bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary and ontogenetic changes of the anatomical organization and modularity in the skull of archosaurs
Authors: Lee Hiu Wai , Esteve-Altava Borja , Abzhanov Arkhat 
Published: February 2020

AbstractComparative anatomy studies of the skull of archosaurs provide insights on the mechanisms of evolution for the morphologically and functionally diverse species of crocodiles and birds. One of the key attributes of skull evolution is the anatomical changes associated with the physical arrangement of cranial bones. Here, we compare the changes in anatomical organization and modularity of the skull of extinct and extant archosaurs using an Anatomical Network Analysis approach. We show that the number of bones, their topological arrangement, and modular organization can discriminate birds from non-avian dinosaurs, and crurotarsans. We could also discriminate extant taxa from extinct species when adult birds were included. By comparing within the same framework, juveniles and adults for crown birds and alligator(Alligator mississippiensis),we find that adult and juvenile alligator skulls are topologically similar, whereas juvenile bird skulls have a morphological complexity and anisomerism more similar to those of non-avian dinosaurs and crurotarsans than of their own adult forms. Clade-specific ontogenetic differences in skull organization, such as extensive postnatal fusion of cranial bones in crown birds, can explain this pattern. The fact that juvenile and adult skulls in birds do share a similar anatomical integration suggests the presence of a specific constraint to their ontogenetic growth.
Δ-dN/dS: A New Criteria to Distinguish among Different Selection Modes in Gene Evolution
Authors: Gu Xun 
Published: February 2020

AbstractOne of the most widely-used measures for protein evolution is the ratio of nonsynonymous distance (dN) to synonymous distance (dS). Under the assumption that synonymous substitutions in the coding region are selectively neutral, thedN/dSratio can be used to test the adaptive evolution ifdN/dS>1 statistically significantly. However, due to selective constraints imposed on amino acid sites, most encoding genes demonstratedN/dS<1. As a result,dN/dSof a gene is less than 1, even some sites may have experienced positive selections. In this paper, we develop a new criterion, calledΔ-dN/dS, for positive selection testing by introducing an indexH, which is a relative measure of rate variation among sites. Under the context of strong purifying selection at some amino acid sites, our model predictsdN/dS=1-Hfor the neutral evolution,dN/dS<1-Hfor the nearly-neutral selection, anddN/dS>1-Hfor the adaptive evolution. The potential of this new method for resolving the neutral-adaptive debates has been illustrated by case studies. For over 4000 vertebrate genes, virtually all of them showeddN/dS<1-H, indicating the dominant role of the nearly-neutral selection in molecular evolution. Moreover, we calculated thedN/dSratio for cancer somatic mutations of a human gene, specifically denoted byCN/CS. For over 4000 human genes in cancer genomics, about 55% of genes showed 1-H<CN/CS<1, about 45% of genes showedCN/CS<1, whereas less than 1% of genes showedCN/CS<1-H. Together our analysis suggested driver mutations, i.e., those initiate and facilitate carcinogenesis, confer a selective advantage on cancer cells, leading toCN/CS>1 (strong positive selection) or 1-H<CN/CS<1 (weak positive selection, combined with strong purifying selection), whereas nearly neutral selection due to reduced effective clonal size is highly unlikely in cancer evolution.
Mixed Culture of Bacterial Cell for Large Scale DNA Storage
Authors: Hao Min , Qiao Hongyan , Gao Yanmin , Wang Zhaoguan , Qiao Xin , Chen Xin , Qi Hao 
Published: February 2020

AbstractDNA emerged as novel material for mass data storage, the serious problem human society is facing. Taking advantage of current synthesis capacity, massive oligo pool demonstrated its high-potential in data storage in test tube. Herein, mixed culture of bacterial cells carrying mass oligo pool that was assembled in a high copy plasmid was presented as a stable material for large scale data storage. Living cells data storage was fabricated by a multiple-steps process, assembly, transformation and mixed culture. The underlying principle was explored by deep bioinformatic analysis. Although homology assembly showed sequence context dependent bias but the massive digital information oligos in mixed culture were constant over multiple successive passaging. In pushing the limitation, over ten thousand distinct oligos, totally 2304 Kbps encoding 445 KB digital data including texts and images, were stored in bacterial cell, the largest archival data storage in living cell reported so far. The mixed culture of living cell data storage opens up a new approach to simply bridge the in vitro and in vivo storage system with combined advantage of both storage capability and economical information propagation.
A Sequence-Pair-Classification-Based Method for Detecting and Correcting Under-Clustered Gene Families
Authors: Yadav Akshay , Fernández-Baca David , Cannon Steven B. 
Published: February 2020

AbstractGene families are groups of genes that have descended from a common ancestral gene present in the species under study. Current, widely used gene family building algorithms can produce family clusters that may be fragmented or missing true family sequences (under-clustering). Here we present a classification method based on sequence pairs that, first, inspects given families for under-clustering and then predicts the missing sequences for the families using family-specific alignment score cutoffs. We have tested this method on a set of curated, gold-standard (“true”) families from the Yeast Gene Order Browser (YGOB) database, including 20 yeast species, as well as a test set of intentionally under-clustered (“deficient”) families derived from the YGOB families. For 83% of the modified yeast families, our pair-classification method was able to reliably detect under-clustering in “deficient” families that were missing 20% of sequences relative to the full/” true” families. We also attempted to predict back the missing sequences using the family-specific alignment score cutoffs obtained during the detection phase. In the case of “pure” under-clustered families (under-clustered families with no “wrong”/unrelated sequences), for 78% of families the prediction precision and recall was ≥0.75, with mean precision = 0.928 and mean recall = 0.859. For “impure” under-clustered families, (under-clustered families containing closest sequences from outside the family, in addition to missing true family sequences), the prediction precision and recall was ≥0.75 for 63% of families with mean precision = 0.790 and mean recall = 0.869. To check if our method can detect and correct incomplete families obtained using existing family building methods, we attempted to correct 374 under-clustered yeast families produced using the OrthoFinder tool. We were able to predict missing sequences for at least 19 yeast families with mean precision of 0.9 and mean recall of 0.65. We also analyzed 14,663 legume families built using the OrthoFinder program, with 14 legume species. We were able to identify 1,665 OrthoFinder families that were missing one or more sequences - sequences which were previously un-clustered or clustered into unusually small families. Further, using a simple merging strategy, we were able to merge 2,216 small families into 933 under-clustered families using the predicted missing sequences. Out of the 933 merged families, we could confirm correct mergings in at least 534 families using the maximum-likelihood phylogenies of the merged families. We also provide recommendations on different types of family-specific alignment score cutoffs that can be used for predicting the missing sequences based on the “purity” of under-clustered families and the chosen precision and recall for prediction. Finally, we provide the containerized version of the pair-classification method that can be applied on any given set of gene families.
ALG-2 and Peflin Stimulate or Inffibit Copii Targeting and Secretion in Response to Calcium Signaling
Authors: Sargeant John , Seiler Danette , Costain Tucker , Madreiter-Sokolowski Corina , Gordon David E. , Peden Andrew A. , Malli Roland , Graier Wolfgang F. , Ray Jesse C. 
Published: February 2020

ABSTRACTER-to-Golgi transport is the first step in the constitutive secretory pathway which, unlike regulated secretion, is believed to proceed non-stop regardless of Ca2+flux. Rowever, here we demonstrate that penta-EF hand (PEF) proteins ALG-2 and peflin constitute a hetero-bifunctional COPII regulator that responds to Ca2+signaling by adjusting the ER export rate of COPII-sorted cargos up or down by ~50%. At steady-state Ca2+, ALG-2/peflin hetero-complexes bind to ER exit sites (ERES) through the ALG-2 subunit to confer a low, buffered secretion rate, while peflin-lacking ALG-2 complexes markedly stimulate secretion. During Ca2+signaling, ALG-2 complexes lacking peflin can either increase or decrease the secretion rate depending on signaling intensity and duration-phenomena that could contribute to cellular growth and intercellular communication, following secretory increases, or protection from excitotoxicity and infection following decreases. In epithelial normal rat kidney (NRK) cells, the Ca2+-mobilizing agonist ATP causes ALG-2 to depress ER export, while in neuroendocrine PC12 cells, Ca2+mobilization by ATP results in ALG-2-dependent enhancement of secretion. Within the NRK cell model, distinct Ca2+signaling patterns can produce opposing ALG-2-dependent effects on secretion. Mechanistically, ALG-2-dependent depression of secretion involves decreased COPTT outer shell and increased peflin targeting to ERES, while ALG-2-dependent enhancement of secretion involves increased COPTT outer shell and decreased peflin at ERES. PEF protein complexes represent a true regulator of transport as they are dispensable for secretion yet adjust the secretion rate to physiological conditions. Their dynamics affects secretion of important physiological cargoes such as collagen T and significantly impacts ER stress.
Global proteomics ofUbqln2-based murine models of ALS
Authors: Whiteley Alexandra M. , Prado Miguel A. , de Poot Stefanie A.H. , Paulo Joao A. , Ashton Marissa , Dominguez Sara , Weber Martin , Ngu Hai , Szpyt John , Jedrychowski Mark P. , Easton Amy , Gygi Steven P. , Kurz Thimo , Monteiro Mervyn J. , Brown Eric J. , Finley Daniel 
Published: February 2020

AbstractFamilial forms of neurodegenerative diseases commonly involve mutation of aggregation-prone proteins or components of the protein degradation machinery that act on aberrant proteins.Ubqln2encodes a member of the UBL/UBA family of proteasome shuttle factors that is thought to facilitate proteasomal degradation of substrates, and mutation of this gene results in a familial form of ALS/FTD in humans. HowUbqln2dysfunction leads to neurodegeneration, however, remains uncertain. We undertook a comprehensive study to identify proteomic changes uponUbqln2perturbation in multiple murine models ofUbqln2-mediated neurodegenerative disease. By performing quantitative multiplexed proteomics on neural tissues of affected animals, we identified a small group of proteins whose abundance is tightly linked to UBQLN2 function: the ubiquitin ligase TRIM32 and two retroelement-derived proteins, PEG10 and CXX1B. Further studies using cultured cells of human origin, including induced neurons, found similar changes in protein abundance uponUbqln2loss, and pulse-chase studies suggested that PEG10 and TRIM32 are direct clients of UBQLN2. In conclusion, our study provides a deep understanding of the proteomic landscape of ALS-relatedUbqln2mutants and identifies candidate client proteins that are alteredin vivoin disease models and whose degradation is promoted by UBQLN2.
Cytoplasmic sharing through apical membrane remodeling
Authors: Peterson Nora G. , Stormo Benjamin M. , Schoenfelder Kevin P. , King Juliet S. , Lee Rayson R. S. , Fox Donald T. 
Published: February 2020

ABSTRACTMultiple nuclei sharing a common cytoplasm are found in diverse tissues, organisms, and diseases. Yet, multinucleation remains a poorly understood biological property. Cytoplasm sharing invariably involves plasma membrane breaches. In contrast, we discovered cytoplasm sharing without membrane breaching in highly resorptiveDrosophilarectal papillae. During a six-hour developmental window, 100 individual papillar cells assemble a multinucleate cytoplasm, allowing passage of proteins of at least 27kDa throughout papillar tissue. Papillar cytoplasm sharing does not employ canonical mechanisms such as failed cytokinesis or muscle fusion pore regulators. Instead, sharing requires gap junction proteins (normally associated with transport of molecules <1kDa), which are positioned by membrane remodeling GTPases. Our work reveals a new role for apical membrane remodeling in converting a multicellular epithelium into a giant multinucleate cytoplasm.ONE SENTENCE SUMMARYApical membrane remodeling in a resorptiveDrosophilaepithelium generates a shared multinuclear cytoplasm.
Dissimilatory Nitrate Reduction to Ammonium in the Cable BacteriumCa. Electronema Sp. GS
Authors: Marzocchi Ugo , Thorup Casper , Dam Ann-Sofie , Schramm Andreas , Risgaard-Petersen Nils 
Published: February 2020

ABSTRACTCable bacteria are filamentous Desulfobulbaceae that split the energy-conserving reaction of sulphide oxidation into two half reactions occurring in distinct cells. Cable bacteria can use nitrate, but the reduction pathway is unknown, making it difficult to assess their direct impact on the N-cycle. Here we show that the freshwater cable bacteriumCa.Electronema sp. GS performs dissimilatory nitrate reduction to ammonium (DNRA).15NO3−-amended sediment withCa.Electronema sp. GS showed higher rates of DNRA and nitrite production than sediment withoutCa.Electronema sp. GS. Electron flux from sulphide oxidation, inferred from electric potential measurements, matched the electron flux needed to drive cable bacteria-mediated nitrate reduction.Ca.Electronema sp. GS expressed a completenapoperon for periplasmic nitrate reduction to nitrite, and genes encoding a periplasmic multiheme cytochrome (pMHC), homolog to a pMHC that can catalyse nitrite reduction to ammonium inCa.Maribeggiatoa. Phylogenetic analysis suggests that the capacity for DNRA was acquired in multiple events through horizontal gene transfer from different organisms, before cable bacteria split into different salinity niches. The architecture of the nitrate reduction system suggests absence of energy conservation through oxidative phosphorylation, indicating that cable bacteria primarily conserve energy through the half reaction of sulfide oxidation.
Unifying the Ambivalent Mechanisms of Protein-Stabilising Osmolytes
Authors: Mukherjee Mrinmoy , Mondal Jagannath 
Published: February 2020

AbstractThe mechanism of protein stabilization by zwiterionic osmolytes has remained a long-standing puzzle. While the prevalent mechanistic hypothesis suggests an ‘osmo-phobic’ model in which osmolytes are assumed to stabilize proteins by preferentially excluding themselves from the protein surface, emerging evidences of preferential binding of popular osmolyte trimethyl amine N-oxide (TMAO) with hydrophobic macromolecules contradict this view. Here we address these contrasting perspectives by investigating the folding mechanism of a set of mini proteins in aqueous solutions of two different osmolytes glycine and TMAO, via free energy simulations. Our results demonstrate that, while both osmolytes are found to stabilize the folded conformation of the mini proteins, their mechanism of actions are mutually diverse: Specifically, glycine always depletes from the surface of all mini proteins, thereby conforming to the osmophobic model; but TMAO is found to display ambivalent signatures of protein-specific preferential binding and exclusion to/from the protein surface. At molecular level, the presence of an extended hydrophobic patch in protein topology is found to be recurrent motif in proteins leading to favorable binding with TMAO. Finally, an analysis based upon the preferential interaction theory and folding free energetics reveals that irrespective of preferential binding vs exclusion of osmolytes, it is therelativepreferential depletion of osmolytes on transition from folded to unfolded conformation of proteins, which drives the overall conformational equilibrium towards the folded state in presence of osmolytes. Taken together, moving beyond the model system and hypothesis, this work brings out ambivalent mechanism of osmolytes on proteins and provides an unifying justification.
Instability of aquaglyceroporin (AQP) 2 contributes to drug resistance inTrypanosoma brucei
Authors: Quintana Juan F. , Bueren-Calabuig Juan , Zuccotto Fabio , de Koning Harry P. , Horn David , Field Mark C. 
Published: February 2020

AbstractDefining mode of action is vital for both developing new drugs and predicting potential resistance mechanisms. African trypanosome pentamidine and melarsoprol sensitivity is predominantly mediated by aquaglyceroporin 2 (TbAQP2), a channel associated with water/glycerol transport. TbAQP2 is expressed at the flagellar pocket membrane and chimerisation with TbAQP3 renders parasites resistant to both drugs. Two models for how TbAQP2 mediates pentamidine sensitivity have emerged; that TbAQP2 mediates pentamidine translocation or via binding to TbAQP2, with subsequent endocytosis, but trafficking and regulation of TbAQPs is uncharacterised. We demonstrate that TbAQP2 is organised as a high order complex, is ubiquitylated and transported to the lysosome. Unexpectedly, mutation of potential ubiquitin conjugation sites, i.e. cytoplasmic lysine residues, reduced folding and tetramerization efficiency and triggered ER retention. Moreover, TbAQP2/TbAQP3 chimerisation also leads to impaired oligomerisation, mislocalisation, and increased turnover. These data suggest that TbAQP2 stability is highly sensitive to mutation and contributes towards emergence of drug resistance.
The HPA stress axis shapes aging rates in long-lived, social mole-rats
Authors: Sahm Arne , Hoffmann Steve , Koch Philipp , Henning Yoshiyuki , Bens Martin , Groth Marco , Burda Hynek , Begall Sabine , Ting Saskia , Goetz Moritz , Daele Paul Van , Staniszewska Magdalena , Klose Jasmin , Costa Pedro Fragoso , Platzer Matthias , Szafranski Karol , Dammann Philip 
Published: February 2020

AbstractSexual activity and/or reproduction doubles life expectancy in the long-lived rodent genusFukomys. To investigate the molecular mechanisms underlying this phenomenon, we analyzed a total of 636 RNA-seq samples across 15 tissues. This analysis suggests that the differences in life expectancy between reproductive and non-reproductive mole-rats are mainly caused by critical changes in the regulation of the hypothalamic-pituitary-adrenal stress axis, which we further substantiate with a series of independent evidence. In accordance with previous studies, the up-regulation of the proteasome and several so-called “anti-aging molecules”, such as DHEA, is also linked with enhanced life expectancy. On the other hand, several our results oppose crucial findings in short-lived model organisms. For example, we found the up-regulation of the IGF1/GH axis and several other anabolic processes to be compatible with a considerable lifespan prolongation. These contradictions question the extent to which findings from short-lived species can be transferred to longer-lived ones.
Loss of ricePARAQUAT TOLERANCE 3confers enhanced resistance to abiotic stresses and increases grain yield in field
Authors: Alfatih Alamin , Wu Jiu , Jan Sami Ullah , Zhang Zi-Sheng , Xia Jing-Qiu , Xiang Cheng-Bin 
Published: February 2020

ABSTRACTPlants frequently suffer from environmental stresses in nature and have evolved sophisticated and efficient mechanisms to cope with the stresses. To balance between growth and stress response, plants are equipped with efficient means to switch off the activated stress responses when stresses diminish. We previously revealed such an off-switch mechanism conferred by ArabidopsisPQT3, knockout of which significantly enhances resistance to abiotic stresses. To explore whether the rice homologOsPQT3is functionally conserved, we generated three knockout mutants with CRISPR-Cas9 technology. TheOsPQT3knockout mutants (ospqt3) display enhanced resistance to oxidative and salt stress with elevated expression ofOsGPX1,OsAPX1, andOsSOD1. More importantly, theospqt3mutants show significantly enhanced agronomic performance with higher yield compared with the wild type under salt stress in greenhouse as well as in field conditions. We further showed thatOsPQT3was rapidly down regulated in response to oxidative and other abiotic stresses asAtPQT3. Taken together, these results support our previous findings that AtPQT3 acts as an off-switch in stress response, which is well conserved in rice. Therefore,PQT3locus provides a promising candidate for crop improvement with enhanced stress resistance by gene editing technology.
RiceNIN-LIKE PROTEIN 1Rapidly Responds to Nitrogen Deficiency and Improves Yield and Nitrogen Use Efficiency
Authors: Alfatih Alamin , Wu Jie , Zhang Zi-Sheng , Xia Jing-Qiu , Jan Sami Ullah , Yu Lin-Hui , Xiang Cheng-Bin 
Published: February 2020

ABSTRACTNitrogen (N) is indispensable for crop growth and yield, but excessive agricultural application of nitrogenous fertilizers has generated severe environmental problems. A desirable and economical solution to cope with these issues is to improve crop nitrogen use efficiency (NUE). Plant NUE has been a focal point of intensive research worldwide, yet much more has to be learned about its genetic determinants and regulation. Here, we show that riceNIN-LIKE PROTEIN 1(OsNLP1) plays a fundamental role in N utilization. OsNLP1 protein localizes in nucleus and its transcript level is rapidly induced by N starvation. Overexpression ofOsNLP1improves plant growth, grain yield and NUE under different N conditions while knockout ofOsNLP1impairs grain yield and NUE under N limiting conditions. OsNLP1 regulates nitrate and ammonium utilization by cooperatively orchestrating multiple N uptake and assimilation genes. Chromatin immunoprecipitation and yeast-one-hybrid assays show that OsNLP1 can directly bind to the promoter of these genes to activate their expression. Therefore, our results demonstrate that OsNLP1 is a key regulator of N utilization and represents a potential target for improving NUE and yield in rice.One-sentence summaryOsNLP1 rapidly responds to N availability, enhances N uptake and assimilation, and holds great potential in promoting high yield in rice.