bluuebunny/crossref_metadata_2025_split huggingface dataset:
Photolipid excitation triggers depolarizing optocapacitive currents and action potentials
Authors: Bassetto Carlos A. Z. , Pfeffermann Juergen , Yadav Rohit , Strassgschwandtner Simon , Glasnov Toma , Bezanilla Francisco , Pohl Peter 
Published: August 2023

Optically-induced changes in membrane capacitance may regulate neuronal activity without requiring genetic modifications. Previously, they mainly relied on sudden temperature jumps due to light absorption by membrane-associated nanomaterials or water. Yet, nanomaterial targeting or the required high infrared light intensities obstruct broad applicability. Now, we propose a very versatile approach: photolipids (azobenzene-containing diacylglycerols) mediate light-triggered cellular de- or hyperpolarization. As planar bilayer experiments show, the respective currents emerge from millisecond-timescale changes in bilayer capacitance. UV light changes photolipid conformation, which awards embedding plasma membranes with increased capacitance and evokes depolarizing currents. They open voltage-gated sodium channels in cells, generating action potentials. Blue light reduces the area per photolipid, decreasing membrane capacitance and eliciting hyperpolarization. If present, mechanosensitive channels respond to the increased mechanical membrane tension, generating large depolarizing currents that elicit action potentials. Membrane self-insertion of administered photolipids and focused illumination allows cell excitation with high spatiotemporal control.HighlightsRapid photolipid photoisomerization generates optocapacitive currents in planar lipid bilayers and HEK293 cells.These currents originate from photo-induced changes in membrane capacitanceUV light-triggered membrane depolarization opens NaV1.3, evoking action potentials.Blue light-induced mechanosensitive channel opening gives rise to depolarizing currents, which may evoke NaV1.3-mediated action potentials.
Fawn bedsite selection by a large ungulate living in a peri-urban area
Authors: Conteddu Kimberly , Wilson Katie , Amin Bawan , Chari Srivats , Haigh Amy , Griffin Laura L. , Quinn Matthew , Ryan Andrew , Smith Adam F. , Ciuti Simone 
Published: August 2023

AbstractHuman-wildlife conflict in expanding peri-urban and urban areas is of increasing concern, as a result of growing human populations along with the associated anthropogenic footprint on wildlife habitats. Empirical data from wildlife research carried out within human dominated landscapes are key to understanding the effects of human pressures on wildlife ecology and behaviour, exploring wildlife behavioural flexibility (or phenotypic plasticity), and informing wildlife management decisions. Here, we explored how female fallow deer (Dama dama) responded to human and dog presence during the birthing period in the largest walled urban park in Europe. We collected data on 477 bedsites utilised by 283 neonate fawns across three consecutive fawning seasons, gathered fine-scale data on humans and dogs space use, and built Resource Selection Functions at multiple spatial scales. We found that, when choosing bedsites to give birth and leave fawns unattended, fallow deer mothers significantly avoided hotspots of park visitors on foot (and their dogs) along the hiking trail routes. Bedsites were also unlikely to be in close proximity of paved roads used by vehicle traffic. Additionally, fallow deer mothers were found to select for dense understory vegetation for bedsites, providing low visibility to conceal their offspring. Our results provide detailed insights into bedsite spatial and habitat selection by a large herbivore in response to human activities, and we provide clear indications to wildlife managers to preserve established fawning sites and alleviate human-wildlife conflict during a critical period of the deer annual biological cycle.
Impact of age and sex on neuroinflammation following SARS-CoV-2 infection in a murine model
Authors: Krishna Venkatramana D. , Chang Allison , Korthas Holly , Var Susanna R. , Low Walter C. , Li Ling , Cheeran Maxim C-J. 
Published: August 2023

AbstractSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent for the worldwide COVID-19 pandemic, is known to infect people of all ages and both sexes. Senior populations have the greatest risk of severe disease, and sexual dimorphism in clinical outcomes has been reported in COVID-19. SARS-CoV-2 infection in humans can cause damage to multiple organ systems, including the brain. Neurological symptoms are widely observed in patients with COVID-19, with many survivors suffering from persistent neurological and cognitive impairment, potentially accelerating Alzheimer’s disease. The present study aims to investigate the impact of age and sex on the neuroinflammatory response to SARS-CoV-2 infection using a mouse model. Wild-type C57BL/6 mice were inoculated, by intranasal route, with SARS-CoV-2 lineage B.1.351 variant known to infect mice. Older animals and in particular males exhibited a significantly greater weight loss starting at 4 dpi. In addition, male animals exhibited higher viral RNA loads and higher titers of infectious virus in the lung, which was particularly evident in males at 16 months of age. Notably, no viral RNA was detected in the brains of infected mice, regardless of age or sex. Nevertheless, expression of IL-6, TNF-α, and CCL-2 in the lung and brain was increased with viral infection. An unbiased brain RNA-seq/transcriptomic analysis showed that SARS-CoV-2 infection caused significant changes in gene expression profiles in the brain, with innate immunity, defense response to virus, cerebravascular and neuronal functions, as the major molecular networks affected. The data presented in this study show that SARS-CoV-2 infection triggers a neuroinflammatory response despite the lack of detectable virus in the brain. Age and sex have a modifying effect on this pathogenic process. Aberrant activation of innate immune response, disruption of blood-brain barrier and endothelial cell integrity, and supression of neuronal activity and axonogenesis underlie the impact of SARS-CoV-2 infection on the brain. Understanding the role of these affected pathways in SARS-CoV-2 pathogenesis helps identify appropriate points of therapeutic interventions to alleviate neurological dysfunction observed during COVID-19.
Glucose stockpile in the intestinal apical brush border inC. elegans
Authors: Saito Takumi , Kikuchi Kenji , Ishikawa Takuji 
Published: August 2023

AbstractSince understanding the mechanisms of glucose transport is a crucial approach for pathological diseases induced by glucose toxicities such as diabetes, numerous studies have unveiled molecular functions involved in glucose transport in the nematodeCaenorhabditis elegans, a commonly used model organism. However, physicochemical behaviors of glucose in intestinal lumen-to-cell are still elusive. To address that, we here evaluated a diffusion coefficient of glucose in the intestinal apical brush border inC. elegansby fluorescence recovery after photobleaching (FRAP) with fluorescent glucose. Our results indicate that the fluorescent glucose is accumulated in the intestinal brush border, where the diffusion coefficient of glucose is ∼10−8cm2/s, two orders of magnitude slower than that in bulk. Namely, the intestinal brush border is considered to be a highly viscous layer composed of intestinal microvilli and more dominantly glycocalyx. These findings imply that this high concentration of glucose in the viscous layer acts as a stockpile.
WOX11-mediated adventitious lateral root formation modulates tolerance of Arabidopsis to cyst nematode infections
Authors: Willig Jaap-Jan , Guarneri Nina , van Loon Thomas , Wahyuni Sri , Astudillo-Estévez Ivan E. , Xu Lin , Willemsen Viola , Goverse Aska , Sterken Mark G. , Lozano-Torres José L. , Bakker Jaap , Smant Geert 
Published: August 2023

AbstractThe transcription factorWUSCHEL-RELATED HOMEOBOX 11(WOX11) in Arabidopsis initiates the formation of adventitious lateral roots upon mechanical injury in primary roots. Root-invading nematodes also inducede novoroot organogenesis leading to excessive root branching, but it is not known if this symptom of disease involves mediation by WOX11 and if it benefits the plant. Here, we show with targeted transcriptional repression and reporter gene analyses in Arabidopsis that the beet cyst nematodeHeterodera schachtiiactivates WOX11-adventitious lateral rooting from primary roots close to infection sites. The activation of WOX11 in nematode-infected roots occurs downstream of jasmonic acid-dependent damage signaling viaETHYLENE RESPONSIVE FACTOR109, linking adventitious lateral root formation to nematode damage to host tissues. By measuring different root system components, we found that WOX11-mediated formation of adventitious lateral roots compensates for nematode-induced inhibition of primary root growth. Our observations further demonstrate that WOX11-mediated rooting reduces the impact of nematode infections on aboveground plant development and growth. Altogether, we conclude that the transcriptional regulation by WOX11 modulates root system plasticity under biotic stress, which is one of the key mechanisms underlying tolerance of Arabidopsis to cyst nematode infections.
Maternal allergic sensitization affects the T cell modulatory capacity and molecular cargo of milk derived extracellular vesicles
Authors: van Herwijnen Martijn J.C. , Giovanazzi Alberta , Zonneveld Marijke I. , Maqueda Joaquín J. , Kleinjan Marije , Goerdayal Soenita , Völlmy Franziska , van Bruggen - de Haan Arianne , Driedonks Tom A.P. , Arkesteijn Ger J.A. , van Elburg Ruurd M. , van der Meulen Gerbrich N. , Garssen Johan , Oliveira Carla , Altelaar A.F. Maarten , ’t Hoen Peter A.C. , Redegeld Frank A. , Nolte – ’t Hoen Esther N.M. , Wauben Marca H.M. 
Published: August 2023

AbstractBackgroundHuman milk extracellular vesicles (EVs) affect various cell types in the gastrointestinal tract, including T cells, and play a role in the development of the newborn’s immune system by delivering specific molecular cargo to target cells. Although maternal allergic sensitization alters the composition of milk, it is unknown whether this impacts the function of milk EVs. Therefore, we analyzed the T cell modulatory capacity and compared the protein and miRNA cargoes of EVs from milk of allergic and non-allergic mothers.MethodsEVs were isolated from human milk from allergic and non-allergic donors by differential centrifugation, density gradient floatation and size exclusion chromatography. Functional modulation of primary human CD4+ T cells by EVs was assessedin vitro. Proteomic analysis and small RNA sequencing was performed on milk EVs to evaluate protein and miRNA abundance and to identify cellular targets of this EV cargo in relevant T cell signaling pathways.ResultsT cell proliferation, activation and cytokine production were suppressed in the presence of milk EVs. Remarkably, milk EVs from allergic mothers inhibited T cell activation to a lesser extent than EVs from non-allergic mothers. Integrative multi-omics analysis identified EV cargo of which the cellular targets could be linked to differential modulation of T cell activation-associated processes .ConclusionsMilk EVs from non-allergic mothers are stronger inhibitors of T cell activation compared to milk EVs from allergic mothers. This altered functionality might be linked to changes in miRNA and protein cargo that modulate T cell signaling pathways in an integrative manner.
DeGenPrime provides robust primer design and optimization unlocking the biosphere
Authors: Fulghum Bryan , Tanker Sophie , White Richard Allen 
Published: August 2023

AbstractPolymerase chain reaction (PCR) is the world’s most important molecular diagnostic with applications ranging from medicine to ecology. PCR can fail because of poor primer design. The nearest-neighbor thermodynamic properties, picking conserved regions, and filtration via penalty of oligonucleotides form the basis for good primer design.DeGenPrime is a console-based high quality PCR primer design tool that can utilize MSA formats and degenerate bases expanding target range for a single primer set. Our software utilizes thermodynamic properties, filtration metrics, penalty scoring, and conserved region finding of any proposed primer. It has degeneracy, repeated k-mers, relative GC content, and temperature range filters. Minimal penalty scoring is included according to secondary structure self-dimerization metrics, GC clamping, tri- and tetra-loop hairpins and internal repetition.We compared PrimerDesign-M, DegePrime, ConsensusPrimer, and DeGenPrime on acceptable primer yield. PrimerDesign-M, DegePrime, and ConsensusPrimer provided 0%, 11%, and 17% yield respectively for alternative iron nitrogenase (anfD) gene target. DeGenPrime successfully identified quality primers within the conserved regions of the T4-like phage major capsid protein (g23), conserved regions of molybdenum-based nitrogenase (nif), and its alternatives vanadium (vnf) and iron (anf) nitrogenase. DeGenPrime provides a universal and scalable primer design tool for the entire tree of life.
Pandemic preparedness through genomic surveillance: Overview of mutations in SARS-CoV-2 over the course of COVID-19 outbreak
Authors: Najar Fares Z. , Murphy Chelsea L. , Linde Evan , Borin Veniamin A. , Wang Huan , Haider Shozeb , Agarwal Pratul K. 
Published: August 2023

ABSTRACTGenomic surveillance is a vital strategy for preparedness against the spread of infectious diseases and to aid in development of new treatments. In an unprecedented effort, millions of samples from COVID-19 patients have been sequenced worldwide for SARS-CoV-2. Using more than 8 million sequences that are currently available in GenBank’s SARS-CoV-2 database, we report a comprehensive overview of mutations in all 26 proteins and open reading frames (ORFs) from the virus. The results indicate that the spike protein, NSP6, nucleocapsid protein, envelope protein and ORF7b have shown the highest mutational propensities so far (in that order). In particular, the spike protein has shown rapid acceleration in mutations in the post-vaccination period. Monitoring the rate of non-synonymous mutations (Ka) provides a fairly reliable signal for genomic surveillance, successfully predicting surges in 2022. Further, the external proteins (spike, membrane, envelope, and nucleocapsid proteins) show a significant number of mutations compared to the NSPs. Interestingly, these four proteins showed significant changes in Katypically 2 to 4 weeks before the increase in number of human infections (“surges”). Therefore, our analysis provides real time surveillance of mutations of SARS-CoV-2, accessible through the project websitehttp://pandemics.okstate.edu/covid19/. Based on ongoing mutation trends of the virus, predictions of what proteins are likely to mutate next are also made possible by our approach. The proposed framework is general and is thus applicable to other pathogens. The approach is fully automated and provides the needed genomic surveillance to address a fast-moving pandemic such as COVID-19.
The creation-mutation-selection model: simulation and the advantage of sex
Authors: Irlam Gordon 
Published: August 2023

AbstractThe creation-mutation-selection model makes predictions regarding the fitness of asexual and sexual populations in an environment that includes both positive and negative selection. However, for the asexual case, the model predictions depend upon the variance or skewness of the population log fitness distribution, something which the model does not provide. This makes the analytical comparison of the fitness of asexual and sexual populations appear to be intractable. Instead, simulation is required. The fitness of asexual and sexual populations is simulated over a range of plausible parameter values. The fitness is found to agree with the predictions of the creation-mutation-selection model. The cost of asexuality is found to exceed the cost of sex by a very large margin for eukaryotic species today, and probably for the first eukaryotes. Prokaryotes and the mitochondrion are viewed as asexual species for which asexuality incurs little cost.
Optimization of Shoot Regeneration and Application of CRISPR/Cas9 Gene Editing to Cultivated Strawberry (Fragaria×ananassa)
Authors: Kim Jin-Hee , Yoo Cheol-Min , Nguyen Chi D , Huo Heqiang , Lee Seonghee 
Published: August 2023

AbstractEfficient methods of plant transformation and tissue culture are essential to CRISPR/Cas-based gene editing of crops, but neither is well established in cultivated octoploid strawberry (F×ananassa). In the present study, a method for shoot regeneration was established and optimized for two strawberry cultivars commercially grown in Florida, Sweet Sensation® ‘Florida 127’ FL127) and ‘Florida Brilliance’ (FB). Runner segments at the tip, node, and petiole obtained from greenhouse-grown plants were used as explants for comparisons of shoot regeneration rate. FL127 showed the highest frequency of shoot regeneration to a basal Murashige and Skoog media (MS) containing 1 mg·L-1 of TDZ, 0.05 mg·L-1 of BA, and 0.05 mg·L-1 of 2,4-D, while FB showed the best response to a lower concentration of BA (0.01 mg·L-1) in the same media type. The average conversion frequencies of somatic embryos into shoot regenerations from the runner tips (RT) were 42.8% in FL127 and 56.9% in FB, respectively, with RT being the most prolific in shoot generation for both cultivars. Using these optimized tissue conditions,Agrobacterium-mediated CRISPR/Cas9 gene editing was conducted to evaluate the efficiency of transformation and knockout mutations in thephytoene desaturase(FaPDS) gene of FL127. A total of 234 explants treated withAgrobacteriumresulted in an 80.3% regeneration efficiency, with 13.3% of regenerated plants exhibiting partial or complete albino phenotypes. Amplicon sequencing of edited progeny revealed substitutions, insertions, and deletions at the gRNA target sites or flanking regions of allFaPDShomoeologous copies. Our results provide effective methods of tissue culture and transformation for the efficient application of CRISPR-mediated gene editing in cultivated strawberry.
Insertases Scramble Lipids: Molecular Simulations of MTCH2
Authors: Bartoš Ladislav , Menon Anant K. , Vácha Robert 
Published: August 2023

AbstractScramblases play a pivotal role in facilitating bidirectional lipid transport across cell membranes, thereby influencing lipid metabolism, membrane homeostasis, and cellular signaling. MTCH2, a mitochondrial outer membrane protein insertase, has a membrane-spanning hydrophilic groove resembling those that form the lipid transit pathway in known scramblases. Employing both coarse-grained and atomistic molecular dynamics simulations, we show that MTCH2 significantly reduces the free energy barrier for lipid movement along the groove and therefore can indeed function as a scramblase. Notably, the scrambling rate of MTCH2in silicois similar to that of VDAC, a recently discovered scramblase of the outer mitochondrial membrane, suggesting a potential complementary physiological role for these mitochondrial proteins. Finally, our findings suggest that other insertases which possess a hydrophilic path across the membrane like MTCH2, can also function as scramblases.Graphical abstractHighlightsScrambling activity of MTCH2 identified using computer simulationsMTCH2 may act redundantly with VDAC as outer mitochondrial membrane scram-blaseInsertases and scramblases may share a common functional mechanism
Conserved spatiotemporal expression landscape of dominant tRNA genes in human and mouse
Authors: Wu Evan Y. , Landry Laura 
Published: August 2023

AbstractTransfer RNAs are integral for protein synthesis and the interpretation of the information contained in DNA. To date, a few methods, including custom microarrays and custom targeted sequencing, have been used to quantify tRNA. However, methods using available RNA-sequencing data have not yet been reported. We created a bioinformatics pipeline to quantify the highly expressed tRNAs in RNA-Seq effectively, demonstrated by the preserved ratio of the expression levels of two massively duplicated tRNAAlagenes in mouse. Using this quantification, we examined the tRNA expression with relation to tissue type and developmental stage in both human and mouse. Heart exhibited the highest overall tRNA expression for both human and mouse. Furthermore, tRNA expression grew to a peak before decreasing steadily with developmental stage, a trend that was conserved in both human and mouse. The two mitochondrial tRNA genes, tRNASer(TCA)(m) and tRNALeu(TTA)(m), which partly contribute to these trends, have been attributed to various human diseases. The tissue-specific high expression of tRNAGln(CAG) and tRNAGln(CAA) in human brains, especially in hindbrain and cerebellum, suggests their important roles in neurological disorders. In summary, our approach revealed conserved spatiotemporal expression of highly expressed tRNAs in both human and mouse. Our method can be applied to other RNA- Seq data to examine the roles of these tRNAs in different human diseases or scientific studies.
Structure and activation mechanism of the Makes caterpillars floppy 1 toxin
Authors: Belyy Alexander , Heilen Philipp , Hagel Philine , Hofnagel Oliver , Raunser Stefan 
Published: August 2023

AbstractThe bacterial Makes caterpillars floppy 1 (Mcf1) toxin promotes apoptosis in insects, leading to loss of body turgor and death. The molecular mechanism underlying Mcf1 intoxication is poorly understood. Here, we present the cryo-EM structure of Mcf1 fromPhotorhabdus luminescens, revealing a seahorse-like shape with a head and tail. While the three head domains contain two effectors, an activator-binding domain (ABD) and an autoprotease, the tail consists of two translocation as well as three receptor-binding domains. Rearrangement of the tail moves the C-terminus away from the ABD and allows binding of the host cell ADP-ribosylation factor 3, inducing conformational changes that position the cleavage site closer to the protease. This unique activation mechanism that is based on a hook-loop interaction results in three autocleavage reactions and the release of two toxic effectors. Unexpectedly, the BH3-like domain containing ABD is not an active effector. Our findings allow us to understand key steps of Mcf1 intoxication at the molecular level.