bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variation in white spruce needle respiration at the species range limits: a potential impediment to northern expansion
Authors: Griffin Kevin L. , Griffin Zoe M. , Schmiege Stephanie C. , Bruner Sarah G. , Boelman Natalie T. , Vierling Lee A. , Eitel Jan U. H. 
Published: August 2021

AbstractWhite spruce (Picea glauca) spans a massive range from arctic treeline to temperate forests, yet the variability in respiratory physiology and related implications for tree carbon balance at the extremes of this distribution remain as enigmas. Working at both the most northern and southern extents of the white spruce distribution range more than 5000 km apart, we measured the short- term temperature response of dark respiration (R/T) at upper and lower canopy positions.R/T curves were fit to both polynomial and thermodynamic models so that model parameters could be compared among locations, canopy positions, and with previously published data. Respiration measured at 25°C (R25) was 68% lower at the southern location than at the northern location (0.73±0.15 vs. 2.27±0.02 μmol m-2s-1), resulting in a significantly lower (p< 0.01) intercept inR/T response in temperate trees. Only at the southern location did upper canopy leaves have a steeper temperature response than lower canopy leaves, likely reflecting steeper canopy gradients in light. No differences were observed in the maximum temperature of respiration. At the northern range limit respiration is nearly twice that of the averageR25 reported in a global leaf respiration database. This large carbon cost likely challenges tree survival and contributes to restricting the location of the northern treeline. We predict that without significant thermal acclimation, foliage respiration will increase with projected end-of-the-century warming and will likely constrain the future range limits of this important boreal species.Summary StatementWhite spruce (Picea glauca) needle respiration at the northern limit of the species range is three times higher than at the southern range limit (when measured at 25 °C). This high carbon cost likely challenges tree survival and contributes to the location of the northern treeline.
Pulsatile electrical stimulation creates predictable, correctable disruptions in neural firing
Authors: Steinhardt Cynthia R. , Mitchell Diana E. , Cullen Kathleen E. , Fridman Gene Y. 
Published: August 2021

ABSTRACTElectrical stimulation is a key tool in neuroscience, both in brain mapping studies and in many therapeutic applications such as cochlear, vestibular, and retinal neural implants. Due to safety considerations, stimulation is restricted to short biphasic pulses. Despite decades of research and development, neural implants lead to varying restoration of function in patients. In this study, we use computational modeling to provide an explanation for how pulsatile stimulation affects axonal channels and therefore leads to variability in restoration of neural responses. The phenomenological explanation is transformed into equations that predict induced firing rate as a function of pulse rate, pulse amplitude, and spontaneous firing rate. We show that these equations predict simulated responses to pulsatile stimulation with a variety of parameters as well as several features of experimentally recorded vestibular afferent responses to pulsatile stimulation. We then discuss the implications of these effects for improving clinical stimulation paradigms and electrical stimulation-based experiments.
Before trilobite legs:Pygmaclypeatus daziensisreconsidered and the ancestral appendicular organization of Cambrian artiopods
Authors: Schmidt Michel , Hou Xianguang , Zhai Dayou , Mai Huijuan , Belojević Jelena , Chen Xiaohan , Melzer Roland R. , Ortega-Hernández Javier , Liu Yu 
Published: August 2021

SUMMARYThe Cambrian Stage 3 Chengjiang biota in South China is one of the most influential Konservat-Lagerstätten worldwide thanks to the fossilization of diverse non-biomineralizing organisms through pyritization. Despite their contributions to understanding the evolution of early animals, several Chengjiang species remain poorly known due to their scarcity and/or incomplete preservation. Here, we use micro-computed tomography to reveal in detail the ventral appendage organization of the enigmatic non-trilobite artiopodPygmaclypeatus daziensis– one of the rarest euarthropods in Chengjiang – and explore its functional ecology and broader evolutionary significance.Pygmaclypeatus daziensispossesses a set of uniramous antennae and 14 pairs of post-antennal biramous appendages, the latter of which show an unexpectedly high degree of heteronomy based on the localized differentiation of the protopodite, endopodite and exopodite along the antero-posterior body axis. The small body size (less than 2 cm), presence of delicate spinose endites, and well-developed exopodites with multiple paddle-shaped lamellae on the appendages ofP. daziensisindicate a nekto-benthic mode of life, and a scavenging/detritus feeding strategy.Pygmaclypeatus daziensisshows that appendage heteronomy is phylogenetically widespread within Artiopoda – the megadiverse clade that includes trilobites and their relatives with non-biomineralizing exoskeletons – and suggests that a single exopodite lobe with paddle-like lamellae is ancestral for this clade.Abstract FigureCover image:Morphological reconstruction of the non-trilobite artiopodPygmaclypeatus daziensisfrom the early Cambrian (Stage 3) Chengjiang biota in south China. Artwork by Holly Sullivan (https://www.sulscientific.com/).
Kinetochore-mediated microtubule assembly and Augmin-dependent amplification drive k-fiber maturation in mammals
Authors: Almeida Ana C. , Oliveira Joana , Drpic Danica , Cheeseman Liam P. , Damas Joana , Lewin Harris A. , Larkin Denis M. , Aguiar Paulo , Pereira António J. , Maiato Helder 
Published: August 2021

AbstractChromosome segregation in mammals relies on the maturation of a thick bundle of kinetochore-attached microtubules known as k-fibers. How k-fibers mature from initial kinetochore-microtubule attachments remains a fundamental question. By combining functional perturbations in Indian muntjac, a placental mammal with the lowest known chromosome number (n=3) and distinctively large kinetochores, with fixed- and subsecond live-cell super-resolution CH-STED nanoscopy, we uncovered the mechanism by which Augmin mediates k-fiber maturation. Augmin promoted kinetochore microtubule turnover by sustaining microtubule formation from kinetochores and poleward flux, regardless of pioneer centrosomal microtubules. Tracking of microtubule growth events within individual k-fibers revealed a wide angular dispersion, consistent with Augmin-mediated branched microtubule nucleation. Augmin depletion reduced the frequency of microtubule growth events within k-fibers and hampered normal repair after acute k-fiber injury by laser microsurgery. Our work underscores the contribution of microtubule formation from kinetochores and Augmin-mediated microtubule amplification for k-fiber maturation and spindle assembly in mammals.
Comparative secretomics identifies conserved WAxR motif-containing effectors in rust fungi that suppress cell death in plants
Authors: Jaswal Rajdeep , Dubey Himanshu , Kiran Kanti , Rawal Hukam , Rajarammohan Sivasubramanian , Prasad Pramod , Bhardwaj Subhash C , Sonah Humira , Deshmukh Rupesh , Gupta Naveen , Sharma Tilak Raj 
Published: August 2021

AbstractIdentification of novel effectors with conserved features has always remained a challenge in plant-pathogen interaction studies. The introduction of the genomics era in plant-pathogen studies has led to the identification of significant candidate effectors with novel motifs such as RxLR and dEER motifs. However, in the case of fungal pathogens, limited conserved motifs associated with effectors have been discovered yet. In the present study, we have performed comparative secretome analysis for major plant pathogens of diverse nutrition mechanisms with the aim of dissecting the features underlying their corresponding secretome and conserved motifs. We showed that rust fungi possess the lowest Cell wall degrading enzymes (CWDEs) consortium lower than other biotrophic pathogens. We also showed rust fungi possess the highest secretory superoxide dismutase (SOD) than other studied plant pathogens. Further, we prioritized the candidate secretory effectors proteins (CSEPs) of all the studied pathogens by combining various effector mining parameters to highlight the candidates with potential effector features. A novel WAxR motif in conjugation with the Y/F/WxC (FGC) motif was identified in the effectors of variousP. striiformisraces present globally. The WAxR/WAxR like motifs ( WxxR, WAxx, xAxR) containing effectors were also found in the secretome of other rust fungi. Further, the functional validation of two candidate effectors with WAxR motif fromP. striiformis Yr9showed that these effectors localize to the nucleus as well as cytoplasm, and are able to suppress BAX induced cell death inNicotiana benthamiana. The mutation analysis of individual residues of the WAxR motif (W, A, R) however did not affect the cell death suppression nor subcellular localization of these effectors. Overall, the current study reports the presence of novel motifs in large numbers of effectors of rust fungi with cell death suppression features.HighlightsSecretome analysis of various plant pathogens performedA prioritization list for candidate effectors designedA novel WAxR motif was discovered in rust fungal effector proteinsTwo WAxR candidate effectors were functionally validated
How synonymous mutations alter enzyme structure and function over long time scales
Authors: Jiang Yang , Neti Syam Sundar , Sitarik Ian , Pradhan Priya , To Philip , Xia Yingzi , Fried Stephen D. , Booker Squire J. , O’Brien Edward P. 
Published: August 2021

AbstractThe specific activity of enzymes can be altered over long time scales in cells by synonymous mutations, which change an mRNA molecule’s sequence but not the encoded protein’s primary structure. How this happens at the molecular level is unknown. Here, we investigate this issue by applying multiscale modeling to threeE. colienzymes - type III chloramphenicol acetyltransferase, D-alanine–D-alanine ligase B, and dihydrofolate reductase. This modeling involves coarse-grained simulations of protein synthesis and post-translational behavior, all-atom simulations as a test of robustness, and QM/MM calculations to characterize enzymatic function. We first demonstrate that our model predicts experimentally measured changes in specific activity due to synonymous mutations. Then, we show that changes in codon translation rates induced by synonymous mutations cause shifts in co-translational and post-translational folding pathways that kinetically partition molecules into subpopulations that very slowly interconvert to the native, functional state. These long-lived states exhibit reduced catalytic activity, as demonstrated by their increased activation energies for the reactions they carry out. Structurally, these states resemble the native state, with localized misfolding near the active sites of the enzymes. The localized misfolding involves noncovalent lasso entanglements - a topology in which the protein backbone forms a loop closed by noncovalent native contacts which is then threaded by another portion of the protein. Such entanglements are often kinetic traps, as they can require a large proportion of the protein to unfold, which is energetically unfavorable, before they can disentangle and attain the native state. The near-native structures of these misfolded states allow them to bypass the proteostasis machinery and remain soluble, as they exhibit similar hydrophobic surface areas as the native state. These entangled structures persist in all-atom simulations as well, indicating that these conclusions are independent of model resolution. Moreover, the structures of long-lived entangled states are supported by agreement with limited-proteolysis mass spectrometry results. Thus, synonymous mutations cause shifts in the co- and post-translational structural ensemble of proteins, whose altered subpopulations lead to long-term changes in the specific activities of some enzymes. The formation of entangled subpopulations is a plausible mechanism through which changes in translation elongation rate alter ensemble-averaged specific activities, which can ultimately affect the efficiency of biochemical pathways and phenotypic traits.
Utilizing Digital Pathology to Quantify Stromal Caveolin-1 Expression in Malignant and Benign Ovarian Tumors: Associations with Clinicopathological Parameters and Clinical Outcomes
Authors: Saeed-Vafa Daryoush , Marchion Douglas C. , McCarthy Susan M , Hakam Ardeshir , Lopez Alexis , Wenham Robert M. , Apte Sachin M. , Chen Dung-Tsa , Magliocco Anthony M. , Lancaster Jonathan M. , Reid Brett M. , Permuth Jennifer B. 
Published: August 2021

AbstractLoss of stromal caveolin-1 (Cav-1) is a biomarker of a cancer-associated fibroblast (CAF) phenotype and is related to progression, metastasis, and poor outcomes in several cancers. The objective of this study was to evaluate the clinical significance of Cav-1 expression in invasive epithelial ovarian cancer (OvCa). Epithelial and stromal Cav-1 expression were quantified in serous OvCa and benign ovarian tissue in two, independent cohorts – one quantified expression using immunohistochemistry (IHC) and the other using multiplex immunofluorescence (IF) with digital image analysis designed to target CAF-specific expression. Cav-1 expression was significantly downregulated in OvCa stroma compared to non-neoplastic stroma using both the IHC (p=0.002) and IF (p=1.8×10-13) assays. OvCa stroma showed Cav-1 downregulation compared to tumor epithelium with IHC (p=1.2×10-24). Conversely, Cav-1 expression was higher in OvCa stroma compared to tumor epithelium with IF (p=0.002). There was moderate correlation between IHC and IF methods for stromal Cav-1 expression (r2= 0.69, p=0.006) whereas there was no correlation for epithelial expression (r2=0.006, p=0.98). Irrespective of the staining assay, neither response to therapy or overall survival correlated with the expression level of Cav-1 in the stroma or tumor epithelium. Our findings demonstrate a loss of stromal Cav-1 expression in ovarian serous carcinomas. Studies are needed to replicate these findings and explore therapeutic implications, particularly for immunotherapy response.
The Mechanosensitive Ion Channel MSL10 Modulates Susceptibility toPseudomonas syringaeinArabidopsis thaliana
Authors: Basu Debarati , Codjoe Jennette M. , Veley Kira M. , Haswell Elizabeth S. 
Published: August 2021

ABSTRACTPlants sense and respond to molecular signals associated with the presence of pathogens and their virulence factors. Mechanical signals generated during pathogenic invasion may also be important, but their contributions have rarely been studied. Here we investigate the potential role of a mechanosensitive ion channel, MscS-Like (MSL)10, in defense against the bacterial pathogenPseudomonas syringaeinArabidopsis thaliana. We previously showed that overexpression of MSL10-GFP, phospho-mimetic versions of MSL10, and the gain-of-function allelemsl10-3Gall produce dwarfing, spontaneous cell death, and the hyperaccumulation of reactive oxygen species. These phenotypes are shared by many autoimmune mutants and are frequently suppressed by growth at high temperature in those lines. Here, we found that the same was true for all threeMSL10hypermorphs. In addition, we show that the SGT1/RAR1/HSP90 co-chaperone complex was required for dwarfing and ectopic cell death, PAD4 and SID2 were partially required, and the immune regulators EDS1 and NDR1 were dispensable. AllMSL10hypermorphs exhibited reduced susceptibility to infection byP. syringaestrainPtoDC3000,PtoDC3000 expressing the avirulence genesavrRpt2oravrRpm1, but notPto DC3000 hrpL, and showed an accelerated induction ofPR1expression compared to wild-type plants. Nullmsl10-1mutants were delayed inPR1induction and displayed modest susceptibility to infection by COR-deficientPst. Finally, stomatal closure was reduced inmsl10-1loss-of-function mutants in response toPst COR−. These data show that MSL10 modulates pathogen responses and begin to address the possibility that mechanical signals are exploited by the plant for pathogen perception.
Self-organization of human dorsal-ventral forebrain structures by light induced SHH
Authors: De Santis Riccardo , Etoc Fred , Rosado-Olivieri A. Edwin , Brivanlou Ali H. 
Published: August 2021

SummaryOrganizing centers secrete morphogens that specify the emergence of germ layers and the establishment of the body’s axes during embryogenesis. While traditional experimental embryology tools have been instrumental in dissecting the molecular aspects of organizers in model systems, they are impractical in human in-vitro model systems to quantitatively dissect the relationships between signaling and fate along embryonic coordinates. To systematically study human embryonic organizer centers, we devised a collection of optogenetic ePiggyBac vectors to express a photoactivatable Cre-loxP recombinase, that allows the systematic induction of organizer structures by shining blue-light on hESCs. We used a light stimulus to geometrically confine SHH expression in neuralizing hESCs. This led to the self-organization of mediolateral neural patterns from the organizer. scRNA-seq analysis established that these structures represent the dorsal-ventral forebrain, at the end of the first month of development. Here, we show that morphogen light-stimulation is a scalable tool that induces self-organizing centers.
Cap-independent translation and a precisely localized RNA sequence enable SARS-CoV-2 to control host translation and escape anti-viral response
Authors: Slobodin Boris , Sehrawat Urmila , Lev Anastasia , Ogran Ariel , Fraticelli Davide , Hayat Daniel , Zuckerman Binyamin , Ulitsky Igor , Ben-Shmuel Amir , Bar-David Elad , Levy Haim , Dikstein Rivka 
Published: August 2021

AbstractTranslation of SARS-CoV-2-encoded mRNAs by the host ribosomes is essential for its propagation. Following infection, the early expressed viral protein NSP1 binds the ribosome, represseses translation and induces mRNA degradation, while the host elicits anti-viral response. The mechanisms enabling viral mRNAs to escape this multifaceted repression remain obscure. Here we show that expression of NSP1 leads to destabilization of multi-exon cellular mRNAs, while intron-less transcripts, such as viral mRNAs and anti-viral interferon genes, remain relatively stable. We identified a conserved and precisely located cap-proximal RNA element devoid of guanosines that confers resistance to NSP1-meidated translation inhibition. Importantly, the primary sequence rather than the secondary structure is critical for protection. We further show that the genomic 5’UTR of SARS-CoV-2 exhibits an IRES-like activity and promotes expression of NSP1 in an eIF4E-independent and Torin-1 resistant manner. Upon expression, NSP1 enhances cap-independent translation. However, the sub-genomic 5’UTRs are highly sensitive to eIF4E availability, rendering viral propagation partially sensitive to Torin-1. The combined NSP1-mediated degradation of spliced mRNAs and translation inhibition of single-exon genes, along with the unique features present in the viral 5’UTRs, ensure robust expression of viral mRNAs. These features can be exploited as potential therapeutic targets.
Using expert-elicitation to deliver biodiversity monitoring priorities on a Mediterranean island
Authors: Peyton J. , Hadjistylli M. , Tziortzis I. , Erotokritou E. , Demetriou M. , Samuel-Rhoads Y. , Anastasi V. , Fyttis G. , Hadjioannou L. , Ieronymidou C. , Kassinis N. , Kleitou P. , Kletou D. , Mandoulaki A. , Michailidis N. , Papatheodoulou A. , Payiattas G. , Sparrow D. , Sparrow R. , Turvey K. , Tzirkalli E. , Varnava A.I. , Pescott O.L. 
Published: August 2021

AbstractBiodiversity monitoring plays an essential role in tracking changes in ecosystems, species distributions and abundances across the globe. Data collected through both structured and unstructured biodiversity recording can inform conservation measures designed to reduce, prevent, and reverse declines in valued biodiversity of many types. However, resources for biodiversity monitoring are limited, it is therefore important that funding bodies prioritise actions relative to the requirements in any given region. We addressed this prioritisation requirement through a three-stage process of expert-elicitation, resulting in a prioritised list of twenty biodiversity monitoring needs for Cyprus. Equal priority was assigned to the twenty monitoring needs within three categories: a top nine, a middle five, and a bottom six. The most highly prioritised biodiversity monitoring needs were those related to the development of robust methodologies, and those ensuring a geographic spread of sufficiently skilled and informed contributors. We suggest ways that the results of our expert-elicitation process could be used to support current and future biodiversity monitoring in Cyprus.
Ether anesthetics prevents touch-induced trigger hair calcium-electrical signals excite the Venus flytrap
Authors: Scherzer Sönke , Huang Shouguang , Iosip Anda , Fuchs Ines , Yokawa Ken , AL-Rasheid Khaled A. S. , Heckmann Manfred , Hedrich Rainer 
Published: August 2021

AbstractPlants do not have neurons but operate transmembrane ion channels and can get electrical excited by physical and chemical clues. Among them the Venus flytrap is characterized by its peculiar hapto-electric signaling. When insects collide with trigger hairs emerging the trap inner surface, the mechanical stimulus within the mechanosensory organ is translated into a calcium signal and an action potential (AP). Here we asked how the Ca2+ wave and AP is initiated in the trigger hair and how it is feed into systemic trap calcium-electrical networks. When Dionaea muscipula trigger hairs matures and develop hapto-electric excitability the mechanosensitive anion channel DmMSL10/FLYC1 and voltage dependent SKOR type Shaker K+ channel are expressed in the sheering stress sensitive podium. The podium of the trigger hair is interface to the flytrap’s prey capture and processing networks. In the excitable state touch stimulation of the trigger hair evokes a rise in the podium Ca2+ first and before the calcium signal together with an action potential travel all over the trap surface. In search for podium ion channels and pumps mediating touch induced Ca2+ transients, we, in mature trigger hairs firing fast Ca2+ signals and APs, found OSCA1.7 and GLR3.6 type Ca2+ channels and ACA2/10 Ca2+ pumps specifically expressed in the podium. Like trigger hair stimulation, glutamate application to the trap directly evoked a propagating Ca2+ and electrical event. Given that anesthetics affect K+ channels and glutamate receptors in the animal system we exposed flytraps to an ether atmosphere. As result propagation of touch and glutamate induced Ca2+ and AP long-distance signaling got suppressed, while the trap completely recovered excitability when ether was replaced by fresh air. In line with ether targeting a calcium channel addressing a Ca2+ activated anion channel the AP amplitude declined before the electrical signal ceased completely. Ether in the mechanosensory organ did neither prevent the touch induction of a calcium signal nor this post stimulus decay. This finding indicates that ether prevents the touch activated, glr3.6 expressing base of the trigger hair to excite the capture organ.