bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maximum Likelihood Reconstruction of Ancestral Networks by Integer Linear Programming
Authors: Rajan Vaibhav , Kingsford Carl , Zhang Xiuwei 
Published: March 2019

AbstractMotivationThe study of the evolutionary history of biological networks enables deep functional understanding of various bio-molecular processes. Network growth models, such as the Duplication-Mutation with Complementarity (DMC) model, provide a principled approach to characterizing the evolution of protein-protein interactions (PPI) based on duplication and divergence. Current methods for model-based ancestral network reconstruction primarily use greedy heuristics and yield sub-optimal solutions.ResultsWe present a new Integer Linear Programming (ILP) solution for maximum likelihood reconstruction of ancestral PPI networks using the DMC model. We prove the correctness of our solution that is designed to find the optimal solution. It can also use efficient heuristics from general-purpose ILP solvers to obtain multiple optimal and near-optimal solutions that may be useful in many applications. Experiments on synthetic data show that our ILP obtains solutions with higher likelihood than those from previous methods, and is robust to noise and model mismatch. We evaluate our algorithm on two real PPI networks, with proteins from the families of bZIP transcription factors and the Commander complex. On both the networks, solutions from our ILP have higher likelihood and are in better agreement with independent biological evidence from other studies.AvailabilityA Python implementation is available at https://bitbucket.org/cdal/.Contactvaibhav.rajan@nus.edu.sg
Bone morphogenetic protein 4 gene therapy in mice inhibits myeloma tumor growth, but has a negative impact on bone
Authors: Westhrin Marita , Holien Toril , Zahoor Muhammad , Moen Siv Helen , Buene Glenn , Størdal Berit , Hella Hanne , Yuan Huipin , de Bruijn Joost D , Martens Anton , Groen Richard WJ , Bosch Fatima , Smith Ulf , Sponaas Anne-Marit , Sundan Anders , Standal Therese 
Published: March 2019

AbstractMultiple myeloma is characterized by accumulation of malignant plasma cells in the bone marrow. Most patients suffer from an osteolytic bone disease, caused by increased bone degradation and reduced bone formation. Bone morphogenetic protein 4 (BMP4) is important for both pre- and postnatal bone formation and induces growth arrest and apoptosis of myeloma cells. BMP4-treatment of myeloma patients could have the potential to reduce tumor growth and restore bone formation. We therefore explored BMP4 gene therapy in a human-mouse model of multiple myeloma where humanized bone scaffolds were implanted subcutaneously in RAG2−/−γC−/−mice. Mice were treated with adeno-associated virus serotype 8 BMP4 vectors (AAV8-BMP4) to express BMP4 in the liver. When mature BMP4 was detectable in the circulation, myeloma cells were injected into the scaffolds and tumor growth was examined by weekly imaging. Strikingly, the tumor burden was reduced in AAV8-BMP4 mice compared with the AAV8-CTRL mice, suggesting that increased circulating BMP4 reduced tumor growth. BMP4-treatment also prevented bone loss in the scaffolds, most likely due to reduced tumor load. To delineate the effects of BMP4 overexpression on bone per se, without direct influence from cancer cells, we examined the unaffected, non-myeloma femurs by μCT. Surprisingly, the AAV8-BMP4 mice had significantly reduced trabecular bone volume, trabecular numbers, as well as significantly increased trabecular separation compared with the AAV8-CTRL mice. There was no difference in cortical bone parameters between the two groups. Taken together, BMP4 gene therapy inhibited myeloma tumor growth, but also reduced the amount of trabecular bone in mice. Our data suggest that care should be taken when considering using BMP4 as a therapeutic agent.
Cladocopium community divergence in two Acropora coral hosts across multiple spatial scales
Authors: Davies SW , Moreland K , Wham DC , Kanke MR , Matz MV 
Published: March 2019

AbstractMany broadly-dispersing corals acquire their algal symbionts (Symbiodiniaceae) ‘horizontally’ from their environment upon recruitment. Horizontal transmission could promote coral fitness across diverse environments provided that corals can associate with divergent algae across their range and that these symbionts exhibit reduced dispersal potential. Here we quantified community divergence of Cladocopium algal symbionts in two coral host species (Acropora hyacinthus, Acropora digitifera) across two spatial scales (reefs on the same island, and between islands) across the Micronesian archipelago using microsatellites. We find that both hosts associated with two genetically distinct Cladocopium lineages (C40, C21), confirming that Acropora coral hosts associate with a range of Cladocopium symbionts across this region. Both C40 and C21 exhibited extensive clonality. Clones not only existed across host conspecifics living on the same reef, but also spanned host species, reef sites within islands, and even different islands. Both Cladocopium lineages exhibited moderate host specialization and divergence across islands. In addition, within every island, algal symbiont communities were significantly clustered by both host species and reef site, highlighting that coral-associated Cladocopium communities are structured across small spatial scales and within hosts on the same reef. This is in stark contrast to their coral hosts, which never exhibited significant genetic divergence between reefs on the same island. These results support the view that horizontal transmission could improve local fitness for broadly dispersing Acropora coral species.
A validated workflow for rapid taxonomic assignment and monitoring of a national fauna of bees (Apiformes) using high throughput barcoding
Authors: Creedy Thomas J. , Norman Hannah , Tang Cuong Q. , Chin Kai Qing , Andujar Carmelo , Arribas Paula , O’Connor Rory , Carvell Claire , Notton David G. , Vogler Alfried P. 
Published: March 2019

ABSTRACTImproved taxonomic methods are needed to quantify declining populations of insect pollinators. This study devises a high-throughput DNA barcoding protocol for a regional fauna (United Kingdom) of bees (Apiformes), consisting of reference library construction, a proof-of-concept monitoring scheme, and the deep barcoding of individuals to assess potential artefacts and organismal associations. A reference database of Cytochrome Oxidase subunit 1 (cox1) sequences including 92.4% of 278 bee species known from the UK showed high congruence with morphological taxon concepts, but molecular species delimitations resulted in numerous split and (fewer) lumped entities within the Linnaean species. Double tagging permitted deep illumina sequencing of 762 separate individuals of bees from a UK-wide survey. Extracting the target barcode from the amplicon mix required a new protocol employing read abundance and phylogenetic position, which revealed 180 molecular entities of Apiformes identifiable to species. An additional 72 entities were ascribed to mitochondrial pseudogenes based on patterns of read abundance and phylogenetic relatedness to the reference set. Clustering of reads revealed a range of secondary Operational Taxonomic Units (OTUs) in almost all samples, resulting from traces of insect species caught in the same traps, organisms associated with the insects including a known mite parasite of bees, and the common detection of human DNA, besides evidence for low-level cross-contamination in pan traps and laboratory steps. Custom scripts were generated to conduct critical steps of the bioinformatics protocol. The resources built here will greatly aid DNA-based monitoring to inform management and conservation policies for the protection of pollinators.
LTK is an ER-resident receptor tyrosine kinase that regulates secretion
Authors: Centonze Federica G. , Reiterer Veronika , Nalbach Karsten , Saito Kota , Pawlowski Krzysztof , Behrends Christian , Farhan Hesso 
Published: March 2019

AbstractThe endoplasmic reticulum (ER) is a key regulator of cellular proteostasis because it controls folding, sorting and degradation of secretory proteins. Much has been learned about how environmentally triggered signaling pathways regulate ER function, but only little is known about local signaling at the ER. The identification of ER-resident signaling molecules will help gain a deeper understanding of the regulation of ER function and thus of proteostasis. Here, we show that leukocyte tyrosine kinase (LTK) is an ER-resident receptor tyrosine kinase. Depletion of LTK as well as its pharmacologic inhibition reduces the number of ER exit sites and slows ER-to-Golgi transport. Furthermore, we show that LTK interacts with and phosphorylates Sec12. Expression of a phosphoablating mutant of Sec12 reduces the efficiency of ER export. Thus, LTK-to-Sec12 signaling represents the first example of an ER-resident signaling module the potential to regulate proteostasis.
Dual activity of PNGM-1, a metallo-β-lactamase and tRNase Z, pinpoints the evolutionary origin of subclass B3 metallo-β-lactamases
Authors: Lee Jung Hun , Takahashi Masayuki , Jeon Jeong Ho , Kang Lin-Woo , Seki Mineaki , Park Kwang Seung , Hong Myoung-Ki , Park Yoon Sik , Kim Tae Yeong , Karim Asad Mustafa , Lee Jung-Hyun , Nashimoto Masayuki , Lee Sang Hee 
Published: March 2019

AbstractAntibiotic resistance is a steadily increasing global problem which could lead to a fundamental upheaval in clinical care with the potential to return us to the pre-antibiotic era1-4. The production of β-lactamases, a group of enzymes that confer antibiotic resistance in Gram-negative bacteria, is now one of the major barriers in treating Gram-negative infections5. β-Lactamases are classified according to their catalytic mechanisms into serine β-lactamases and metallo-β-lactamases6,7. There are functional and structural similarities between serine β-lactamases and penicillin-binding proteins, and so serine β-lactamases are thought to have evolved from a penicillin-binding protein7,8. Given the functional and structural differences between serine β-lactamases and metallo-β-lactamases, metallo-β-lactamases are thought to have evolved from a protein other than a penicillin-binding protein, but to date this ancestor remains unknown8-11. We discovered PNGM-1, the first subclass B3 metallo-β-lactamase, in deep-sea sediments that predate the antibiotic era12. Here we discover the dual activity of PNGM-1, pinpointing the evolutionary origin of subclass B3 metallo-β-lactamases. Phylogenetic analysis suggested that PNGM-1 could yield insights into the evolutionary origin of subclass B3 metallo-β-lactamases. We reveal the structural similarities between tRNase Zs and PNGM-1, which prompted us to investigate their evolutionary relationship and the possibility of them possessing dual enzymatic activities. We demonstrate that PNGM-1 has dual activity with both true metallo-β-lactamase and tRNase Z activity, suggesting that PNGM-1 is thought to have evolved from a tRNase Z. We also show kinetic and structural comparisons between PNGM-1 and other proteins including subclass B3 metallo-β-lactamases and tRNase Zs. These comparisons revealed that the B3 metallo-β-lactamase activity of PNGM-1 is a promiscuous activity and subclass B3 metallo-β-lactamases are thought to have evolved through PNGM-1 activity. Our work provides a foundation for the evolution of tRNase Z into subclass B3 metallo-β-lactamases through the dual activity of PNGM-1.
CytoGPS: A Web-Enabled Karyotype Analysis Tool for Cytogenetics
Authors: Abrams Zachary B. , Zhang Lin , Abruzzo Lynne V. , Heerema Nyla A. , Li Suli , Dillon Tom , Rodriguez Ricky , Coombes Kevin R. , Payne Philip R. O. 
Published: March 2019

AbstractKaryotype data are the most common form of genetic data that is regularly used clinically. They are collected as part of the standard of care in many diseases, particularly in pediatric and cancer medicine contexts. Karyotypes are represented in a unique text-based format, with a syntax defined by the International System for human Cytogenetic Nomenclature (ISCN). While human-readable, ISCN is not intrinsically machine-readable. This limitation has prevented the full use of complex karyotype data in discovery science use cases. To enhance the utility and value of karyotype data, we developed a tool named CytoGPS. CytoGPS first parses ISCN karyotypes into a machine-readable format. It then converts the ISCN karyotype into a binary Loss-Gain-Fusion (LGF) model, which represents all cytogenetic abnormalities as combinations of loss, gain, or fusion events, in a format that is analyzable using modern computational methods. Such data is then made available for comprehensive “downstream” analyses that previously were not feasible.Availability and ImplementationFreely available at https://cytogps.orgContactprpayne@wustl.eduSupplementary informationNot applicable
Biotic interactions affect fitness across latitudes, but only drive local adaptation in the tropics
Authors: Hargreaves Anna L. , Germain Rachel M. , Bontrager Megan , Persi Joshua , Angert Amy L. 
Published: March 2019

AbstractLocal adaptation to broad-scale environmental heterogeneity can increase species’ distributions and diversification, but which environmental components commonly drive local adaptation— particularly the importance of biotic interactions—is unclear. Biotic interactions should drive local adaptation when they impose consistent divergent selection; if this is common we expect experiments to detect more frequent and stronger local adaptation when biotic interactions are left intact. We tested this hypothesis using a meta-analysis of common-garden experiments from 138 studies (149 taxa). Across studies, local adaptation was common and biotic interactions affected fitness. Nevertheless, local adaptation was neither more common nor stronger when biotic interactions were left intact, either between experimental treatments within studies (control vs. biotic interactions experimentally manipulated) or between studies that used natural vs. biotically-altered transplant environments. However, tropical studies, which comprised only 7% of our data, found strong local adaptation in intact environments but not when negative biotic interactions were ameliorated, suggesting that interactions frequently drive local adaptation in the tropics. Our results suggest that biotic interactions often fail to drive local adaptation even though they affect fitness, perhaps because the temperate-zone biotic environment is less predictable at the spatiotemporal scales required for local adaptation.
Chrysin, but not flavone backbone, decreases anxiety-like behavior in animal screens
Authors: German-Ponciano León Jesús , Costa Bruna Patrícia Dutra , Feitosa Leonardo Miranda , dos Santos Campos Kimberly , da Silva Chaves Suianny Nayara , Cueto-Escobedo Jonathan , Lima-Maximino Monica , Rodríguez-Landa Juan Francisco , Maximino Caio 
Published: March 2019

AbstractChrysin (5,7-dihydroxyflavone), a nutraceutical flavonoid present in diverse plants, has a backbone structure shared with the flavone backbone, with additional hydroxyl groups that confers its antioxidant properties and effects at the GABAA receptor complex. However, whether these effects are due to the hydroxyl groups is unknown. Here we report the effects of chrysin or the flavone backbone (1 mg/kg) in rats subjected to the elevated plus-maze and the locomotor activity test, as well as in the zebrafish evaluated in light/dark model. Chrysin, but not flavone, increased entries and time in the open arms of the elevated plus-maze, as well as time on white compartment of the light/dark model in zebrafish. These effects were comparable to diazepam, and were devoid of motor effects in both tests, as well as in the locomotor activity test. On the other hand, flavone decreased risk assessment in the light/dark test but increased rearing in the locomotor activity test in rats, suggesting effects threat information gathering; important species differences suggest new avenues of research. It is suggested that the specific effects of chrysin in relation to flavone include more of a mechanism of action in which in addition to its action at the GABAA/benzodiazepine receptor complex also could be involved its free radical scavenging abilities, which require specific research.Preprinthttps://doi.org/10.1101/575514;Data and scriptshttps://github.com/lanec-unifesspa/chrysin
Single-base mapping of m6A by an antibody-independent method
Authors: Zhang Zhang , Chen Li-Qian , Zhao Yu-Li , Yang Cai-Guang , Roundtree Ian A , Zhang Zijie , Ren Jian , Xie Wei , He Chuan , Luo Guan-Zheng 
Published: March 2019

AbstractN6-methyladenosine (m6A) is one of the most abundant mRNA modifications in eukaryotes, involved in various pivotal processes of RNA metabolism. The most popular high-throughput m6A identification method depends on the anti-m6A antibody but suffers from poor reproducibility and limited resolution. Exact location information is of great value for understanding the dynamics, machinery and functions of m6A. Here we developed a precise and high-throughput antibody-independent m6A identification method based on the m6A-sensitive RNA endoribonuclease (m6A-sensitive RNA-Endoribonuclease-Facilitated sequencing or m6A-REF-seq). Whole-transcriptomic, single-base m6A maps generated by m6A-REF-seq quantitatively displayed an explicit distribution pattern with enrichment on stop codons. Independent methods were used to validate the methylation status and abundance of individual m6A sites, confirming the high reliability and accuracy of m6A-REF-seq. We applied this method on five tissues from human, mouse and rat, showing that m6A sites were conserved with single nucleotide specificity and tend to cluster among species.
Btbd6-dependent Plzf recruitment to Cul3 E3 ligase complexes through BTB domain heterodimerization
Authors: Ismail Mohamed , Martin Stephen R. , Ball Neil J. , Taylor Ian A. , Howell Steven , Wilkinson David G. , Smerdon Stephen J. 
Published: March 2019

AbstractThe Cul3 adaptor Btbd6 plays crucial roles in neural development by driving the ubiquitin-dependent degradation of promyelocytic zinc finger transcription factor (Plzf). Btbd6 has conserved motifs, BTB-BACK-PHR, and by analogy with other BTB-BACK adaptors, might be expected to bind to Cul3 through the BTB-BACK domain, and to substrate through the PHR domain. However, we now present a mode of adaptor-substrate interaction through heterodimerisation between the normally homodimeric BTB domains of Btbd6 and Plzf. This heterodimerization appears to occur through monomer exchange that is detected only at or near physiological concentrations. The Btbd6-Plzf heterodimer thus formed assembles into a ternary complex with Cul3. In addition we show that the BTB and PHR domains of Btbd6 promote localisation in the nucleus and that the BACK domain contains a nuclear export signal. Our findings support a model whereby Btbd6 moves into and out of the nucleus, iteratively ‘sweeping’ Plzf into the cytoplasm and enabling complex formation with Cul3 that presents Plzf for ubiquitination.HighlightsA general mechanism for recruitment of BTB domain-containing substrates by BTBdomain adaptors for the Cul3 E3 ligase complexNuclear export of the Plzf/Btbd6 complex mediated by a NES within the Btbd6 BACK domainCul3-dependent Plzf ubiquitylation through heterodimerisation of BTB domains on adaptor and substrate by monomer exchang
Watered-down biodiversity? A comparison of metabarcoding results from DNA extracted from matched water and bulk tissue biomonitoring samples
Authors: Hajibabaei Mehrdad , Porter Teresita M. , Robinson Chloe V. , Baird Donald J. , Shokralla Shadi , Wright Michael 
Published: March 2019

AbstractBiomonitoring programs have evolved beyond the sole use of morphological identification to determine the composition of invertebrate species assemblages in an array of ecosystems. The application of DNA metabarcoding in freshwater systems for assessing benthic invertebrate communities is now being employed to generate biological information for environmental monitoring and assessment. A possible shift from the extraction of DNA from net-collected bulk benthic samples to its extraction directly from water samples for metabarcoding has generated considerable interest based on the assumption that taxon detectability is comparable when using either method. To test this, we studied paired water and benthos samples from a taxon-rich wetland complex, to investigate differences in the detection of taxa from each sample type. We demonstrate that metabarcoding of DNA extracted directly from water samples is a poor surrogate for DNA extracted from bulk benthic samples, focusing on key bioindicator groups. Our results continue to support the use of bulk benthic samples as a basis for metabarcoding-based biomonitoring, with nearly three times greater total richness in benthic samples compared to water samples. We also demonstrated that few arthropod taxa are shared between collection methods, with a notable lack of key bioindicator EPTO taxa in the water samples. Although species coverage in water could likely be improved through increased sample replication and/or increased sequencing depth, benthic samples remain the most representative, cost-effective method of generating aquatic compositional information via metabarcoding.
Refinement of the primate corticospinal pathway during prenatal development
Authors: Ribeiro Gomes Ana Rita , Olivier Etienne , Killackey Herbert P. , Giroud Pascale , Berland Michel , Knoblauch Kenneth , Dehay Colette , Kennedy Henry 
Published: March 2019

AbstractPerturbation of the developmental refinement of the corticospinal pathway leads to motor disorders. In non-primates developmental refinement is well documented, however in primates invasive investigations of the developing corticospinal pathway have been confined to neonatal and postnatal stages when refinement is relatively modest.Here, we investigated the developmental changes in the distribution of corticospinal projection neurons in cynomolgus monkey. Injections of retrograde tracer at the cervical levels of the spinal cord at embryonic day (E) 95 and E105 show that (i) areal distribution of back-labeled neurons is more extensive than in the neonate and dense labeling is found in prefrontal, limbic, temporal and occipital cortex; (ii) distributions of contra- and ipsilateral projecting corticospinal neurons are comparable in terms of location and numbers of labeled neurons, in contrast to the adult where the contralateral projection is an order of magnitude higher than the ipsilateral projection. Findings from one largely restricted injection suggest a hitherto unsuspected early innervation of the gray matter.In the fetus there was in addition dense labeling in the central nucleus of the amygdala, the hypothalamus, the subthalamic nucleus and the adjacent region of the zona incerta, subcortical structures with only minor projections in the adult control.