bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain-wide continuous functional ultrasound imaging for real-time monitoring of hemodynamics during ischemic stroke
Authors: Brunner Clément , Denis Nielsen Lagumersindez , Gertz Karen , Grillet Micheline , Montaldo Gabriel , Endres Matthias , Urban Alan
Published: January 2022

Ischemic stroke occurs with no warning, and therefore, very little is known about hemodynamic perturbations in the brain immediately after stroke onset. Here, functional ultrasound imaging was used to monitor variations in relative cerebral blood volume (rCBV) compared to baseline. rCBV levels were analyzed brain-wide and continuously at high spatiotemporal resolution (100μm, 2Hz) until 70mins after stroke onset in rats. We compared two stroke models, with either a permanent occlusion of the middle cerebral artery (MCAo) or a tandem occlusion of both the common carotid and middle cerebral arteries (CCAo+MCAo). We observed a typical hemodynamic pattern, including a quick drop of the rCBV after MCAo, followed by spontaneous reperfusion of several brain regions located in the vicinity of the ischemic core. The severity and location of the ischemia were highly variable between animals. Still, both parameters were, on average, in good agreement with the final ischemic lesion volume measured 24hrs after stroke onset for the MCAo but not the CCAo+MCAo model. For the latter, we observed that the infarct was extended to regions that were initially not ischemic and located rostrally of the ischemic core. These regions strongly colocalize with the origin of transient hemodynamic events associated with spreading depolarizations.
Therapeutic Interruption of T Cell Development Generates High-Affinity T Cells That Escape Exhaustion and Improve Cancer Immunotherapy
Authors: Dhuey Erica , Oldridge Olivia , Ravishankar Roshan , Dada Hannah , Yu Yongjun , Anderson Mark S. , Minn Andy J.
Published: January 2022

Availability of effective anti-tumor T cells is limited by cancer immunoediting, which depletes neoantigens, and central tolerance, which eliminates developing T cells with high-affinity T cell receptors (TCRs) against tumor self-antigens. Remaining tumor-reactive T cells are often exhausted after immune checkpoint blockade (ICB). Whether endogenous T cells with high- affinity TCRs against tumor self-antigens can be generated to circumvent exhaustion and reject neoantigen-poor tumors is unclear. We show that transiently interrupting central tolerance through RANKL blockade unleashes T cells possessing TCRs with self-reactive features that enable ICB to reject poorly immunogenic tumors. Upon recognition of tumor self-antigens, these T cells exhibit enhanced TCR signaling, enrichment in NFAT/AP-1 genes, and lymph node priming. Consequently, memory-precursor T cells against tumor self-antigens are generated, avoid exhaustion, and become effector-memory cells with transcriptional features associated with clinical ICB response. Thus, interrupting central tolerance provides T cells with tumor- directed autoreactivity that avoid exhaustion and improve immunotherapy.
Visualizing Synaptic Dopamine Efflux with a 2D Nanofilm
Authors: Bulumulla Chandima , Krasley Andrew T. , Walpita Deepika , Beyene Abraham G.
Published: January 2022

Chemical neurotransmission constitutes one of the fundamental modalities of communication between neurons. Monitoring release of these chemicals has traditionally been difficult to carry out at spatial and temporal scales relevant to neuron function. To understand chemical neurotransmission more fully, we need to improve the spatial and temporal resolutions of measurements for neurotransmitter release. To address this, we engineered a chemi-sensitive, two-dimensional nanofilm that facilitates subcellular visualization of the release and diffusion of the neurochemical dopamine with synaptic resolution, quantal sensitivity, and simultaneously from hundreds of release sites. Using this technology, we were able to monitor the spatiotemporal dynamics of dopamine release in dendritic processes, a poorly understood phenomenon. We found that dopamine release is broadcast from a subset of dendritic processes as hotspots that have a mean spatial spread of ≈3.2 µm (full width at half maximum) and are observed with a mean spatial frequency of 1 hotspot per ≈7.5 µm of dendritic length. Major dendrites of dopamine neurons and fine dendritic processes, as well as dendritic arbors and dendrites with no apparent varicose morphology participated in dopamine release. Remarkably, these release hotspots colocalized with Bassoon, suggesting that Bassoon may contribute to organizing active zones in dendrites, similar to its role in axon terminals.
Knockout of Bbs10 results in lack of cone electrical function and progressive retinal degeneration of rods and cones
Authors: Mayer Sara K. , Thomas Jacintha , Helms Megan , Kothapalli Aishwarya , Cherascu Ioana , Salesevic Adisa , Stalter Elliot , Wang Kai , Datta Poppy , Searby Charles , Seo Seongjin , Hsu Ying , Bhattarai Sajag , Sheffield Val C. , Drack Arlene V.
Published: January 2022

Bardet Biedl Syndrome (BBS) is an autosomal recessive disorder caused by mutations in at least 22 different genes. A constant feature is early onset retinal degeneration leading to blindness, with variable central obesity, polydactyly, renal failure, and developmental anomalies. BBS type 10 (BBS10) is a common form caused by mutations in the BBS10 gene encoding a chaperonin-like protein. There are currently no treatments for the progressive vision loss. To aid in treatment development, a BBS10 mouse model was developed by knocking out the Bbs10 gene. Using optical coherence tomography (OCT), electroretinography (ERG), and a visually guided swim assay (VGSA), we demonstrate that Bbs10-/- mice have progressive retinal degeneration. Cone electrical function was absent although cones were anatomically present on histology and retained partial function based on VGSA. The retinal outer nuclear layer (photoreceptor nuclei) progressively thinned as demonstrated on OCT and histology, and rod electrical activity decreased over time on ERG. These phenotypes are more rapidly progressive than retinal degeneration in the Bbs1M390R/M390R knock-in mouse. They are consistent with a cone-rod dystrophy distinct from typical rod-cone degeneration in retinitis pigmentosa and recapitulate aspects of retinal degeneration observed in humans with BBS10. This study has implications for BBS10 gene therapy.
Framework for Denoising Monte Carlo Photon Transport Simulations Using Deep Learning
Authors: Ardakani Matin Raayai , Yu Leiming , Kaeli David R. , Fang Qianqian
Published: January 2022

Significance

The Monte Carlo (MC) method is widely used as the gold-standard for modeling light propagation inside turbid media like human tissues, but combating its inherent stochastic noise requires one to simulate large number photons, resulting in high computational burdens.

Aim

We aim to develop an effective image denoising technique using deep learning (DL) to dramatically improve low-photon MC simulation result quality, equivalently bringing further acceleration to the MC method.

Approach

We have developed a cascade-network combining DnCNN with UNet, in the meantime, extended a range of established image denoising neural-network architectures, including DnCNN, UNet, DRUNet, and ResMCNet, in handling three-dimensional (3-D) MC data and compared their performances against model-based denoising algorithms. We have also developed a simple yet effective approach to create synthetic datasets that can be used to train DL based MC denoisers.

Results

Overall, DL based image denoising algorithms exhibit significantly higher image quality improvements over traditional model-based denoising algorithms. Among the tested DL denoisiers, our Cascade network yields a 14 - 19 dB improvement in signal-noise ratio (SNR), which is equivalent to simulating 25 × to 78 × more photons. Other DL-based methods yielded similar results, with our method performing noticeably better with low-photon inputs, and ResMCNet along with DRUNet performing better with high-photon inputs. Our Cascade network achieved the highest quality when denoising complex domains, including brain and mouse atlases.

Conclusion

Incorporating state-of-the-art DL denoising techniques can equivalently reduce the computation time of MC simulations by one to two orders of magnitude. Our open-source MC denoising codes and data can be freely accessed at http://mcx.space/.
Risk Factors for Delirium in Elderly Patients After Lumbar Spinal Fusion
Authors: Gold Colin , Ray Emanuel , Christianson David , Park Brian , Kournoutas Ioannis A , Kahn Taimur A , Perez Eli A. , Berger Joel I. , Sander Katie , Igram Cassim A. , Pugely Andrew , Olinger Catherine R. , Carnahan Ryan , Chen Pei-fu , Mueller Rashmi , Hitchon Patrick , Howard Matthew A. , Banks Matthew , Sanders Robert D. , Woodroffe Royce W.
Published: January 2022

Background Context

Postoperative delirium is a clinically significant acute disorder of consciousness especially prevalent in older adult patients, of which more than 100,000 per year undergo spinal fusion surgery. There are no proven preventative therapies, and delirium is associated with increased postoperative complications, functional decline, morbidity, and mortality.

Purpose

To identify perioperative risk factors for postoperative delirium (POD) after lumbar spinal fusion procedures in patients aged 65 or older.

Study Design

Retrospective Review

Patient Sample

702 patients who underwent lumbar spinal fusion surgery from 11/13/2017 to 1/30/2021.

Outcome Measures

The primary outcome was the presence of postoperative delirium assessed by the Delirium Observation Screening Scale (DOSS) and Confusion Assessment Method for the ICU (CAM-ICU).

Methods

Demographic, surgical, and perioperative data were obtained from the electronic medical records. The primary outcome was presence of postoperative delirium. Univariate and multivariate analyses were performed. A binomial logistic regression model was designed using a custom written MATLAB script.

Results

Of the 702 patients included in the study, 173 (24.6%) developed POD. Our analysis revealed that older age (p < 0.001), lower preoperative hemoglobin (p < 0.001), and higher ASA grade (p < 0.001), were significant preoperative risk factors for developing POD. The only significant intraoperative risk factor was a higher number of spinal levels that were instrumented (p < 0.001). Higher pain scores on postoperative day 1 (p < 0.001), and lower postoperative hemoglobin (p < 0.001) were associated with increased POD; as were ICU admission (p < 0.001) and increased length of ICU stay (p < 0.001). Patients who developed POD had a longer hospital stay (p < 0.001) with lower rates of discharge to home as opposed to an inpatient facility (p < 0.001).

Conclusions

Risk factors for older adults undergoing lumbar spinal fusion surgery include advanced age, lower preoperative and postoperative hemoglobin, higher ASA grade, greater extent of surgery, and higher postoperative pain scores. Patients with delirium had a higher incidence of postoperative ICU admission, increased length of stay, decreased likelihood of discharge to home and increased mortality, all consistent with prior studies. Further studies will determine whether adequate management of anemia and pain lead to a reduction in the incidence of postoperative delirium in these patients.
The relationship between work disability and subsequent suicide or self-harm: A systematic scoping review
Authors: Collie Alex , Gray Shannon Elise
Published: January 2022

Background

Work disability occurs when an injury, illness or other health condition limits the ability of a worker to participate in paid employment. Several lines of evidence suggest that people with work disability are also at increased risk of suicide and intentional self-harm, however the evidence on this relationship has not previously been the subject of systematic review.

Objective

This systematic scoping review aims to assess and summarise the research literature regarding the relationship between work disability and subsequent suicide or intentional self-harm.

Methods

Peer-reviewed quantitative and qualitative studies published in English from 1st January 2000 were included if they reported suicide or self-harm outcomes in people aged 15 years or older with work disability. Narrative synthesis summarised findings according to the system of work disability income support.

Results

Literature search yielded 859 records of which 47 eligible studies were included, including nine set in workers’ compensation, 20 in sickness absence, 13 in disability pension systems, and five from mixed cohorts. Of 44 quantitative studies, 41 reported a positive relationship between work disability and suicidal behaviour. The relationship is observed consistently across nations, work disability income support systems and in people with a range of health conditions. Several factors elevate risk of suicidal behaviour, including presence of mental health conditions and longer work disability duration. There were few quality studies in some nations and no suicide prevention interventions.

Conclusion

The risk of suicide and intentional self-harm is elevated in people experiencing work disability. While further observational research is required to fill evidence gaps, this review suggests the need for governments, employers and those involved in the delivery of care and support to people with work disability to focus on identification and monitoring of those at greatest risk of suicidal behaviour, as well as suicide prevention.
Complex genetics cause and constrain fungal persistence in different parts of the mammalian body
Authors: Mullis Martin N. , Ghione Caleb , Lough-Stevens Michael , Goldstein Ilan , Matsui Takeshi , Levy Sasha F. , Dean Matthew D. , Ehrenreich Ian M.
Published: January 2022

Determining how genetic polymorphisms enable certain fungi to persist in mammalian hosts can improve understanding of opportunistic fungal pathogenesis, a source of substantial human morbidity and mortality. We examined the genetic basis of fungal persistence in mice using a cross between a clinical isolate and the lab reference strain of the budding yeastSaccharomyces cerevisiae. Employing chromosomally-encoded barcodes, we tracked the relative abundances of 822 genotyped, haploid segregants in multiple organs over time and performed linkage mapping of their persistence in hosts. Detected loci showed a mix of general and antagonistically pleiotropic effects across organs. General loci showed similar effects across all organs, while antagonistically pleiotropic loci showed contrasting effects in the brain and the kidneys, liver, and spleen. Persistence in an organ required both generally beneficial alleles and organ-appropriate pleiotropic alleles. This genetic architecture resulted in many segregants persisting in the brain or in non-brain organs, but few segregants persisting in all organs. These results show complex combinations of genetic polymorphisms collectively cause and constrain fungal persistence in different parts of the mammalian body.
Comparison of Two Individual Identification Algorithms for Snow Leopards after Automated Detection
Authors: Blount Drew , Bohnett Eve , Holmberg Jason , Parham Jason , Faryabi Sorosh Poya , Johansson Örjan , An Li , Ahmad Bilal , Khan Wajid , Ostrowski Stephane
Published: January 2022

1. Photo-identification of individual snow leopards (Panthera uncia) is the primary technique for density estimation for the species. A high volume of images from multiple projects, combined with pre-existing historical catalogs, has made identifying snow leopard individuals within the images cost- and time-intensive. 2. To speed the classification among a high volume of photographs, we trained and evaluated image classification methods for PIE v2 (a triplet loss network), and we compared PIE’s accuracy to the HotSpotter algorithm (a SIFT based algorithm). Analyzed data were collected from a curated catalog of free-ranging snow leopards photographed across years (2012-2019) in Afghanistan and from samples in captivity provided by zoos from Finland, Sweden, Germany, and the United States. 3. Results show that PIE outperforms HotSpotter. We also found weaknesses in the initial PIE model, like a minor amount of background matching, which was addressed, although likely not fully resolved, by applying background subtraction (BGS) and left-right mirroring (LR) methods. The PIE BGS LR model combined with Hotspotter showed a Rank-1: 85%, Rank-5: 95%, Rank-20: 99%. 4. Overall, our results recommend implementing PIE v2 simultaneously with HotSpotter on Whiskerbook.org.
Imbalance of Neuregulin1-ErbB2/3 signaling underlies altered myelin homeostasis in models of Charcot-Marie-Tooth disease type 4H
Authors: El-Bazzal Lara , Ghata Adeline , Estève Clothilde , Quintana Patrice , Roeckel-Trévisiol Nathalie , Lembo Frédérique , Lenfant Nicolas , Mégarbané Andre , Borg Jean-Paul , Lévy Nicolas , Bartoli Marc , Poitelon Yannick , Roubertoux Pierre L. , Delague Valérie , Bernard-Marissal Nathalie
Published: January 2022

Charcot Marie Tooth disease (CMT) is one of the most common inherited neurological disorders, affecting either axons from the motor and/or sensory neurons or Schwann cells (SC) of the peripheral nervous system, and caused by more than 100 genes. We previously identified mutations in FGD4, as responsible for CMT4H, an autosomal recessive demyelinating form of CMT. FGD4 encodes FRABIN a GDP/GTP nucleotide exchange factor (GEF), particularly for the small GTPase cdc42. Remarkably, nerves from patients with CMT4H display excessive redundant myelin called outfoldings that arise from focal hypermyelination, suggesting that FRABIN could play a role in the control of PNS myelination. To gain insights into the role of FGD4/FRABIN in SC myelination, we generated a knock-out mouse model, with conditional ablation of fgd4 in SC. We showed that the specific deletion of FRABIN in SCs leads to aberrant myelination in vitro, in dorsal root ganglion (DRG)/SCs cocultures as well in vivo, in distal sciatic nerves. We observed that those myelination defects are related to an upregulation of some interactors of the NRG1 type III/ErbB2/3 signaling pathway, which is known to ensure a proper level of myelination in the PNS. Based on a yeast two-hybrid screen, we identified SNX3 as a new partner of FRABIN, which is involved in the regulation of endocytic trafficking. Interestingly, we showed that loss of FRABIN impairs endocytic trafficking which may contribute to the defective NRG1 type III/ErbB2/3 signaling and myelination. Finally, we showed that the reestablishment of proper levels of the NRG1 type III/ErbB2/3 pathway using Niacin treatment reduces myelin outfoldings in nerves of CMT4H mice. Overall, our work reveals a new role of FRABIN in the regulation of NRG1 type III/ErbB2/3 NRG1signaling and myelination and opens future therapeutic strategies based on the modulation of NRG1 type III/ErbB2/3 NRG1to reduce CMT4H pathology and more generally others demyelinating CMT.
Wearing an Eye Mask During Overnight Sleep Improves Episodic Learning and Alertness
Authors: Greco Viviana , Bergamo Damiana , Cuoccio Paola , Konkoly Karen R. , Lombardo Kike Muñoz , Lewis Penelope A.
Published: January 2022

Ambient light can influence sleep structure and timing. We explored how wearing an eye-mask to block light during overnight sleep impacts on memory and alertness, changes that could benefit everyday tasks like studying or driving. In Experiment 1, ninety-four 18–35-year-olds wore an eye-mask while they slept every night for a week and underwent a control condition in which light was not blocked for another week. Five habituation nights were followed by a cognitive battery on the sixth and seventh days. This revealed superior episodic encoding and an improvement on alertness when using the mask. In Experiment 2, thirty-five 18–35-year-olds used a wearable device to monitor sleep with and without the mask. This replicated the encoding benefit and showed that it was predicted by time spent in slow wave sleep. Our findings suggest that wearing an eye-mask during overnight sleep can improve episodic encoding and alertness the next day.

Statement of relevance

Sleep is crucial for alertness and for preparing the human brain to encode new information. However, it can be disrupted by external stimuli such as light or sounds. This study explored wearing an eye mask as a potential cognitive enhancer which protects overnight sleep by blocking ambient light. We found that wearing a mask increased alertness and facilitated the encoding of novel information the next day. Furthermore, the benefit to memory was predicted by time spent in slow wave sleep while wearing the mask. This suggests wearing an eye mask during sleep is an effective, economical, and non-invasive behaviour that could benefit cognitive function and lead to measurable impacts on every-day life.
Evolution ofDaphniapopulation dynamics following invasion by a non-native predator
Authors: Einum Sigurd , Ullern Emil R. , Walsh Matthew , Burton Tim
Published: January 2022

Predators are frequently observed to cause evolutionary responses in prey phenotypes, which may, in turn, translate into evolutionary shifts in prey population dynamics. Although a link between predation and population growth has been demonstrated in experimental evolution studies, insights from natural populations are lacking.

Here we tested for evolutionary changes in the population dynamics of the herbivorous water fleaDaphnia pulicariain response to the invasion of the predatory spiny water flea (Bythotrephes longimanus) in the Great Lakes region, USA. Using a resurrection ecological approach and a 3-month population growth experiment (in the absence of predation) we compared population dynamics in daphnia from pre- and post-invasion time periods.

Post-invasion daphnia were able to maintain an overall higher population abundance throughout the growth experiment, both in terms of the number of individuals (28% higher) and total population biomass (33% higher). Estimation of population dynamics parameters from a theta-logistic model suggested that this was achieved through an increase in intrinsic population growth rate as well as increased carrying capacity.

The observed difference in intrinsic rate of increase could not be predicted based on previous measurements of life-history traits in these clones. This indicates that care should be taken when extrapolating from a few life history traits measured in isolated individuals under controlled conditions to population dynamics.

Whereas previous experimental evolution studies of predator-prey interactions have demonstrated that genotypes that have evolved under predation have inferior population growth when the predator is absent, this was not the case for theDaphnia. We suggest that complexities in ecological interactions of natural ecosystems, such as the potential for spatial and temporal avoidance of predation, makes it challenging to provide general predictions about evolutionary responses in population dynamics to predators.
Ex vivoandin vivoevidence that cigarette smoke-exposed T regulatory cells impair host immunity againstMycobacterium tuberculosis
Authors: Bai Xiyuan , Verma Deepshikha , Garcia Cindy , Musheyev Ariel , Kim Kevin , Fornis Lorelenn , Griffith David E. , Li Li , Whittel Nicholas , Gadwa Jacob , Ohanjanyan Tamara , Ordway Diane , Chan Edward D.
Published: January 2022

A strong epidemiologic link exists between exposure to cigarette smoke (CS) and increased susceptibility to tuberculosis (TB).In vitromacrophage andin vivomurine studies showed that CS and nicotine impair host-protective immune cells againstMycobacterium tuberculosis(MTB) infection. However, little is known about how CS may affect immunosuppressive cells in the context ofMTBinfection. Thus, we investigated whether CS-exposed T regulatory cells (Tregs) could exacerbateMTBinfection in co-culture with human macrophages and in the adoptive transfer of Tregs from air- and CS-exposed mice. We found that exposure of primary human Tregs to CS extract impaired the ability of human monocyte-derived macrophages to control anMTBinfection by inhibiting phagosome-lysosome fusion and autophagosome formation. Neutralization of CTLA-4 on the CS extract-exposed Tregs abrogated the impaired control ofMTBinfection in macrophage and Treg co-cultures. In Foxp3+GFP+DTR+(Thy1.2) mice depleted of endogenous Tregs, adoptive transfer of Tregs from donor CS-exposed B6.PL(Thy1.1) mice with subsequentMTBinfection of the recipient Thy1.2 mice resulted in a greater burden ofMTBin the lungs and spleens than those that received Tregs from airexposed mice. Mice that received Tregs from CS-exposed mice and then infected withMTBhad modest but significantly reduced numbers of interleukin-12-positive dendritic cells and interferon-gamma-positive CD4+T cells in the lungs and increased number of programmed cell death protein-1 positive CD4+T cells in both the lungs and spleens.
Number neurons in the nidopallium of young domestic chicks
Authors: Kobylkov Dmitry , Mayer Uwe , Zanon Mirko , Vallortigara Giorgio
Published: January 2022

Numerical cognition is ubiquitous in the animal kingdom. Domestic chicks are a widely used developmental model for studying numerical cognition. Soon after hatching, chicks can perform sophisticated numerical tasks. Nevertheless, the neural basis of their numerical abilities has remained unknown. Here, we describe for the first time number neurons in the caudal nidopallium (functionally equivalent to the mammalian prefrontal cortex) of young domestic chicks. Number neurons that we found in young chicks showed remarkable similarities to those in the prefrontal cortex and caudal nidopallium of adult animals. Thus, our results suggest that numerosity perception based on the labeled-line code provided by number neurons might be an inborn feature of the vertebrate brain.

Significance

Numerosity, i.e. the number of items in a set, is a significant aspect in the perception of the environment. Behavioural and in silico experiments suggest that number sense belongs to a core knowledge system and can be present already at birth. However, neurons sensitive to the number of visual items have been so far described only in the brain of adult animals. Therefore, it remained unknown to what extent their selectivity would depend on visual learning and experience. We found number neurons in the caudal nidopallium (a higher associative area with functional similarities to the mammalian prefrontal cortex) of very young, numerically naïve domestic chicks. This result suggests that numerosity perception is possibly an inborn feature of the vertebrate brain.
Control of Ribosomal RNA Synthesis by Hematopoietic Transcription Factors
Authors: Antony Charles , George Subin S. , Blum Justin , Somers Patrick , Thorsheim Chelsea L. , Wu-Corts Dexter J. , Ai Yuxi , Gao Long , Lv Kaosheng , Tremblay Michel G. , Moss Tom , Tan Kai , Wilusz Jeremy E. , Ganley Austen R. D. , Pimkin Maxim , Paralkar Vikram R.
Published: January 2022

Ribosomal RNAs (rRNAs) are the most abundant cellular RNAs, and their synthesis from rDNA repeats by RNA Polymerase I accounts for the bulk of all transcription. Despite substantial variation in rRNA transcription rates across cell types, little is known about cell-type-specific factors that bind rDNA and regulate rRNA transcription to meet tissue-specific needs. Using hematopoiesis as a model system, we mapped about 2200 ChIP-Seq datasets for 250 transcription factors (TFs) and chromatin proteins to human and mouse rDNA, and identified robust binding of multiple TF families to canonical TF motifs on rDNA. Using a 47S-FISH-Flow assay developed for nascent rRNA quantification, we demonstrated that targeted degradation of CEBPA (C/EBP alpha), a critical hematopoietic TF with conserved rDNA binding, caused rapid reduction in rRNA transcription due to reduced Pol I occupancy. Our work identifies numerous potential rRNA regulators, and provides a template for dissection of TF roles in rRNA transcription.

HIGHLIGHTS

Multiple cell-type-specific transcription factors (TFs) bind canonical motifs on rDNA.

The hematopoietic TF CEBPA binds to active rDNA alleles at a conserved site.

CEBPA promotes Polymerase I occupancy and rRNA transcription in myeloid progenitors.

We present ‘47S-FISH-Flow,’ a sensitive assay to quantify nascent rRNA.
PopB-PcrV Interactions are Essential for Pore Formation in the Pseudomonas aeruginosa Type III Secretion System Translocon
Authors: Kundracik Emma Caitlin , Trichka Josephine , Díaz Aponte José Enrique , Rietsch Arne
Published: January 2022

The type III secretion system (T3SS) is a syringe-like virulence factor which delivers bacterial proteins directly into the cytoplasm of host cells. An essential component of the system is the translocon, which creates a pore in the host cell membrane through which proteins are injected. In Pseudomonas aeruginosa, the translocation pore is formed by proteins PopB and PopD and attaches to the T3SS needle via the needle tip protein PcrV. The pore is multimeric, but the exact stoichiometry and structure of the pore are unknown. We took a genetic approach to map contact points within the system by taking advantage of the fact that the translocator proteins of Pseudomonas aeruginosa and the related Aeromonas hydrophila T3SS are incompatible and cannot be freely exchanged. We created chimeric versions of P. aeruginosa PopB and A. hydrophila AopB to intentionally disrupt and restore protein-protein interactions. We identified a chimeric B-translocator that specifically breaks an interaction with the needle tip protein and interferes with the formation of the translocation pore. Breaking the interaction did not disrupt membrane insertion, arguing that the needle tip protein chaperones formation of the translocation pore.
Staphylococcal protein A inhibits IgG-mediated phagocytosis by blocking the interaction of IgGs with FcγRs and FcRn
Authors: Cruz Ana Rita , Bentlage Arthur E. H. , Blonk Robin , de Haas Carla J. C. , Aerts Piet C. , Scheepmaker Lisette M. , Bouwmeester Inge G. , Lux Anja , van Strijp Jos A. G. , Nimmerjahn Falk , van Kessel Kok P. M. , Vidarsson Gestur , Rooijakkers Suzan H. M.
Published: January 2022

Immunoglobulin G molecules are crucial for the human immune response against bacterial infections. IgGs can trigger phagocytosis by innate immune cells, like neutrophils. To do so, IgGs should bind to the bacterial surface via their variable Fab regions and interact with Fcγ receptors (FcγRs) and complement C1 via the constant Fc domain. C1 binding to IgG-labeled bacteria activates the complement cascade, which results in bacterial decoration with C3-derived molecules that are recognized by complement receptors (CRs) on neutrophils. Next to FcγRs and CRs on the membrane, neutrophils also express the intracellular neonatal Fc receptor (FcRn). We previously reported that staphylococcal protein A (SpA), a key immune evasion protein ofStaphylococcus aureus, potently blocks IgG-mediated complement activation and killing ofS. aureusby interfering with IgG hexamer formation. SpA is also known to block IgG-mediated phagocytosis in absence of complement but the mechanism behind it remains unclear. Here we demonstrate that SpA blocks IgG-mediated phagocytosis and killing ofS. aureusthrough inhibition of the interaction of IgGs with FcγRs (FcγRIIa and FcγRIIIb, but not FcγRI) and FcRn. Furthermore, our data show that multiple SpA domains are needed to effectively block IgG1-mediated phagocytosis. This provides a rationale for the fact that SpA fromS. aureuscontains four to five repeats. Taken together, our study elucidates the molecular mechanism by which SpA blocks IgG-mediated phagocytosis and supports the idea that next to FcγRs, also the intracellular FcRn receptor is essential for efficient phagocytosis and killing of bacteria by neutrophils.
A Genome-wide CRISPR Screen Identifies WDFY3 as a Novel Regulator of Macrophage Efferocytosis
Authors: Shi Jianting , Wu Xun , Wang Ziyi , Li Fang , Meng Yujiao , Moore Rebecca M. , Cui Jian , Xue Chenyi , Croce Katherine R. , Yurdagul Arif , Doench John G , Li Wei , Zarbalis Konstantinos S. , Tabas Ira , Yamamoto Ai , Zhang Hanrui
Published: January 2022

Abstracts

Phagocytic clearance of dying cells, termed efferocytosis, must occur efficiently to maintain homeostasis and prevent disease. Yet, our understanding of this important biological process remains incomplete. To search for novel regulators of efferocytosis, we performed a FACS-based genome-wide CRISPR knockout screen in primary murine macrophages. We identified a novel role for WDFY3 in efferocytosis by macrophages. WDFY3 deficiency in macrophages specifically impaired uptake, not binding, of apoptotic cells due to defective actin depolymerization. We further revealed that WDFY3 directly interacts with GABARAP, thus facilitating LC3 lipidation and subsequent lysosomal acidification to permit the degradation of apoptotic cell components. Although the C-terminus of WDFY3 was sufficient to rescue impaired degradation, full-length WDFY3 is still required for regulating uptake. Finally, WDFY3 is required for efficient efferocytosis in vivo in mice and in primary human macrophages. The work expands our knowledge of the mechanisms of macrophage efferocytosis, and more broadly, provides a general strategy for genome-wide CRISPR screen to interrogate complex functional phenotypes in primary macrophages.

Highlights

Functional readout for pooled genome-wide CRISPR screen in primary macrophages.

WDFY3 is discovered as a regulator of macrophage efferocytosis in vitro and in vivo.

WDFY3 deficiency led to impaired uptake, as opposed to binding, of apoptotic cells due to defective actin depolymerization.

WDFY3 directly interacts with GABARAP, facilitating LC3 lipidation and subsequent lysosomal acidification to permit the degradation of apoptotic cell components.

C-terminal WDFY3 is sufficient to regulate the degradation of engulfed apoptotic cells while full-length WDFY is required for regulating uptake.
Modified dN/dS for accounting transition and transversion frequency difference and non-sense substitution in genomes
Authors: Aziz Ruksana , Sen Piyali , Beura Pratyush Kumar , Das Debashis , Dash Madhusmita , Namsa Nima Dondu , Deka Ramesh Chandra , Feil Edward J , Satapathy Siddhartha Sankar , Ray Suvendra Kumar
Published: January 2022

The dN/dS value is estimated in homologous protein coding gene sequences between two closely related organisms for studying selection on the genes. In the usual method of calculation of synonymous (S) and non-synonymous (NS) sites in codons, the transition and transversion rates are considered same as well as no difference of pretermination codons from the other codons regarding NS substitutions is considered. In this study we are proposing a modification in the method by estimating the S and the NS sites in codons by considering difference between the transition and transversion rates and the NS substitutions leading to non-sense codons in pretermination codons. So, the dN/dS value calculated by our approach was higher than that calculated by the earlier method. The modified method was applied in estimating dN/dS in 29 homologous gene sequences ofEscherichia coliandSalmonella enterica. Impact of codon degeneracy and pretermination codons on the dN/dS values estimated by our method were observed clearly. Our method of estimation that considers the above features is a realistic representation of dN/dS values in coding sequences.
Corporate social responsibility and the impact on economic value added: the role of environmental innovation
Authors: Schiessl Djonata , Korelo José Carlos , Mussi Szabo Cherobim Ana Paula
Published: January 2022

Purpose

Corporate social responsibility (CSR) is a common strategy implemented by companies due to social, ethical and policy pressures to reduce its impact on society, economy and environment. However, whether CSR adds or decreases firms’ value remains little explored. Thus, this study aims to evaluate the impact of CSR adoption on companies’ economic value added (EVA). The authors also tested a mechanism of environmental innovation and the moderation role of a firm’s size.

Design/methodology/approach

The authors performed a regression analysis and a mediation process analysis using dataset from 4,287 largest companies worldwide to investigate this issue. The a dataset was collected from Eikon, a Thomson Reuters platform.

Findings

The results revealed four main findings. Companies with high CSR indexes decreased EVA; environmental innovation mediated the effect of CSR on EVA; the firm size positively moderated the effect of CSR on EVA and firm size positively moderated the effect of CSR on environmental innovation.

Originality/value

To the best of the author’s knowledge, this research is the first endeavor to analyze CSR’s effect on EVA and the mediation role of environmental innovation using the most prominent firms worldwide. Furthermore, the results highlight exciting implications for literature, managers and policymakers.
Collaborative literary reasoning as a support for preservice English language arts teachers' learning about disciplinary literacy
Authors: Kane Britnie Delinger , Keene K.C. , Reynolds Sarah
Published: January 2022

Purpose

The purpose of this study is to understand how preservice teachers (PTs) learn about disciplinary literacy in English language arts (ELA). In mathematics and writing, research has found that teachers’ participation in disciplinary work can support their understanding of domain-specific inquiry, problem-solving and argumentation.

Design/methodology/approach

This exploratory, qualitative case study of an English methods course extends that work into ELA, asking how PTs’ participation in collaborative literary reasoning (CLR) influences their understanding of ELA as a discipline and their instructional planning processes.

Findings

Findings indicate that CLR supported PTs to define ELA as a collaborative discipline in which multiple interpretations of literature are valued; to name specific disciplinary literacy practices; to identify a focus and purpose for teachers’ design and revision of lesson plans; and to inform their thinking about text selection and complexity.

Originality/value

This work highlights the potential of collaborative literary reasoning to support PTs’ learning about disciplinary literacy instruction.
Job satisfaction and support in the medical profession: The foundations of efficient organizational healthcare performance
Authors: Gkliati Alexandra , Saiti Anna
Published: January 2022

Purpose

The purpose of the paper is to examine the levels of job satisfaction among doctors who work in Greek public hospitals, to determine the factors that may influence their satisfaction, to examine the contribution that staff support makes to job satisfaction and to investigate the potential impact that an economic recession might have on job satisfaction.

Design/methodology/approach

The sampling process used was stratified sampling and it was applied to all health regions in Greece. An official request to carry out the study was sent to 45 hospitals for the approval of their management. Through random sampling, 5% of the doctors' population was selected from each participating hospital, with the resulting sample consisting of 458 doctors from all the health regions of Greece. An anonymous questionnaire was administered to the sample of medical doctors to gather data on their perception of the work they do in public hospitals.

Findings

Empirical results showed that (1) the most important factor in doctors' job satisfaction appears to be the nature of their job and the high levels of autonomy that they have, and (2) doctors' level of commitment is maintained by enhancing their positive emotions and sense of professional well-being.

Originality/value

A deeper understanding of important concepts of an organization's behavior such as job satisfaction, staff support and their connection with internal organizational structures will facilitate policy makers and those who make decisions on the strategic management of medical staff in public hospitals.
Functionally diverse tree stands reduce herbaceous diversity and productivity via canopy packing
Authors: Zheng Li‐Ting , Chen Han Y. H. , Hautier Yann , Bao Di‐Feng , Xu Ming‐Shan , Yang Bai‐Yu , Zhao Zhao , Zhang Li , Yan En‐Rong
Published: January 2022

There is extensive experimental evidence for the importance of biodiversity in sustaining ecosystem functioning. However, such experiments typically prevent immigration by continuously removing non‐target species, thereby questioning the generality of these findings to real‐world ecosystems. This is particularly true in forest ecosystems where understorey herbaceous species are key biodiversity components but are usually weeded in tree diversity experiments. Consequently, little is known about how tree diversity influences the natural dynamics of understorey herbaceous layers.

We conducted a 3‐year non‐weeded tree diversity experiment composed of eight woody species differing widely in plant economic strategies. We examined how the functional diversity and identity of tree species mixtures drive the temporal dynamics of understorey productivity, functional diversity and composition through canopy packing (CP).

Tree mixtures with high functional diversity experienced increased CP over time, thereby decreasing understorey productivity and diversity. Furthermore, herbaceous communities were dominated by species with functional traits typical of low‐light conditions [lower community‐weighted mean (CWM) of maximum plant height, but larger CWM of specific leaf area] in response to increased CP.

Our results provide mechanistic insights into the role of tree functional diversity in shaping the dynamics of biomass, functional diversity and composition of the understorey herbaceous layer during the early successional period. It is expected that the effects of tree functional diversity would also be relevant over time due to the increasing usage of canopy space. This study highlights the significance of natural community processes in determining the effects of tree diversity on the temporal dynamics of previously neglected ecosystem structures and functioning.

Read the free Plain Language Summary for this article on the Journal blog.
Increased interannual precipitation variability enhances the carbon sink in a semi‐arid grassland
Authors: Ru Jingyi , Wan Shiqiang , Hui Dafeng , Song Jian , Wang Jing
Published: January 2022

The amplifying interannual precipitation variability has been observed globally and is projected to intensify under climate change scenarios. However, its impacts on terrestrial vegetation and carbon (C) sink have not been well investigated.

As part of a field manipulative experiment with three precipitation variabilities (20%, 40% and 60%) in a semi‐arid grassland, this study was conducted to examine the responses of ecosystem C cycling to increased precipitation variability.

Across the 3 experimental years from 2010 to 2012, amplified precipitation variability enhances gross primary productivity (GPP) and ecosystem respiration (ER), as both GPP and ER were more sensitive to above‐ than below‐average precipitation. In addition, the larger responses of GPP than ER to precipitation variability resulted in an enhancement of net ecosystem productivity (NEP), such that NEP increased with the increasing precipitation variability. More species with higher sensitivity to increased precipitation under wet conditions and the insensitivity of root growth to decreased precipitation could largely be responsible for the above observations, which suggest that the semi‐arid grassland was more sensitive to wet treatment yet strongly resistant to drought.

Our results provide empirical evidence that intensified precipitation variability could stimulate grassland C sink. The findings revealed in this study could facilitate the mechanistic understanding and imply the potential positive feedback of climate variability‐terrestrial C sink.

Read the free Plain Language Summary for this article on the Journal blog.
Relationship between cooling time and neurological outcomes in targeted temperature management
Authors: Ahn Seong Jun , Kim Yong Hwan , Lee Jun Ho , Lee Dong Woo , Hwang Seong Youn , Lee Byung Kook , Cho In Soo , Oh Sang Hoon , Cha Kyoung‐Chul ,   KORHN investigators
Published: January 2022

Objectives

The relationship between cooling time (CT) variables and neurological outcomes is controversial. We evaluated the relationship between CT and neurological outcomes in out‐of‐hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM).

Methods

We conducted a multicenter, prospective, and registry‐based study of OHCA survivors treated with TTM. CT was defined as the time from restoration of spontaneous circulation to achievement of the target temperature. The primary outcome was a favorable neurological outcome at 6 months. Multilevel logistic regression analysis was performed to test the relationship between CT and the primary outcome.

Results

Overall, the favorable neurological outcome rates at 6 months were 29.8% in 937 patients. When CT was stratified into categories of 0–3, 3.1–6, 6.1–9, 9.1–12, and >12 h, according to 3‐h intervals, the primary outcome rates were 8.2%, 22.7%, 35.5%, 44.7%, and 44.5%, respectively (p < 0.001). Significant differences were not found in multilevel logistic regression analysis; the adjusted odds ratios (95% confidence interval) of each category for the primary outcome compared to the 0–3‐h group were 0.81 (0.32 to 2.04), 0.77 (0.30 to 2.01), 1.26 (0.43 to 3.68), and 1.06 (0.37 to 3.06).

Conclusions

We did not find a relationship between CT and neurological outcomes at 6 months.
Patient views on emergency department screening and interventions related to housing
Authors: Kelly Audrey , Fazio Daniela , Padgett Deborah , Ran Ziwei , Castelblanco Donna G. , Kumar Diana , Doran Kelly M.
Published: January 2022

Objectives

Emergency departments (EDs) serve as a health care “safety net” and may be uniquely suited to screening for and addressing patients' unmet social needs. We aimed to better understand patient perspectives on ED‐based screening and interventions related to housing instability, as a step toward improving future efforts.

Methods

We present findings from a qualitative study using in‐depth, one‐on‐one interviews with ED patients who had become homeless in the past 6 months. Qualitative interviewees were asked their thoughts on ED staff asking about and helping to address homelessness and housing issues. Interviews were professionally transcribed verbatim. Multiple coders identified interview text segments focused on ED‐based housing screening and intervention, which were then independently analyzed thematically and discussed to reach consensus. Researchers also categorized each participant's overall opinion on ED housing screening and interventions as positive, neutral, or negative.

Results

Qualitative interviews were conducted with 31 patients. Four themes related to ED‐based housing screening and interventions emerged: (1) patients generally welcome ED staff/providers asking about and assisting with their housing situation, with caveats around privacy and respect; (2) ED conversations about housing have potential benefits beyond addressing unmet housing needs; (3) patients may not consider the ED as a site to obtain help with housing; (4) patients' experiences navigating existing housing services can inform best approaches for the ED. Most participants expressed overall positive views of ED staff/providers asking patients about their housing situation.

Conclusions

Study participants generally felt positively about screening and interventions for housing in the ED. Insights from this study can inform future ED‐based housing instability screening and interventions.