bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antagonistic regulation of salt and sugar chemotaxis plasticity by a single chemosensory neuron inCaenorhabditis elegans
Authors: Tomioka Masahiro , Umemura Yusuke , Ueoka Yutaro , Chin Risshun , Katae Keita , Uchiyama Chihiro , Ike Yasuaki , Iino Yuichi 
Published: January 2023

AbstractThe nematodeCaenorhabditis elegansmemorizes various external chemicals, such as ions and odorants, during feeding. Here we find thatC. elegansis attracted to the monosaccharides glucose and fructose after exposure to these monosaccharides in the presence of food; however, it avoids them without conditioning. The attraction to glucose requires a left-sided ASE gustatory neuron called ASEL. ASEL activity increases when glucose concentration decreases. Optogenetic ASEL stimulation promotes forward movements; however, after glucose conditioning, it promotes turning, suggesting that after glucose conditioning, the behavioral output of ASEL activation switches toward glucose. We previously reported that chemotaxis toward sodium ion (Na+), which is sensed by ASEL, increases after Na+conditioning in the presence of food. Interestingly, glucose conditioning decreases Na+chemotaxis, and conversely, Na+conditioning decreases glucose chemotaxis, suggesting the reciprocal inhibition of learned chemotaxis to distinct chemicals. The activation of PKC-1, an nPKC ε/η ortholog, in ASEL promotes glucose chemotaxis and decreases Na+chemotaxis after glucose conditioning. Furthermore, genetic screening identified ENSA-1, an ortholog of the protein phosphatase inhibitor ARPP-16/19, which functions in parallel with PKC-1 in glucose-induced chemotactic learning toward distinct chemicals. These findings suggest that kinase–phosphatase signaling regulates the balance between learned behaviors based on glucose conditioning in ASEL, which might contribute to migration toward chemical compositions where the animals were previously fed.Author summaryCaenorhabditis elegansresponds to compounds that taste salty, bitter, sour, etc. However, its response to sweet compounds is unclear. Here, we show thatC. elegansresponds to glucose through a chemosensory neuron called ASEL.C. elegansavoids high concentrations of glucose and learns to approach glucose after feeding in the presence of high glucose, dependent on the action of ASEL. The ASEL neuron has been reported to respond to salt and promotes salt attraction after feeding in the presence of high salt. We find that the feeding-associated attractive responses to glucose and salt are antagonistic. When encountered with a mixture of salt and glucose during feeding,C. eleganschanges its chemotactic response toward those chemicals according to the balance of each chemical in the mixture.C. elegansmay memorize the concentrations of the chemical mixture during feeding and migrates to the chemical composition previously fed, which may promote opportunities obtaining food. Furthermore, we find that kinase–phosphatase signaling, which modulates neurotransmission, in ASEL is required for chemotaxis based on information processing of salt and glucose.
A CRISPRi/a screening platform to study cellular nutrient transport in diverse microenvironments
Authors: Chidley Christopher , Darnell Alicia M. , Gaudio Benjamin L. , Lien Evan C. , Barbeau Anna M. , Vander Heiden Matthew G. , Sorger Peter K. 
Published: January 2023

ABSTRACTBlocking the import of nutrients essential for cancer cell proliferation represents a therapeutic opportunity, but it is unclear which transporters to target. Here, we report a CRISPRi/a screening platform to systematically interrogate the contribution of specific nutrient transporters to support cancer cell proliferation in environments ranging from standard culture media to tumor models. We applied this platform to identify the transporters of amino acids in leukemia cells and found that amino acid transport is characterized by high bidirectional flux that is dependent on the composition of the microenvironment. While investigating the role of transporters in cystine starved cells, we uncovered a novel role for serotonin uptake in preventing ferroptosis. Finally, we identified transporters essential for cell proliferation in subcutaneous tumors and found that levels of glucose and amino acids can restrain proliferation in that environment. This study provides a framework for the systematic identification of critical cellular nutrient transporters, characterizing the function of such transporters, and studying how the tumor microenvironment impacts cancer metabolism.
Age specific impacts of vegetation functional traits on gastro-intestinal nematode parasite burdens in a large herbivore
Authors: Wiersma Ellis , Pakeman Robin J. , Bal Xavier , Pilkington Jill G. , Pemberton Josephine M. , Nussey Daniel H. , Sweeny Amy R. 
Published: January 2023

ABSTRACTGastro-intestinal nematode (GIN) parasites play an important role in the ecological dynamics of many animal populations. Recent studies suggest fine-scale spatial variation in GIN infection dynamics are important in wildlife systems, but the environmental drivers underlying this variation remain poorly understood.We used data from over two decades of GIN parasite egg counts, host space use, and spatial vegetation data from a long-term study of Soay sheep on St Kilda to test how spatial autocorrelation and vegetation in an individual’s home range predict parasite burden across three age groups. We developed a novel approach to quantify the plant functional traits present in a home range to describe the quality of vegetation present.Effects of space and vegetation varied between age classes. In immature lambs, strongyle parasite faecal egg counts (FEC) were spatially structured, being highest in the north and south of our study area. Independent of host body weight and spatial autocorrelation, plant functional traits predicted parasite egg counts. Higher egg counts were associated with more digestible and preferred plant functional traits, suggesting the association could be driven by host density and habitat preference.In contrast, we found no evidence that parasite FEC were related to plant functional traits in the host home range in yearlings or adult sheep. Adult FEC were spatially structured, with highest burdens in the north-east of our study area, while yearling FEC showed no evidence of spatial structuring.Our findings support the importance of fine-scale environmental variation for wildlife disease ecology and provides new evidence that such effects may vary across demographic groups within a population. Parasite burdens in immature individuals appear more readily influenced by fine-scale spatial variation in the environment, highlighting the importance of such heterogeneity for our understanding of wildlife epidemiology and health.
Single-molecule displacement mapping indicates unhindered intracellular diffusion of small (<~1 kDa) solutes
Authors: Choi Alexander A. , Xiang Limin , Li Wan , Xu Ke 
Published: January 2023

AbstractWhile fundamentally important, the intracellular diffusion of small (<~1 kDa) solutes has been difficult to elucidate due to challenges in both labeling and measurement. Here we quantify and spatially map the translational diffusion patterns of small solutes in mammalian cells by integrating several recent advances. In particular, by executing tandem stroboscopic illumination pulses down to 400-μs separation, we extend single-molecule displacement/diffusivity mapping (SMdM), a super-resolution diffusion quantification tool, to small solutes with high diffusion coefficientsDof >300 μm2/s. We thus show that for multiple water-soluble dyes and dye-tagged nucleotides, intracellular diffusion is dominated by vast regions of high diffusivity ~60-70% of thatin vitro, up to ~250 μm2/s in the fastest cases. Meanwhile, we also visualize sub-micrometer foci of substantial slowdowns in diffusion, thus underscoring the importance of spatially resolving the local diffusion behavior. Together, these results suggest that the intracellular diffusion of small solutes is only modestly scaled down by the slightly higher viscosity of the cytosol over water, but otherwise not further hindered by macromolecular crowding. We thus lift a paradoxically low speed limit for intracellular diffusion suggested by previous experiments.Abstract Graphic
Two conformations of the Tom20 preprotein receptor in the TOM holo complex
Authors: Ornelas Pamela , Bausewein Thomas , Martin Janosch , Morgner Nina , Nussberger Stephan , Kühlbrandt Werner 
Published: January 2023

AbstractThe TOM complex is the main entry point for precursor proteins into mitochondria. Precursor proteins containing targeting sequences are recognized by the TOM complex and imported into the mitochondria. We have determined the structure of the TOM core complex fromNeurospora crassaby single-particle cryoEM at 3.3 Å resolution, showing its interaction with a bound presequence at 4 Å resolution, and of the TOM holo complex including the Tom20 receptor at 6-7 Å resolution. TOM is a transmembrane complex consisting of two β-barrels, three receptor subunits and three short transmembrane subunits. Tom20 has a transmembrane helix and a receptor domain on the cytoplasmic side. We propose that Tom20 acts as a dynamic gatekeeper, guiding precursor proteins into the pores of the TOM complex. We analyze the interactions of Tom20 with other TOM subunits, present insights into the structure of the TOM holo complex, and suggest a translocation mechanism.
Homeostatic Reinforcement Theory Accounts for Sodium Appetitive State- and Taste-Dependent Dopamine Responding
Authors: Duriez Alexia , Bergerot Clemence , Cone Jackson J. , Roitman Mitchell F. , Gutkin Boris 
Published: January 2023

AbstractSeeking and consuming nutrients is essential to survival and maintenance of life. Dynamic and volatile environments require that animals learn complex behavioral strategies to obtain the necessary nutritive substances. While this has been classically viewed in terms of homeostatic regulation, where complex nutrient seeking behaviors are triggered by physiological need, recent theoretical work proposed that such strategies are a result of reinforcement learning processes. This theory also proposed that phasic dopamine (DA) signals play a key role in signaling potentially need-fulfilling outcomes. To examine potential links between homeostatic and reinforcement learning processes, we focus on sodium appetite as sodium depletion triggers state and taste dependent changes in behavior and DA signaling evoked by sodium-related stimuli. We find that both the behavior and the dynamics of DA signaling underlying sodium appetite can be accounted for by extending principles of homeostatic regulation into a reinforcement learning framework (HRRL). We first optimized HRRL-based agents to model sodium-seeking behavior measured in rats. Agents successfully reproduced the state and the taste dependence of behavioral responding for sodium as well as for lithium and potassium salts. We then show that these same agents can account for the regulation of DA signals evoked by sodium tastants in a taste and state dependent manner. Our models quantitatively describe how DA signals evoked by sodium decrease with satiety and increase with deprivation suggesting that phasic DA signals and sodium consumption are down regulated prior to animals reaching satiety. Lastly, our HRRL agents also account for the behavioral and neurophysiological observations that suggest mice cannot distinguish between sodium and lithium containing salts. Our HRRL agents exhibited an equal preference for sodium versus lithium containing solutions, and underestimated the nutritional value of sodium when lithium was concurrently available. We propose that animals use orosensory signals as predictors of the internal impact of the consumed good and our results pose clear targets for future experiments. In sum, this work suggests that appetite-dirven behavior may be driven by reinforcement learning mechanisms that are dynamically tuned by homeostatic need.
Gallionellaceae pangenomic analysis reveals insight into phylogeny, metabolic flexibility, and iron oxidation mechanisms
Authors: Hoover Rene L. , Keffer Jessica L. , Polson Shawn W. , Chan Clara S. 
Published: January 2023

AbstractThe iron-oxidizing Gallionellaceae drive a wide variety of biogeochemical cycles through their metabolisms and biominerals. To better understand the environmental impacts of Gallionellaceae, we need to improve our knowledge of their diversity and metabolisms, especially any novel iron oxidation mechanisms. Here, we used a pangenomic analysis of 103 genomes to resolve Gallionellaceae phylogeny and explore the range of genomic potential. Using a concatenated ribosomal protein tree and key gene patterns, we determined Gallionellaceae has four genera, divided into two groups–iron-oxidizing bacteria (FeOB)Gallionella,Sideroxydans, andFerriphaseluswith known iron oxidases (Cyc2, MtoA) and nitrite-oxidizing bacteria (NOB)CandidatusNitrotoga with nitrite oxidase (Nxr). The FeOB and NOB have similar electron transport chains, including genes for reverse electron transport and carbon fixation. Auxiliary energy metabolisms including S oxidation, denitrification, and organotrophy were scattered throughout the Gallionellaceae FeOB. Within FeOB, we found genes that may represent adaptations for iron oxidation, including a variety of extracellular electron uptake (EEU) mechanisms. FeOB genomes encoded more predictedc-type cytochromes overall, notably more multihemec-type cytochromes (MHCs) with >10 CXXCH motifs. These include homologs of several predicted outer membrane porin-MHC complexes, including MtoAB and Uet. MHCs are known to efficiently conduct electrons across longer distances and function across a wide range of redox potentials that overlap with mineral redox potentials, which can help expand the range of usable iron substrates. Overall, the results of pangenome analyses suggest that the Gallionellaceae generaGallionella,Sideroxydans, andFerriphaselusare primarily iron oxidizers, capable of oxidizing dissolved Fe2+as well as a range of solid iron or other mineral substrates.ImportanceNeutrophilic iron-oxidizing bacteria (FeOB) produce copious iron (oxyhydr)oxides that can profoundly influence biogeochemical cycles, notably the fate of carbon and many metals. To fully understand environmental microbial iron oxidation, we need a thorough accounting of iron oxidation mechanisms. In this study we show the Gallionellaceae FeOB have both known iron oxidases as well as uncharacterized multiheme cytochromes (MHCs). MHCs are predicted to transfer electrons from extracellular substrates and likely confer metabolic capabilities that help Gallionellaceae occupy a range of different iron- and mineral-rich niches. Gallionellaceae appear to specialize in iron oxidation, so it makes sense that they would have multiple mechanisms to oxidize various forms of iron, given the many iron minerals on Earth, as well as the physiological and kinetic challenges faced by FeOB. The multiple iron/mineral oxidation mechanisms may help drive the widespread ecological success of Gallionellaceae.
HOS1 promotes plant tolerance to low-energy stressviathe SnRK1 protein kinase
Authors: Margalha Leonor , Elias Alexandre , Belda-Palazón Borja , Peixoto Bruno , Confraria Ana , Baena-González Elena 
Published: January 2023

ABSTRACTPlants need to integrate internal and environmental signals to mount adequate stress responses. The NUCLEAR PORE COMPLEX (NPC) component HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 1 (HOS1) is emerging as such an integrator, affecting responses to cold, heat, light and salinity. Stress conditions often converge in a low-energy signal that activates SUCROSE NON-FERMENTING 1-RELATED KINASE 1 (SnRK1) to promote stress tolerance and survival. Here, we explored the role of HOS1 in the SnRK1-dependent response to low-energy stress inArabidopsis thaliana, using darkness as a treatment and a combination of genetic, biochemical and phenotypic assays. We show that the induction of starvation genes and plant tolerance to prolonged darkness are defective in thehos1mutant. HOS1 interacts physically with the SnRK1α1 catalytic subunit in yeast-two-hybrid andin planta, and the nuclear accumulation of SnRK1α1 is reduced in thehos1mutant. Likewise, another NPC mutant,nup160, exhibits lower activation of starvation genes and decreased tolerance to prolonged darkness. Importantly, defects in low-energy responses in thehos1background are rescued by fusing SnRK1α1 to a potent nuclear localization signal, or by sugar supplementation during the dark treatment. Altogether, this work demonstrates the importance of HOS1 for the nuclear accumulation of SnRK1α1, which is key for plant tolerance to low-energy conditions.
Export of diverse and bioactive peptides through a type I secretion system
Authors: Kim Sun-Young , Parker Jennifer K. , Gonzalez-Magaldi Monica , Telford Mady S. , Leahy Daniel J. , Davies Bryan W. 
Published: January 2023

AbstractMicrocins are peptide antibiotics secreted by Gram-negative bacteria that inhibit the growth of neighboring microbes. They are exported from the cytosol to the environment in a one-step process through a specific type I secretion system (T1SS). While the rules governing export of natural or non-native substrates have been resolved for T1SSs that secrete large proteins, relatively little is known about substrate requirements for peptides exported through T1SSs that secrete microcins. Here, we investigate the prototypic microcin V T1SS fromEscherichia coliand show it can export a remarkably wide range of natural and synthetic peptides. We demonstrate that secretion through this system is not affected by peptide charge or hydrophobicity and appears only constrained by peptide length. A varied range of bioactive peptides, including an antibacterial peptide, a microbial signaling factor, a protease inhibitor, and a human hormone, can all be secreted and elicit their intended biological effect. Secretion through this system is not limited toE. coli, and we demonstrate its function in additional Gram-negative species that can inhabit the gastrointestinal tract. Our findings uncover the highly promiscuous nature of peptide export thorough the microcin V T1SS, which has implications for native cargo capacity and use of Gram-negative bacteria for peptide research and delivery.ImportanceMicrocin type I secretion systems in Gram-negative bacteria transport antibacterial peptides from the cytoplasm to the extracellular environment in single step. In nature, each microcin secretion system is generally paired with a specific peptide. We know little about the export capacity of these transporters and how peptide sequence influences secretion. Here, we investigate the microcin V type I secretion system. Remarkably, our studies show this system can export diverse peptides and is only limited by peptide length. Furthermore, we demonstrate that various bioactive peptides can be secreted, and this system can be used in Gram-negative species that colonize the gastrointestinal tract. These finding expand our understanding of secretion through type I systems and their potential uses in peptide applications.
IL-4 downregulates BCL6 to promote memory B cell selection in germinal centers
Authors: Shehata Laila , Thouvenel Christopher D. , Hondowicz Brian D. , Pew Lucia A. , Rawlings David J. , Choi Jinyong , Pepper Marion 
Published: January 2023

SummaryGerminal center (GC)-derived memory B cells (MBCs) are critical for humoral immunity as they differentiate into protective antibody-secreting cells during re-infection. GC formation and cellular interactions within the GC have been studied in detail, yet the exact signals that allow for the selection and exit of MBCs are not understood. Here, we show that IL-4 signaling in GC B cells directly downregulates BCL6 via negative autoregulation to release cells from the GC program and promote MBC formation. This selection event requires additional survival cues and can therefore result in either GC exit or death. We demonstrate that both increasing IL-4 bioavailability or limiting IL-4 signaling disrupt MBC selection stringency. In this way, IL-4 control of BCL6 expression serves as a tunable switch within the GC to tightly regulate MBC selection and affinity maturation.
Scientometric, fuzzy NGT and DEMATEL analysis for determining sustainable business practices for entrepreneurial firms
Authors: Patra Bhairab Chandra , Lenka Usha 
Published: January 2023

PurposeThe purpose of this article is to (1) map the most important topics in the domain of sustainable business practices for entrepreneurial firms in emerging countries, (2) identify important terms in the various dimensions of sustainability in business and (3) identify the important practices and prioritize the practices.Design/methodology/approachThis study has adopted a unique methodology that combines state-of-art scientometric analysis with the fuzzy nominal group technique (NGT) and fuzzy decision-making trial and evaluation laboratory (DEMATEL). Results obtained from the co-occurrence analysis in scientometrics were further mapped through NGT to obtain the list of the most important topics in the domain. The factors affecting sustainable business practices obtained through topic mapping were analyzed through fuzzy DEMATEL to obtain the cause-and-effect relation of variables.FindingsThe scale of firms, leadership, uncertainty, gender, country/location, education and tourism were found to be the factors affecting the sustainable business practices of entrepreneurial firms. The sustainable business practices for entrepreneurial firms were (1) innovation, (2) resilience, (3) policy, (4) business ethics and virtue ethics, (5) business model, (6) upcycling and value creation, (7) collaboration and (8) triple bottom line.Practical implicationsPolicymakers in entrepreneurial firms, as well as other organizations, can implement the identified sustainable business practices to obtain optimum results and smooth functioning of the companies. The research framework obtained can be tested using exploratory methods.Originality/valueVery few researchers have used the technique of scientometric analysis to identify the sustainable business practices of entrepreneurial firms, and to the best of the knowledge of the authors, no earlier researcher has attempted to use the technique of topic mapping, fuzzy NGT and fuzzy DEMATEL in combination.