bluuebunny/crossref_metadata_2025_split huggingface dataset:
Moonlight synchronous flights across three western palearctic swifts mirror size dependent prey preferences
Authors: Hufkens Koen , Meier Christoph M. , Evens Ruben , Paredes Josefa Arán , Karaardiç Hakan , Vercauteren Stef , Gysel Ann Van , Fox James W. , Pacheco Carlos Miguel , da Silva Luis P. , Fernandes Sandra , Henriques Pedro , Elias Gonçalo , Costa Luís T. , Poot Martin , Kearsley Lyndon 
Published: April 2023

AbstractRecent studies have suggested the presence of moonlight mediated behaviour in avian aerial insectivores, such as swifts. At the same time swift species also show differences in prey (size) preferences. Here, we use the combined analysis of state-of-the-art activity logger data across three swift species, the Common, Pallid and Alpine swifts, to quantify flight height and activity responses to crepuscular and nocturnal light conditions. Our results show a significant response in flight heights to moonlight illuminance for Common and Pallid swifts, while a moonlight driven response is absent in Alpine swifts. Swift flight responses followed the size dependent altitude gradient of their insect prey. We show a weak relationship between night-time illuminance driven responses and twilight ascending behaviour, suggesting a decoupling of both crepuscular and night-time behaviour. We suggest that swifts optimise their flight behaviour to adapt to favourable night-time light conditions, driven by light responsive and size-dependent vertical insect stratification and weather conditions.
Slow gamma oscillations in the mouse olfactory bulb are correlated with sniffing in the dark period
Authors: Mochizuki-Koike Ryosuke , Okada Mami , Ikegaya Yuji , Matsumoto Nobuyoshi 
Published: April 2023

AbstractNeural activity in the olfactory bulb is reflected in local field potentials (LFPs). Functionally, LFPs in the olfactory bulb are categorized into different frequency bands: 1-4 Hz, 6-12 Hz, 25-50 Hz, and 65-130 Hz, which respectively correspond to respiration, sniffing, slow gamma, and fast gamma oscillations. While gamma oscillations in the olfactory bulb are modulated by respiration and sniffing, it remains unknown how and whether the modulation of LFP oscillations is affected by the time of day. To address this question, we recorded LFPs in the olfactory bulb, hippocampus, and neocortex of unrestrained mice for up to 3 d. For each recording site, we calculated the correlation coefficients of normalized LFP powers between pairs of frequency bands in the three regions during the dark and light periods. We then compared these correlations with those generated by surrogate data to investigate whether the correlation was statistically significant. We found that the correlation between sniffing and slow gamma oscillations was higher in the dark period than in the light period. Our finding has the potential to shed light on the coding scheme of olfactory information that is dependent on the light/dark cycle.
Dorsal peduncular cortex activity modulates affective behavior and fear extinction in mice
Authors: Botterill Justin J. , Khlaifia Abdessattar , Appings Ryan , Wilkin Jennifer , Violi Francesca , Premachandran Hanista , Cruz-Sanchez Arely , Canella Anna Elisabete , Patel Ashutosh , Zaidi S. Danyal , Arruda-Carvalho Maithe 
Published: April 2023

AbstractThe medial prefrontal cortex (mPFC) is critical to cognitive and emotional function and underlies many neuropsychiatric disorders, including mood, fear and anxiety disorders. In rodents, disruption of mPFC activity affects anxiety- and depression-like behavior, with specialized contributions from its subdivisions. The rodent mPFC is divided into the dorsomedial prefrontal cortex (dmPFC), spanning the anterior cingulate cortex (ACC) and dorsal prelimbic cortex (PL), and the ventromedial prefrontal cortex (vmPFC), which includes the ventral PL, infralimbic cortex (IL), and in some studies the dorsal peduncular cortex (DP) and dorsal tenia tecta (DTT). The DP/DTT have recently been implicated in the regulation of stress- induced sympathetic responses via projections to the hypothalamus. While many studies implicate the PL and IL in anxiety-, depression-like and fear behavior, the contribution of the DP/DTT to affective and emotional behavior remains unknown. Here, we used chemogenetics and optogenetics to bidirectionally modulate DP/DTT activity and examine its effects on affective behaviors, fear and stress responses in C57BL/6J mice. Acute chemogenetic activation of DP/DTT significantly increased anxiety-like behavior in the open field and elevated plus maze tests, as well as passive coping in the tail suspension test. DP/DTT activation also led to an increase in serum corticosterone levels and facilitated auditory fear extinction learning and retrieval. Activation of DP/DTT projections to the dorsomedial hypothalamus (DMH) acutely decreased freezing at baseline and during extinction learning, but did not alter affective behavior. These findings point to the DP/DTT as a new regulator of affective behavior and fear extinction in mice.
Photosynthesis in the biomass model speciesLemna minordisplays plant-conserved and species-specific features
Authors: Liebers Monique , Hommel Elisabeth , Grübler Björn , Danehl Jakob , Offermann Sascha , Pfannschmidt Thomas 
Published: April 2023

AbstractLemnaceaeare aquatic freshwater plants with extraordinary high growth rates. We have studied selected physiological and molecular photosynthesis properties of the duckweedLemna minorand compared these to the terrestrial model speciesArabidopsis thaliana. LemnaandArabidopsisplants grown under identical light intensities displayed similar photosynthesis characteristics, however,Lemnaexhibited slighty better quenching efficiencies pointing to improved light utilization in the duckweed. Western-immuno-blot analyses of representative photosynthesis proteins suggest various post-translational modifications inLemnathat might be associated to this. Phospho-threonine phosphorylation patterns of thylakoid membranes uncovered differences between the two species. Testing the photosystem II antenna association ofLemna minorin dark and light by 77K chlorophyll fluorescence emission experiments, however, revealed a typical association as reported in terrestrial plants. High light stress experiments causing photoinhibition and subsequent recovery from it were not substantially different inLemnawhen compared toArabidopsis. We hypothesize that the molecular differences inLemnaphotosynthesis proteins are associated with evolutionary adaptations to the aquatic life style and ultimately with the high growth rates. We also developed a video imaging approach forLemnamultiplication at high magnification that will be useful to assess the impact of external factors onLemnaphotosynthesis and growth.
TheDrosophila drop-deadgene is required for eggshell integrity
Authors: Sheahan Tayler D. , Grewal Amanpreet , Korthauer Laura E. , Blumenthal Edward M. 
Published: April 2023

AbstractThe eggshell of the fruit flyDrosophila melanogasteris a useful model for understanding the synthesis of a complex extracellular matrix. The eggshell is synthesized during mid-to-late oogenesis by the somatic follicle cells that surround the developing oocyte. We previously reported that female flies mutant for the genedrop-dead(drd) are sterile, but the underlying cause of the sterility remained unknown. In this study, we examined the role ofdrdin eggshell synthesis. We show that eggs laid bydrdmutant females are fertilized but arrest early in embryogenesis, and that the innermost layer of the eggshell, the vitelline membrane, is abnormally permeable to dye in these eggs. In addition, the major vitelline membrane proteins fail to become crosslinked by nonreducible bonds, a process that normally occurs during egg activation following ovulation, as evidenced by their solubility and detection by Western blot in laid eggs. In contrast, the Cp36 protein, which is found in the outer chorion layers of the eggshell, becomes crosslinked normally. To link thedrdexpression pattern with these phenotypes, we show thatdrdis expressed in the ovarian follicle cells beginning in mid-oogenesis, and, importantly, that alldrdmutant eggshell phenotypes could be recapitulated by selective knockdown ofdrdexpression in the follicle cells. To determine whetherdrdexpression was required for the crosslinking itself, we performedin vitroactivation and crosslinking experiments. The vitelline membranes of control egg chambers could become crosslinked either by incubation in hyperosmotic medium, which activates the egg chambers, or by exogenous peroxidase and hydrogen peroxide. In contrast, neither treatment resulted in the crosslinking of the vitelline membrane indrdmutant egg chambers. These results indicate thatdrdexpression in the follicle cells is necessary for vitelline membrane proteins to serve as substrates for peroxidase-mediated cross-linking at the end of oogenesis.
Gut microbiota and metabolites drive chronic sickle cell disease pain
Authors: Sadler Katelyn E. , Atkinson Samantha N. , Ehlers Vanessa L. , Waltz Tyler B. , Hayward Michael , Rodríguez García Dianise M. , Salzman Nita H. , Stucky Cheryl L. , Brandow Amanda M. 
Published: April 2023

AbstractPain is a debilitating symptom and leading reason for hospitalization of individuals with sickle cell disease. Chronic sickle cell pain is poorly managed because the biological basis is not fully understood. Using transgenic sickle cell mice and fecal material transplant, we determined that the gut microbiome drives persistent sickle cell pain. In parallel patient and mouse analyses, we identified bilirubin as one metabolite that induces sickle cell pain by altering vagus nerve activity. Furthermore, we determined that decreased abundance of the gut bacteriaAkkermansia mucinophilais a critical driver of chronic sickle cell pain. These experiments demonstrate that the sickle cell gut microbiome drives chronic widespread pain and identify bacterial species and metabolites that should be targeted for chronic sickle cell disease pain management.One-Sentence SummaryGut microbes and metabolites drive chronic sickle cell disease pain by altering vagus nerve activity.
Imetelstat-Mediated Alterations in Fatty Acid Metabolism To Induce Ferroptosis As Therapeutic Strategy for Acute Myeloid Leukemia
Authors: Bruedigam Claudia , Porter Amy H. , Song Axia , Vroeg in de Wei Gerjanne , Stoll Thomas , Straube Jasmin , Cooper Leanne , Cheng Guidan , Kahl Vivian F. S. , Sobinoff Alexander P. , Ling Victoria Y. , Jebaraj Billy Michael Chelliah , Janardhanan Yashaswini , Haldar Rohit , Bray Laura J. , Bullinger Lars , Heidel Florian H. , Kennedy Glen A. , Hill Michelle M. , Pickett Hilda A. , Abdel-Wahab Omar , Hartel Gunter , Lane Steven W. 
Published: April 2023

ABSTRACTTelomerase enables replicative immortality in most cancers including acute myeloid leukemia (AML). Imetelstat is a first-in-class telomerase inhibitor with clinical efficacy in myelofibrosis and myelodysplastic syndromes. Here, we develop an AML patient-derived xenograft (PDX) resource, and perform integrated genomics, transcriptomics, and lipidomics analyses combined with functional genetics to identify key mediators of imetelstat efficacy. In a randomized Phase II-like preclinical trial in PDX, imetelstat effectively diminishes AML burden, and preferentially targets subgroups containing mutantNRASand oxidative stress-associated gene expression signatures. Unbiased, genome-wide CRISPR/Cas9 editing identifies ferroptosis regulators as key mediators of imetelstat efficacy. Imetelstat promotes the formation of polyunsaturated fatty acid-containing phospholipids, causing excessive levels of lipid peroxidation and oxidative stress. Pharmacological inhibition of ferroptosis diminishes imetelstat efficacy. We leverage these mechanistic insights to develop an optimized therapeutic strategy using oxidative stress-inducing chemotherapy to sensitize patient samples to imetelstat causing significant disease control in AML.
Epigenetic control of myogenic identity of human muscle stem cells in Duchenne Muscular Dystrophy
Authors: Massenet Jimmy , Weiss-Gayet Michèle , Bandukwala Hina , Magnan Mélanie , Hubas Arnaud , Nusbaum Patrick , Desguerre Isabelle , Gitiaux Cyril , Dilworth F Jeffrey , Chazaud Bénédicte 
Published: April 2023

AbstractIn Duchenne Muscular Dystrophy (DMD), the absence of the subsarcolemmal dystrophin protein leads to repeated myofiber damages inducing cycles of muscle regeneration that is driven by muscle stem cells (MuSCs). With time, MuSC regenerative capacities are overwhelmed, leading to fibrosis and muscle atrophy. Whether MuSCs from DMD muscle have intrinsic defects that limit regenerative potential or are disrupted by their degenerative/regenerative environment is unclear. We investigated cell behavior and gene expression in human using MuSCs derived from DMD or healthy muscles. We found that proliferation, differentiation and fusion were not altered in DMD-MuSCs, but with time, they lost their myogenic identity twice as fast as healthy MuSCs. The rapid drift towards a fibroblast-like cell identity was observed at the clonal level, and resulted from the altered expression of epigenetic enzymes required to maintain the myogenic cell fate. Indeed, the re-expression ofCBX3,SMC3,H2AFVandH3F3Bprevented the MuSC identity drift. Amongst the epigenetic changes, a closing of chromatin at the gene encoding the transcription factorMEF2Bcaused a down-regulation of its expression and a loss of the myogenic fate. Thus, MEF2B is a key mediator of the myogenic identity in human MuSCs, that is altered in DMD pathology.
Social status in zebrafish modulates the behavioral response to 5-HT2C receptor agonists and antagonists
Authors: de Oliveira Larissa Nunes , Alves Nuno Felix Paiva , Soares Marta Candeias , Maximino Caio 
Published: April 2023

AbstractThe effects of previous social experiences on social behavior have been demonstrated across species both in cooperative and competitive contexts. In dominance-subordinate hierarchies, differences across social ranks have been observed in many different mechanisms. Dominance hierarchies interfere in defensive behavior, where subordinate animals present a greater defensive behavior, regarding potential threats (“anxiety-like behavior”), than dominant animals. The serotonergic system plays a key role in regulating and mediating threat responses, including 5-HT2 receptors in the types of proximal threat responses modulated by the stress of social defeat. We separated 148 adult zebrafish in pairs, and allowed to interact for five days; after that, the dominant-subordinate rank was determined, and animals were treated with a 5-HT2Creceptor agonist (MK-212) or antagonist (RS-102221) before being observed in the novel tank test. While MK-212 increased bottom-dwelling, erratic swimming, and freezing across all statuses, RS-102221 decreased these variables in dominants but increased them in subordinates. Moreover, the effects of MK-212 were larger in subordinates than in controls or dominants, suggesting a sensitization of the 5-HT2Creceptor.
HIV-1 infection of genetically engineered iPSC-derived central nervous system-engrafted microglia in a humanized mouse model
Authors: Min Alice K. , Javidfar Behnam , Missall Roy , Doanman Donald , Durens Madel , Vil Samantha St , Masih Zahra , Graziani Mara , Mordelt Annika , Marro Samuele , de Witte Lotje , Chen Benjamin K. , Swartz Talia H. , Akbarian Schahram 
Published: April 2023

AbstractThe central nervous system (CNS) is a major human immunodeficiency virus type 1 reservoir. Microglia are the primary target cell of HIV-1 infection in the CNS. Current models have not allowed the precise molecular pathways of acute and chronic CNS microglial infection to be tested with in vivo genetic methods. Here, we describe a novel humanized mouse model utilizing human-induced pluripotent stem cell-derived microglia to xenograft into murine hosts. These mice are additionally engrafted with human peripheral blood mononuclear cells that served as a medium to establish a peripheral infection that then spread to the CNS microglia xenograft, modeling a trans-blood-brain barrier route of acute CNS HIV-1 infection with human target cells. The approach is compatible with iPSC genetic engineering, including inserting targeted transgenic reporter cassettes to track the xenografted human cells, enabling the testing of novel treatment and viral tracking strategies in a comparatively simple and cost-effective wayvivomodel for neuroHIV.ImportanceOur mouse model is a powerful tool for investigating the genetic mechanisms governing CNS HIV-1 infection and latency in the CNS at a single-cell level. A major advantage of our model is that it uses iPSC-derived microglia, which enables human genetics, including gene function and therapeutic gene manipulation, to be exploredin vivo, which is more challenging to study with current hematopoietic stem cell-based models for neuroHIV. Our transgenic tracing of xenografted human cells will provide a quantitative medium to develop new molecular and epigenetic strategies for reducing the HIV-1 latent reservoir and to test the impact of therapeutic inflammation-targeting drug interventions on CNS HIV-1 latency.
Enhancedin VivoBlood Brain Barrier Transcytosis of Macromolecular Cargo Using an Engineered pH-sensitive Mouse Transferrin Receptor Binding Nanobody
Authors: Esparza Thomas J. , Su Shiran , Francescutti Caroline M. , Rodionova Elvira , Kim Joong Hee , Brody David L. 
Published: April 2023

ABSTRACTBackgroundThe blood brain barrier limits entry of macromolecular diagnostic and therapeutic cargos. Blood brain barrier transcytosis via receptor mediated transport systems, such as the transferrin receptor, can be used to carry macromolecular cargos with variable efficiency. Transcytosis involves trafficking through acidified intracellular vesicles, but it is not known whether pH-dependent unbinding of transport shuttles can be used to improve blood brain barrier transport efficiency.MethodsA mouse transferrin receptor binding nanobody, NIH-mTfR-M1, was engineered to confer greater unbinding at pH 5.5 vs 7.4 by introducing multiple histidine mutations. The histidine mutant nanobodies were coupled to neurotensin forin vivofunctional blood brain barrier transcytosis testing via central neurotensin-mediated hypothermia in wild-type mice. Multi-nanobody constructs including the mutant M1R56H, P96H, Y102Hand two copies of the P2X7 receptor-binding 13A7 nanobody were produced to test proof-of-concept macromolecular cargo transportin vivousing quantitatively verified capillary depleted brain lysates andin situhistology.ResultsThe most effective histidine mutant, M1R56H, P96H, Y102H-neurotensin, caused >8°C hypothermia after 25 nmol/kg intravenous injection. Levels of the heterotrimeric construct M156,96,102His-13A7-13A7 in capillary depleted brain lysates peaked at 1 hour and were 60% retained at 8 hours. A control construct with no brain targets was only 15% retained at 8 hours. Addition of the albumin-binding Nb80 nanobody to make M1R56H, P96H, Y102H-13A7-13A7-Nb80 extended blood half-life from 21 minutes to 2.6 hours. At 30-60 minutes, biotinylated M1R56H, P96H, Y102H-13A7-13A7-Nb80 was visualized in capillaries usingin situhistochemistry, whereas at 2-16 hours it was detected in diffuse hippocampal and cortical cellular structures. Levels of M1R56H, P96H, Y102H-13A7-13A7-Nb80 reached more than 3.5 percent injected dose/gram of brain tissue after 30 nmol/kg intravenous injection. However, higher injected concentrations did not result in higher brain levels, compatible with saturation and an apparent substrate inhibitory effect.ConclusionThe pH-sensitive mouse transferrin receptor binding nanobody M1R56H, P96H, Y102Hmay be a useful tool for rapid and efficient modular transport of diagnostic and therapeutic macromolecular cargos across the blood brain barrier in mouse models. Additional development will be required to determine whether this nanobody-based shuttle system will be useful for imaging and fast-acting therapeutic applications.
WNK1 enforces macrophage lineage fidelity
Authors: Trzeciak Alissa J. , Rojas Waleska Saitz , Liu Zong-Lin , Krebs Adam S. , Wang Zhaoquan , Saavedra Pedro H. V. , Miranda Isabella C. , Lipshutz Allie , Xie Jian , Huang Chou-Long , Overholtzer Michael , Glickman Michael S. , Parkhurst Christopher N. , Vierbuchen Thomas , Lucas Christopher D. , Perry Justin S. A. 
Published: April 2023

SummaryThe appropriate development of macrophages, the body’s professional phagocyte, is essential for organismal development, especially in mammals. This dependence is exemplified by the observation that loss-of-function mutations in colony stimulating factor 1 receptor (CSF1R) results in multiple tissue abnormalities owing to an absence of macrophages. Despite this importance, little is known about the molecular and cell biological regulation of macrophage development. Here, we report the surprising finding that the chloride-sensing kinase With-no-lysine 1 (WNK1) is required for development of tissue-resident macrophages (TRMs). Myeloid-specific deletion ofWnk1resulted in a dramatic loss of TRMs, disrupted organ development, systemic neutrophilia, and mortality between 3 and 4 weeks of age. Strikingly, we found that myeloid progenitors or precursors lacking WNK1 not only failed to differentiate into macrophages, but instead differentiated into neutrophils. Mechanistically, the cognate CSF1R cytokine macrophage-colony stimulating factor (M-CSF) stimulates macropinocytosis by both mouse and human myeloid progenitors and precursor cells. Macropinocytosis, in turn, induces chloride flux and WNK1 phosphorylation. Importantly, blocking macropinocytosis, perturbing chloride flux during macropinocytosis, and inhibiting WNK1 chloride-sensing activity each skewed myeloid progenitor differentiation from macrophages into neutrophils. Thus, we have elucidated a role for WNK1 during macropinocytosis and discovered a novel function of macropinocytosis in myeloid progenitors and precursor cells to ensure macrophage lineage fidelity.Highlights-Myeloid-specific WNK1 loss causes failed macrophage development and premature death-M-CSF-stimulated myeloid progenitors and precursors become neutrophils instead of macrophages-M-CSF induces macropinocytosis by myeloid progenitors, which depends on WNK1-Macropinocytosis enforces macrophage lineage commitment