bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic product-precursor relationships underlie cuticular lipid accumulation on maize silks
Authors: Chen Keting , Alexander Liza E. , Mahgoub Umnia , Okazaki Yozo , Higashi Yasuhiro , Takano Kouji , Loneman Derek , Dennison Tesia S. , Lopez Miriam , Claussen Reid , Peddicord Layton , Saito Kazuki , Lauter Nick , Dorman Karin S. , Nikolau Basil J. , Yandeau-Nelson Marna D. 
Published: April 2021

ABSTRACTThe hydrophobic cuticle is the first line of defense between aerial portions of a plant and the external environment. On maize silks, the cuticular cutin matrix is infused with cuticular lipids, consisting of a homologous series of very-long-chain fatty acids (VLCFAs), aldehydes, and hydrocarbons that serve as precursors, intermediates, and end-products of the elongation, reduction, and decarbonylation reactions of the hydrocarbon-producing pathway. To deconvolute the potentially confounding impacts of the silk microenvironment and silk development on the hydrocarbon-producing pathway, spatio-temporal cuticular lipid profiling was conducted on the agronomically important inbreds B73 and Mo17, and their reciprocal hybrids. Statistical interrogation via multivariate analyses of the metabolite abundances of the hydrocarbon-producing pathway demonstrate that the cellular VLCFA pool is positively correlated with the cuticular lipid metabolome, and this metabolome is primarily affected by the silk microenvironment and the plant genotype. Moreover, genotype has a major effect on the pathway, with increased cuticular hydrocarbon and concomitant reduction of cuticular VLCFA accumulation on B73 silks, suggesting that conversion of VLCFAs to hydrocarbons is more effective in B73 than Mo17. Statistical modeling of the ratios between cuticular hydrocarbons and cuticular VLCFAs reveals the complexity of the product-precursor ratio relationship, demonstrating a significant role of precursor chain length. Longer-chain VLCFAs are preferentially utilized as precursors for hydrocarbon biosynthesis. Collectively, these findings demonstrate maize silks as an effective and novel system for dissection of the complex dynamics of cuticular lipid accumulation in plants.One-sentence SummaryThe product-precursor ratios in the cuticular hydrocarbon-producing pathway are impacted by fatty acid precursor chain length, plant genotype and the spatio-temporal dynamic gradients of maize silks.
Dynamic functional connectivity links with treatment response of electroconvulsive therapy in major depressive disorder
Authors: Sendi Mohammad S. E. , Dini Hossein , Sui Jing , Fu Zening , Espinoza Randall , Narr Katherine , Qi Shile , Abbott Christopher C. , van Rooij Sanne , Riva-Posse Patricio , Mayberg Helen S. , Calhoun Vince D. 
Published: April 2021

AbstractBackgroundElectroconvulsive Therapy (ECT) is one of the most effective treatments for major depressive disorder (DEP). There is recently increasing attention to evaluate ECT’s effect on resting-state functional magnetic resonance imaging (rs-fMRI). This study aims to compare rs-fMRI of DEP patients with healthy participants, investigate whether dynamic functional network connectivity network (dFNC) estimated from rs-fMRI predicts the ECT outcome, and explore the effect of ECT on brain network states.MethodResting-state fMRI data were collected from 119 patients with depression or DEP (76 females), and 61 Healthy (HC) participants (34 females) with an age mean of 52.25 (N=180) years old. The pre-ECT and post-ECT Hamilton Depression Rating Scale (HDRS) were 25.59±6.14 and 11.48±9.07, respectively. Twenty-four independent components from default mode (DMN) and cognitive control network (CCN) were extracted using group-independent component analysis from pre-ECT and post-ECT rs-fMRI. Then, the sliding window approach was used to estimate the pre-and post-ECT dFNC of each participant. Next, k-means clustering was separately applied to pre-ECT dFNC and post-ECT dFNC to assess three distinct states from each participant. We calculated the amount of time each individual spends in each state, called occupancy rate or OCR. Next, we compared OCR values between HC and DEP participants. We also calculated the partial correlation between pre-ECT OCRs and HDRS change while controlling for age, gender, number of treatment, and site. Finally, we evaluated the effectiveness of ECT by comparing pre-and post-ECT OCR of DEP and HC participants.ResultsThe main findings include: 1) DEP patients had significantly lower OCR values than the HC group in a state, where connectivity between CCN and DMN was relatively higher than other states (corrected p= 0.015), 2) Pre-ECT OCR of state, with more negative connectivity between CCN and DMN components, predicted the HDRS changes (R=0.23 corrected p=0.03). This means that those DEP patients who spend less time in this state showed more HDRS change, and 3) The post-ECT OCR analysis suggested that ECT increased the amount of time DEP patients spend in state 2 (corrected p=0.03). Finally, we found ECT increases the total traveled distance in DEP.ConclusionOur finding suggests that dFNC features, estimated from CCN and DMN, show promise as a predictive biomarker of the ECT outcome of DEP patients. Also, this study identified a possible underlying mechanism associated with the ECT effect in DEP patients.
A meta-analysis of Microarray Data is Effective for Identifying Gravity-Sensitive Genes
Authors: Liang Yin , Wang Mengxue , Liu Yun , Wang Chen , Takahashi Ken , Naruse Keiji 
Published: April 2021

AbstractGravity affects the function and maintenance of organs, such as bones, muscles, and the heart. Several studies have used DNA microarrays to identify genes with altered expressions in response to gravity. However, it is technically challenging to combine the results from various microarray datasets because of their different data structures. We hypothesized it is possible to identify common changes in gene expression from the DNA microarray datasets obtained under various conditions and methods. In this study, we grouped homologous genes to perform a meta-analysis of multiple vascular endothelial cell and skeletal muscle datasets. According to the t-distributed stochastic neighbor embedding (t-SNE) analysis, the changes in the gene expression pattern in vascular endothelial cells formed specific clusters. We also identified candidate genes in endothelial cells that responded to gravity. Further, we exposed human umbilical vein endothelial cells to simulated microgravity using a clinostat and measured the expression levels of the candidate genes. Gene expression analysis using qRT-PCR revealed that the expression level of the prostaglandin transporter geneSLCO2A1decreased in response to microgravity, consistent with the meta-analysis of microarray datasets. Furthermore, the direction of gravity affected the expression level ofSLCO2A1, buttressing the finding that its expression was affected by gravity. These results suggest that a meta-analysis of DNA microarray datasets may help identify new target genes previously overlooked in individual microarray analyses.
Multiplexed 3D atlas of state transitions and immune interactions in colorectal cancer
Authors: Lin Jia-Ren , Wang Shu , Coy Shannon , Chen Yu-An , Yapp Clarence , Tyler Madison , Nariya Maulik K. , Heiser Cody N. , Lau Ken S. , Santagata Sandro , Sorger Peter K. 
Published: April 2021

SUMMARYAdvanced solid cancers are complex assemblies of tumor, immune, and stromal cells characterized by high intratumoral variation. We use highly multiplexed tissue imaging, 3D reconstruction, spatial statistics, and machine learning to identify cell types and states underlying morphological features of known diagnostic and prognostic significance in colorectal cancer. Quantitation of these features in high-plex marker space reveals recurrent transitions from one tumor morphology to the next, some of which are coincident with long-range gradients in the expression of oncogenes and epigenetic regulators. At the tumor invasive margin, where tumor, normal, and immune cells compete, T-cell suppression involves multiple cell types and 3D imaging shows that seemingly localized 2D features such as tertiary lymphoid structures are commonly interconnected and have graded molecular properties. Thus, while cancer genetics emphasizes the importance of discrete changes in tumor state, whole-specimen imaging reveals large-scale morphological and molecular gradients analogous to those in developing tissues.
Effective Therapy Targeting Cytochromebc1PreventsBabesiaErythrocytic Development and Protects from Lethal Infection
Authors: Chiu Joy E. , Renard Isaline , Pal Anasuya C. , Singh Pallavi , Vydyam Pratap , Thekkiniath Jose , Kumar Madelyn , Gihaz Shalev , Pou Sovitj , Winter Rolf W. , Dodean Rozalia , Nilsen Aaron C. , Riscoe Michael K. , Doggett J. Stone , Mamoun Choukri Ben 
Published: April 2021

AbstractTargeting conserved metabolic processes that are essential for viability of pathogens, such asPlasmodiumandBabesiathat cause blood-borne diseases, is an effective strategy to eliminate malaria and babesiosis infections with no recrudescence. One interesting target is the mitochondrial cytochromebc1complex, which could be inhibited by drugs such as endochin-like quinolones (ELQ) and atovaquone. We used the tick-transmitted and culturable blood-borne pathogenBabesia duncanito evaluate the structure-activity relationship, safety, efficacy and mode of action of ELQs. We identified a potent and highly selective ELQ prodrug (ELQ-502), which alone or in combination with atovaquone eliminatesB. microtiandB. duncaniinfectionsin vitroand in mouse models of parasitemia and lethal infection. The strong efficacy at low dose, excellent safety, bioavailability and long half-life of this experimental therapy makes it an ideal clinical candidate for the treatment of human infections caused byBabesiaand its closely related apicomplexan parasites.
Root meristem shaping via brassinosteroid-controlled cell geometry
Authors: Fridman Y. , Strauss S. , Horev G. , Ackerman-Lavert M. , Benaim A Reiner , Lane B , Smith R.S. , Savaldi-Goldstein S. 
Published: April 2021

AbstractGrowth extent and direction determine cell and whole-organ architecture. How they are spatiotemporally modulated to control size and shape? Here we tackled this question by studying the effect of brassinosteroid (BR) signaling on the structure of the root meristem. Quantification of the 3D geometry of thousands of individual meristematic cells across different tissue types showed that modulation of BR signaling yields distinct changes in growth rate and anisotropy, which affects the time cells spend in the meristem and has a strong impact on final root form. By contrast, the hormone effect on cell volume was minor, establishing cell volume as invariant to the effect of BR. Thus, BR has highest effect on cell shape and growth anisotropy, regulating overall radial growth of the meristem, while maintaining a coherent distribution of cell sizes. Moving from single-cell quantification to the whole organ, we developed a computational model of radial growth that demonstrates how differential growth regulation by BR between the inner and outer tissues shapes the meristem. The model explains the unintuitive outcomes of tissue-specific perturbation of BR signaling and suggests that the inner and outer tissues have independent but coordinated roles in growth regulation.
HaloTag9: an engineered protein tag to improve fluorophore performance
Authors: Frei Michelle S. , Tarnawski Miroslaw , Roberti Julia , Koch Birgit , Hiblot Julien , Johnsson Kai 
Published: April 2021

AbstractHaloTag9 is an engineered variant of HaloTag7 with up to 40% higher brightness and increased fluorescence lifetime when labeled with fluorogenic rhodamines. Moreover, combining HaloTag9 with HaloTag7 and other fluorescent probes enabled live-cell multiplexing using a single fluorophore and the generation of a fluorescence lifetime-based biosensor. The increased brightness of HaloTag9 and its use in fluorescence lifetime multiplexing makes it a powerful tool for live-cell imaging.
Analysis of glycosylation and disulfide bonding of wild-type SARS-CoV-2 spike glycoprotein
Authors: Zhang Shijian , Go Eden P. , Ding Haitao , Anang Saumya , Kappes John C. , Desaire Heather , Sodroski Joseph 
Published: April 2021

ABSTRACTThe SARS-CoV-2 coronavirus, the etiologic agent of COVID-19, uses its spike (S) glycoprotein anchored in the viral membrane to enter host cells. The S glycoprotein is the major target for neutralizing antibodies elicited by natural infection and by vaccines. Approximately 35% of the SARS-CoV-2 S glycoprotein consists of carbohydrate, which can influence virus infectivity and susceptibility to antibody inhibition. We found that virus-like particles produced by coexpression of SARS-CoV-2 S, M, E and N proteins contained spike glycoproteins that were extensively modified by complex carbohydrates. We used a fucose-selective lectin to enrich the Golgi-resident fraction of a wild-type SARS-CoV-2 S glycoprotein trimer, and determined its glycosylation and disulfide bond profile. Compared with soluble or solubilized S glycoproteins modified to prevent proteolytic cleavage and to retain a prefusion conformation, more of the wild-type S glycoprotein N-linked glycans are processed to complex forms. Even Asn 234, a significant percentage of which is decorated by high-mannose glycans on soluble and virion S trimers, is predominantly modified in the Golgi by processed glycans. Three incompletely occupied sites of O-linked glycosylation were detected. Viruses pseudotyped with natural variants of the serine/threonine residues implicated in O-linked glycosylation were generally infectious and exhibited sensitivity to neutralization by soluble ACE2 and convalescent antisera comparable to that of the wild-type virus. Unlike other natural cysteine variants, a Cys15Phe (C15F) mutant retained partial, but unstable, infectivity. These findings enhance our understanding of the Golgi processing of the native SARS-CoV-2 S glycoprotein carbohydrates and could assist the design of interventions.
Global ubiquitylation analysis of mitochondria in primary neurons identifies physiological Parkin targets following activation of PINK1
Authors: Antico Odetta , Ordureau Alban , Stevens Michael , Singh Francois , Gierlinski Marek , Barini Erica , Rickwood Mollie L. , Prescott Alan , Toth Rachel , Ganley Ian G. , Harper J. Wade , Muqit Miratul M. K. 
Published: April 2021

SUMMARYAutosomal recessive mutations in PINK1 and Parkin cause Parkinson’s disease. How activation of PINK1 and Parkin leads to elimination of damaged mitochondria by mitophagy is largely based on cell culture studies with few molecular studies in neurons. Herein we have undertaken a global proteomic-analysis of mitochondria from mouse neurons to identify ubiquitylated substrates of endogenous Parkin activation. Comparative analysis with human iNeuron datasets revealed a subset of 49 PINK1-dependent diGLY sites upregulated upon mitochondrial depolarisation in 22 proteins conserved across mouse and human systems. These proteins were exclusively localised at the mitochondrial outer membrane (MOM) including, CISD1, CPT1α, ACSL1, and FAM213A. We demonstrate that these proteins can be directly ubiquitylated by Parkinin vitro. We also provide evidence for a subset of cytoplasmic proteins recruited to mitochondria that undergo PINK1 and Parkin independent ubiquitylation including SNX3, CAMK2α and CAMK2β indicating the presence of alternate ubiquitin E3 ligase pathways that are activated by mitochondrial depolarisation in neurons. Finally we have developed an online resource to visualise mitochondrial ubiquitin sites in neurons and search for ubiquitin components recruited to mitochondria upon mitochondrial depolarisation, MitoNUb. This analysis will aid in future studies to understand Parkin activation in neuronal subtypes. Our findings also suggest that monitoring ubiquitylation status of the 22 identified MOM proteins may represent robust biomarkers for PINK1 and Parkin activityin vivo.
Expanding Asgard members in the domain of Archaea shed new light on the origin of eukaryotes
Authors: Xie Ruize , Wang Yinzhao , Huang Danyue , Hou Jialin , Li Liuyang , Hu Haining , Zhao Xiaoxiao , Wang Fengping 
Published: April 2021

AbstractThe hypothesis that eukaryotes originated from within the domain Archaea has been strongly supported by recent phylogenomic analyses placing Heimdallarchaeota from the Asgard superphylum as the closest known archaeal sister-group to eukaryotes. At present, only six phyla are described in the Asgard superphylum, which limits our understanding of the relationship between eukaryotes and archaea, as well as the evolution and ecological functions of the Asgard archaea. Here, we describe five previously unknown phylum-level Asgard archaeal lineages, tentatively named Tyr-, Sigyn-, Freyr-, Njord- and Balderarchaeota. Comprehensive phylogenomic analyses further supported the origin of eukaryotes within Archaea and a new Asgard lineage Njordarchaeota was supposed as the known closest branch with the eukaryotic nuclear host lineage. Metabolic reconstruction suggests that the Asgard archaea described here have potential to fix inorganic carbon via the Wood-Ljungdahl pathway and degrade organic matters except Njordarchaeota, which may possess a heterotrophic lifestyle with capability of peptides and amino acids utilization. Additionally, the Ack/Pta pathway for homoacetogenesis andde novoanaerobic cobalamin biosynthesis pathway were found in Balderarchaeota and Tyrarchaeota, respectively. This study largely expands the Asgard superphylum, provides additional evidences to support the 2-domain life tree and sheds new light on the evolution of eukaryotes.
Non-parametric synergy modeling with Gaussian processes
Authors: Shapovalova Yuliya , Heskes Tom , Dijkstra Tjeerd 
Published: April 2021

AbstractBackgroundUnderstanding the synergetic and antagonistic effects of combinations of drugs and toxins is vital for many applications, including treatment of multifactorial diseases and ecotoxicological monitoring. Synergy is usually assessed by comparing the response of drug combinations to a predicted non-interactive response from reference (null) models. Possible choices of null models are Loewe additivity, Bliss independence and the recently rediscovered Hand model. A different approach is taken by the MuSyC model, which directly fits a generalization of the Hill model to the data. All of these models, however, fit the dose-response relationship with a parametric model.ResultsWe propose the Hand-GP model, a non-parametric model based on the combination of the Hand model with Gaussian processes. We introduce a new logarithmic squared exponential kernel for the Gaussian process which captures the logarithmic dependence of response on dose. From the monotherapeutic response and the Hand principle, we construct a null reference response and synergy is assessed from the difference between this null reference and the Gaussian process fitted response. We evaluated performance of our model on a simulated data from Greco, two simulated data sets of our own design and two benchmark data sets from Chou and Talalay. We compare the Hand-GP model to standard synergy models and show that our model performs better than these standards. We also compare our model to the MuSyC model as example of a recent method which also fits a complete dose-response surface. Also in this case, the Hand-GP model performs better.ConclusionThe Hand-GP model is a flexible model to capture synergy. Its non-parametric natures allows it to model a wide variety of response patterns.
The interplay between growth rate and nutrient quality defines gene expression capacity
Authors: Kim Juhyun , Darlington Alexander P.S. , Bates Declan G. , Jimenez Jose I. 
Published: April 2021

AbstractThe gene expression capacity of bacterial cells depends on the interplay between growth and the availability of the transcriptional and translational machinery. Growth rate is widely accepted as the global physiological parameter controlling the allocation of cell resources. This allocation has an impact on the ability of the cell to produce both host and heterologous proteins required for synthetic circuits and pathways. Understanding the relationship between growth and resources is key for the efficient design of artificial genetic constructs, however, it is obscured by the mutual dependence of growth and gene expression on each other. In this work, we investigate the individual contributions of molecular factors, growth rate and metabolism to gene expression by investigating the behaviour of bacterial cells growing in chemostats in growth-limited conditions. We develop a model of the whole cell that captures trade-offs in gene expression arising from the individual contributions of different factors, and validate it by analysing gene couplings which emerge from competition for the gene expression machinery. Our results show that while growth rate and molecular factors, such as the number of rRNA operons, set the abundance of transcriptional and translational machinery available, it is metabolism that governs the usage of those resources by tuning elongation rates. We show that synthetic gene expression capacity can be maximised by using low growth in a high-quality medium. These findings provide valuable insights into fundamental trade-offs in microbial physiology that will inform future strain and bioprocesses optimisation.
Consumer appreciation of a shark-free eco-label for small pelagics
Authors: Mulazzani Luca , Piredda Laura , Cerjak Marija , Camanzi Luca 
Published: April 2021

PurposeThe objective of this study is to assess if Italian fish consumers are sensible to shark protection and if they would contribute paying more for small pelagic fishes coming from fisheries that are certified as “shark-free”.Design/methodology/approachContingent valuation is used to estimate willingness to pay with a double approach, including a dichotomous choice and an open-ended question. Inconsistency between the two answers is allowed. This allows the correction of two sources of bias (i.e. preference uncertainty and anchoring effect) and has permitted that the two estimation methods converged to the same result.FindingsConsumers show interest for the “shark-free” label. Premium price is estimated at +26%. Variables affecting willingness to pay (WTP) in the sample are age, income, environmental attitude, knowledge of organic labels and frequency of small pelagics' consumption. Results need to be confirmed by a replication on a larger (probabilistic) sample and with a different distribution of bids.Originality/valueEcosystems provide different benefits to humankind, including non-use services, such as the satisfaction to know that a species is well conserved. Generally, appreciation is higher for what are considered charismatic species. In this paper, the authors investigate if sharks can be considered charismatic species despite their “bad reputation”. The interest in shark survival is measured indirectly using a “shark-free” label on a commercial species like anchovy, allowing to increase the value added of this low-price species.