is seen.
Tautomerism troubles: proton transfer modifies the stereochemical assignments in diastereoisomeric structures of spirocyclic 5-methyl-2H-imidazol-4-amine dimers
Authors: Blade Helen , Horton Peter N. , Morrison James A. , Orton James B. , Sullivan Rachel A. , Coles Simon J.
Published: November 2021

During the racemization of a novel pharmaceutical spirocyclic imidazole–amine compound, namely, 6′-bromo-N-(6′-bromo-4-methoxy-4′′-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2′′-imidazol]-5′′-yl)-4-methoxy-4′′-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2′′-imidazol]-5′′-imine, C36H41Br2N5O2, two impurities were isolated. These impurities were clearly dimers from mass spectroscopic analysis, however single-crystal diffraction characterization was required for the assignment of stereochemistry. The single-crystal diffraction results revealed subtly different structures to those proposed, due to an unexpected proton transfer. The dimers contain four stereocentres, but two of primary interest, and are centrosymmetric, so after careful structure refinement and close inspection it was possible to unambiguously assign the stereochemistry of both the homochiral [(S),(S)- and (R),(R)-] and the heterochiral [(S),(R)- and (R),(S)-] compounds.
Nitrosonium tetrafluoridoborate, NOBF4
Authors: Lozinšek Matic
Published: November 2021

The crystal structure of oxidonitrogen(1+) tetrafluoridoborate (nitrosonium tetrafluoridoborate), NO+BF4
−, was refined on the basis of single-crystal X-ray diffraction data at 150 K. The compound crystallizes in the baryte structure type with orthorhombic Pnma symmetry. The crystal structure exhibits cationic disorder with equal occupation of N and O atoms at the same site.
Attributes of product advantage and choices for manufacturer–retailer formal governance: the case of new product launch
Authors: Zheng Songyue , Qian Liping , Yang Pianpian
Published: November 2021

Purpose

This study examined how the technological (tech) advantage and market advantage of new products influence the level of formal channel governance and, in turn, affect the success of new products in the presence of relational governance.

Design/methodology/approach

The hypotheses are tested using the partial least squares approach to analyse survey data collected from 392 retailers of customer goods in China.

Findings

The results indicate that tech advantage and market advantage lead to an increase in retailers' transaction-specific investments (TSIs) and contract explicitness, respectively; the positive effect of market advantage on a retailer's TSIs will gradually decrease and will even become negative beyond a certain point. The relational governance mechanism can substitute for the effects of contract explicitness on improving new product success.

Originality/value

This research provides a new perspective for understanding new product advantage and exerts an initial effort to empirically distinguish between tech advantage and market advantage. It enriches the innovation literature by examining the governance of new product launches through retailers and explores the effects of formal and informal governance on channel cooperation performance in the new product launch stage.
Performance analysis of selected metaheuristic optimization algorithms applied in the solution of an unconstrained task
Authors: Knypiński Łukasz
Published: November 2021

Purpose

The purpose of this paper is to execute the efficiency analysis of the selected metaheuristic algorithms (MAs) based on the investigation of analytical functions and investigation optimization processes for permanent magnet motor.

Design/methodology/approach

A comparative performance analysis was conducted for selected MAs. Optimization calculations were performed for as follows: genetic algorithm (GA), particle swarm optimization algorithm (PSO), bat algorithm, cuckoo search algorithm (CS) and only best individual algorithm (OBI). All of the optimization algorithms were developed as computer scripts. Next, all optimization procedures were applied to search the optimal of the line-start permanent magnet synchronous by the use of the multi-objective objective function.

Findings

The research results show, that the best statistical efficiency (mean objective function and standard deviation [SD]) is obtained for PSO and CS algorithms. While the best results for several runs are obtained for PSO and GA. The type of the optimization algorithm should be selected taking into account the duration of the single optimization process. In the case of time-consuming processes, algorithms with low SD should be used.

Originality/value

The new proposed simple nondeterministic algorithm can be also applied for simple optimization calculations. On the basis of the presented simulation results, it is possible to determine the quality of the compared MAs.
Data repair of density-based data cleaning approach using conditional functional dependencies
Authors: Al-Janabi Samir , Janicki Ryszard
Published: November 2021

Purpose

Data quality is a major challenge in data management. For organizations, the cleanliness of data is a significant problem that affects many business activities. Errors in data occur for different reasons, such as violation of business rules. However, because of the huge amount of data, manual cleaning alone is infeasible. Methods are required to repair and clean the dirty data through automatic detection, which are data quality issues to address. The purpose of this work is to extend the density-based data cleaning approach using conditional functional dependencies to achieve better data repair.

Design/methodology/approach

A set of conditional functional dependencies is introduced as an input to the density-based data cleaning algorithm. The algorithm repairs inconsistent data using this set.

Findings

This new approach was evaluated through experiments on real-world as well as synthetic datasets. The repair quality was determined using the F-measure. The results showed that the quality and scalability of the density-based data cleaning approach improved when conditional functional dependencies were introduced.

Originality/value

Conditional functional dependencies capture semantic errors among data values. This work demonstrates that the density-based data cleaning approach can be improved in terms of repairing inconsistent data by using conditional functional dependencies.
A content analysis of hospitality research's research methods in the 2010s
Authors: Shum Cass , Garlington Jaimi , Ghosh Ankita , Baloglu Seyhmus
Published: November 2021

Purpose

This study aims to describe the development of hospitality research in terms of research methods and data sources used in the 2010s.

Design/methodology/approach

Content analyses of the research methods and data sources used in original hospitality research published in the 2010s in the Cornell Hospitality Quarterly (CQ), International Journal of Hospitality Management (IJHM), International Journal of Contemporary Hospitality Management (IJCHM), Journal of Hospitality and Tourism Research (JHTR) and International Hospitality Review (IHR) were conducted. It describes whether the time span, functional areas and geographic regions of data sources were related to the research methods and data sources.

Findings

Results from 2,759 original hospitality empirical articles showed that marketing research used various research methods and data sources. Most finance articles used archival data, while most human resources articles used survey designs with organizational data. In addition, only a small amount of research used data from Oceania, Africa and Latin America.

Research limitations/implications

This study sheds some light on the development of hospitality research in terms of research method and data source usage. However, it only focused on five English-based journals from 2010–2019. Therefore, future studies may seek to understand the impact of the COVID-19 pandemic on research methods and data source usage in hospitality research.

Originality/value

This is the first study to examine five hospitality journals' research methods and data sources used in the last decade. It sheds light on the development of hospitality research in the previous decade and identifies new hospitality research avenues.
Policy turmoil in China: a barrier for FDI flows?
Authors: Su Chi Wei , Meng Xian-Li , Tao Ran , Umar Muhammad
Published: November 2021

Purpose

This research examines the dynamic interrelationship between economic policy uncertainty (EPU) and the inflows of foreign direct investment (IFDI) in China.

Design/methodology/approach

This research used the Granger causality and sub-sample time-varying rolling window causality method.

Findings

The empirical results reveal that EPU tends to have a negative impact on the IFDI in most periods that have been taken into consideration. However, there has been a positive relationship observed between the periods of the US subprime crisis. That is to say that the uncertainty of the Chinese economic policy does not always impede the IFDI. These results are supported by the general equilibrium model, which states that there are certain influences that come into play when moving from EPU to IFDI. On the other hand, the IFDI exert a positive influence on EPU during times of economic crisis and trade war, which indicates that the uncertainty in the economy may increase due to the sudden soar of foreign investment.

Originality/value

During tense global trade situations and complicated economic scenarios, the results suggest the Chinese government should dedicate itself to expanding its initiatives to open up and improve the domestic business environment in order to increase the foreign investors' confidence and prevent the decline in the IFDI. In addition to this, it also suggests that multinational companies pay attention to the policy environment of the host country, especially when they decide to invest there.
Selection of resilient suppliers in manufacturing industries post-COVID-19: implications for economic and social sustainability in emerging economies
Authors: Majumdar Abhijit , S Jeevaraj , Kaliyan Mathiyazhagan , Agrawal Rohit
Published: November 2021

Purpose

Selection of resilient suppliers has attracted the attention of researchers in the past one decade. The devastating effect of COVID-19 in emerging economies has provided great impetus to the selection of resilient suppliers. Under volatile and uncertain business scenarios, supplier selection is often done under imprecise and incomplete information, making the traditional decision-making methods ineffective. The purpose of this paper is to demonstrate the application of a fuzzy decision-making method for resilient supplier selection.

Design/methodology/approach

A group of three decision makers was considered for evaluating various alternatives (suppliers) based on their performance under different primary, sustainability and resilience criteria. Experts' opinion about each criterion and alternative was captured in linguistic terms and was modelled using fuzzy numbers. Then, an algorithm for solving resilient supplier selection problem based on the trapezoidal intuitionistic fuzzy technique for order preference by similarity to ideal solution (TrIFTOPSIS) was introduced and demonstrated through a case study.

Findings

A closeness coefficient was used to rank the suppliers based on their distances from intuitionistic fuzzy positive-ideal solution and intuitionistic fuzzy negative-ideal solution. Finally, the proposed fuzzy decision making model was applied to a real problem of supplier selection in the clothing industry.

Originality/value

The presented TrIFTOPSIS model provides an effective route to prioritise and select resilient suppliers under imprecise and incomplete information. This is the first application of intuitionistic fuzzy multi-criteria decision-making for resilient supplier selection.