bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venom protection by broadly neutralizing antibody from a snakebite subject
Authors: Glanville Jacob , Andrade Joel Christian , Bellin Mark , Kim Sangil , Pletnev Sergei , Tsao David , Verardi Raffaello , Bedi Rishi , Liao Sindy , Newland Raymond , Bayless Nicholas L. , Youssef Sawsan , Tully Ena , Zhang Baoshan , Bylund Tatsiana , Kim Sujeong , Liu Tracy , Kwong Peter D. 
Published: September 2022

AbstractSnake envenomation is a neglected tropical disease, causing >100,000 deaths and 300,000 permanent disabilities in humans annually. Could monoclonal antibody technology provide a solution? Here, we recover Centi-3FTX-D09, a potent broadly neutralizing antivenom antibody from the B-cell memory of a human subject with snake venom exposure. Centi-3FTX-D09 recognized a conserved neutralizing epitope on long 3-finger toxins (3FTXs), a dominant snake neurotoxin. Crystal structures of Centi-3FTX-D09 in complex with 3FTXs from mamba, taipan, krait, and cobra revealed epitope mimicry of the interface between these neurotoxins and their host target, the nicotinic acetylcholine receptor. Centi-3FTX-D09 providedin-vivoprotection against diverse recombinant long 3FTXs,in-vivorescue from whole venom challenge from cobras, black mamba, and king cobra, and, when combined with the phospholipase inhibitor varespladib,in-vivoprotection extending to a majority of tested elapid venoms. Thus, a single antibody can broadly neutralize long neurotoxins and contribute to broad protection from envenomation.
Spatial Heterogeneity of Brain Lipids in SIV-infected Macaques Treated with Antiretroviral Therapy
Authors: White Cory J. , Gausepohl Andrew M. , Wilkins Hannah N. , Eberhard Colten D. , Orsburn Benjamin C. , Williams Dionna W. 
Published: September 2022

ABSTRACTHuman immunodeficiency virus (HIV) infection continues to promote neurocognitive impairment, mood disorders, and brain atrophy even in the modern era of viral suppression. Brain lipids are vulnerable to HIV-associated energetic strain and contribute to HIV-associated neurologic dysfunction due to alterations in lipid breakdown and structural lipid composition. HIV neuropathology is region dependent, yet there has not been comprehensive characterization of the spatial heterogeneity of brain lipids during infection that may impact neurologic function. To address this gap, we evaluated the spatial lipid distribution using matrix laser desorption/ionization imaging mass spectrometry (MALDI-IMS) across four brain regions (parietal cortex, midbrain, thalamus, and temporal cortex), as well as kidney for a peripheral tissue control, in a virally suppressed simian immunodeficiency virus (SIV)-infected rhesus macaque. We assessed lipids indicative of fat breakdown [acylcarnitines (CARs)] and critical structural lipids [phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs)] across fatty acid chain lengths and degrees of unsaturation. CARs with very long-chain, polyunsaturated fatty acids (PUFAs) were more abundant across all brain regions than shorter chain, saturated or monounsaturated species. We observed distinct brain lipid distribution patterns for CARs and PCs. However, no clear expression patterns emerged for PEs. Surprisingly, kidney was nearly devoid of ions corresponding to PUFAs common in brain. PE’s and PC’s with PUFAs had little intensity and less density than other species and, only one CAR species was observed in kidney at high intensity. Overall, our study provides substantial evidence for persistent bioenergetic changes to the brain despite viral suppression, including region-dependent mobilization of CARs for oxidation and disparities in the presence of key phospholipids necessary for maintaining proper brain structure and function. These data indicate that region-specific interventions to restore proper lipid metabolism are essential for treating HIV neurologic disease in the era of antiretroviral therapy.Graphical Abstract
Evolutionary history of Euteliidae (Lepidoptera, Noctuoidea)
Authors: Zahiri Reza , Holloway Jeremy D. , Rota Jadranka , Schmidt B. Christian , Pellinen Markku J. , Kitching Ian J. , Miller Scott E. , Wahlberg Niklas 
Published: September 2022

AbstractThe Euteliidae stand apart in the Noctuoidea as the second smallest family, but most highly specialized in terms of larval hostplant relationships, favouring plant families with high levels of resin or latex, including the family dominant in Oriental lowland forests, the Dipterocarpaceae. Given the proportionally large foliage biomass represented by dipterocarps, exploitation of this abundant resource by lepidopteran defoliators is surprisingly low, and the Euteliidae may have achieved this through pre-adaption to dipterocarp chemical defences. Therefore, to assess this, we performed a molecular phylogenetic analysis on the family Euteliidae to clarify deep divergences and elucidate evolutionary relationships at the level of the subfamily, tribe, and genus. Our dataset consists of 6.3 kbp of one mitochondrial and seven nuclear DNA loci and was analyzed using model-based phylogenetic methods, i.e., maximum likelihood and Bayesian inference. We attempted to diagnose apomorphic morphological character states for Euteliidae and each monophyletic group within the family. Additionally, the evolution of hostplant use was reconstructed and a molecular-dating approach was conducted to assess the ages of major lineages within Euteliidae. We present an updated phylogenetic hypothesis for Euteliidae consisting of two strongly supported subfamilies: Euteliinae and Stictopterinae. Within Stictopterinae there are two tribes: Stictopterini and Odontodini. Several genera (e.g.,Targalla, Paectes, Marathyssa, Eutelia) were found to be polyphyletic and require taxonomic revision. Two new genera (NiklasteliaandPellinentelia) are described and several taxonomic changes (e.g., new combinations and new synonymies) are made. The Neotropical genusThyriodes, currently included in Euteliidae, is found to be associated with Erebinae (Erebidae). The divergence time estimate for the split between the Euteliidae and Noctuidae is at 53 my, and the Euteliidae split into the subfamilies Euteliinae and Stictopterinae at 42 my. In Stictopterinae, the tribes Stictopterini and Odontodini split at 31 my and the Euteliinae began a much more complex diversification at 34 my. Ancestral hostplant reconstruction identified Malpighiales (e.g., Clusiaceae) as the ancestral larval hostplant order for the family Euteliidae. The ancestors of Stictopterinae also appear to have been Malpighiales feeders, but then split into exclusive specialisms on Malvales (Odontodini) and Malpighiales (Stictopterini) hostplants. Larvae of Stictopterini appear to be restricted to Clusiaceae, apart from a few records from Dipterocarpaceae. In Euteliinae, Anacardiaceae are predominant as larval hosts. Thus, all hosts in the family are lactiferous, possibly providing some degree of pre-adaptation for exploiting Dipterocarpaceae.
A conserved role for stomatin domain genes in olfactory behavior
Authors: Liang Xiaoyu , Taylor Morgan , Napier-Jameson Rebekah , Calovich-Benne Canyon , Norris Adam 
Published: September 2022

ABSTRACTThe highly-conserved stomatin domain has been identified in genes throughout all classes of life. In animals, different stomatin domain-encoding genes have been implicated in the function of the kidney, red blood cells, and specific neuron types, though the underlying mechanisms remain unresolved. In one well-studied example of stomatin domain gene function, theC. elegansgenemec-2and its mouse homologueStoml3are required for the function of mechanosensory neurons, where they modulate the activity of mechanosensory ion channels on the plasma membrane. Here we identify an additional shared function formec-2andStoml3in a very different sensory context, that of olfaction. In worms, we find that a subset of stomatin domain genes are expressed in olfactory neurons, but onlymec-2is strongly required for olfactory behavior.mec-2acts cell-autonomously and does not have any observable effect on olfactory neuron development or morphology, but modestly reduces olfactory neuron activity. We generate aStoml3knockout mouse and demonstrate that, like its worm homologuemec-2, it is required for olfactory behavior. In mice,Stoml3is not required for odor detection, but is required for odor discrimination. Therefore, in addition to their shared roles in mechanosensory behavior,mec-2andStoml3also have a shared role in olfactory behavior.
Positive, negative and engineered durotaxis
Authors: Sáez P. , Venturini C. 
Published: September 2022

AbstractCell migration is a physical process central to life. Among others, it regulates embryogenesis, tissue regeneration and tumor growth. Therefore, understanding and controlling cell migration represent fundamental challenges in science. Specifically, the ability of cells to follow stiffness gradients, known as durotaxis, is ubiquitous across most cell types. Even so, certain cells follow positive stiffness gradients while others move along negative gradients. How the physical mechanisms involved in cell migration works to enable a wide range of durotactic responses is still poorly understood. Here, we provide a mechanistic rationale of durotaxis by integrating stochastic clutch models for cell adhesion with an active gel theory of cell migration. We show that positive and negative durotaxis found across cell types are explained by asymmetries in the cell adhesion dynamics. We rationalize durotaxis by an asymmetric mechanotransduction in the cell adhesion behavior that further polarizes the intracellular retrograde flow and the protruding velocity at the cell membrane. Our theoretical framework confirms previous experimental observations and explains positive and negative durotaxis. Moreover, we show how durotaxis can be engineer to manipulate cell migration, which has important implications in biology, medicine and bioengineering.
Neuronal activity-related transcription is blunted in immature compared to mature dentate granule cells
Authors: Parylak Sarah L , Qiu Fan , Linker Sara B , Gallina Iryna S , Lim Christina K , Preciado David , McDonald Aidan H , Gage Fred H 
Published: September 2022

ABSTRACTImmature dentate granule cells (DGCs) generated in the hippocampus during adulthood are believed to play a unique role in dentate gyrus function. Although immature DGCs have hyperexcitable membrane properties in vitro, the consequences of this hyperexcitability in vivo remain unclear. In particular, the relationship between experiences that activate the dentate gyrus, such as exploration of a novel environment (NE), and downstream molecular processes that modify dentate gyrus circuitry in response to cellular activation are unknown in this cell population. We first performed quantification of immediate early gene proteins in immature (5-week-old) and mature (13-week-old) DGCs from mice exposed to a NE. Paradoxically, we observed lower immediate early gene protein expression in hyperexcitable immature DGCs. We then isolated nuclei from active and inactive immature DGCs and performed single nuclei RNA-Sequencing. Compared to mature nuclei collected from the same animal, immature DGC nuclei showed less activity-induced transcriptional change, even though they were classified as active based on expression of ARC protein. These results demonstrate that the coupling of spatial exploration, cellular activation, and transcriptional change differs between immature and mature DGCs, with blunted activity-induced changes in immature cells.
DomainRank: Improving Biological Data Sets With Domain Knowledge and Google’s PageRank
Authors: Schneider Michael , Rappsilber Juri , Brock Oliver 
Published: September 2022

AbstractMotivationThe quality of biological data crucially affects progress in science. This quality can be improved with better measurement devices, more sophisticated experimental designs, or repetitious measurements. Each of these options is associated with substantial costs. We present a simple computational tool as an alternative. This algorithmic tool, called DomainRank, leverages simple domain knowledge and overlapping information content in biological network data to improve measurement quality at a negligible cost. Following the simple computational template of Domain-Rank, researchers can boost the confidence of their own data with little effort.ResultsWe demonstrate the performance of DomainRank in three test cases: DomainRank finds 14.9% more interactions in quantitative proteomics experiments, improves the precision of predicted residue-residue contacts from co-evolutionary data by up to 11.6% (averaged over 882 proteins), and identifies 89.2% more cross-links in photo-crosslinking/mass spectrometry (photo-CLMS) experiments. Although our proposed template is specialized on biological network data, we view this approach as an universal computational tool for data improvement that could be routinely applied in many disciplines.AvailabilityAn implementation of DomainRank is freely available: https://github.com/Rappsilber-Laboratory/pagerank-refine
ROCKETS - a novel one-for-all toolbox for light sheet microscopy in drug discovery
Authors: Mueller Joerg PJ , Dobosz Michael , O’Brien Nils , Giusti Anna Maria , Lechmann Martin , Osl Franz , Wolf Ann-Katrin , Sauer Markus , Herting Frank , Umana Pablo , Colombetti Sara , Pöschinger Thomas , Beilhack Andreas 
Published: September 2022

AbstractAdvancing novel immunotherapy strategies requires refined tools in preclinical research to thoroughly assess drug targets, biodistribution, safety, and efficacy. Light sheet fluorescence microscopy (LSFM) offers unprecedented fast volumetric ex vivo imaging of large tissue samples in high resolution. Yet, to date laborious and unstandardized tissue processing procedures have limited throughput and broader applications in immunological research. Therefore, we have developed a simple and harmonized protocol for processing, clearing and imaging of all mouse organs and even entire mouse bodies. Applying this Rapid Optical Clearing Kit for Enhanced Tissue Scanning (ROCKETS) in combination with LSFM allowed us to comprehensively study the in vivo biodistribution of an antibody targeting Epithelial Cell Adhesion Molecule (EpCAM) in 3D. Quantitative high-resolution scans of whole organs did not only reveal known EpCAM expression patterns but, importantly, uncovered several new EpCAM-binding sites. We identified choroid plexi in the brain and duodenal papillae as unexpected locations of high EpCAM-expression. These tissue locations may be considered as particularly sensitive sites due their importance for liquor production or as critical junctions draining bile and digestive pancreatic enzymes into the small bowel, respectively. These newly gained insights appear highly relevant for clinical translation of EpCAM-addressing immunotherapies. Thus, ROCKETS in combination with LSFM may help to set new standards for preclinical evaluation of immunotherapeutic strategies. Conclusively, we propose ROCKETS as an ideal platform for a broader application of LSFM in immunological research optimally suited for quantitative co-localization studies of immunotherapeutic drugs and defined cell populations in the microanatomical context of organs or even whole mice.
Biomimetic S-Adenosylmethionine Regeneration Starting from Different Byproducts Enables Biocatalytic Alkylation with Radical SAM Enzymes
Authors: Gericke Lukas , Mhaindarkar Dipali , Karst Lukas , Jahn Sören , Kuge Marco , Mohr Michael K. F. , Gagsteiger Jana , Cornelissen Nicolas V. , Wen Xiaojin , Mordhorst Silja , Jessen Henning J. , Rentmeister Andrea , Seebeck Florian P. , Layer Gunhild , Loenarz Christoph , Andexer Jennifer N. 
Published: September 2022

AbstractS-Adenosylmethionine (SAM) is an enzyme cofactor involved in methylation, aminopropyl transfer, and radical reactions. This versatility renders SAM-dependent enzymes of great interest in biocatalysis. The usage of SAM analogues adds to this diversity. However, high cost and instability of the cofactor impedes the investigation and usage of these enzymes. While SAM regeneration protocols from the methyltransferase (MT) byproductS-adenosylhomocysteine are available, aminopropyl transferases and radical SAM enzymes are not covered. Here, we report an efficient one-pot system to supply or regenerate SAM and SAM analogues for all three enzyme classes. The system’s flexibility is showcased by the transfer of an ethyl group with a cobalamin-dependent radical SAM MT usingS-adenosylethionine as a cofactor. This shows the potential of SAM (analogue) supply and regeneration for the application of diverse chemistry, as well as for mechanistic studies using cofactor analogues.
Reprogramming Adeno-Associated Virus Tropism Via Displayed Peptides Tiling Receptor-Ligands
Authors: Portell Andrew , Ford Kyle M. , Suhardjo Amanda , Rainaldi Joseph , Bublik Mark N. , Sanghvi Milan , Kumar Aditya , Wing Madeleine K. , Palmer Nathan D. , Le Duy An , Kalahasti Nikitha , Dailamy Amir , Mali Prashant 
Published: September 2022

ABSTRACTAdeno-associated viruses (AAVs) are common gene therapy vectors, however, their effectiveness is hindered by poor target tissue transduction and off-target delivery. Hypothesizing that naturally occurring receptor-ligand interactions could be repurposed to engineer tropism, we fragmented all annotated protein ligands known to bind human receptors into tiling 20-mer peptides and displayed these onto the surface loops of AAV5 and AAV9 capsids at two sites. The resulting four capsid libraries, comprising >1 million AAV variants, were screened across 9 tissues in C57BL/6 mice. Tracking variant abundance, we identified >250,000 variants which packaged into capsids, and >15,000 variants which efficiently transduced at least one mouse organ. We individually validated 21 AAV variants with 74.3% of the organ tropism predictions accurately reproducing, confirming overall screen efficacy. Systematic ligand tiling enabled prediction of putative AAV-receptor interactions, which we successfully validated by targeted genetic perturbations. Comprehensive peptide tiling also enabled examination of homologous peptide activity. Interestingly, we observed functional peptides tended to be derived from specific domains on ligands. Notably, certain peptides also displayed consistent activity across mice strains, capsid insertion contexts, and capsid serotypes, including novel immune orthogonal serotypes. Further analyses of displayed peptides revealed that biophysical attributes were highly predictive of AAV variant packaging, and there was a machine learnable relationship between peptide sequence and tissue tropism. We anticipate this comprehensive ligand peptide tiling and display approach will enable engineering of tropism across diverse viral, viral-like, and non-viral delivery platforms, and shed light into basic receptor-ligand biology.
Mapping of the bs5 and bs6 non-race-specific recessive resistances against bacterial spot of pepper
Authors: Sharma Anuj , Li Jian , Wente Rebecca , Minsavage Gerald V. , Gill Upinder S. , Ortega Arturo , Vallejos C. Eduardo , Hart John P. , Staskawicz Brian J. , Mazourek Michael R. , Stall Robert E. , Jones Jeffrey B. , Hutton Samuel F. 
Published: September 2022

AbstractBacterial spot caused by Xanthomonas euvesicatoria is a major disease of pepper (Capsicum annuum L.) in warm and humid production environments. Use of genetically resistant cultivars is an effective approach to manage bacterial spot. Two recessive resistance genes, bs5 and bs6, confer non-race-specific resistance against bacterial spot. The objective of our study was to map these two loci in the pepper genome. We used a genotyping-by-sequencing approach to initially map the position of the two resistances. Segregant populations for bs5 and bs6 were developed by crossing susceptible Early CalWonder (ECW) with near-isogenic lines ECW50R (bs5 introgression) or ECW60R (bs6 introgression). Following fine-mapping, bs5 was delimited to a ~535 Kbp interval on chromosome 3, and bs6 to a ~666 Kbp interval in chromosome 6 of pepper. We also identified 14 and 8 candidate resistance genes for bs5 and bs6, respectively, based on predicted protein coding polymorphisms between ECW and the corresponding resistant parent. Mapping of bs5 and bs6 will facilitate their use in breeding programs through marker-assisted selection and is also a crucial step towards understanding the mechanisms of resistance.Key messageTwo recessive bacterial spot resistance genes were mapped in the pepper genome, which will facilitate their advancement in commercial pepper for management of all races of Xanthomonas euvesicatoria.
A circadian-like gene network regulates heterochronic miRNA transcription inC. elegans
Authors: Kinney Brian , Sahu Shubham , Stec Natalia , Hills-Muckey Kelly , Adams Dexter W. , Wang Jing , Jaremko Matt , Joshua-Tor Leemor , Keil Wolfgang , Hammell Christopher M. 
Published: September 2022

AbstractDevelopmental robustness relies on precise control of the timing and order of cellular events. InC. elegans, the invariant sequence of post-embryonic cell fate specification is controlled by oscillatory patterns of heterochronic microRNA transcription that are phase-locked with the larval molting cycle1-4. How these transcriptional patterns are generated and how microRNA dosage is controlled is unknown. Here we show that transcriptional pulses of thelin-4heterochronic microRNA are produced by two nuclear hormone receptors, NHR-85 and NHR-23, whose mammalian orthologs, Rev-Erb and ROR, function in the circadian clock. While Rev-Erb and ROR play antagonistic roles in regulating once-daily transcription5-7, we find that NHR-85 and NHR-23 bind cooperatively as heterodimers tolin-4regulatory elements to induce a single brief pulse of expression during each larval stage. We demonstrate that the timing and duration oflin-4transcriptional pulses are programmed by the phased overlap of NHR-85 and NHR-23 protein expression and that these regulatory interactions are post-transcriptionally controlled by LIN-42, the circadian Period ortholog inC. elegans. These findings suggest that an evolutionary rewiring of the circadian clock machinery is co-opted in nematodes to generate periodic transcriptional patterns that define cell fate progression.