bluuebunny/crossref_metadata_2025_split huggingface dataset:
PHYTOCHROME INTERACTING FACTORS PIF4 and PIF5 promote heat stress induced leaf senescence in Arabidopsis
Authors: Li Na , Bo Cunpei , Zhang Yuanyuan , Wang Lei 
Published: April 2021

Abstract
Leaf senescence can be triggered by multiple abiotic stresses including darkness, nutrient limitation, salinity, and drought. Recently, heatwaves have been occurring more frequently, and they dramatically affect plant growth and development. However, the underlying molecular networks of heat stress-induced leaf senescence remain largely uncharacterized. Here we showed that PHYTOCHROME INTERACTING FACTOR 4 (PIF4) and PIF5 proteins could efficiently promote heat stress-induced leaf senescence in Arabidopsis. Transcriptomic profiling analysis revealed that PIF4 and PIF5 are likely to function through multiple biological processes including hormone signaling pathways. Further, we characterized NAC019, SAG113, and IAA29 as direct transcriptional targets of PIF4 and PIF5. The transcription of NAC019, SAG113, and IAA29 changes significantly in daytime after heat treatment. In addition, we demonstrated that PIF4 and PIF5 proteins were accumulated during the recovery after heat treatment. Moreover, we showed that heat stress-induced leaf senescence is gated by the circadian clock, and plants might be more actively responsive to heat stress-induced senescence during the day. Taken together, our findings proposed important roles for PIF4 and PIF5 in mediating heat stress-induced leaf senescence, which may help to fully illustrate the molecular network of heat stress-induced leaf senescence in higher plants and facilitate the generation of heat stress-tolerant crops.
Low-temperature acclimation and legacy effects of summer water deficits in olive freezing resistance
Authors: Arias Nadia S , Scholz Fabián G , Goldstein Guillermo , Bucci Sandra J 
Published: April 2021

Abstract
Low temperatures and drought are the main environmental factors affecting plant growth and productivity across most of the terrestrial biomes. The objective of this study was to analyze the effects of water deficits before the onset of low temperatures in winter to enhance freezing resistance in olive trees. The study was carried out near the coast of Chubut, Argentina. Plants of five olive cultivars were grown outdoor in pots and exposed to different water deficit treatments. We assessed leaf water relations, ice nucleation temperature (INT), cell damage (LT50), plant growth and leaf nitrogen content during summer and winter in all cultivars and across water deficit treatments. Leaf INT and LT50 decreased significantly from summer to winter within each cultivar and between treatments. We observed a trade-off between resources allocation to freezing resistance and vegetative growth, such that an improvement in resistance to sub-zero temperatures was associated with lower growth in tree height. Water deficit applied during summer increased the amount of osmotically active solutes and decreased the leaf water potentials. This type of legacy effect persists during the winter after the water deficit even when treatment was removed by natural rainfalls.
Weevil borers affect the spatio-temporal dynamics of banana Fusarium wilt
Authors: Heck Daniel , Alves Gabriel , Mizubuti Eduardo S. G. 
Published: April 2021

AbstractDispersal of propagules of a pathogen has remarkable effects on the development of epidemics. Previous studies suggested that insect pests play a role in the development of Fusarium wilt (FW) epidemics in banana fields. We provided complementary evidence for the involvement of two insect pests of banana, the weevil borer (Cosmopolites sordidusL. - WB) and the false weevil borer (Metamasius hemipterusL. - FWB), in the dispersal ofFusarium oxysporumf. sp.cubense(Foc) using a comparative epidemiology approach under field conditions. Two banana plots located in a field with historical records of FW epidemics were used, one was managed withBeauveria bassianato reduce the population of weevils, and the other was left withoutB. bassianaapplications. The number of WB and FWB was monitored biweekly and the FW incidence was quantified bimonthly during two years. The population of WB and the incidence (6.7%) of FW in the plot managed withB. bassianawere lower than in the plot left unmanaged (13%). The monomolecular model best fitted the FW disease progress data and, as expected, the average estimated disease progress rate was lower in the plot managed with the entomopathogenic fungus (r= 0.0024) compared to the unmanaged plot (r= 0.0056). Aggregation of FW was higher in the field with WB management. WB affected the spatial and temporal dynamics of FW epidemics under field conditions and brought evidence that managing the insects may reduce FW of bananas intensity.
Nutrient cycling is an important mechanism for homeostasis in plant cells
Authors: Dreyer Ingo 
Published: April 2021

AbstractHomeostasis in living cells refers to the steady state of internal, physical, and chemical conditions. It is maintained by self-regulation of the dynamic cellular system. In order to gain insight into homeostatic mechanisms that keep cytosolic nutrient concentrations in plant cells within a homeostatic range, I performed computational cell biology experiments. Systems of membrane transporters were modelled mathematically followed by the simulation of their dynamics. The detailed analyses of ‘what-if’ scenarios demonstrate that a single transporter type for a nutrient, irrespective whether it is a channel or a co-transporter, is not sufficient to set a desired cytosolic concentration. A cell cannot flexibly react on different external conditions. At least two different transporter types for the same nutrient are required, which are energized differently. The gain of flexibility in adjusting the nutrient concentration was accompanied by the establishment of energy-consuming nutrient cycles at the membrane suggesting that these sometimes called ‘futile’ cycles are not as futile as they appear. This understanding may help in future to design new strategies for increasing nutrient use efficiency of crop plants taking into account the complex interplay of transporter networks at the cellular level.One sentence summaryFirst principles of membrane transport explain why the maintenance of a constant cytosolic nutrient concentration is often accompanied by the ‘futile’ cycling of the nutrient across the membrane.
Activation of GPR116/ADGRF5 by its tethered agonist requires key amino acids in extracellular loop 2 of the transmembrane region
Authors: Bridges James P. , Safina Caterina , Pirard Bernard , Brown Kari , Filuta Alyssa , Bouhelal Rochdi , Patel Sejal , Seuwen Klaus , Miller William E. , Ludwig Marie-Gabrielle 
Published: April 2021

AbstractThe mechanistic details of the tethered agonist mode of activation for adhesion GPCRs has not been completely deciphered. We set out to investigate the physiologic importance of autocatalytic cleavage upstream of the agonistic peptide sequence, an event necessary for NTF displacement and subsequent receptor activation. To examine this hypothesis, we characterized tethered agonist-mediated activation of GPR116in vitroandin vivo. A knock-in mouse expressing a non-cleavable GPR116 mutant phenocopies the pulmonary phenotype of GPR116 knock-out mice, demonstrating that tethered agonist-mediated receptor activation is indispensable for functionin vivo. Using site-directed mutagenesis and species swapping approaches we identified key conserved amino acids for GPR116 activation in the tethered agonist sequence and in extracellular loops 2/3 (ECL2/3). We further highlight residues in transmembrane7 (TM7) that mediate stronger signaling in mouse versus human GPR116 and recapitulate these findings in a model supporting tethered agonist:ECL2 interactions for GPR116 activation.Grant supportThis work was supported in part by HL131634 (JPB) from the National Heart, Lung and Blood Institute of the National Institutes of Health.
Downregulation of NCL attenuates tumor formation and growth in cervical cancer by targeting the PI3K/AKT pathway
Authors: Ying Jun , Pan Ruowang , Tang Zhouhao , Zhu Jiayin , Ren Ping , Lou Yang , Zhang Enyong , Huang Dadao , Hu Penghong , Li Dong , Bao Qiyu , Li Peizhen 
Published: April 2021

AbstractNucleolin (NCL, C23) is a multifunctional phosphoprotein that plays a vital role in modulating the survival, proliferation and apoptosis of cancer cells. However, the effects of NCL on cervical cancer and the underlying mechanisms behind this are poorly understood. In the study presented here, Hela cells were transfected with shRNAs targeting the endogenous NCL gene (sh-NCL-Hela). NCL knockdown inhibited cell proliferation and promoted apoptosis bothin vivoandin vitro. Mechanistic studies revealed that NCL knockdown inhibited the PI3K/AKT pathway by upregulating FGF, ITGA, TNXB, VEGF, Caspase 3, and Bax, as well as by downregulating AKT, GNB4, CDK6, IL6R, LAMA, PDGFD, PPP2RSA and BCL-2. In addition, the expression levels of apoptosis-related genes after using a PI3K inhibitor LY294002 were consistent with shRNA studies, while treatment with a 740Y-P agonist showed the opposite effect. Altogether, this study uncovered that downregulation of NCL may be a novel treatment strategy for cervical cancer.
Changes in body shape implicate cuticle stretch inC. elegansgrowth control
Authors: Nyaanga Joy , Goss Christina , Zhang Gaotian , Ahmed Hannah N. , Andersen Elliot J. , Miller Isabella R. , Rozenich Justine K. , Swarthout Iris L. , Vaughn Jordan A. , Mangan Niall M. , Shirman Sasha , Andersen Erik C. 
Published: April 2021

AbstractGrowth control establishes organism size, requiring mechanisms to sense and adjust growth during development. Studies of single cells revealed that size homeostasis uses distinct control methods. In multicellular organisms, mechanisms that regulate single cell growth must integrate control across organs and tissues during development to generate adult size and shape. We leveraged the roundwormCaenorhabditis elegansas a scalable and tractable model to collect precise growth measurements of thousands of individuals, measure feeding behavior, and quantify changes in animal size and shape during a densely sampled developmental time course. As animals transitioned from one developmental stage to the next, we observed changes in body aspect ratio while body volume remained constant. Then, we modeled a physical mechanism by which constraints on cuticle stretch could cause changes inC. elegansbody shape. The model-predicted shape changes are consistent with those observed in the data. Theoretically, cuticle stretch could be sensed by the animal to initiate larval-stage transitions, providing a means for physical constraints to influence developmental timing and growth rate inC. elegans.HighlightsBody size measurements of thousands of animals in a dense developmental time courseGrowth rate exhibits nonlinear dynamics in both length and widthChanges in body shape but not volume occur during periods of increased quiescenceDynamics of animal shape consistent with a length-based threshold in cuticle stretchModeling of cuticle stretch dynamics suggests a novel mode for growth control
Host defense mechanisms induce genome instability in an opportunistic fungal pathogen
Authors: Smith Amanda , Hickman Meleah A. 
Published: April 2021

AbstractThe ability to generate genetic variation facilitates rapid adaptation in stressful environments. The opportunistic fungal pathogenCandida albicansfrequently undergoes large-scale genomic changes, including aneuploidy and loss-of heterozygosity (LOH), following exposure to physiological stressors and host environments. However, the specific host factors that induceC. albicansgenome instability remains largely unknown. Here, we leveraged genetically-tractable nematode hosts to specifically investigate the innate immune components driving host-associatedC. albicansgenome instability, which include host production of antimicrobial peptides (AMPs) and reactive oxygen species (ROS).C. albicansassociated with wildtype, immunocompetent hosts carried multiple large-scale genomic changes including LOH, whole chromosome, and segmental aneuploidies. In contrast,C. albicansassociated with immunocompromised hosts deficient in AMPs or ROS production had reduced LOH frequencies and fewer, if any, additional genomic changes. We also found thatC. albicans cap1Δ/Δ strains deficient in ROS detoxification, were more susceptible to host-produced ROS genome instability compared to wildtypeC. albicans. Further, genomic perturbations resulting from host-produced ROS are mitigated by the addition of antioxidants. Taken together, this work suggests that host-produced ROS and AMPs induces genotypic plasticity inC. albicanswhich may facilitate rapid adaptation and lead to phenotypic changes.
Polymer additives to personal protective equipment can inactivate pathogens
Authors: Dogan Alan B. , Dabkowski Katherine , von Recum Horst A. 
Published: April 2021

AbstractFace masks have been proven to be medicine’s best public health tool for preventing transmission of airborne pathogens. However, in situations with continuous exposure, lower quality and “do-it-yourself” face masks cannot provide adequate protection against pathogens, especially when mishandled. In addition, the use of multiple face masks each day places a strain on personal protective equipment (PPE) supply and is not environmentally sustainable. Therefore, there is a significant clinical and commercial need for a reusable, pathogen-inactivating face mask. Herein, we propose adding quaternary poly(dimethylaminohexadecyl methacrylate), q(PDMAHDM), abbreviated to q(PDM), to existing fabric networks to generate “contact-killing” face masks – effectively turning cotton, polypropylene, and polyester into pathogen resistant materials. It was found that q(PDM)-integrated face masks were able to inactivate both Gram-positive and Gram-negative bacteria in liquid culture and aerosolized droplets. Furthermore, q(PDM) was electrospun into homogeneous polymer fibers, which makes the polymer practical for low-cost, scaled-up production.Graphical Abstract
Phagocytic Uptake of Polymeric Particles by Immune cells Under Flow Conditions
Authors: Srinivas Megha , Sharma Preeti , Jhunjhunwala Siddharth 
Published: April 2021

AbstractParticles injected intravenously are thought to be cleared by macrophages residing in the liver and spleen, but they also encounter circulating immune cells. It remains to be established if the circulating cells can take up particles while flowing, and if the uptake capacity is similar under static and flow conditions. Here, we use an in vitro peristaltic pump setup that mimics pulsatile blood flow to determine if immune cells take up particles under constant fluidic flow. We use polystyrene particles of varying sizes as the model of a polymeric particle for these studies. Our results show that the immune cells do phagocytose under flow conditions. We demonstrate that cell lines representing myeloid cells, primary human neutrophils and monocytes take up sub-micrometer-sized particles at similar or better rates under flow compared to static conditions. Experiments with whole human blood show that even under the crowding effects of red blood cells, neutrophils and monocytes take up particles while flowing. Together, these data suggest that circulating immune cells are likely to phagocytose intravenously injected particulates, which has implications for design of particles to evade or target these cells.
The Exon Junction Complex Core Represses Caner-specific Mature mRNA Re-splicing: A Potential Key Role in Terminating Splicing
Authors: Otani Yuta , Fujita Ken-ichi , Kameyama Toshiki , Mayeda Akila 
Published: April 2021

ABSTRACTUsing the TSG101 pre-mRNA, we previously discovered cancer-specific resplicing of mature mRNA that generates aberrant transcripts/proteins. The fact that mRNA is aberrantly re-spliced in various cancer cells implies there must be an important mechanism to prevent deleterious re-splicing on the spliced mRNA in normal cells. We thus postulated that the mRNA re-splicing is controlled by specific repressors, and we searched for repressor candidates by siRNA-based screening for mRNA re-splicing activity. We found that knockdown of EIF4A3, which is a core component of the exon junction complex (EJC), significantly promoted mRNA re-splicing. Remarkably, we could recapitulate cancer-specific mRNA resplicing in normal cells by knock-down of any of the core EJC proteins, EIF4A3, MAGOH or RBM8A (Y14), implicating the EJC core as the repressor of mRNA re-splicing often observed in cancer cells. We propose that the EJC core is a critical mRNA quality control factor to prevent over-splicing of mature mRNA.
Anatomy and Development of the Pectoral Fin Vascular Network in the Zebrafish
Authors: Paulissen Scott , Castranova Daniel , Krispin Shlomo , Burns Margaret , Weinstein Brant M. 
Published: April 2021

ABSTRACTThe pectoral fins of teleost fish are analogous structures to human forelimbs, and the developmental mechanisms directing their initial growth and patterning are conserved between fish and tetrapods. The forelimb vasculature is critical for limb function, and it appears to play important roles during development by promoting development of other limb structures, but the steps leading to its formation are poorly understood. In this study, we use high-resolution imaging to document the stepwise assembly of the zebrafish pectoral fin vasculature. We show that fin vascular network formation is a stereotyped, choreographed process that begins with the growth of an initial vascular loop around the pectoral fin. This loop connects to the dorsal aorta to initiate pectoral vascular circulation. Pectoral fin vascular development continues with concurrent formation of three elaborate vascular plexuses, one in the distal fin that develops into the fin ray vasculature and two near the base of the fin in association with the developing fin musculature. Our findings detail a complex yet highly choreographed series of steps involved in the development of a complete, functional organ-specific vascular network.SUMMARY STATEMENTThe stereotyped assembly of the pectoral fin vasculature is documented from first migratory sprout into the limb bud, to the adult-like form of the four week old larva.
An immunoinformatics approach to study the epitopes contributed by Nsp13 of SARS-CoV-2
Authors: Kumar Sushant , Azad Gajendra Kumar 
Published: April 2021

ABSTRACTThe on-going coronavirus disease-19 (COVID-19) pandemic caused by SARS-CoV-2 has infected hundreds of millions of people and killed more than two million people worldwide. Currently, there are no effective drugs available for treating SARS-CoV-2 infections; however, vaccines are now being administered worldwide to control this virus. In this study, we have studied SARS-CoV-2 helicase, Nsp13, which is critical for viral replication. We compared the Nsp13 sequences reported from India with the first reported sequence from Wuhan province, China to identify and characterize the mutations occurring in this protein. To correlate the functional impact of these mutations, we characterised the most prominent B cell and T cell epitopes contributed by Nsp13. Our data revealed twenty-one epitopes, which exhibited high antigenicity, stability and interactions with MHC class-I and class-II molecules. Subsequently, the physiochemical properties of these epitopes were also analysed. Furthermore, several of these Nsp13 epitopes harbour mutations, which were further characterised by secondary structure and per-residue disorderness, stability and dynamicity predictions. Altogether, we report the candidate epitopes of Nsp13 that may help the scientific community to understand the evolution of SARS-CoV-2 variants and their probable implications.
SARS-CoV-2 B.1.1.7 infection of Syrian hamster does not cause more severe disease and is protected by naturally acquired immunity
Authors: Nuñez Ivette A. , Lien Christopher Z. , Selvaraj Prabhuanand , Stauft Charles B. , Liu Shufeng , Starost Matthew F. , Wang Tony T. 
Published: April 2021

AbstractEpidemiological studies have revealed the emergence of multiple SARS-CoV-2 variants of concern (VOC), including the lineage B.1.1.7 that is rapidly replacing old variants. The B.1.1.7 variant has been linked to increased morbidity rates, transmissibility, and potentially mortality (1). To assess viral fitness in vivo and to address whether the B.1.1.7 variant is capable of immune escape, we conducted infection and re-infection studies in naïve and convalescent Syrian hamsters (>10 months old). Hamsters infected by either a B.1.1.7 variant or a B.1 (G614) variant exhibited comparable viral loads and pathology. Convalescent hamsters that were previously infected by the original D614 variant were protected from disease following B.1.1.7 challenge with no observable clinical signs or lung pathology. Altogether, our study did not find that the B.1.1.7 variant significantly differs from the B.1 variant in pathogenicity in hamsters and that natural infection-induced immunity confers protection against a secondary challenge by the B1.1.7 variant.
Discovery and in-vitro evaluation of potent SARS-CoV-2 entry inhibitors
Authors: Acharya Arpan , Pandey Kabita , Thurman Michellie , Klug Elizabeth , Trivedi Jay , Lorson Christian L. , Singh Kamal , Byrareddy Siddappa N. 
Published: April 2021

AbstractSARS-CoV-2 infection initiates with the attachment of spike protein to the ACE2 receptor. While vaccines have been developed, no SARS-CoV-2 specific small molecule inhibitors have been approved. Herein, utilizing the crystal structure of the ACE2/Spike receptor binding domain (S-RBD) complex in computer-aided drug design (CADD) approach, we docked ∼8 million compounds within the pockets residing at S-RBD/ACE2 interface. Five best hits depending on the docking score, were selected and tested for their in vitro efficacy to block SARS-CoV-2 replication. Of these, two compounds (MU-UNMC-1 and MU-UNMC-2) blocked SARS-CoV-2 replication at sub-micromolar IC50 in human bronchial epithelial cells (UNCN1T) and Vero cells. Furthermore, MU-UNMC-2 was highly potent in blocking the virus entry by using pseudoviral particles expressing SARS-CoV-2 spike. Finally, we found that MU-UNMC-2 is highly synergistic with remdesivir (RDV), suggesting that minimal amounts are needed when used in combination with RDV, and has the potential to develop as a potential entry inhibitor for COVID-19.
HAP40 orchestrates huntingtin structure for differential interaction with polyglutamine expanded exon 1
Authors: Harding Rachel J. , Deme Justin C. , Hevler Johannes F. , Tamara Sem , Lemak Alexander , Cantle Jeffrey P. , Szewczyk Magdalena M. , Zuo Xiaobing , Loppnau Peter , Seitova Alma , Hutchinson Ashley , Fan Lixin , Schapira Matthieu , Carroll Jeffrey B. , Heck Albert J. R. , Lea Susan M. , Arrowsmith Cheryl H. 
Published: April 2021

AbstractHuntington’s disease results from expansion of a glutamine-coding CAG tract in the huntingtin (HTT) gene, producing an aberrantly functioning form of HTT. Both wildtype and disease-state HTT form a hetero-dimer with HAP40 of unknown functional relevance. We demonstratein vivothat HTT and HAP40 cellular abundance are coupled. Integrating data from a 2.6 Å cryo-electron microscopy structure, cross-linking mass spectrometry, small-angle X-ray scattering, and modeling, we provide a near-atomic-level view of HTT, its molecular interaction surfaces and compacted domain architecture, orchestrated by HAP40. Native mass-spectrometry reveals a remarkably stable hetero-dimer, potentially explaining the cellular inter-dependence of HTT and HAP40. The polyglutamine tract containing N-terminal exon 1 region of HTT is dynamic, but shows greater conformational variety in the mutant than wildtype exon 1. By providing novel insight into the structural consequences of HTT polyglutamine expansion, our data provide a foundation for future functional and drug discovery studies targeting Huntington’s disease.