bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell twisting during desiccation reveals axial asymmetry in wall organization
Authors: Keynia Sedighe , Davis Thomas C. , Szymanski Daniel B. , Turner Joseph A. 
Published: November 2021

AbstractPlant cell size and shape are tuned to their function and specified primarily by cellulose microfibril (CMF) patterning of the cell wall. Arabidopsis thaliana leaf trichomes are responsible for protecting plants against environmental elements and are unicellular structures that employ a highly anisotropic cellulose wall to extend and taper, generating pointed branches. During elongation, the mechanisms by which shifts in fiber orientation generate cells with predictable sizes and shapes are unknown. Specifically, the axisymmetric growth of trichome branches is often thought result from axisymmetric CMF patterning. Here, we analyzed the direction and degree of twist of branches after desiccation to reveal the presence of an asymmetric cell wall organization with a left-hand bias. CMF organization, quantified using computational modeling, suggests a limited reorientation of microfibrils during growth and maximum branch length limited by the wall axial stiffness. The model provides a mechanism for CMF asymmetry, which occurs after the branch bending stiffness becomes low enough that ambient bending affects the principal stresses. After this stage, the CMF synthesis results in a constant bending stiffness for longer branches. The resulting natural frequency of branches after a length of 200 μm falls within the range of the sounds associated with many insects.Statement of significanceThe growth of plant cell walls is governed by the direction of cellulose synthesis but the factors that influence the overall wall anisotropy are only partially understood. The twist of leaf trichome branches after desiccation reveals a left-handed asymmetry in cell wall organization even though the geometry is axisymmetric. This surprising behavior provides information about the directionality of cellulose synthesis control in plant cells.
SARS-CoV-2 variants of concern remain dependent on IFITM2 for efficient replication in human lung cells
Authors: Nchioua Rayhane , Schundner Annika , Kmiec Dorota , Prelli-Bozzo Caterina , Zech Fabian , Koepke Lennart , Graf Alexander , Krebs Stefan , Blum Helmut , Frick Manfred , Sparrer Konstantin M. J. , Kirchhoff Frank 
Published: November 2021

ABSTRACTIt has recently been shown that an early SARS-CoV-2 isolate (NL-02-2020) hijacks interferon-induced transmembrane proteins (IFITMs) for efficient replication in human cells. To date, several “Variants of Concern” (VOCs) showing increased infectivity and resistance to neutralization have emerged and globally replaced the early viral strains. Here, we determined whether the four SARS-CoV-2 VOCs (Alpha, Beta, Gamma and Delta) maintained the dependency on IFITM proteins for efficient replication. We found that depletion of IFITM2 strongly reduces viral RNA production by all four VOCs in the human epithelial lung cancer cell line Calu-3. Silencing of IFITM1 had little effect, while knock-down of IFITM3 resulted in an intermediate phenotype. Strikingly, depletion of IFITM2 generally reduced infectious virus production by more than four orders of magnitude. In addition, an antibody directed against the N-terminus of IFITM2 inhibited SARS-CoV-2 VOC replication in iPSC-derived alveolar epithelial type II cells thought to represent major viral target cells in the lung. In conclusion, endogenously expressed IFITM proteins (especially IFITM2) are critical cofactors for efficient replication of genuine SARS-CoV-2 VOCs, including the currently dominating Delta variant.IMPORTANCERecent results showed that an early SARS-CoV-2 isolate requires endogenously expressed IFITM proteins for efficient infection. However, whether IFITMs are also important cofactors for infection of emerging SARS-CoV-2 VOCs that out-competed the original strains and currently dominate the pandemic remained to be determined. Here, we demonstrate that depletion of endogenous IFITM2 expression almost entirely prevents the production of infectious Alpha, Beta, Gamma and Delta VOC SARS-CoV-2 virions in a human lung cell line. In comparison, silencing of IFITM1 had little impact, while knock-down of IFITM3 had intermediate effects on viral replication. Finally, an antibody targeting the N-terminus of IFITM2 inhibited SARS-CoV-2 VOC replication in iPSC-derived alveolar epithelial type II cells. Our results show that SARS-CoV-2 VOCs including the currently dominant Delta variant are dependent on IFITM2 for efficient replication suggesting that IFITM proteins play a key role in viral transmission and pathogenicity.
Upregulation of CREB1 and FOXO1 transcription factor pathways in Neuregulin-1 mediated neuroprotection following ischemic stroke
Authors: Bennett Kimberly R. , Surles-Zeigler Monique C. , Augello Catherine J. , Ako Etchi , Rodgers Victor G. J. , Ford Byron D. 
Published: November 2021

AbstractNeuregulin-1 (NRG-1) is growth factor that has been investigated for its neuroprotective properties following ischemic stroke. While NRG-1 has shown significant promise in preventing neuronal damage following stroke, the mechanisms behind its neuroprotective effects are unclear. The goal of this research was to investigate the effects of NRG-1 treatment on ischemia-induced gene expression profiles following a permanent middle cerebral artery occlusion (MCAO) in rats. Rats were sacrificed twelve hours following MCAO and either vehicle or NRG-1 treatment. RNA extracted from the peri-infarct cortex of the brain was hybridized to an Affymetrix Rat Genome 2.0st Microarray Gene Chip. Data were analyzed using the Affymetrix Transcriptome Analysis Console (TAC) 4.0 software and the STRING Protein-Protein Interaction Networks database. Our results showed that NRG-1 delivery increased the regulation of pro-survival genes. Most notably, NRG-1 treatment upregulated the CREB1 and FOXO1 transcription factor pathways which are involved in increasing anti-inflammatory and cell proliferation responses and decreasing apoptosis and oxidative stress responses, respectively. Luminex multiplex transcription factor assays demonstrated that the activities of CREB1 and FOXO1 were increased by NRG-1 treatment with MCAO. These findings provide novel insight into the molecular mechanisms involved in NRG-1 mediated neuroprotection.
Selective YAP activation in Procr cells is essential for ovarian stem/progenitor expansion and epithelium repair
Authors: Wang Jingqiang , He Lingli , Xie Zhiyao , Yu Wentao , Bai Lanyue , Wang Zuoyun , Lu Yi , Liu Chunye , Fu Junfen , Zhang Lei , Zeng Yi Arial 
Published: November 2021

AbstractOvarian surface epithelium (OSE) undergoes recurring ovulatory rupture and OSE stem cells rapidly generate new cells for the repair. How the stem cell senses the rupture and promptly turns on proliferation is unclear. Our previous study has identified that Protein C Receptor (Procr) marks OSE progenitors. In this study, we observed decreased adherent junction and selective activation of YAP signaling in Procr progenitors at OSE rupture site. OSE repair is impeded upon deletion of Yap in these progenitors. Interestingly, Procr+ progenitors show lower expression of Vgll4, an antagonist of YAP signaling. Overexpression of Vgll4 in Procr+ cells hampers OSE repair and progenitor proliferation, indicating that selective low Vgll4 expression in Procr+ progenitors is critical for OSE repair. In addition, YAP activation promotes transcription of the OSE stemness gene Procr. The combination of increased cell division and Procr expression leads to expansion of Procr+ progenitors surrounding the rupture site. These results illustrate a YAP- dependent mechanism by which the stem/progenitor cells recognize the ovulatory rupture, and rapidly multiply their numbers, highlighting a YAP- induced stem cell expansion strategy.
Identification, Characterization, and Mapping of Expressed Sequence Tags from an Embryonic Zebrafish Heart cDNA Library
Authors: Ton Christopher , Hwang David M. , Dempsey Adam A. , Tang Hong-Chang , Yoon Jennifer , Lim Mindy , Mably John D. , Fishman Mark C. , Liew Choong-Chin 
Published: November 2021

The generation of expressed sequence tags (ESTs) has proven to be a rapid and economical approach by which to identify and characterize expressed genes. We generated 5102 ESTs from a 3-d-old embryonic zebrafish heart cDNA library. Of these, 57.6% matched to known genes, 14.2% matched only to other ESTs, and 27.8% showed no match to any ESTs or known genes. Clustering of all ESTs identified 359 unique clusters comprising 1771 ESTs, whereas the remaining 3331 ESTs did not cluster. This estimates the number of unique genes identified in the data set to be approximately 3690. A total of 1242 unique known genes were used to analyze the gene expression patterns in the zebrafish embryonic heart. These were categorized into seven categories on the basis of gene function. The largest class of genes represented those involved in gene/protein expression (25.9% of known transcripts). This class was followed by genes involved in metabolism (18.7%), cell structure/motility (16.4%), cell signaling and communication (9.6%), cell/organism defense (7.1%), and cell division (4.4%). Unclassified genes constituted the remaining 17.91%. Radiation hybrid mapping was performed for 102 ESTs and comparison of map positions between zebrafish and human identified new synteny groups. Continued comparative analysis will be useful in defining the boundaries of conserved chromosome segments between zebrafish and humans, which will facilitate the transfer of genetic information between the two organisms and improve our understanding of vertebrate evolution.[The sequence data described in this paper have been submitted to the GenBank data library under accession nos.BE693120–BE693210 and BE704450.]
Identification and Characterization of the Potential Promoter Regions of 1031 Kinds of Human Genes
Authors: Suzuki Yutaka , Tsunoda Tatsuhiko , Sese Jun , Taira Hirotoshi , Mizushima-Sugano Junko , Hata Hiroko , Ota Toshio , Isogai Takao , Tanaka Toshihiro , Nakamura Yusuke , Suyama Akira , Sakaki Yoshiyuki , Morishita Shinichi , Okubo Kousaku , Sugano Sumio 
Published: November 2021

To understand the mechanism of transcriptional regulation, it is essential to identify and characterize the promoter, which is located proximal to the mRNA start site. To identify the promoters from the large volumes of genomic sequences, we used mRNA start sites determined by a large-scale sequencing of the cDNA libraries constructed by the “oligo-capping” method. We aligned the mRNA start sites with the genomic sequences and retrieved adjacent sequences as potential promoter regions (PPRs) for 1031 genes. The PPR sequences were searched to determine the frequencies of major promoter elements. Among 1031 PPRs, 329 (32%) contained TATA boxes, 872 (85%) contained initiators, 999 (97%) contained GC box, and 663 (64%) contained CAAT box. Furthermore, 493 (48%) PPRs were located in CpG islands. This frequency of CpG islands was reduced in TATA+/Inr+PPRs and in the PPRs of ubiquitously expressed genes. In the PPRs of the CGM2 gene, the DRA gene, and theTM30pl genes, which showed highly colon specific expression patterns, the consensus sequences of E boxes were commonly observed. The PPRs were also useful for exploring promoter SNPs.[The nucleotide sequences described in this paper have been deposited in the DDBJ, EMBL, and GenBank data libraries under accession nos.AU098358–AU100608.]
The Nuclear Receptor Superfamily Has Undergone Extensive Proliferation and Diversification in Nematodes
Authors: Sluder Ann E. , Mathews Siuyien Wong , Hough David , Yin Viravuth P. , Maina Claude V. 
Published: November 2021

The nuclear receptor (NR) superfamily is the most abundant class of transcriptional regulators encoded in the Caenorhabditis elegans genome, with >200 predicted genes revealed by the screens and analysis of genomic sequence reported here. This is the largest number of NR genes yet described from a single species, although our analysis of available genomic sequence from the related nematode Caenorhabditis briggsae indicates that it also has a large number. Existing data demonstrate expression for 25% of theC. elegans NR sequences. Sequence conservation and statistical arguments suggest that the majority represent functional genes. An analysis of these genes based on the DNA-binding domain motif revealed that several NR classes conserved in both vertebrates and insects are also represented among the nematode genes, consistent with the existence of ancient NR classes shared among most, and perhaps all, metazoans. Most of the nematode NR sequences, however, are distinct from those currently known in other phyla, and reveal a previously unobserved diversity within the NR superfamily. In C. elegans, extensive proliferation and diversification of NR sequences have occurred on chromosome V, accounting for > 50% of the predicted NR genes.[The sequence data described in this paper have been submitted to the GenBank data library under accession nos.AF083222–AF083225 and AF083251–AF083234.]
Isolation of Zebrafish gdf7 and Comparative Genetic Mapping of Genes Belonging to the Growth/Differentiation Factor 5, 6, 7 Subgroup of the TGF-β Superfamily
Authors: Davidson Alan J. , Postlethwait John H. , Yan Yi-Lin , Beier David R. , van Doren Cherie , Foernzler Dorothee , Celeste Anthony J. , Crosier Kathryn E. , Crosier Philip S. 
Published: November 2021

The Growth/differentiation factor (Gdf)5, 6, 7 genes form a closely related subgroup belonging to the TGF-β superfamily. In zebrafish, there are three genes that belong to the Gdf5, 6, 7subgroup that have been named radar, dynamo, andcontact. The genes radar and dynamo both encode proteins most similar to mouse GDF6. The orthologous identity of these genes on the basis of amino acid similarities has not been clear. We have identified gdf7, a fourth zebrafish gene belonging to the Gdf5, 6, 7 subgroup. To assign correct orthologies and to investigate the evolutionary relationships of the human, mouse, and zebrafish Gdf5, 6, 7subgroup, we have compared genetic map positions of the zebrafish and mammalian genes. We have mapped zebrafish gdf7 to linkage group (LG) 17, contact to LG9, GDF6 to human chromosome (Hsa) 8 and GDF7 to Hsa2p. The radar anddynamo genes have been localized previously to LG16 and LG19, respectively. A comparison of syntenies shared among human, mouse, and zebrafish genomes indicates that gdf7 is the ortholog of mammalian GDF7/Gdf7. LG16 shares syntenic relationships with mouse chromosome (Mmu) 4, including Gdf6. Portions of LG16 and LG19 appear to be duplicate chromosomes, thus suggesting thatradar and dynamo are both orthologs of Gdf6. Finally, the mapping data is consistent with contact being the zebrafish ortholog of mammalian GDF5/Gdf5.[The sequence data described in this paper have been submitted to the GenBank data library under accession numbers AF113022 and AF113023.]
An Effective Approach for Analyzing “Prefinished” Genomic Sequence Data
Authors: Kuehl Peter M. , Weisemann Jane M. , Touchman Jeffrey W. , Green Eric D. , Boguski Mark S. 
Published: November 2021

Ongoing efforts to sequence the human genome are already generating large amounts of data, with substantial increases anticipated over the next few years. In most cases, a shotgun sequencing strategy is being used, which rapidly yields most of the primary sequence in incompletely assembled sequence contigs (“prefinished” sequence) and more slowly produces the final, completely assembled sequence (“finished” sequence). Thus, in general, prefinished sequence is produced in excess of finished sequence, and this trend is certain to continue and even accelerate over the next few years. Even at a prefinished stage, genomic sequence represents a rich source of important biological information that is of great interest to many investigators. However, analyzing such data is a challenging and daunting task, both because of its sheer volume and because it can change on a day-by-day basis. To facilitate the discovery and characterization of genes and other important elements within prefinished sequence, we have developed an analytical strategy and system that uses readily available software tools in new combinations. Implementation of this strategy for the analysis of prefinished sequence data from human chromosome 7 has demonstrated that this is a convenient, inexpensive, and extensible solution to the problem of analyzing the large amounts of preliminary data being produced by large-scale sequencing efforts. Our approach is accessible to any investigator who wishes to assimilate additional information about particular sequence data en route to developing richer annotations of a finished sequence.[Our software system is available via an extensive web supplement to this article at http://www.ncbi.nlm.nih.gov/Kuehl/prefinished.]
Analysis of 148 kb of Genomic DNA Around thewnt1Locus ofFugu rubripes
Authors: Gellner Klaus , Brenner Sydney 
Published: November 2021

The analysis of the sequence of ∼150 kb of a genomic region corresponding to thewnt1gene of the Japanese pufferfishFugu rubripesconfirms the compact structure of the genome. Fifteen genes were found in this region, and 26.6% of the analyzed sequence is coding sequence. With an average intergenic distance of <5 kb, this gene density is comparable to that ofCaenorhabditis elegans. The compactness of this region corresponds to the reduction of the overall size of the genome, consistent with the conclusion that the gene number inFuguand human genomes is approximately the same. Eight of the genes have been mapped in the human genome and all of them are found in the chromosomal band 12q13, indicating a high degree of synteny in both species,Fuguand human. Comparative sequence analysis allows us to identify potential regulatory elements forwnt1andARF3, which are common to fish and mammals.[The sequence data described in this paper have been submitted to GenBank under accession no.AF056116.]
DNA Sequence Chromatogram Browsing Using JAVA and CORBA
Authors: Parsons Jeremy D. , Buehler Eugen , Hillier LaDeana 
Published: November 2021

DNA sequence chromatograms (traces) are the primary data source for all large-scale genomic and expressed sequence tags (ESTs) sequencing projects. Access to the sequencing trace assists many later analyses, for example contig assembly and polymorphism detection, but obtaining and using traces is problematic. Traces are not collected and published centrally, they are much larger than the base calls derived from them, and viewing them requires the interactivity of a local graphical client with local data. To provide efficient global access to DNA traces, we developed a client/server system based on flexible Java components integrated into other applications including an applet for use in a WWW browser and a stand-alone trace viewer. Client/server interaction is facilitated by CORBA middleware which provides a well-defined interface, a naming service, and location independence.[The software is packaged as a Jar file available from the following URL: http://www.ebi.ac.uk/∼jparsons. Links to working examples of the trace viewers can be found athttp://corba.ebi.ac.uk/EST. All the Washington University mouse EST traces are available for browsing at the same URL.]
An Efficient DNA Sequencing Strategy Based on the Bacteriophage Mu in Vitro DNA Transposition Reaction
Authors: Haapa Saija , Suomalainen Sini , Eerikäinen Simo , Airaksinen Matti , Paulin Lars , Savilahti Harri 
Published: November 2021

A highly efficient DNA sequencing strategy was developed on the basis of the bacteriophage Mu in vitro DNA transposition reaction. In the reaction, an artificial transposon with a chloramphenicol acetyltransferase (cat) gene as a selectable marker integrated into the target plasmid DNA containing a 10.3-kb mouse genomic insert to be sequenced. Bacterial clones carrying plasmids with the transposon insertions in different positions were produced by transforming transposition reaction products into Escherichia coli cells that were then selected on appropriate selection plates. Plasmids from individual clones were isolated and used as templates for DNA sequencing, each with two primers specific for the transposon sequence but reading the sequence into opposite directions, thus creating a minicontig. By combining the information from overlapping minicontigs, the sequence of the entire 10,288-bp region of mouse genome including six exons of mouse Kcc2 gene was obtained. The results indicated that the described methodology is extremely well suited for DNA sequencing projects in which considerable sequence information is on demand. In addition, massive DNA sequencing projects, including those of full genomes, are expected to benefit substantially from the Mu strategy.[The sequence data reported in this paper have been submitted to the GenBank data library under accession no. AJ011033.]
Genomic Structure and Comparative Analysis of Nine Fugu Genes: Conservation of Synteny with Human Chromosome Xp22.2–p22.1
Authors: Brunner Bodo , Todt Tilman , Lenzner Steffen , Stout Karen , Schulz Ute , Ropers Hans-Hilger , Kalscheuer Vera M. 
Published: November 2021

The pufferfish Fugu rubripes has a compact 400-Mb genome that is ∼7.5 times smaller than the human genome but contains a similar number of genes. Focusing on the distal short arm of the human X chromosome, we have studied the evolutionary conservation of gene orders in Fugu and man. Sequencing of 68 kb of Fugugenomic DNA identified nine genes in the following order: (SCML2)-STK9, XLRS1, PPEF-1, KELCH2, KELCH1, PHKA2, AP19, and U2AF1-RS2. Apart from an evolutionary inversion separatingAP19 and U2AF1-RS2 from PHKA2, gene orders are identical in Fugu and man, and all nine human homologs map to the Xp22 band. All Fugu genes were found to be smaller than their human counterparts, but gene structures were mostly identical. These data suggest that genomic sequencing in Fugu is a powerful and economical strategy to predict gene orders in the human genome and to elucidate the structure of human genes.[Sequence data for this article were deposited with the EMBL/GenBank data libraries under accession nos. AJ011381 and AF094327.]
Genomic Characterization of Human DSPG3
Authors: Deere Michelle , Dieguez Jose L. , Yoon Sung-Joo Kim , Hewett-Emmett David , de la Chapelle Albert , Hecht Jacqueline T. 
Published: November 2021

DSPG3, the human homolog to chick PG-Lb, is a member of the small leucine-rich repeat proteoglycan (SLRP) family, including decorin, biglycan, fibromodulin, and lumican. In contrast to the tissue distribution of the other SLRPs, DSPG3 is predominantly expressed in cartilage. In this study, we have determined that the human DSPG3 gene is composed of seven exons: Exon 2 ofDSPG3 includes the start codon, exons 4–7 code for the leucine-rich repeats, exons 3 and 7 contain the potential glycosaminoglycan attachment sites, and exon 7 contains the potential N-glycosylation sites and the stop codon. We have identified two polymorphic variations, an insertion/deletion composed of 19 nucleotides in intron 1 and a tetranucleotide (TATT)n repeat in intron 5. Analysis of 1.6 kb of upstream promoter sequence ofDSPG3 reveals three TATA boxes, one of which is 20 nucleotides before the transcription start site. The transcription start site precedes the translation start site by 98 nucleotides. There are 14 potential binding sites for SOX9, a transcription factor present in cartilage, in the promoter, and in the first intron of DSPG3. We have examined the evolution of the SLRP gene family and found that gene products clustered together in the evolutionary tree are encoded by genes with similarities in genomic structure. Hence, it appears that the majority of the introns in the SLRP genes were inserted after the differentiation of the SLRP genes from an ancestral gene that was most likely composed of 2–3 exons.[The sequence data described in this paper have been submitted to GenBank under accession nos.AF031658 and U63814.]