bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural robustness affects the engineerability of aminoacyl-tRNA synthetases for genetic code expansion
Authors: Grasso Katherine T. , Yeo Megan Jin Rae , Hillenbrand Christen M. , Ficaretta Elise D. , Italia James S. , Huang Rachel L. , Chatterjee Abhishek 
Published: November 2019

AbstractThe ability to engineer the substrate specificity of natural aminoacyl-tRNA synthetase/tRNA pairs facilitates the site-specific incorporation of noncanonical amino acids (ncAAs) into proteins. The Methanocaldococcus jannaschii derived tyrosyl-tRNA synthetase (MjTyrRS)/tRNA pair has been engineered to incorporate numerous ncAAs into protein expressed in bacteria. However, it cannot be used in eukaryotic cells due to cross-reactivity with its host counterparts. The E. coli derived tyrosyl-tRNA synthetase (EcTyrRS)/tRNA pair offers a suitable alternative to this end, but a much smaller subset of ncAAs has been genetically encoded using this pair. Here we report that this discrepancy, at least partly, stems from the lower structural robustness of EcTyrRS relative to MjTyrRS. We show that engineered TyrRS mutants in general exhibit significantly lower thermostability relative to their wild-type counterparts. Derived from a thermophilic archaeon, MjTyrRS is a remarkably sturdy protein and tolerates extensive active site engineering without a catastrophic loss of stability at physiological temperature. In contrast, EcTyrRS exhibits significantly lower thermostability, rendering some of its engineered mutants insufficiently stable at physiological temperature. Our observations identify the structural robustness of an aaRS as an important factor that significantly influences how extensively it can be engineered. To overcome this limitation, we have further developed chimeras between EcTyrRS and its homolog from a thermophilic bacteria, which offer an optimal balance between thermostability and activity. We show that the chimeric bacterial TyrRSs show enhanced tolerance for destabilizing active site mutations, providing a potentially more engineerable platform for genetic code expansion.
Understory light quality affects leaf pigments and leaf phenology in different plant functional types
Authors: Brelsford CC , Trasser M , Paris T , Hartikainen SM , Robson TM 
Published: November 2019

AbstractUnderstory plant species take on different functional strategies, whereby some exploit periods of available light in springtime before the canopy closes, and others also benefit from sunlight later in autumn when the canopy opens again. These strategies involve understory species coordinating phenological events to pre-empt canopy leaf out and to extend their growing season beyond canopy leaf senescence, meanwhile accumulating photo-protective pigments which mitigate periods of high-light exposure. Canopy closure brings shade to the understory, but also causes drastic changes in light quality. Whilst many experiments manipulating spectral quality have revealed understory plant responses to the changing R:FR ratio in shade, effect of the blue and UV regions have been examined very little. We installed filters attenuating short wavelength regions of the solar spectrum in a forest understory in southern Finland, creating the following treatments: a transparent control filter, and filters attenuating UV radiation < 350 nm, all UV radiation, and both UV and blue light. In eight understory species, representing different plant functional types, we repeatedly assessed leaf optical properties to obtain epidermal flavonol and anthocyanin contents from leaf emergence in spring to leaf senescence in autumn, during both 2017 and 2018. Flavonols responded more to seasonal changes in light quality in relatively light-demanding species than in shade-tolerant and wintergreen species; and were particularly responsive to blue light. However, anthocyanins were largely unaffected by our filter treatments, suggesting that other cues such as cold temperatures govern their seasonal variation. UV radiation only accelerated leaf senescence inAcer platanoidesseedlings, but blue light accelerated leaf senescence in all species measured apart fromQuercus robur. In summary, seasonal changes in understory solar radiation in the blue and UV regions affected leaf pigments and leaf phenology; particularly for more light-demanding species. An increase in canopy duration under climate change will extend the period of shade in the understory, with consequences for the spectral cues available to understory plants. The resultant reduction in blue and UV radiation in shade, could delay leaf senescence in the understory even further.
Phylodynamics of sunflower chlorotic mottle virus, a re-emerging pathosystem
Authors: Mederos Dariel Cabrera , Torres Carolina , Bejerman Nicolás , Trucco Verónica , Lenardon Sergio , Mora Michel Leiva , Giolitti Fabián 
Published: November 2019

AbstractDistribution and epidemiological patterns of sunflower chlorotic mottle virus (SCMoV) in sunflower (Helianthus annuusL.) growing areas in Argentina were studied from 2006 to 2017. The virus was detected exclusively in the Pampas region (Entre Ríos, Santa Fe, Córdoba, La Pampa and Buenos Aires provinces). Phylodynamic analyses performed using the coat protein gene of SCMoV isolates from sunflower and weeds dated the most recent common ancestor (MRCA) back to 1887 (HPD95% = 1572-1971), which coincides with the dates of sunflower introduction in Argentina. The MRCA was located in the south of Buenos Aires province and was associated with sunflower host (posterior probability for the ancestral host, ppah= 0.98). The Bayesian phylodynamic analyses revealed the dispersal patterns of SCMoV, suggesting a link between natural host diversity, crop displacement by human activities and virus spread.
Ytterbium-doped fibre femtosecond laser offers robust design with deep and precise microsurgery
Authors: Harreguy MB , Marfil V , Gabel CV , Chung SH , Haspel G 
Published: November 2019

AbstractLaser microsurgery is a powerful tool for neurobiology used to ablate cells and sever neurites in-vivo. We compare a relatively new laser source to two well-established designs. Rare-earth-doped mode-locked fibre laser that produce high power pulsed radiation recently gained popularity for industrial uses. Such systems are manufactured at high standards of robustness and low maintenance requirements typical of solid-state lasers. We demonstrate that an Ytterbium-doped fibre femtosecond laser is comparable in precision to other femtosecond lasers, but with added reliability. It is more precise and can lesion deeper in tissue than a solid-state nanosecond laser. These advantages are not specific to the model system ablated for our demonstration, namely neurites in the nematode C. elegans, but are applicable to other systems and transparent tissue where a precise submicron resolution dissection is required.
Genome-wide DNA methylation analysis of heavy cannabis exposure in a New Zealand longitudinal cohort
Authors: Osborne Amy J. , Pearson John F. , Noble Alexandra J. , Gemmell Neil J. , Horwood L. John , Boden Joseph M. , Benton Miles , Macartney-Coxson Donia P. , Kennedy Martin A. 
Published: November 2019

ABSTRACTCannabis use is of increasing public health interest globally. Here we examined the effect of cannabis use, with and without tobacco, on genome-wide DNA methylation in a longitudinal birth cohort (Christchurch Health and Development Study). We found the most differentially methylated sites in cannabis with tobacco users were in the AHRR and F2RL3 genes, replicating previous studies on the effects of tobacco. Cannabis-only users had no evidence of differential methylation in these genes, or at any other loci at the epigenomewide significance level (P<10−7). However, there were 521 sites differentially methylated at P<0.001 which were enriched for genes involved in cardiomyopathy and neuronal signalling. Further, the most differentially methylated loci were associated with genes with reported roles in brain function (e.g. TMEM190, MUC3L, CDC20 and SP9). We conclude that the effects of cannabis use on the mature human blood methylome differ from, and are less pronounced than, the effects of tobacco use, and that larger sample sizes are required to investigate this further.
Independent evolution of cutaneous lymphoma subclones in different microenvironments of the skin
Authors: Iyer Aishwarya , Hennessey Dylan , O’Keefe Sandra , Patterson Jordan , Wang Weiwei , Wong Gane Ka-Shu , Gniadecki Robert 
Published: November 2019

AbstractMycosis fungoides (MF) is the most common, yet incurable, cutaneous T-cell lymphoma. We have recently shown that the disease is initiated by hematogenous seeding the skin with clonotypically diverse neoplastic T-cells which proliferate accumulating numerous mutations and produce lesions of high intratumoral heterogeneity (ITH). A characteristic but a poorly studied feature of MF is epidermotropism, the tendency to infiltrate skin epithelial layer (epidermis) in addition to the vascularized dermis. By sequencing the exomes of the microdissected clusters of lymphoma cells from the epidermis and the dermis, we found that those microenvironments harbored different malignant clonotypes and exhibited different patterns of driver gene mutation. Phylogenetic relationships between cancer subclones witnessed to the independent mutational evolution in the epidermis and dermis. Thus, the invasion of MF to different skin layers does not occur by gradual infiltration of the expanding tumor mass, but is caused by separate seeding processes with different malignant clones that develop independently of one another via a neutral, branched evolution. In conclusion, tissue microenvironments shape the subclonal architecture in MF leading to “ecological heterogeneity” which contributes to the total ITH. Since ITH adversely affects cancer prognosis, targeting the microenvironment may present therapeutic opportunities in MF and other cancers.
CTP synthase forms cytoophidia in archaea
Authors: Zhou Shuang , Xiang Hua , Liu Ji-Long 
Published: November 2019

AbstractCTP synthase (CTPS) is an important metabolic enzyme that catalyzes the rate-limiting reaction of de novo synthesis of the nucleotide CTP. Since 2010, a series of studies have demonstrated that CTPS can form filamentous structures termed cytoophidia in bacteria and eukaryotes. However, it remains unknown whether cytoophidia exist in archaea, the third domain of life. UsingHaloarcula hispanicaas a model system, here we demonstrate that CTPS forms distinct intracellular compartments in archaeal cells. Under stimulated emission depletion (STED) microscopy, we find that some HhCTPS compartments have elongated filamentous structures, resembling cytoophidia in bacteria and eukaryotes. WhenHaloarculacells are cultured in low-salt medium, the occurrence of cytoophidia increases dramatically. Moreover, overexpression of CTPS or glutamine analog treatment promotes cytoophidium assembly inH. hispanica.Our study reveals that CTPS forms cytoophidia in all three domains of life, suggesting that this is an ancient property of CTPS.
Grid pattern development, distortions and topological defects may depend on distributed anchoring
Authors: Mørreaunet Maria , Hägglund Martin 
Published: November 2019

AbstractThe firing pattern of grid cells in rats has been shown to exhibit elastic distortions that compresses and shears the pattern and suggests that the grid is locally anchored. Anchoring points may need to be learned to account for different environments. We recorded grid cells in animals encountering a novel environment. The grid pattern was not stable but moved between the first few sessions predicted by the animals running behavior. Using a learning continuous attractor network model, we show that learning distributed anchoring points may lead to such grid field movement as well as previously observed shearing and compression distortions. The model further predicted topological defects comprising a pentagonal/heptagonal break in the pattern. Grids recorded in large environments were shown to exhibit such topological defects. Taken together, the final pattern may be a compromise between local network attractor states driven by self-motion signals and distributed anchoring inputs from place cells.
Mathematical modeling of plant cell fate transitions controlled by hormonal signals
Authors: Klawe Filip Z. , Stiehl Thomas , Bastian Peter , Gaillochet Christophe , Lohmann Jan U. , Marciniak-Czochra Anna 
Published: November 2019

AbstractCoordination of fate transition and cell division is crucial to maintain the plant architecture and to achieve efficient production of plant organs. In this paper, we analysed the stem cell dynamics at the shoot apical meristem (SAM) that is one of the plant stem cells locations. We designed a mathematical model to elucidate the impact of hormonal signaling on the fate transition rates between different zones corresponding to slowly dividing stem cells and fast dividing transit amplifying cells. The model is based on a simplified two-dimensional disc geometry of the SAM and accounts for a continuous displacement towards the periphery of cells produced in the central zone. Coupling growth and hormonal signaling results in a non-linear system of reaction-diffusion equations on a growing domain with the growth velocity depending on the model components. The model is tested by simulating perturbations in the level of key transcription factors that maintain SAM homeostasis. The model provides new insights on how the transcription factor HECATE is integrated in the regulatory network that governs stem cell differentiation.SummaryPlants continuously generate new organs such as leaves, roots and flowers. This process is driven by stem cells which are located in specialized regions, so-called meristems. Dividing stem cells give rise to offspring that, during a process referred to as cell fate transition, become more specialized and give rise to organs. Plant architecture and crop yield crucially depend on the regulation of meristem dynamics. To better understand this regulation, we develop a computational model of the shoot meristem. The model describes the meristem as a two-dimensional disk that can grow and shrink over time, depending on the concentrations of the signalling factors in its interior. This allows studying how the non-linear interaction of multiple transcription factors is linked to cell division and fate-transition. We test the model by simulating perturbations of meristem signals and comparing them to experimental data. The model allows simulating different hypotheses about signal effects. Based on the model we study the specific role of the transcription factor HECATE and provide new insights in its action on cell dynamics and in its interrelation with other known transcription factors in the meristem.
Potpourri: An Epistasis Test Prioritization Algorithm via Diverse SNP Selection
Authors: Caylak Gizem , Tastan Oznur , Cicek A. Ercument 
Published: November 2019

AbstractGenome-wide association studies explain a fraction of the underlying heritability of genetic diseases. Investigating epistatic interactions between two or more loci help closing this gap. Unfortunately, sheer number of loci combinations to process and hypotheses to test prohibit the process both computationally and statistically. Epistasis test prioritization algorithms rank likely-epistatic SNP pairs to limit the number of tests. Yet, they still suffer from very low precision. It was shown in the literature that selecting SNPs that are individually correlated with the phenotype and also diverse with respect to genomic location, leads to better phenotype prediction due to genetic complementation. Here, we propose that an algorithm that pairs SNPs from such diverse regions and ranks them can improve prediction power. We propose an epistasis test prioritization algorithm which optimizes a submodular set function to select a diverse and complementary set of genomic regions that span the underlying genome. SNP pairs from these regions are then further ranked w.r.t. their co-coverage of the case cohort. We compare our algorithm with the state-of-the-art on three GWAS and show that (i) we substantially improve precision (from 0.003 to 0.652) while maintaining the significance of selected pairs, (ii) decrease the number of tests by 25 folds, and (iii) decrease the runtime by 4 folds. We also show that promoting SNPs from regulatory/coding regions improves the performance (up to 0.8). Potpourri is available at http:/ciceklab.cs.bilkent.edu.tr/potpourri.
Research of the mechanism on miRNA193 in exosomes promotes cisplatin resistance in esophageal cancer cells
Authors: Shi Shifeng , Huang Xin , Ma Xiao , Zhu Xiaoyan , Zhang Qinxian 
Published: November 2019

AbstractPurposeChemotherapy resistance of esophageal cancer is a key factor affecting the postoperative treatment of esophageal cancer. Among the media that transmit signals between cells, the exosomes secreted by tumor cells mediate information transmission between tumor cells, which can make sensitive cells obtain resistance. Although some cellular exosomes play an important role in tumor’s acquired drug resistance, the related action mechanism is still not explored specifically.MethodsTo elucidate this process, we constructed a cisplatin-resistant esophageal cancer cell line, and proved that exosomes conferring cellular resistance in esophageal cancer can promote cisplatin resistance in sensitive cells. Through high-throughput sequencing analysis of the exosome and of cells after stimulation by exosomes, we determined that the miRNA193 in exosomes conferring cellular resistance played a key role in sensitive cells acquiring resistance to cisplatin. In vitro experiments showed that miRNA193 can regulate the cell cycle of esophageal cancer cells and inhibit apoptosis, so that sensitive cells can acquire resistance to cisplatin. An in vivo experiment proved that miRNA193 can promote tumor proliferation through the exosomes, and provide sensitive cells with slight resistance to cisplatin.ResultsSmall RNA sequencing of exosomes showed that exosomes in drug-resistant cells have 189 up-regulated and 304 down-regulated miRNAs; transcriptome results showed that drug-resistant cells treated with drug-resistant cellular exosomes have 3446 high-expression and 1709 low-expression genes; correlation analysis showed that drug-resistant cellular exosomes mainly affect the drug resistance of sensitive cells through paths such as cytokine–cytokine receptor interaction, and the VEGF and Jak-STAT signaling pathways; miRNA193, one of the high-expression miRNAs in drug-resistant cellular exosomes, can promote drug resistance by removing cisplatin’s inhibition of the cell cycle of sensitive cells.ConclusionSensitive cells can become resistant to cisplatin through acquired drug-resistant cellular exosomes, and miRNA193 can make tumor cells acquire cisplatin resistance by regulating the cell cycle.
Role ofTrypanosoma cruzinucleoside diphosphate kinase 1 in DNA-damage responses
Authors: Reigada Chantal , Sayé Melisa , Di Girolamo Fabio , Valera-Vera Edward A. , Pereira Claudio A. , Miranda Mariana R. 
Published: November 2019

AbstractNME23/NDPK proteins are well conserved proteins found in all living organism. Besides their catalytic activity of nucleoside diphosphate kinase (NDPK) they are considered multifunctional, which were first characterized as non-metastatic proteins in mammalian cells. Later, increasing evidences placed NME/NDPK as proteins involved in DNA stability such as gene regulation and DNA-repair. TcNDPK1 is the canonical NDPK isoform present in the parasiteTrypanosoma cruzi, orthologous to NME23-H1/H2 which has been shown to have in vitro nuclease activity and DNA-binding properties. In the present study we investigate the role of TcNDPK1 in DNA-damage responses using heterologous gene expression systems and over-expression in epimastigote cells. We found that different strains of bacteria, WT andndk-mutants, expressing the enzyme decreased about 5 fold and 18 fold the spontaneous mutation rate, respectively. In addition, yeasts lacking the endogenous geneYNK1(YNK1-) and expressing TcNDPK1, were significantly more resistant to different concentrations of hydrogen peroxide and were less sensible to UV radiation than controls. Parasites over-expressing TcNDPK1 were able to withstand different genotoxic stresses caused by hydrogen peroxide, phleomycin and hidroxyurea. In addition, under oxidative damage, TcNDPK1 over-expressing parasites presented lesser genomic damage and augmented levels of poly(ADP)ribose and poly(ADP)ribose polymerase, an enzyme involved in DNA repair. These results strongly suggest that TcNDPK1 is involved in the maintenance of parasite genomic-DNA integrity, thus, giving rise to a novel function.
Human Bocavirus Prevalence In Children With Acute Gastroenteritis From Rural Communities In The Northen Region Of South Africa
Authors: Rikhotso Mpumelelo Casper , Khumela Ronewa , Kabue Jean Pierre , Traoré Afsatou Ndama , Potgieter Natasha 
Published: November 2019

AbstractBACKGROUNDAcute gastroenteritis (AGE) is a leading cause of morbidity and mortality in young children worldwide. Human Bocavirus (HBoV) is an emerging virus globally associated with diarrhea. The aim of this study was to demonstrate the prevalence of HBoV genotypes in children (≤5 years) from rural communities in South Africa (SA) suffering from AGE.MATERIAL AND METHODA total of 141 fecal samples of children ≤5 years with acute gastroenteritis (AGE) were collected from rural Primary Health Care facilities in the Vhembe district of SA between June 2017 and July 2018. Clinical symptoms and demographic data were also recorded. A total of 102 (72%) were outpatients and 39 (28%) were hospitalized patients. Human Bocavirus (HBoV) genotypes were determined using Real-Time Multiplex PCR. DNA extracts of positive samples were confirmed by conventional PCR targeting the NS1 gene. Co-infection with other enteric viruses were determined in HBoV positive samples using Real-Time PCR.RESULTSHBoV was detected in 8 (5.7%) children with AGE. Children were in the age group between 1-24 months. HBoV1 and HBoV3 genotypes were each detected in 3 (37.5%) stool samples and HBoV2 in 2 (25%) stool samples. Co-infection with other enteric viruses included Rotavirus (37.5%); Adenovirus (37.5%); Norovirus (25%) and Astrovirus (12.5%).CONCLUSIONHBoV infections could be seen as a potential emerging diarrheal pathogen in South Africa. Further studies are required to understand the role of HBoV infections in children and adults with acute gastroenteritis.Author summaryAcute gastroenteritis (AGE) is recognized as a major cause for mortality in children ≤5 years of age in Africa and other developing countries. Viruses known to be involved in AGE includes Rotavirus, Norovirus, Astrovirus and Adenovirus and have been reported globally. Recently the Human Bocavirus (HBoV) have been reported in numerous studies globally as a potential cause of diarrhea. In this study, the prevalence and genetic diversity of human Bocavirus in children with AGE from rural communities in Limpopo, South Africa were investigated. In total, 141 stool samples from children ≤ 5 years with AGE were assessed for the presence of HBoV using Real-Time PCR. HBoV were detected in 8 (5.7%) patients and included 3 positive samples for HBoV1 and HBoV3 respectively and 2 positive for HBoV2. No HBoV4 were detected. Among the 8 positive HBoV samples, co-infection with other enteric viruses were found in 7 (87.5%) samples, while mono infection with HBoV alone was detected in 1 (12.5%) patient. HBoV mixed infection with Rotavirus (3/8; 37.5%); Adenovirus (3/8; 37.5%); Norovirus (2/8; 25%) and Astrovirus (1/8; 12.5%) were observed in this study. This study reported for the first time on the prevalence of human Bocavirus in children with AGE from rural communities in South Africa.