bluuebunny/crossref_metadata_2025_split huggingface dataset:
Xenoantigen Deletion and Chemical Immunosuppression Can Prolong Renal Xenograft Survival
Authors: Adams Andrew B. , Kim Steven C. , Martens Gregory R. , Ladowski Joseph M. , Estrada Jose L. , Reyes Luz M. , Breeden Cindy , Stephenson Allison , Eckhoff Devin E. , Tector Matt , Tector Alfred Joseph 
Published: July 2018

Objective:
Xenotransplantation using pig organs could end the donor organ shortage for transplantation, but humans have xenoreactive antibodies that cause early graft rejection. Genome editing can eliminate xenoantigens in donor pigs to minimize the impact of these xenoantibodies. Here we determine whether an improved cross-match and chemical immunosuppression could result in prolonged kidney xenograft survival in a pig-to-rhesus preclinical model.

Methods:
Double xenoantigen (Gal and Sda) knockout (DKO) pigs were created using CRISPR/Cas. Serum from rhesus monkeys (n = 43) was cross-matched with cells from the DKO pigs. Kidneys from the DKO pigs were transplanted into rhesus monkeys (n = 6) that had the least reactive cross-matches. The rhesus recipients were immunosuppressed with anti-CD4 and anti-CD8 T-cell depletion, anti-CD154, mycophenolic acid, and steroids.

Results:
Rhesus antibody binding to DKO cells is reduced, but all still have positive CDC and flow cross-match. Three grafts were rejected early at 5, 6, and 6 days. Longer survival was achieved in recipients with survival to 35, 100, and 435 days. Each of the 3 early graft losses was secondary to IgM antibody-mediated rejection. The 435-day graft loss occurred secondary to IgG antibody-mediated rejection.

Conclusions:
Reducing xenoantigens in donor pigs and chemical immunosuppression can be used to achieve prolonged renal xenograft survival in a preclinical model, suggesting that if a negative cross-match can be obtained for humans then prolonged survival could be achieved.
Heterochromatin-enriched assemblies reveal the sequence and organization of theDrosophila melanogasterY chromosome
Authors: Chang Ching-Ho , Larracuente Amanda M. 
Published: July 2018

ABSTRACTHeterochromatic regions of the genome are repeat-rich and gene poor, and are therefore underrepresented in even in the best genome assemblies. One of the most difficult regions of the genome to assemble are sex-limited chromosomes. TheDrosophila melanogasterY chromosome is entirely heterochromatic, yet has wide-ranging effects on male fertility, fitness, and genome-wide gene expression. The genetic basis of this phenotypic variation is difficult to study, in part because we do not know the detailed organization of the Y chromosome. To study Y chromosome organization inD. melanogaster, we develop an assembly strategy involving thein silicoenrichment of heterochromatic long single-molecule reads and use these reads to create targetedde novoassemblies of heterochromatic sequences. We assigned contigs to the Y chromosome using Illumina reads to identify male-specific sequences. Our pipeline extends theD. melanogasterreference genome by 11.9-Mb, closes 43.8% of the gaps, and improves overall contiguity. The addition of 10.6 MB of Y-linked sequence permitted us to study the organization of repeats and genes along the Y chromosome. We detected a high rate of duplication to the pericentric regions of the Y chromosome from other regions in the genome. Most of these duplicated genes exist in multiple copies. We detail the evolutionary history of one sex-linked gene family—crystal-Stellate. While the Y chromosome does not undergo crossing over, we observed high gene conversion rates within and between members of thecrystal-Stellategene family,Su(Ste), andPCKR, compared to genome-wide estimates. Our results suggest that gene conversion and gene duplication play an important role in the evolution of Y-linked genes.
Early genome activation in Drosophila is extensive with an initial tendency for aborted transcripts and retained introns
Authors: Kwasnieski Jamie C , Orr-Weaver Terry L , Bartel David P 
Published: July 2018

AbstractControl of metazoan embryogenesis shifts from maternal to zygotic gene products as the zygotic genome becomes transcriptionally activated. In Drosophila, zygotic genome activation (ZGA) begins with a minor wave, but technical challenges have hampered the identification of early transcripts or obscured the onset of their transcription. Here, we develop an approach to isolate transcribed mRNAs and apply it over the course of the minor wave and the start of the major wave of Drosophila ZGA. Our results increase known genes of the minor wave by 10 fold and show that this wave is continuous and gradual. Transposable-element mRNAs are also produced, but discontinuously. Genes in the early and middle part of the minor wave are short with few if any introns, and their transcripts are frequently aborted and tend to have retained introns, suggesting that inefficient splicing as well as rapid cell divisions constrain the lengths of early transcripts.
Cancerous phenotypes associated with hypoxia-inducible factors are not influenced by the volatile anesthetic isoflurane in renal cell carcinoma
Authors: Sumi Chisato , Matsuo Yoshiyuki , Kusunoki Munenori , Shoji Tomohiro , Uba Takeo , Iwai Teppei , Bono Hidemasa , Hirota Kiichi 
Published: July 2018

AbstractThe possibility that anesthesia during cancer surgery may affect cancer recurrence, metastasis, and patient prognosis has become one of the most important topics of interest in cancer treatment. For example, the volatile anesthetic isoflurane was reported in several studies to induce hypoxia-inducible factors, and thereby enhance malignant phenotypesin vitro. Indeed, these transcription factors are considered critical regulators of cancer-related hallmarks, including “sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, replicative immortality, angiogenesis, invasion, and metastasis.” This study aimed to investigate the impact of isoflurane on the growth and migration of derivatives of the renal cell line RCC4. We indicated that isoflurane treatment did not positively influence cancer cell phenotypes, and that hypoxia-inducible factors (HIFs) maintain hallmark cancer cell phenotypes including gene expressions signature, metabolism, cell proliferation and cell motility. The present results indicate that HIF activity is not influenced by the volatile anesthetic isoflurane.
Molecular typing and macrolide resistance analyses ofTreponema pallidumin heterosexuals and men who have sex with men communities in Japan, 2017
Authors: Kanai Mizue , Arima Yuzo , Nishiki Shingo , Shimuta Ken , Itoda Ichiro , Matsui Tamano , Oishi Kazunori , Ohnishi Makoto , Nakayama Shu-ichi 
Published: July 2018

AbstractIn recent years, syphilis notifications have increased dramatically in Japan. We performed molecular typing and analyzed macrolide resistance ofTreponema pallidumsamples collected from four clinics and a hospital in Tokyo and Osaka prefectures in 2017.Macrolide resistant strain type 14d/f was found significantly more in heterosexual syphilis cases compared with those strains identified in men who have sex with men (MSM) syphilis cases. The proportion of 14d/f among heterosexuals was 79% (31/39) compared to 37% (7/19) among MSM [OR, 6.6 (95% CI, 1.7 to 26.7); P=0.002]. 83% (50/60) of the strains were identified as macrolide resistant with an A2058G mutation at the 23S rRNA gene. 90% (35/39) of the heterosexual strains were macrolide resistant, relative to 58% (11/19) of MSM strains; the odds of having the resistant mutation was considerably higher in heterosexuals compared with MSM [OR, 6.4 (95% CI, 1.3 to 33.5); P=0.02]. Heterosexual females and males showed similar distributions, and the results remained the same when restricted to men.The strain type distribution and frequency of macrolide resistance differed substantially between heterosexual and MSM syphilis samples, suggesting distinct epidemiologic profiles for the two communities and insight into syphilis transmission dynamics in Japan.
Temporal Small RNA Expression Profiling Under Drought Reveals a Potential Regulatory Role of snoRNAs in Drought Responses of Maize
Authors: Zheng Jun , Zeng Erliang , Du Yicong , He Cheng , Hu Ying , Jiao Zhenzhen , Wang Kai , Li Wenxue , Ludens Maria , Fu Junjie , Wang Haiyan , White Frank F. , Wang Guoying , Liu Sanzhen 
Published: July 2018

AbstractSmall RNAs (sRNAs) are short noncoding RNAs that play roles in many biological processes, including drought responses in plants. However, how the expression of sRNAs dynamically changes with the gradual imposition of drought stress in plants is largely unknown. We generated time-series sRNA sequence data from maize seedlings under drought stress and under well-watered conditions at the same time points. Analyses of length, functional annotation, and abundance of 736,372 non-redundant sRNAs from both drought and well-watered data, as well as genome copy number and chromatin modifications at the corresponding genomic regions, revealed distinct patterns of abundance, genome organization, and chromatin modifications for different sRNA classes of sRNAs. The analysis identified 6,646 sRNAs whose regulation was altered in response to drought stress. Among drought-responsive sRNAs, 1,325 showed transient down-regulation by the seventh day, coinciding with visible symptoms of drought stress. The profiles revealed drought-responsive microRNAs, as well as other sRNAs that originated from ribosomal RNAs (rRNAs), splicing small nuclear RNAs, and small nucleolar RNAs (snoRNA). Expression profiles of their sRNA derivers indicated that snoRNAs might play a regulatory role through regulating stability of rRNAs and splicing small nuclear RNAs under drought condition.
Repeats Of Unusual Size in Plant Mitochondrial Genomes: Identification, Incidence and Evolution
Authors: Wynn Emily L. , Christensen Alan C. 
Published: July 2018

AbstractPlant mitochondrial genomes have excessive size relative to coding capacity, a low mutation rate in genes and a high rearrangement rate. They also have non-tandem repeats in two size groups: a few large repeats which cause isomerization of the genome by recombination, and numerous repeats longer than 50bp, often found in exactly two copies per genome. It appears that repeats in the size range from several hundred to a few thousand base pair are underrepresented. The repeats are not well-conserved between species, and are infrequently annotated in mitochondrial sequence assemblies. Because they are much larger than expected by chance we call them Repeats Of Unusual Size (ROUS). The repeats consist of two functional classes, those that are involved in genome isomerization through frequent crossing over, and those for which crossovers are rare unless there are mutations in DNA repair genes, or the rate of double-strand breakage is increased. We systematically described and compared these repeats, which are important clues to mechanisms of DNA maintenance in mitochondria. We developed a tool to find non-tandem repeats and analyzed the complete mitochondrial sequences from 135 plant species. We observed an interesting difference between taxa: the repeats are larger and more frequent in the vascular plants. Analysis of closely related species also shows that plant mitochondrial genomes evolve in dramatic bursts of breakage and rejoining, complete with DNA sequence gain and loss, and the repeats are included in these events. We suggest an adaptive explanation for the existence of the repeats and their evolution.
High resolution discovery of chromatin interactions
Authors: Guo Yuchun , Krismer Konstantin , Closser Michael , Wichterle Hynek , Gifford David K. 
Published: July 2018

ABSTRACTChromatin interaction analysis by paired-end tag sequencing (ChIA-PET) is a method for the genome-wide de novo discovery of chromatin interactions. Existing computational methods typically fail to detect weak or dynamic interactions because they use a peak-calling step that ignores paired-end linkage information. We have developed a novel computational method called Chromatin Interaction Discovery (CID) to overcome this limitation with an unbiased clustering approach for interaction discovery. CID outperforms existing chromatin interaction detection methods with improved sensitivity, replicate consistency, and concordance with other chromatin interaction datasets. In addition, CID also outperforms other methods in discovering chromatin interactions from HiChIP data. We expect that the CID method will be valuable in characterizing 3D chromatin interactions and in understanding the functional consequences of disease-associated distal genetic variations.
Tracking key virulence loci encoding aerobactin and salmochelin siderophore synthesis inKlebsiella pneumoniae
Authors: Lam Margaret M. C. , Wyres Kelly L. , Judd Louise M. , Wick Ryan R. , Jenney Adam , Brisse Sylvain , Holt Kathryn E. 
Published: July 2018

ABSTRACTBackgroundKlebsiella pneumoniaeis a recognised agent of multidrug-resistant (MDR) healthcare-associated infections, however individual strains vary in their virulence potential due to the presence of mobile accessory genes. In particular, gene clusters encoding the biosynthesis of siderophores aerobactin (iuc) and salmochelin (iro) are associated with invasive disease and are common amongst hypervirulentK. pneumoniaeclones that cause severe community-associated infections such as liver abscess and pneumonia. Concerninglyiuchas also been reported in MDR strains in the hospital setting, where it was associated with increased mortality, highlighting the need to understand, detect and track the mobility of these virulence loci in theK. pneumoniaepopulation.MethodsHere we examined the genetic diversity, distribution and mobilisation ofiucandiroloci among 2503K. pneumoniaegenomes using comparative genomics approaches, and developed tools for tracking them via genomic surveillance.ResultsIroandiucwere detected at low prevalence (<10%). Considerable genetic diversity was observed, resolving into fiveiroand sixiuclineages that show distinct patterns of mobilisation and dissemination in theK. pneumoniaepopulation. The major burden ofiucandiroamongst the genomes analysed was due to two linked lineages (iuc1/iro1, 74% andiuc2/iro2, 14%), each carried by a distinct non-self-transmissible IncFIBKvirulence plasmid type that we designate KpVP-1 and KpVP-2. These dominant types also carry hypermucoidy (rmpA) determinants and include all previously described virulence plasmids ofK. pneumoniae. The otheriucandirolineages were associated with diverse plasmids, including some carrying FII conjugative transfer regions and some imported fromE. coli; the exceptions wereiro3(mobilised byICEKp1), andiuc4(fixed in the chromosome ofK. pneumoniaesubspeciesrhinoscleromatis).Iro/iucMGEs appear to be stably maintained at high frequency within known hypervirulent strains (ST23, ST86, etc), but were also detected at low prevalence in others such as MDR strain ST258.ConclusionsIucandiroare mobilised inK. pneumoniaevia a limited number of MGEs. This study provides a framework for identifying and tracking these important virulence loci, which will be important for genomic surveillance efforts including monitoring for the emergence of hypervirulent MDRK. pneumoniaestrains.
Comparative genomics-first approach to understand diversification of secondary metabolite biosynthetic pathways in symbiotic dinoflagellates
Authors: Beedessee Girish , Hisata Kanako , Roy Michael C. , Van Dolah Frances M. , Satoh Noriyuki , Shoguchi Eiichi 
Published: July 2018

AbstractSymbiotic dinoflagellates of the genus Symbiodinium are photosynthetic and unicellular. They possess smaller nuclear genomes than other dinoflagellates and produce structurally specialized, biologically active, secondary metabolites. Polyketide biosynthetic genes of toxic dinoflagellates have been studied extensively using transcriptomic analyses; however, a comparative genomic approach to understand secondary metabolism has been hampered by their large genome sizes. Here, we use a combined genomic and metabolomics approach to investigate the structure and diversification of secondary metabolite genes to understand how chemical diversity arises in three decoded Symbiodinium genomes (A3, B1 and C). Our analyses identify 71 polyketide synthase and 41 non-ribosomal peptide synthetase genes from two newly decoded genomes of clades A3 and C. Additionally, phylogenetic analyses indicate that almost all of the gene families are derived from lineage-specific gene duplications in Symbiodinium clades, suggesting divergence for environmental adaptation. Few metabolic pathways are conserved among the three clades and we detect metabolic similarity only in the recently diverged clades, B1 and C. We establish that secondary metabolism protein architecture guides substrate specificity and that gene duplication and domain shuffling have resulted in diversification of secondary metabolism genes.
Does the interaction between partnership status and average progesterone level predict women’s preferences for facial masculinity?
Authors: DeBruine Lisa M , Hahn Amanda C , Jones Benedict C 
Published: July 2018

AbstractMany studies have attempted to identify biological factors that reliably predict individual differences in women’s preferences for masculine male faces. Marcinkowska et al. (2018, Hormones & Behavior) recently reported that women’s (N=102) preferences for facial masculinity were predicted by the interaction between their relationship status (partnered versus unpartnered) and average progesterone level. Because previous findings for between-women differences in masculinity preferences have often not replicated well, we attempted to replicate Marcinkowska et al’s result in an open data set from another recent study that had not tested this hypothesis (Jones et al., 2018 Psychological Science). In this sample of 316 women, we found that facial masculinity preferences were predicted by the interaction between women’s relationship status and average progesterone level, consistent with Marcinkowska et al’s results. Together, these findings suggest that the combined effects of relationship status and average progesterone level may predict facial masculinity preferences relatively reliably.
An unbiased template of theDrosophilabrain and ventral nerve cord
Authors: Bogovic John A , Otsuna Hideo , Heinrich Larissa , Ito Masayoshi , Jeter Jennifer , Meissner Geoffrey , Nern Aljoscha , Colonell Jennifer , Malkesman Oz , Ito Kei , Saalfeld Stephan 
Published: July 2018

AbstractThe fruit flyDrosophila melanogasteris an important model organism for neuroscience with a wide array of genetic tools that enable the mapping of individuals neurons and neural subtypes. Brain templates are essential for comparative biological studies because they enable analyzing many individuals in a common reference space. Several central brain templates exist forDrosophila, but every one is either biased, uses sub-optimal tissue preparation, is imaged at low resolution, or does not account for artifacts. No publicly availableDrosophilaventral nerve cord template currently exists. In this work, we created high-resolution templates of theDrosophilabrain and ventral nerve cord using the best-available technologies for imaging, artifact correction, stitching, and template construction using groupwise registration. We evaluated our central brain template against the four most competitive, publicly available brain templates and demonstrate that ours enables more accurate registration with fewer local deformations in shorter time.
The application of Hadoop in Structural Bioinformatics
Authors: Alnasir Jamie , Shanahan Hugh P. 
Published: July 2018

AbstractThe paper reviews the use of the Hadoop platform in Structural Bioinformatics applications. Specifically, we review a number of implementations using Hadoop of high-throughput analyses, e.g. ligand-protein docking and structural alignment, and their scalability in comparison with other batch schedulers and MPI. We find that these deployments for the most part use known executables called from MapReduce rather than rewriting the algorithms. The scalability exhibits a variable behaviour in comparison with other batch schedulers, particularly as direct comparisons on the same platform are generally not available. We do note there is some evidence that MPI implementations scale better than Hadoop. A significant barrier to the use of the Hadoop ecosystem is the difficulty of the interface and configuration of a resource to use Hadoop. This will improve over time as interfaces to Hadoop e.g. Spark improve, usage of cloud platforms (e.g. Azure and AWS) increases and approaches such as the Workflow Definition Language are taken up.
Joint Speed Discrimination and Augmentation For Prosthesis Feedback
Authors: Earley Eric J. , Johnson Reva E. , Hargrove Levi J. , Sensinger Jon W. 
Published: July 2018

AbstractSensory feedback is critical in fine motor control, learning, and adaptation. However, robotic prosthetic limbs currently lack the feedback segment of the communication loop between user and device. Artificial sensory feedback can close this gap, but sometimes this improvement only persists when users cannot see their prosthesis. suggesting the provided feedback is redundant with vision. Thus, given the choice, users rely on vision over artificial feedback. To effectively augment vision, sensory feedback must provide information that vision cannot provide or provides poorly. Although vision is known to be less precise at estimating speed than position, no work has compared speed precision of biomimetic arm movements. In this study, we investigated the uncertainty of visual speed estimates as defined by different virtual arm movements. We found that uncertainty was greatest for visual estimates of joint speeds, compared to absolute or linear endpoint speeds. Furthermore, this uncertainty increased when the joint reference frame speed varied over time, potentially caused by an overestimation of joint speed. Finally, we demonstrate a joint-based sensory feedback paradigm capable of significantly reducing joint speed uncertainty when paired with vision. Ultimately, this work may lead to improved prosthesis control and capacity for motor learning.
3D-printable tools for developmental biology: Improving embryo injection and screening techniques through 3D-printing technology
Authors: Truchado-Garcia Marta , Harland Richard M. , Abrams Michael J. 
Published: July 2018

ABSTRACTDevelopmental biology requires rapid embryo injections and screening. We applied new affordable high-resolution 3D-printing to createfiveeasily modifiable stamp-mold tools that greatly increase injection and screening speed, while simultaneously reducing the harmful aspects of these processes. We designed two stamps that use different approaches to improve the injection efficiency for two different types of embryo, first for embryos from the snailCrepidula fornicata, and second, for those from the spiderParasteatoda tepidariorum. Both drastically improved injection speeds and embryo survival rates, even in novice hands. The other three tools were designed for rapid side-by-side organism orientating and comparison. The first screening tool allows for optimal imaging inXenopus laevistadpoles, while the second and third facilitate rapid high-throughput screening ofXenopus tropicalistadpoles andDanio reriojuveniles, respectively. These designs can act as templates for many injection or screening applications.