bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protection against avian coronavirus conferred by oral vaccination with live bacteria secreting LTB-fused viral proteins
Authors: Lublin Avishai , Katz Chen , Gruzdev Nady , Yadid Itamar , Bloch Itai , Farnoushi Yigal , Simanov Luba , Berkovitz Asaf , Elyahu Dalia , Pitcovskib Jacob , Shahar Ehud 
Published: October 2021

AbstractThe devastating impact of infectious bronchitis (IB) triggered by the IB virus (IBV), on poultry farms is generally curbed by livestock vaccination with live attenuated or inactivated vaccines. Yet, this approach is challenged by continuously emerging variants and by time limitations of vaccine preparation techniques. This work describes the design and evaluation of an anti-IBV vaccine comprised ofE. coliexpressing and secreting viral spike 1 subunit (S1) and nucleocapsid N-terminus and C-terminus polypeptides fused to heat-labile enterotoxin B (LTB) (LS1, LNN, LNC, respectively). Following chicken oral vaccination, anti-IBV IgY levels and cellular-mediated immunity as well as protection against virulent IBV challenge, were evaluated 14 days following the booster dose. Oral vaccination induced IgY levels that exceeded those measured following vaccination with each component separately. Following exposure to inactivated IBV, splenocytes isolated from chicks orally vaccinated with LNN or LNC -expressing bacteria, showed a higher percentage of CD8+cells as compared to splenocytes isolated from chicks vaccinated with wild type or LTB-secretingE. coliand to chicks subcutaneously vaccinated. Significant reduction in viral load and percent of shedders in the vaccinated chicks was evident starting 3 days following challenge with 107.5EID50/ml virulent IBV. Taken together, orally delivered LTB-fused IBV polypeptide-expressing bacteria induced virus-specific IgY antibody production and was associated with significantly shorter viral shedding on challenge with a live IBV. The proposed vaccine design and delivery route promise an effective and rapidly adaptable means of protecting poultry farms from devastating IB outbreaks.HighlightsMucosal vaccination was shown particularly beneficial against respiratory viruses.An anti-IBV vaccine composed of three IBV polypeptides fused to LTB was designed.Vaccine composed of bacteria secreting polypeptides was orally delivered.Vaccine induced specific immune responses and shortened viral shedding duration.
Functional interaction between Drosophila olfactory sensory neurons and their support cells
Authors: Prelic Sinisa , Mahadevan Venkatesh Pal , Venkateswaran Vignesh , Lavista-Llanos Sofia , Hansson Bill S. , Wicher Dieter 
Published: October 2021

AbstractInsects detect volatile chemicals using antennae, which house a vast variety of olfactory sensory neurons (OSNs) that innervate hair-like structures called sensilla where odor detection takes place. In addition to OSNs, the antenna also hosts various support cell types. These include the triad of trichogen, tormogen and thecogen support cells that lie adjacent to their respective OSNs. The arrangement of OSN supporting cells occurs stereotypically for all sensilla and is widely conserved in evolution. While insect chemosensory neurons have received considerable attention, little is known about the functional significance of the cells that support them. For instance, it remains unknown whether support cells play an active role in odor detection, or only passively contribute to homeostasis, e.g. by maintaining sensillum lymph composition. To investigate the functional interaction between OSNs and support cells, we used optical and electrophysiological approaches in Drosophila. First, we characterized the distribution of various supporting cells using genetic markers. By means of an ex vivo antennal preparation and genetically-encoded Ca2+ and K+ indicators, we then studied the activation of these auxiliary cells during odor presentation in adult flies. We observed acute responses and distinct differences in Ca2+ and K+ fluxes between support cell types. Finally, we observed alterations in OSN responses upon thecogen cell ablation in mature adults. Upon inducible ablation of thecogen cells, we notice a gain in mechanical responsiveness to mechanical stimulations during single-sensillum recording, but a lack of change to neuronal resting activity. Taken together, these results demonstrate that support cells play a more active and responsive role during odor processing than previously thought. Our observations thus reveal that support cells functionally interact with OSNs and may be important for the extraordinary ability of insect olfactory systems to dynamically and sensitively discriminate between odors in the turbulent sensory landscape of insect flight.
A class of identifiable phylogenetic birth-death models
Authors: Legried Brandon , Terhorst Jonathan 
Published: October 2021

AbstractIn a striking result, Louca and Pennell (2020) recently proved that a large class of phylogenetic birth-death models are statistically unidentifiable from lineage-through-time (LTT) data: any pair of sufficiently smooth birth and death rate functions is “congruent” to an infinite collection of other rate functions, all of which have the same likelihood for any LTT vector of any dimension. As Louca and Pennell argue, this fact has distressing implications for the thousands of studies that have utilized birth-death models to study evolution.In this paper, we qualify their finding by proving that an alternative and widely used class of birth-death models is indeed identifiable. Specifically, we show that piecewise constant birth-death models can, in principle, be consistently estimated and distinguished from one another, given a sufficiently large extant time tree and some knowledge of the present-day population. Subject to mild regularity conditions, we further show that any unidentifiable birth-death model class can be arbitrarily closely approximated by a class of identifiable models. The sampling requirements needed for our results to hold are explicit, and are expected to be satisfied in many contexts such as the phylodynamic analysis of a global pandemic.
Trans-epithelial migration is essential for neutrophil activation during RSV infection
Authors: Robinson Elisabeth , Herbert Jenny Amanda , Palor Machaela , Ren Luo , Larken Isobel , Patel Alisha , Moulding Dale , Cortina-Borja Mario , Smyth Rosalind Louise , Smith Claire Mary 
Published: October 2021

AbstractThe recruitment of neutrophils to the infected airway occurs early following respiratory syncytial virus (RSV) infection and high numbers of activated neutrophils in airway and blood is associated with the development of severe disease. Here, we investigated whether trans-epithelial migration across primary human airway epithelial cells (AECs) is sufficient and necessary for neutrophil activation during RSV infection. Using flow cytometry, we identified three populations of neutrophils in our in vitro model; those in suspension in basolateral and apical compartments and those that migrated and adhered to AECs. After 1h incubation, the number of adherent neutrophils was significantly greater following RSV infection compared to mock infected. We found that, when migration occurred, neutrophil expression of CD11b, CD62L, CD64, NE and MPO increased in all compartments. However, this did not occur when neutrophils were prevented from migrating. This suggests that the heightened neutrophil activation we detected in the basolateral compartment may be due to reverse migrating neutrophils, as has been suggested by clinical observations. Using live-cell fluorescent microscopy, we then profiled the early temporal and spatial movement and adherence of human neutrophils during migration. Our findings suggest three main phases of early neutrophil recruitment and behaviour in the airways during RSV infection, with neutrophil recruitment, activation and adherence to RSV infected AECs, with clustering, occurring within the first 20 minutes. This work and the model we developed could provide new insight into how neutrophil activation and a dysregulated neutrophil response to RSV mediates disease severity.Graphical AbstractBuilding on previous work of neutrophil function we propose 3 main phases of early neutrophil recruitment and behaviour in the airways during RSV infection. Phase 1. Initial chemotaxis and adherence: Here unstimulated circulating neutrophils expressing baseline levels of CD11b migrate across infected AECs in response to chemotactic signals in the apical supernatant. Some neutrophils remain adherent to the infected AECs. Phase 2: Activation and reverse migration: once on the apical side of the epithelium, neutrophils increase expression of CD11b and other activation associated markers, and some ‘activated’ neutrophils undergo reverse migration. Neutrophils with greater expression of CD11b are detected on the basolateral side Phase 3: Amplified chemotaxis and clustering: after 20 minutes, adherent neutrophils begin to rapidly cluster on RSV infected primary airway epithelial cells cultures, mediated by signalling from a dying neutrophil. Drawing created using BioRender.com.
Brain State-Dependent Modulation of Thalamic Visual Processing by Cortico-thalamic Feedback
Authors: Reinhold Kimberly , Resulaj Arbora , Scanziani Massimo 
Published: October 2021

SummaryThe behavioral state of a mammal impacts how the brain responds to visual stimuli as early as in the dorsolateral geniculate nucleus of the thalamus (dLGN), the primary relay of visual information to the cortex. A clear example of this is the markedly stronger response of dLGN neurons to higher temporal frequencies of the visual stimulus in alert as compared to quiescent animals. The dLGN receives strong feedback from the visual cortex, yet whether this feedback contributes to these state-dependent responses to visual stimuli is poorly understood. Here we show that in mice, silencing cortico-thalamic feedback abolishes state-dependent differences in the response of dLGN neurons to visual stimuli. This holds true for dLGN responses to both temporal and spatial features of the visual stimulus. These results reveal that the state-dependent shift of the response to visual stimuli in an early stage of visual processing depends on cortico-thalamic feedback.
Temperature impacts on fish physiology and resource abundance lead to faster growth but smaller fish sizes and yields under warming
Authors: Lindmark Max , Audzijonyte Asta , Blanchard Julia , Gårdmark Anna 
Published: October 2021

AbstractResolving the combined effect of climate warming and exploitation in a food web context is key for predicting future biomass production, size-structure, and potential yields of marine fishes. Previous studies based on mechanistic size-based food web models have found that bottom-up processes are important drivers of size-structure and fisheries yield in changing climates. However, we know less about the joint effects of ‘bottom-up’ and physiological effects of temperature; how do temperature effects propagate from individual-level physiology through food webs and alter the size-structure of exploited species in a community? Here we assess how a species-resolved size-based food web is affected by warming through both these pathways, and by exploitation. We parameterize a dynamic size spectrum food web model inspired by the offshore Baltic Sea food web, and investigate how individual growth rates, size-structure, relative abundances of species and yields are affected by warming. The magnitude of warming is based on projections by the regional coupled model system RCA4-NEMO and the RCP 8.5 emission scenario, and we evaluate different scenarios of temperature dependence on fish physiology and resource productivity. When accounting for temperature-effects on physiology in addition to on basal productivity, projected size-at-age in 2050 increases on average for all fish species, mainly for young fish, compared to scenarios without warming. In contrast, size-at-age decreases when temperature affects resource dynamics only, and the decline is largest for young fish. Faster growth rates due to warming, however, do not always translate to larger yields, as lower resource carrying capacities with increasing temperature tend to result in declines in the abundance of larger fish and hence spawning stock biomass. These results suggest that to understand how global warming affects the size structure of fish communities, both direct metabolic effects and indirect effects of temperature via basal resources must be accounted for.
Sequential Temporal Anticipation Characterized by Neural Power Modulation and in Recurrent Neural Networks
Authors: Teng Xiangbin , Zhang Ru-Yuan 
Published: October 2021

AbstractRelevant prospective moments arise intermittently, while most of time is filled with irrelevant events, or noise, that constantly bombard our sensory systems. Thus, anticipating a few key moments necessitates disregarding what lies between the present and the future – the noise. Here, through examining how the brain and the recurrent neural networks (RNNs) anticipate a sequence of prospective moments without relying on any external timing cues, we provided a reinterpretation of temporal anticipation. We first designed a “premembering” task, where we marked three temporal locations in white noise and asked human listeners to detect a tone at one of these points. Using power modulation analyses, we investigated the memory-guided anticipatory processes in trials involving only flat noise. Our research revealed a unique neural-power modulation pattern for sequential temporal anticipation: neural power within the alpha-beta band range fluctuates over time, accurately identifying the marked locations on a sub-second scale and correlating with tone detection performance. To understand the functional roles of these neural modulations, we utilized RNNs optimized for the behavioral task. The hidden dynamics of the RNNs mirrored the neural modulations, and additional analyses and perturbations on the RNNs indicated that the neural power modulations in the alpha-beta band resulted from selective suppression of irrelevant noise periods and heightened sensitivity to anticipated temporal locations. Our behavioral, neural, and modeling findings collectively indicate that sequential temporal anticipation involves a process of dynamic gain control: anticipating a few significant moments involves actively disregarding irrelevant events that frequently occur.
Pioglitazone administration restores a PPARG-dependent transcriptional network and ATP levels within skeletal muscles of mice implanted with patient-derived breast tumors
Authors: Stanton David A. , Wilson Hannah E. , Chapa Matthew G. , Link Jessica N. , Geldenhuys Werner , Pistilli Emidio E. 
Published: October 2021

AbstractBackgroundFatigue is common in patents with breast cancer (BC), and can occur in patients with early stage disease and in the absence of muscle wasting (i.e. cachexia). We have reported transcriptional and proteomic alterations in muscles from BC patients, which are associated with fatigue. Mice implanted with human BC xenografts recapitulate the muscle molecular composition changes seen in patients, coupled with a greater rate of contraction-induced fatigue. Multiple bioinformatics platforms in both human and mouse muscles have identified peroxisome proliferator activated receptor gamma (PPARG) as central to this phenotype, with multiple PPARG target genes downregulated in response to tumor growth. The current study tested the hypothesis that the PPARG agonist pioglitazone (pio), a commonly prescribed diabetes drug, would rescue the transcriptional alterations observed in muscles of tumor-bearing mice.MethodsSixteen female NSG mice were implanted with breast cancer patient-derived orthotopic xenografts (BC-PDOX) via transplantation of Her2/neu+human tumor fragments. BC-PDOX mice were randomly assigned to a treatment group that received daily oral pio at 30 mg.kg-1(n=8), or a control group that received a similar volume of vehicle (n=8). Treatment was initiated when tumors reached a volume of 600mm3, and lasted for 2-weeks. Hindlimb muscles were isolated from BC-PDOX and non-tumor bearing mice for RNA-sequencing, gene expression validation, and ATP quantification. Differentially expressed genes (DEGs) in muscles from BC-PDOX mice relative to non-tumor bearing controls were identified using DESeq2, and multiple bioinformatics platforms were employed to contextualize the DEGs.ResultsWe found that the administration of pio restored the muscle gene expression patterns of BC-PDOX mice to a profile resembling muscles of non-tumor bearing NSG control mice. Validation of skeletal muscle gene expression by qPCR confirmed pio increased the expression of PPARG target genes in skeletal muscles. Isolated mitochondria from muscles of BC-PDOX mice treated with pio contained greater levels of ATP. There were no differences in body weights, muscle weights, or tumor volumes in pio vs. vehicle treated BC-PDOX mice.ConclusionsThese data demonstrate that oral pio supplementation rescues the BC-associated downregulation of PPARG target genes in skeletal muscle. Additionally, muscles from BC-PDOX mice treated with pio had greater levels of ATP, which would be associated a more fatigue-resistant muscle phenotype. Therefore, we propose that the FDA-approved and generic diabetes drug, pio, be considered as a supportive therapy for the treatment of BC-associated muscle fatigue.
RecA and RecB: probing complexes of DNA repair proteins with mitomycin C in live Escherichia coli with single-molecule sensitivity
Authors: Payne-Dwyer Alex L. , Syeda Aisha H. , Shepherd Jack W. , Frame Lewis , Leake Mark. C. 
Published: October 2021

AbstractThe RecA protein and RecBCD complex are key bacterial components for the maintenance and repair of DNA. RecBCD is a helicase-nuclease that uses homologous recombination to resolve double-stranded DNA breaks. It also facilitates coating of single-stranded DNA with RecA to form RecA filaments, a vital step in the double-stranded break DNA repair pathway. However, questions remain about the mechanistic roles of RecA and RecBCD in live cells. Here, we use millisecond super-resolved fluorescence microscopy to pinpoint the spatial localization of fluorescent reporters of RecA or RecB at physiological levels of expression in individual live Escherichia coli cells. By introducing the DNA crosslinker mitomycin C, we induce DNA damage and quantify the resulting steady state changes in stoichiometry, cellular protein copy number and molecular mobilities of RecA and RecB. We find that both proteins accumulate in molecular hotspots to effect repair, resulting in RecA stoichiometries equivalent to several hundred molecules that assemble largely in dimeric subunits before DNA damage, but form periodic subunits of approximately 3-4 molecules within mature filaments of several thousand molecules. Unexpectedly, we find that the physiologically predominant forms of RecB are not only rapidly diffusing monomers, but slowly diffusing dimers.
A mitochondrial electron transport chain with atypical subunit composition confers oxygen sensitivity to a mammalian chemoreceptor
Authors: Timón-Gómez Alba , Scharr Alexandra L. , Wong Nicholas Y. , Ni Erwin , Roy Arijit , Liu Min , Chau Julisia , Lampert Jack L. , Hireed Homza , Kim Noah S. , Jan Masood , Gupta Alexander R. , Day Ryan W. , Gardner James M. , Wilson Richard J. A. , Barrientos Antoni , Chang Andy J. 
Published: October 2021

AbstractThe carotid body (CB) is the major chemoreceptor for blood oxygen in the control of ventilation in mammals, contributing to physiological adaptation to high altitude, pregnancy, and exercise, and its hyperactivity is linked to chronic conditions such as sleep-disorder breathing, hypertension, chronic heart failure, airway constriction, and metabolic syndrome (1–3). Upon acute hypoxia (PO2=100 mmHg to <80 mmHg), K+ channels on CB glomus cells are inhibited, causing membrane depolarization to trigger Ca+2 influx and neurotransmitter release that stimulates afferent nerves (1–3). A longstanding model proposes that the CB senses hypoxia through atypical mitochondrial electron transport chain (ETC) metabolism that is more sensitive to decreases in oxygen than other tissues. This model is supported by observations that ETC inhibition by pharmacology and gene knockout activates CB sensory activity and that smaller decreases in oxygen concentration inhibit ETC activity in CB cells compared to other cells (1–5). Determining the composition of atypical ETC subunits in the CB and their specific activities is essential to delineate molecular mechanisms underlying the mitochondrial hypothesis of oxygen sensing. Here, we identify HIGD1C, a novel hypoxia inducible gene domain factor isoform, as an ETC Complex IV (CIV) protein highly and selectively expressed in glomus cells that mediates acute oxygen sensing by the CB. We demonstrate that HIGD1C negatively regulates oxygen consumption by CIV and acts with the hypoxia-induced CIV subunit COX4I2 to enhance the sensitivity of CIV to hypoxia, constituting an important component of mitochondrial oxygen sensing in the CB. Determining how HIGD1C and other atypical CIV proteins expressed in the CB work together to confer exquisite oxygen sensing to the ETC will help us better understand how tissue- and condition-specific CIV subunits contribute to physiological function and disease (6) and allow us to potentially target these proteins to treat chronic diseases characterized by CB dysfunction (7).
Time and spatial trends in landing per unit of effort as support to fisheries management in a multi-gear coastal fishery
Authors: Leitão P. , Sousa L. , Castro M. , Campos A. 
Published: October 2021

AbstractLandings by the multi-gear coastal fleet operating off the Portuguese continental coast include near 300 species, from which only a few are the object of management plans. In this study, daily landings (kg trip_1) are used, along with an effort indicator, vessel length overall (LoA), to obtain landings per unit of effort (LPUE) as a proxy for the species relative abundance for a total of 48 species. LPUE indices were then used as a response variable in linear models where year (2012-2016), season, region (north and south) and NAO index were included as explanatory variables. Season and region effects were found to significantly affect species abundance for a total of 41 and 40 species respectively, while interannual effects were found to be significant for 19 species, and finally, the NAO index for 3 species. Global LPUE density maps are presented for a number of selected species and a subsample of trips where VMS records were available. For the species analysed, it is proposed that geographic and seasonal changes in LPUE indexes can be used to understand trends in abundance and obtain information that can be used in support of the definition of regional management plans.