bluuebunny/crossref_metadata_2025_split huggingface dataset:
In VivoBiocompatibility of ZIF-8 for Slow Release via Intranasal Administration
Authors: Kumari Sneha , Howlett Thomas S. , Ehrman Ryanne N. , Koirala Shailendra , Trashi Orikeda , Trashi Ikeda , Wijesundara Yalini H. , Gassensmith Jeremiah J. 
Published: January 2023

AbstractZeolitic Imidazolate Framework-8 (ZIF-8) is becoming popular in research for its potential in antigen protection and for providing a thermally stable, slow-release platform. While papers applying these materials for immunological applications are aplenty in literature, studies that explore the biosafety of ZIF-8 in mammals—especially when administered intranasally—are not well represented. We checked the body clearance of uncoated and ZIF-coated liposomes and observed that the release slowed as ZIF-8 is easily degraded by mucosal fluid in the nasal cavity. We delivered varying doses of ZIF-8, checked their short- and long-term effects on diagnostic proteins found in blood serum, and found no noticeable differences from the saline control group. We also studied their lung diffusing capacity and tissue morphology; neither showed significant changes in morphology or function.Abstract FigureGraphical Abstract:General overview of the investigation
Comparative plant growth responses in a crop-weed mix – a case study ofZea mays(L.) andEleusine indica(L.) Gaertn
Authors: Ikhajiagbe Beckley , Musa Saheed Ibrahim , Ekhator Efuwa Famous 
Published: January 2023

AbstractThe comparative plant growth responses ofZea maysandEleusine indicawere monitored in this studyunder an open field experiment.Both crop and weed were grown separately on the bowls and also in a crop-weed mix. Crop-weed mix were studied in different proportions. The experiment started first by acclimatizing theE. indicaon the soil for a period of three days before sowing the maize. Forty (40) days after plant interactions, results showed significant decreases in plant heights and of both maize andE. indicadepending on the ratio of both plants in the crop-weed mix.comparative to individual height. Similarly, significant decreases in leaf area was reported inE. indica(p=0.015) owing to the interaction. In the control, leaf area was 11.4cm2, but this decreased significantly to 5.94cm2in the 2e3m mix. Similar decreases in maize leaf area have been reported with leaf area values being low (4.32cm2)in the 5e3m mix compared to 19.9cm2in the control (1m). Changes in prominent root length showed a significant decrease between the controlE. indicaand the crop-weed mix. Similar result was observed for maize plant. Although shoot – root ratio was 1.0 in the control weed (1e), a higher value (4.5) was observed in 1m1e followed by 3.5 in the 1m3e and 2m3e mix respectively. For maize plant however, the shoot-root ratio was 4.5 in the control (1m), but reduced to 1.5 in the 1e3m mix. The maize plant was also observed to release allelochemicals, which further indicate its competitive strength.
Temperature and food chain length, but not latitude, explain region-specific kelp forest responses to an unprecedented heatwave
Authors: Starko Samuel , Timmer Brian , Reshitnyk Luba , Csordas Matthew , McHenry Jennifer , Schroeder Sarah , Hessing-Lewis Margot , Costa Maycira , Zielinksi Amanda , Zielinksi Rob , Cook Sarah , Underhill Rob , Boyer Leanna , Fretwell Christopher , Yakimishyn Jennifer , Heath William A. , Gruman Christine , Baum Julia K. , Neufeld Christopher J. 
Published: January 2023

AbstractKelp forests are among the most abundant coastal marine habitats but are vulnerable to the impacts of climate change. Between 2014 and 2016, an unprecedented heatwave and associated changes in trophic dynamics threatened kelp forests across the Northeast Pacific, with impacts documented from Mexico to Alaska. However, responses have varied substantially and remain poorly characterized across large stretches of coast, especially British Columbia (B.C.), which represents a significant percentage of the range of floating kelp species in the Northeast Pacific. Here, we explore variation in floating kelp (Macrocystis, Nereocystis) persistence pre- and post-heatwave across a >675 km latitudinal gradient, asking whether B.C. kelp forests are of conservation concern. We assembled and analyzed available quantitative kelp data, comparing snapshots of kelp extent before (1994 – 2007) and after (2018 – 2021) the heatwave in 11 regions spanning a range of temperature and sea otter-occupancy statuses, and contextualizing these with time series analyses, where available (n = 7 regions). We provide strong evidence that kelp forests have declined in many regions but with evidence of refugia at both local and regional scales. Kelp forest persistence was negatively correlated with summer sea temperatures in southern B.C., where temperatures varied by ~6°C across sites, at times exceeding species’ thermal tolerances. Kelp dynamics in northern regions appeared instead to be modulated by top-down control by urchins and sea otters. Our results demonstrate that B.C.’s kelp forest have been substantially reduced in recent years but that regional and local-scale factors influence the resilience of forests to large-scale perturbations.
Secretion encoded single-cell sequencing (SEC-seq) uncovers gene expression signatures associated with high VEGF-A secretion in mesenchymal stromal cells
Authors: Udani Shreya , Langerman Justin , Koo Doyeon , Baghdasarian Sevana , Cheng Brian , Kang Simran , Soemardy Citradewi , de Rutte Joseph , Plath Kathrin , Di Carlo Dino 
Published: January 2023

AbstractCells secrete numerous bioactive molecules essential for the function of healthy organisms. However, there are no scalable methods to link individual cell secretions to their transcriptional state. By developing and using secretion encoded single-cell sequencing (SEC-seq), which exploits hydrogel nanovials to capture individual cells and their secretions, we simultaneously measured the secretion of vascular endothelial growth factor A (VEGF-A) and the transcriptome for thousands of individual mesenchymal stromal cells (MSCs). We found that VEGF-A secretion is heterogeneous across the cell population and lowly correlated with theVEGFAtranscript level. While there is a modest population-wide increase in VEGF-A secretion by hypoxic induction, highest VEGF-A secretion across normoxic and hypoxic culture conditions occurs in a subpopulation of MSCs characterized by a unique gene expression signature. Taken together, SEC-seq enables the identification of specific genes involved in the control of secretory states, which may be exploited for developing means to modulate cellular secretion for disease treatment.
Enkurin: A novel marker for myeloproliferative neoplasms from platelet, megakaryocyte, and whole blood specimens
Authors: Seetharam Sumanth Mosale , Liu Yi , Wu Jason , Fechter Lenn , Murugesan Kanagavel , Maecker Holden , Gotlib Jason , Zehnder James , Paulmurugan Ramasamy , Krishnan Anandi 
Published: January 2023

AbstractImpaired protein homeostasis, though well established in age-related disorders, has been linked in recent research with the pathogenesis of myeloproliferative neoplasms (MPNs). As yet, however, little is known about MPN-specific modulators of proteostasis, thus impeding our ability for increased mechanistic understanding and discovery of additional therapeutic targets. Loss of proteostasis, in itself, is traced to dysregulated mechanisms in protein folding and intracellular calcium signaling at the endoplasmic reticulum (ER). Here, usingex vivoandin vitrosystems (includingCD34+cultures from patient bone marrow, and healthy cord/peripheral blood specimens), we extend our prior data from MPN patient platelet RNA sequencing, and discover select proteostasis-associated markers at RNA and/or protein levels in each of platelets, parent megakaryocytes, and whole blood specimens. Importantly, we identify a novel role in MPNs for enkurin (ENKUR), a calcium mediator protein, implicated originally only in spermatogenesis. Our data reveal consistentENKURdownregulation at both RNA and protein levels across MPN patient specimens and experimental models, with a concomitant upregulation of a cell cycle marker,CDC20. Silencing ofENKURby shRNA in CD34+derived megakaryocytes further confirm this association withCDC20at both RNA and protein levels; and indicate a likely role for thePI3K/Aktpathway. The inverse association ofENKURandCDC20expression was further confirmed upon treatment with thapsigargin (an agent that causes protein misfolding in the ER by selective loss of calcium) in both megakaryocyte and platelet fractions at RNA and protein levels. Together, our work sheds light on enkurin as a novel marker of MPN pathogenesis beyond the genetic alterations; and indicates further mechanistic investigation into a role for dysregulated calcium homeostasis, and ER and protein folding stress in MPN transformation.VISUAL ABSTRACTKey PointsEnkurin, a calcium adaptor protein, is identified as a novel marker of pathogenesis in MPNs.MPN megakaryocyte and platelet expression of enkurin at RNA and protein levels is inversely associated with a cell differentiation cycle gene, CDC20.Likely role for dysregulated calcium homeostasis, and ER and protein folding stress in MPN transformation.
Adaptive evolution of carnivory inNepenthespitcher plants: a comparative transcriptomics and proteomics perspective
Authors: Scharmann M , Metali F , Grafe T U , Widmer A 
Published: January 2023

AbstractWhile trait diversity associated with evolutionary radiations is easily recognized, their function and adaptive relevance often remain elusive. Here we study the evolution of carnivory genes inNepenthes, an iconic radiation of carnivorous pitcher plants. We investigate 13 species chosen to represent the diversity of nutrient acquisition strategies, geography and climates covered by the genus. Using a combination of proteomics and transcriptomics, we discovered thatNepenthessecrete hundreds of enzymes and antimicrobial proteins into their digestive fluids. Further genes related to plant carnivory were uncovered by analyses of gene expression changes induced by experimental feeding of starvedNepenthestraps. Feeding status appears to affect the relative abundance of nearly 35% of all expressed genes, and may be accompanied by a strong physiological shift away from photosynthesis towards heterotrophy, proteolysis, and protein synthesis. Among the many thousand genes showing signatures of adaptive evolution in sequence or expression level within theNepenthesradiation, the secreted pitcher fluid proteins and the carnivory-related genes were over-represented. A bias towards carnivory genes, and towards trap-expressed genes versus leaf-expressed genes, was also observed among the genes differing in expression in a young pair of sister species. Together, our results suggest that the molecular basis of the carnivorous syndrome was disproportionally targeted by positive selection during theNepenthesradiation. This study demonstrates how the evolutionary relevance of putative key traits can be tested at the level of underlying genes.
Viral and bacterial ecogenomics in globally expanding red snow blooms
Authors: Barno Adam R. , Green Kevin , Rohwer Forest , Silveira Cynthia B. 
Published: January 2023

AbstractChlamydomonasalgal blooms give snowmelt a red color, reducing snow albedo and creating a runaway effect that accelerates snow melting. The occurrence of red snow is predicted to grow in polar and subpolar regions with increasing global temperatures. Here, a global metaanalysis of microbial abundances showed that red snow had higher microbial abundances than white snow. We hypothesize that the increased microbial densities affect virus-bacteria interactions in snow, with potential effects on snowmelt dynamics. A genomic analysis of viral and bacterial communities in red and white snow from the Whistler region of British Columbia, Canada, identified 792 putative viruses infecting bacteria. The most abundant putative snow viruses displayed low genomic similarity with known viruses. We recovered the complete circular genomes of nine putative viruses, two of which were classified as temperate. Genomes of putative snow viruses encoded genes involved in energy metabolisms, such as NAD+synthesis and salvage pathways. In model phages, these genes facilitate increased viral particle production and lysis rates. Yet, the frequency of temperate phages was positively correlated with microbial abundance in the snow samples. These results suggest the increased significance of temperate virus-bacteria interactions as microbial densities increase during snowmelt. We propose that this virus-bacteria dynamic may facilitate the red snow algae growth stimulated by bacteria, representing a potential biological feedback on snowmelt rates.
Theory and practice of using cell strainers to sortCaenorhabditis elegansby size
Authors: Lanier Vincent J. , White Amanda M. , Faumont Serge , Lockery Shawn R. 
Published: January 2023

AbstractThe nematodeCaenorhabditis elegansis a model organism widely used in basic, translational, and industrial research.C. elegansdevelopment is characterized by five morphologically distinct stages, including four larval stages and the adult stage. Stages differ in a variety of aspects including size, gene expression, physiology, and behavior. Enrichment for a particular developmental stage is often the first step in experimental design. When many hundreds of worms are required, the standard methods of enrichment are to grow a synchronized population of hatchlings for a fixed time, or to sort a mixed population of worms according to size. Current size-sorting methods have higher throughput than synchronization and avoid its use of harsh chemicals. However, these size-sorting methods currently require expensive instrumentation or custom microfluidic devices, both of which are unavailable to the majorityC. eleganslaboratories. Accordingly, there is a need for inexpensive, accessible sorting strategies. We investigated the use of low-cost, commercially available cell strainers to filterC. elegansby size. We found that the probability of recovery after filtration as a function of body size for cell strainers of three different mesh sizes is well described by logistic functions. Application of these functions to predict filtration outcomes revealed non-ideal properties of filtration of worms by cell strainers that nevertheless enhanced filtration outcomes. Further, we found that serial filtration using a pair of strainers that have different mesh sizes can be used to enrich for particular larval stages with a purity close to that of synchronization, the most widely used enrichment method. Throughput of the cell strainer method, up to 14,000 worms per minute, greatly exceeds that of other enrichment methods. We conclude that size sorting by cell strainers is a useful addition to the array of existing methods for enrichment of particular developmental stages inC. elegans.
TCDD dysregulation of lncRNA expression, liver zonation and intercellular communication across the liver lobule
Authors: Karri Kritika , Waxman David J. 
Published: January 2023

AbstractThe persistent environmental aryl hydrocarbon receptor agonist and hepatotoxin TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) induces hepatic lipid accumulation (steatosis), inflammation (steatohepatitis) and fibrosis. Thousands of liver-expressed, nuclear-localized lncRNAs with regulatory potential have been identified; however, their roles in TCDD-induced hepatoxicity and liver disease are unknown. We analyzed single nucleus (sn)RNA-seq data from control and chronic TCDD-exposed mouse liver to determine liver cell-type specificity, zonation and differential expression profiles for thousands of IncRNAs. TCDD dysregulated >4,000 of these lncRNAs in one or more liver cell types, including 684 lncRNAs specifically dysregulated in liver non-parenchymal cells. Trajectory inference analysis revealed major disruption by TCDD of hepatocyte zonation, affecting >800 genes, including 121 IncRNAs, with strong enrichment for lipid metabolism genes. TCDD also dysregulated expression of >200 transcription factors, including 19 Nuclear Receptors, most notably in hepatocytes and Kupffer cells. TCDD-induced changes in cell–cell communication patterns included marked decreases in EGF signaling from hepatocytes to non-parenchymal cells and increases in extracellular matrix-receptor interactions central to liver fibrosis. Gene regulatory networks constructed from the snRNA-seq data identified TCDD-exposed liver network-essential lncRNA regulators linked to functions such as fatty acid metabolic process, peroxisome and xenobiotic metabolic. Networks were validated by the striking enrichments that predicted regulatory IncRNAs showed for specific biological pathways. These findings highlight the power of snRNA-seq to discover functional roles for many xenobiotic-responsive lncRNAs in both hepatocytes and liver non-parenchymal cells and to elucidate novel aspects of foreign chemical-induced hepatotoxicity and liver disease, including dysregulation of intercellular communication within the liver lobule.
Protein language model embedded geometric graphs power inter-protein contact prediction
Authors: Si Yunda , Yan Chengfei 
Published: January 2023

AbstractAccurate prediction of contacting residue pairs between interacting proteins is very useful for structural characterization of protein-protein interactions (PPIs). Although significant improvement has been made in inter-protein contact prediction recently, there is still large room for improving the prediction accuracy. Here we present a new deep learning method referred to as PLMGraph-Inter for inter-protein contact prediction. Specifically, we employ rotationally and translationally invariant geometric graphs obtained from structures of interacting proteins to integrate multiple protein language models, which are successively transformed by graph encoders formed by geometric vector perceptrons and residual networks formed by dimensional hybrid residual blocks to predict inter-protein contacts. Extensive evaluation on multiple test sets illustrates that PLMGraph-Inter outperforms five top inter-protein contact prediction methods, including DeepHomo, GLINTER, CDPred, DeepHomo2 and DRN-1D2D_Inter by large margins. In addition, we also show that the prediction of PLMGraph-Inter can complement the result of AlphaFold-Multimer. Finally, we show leveraging the contacts predicted by PLMGraph-Inter as constraints for protein-protein docking can dramatically improve its performance for protein complex structure prediction.
Innate immunity can distinguish beneficial from pathogenic rhizosphere microbiota
Authors: Thoms David , Chen Melissa Y. , Liu Yang , Moreira Zayda Morales , Luo Youqing , Song Siyu , Wang Nicole R. , Haney Cara H. 
Published: January 2023

AbstractFor optimal growth and development, hosts depend on their ability to promote healthy symbiotic interactions while restricting pathogen growth. To ask whether hosts can distinguish phylogenetically similar pathogens and beneficial bacteria, we used two closely related plant-associated strains ofPseudomonas fluorescenswhere one is beneficial and the other exhibits toxin-dependent virulence. We show that while the two strains co-existin vitro, the beneficial outcompetes that pathogenin planta. Using several readouts for plant innate immunity, we found that the beneficial and pathogenic strains elicit mechanistically distinct immune responses that occur in distinct root compartments. We show that while both the pathogenic and beneficial bacterial have plant recognizable MAMPs, the pathogen uniquely induces MAMP-independent immune responses. We found that the pathogen induces both a toxin-independent and a unique toxin-dependent defense response that remains intact in immune signaling mutants includingbak1/bkk1andnpr1/4D. We conclude that hosts can distinguish between phylogenetically similar microbes.
Mechanism underlying delayed rectifying in human voltage-mediated activation Eag2 channel
Authors: Zhang Mingfeng , Shan Yuanyue , Pei Duanqing 
Published: January 2023

AbstractVoltage gradient is a general physical cue that regulates diverse biological function through voltage-gated ion channels. How voltage sensing mediates ion flows remains unknown at the molecular level. Here, we report six conformations of the human Eag2 (hEag2) ranging from closed, pre-open, open, and pore dilation but non-conducting states captured by cryo-electron microscopy (cryo-EM). These multiple states illuminate dynamics of selectivity filter and ion permeating pathway with delayed rectifier property and Cole-Moore effect at the atomic level. Mechanistically, a short S4-S5 linker is coupled with the constrict sites to mediate voltage transducing in a non-domain-swapped configuration, resulting transitions for constrict sites of F464s and Q472s from gating to open state stabilizing for voltage energy transduction. Meanwhile, an additional ion occupied at positions S6 potassium ion confers the delayed rectifier property and Cole-Moore effects. These results provide novel insight into voltage transducing and potassium current across membrane, and shed light on the long-sought Cole-Moore effects.
Sugar signaling modulates SHOOT MERISTEMLESS expression and meristem function in Arabidopsis
Authors: Lopes Filipa L. , Formosa-Jordan Pau , Malivert Alice , Margalha Leonor , Confraria Ana , Feil Regina , Lunn John E. , Jönsson Henrik , Landrein Benoît , Baena-González Elena 
Published: January 2023

SUMMARYIn plants, development of all above-ground tissues is controlled by the shoot apical meristem (SAM) which balances cell proliferation and differentiation to allow life-long growth. To maximize fitness and survival, meristem activity is adjusted to the prevailing conditions through a poorly understood integration of developmental signals with environmental and nutritional information. Here, we show that sugar signals influence SAM function by altering the protein levels of SHOOT MERISTEMLESS (STM), a key regulator of meristem maintenance. STM is less abundant in the inflorescence meristems of plants grown or treated under limiting light conditions, with lower STM levels correlating with lower sugar content in these meristems. Additionally, sucrose but not light is sufficient to sustain STM accumulation in excised inflorescences. Plants overexpressing the α1-subunit of SUCROSE-NON-FERMENTING1-RELATED KINASE 1 (SnRK1) accumulate less STM protein under optimal light conditions, despite higher sugar accumulation in the meristem. Furthermore, SnRK1α1 interacts physically with STM, suggesting a direct local repression. Surprisingly, silencingSnRK1αin the meristem leads to reducedSTMexpression and severe developmental phenotypes previously associated with STM loss-of-function. Altogether, we demonstrate that sugars promote STM accumulation and that the SnRK1 sugar sensor plays a dual role in the SAM, limiting STM abundance under unfavorable conditions but being required for overall meristem organization and integrity. This highlights the importance of sugars and SnRK1 signaling for the proper coordination of meristem activities.