bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loop 1 of APOBEC3C regulates its antiviral activity against HIV-1
Authors: Jaguva Vasudevan Ananda Ayyappan , Balakrishnan Kannan , Gertzen Christoph G. W. , Borvető Fanni , Zhang Zeli , Sangwiman Anucha , Held Ulrike , Küstermann Caroline , Banerjee Sharmistha , Schumann Gerald G. , Häussinger Dieter , Bravo Ignacio G. , Gohlke Holger , Münk Carsten 
Published: February 2020

ABSTRACTAPOBEC3 deaminases (A3s) provide mammals with an anti-retroviral barrier by catalyzing dC-to-dU deamination on viral ssDNA. Within primates, A3s have evolved diverselyviagene duplications and fusions. Human APOBEC3C (hA3C) efficiently restricts the replication of viral infectivity factor (vif)-deficientSimian immunodeficiency virus(SIVΔvif), but for unknown reasons, it inhibits HIV-1Δvifweakly. In catarrhines (Old World monkeys and apes), the A3C loop 1 displays the conserved amino acid pair WE, while the corresponding consensus sequence in A3F and A3D is the largely divergent pair RK, which is also the inferred ancestral sequence for the last common ancestor of A3C|D|F in primates. Here, we report that modifying the WE residues in hA3C loop 1 to RK leads to stronger interactions with ssDNA substrate, facilitating catalytic function, which resulted in a drastic increase in both deamination activity and the ability to restrict HIV-1 and LINE-1 replication. Conversely, the modification hA3F_WE resulted only in a marginal decrease in HIV-1Δvifinhibition. The two series of ancestral gene duplications that generated A3C, A3D-CTD and A3F-CTD allowed neo/subfunctionalization: A3F-CTD maintained the ancestral RK residues in loop 1, while strong evolutionary pressure selected for the RK→WE modification in catarrhines A3C, possibly allowing for novel substrate specificity and function.AUTHOR SUMMARYThe restriction factors of the APOBEC3 (A3) family of cytidine deaminases inhibit the replication of Vif-deficient retroviruses mainly by mutating their viral genomes. While there are seven A3 proteins (A3A-A3H) found in humans only A3G and A3F potently inhibit HIV-1 replication. A3C in general and its retroviral restriction capacity have not been widely studied probably due to its weak anti-HIV-1 activity, however, it displays a strong antiviral effect against SIV. Understanding the role of A3C is important because it is highly expressed in CD4+ T cells, is upregulated upon HIV-1 infection, and is distributed cell-wide. In this study, we report that replacing two residues in loop 1 of A3C protein with conserved positively-charged amino acids enhance the substrate DNA binding, which markedly facilitates its deamination-dependent antiviral activity against HIV-1 as well as increasing the restriction of LINE-1 retroelements. Furthermore, our evolutionary analysis demonstrates that the pressure that caused the loss of potential loop 1 residues occurred only in A3C but not in primate homologues. Overall, our study highlights the possibility of A3C acting as a super restriction factor, however, this was likely evolutionarily selected against to achieve a balance between anti-viral/anti-LINE-1 activity and genotoxicity.
Highly replicated evolution of parapatric ecotypes
Authors: James Maddie E. , Arenas-Castro Henry , Groh Jeffrey S. , Allen Scott L. , Engelstädter Jan , Ortiz-Barrientos Daniel 
Published: February 2020

AbstractParallel evolution of ecotypes occurs when selection independently drives the evolution of similar traits across similar environments. The multiple origin of ecotypes is often inferred on the basis of a phylogeny which clusters populations according to geographic location and not by the environment they occupy. However, the use of phylogenies to infer parallel evolution in closely related populations is problematic because gene flow and incomplete lineage sorting can uncouple the genetic structure at neutral markers from the colonization history of populations. Here, we demonstrate multiple origins within ecotypes of an Australian wildflower,Senecio lautus. We observed strong genetic structure as well as phylogenetic clustering by geography and show that this is unlikely due to gene flow between parapatric ecotypes, which is surprisingly low. We further confirm this analytically by demonstrating that phylogenetic distortion due to gene flow often requires higher levels of migration than those observed inS. lautus. Our results imply that selection can repeatedly create similar phenotypes despite the perceived homogenizing effects of gene flow.
Activator protein-1 transactivation of the major immediate early locus is a determinant of cytomegalovirus reactivation from latency
Authors: Krishna Benjamin A. , Wass Amanda B. , O’Connor Christine M. 
Published: February 2020

AbstractHuman cytomegalovirus (HCMV) is a ubiquitous pathogen that latently infects hematopoietic cells and has the ability to reactivate when triggered by immunological stress. This reactivation causes significant morbidity and mortality in immune-deficient patients, who are unable to control viral dissemination. While a competent immune system helps prevent clinically detectable viremia, a portrait of the factors that induce reactivation following the proper cues remains incomplete. Our understanding of the complex molecular mechanisms underlying latency and reactivation continue to evolve. We previously showed the HCMV-encoded G-protein coupled receptorUS28is expressed during latency and facilitates latent infection by attenuating the activator protein-1 (AP-1) transcription factor subunit, c-fos, expression and activity. We now show AP-1 is a critical component for HCMV reactivation. Pharmacological inhibition of c-fos significantly attenuates viral reactivation. In agreement, infection with a virus in which we disrupted the proximal AP-1 binding site in the major immediate early (MIE) enhancer results in inefficient reactivation compared to wild type. Concomitantly, AP-1 recruitment to the MIE enhancer is significantly decreased following reactivation of the mutant virus. Further, AP-1 is critical for de-repression of MIE-driven transcripts and downstream early and late genes, while immediate early genes from other loci remain unaffected. Our data also reveal MIE transcripts driven from the MIE promoter, the distal promoter, and the internal promoter, iP2, are dependent upon AP-1 recruitment, while iP1-driven transcripts are AP-1-independent. Collectively, our data demonstrate AP-1 binding to and activation of the MIE enhancer is a key molecular process controlling reactivation from latency.Significance StatementHuman cytomegalovirus (HCMV) is a common pathogen that infects the majority of the population for life. This infection poses little threat in immunologically healthy individuals, but can be fatal in people with compromised immune systems. Our understanding of the mechanisms underlying latency and reactivation remains incomplete. Here, we show the cellular transcription factor, AP-1, is a key to regulating HCMV reactivation. Our findings reveal AP-1 binding to the major immediate early enhancer/promoter is critical for switching this locus from one that is repressed during latency to one that is highly active following reactivation. Our work provides a novel mechanism HCMV exploits to reactivate, highlighting AP-1 as a potential target to prevent HCMV reactivation.
Efficiency of biological and chemical inducers for controlling Septoria tritici leaf blotch (STB) on wheat (Triticum aestivumL.)
Authors: Bellameche Fares , Pedrazzini Chiara , Mauch-Mani Brigitte , Mascher Fabio 
Published: February 2020

AbstractThe hemibiotrophic fungusZymoseptoria triticiis the causative agent of Septoria tritici leaf blotch (STB) disease of wheat (Triticum aestivumL.), the economically most damaging disease of wheat in Europe. Today, ecofriendly plant protection methods compatible with sustainable agriculture are strongly desirable. Here, we applied the two chemical inducers β-aminobutyric acid (BABA) and benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH) and the two biotic inducersPseudomonas protegensCHA0 (CHA0) andP. chlororaphisPCL1391 (PCL) on the roots of wheat seedlings in order to test their ability to induce resistance against STB. At 21 days after inoculation, only plants treated with BABA showed a smaller area covered by lesions and less pycnidia compared to the untreated control plants. We evaluated spore germination and fungal development on inoculated wheat leaves at early infection stages using calcofluor white staining. Overall, spores ofZ. triticigerminated less on plants soil-drenched with BABA and BTH and their hyphal growth was significantly delayed. On the contrary, CHA0 and PCL seed treatments did not affect fungal growth in wheat leaves. In conclusion, BABA efficiently enhanced plant resistance toZ. tritici, BTH delayed fungal development at early stages while the two biotic inducers did not enhance resistance against STB disease.
Biotic and abiotic factors predict the biogeography of soil microbes in the Serengeti
Authors: Stevens Bo Maxwell , Lee Sonderegger Derek , Johnson Nancy Collins 
Published: February 2020

AbstractField-based observational research is the first step in understanding the factors that predict the biogeography and community structure of soil microbes. The Serengeti National Park in Tanzania is an ideal location for this type of research because active volcanoes generate strong environmental gradients due to ash deposition and a rain shadow. Also, as one of the last remaining naturally grazed ecosystems on Earth, the Serengeti provides insights about the influence of herbivory on microbial communities. We used 16S rRNA amplicons to characterize bacterial and archaeal communities in soils from a 13-year herbivore removal experiment to study the influence of environmental factors and grazing on the natural distribution of soil microbes. We collected soil samples from seven sites, each with three naturally grazed plots and three plots that were fenced to prevent grazing by large mammalian herbivores. Soil fertility (phosphorus, nitrogen, iron, calcium, organic matter), texture, and pH were measured at each plot. Beta diversity of bacterial and archaeal communities was most strongly correlated with soil texture (R2= 32.4%). The abundance of many operational taxonomic units (OTUs) were correlated with soil texture, and the evenness of taxa within samples increased with fine-textured soil. Removal of grazing shifted community structure, with 31 OTUs that were significant indicator taxa of the ungrazed treatment and three OTUs that were significant indicators of the grazed treatment.ImportanceOur results show that in this regional scale study, soil texture was the best environmental predictor, and grazing by large mammals also structures bacterial and archaeal communities. When large mammals are removed, as humans have been doing for millenia, there are cascading effects into the microbial world that can influence ecosystem functions like carbon and nitrogen cycles. These empirical findings from a natural tropical savannah can help inform models of the global distribution and function of soil microbes.
NSC348884 cytotoxicity is not mediated by inhibition of nucleophosmin oligomerization
Authors: Šašinková Markéta , Heřman Petr , Holoubek Aleš , Strachotová Dita , Otevřelová Petra , Grebeňová Dana , Kuželová Kateřina , Brodská Barbora 
Published: February 2020

AbstractOligomerization of the nucleolar phosphoprotein nucleophosmin (NPM) is mediated by its N-terminal domain. In acute myeloid leukemia, a frequent NPM mutation occurring at the C-terminus causes NPM delocalization to the cytoplasm. Due to formation of NPM heterooligomers, the wild-type NPM as well as many of NPM interaction partners are also delocalized. Proper localization and function of mislocalized proteins in the cells with mutated NPM may be restored by targeting NPM oligomerization. We introduce a reliable set of complementary methods for monitoring NPM oligomerization in both cell lysates and live cells. Using this methodological background we show that a putative inhibitor of NPM oligomerization, NSC348884, does not prevent formation of NPM oligomers in leukemia cells. Instead, we reveal that the observed cytotoxic effect of NSC348884 is associated with changes in cell adhesion signaling.
Study ofStaphylococcus aureusBiofilm Ability to Destroy Bone Matrix in Absences of Host Immunity
Authors: Al Ghaithi ahmed , Al Mastari Sultan , Husband John , al kindi Mohammed , Al Bimani Atika 
Published: February 2020

AbstractPurposeOsteomyelitis is an infectious bone process leading to bone necrosis and destruction. Published reports on pathogen biofilm thus far have focused on indirect bone resorption mediated by host cells and factors secondary to immune system activation. However, direct bone resorption due to biofilm pathogen has not been adequately studied yet. This study aims to investigate the effect of biofilm pathogen in ex-vivo human bones in the absence of the host immune response using Raman spectroscopy and Scanning electron microscopy.MethodsBone samples collected from patients who underwent knee replacement surgeries were inoculated withStaphylococcus aureusbacteria. Bacterial direct effects on the bone quality were then examined, at various time intervals, using Raman spectroscopy and scanning electron microscopy.ResultsRaman spectroscopy and scanning electron demonstrated the destruction of bone structure and drop in bone quality.ConclusionThis experiment shows the direct effect of bacteria on bone during osteomyelitis in addition to the recognised destruction caused by the host immune system.
Brucellaspecies circulating in wildlife in Serengeti ecosystem, Tanzania
Authors: Sambu R. M. , Mathew C. , Nonga H.E. , Lukambagire A. S. , Yapi Richard B. , Fokou G. , Keyyu J. , Bonfoh B. , Kazwala R. R 
Published: February 2020

AbstractBackgroundBrucellosis is a bacterial zoonosis of public health and economic importance world-wide. It affects a number of domestic animals, wildlife and humans. This study was carried out to determine circulatingBrucellaspecies in wildlife in Serengeti ecosystem using molecular techniques.MethodologyA total of 189 samples including EDTA blood, serum and amniotic fluid from buffalos, lions, wildebeest, impala, zebra and hyena that were collected in relation to different cross-sectional studies conducted in the Serengeti ecosystem in Tanzania were used. Multiplex polymerase chain reaction AMOS-PCR and quantitative Real-Time PCR (qPCR) targeting the genus specific surface protein bcsp31 gene and the insertion sequence IS711element downstream of thealkBgene forB. abortusandBMEI1162 gene forB. melitensiswere employed on the samples.ResultsResults indicated that out of 189 samples examined, 12 (6.4%) and 22 (11.6%) containedBrucellaDNA as detected by AMOS-PCR and qPCR, respectively. Most of the positive samples were from lions (52.6%) and buffaloes (19.6%). Other animals that were positive included wildebeest, impala, zebra and hyena. Out of 22 positive samples, 16 (66.7%) were identified asB. abortusand the rest wereB. melitensis.ConclusionDetection of zoonoticBrucellaspecies in wildlife suggests that livestock and humans at the interface areas where there is high interaction are at risk of acquiring the infection. Therefore, public education to interrupt risky transmission practices is needed. The findings also shed light on the transmission dynamics around interface areas and the role of wildlife in transmission and maintenance ofBrucellainfection in the region.
Non-linear Computation Between Neighboring Dendritic Hotspots in Rat CA1 Hippocampal Interneurons
Authors: Kaszás Attila , Szadai Zoltán , Spitzer Klaudia , Katona Gergely , Tóth Éva , Tamás Gábor , Rózsa Balázs 
Published: February 2020

ABSTRACTDendritic hotspots have been shown to play a determining role as local activity foci during sensory information coding and memory formation in cortical neuronsin vivo. Here we aim to reveal the characteristics of co-activating more dendritic hotspots themselves within a dynamic time window. Using electrical stimulation and patterned two-photon uncaging for the coincident activation of two neighboring dendritic hotspots in rat hippocampal CA1 interneurons, the evoked local dendritic Ca2+and the associated excitatory postsynaptic potentials (EPSPs) summed supralinearly. Between active hotspots, supralinearity was present in a relatively broad temporal (∼10 ms) and spatial (∼30 µm) window, mediated by NMDA receptors. Though at larger inter-hotspot distances (>30 µm) supralinear summation of EPSPs was replaced by sublinear integration, the summation of dendritic Ca2+responses remained supralinear. The inter-hotspot integration represents a novel signal integration state, extending the interaction distance between dendritic inputs, and allowing long-range coincidence detection.
The Arabidopsis geneRGOmediates cytokinin responses and increases seed yield
Authors: Murmu Jhadeswar , Allard Ghislaine , Chabot Denise , Nambara Eiji , Datla Raju , Hepworth Shelley , Subramaniam Rajagopal , Singh Jas 
Published: February 2020

AbstractA novel gene,At1g77960, fromArabidopsis thalianawas characterized.At1g77960transcripts accumulate to very high levels in plants ectopically overexpressing theGolden2-like1(GLK1) transcription factor and is designated as aResponse toGLK1Overexpression(RGO) gene.RGOencodes a protein with domains of tandem QH and QN repeats. Transcripts and promoter GUS reporter analyses indicated thatRGOis expressed in roots, leaves, stems, floral and siliques tissues but not in seeds. Expression of the RGO:YFP fusion protein demonstrated thatRGOis localized to the endoplasmic reticulum. MicroRNA mediated silencing ofRGOresulted in severe reductions in vegetative and root growth, delayed flowering and reduced seed yield and viability, suggesting thatRGOis essential for plant development. Conversely, ectopic overexpression ofRGOresulted in enhanced vegetative growth including increased axillary bud formation and a 20% higher seed yield. Stable overexpression ofRGOinBrassica napusalso produced a similar increase in seed yield. Cytokinin (CK) response assays including root growth, green calli formation from excised hypocotyls and chlorophyll retention during dark-induced senescence suggest that one role ofRGOis to mediate CK responses in plant development. These results suggest thatRGOcould be a target gene for increasing crop seed yields.One-sentence summaryRGO, a novel gene from Arabidopsis, is essential for plant development, mediates CK signaling and increases seed yield in Arabidopsis and rapeseed when overexpressed.
Time-restricted feeding from adulthood to old age improves biconditional associative learning in geriatric rats regardless of macronutrient composition
Authors: Hernandez Abbi R. , Federico Quinten P. , Burke Sara N. 
Published: February 2020

AbstractDeclining health and cognition are hallmarks of advanced age that reduce both the quality and length of the lifespan. While caloric restriction has been highlighted as a dietary intervention capable of improving the healthspan by restoring metabolic function in late life, time-restricted feeding and changes in dietary macronutrient composition may be more feasible alternatives with similar health outcomes. To investigate the potential of these two interventions, a pilot cohort of fully mature adult rats were placed on a time-restricted feeding regimen of a ketogenic or micronutrient and calorically matched control diet from 8 to 21 months of age. A third group of rats was permitted to eat standard chowad libitum. At 22 months, all rats were then placed on time-restricted feeding and tested on a biconditional association task. While the data presented here are preliminary (small sample size of 3-4/diet group), additional animals are currently undergoing the feeding regimen, and will be added into the behavioral studies at a later date. For the current data, regardless of dietary composition, time-restricted-fed rats performed significantly better thanad libitum-fed rats. This observation could not be accounted for by differences in motivation, procedural or sensorimotor impairments, indicating that mid-life dietary interventions capable of preventing metabolic impairments may also serve to prevent age-related cognitive decline.
Comparative transcriptomics across nematode life cycles reveal gene expression conservation and correlated evolution in adjacent developmental stages
Authors: Lu Min R. , Lai Cheng-Kuo , Liao Ben-Yang , Tsai Isheng Jason 
Published: February 2020

AbstractNematodes are highly abundant animals with diverse habitats and lifestyles. Some are free-living while others parasitize animals or plants, and among the latter, infection abilities change across developmental stages to infect hosts and complete life cycles. Although parasitism has independently arisen multiple times over evolutionary history, common pressures of parasitism—such as adapting to the host environment, evading and subverting the host immune system, and changing environments across life cycles—have led phenotypes and developmental stages among parasites to converge. To determine the relationship between transcriptome evolution and morphological divergences among nematodes, we compared 48 transcriptomes of different developmental stages across eight nematode species. The transcriptomes were clustered broadly into embryo, larva, and adult stages, suggesting that gene expression is conserved to some extent across the entire nematode life cycle. Such patterns were partly accounted for by tissue-specific genes—such as those in oocytes and the hypodermis—being expressed at different proportions. Although nematodes typically have 3-5 larval stages, the transcriptomes for these stages were found to be highly correlated within each species, suggesting high similarity among larval stages across species. For theCaenorhabditis elegans-C. briggsaeandStrongyloides stercoralis-S. venezuelensiscomparisons, we found that around 50% of genes were expressed at multiple stages, whereas half of their orthologues were also expressed in multiple but different stages. Such frequent changes in expression have resulted in concerted transcriptome evolution across adjacent stages, thus generating species-specific transcriptomes over the course of nematode evolution. Our study provides a first insight into the evolution of nematode transcriptomes beyond embryonic development.