bluuebunny/crossref_metadata_2025 huggingface dataset:
Single Cell Transcriptomic Landscape of Diabetic Foot Ulcers
Authors: Theocharidis Georgios , Thomas Beena E. , Sarkar Debasree , Pilcher William JR , Dwivedi Bhakti , Sandoval-Schaefer Teresa , Sîrbulescu Ruxandra F. , Kafanas Antonios , Mezghani Ikram , Wang Peng , Lobao Antonio , Vlachos Ioannis , Dash Biraja , Hsia Henry C. , Horsley Valerie , Bhasin Swati S. , Veves Aristidis , Bhasin Manoj
Published: March 2021

To understand the diabetic wound healing microenvironment, we profiled 174,962 single cells from foot, forearm, and PBMCs using single-cell RNA sequencing (scRNASeq) approach. Our analysis shows enrichment of a unique population of fibroblasts overexpressingMMP1, MMP3, MMP11, HIF1A, CHI3L1, andTNFAIP6genes and M1 macrophage polarization in the DFU patients with healing wounds. Further, scRNASeq of spatially separated samples from same patient and spatial transcriptomics (ST) revealed preferential localization of these healing associated fibroblasts toward deep wound/ulcer bed as compared to wound edge or non-wounded skin. ST also validated our findings of higher enrichment of M1 macrophages in healers and M2 macrophages in non-healers. Our analysis provides deep insights into the wound healing microenvironment, identifying cell types that could be critical in promoting DFU healing, and may inform novel therapeutic approaches for DFU treatment.
Behavioral read out of population value signals in primate orbitofrontal cortex
Authors: McGinty Vincent B. , Lupkin Shira M.
Published: March 2021

The primate orbitofrontal cortex (OFC) has long been recognized for its role in value-based decisions; however, the exact mechanism linking OFC value representations to decision outcomes has remained elusive. To address this question we show for the first time that trial-wise variability in choices can be explained by variability in value signals decoded from many simultaneously recorded OFC neurons. Mechanistically, this relationship is consistent with the projection of activity within a low-dimensional value-encoding subspace onto a potentially higher-dimensional, behaviorally-potent output subspace.
Neural Correlates of Reactivation and Vividness Reveal Separable Contributions to Objective and Subjective Measures of Episodic Memory
Authors: Barker Ryan M. , St-Laurent Marie , Buchsbaum Bradley R.
Published: March 2021

Episodic recollections vary in fidelity, sharpness, and strength—qualities that can be examined using both introspective judgements of mental states and objective measures of brain activity. Subjective and objective measures are both valid ways of “reading out” the content of someone’s internal mnemonic states, each with different strengths and weaknesses. St-Laurent and colleagues (2015) investigated the neural correlates of memory vividness ratings and neural reactivation during memory recall and found considerable overlap, suggesting common neural basis underlying these different markers of successful recollection. Here we extended this work with a much more extensive examination in which we used meta-analytic methods to pool four neuroimaging datasets in order to compare and contrast the neural substrates of neural reactivation and vividness judgements. While reactivation and vividness judgements correlated positively with one another and were associated with common univariate activity in the dorsal attention network and anterior hippocampus, some differences were also observed. Vividness judgments were tied to stronger activation in the striatum and dorsal attention network, together with suppression of default mode network nodes, and we also observed a trend for reactivation to be more closely associated with early visual cortex activity. A mediation analysis found support for the hypothesis that neural reactivation is necessary for vivid recollection, with activity in the anterior hippocampus associated with greater reactivation. Our results suggest that neural reactivation and vividness judgements reflect common recollective processing but differ in the extent to which they engage effortful, attentional processing. Additionally, the similarity between reactivation and vividness appears to arise, partly, through hippocampal processing during recollection.
3D soft hydrogels induce human mesenchymal stem cells “deep” quiescence
Authors: Gomes David Boaventura , Henriques Lourenço Ana Filipa , Tomasina Clarissa , Chömpff Bryan , Liu Hong , Bouvy Nicole , Camarero-Espinosa Sandra , Moroni Lorenzo
Published: March 2021

Human mesenchymal stem/stromal cells (hMSCs) present a great opportunity for tissue regeneration due to their multipotent capacity. However, when cultured on 2D tissue culture polystyrene (TCPS) plates, hMSCs lose their differentiation capacity and clinical potential. It has been reported that cells need a more physiologically relevant micro-environment that allows them to maintain their phenotype. Here, we have developed a 3D alginate hydrogel functionalized with the Arg-Gly-Asp (RGD) sequence and having low mechanical stiffness that mimics the mechanical properties (>5 KPa) of bone marrow. hMSCs cultured in these hydrogels appeared to be halted in G1phase of the cell cycle and to be non-proliferative, as shown by flow cytometry and 5-Ethynyl-2’-deoxyuridine (EdU) staining, respectively. Their quiescent state was characterized by an upregulation of enhancer of zeste homolog 1 (EZH1) at the gene level, forkhead box O3 (FoxO3) and cyclin-dependent kinase inhibitor 1B (p27) at the gene and protein levels compared to hMSCs grown in 2D TCPS. Comparative studies in 3D hydrogels of alginate-RGD presenting higher concentration of the peptide or in collagen hydrogels revealed that independently of the concentration of RGD or the chemistry of the adhesion motives, hMSCs cultured in 3D presented a similar phenotype.

This quiescent phenotype was exclusive of 3D cultures. In 2D, even when cells were starved of fetal bovine serum (FBS) and became also non-proliferative, the expression of these markers was not observed. We propose that this difference may be the result of mammalian target of rapamycin complex 1 (mTORC1) being downregulated in hMSCs cultured in 3D hydrogels, which induces cells to be in “deep” quiescence and be kept aliveex vivofor a long period of time. Our results represent a step forward towards understanding hMSCs quiescence and its molecular pathways, providing more insight for hMSCs cell therapies.
A dynamic equilibrium between TTP and CPEB4 controls mRNA stability and inflammation resolution
Authors: Suñer Clara , Sibilio Annarita , Martín Judit , Castellazzi Chiara Lara , Reina Oscar , Dotu Ivan , Caballé Adrià , Rivas Elisa , Calderone Vittorio , Díez Juana , Nebreda Angel R. , Méndez Raúl
Published: March 2021

Temporal control of inflammation is critical to avoid pathological developments, and is largely defined through the differential stabilities of mRNAs. While TTP-directed mRNA deadenylation is known to destabilize ARE-containing mRNAs, this mechanism alone cannot explain the variety of mRNA expression kinetics observed during inflammation resolution. Here we show that inflammation resolution requires CPEB4 expression,in vitroandin vivo. Our results identify that CPEB4-directed polyadenylation and TTP-mediated deadenylation compete during the resolutive phase of the LPS response to uncouple the degradation of pro-inflammatory mRNAs from the sustained expression of anti-inflammatory mRNAs. The outcome of this equilibrium is quantitatively defined by the relative number of CPEs and AREs in each mRNA, and further shaped by the coordinated regulation by the MAPK signalling pathway of the levels and activities of their trans-acting factors, CPEB4 and TTP. Altogether, we describe a temporal- and transcript-specific regulatory network controlling the extent of the inflammatory response.
Seronegative MSM at high-risk of HIV-1 acquisition show Immune quiescent profile with normal immune response against common antigens
Authors: Ossa-Giraldo Ana C. , Blanquiceth Yurany , Flórez-Álvarez Lizdany , Contreras-Ramírez Katherin , Rojas Mauricio , Hernandez Juan C. , Zapata Wildeman
Published: March 2021

HIV infection still represents a major public health problem worldwide, and a vaccine remains elusive. The study of HIV-exposed seronegative individuals (HESN) brings important information about the natural resistance to HIV, allows a better understanding of the infection and opens doors for new preventive and therapeutic strategies. Among HESN groups there are some men who have sex with men (MSM) with high-risk sexual behaviors, who represent an adequate cohort for the study of HESN because of their major exposure to HIV in the absence of infection. This study aimed to compare the immunological profile of Colombian seronegative MSM with different risk sexual behaviors. Sixty MSM at high-risk (n=16) and low-risk (n=44) of HIV-1 acquisition were included. No sex worker nor homozygous delta 32 mutation subjects were included. All the participants were negative for anti-HIV-1/2 antibodies and HIV-1 proviral DNA. The high-risk MSM presented a higher frequency of sexual partners in the last 3 months previous to the study’s enrollment (Median 30 vs. 2), lifetime sexual partners (Median 1708 vs. 26), and unprotected anal intercourse (Median 12.5 vs. 2) than low-risk MSM. This group also showed a quiescent profile of T cells and NK cells, with a significantly lower percentage of CD4+CD38+, CD4+HLADR-CD38+, CD4+Ki67+ T cells, NKG2D+ NK cells (CD3-CD16+CD56+), a significantly higher percentage of CD4+HLADR-CD38- and a tendency to show a higher percentage of CD8+HLADR+CD38-T cells, than the low-risk group. Likewise, they showed higher mRNA levels of Serpin A1 from PBMCs. The results suggest that this cohort of MSM could be HESN individuals and their resistance would be explained by a quiescent profile of T cells and NK cells, and increased expression of Serpin A1. It is necessary to continue the study of MSM at high-risk of exposure to HIV-1 to better understand the natural resistance to HIV.
Stereo Slant Discrimination of Planar 3D Surfaces: Standard vs. Planar Cross-Correlation
Authors: Oluk Can , Bonnen Kathryn , Burge Johannes , Cormack Lawrence K. , Geisler Wilson S.
Published: March 2021

Binocular stereo cues are important for discriminating 3D surface orientation, especially at near distances. We devised a single-interval task where observers discriminated the slant of a densely textured planar test surface relative to a textured planar surround reference surface. Although surfaces were rendered with correct perspective, the stimuli were designed so that the binocular cues dominated performance. Slant discrimination performance was measured as a function of the reference slant and the level of uncorrelated white noise added to the test-plane images in the left and right eye. We compared human performance with an approximate ideal observer (planar cross correlation, PCC) and two sub-ideal observers. The PCC observer uses the image in one eye and back projection to predict the test image in the other eye for all possible slants, tilts, and distances. The estimated slant, tilt, and distance are determined by the prediction that most closely matches the measured image in the other eye. The first sub-ideal observer (local PCC, LPCC) applies planar cross correlation over local neighborhoods and then pools estimates across the test plane. The second sub-optimal observer (standard cross correlation, SCC), uses only positional disparity information. We find that the ideal observer (PCC) and the first sub-ideal observer (LPCC) outperform the second sub-ideal observer (SCC), demonstrating the benefits of structural disparities. We also find that all three model observers can account for human performance, if two free parameters are included: a fixed small level of internal estimation noise, and a fixed overall efficiency scalar on slant discriminability.

Precis

We measured human stereo slant discrimination thresholds for accurately-rendered textured surfaces designed so that performance is dominated by binocular-disparity cues. We compared human performance with an approximate ideal observer and two sub-ideal observers.
Generation of fluorescent HCV pseudoparticles to study early viral entry events-involvement of Rab1a in HCV entry
Authors: Bhattacharjee Chayan , Mukhopadhyay Aparna
Published: March 2021

Understanding the early events in viral biology holds the key to the development of preventives. In this study fluorescent Hepatitis C Virus pseudoparticles have been generated where the envelope glycoprotein has a GFP tag. Using these pseudoparticles entry assays were conducted where the entry of the pseudoparticles was tracked via confocal microscopy. Using this system, fusion of host and viral membranes is predicted to occur within 15 minutes of entry in HCV. Using cells with a knockdown for Rab1a, HCV trafficking was observed to be altered, indicating a role of Rab1a in HCV trafficking. In conclusion, this study reports the generation and use of fluorescent pseudoparticles which may be used to understand the early events of viral entry. This system may be adapted for the study of other enveloped viruses as well.

Highlights

Fluorescent HCV pseudoparticles have been created to study early entry events.

HCV entry tracking via confocal microscopy reveals fusion within 15 minutes.

Rab1a is important for HCV trafficking within the cell.
Exponentiating pixel values for data augmentation to improve deep learning image classification in chest X-rays
Authors: Usuzaki Takuma , Takahashi Kengo , Shimokawa Daiki , Shibuya Kiichi
Published: March 2021

A previous study reported that exponentiating pixel values of a medical can be used for DA through enhancing contrast of the image. However, it is still unclear whether exponentiating pixel values of CXR images can be used for DA with CNN. The aim of this study is to evaluate the effectiveness of exponentiating pixel values for DA using CNN in the task of classifying normal and abnormal CXR images. In constructing an image for DA, each pixel value of the original images was exponentiated by the exponent ranging from 1 to 10, incrementing by 0.5. We call this image as exponentiated image (EI). For each exponent (1.0, 1.5, 1.5, 2.0,…, 10.0), the CNN model was trained using the original training dataset and EI for 40 epochs. Test accuracy was calculated at the end of each epoch using the test dataset. The maximum test accuracy (MTA) among the 40 test accuracies was saved for statistical analysis. This process was repeated 50 times for each exponent (1.0, 1.5, 1.5, 2.0,…, 10.0). The mean MTA for each exponent (1.5, 1.5, 2.0,…, 10.0) was compared using Student’s t-test, to that of 1.0. The mean MTA when the exponent was 1.0 was 0.749 (reference). The mean MTA was higher than the reference at exponent values 4.5(MTA=0.762, p-value=0.014), 5.0(0.762, 0.019), 5.5(0.772, 2.9 × 10-5), and 6.5(0.763, 0.010). Exponentiating pixel values can be used for DA with CNN to classify normal and abnormal CXR images.
Epigenetic switching outcompetes genetic mutations during adaptation to fluctuating environments
Authors: Stajic Dragan , Bank Claudia , Gordo Isabel
Published: March 2021

Epigenetic inheritance allows for the emergence of phenotypic plasticity in clonal populations and enables the rapid stochastic switching between distinct phenotypes. In natural environments, where stress conditions can recurrently fluctuate, clones with an epigenetic control of genes targeted by selection should be fitter than clones that rely solely on genetic mutation. To test this prediction, we engineered switcher and non-switcher yeast strains, where the uracil biosynthesis geneURA3is under fluctuating selection. Competitions of clones with an epigenetically controlledURA3with clones without switching ability (SIR3knock-out), show that epigenetic switching dominates under rapidly changing stresses. We further show that this advantage depends both on the switching rate and the period of environmental fluctuations. Remarkably, epigenetic clones with a high, but not with a low, rate of switching can co-exist with non-switchers even under a constant selective pressure, consistent with different constraints on the evolution of the rate of epigenetic switching.
Profiling of cytokines, chemokines and growth factors in saliva and gingival crevicular fluid
Authors: Liu Yong , Zhao Renping , Reda Bashar , Yang Wenjuan , Hannig Matthias , Qu Bin
Published: March 2021

In saliva and gingival crevicular fluid (GCF) soluble factors such as cytokines, chemokines and growth factors have shown a great potential serving as biomarkers for early detection and/or diagnosis of oral and systemic diseases. However, GCF and saliva, which one is a better source is still under debate. This study aimed to gain an overview of cytokines, chemokines and growth factors in saliva and GCF to pave the way for selecting suitable oral fluids for oral and systemic diseases. Multiplex cytokine assay was conducted to determine concentrations of cytokines, chemokines and growth factors in saliva and GCF samples from healthy subjects. The protocol for sample collection was carefully optimized. Stabilization, repeatability, and donor variation of the profiles were analyzed. We found that for different donors, cytokine and chemokine profiles showed unique patterns in saliva but similar patterns in GCF. In terms of growth factors, the profiles were individualized in saliva and GCF. All profiles stayed stable for the same healthy individual. In saliva, profiles of cytokines, chemokines and growth factors are individualized for different donors. In GCF, profiles of cytokines and chemokines are similar. Other factors, such as growth factors and T helper-related cytokines, are highly variable in donors. Profiles of soluble factors are not correlated in saliva and GCF. The comprehensive cytokine profiles in saliva and GCF reported in this work would serve as a good base for choosing promising cytokines for developing biomarkers in oral fluids.
TNF Blockade Reduces Prostatic Hyperplasia and Inflammation while Limiting BPH Diagnosis in Patients with Autoimmune Disease
Authors: Vickman Renee E. , Aaron-Brooks LaTayia , Zhang Renyuan , Lanman Nadia A. , Lapin Brittany , Gil Victoria , Greenberg Max , Sasaki Takeshi , Cresswell Gregory M. , Broman Meaghan M. , Petkewicz Jacqueline , Talaty Pooja , Helfand Brian T. , Glaser Alexander P. , Wang Chi-Hsiung , Franco Omar E. , Ratliff Timothy L. , Nastiuk Kent L. , Crawford Susan E. , Hayward Simon W.
Published: March 2021

Benign prostatic hyperplasia (BPH) is ostensibly linked to autoimmune (AI) diseases, but whether the prostate is a target of systemic inflammation associated with AI conditions is unknown. Prostatic inflammation is linked to fibrosis, hyperplasia, and reduced responses to BPH-related medical therapies. This study was conducted to determine if AI disease correlates with BPH diagnosis and whether systemic targeting of an inflammatory mediator limits prostatic inflammation and hyperplasia. Patient medical records (n=112,152) were evaluated to determine BPH prevalence among different AI diseases. Inflammatory cells from human BPH tissues were analyzed by single-cell (sc)RNA-seq and the tumor necrosis factor (TNF)α-antagonist etanercept was tested in two murine models of prostatic enlargement. BPH prevalence was significantly higher among patients with AI disease compared to unaffected individuals. However, AI patients treated with TNFα-antagonists had a significantly reduced incidence of BPH. Data from scRNA- seq identified macrophages as a dominant source of TNFα andin vitroassays confirmed that TNFα stimulates BPH-derived fibroblast proliferation. In the AI patient cohort and murine models, systemic treatment with TNFα-antagonists decreased prostatic epithelial proliferation, macrophage infiltration, and epithelial NFκB activation compared to control tissues. These studies are the first to show that patients with AI diseases have a heightened susceptibility to BPH and that the TNFα-signaling axis is important for BPH pathogenesis. Macrophage-secreted TNFα may mechanistically drive BPH via chronic activation of the signaling axis and NFκB. TNFα blockade appears to be a promising new pharmacological approach to target inflammation and suppress BPH.

One sentence summary

Patient data and mouse models suggest that repurposing tumor necrosis factor alpha blockade reduces inflammation-mediated prostatic hyperplasia.
Embryo development inCarica papayaLinn
Authors: Acevedo-Benavides Miguel , Bolaños-Villegas Pablo
Published: March 2021

Papaya (Carica papayaLinn.) is a tropical plant whose draft genome has been sequenced. Papaya produces large fruits rich in vitamins A and C and is an important cash crop in developing countries. Nonetheless, little is known about how the female gametophyte develops, how it is fertilized and how it develops into a mature seed containing an embryo and an endosperm. The Papaya female gametophyte displays aPolygonum-type architecture consisting of two synergid cells, an egg cell, a central cell, and three antipodal cells. Reports are available of the presumed existence of varieties in which cross fertilization is bypassed and autonomous development of embryos occurs (e.g., apomixis). In this study, we analyzed the development of female gametophytes in a commercial Hawaiian parental line and in the presumed apomictic Costa Rican line L1. Samples were collected before and after anthesis to compare the overall structure, size and transcriptional patterns of several genes that may be involved in egg and endosperm cell fate and proliferation. These genes were the putative papaya homologs ofARGONAUTE9(AGO9),MEDEA(MEA),RETINOBLASTOMA RELATED-1(RBR1), andSLOW WALKER-1(SWA1). Our results suggest that its feasible to identify the contour of structural features ofPolygonum-type development, and that in bagged female flowers of line L1 we might have observed autonomous development of embryo-like structures. Possible downregulation of papaya homologs forAGO9, MEA, RBR1andSWA1was observed in embryo sacs from line L1 before and after anthesis, which may suggest a tentative link between suspected apomixis and transcriptional downregulation of genes for RNA-directed DNA methylation, histone remodelers, and rRNA processing. Most notably, the large size of the papaya embryo sac suggests that it could be a cytological alternative toArabidopsis thalianafor study. Significant variation in embryo sac size was observed between the varieties under study, suggesting wide differences in the genetic regulation of anatomical features.
NCoR1 and SMRT fine-tune inflammatory versus tolerogenic balance in dendritic cells by differentially regulating STAT3 signaling
Authors: Jha Atimukta , Ahad Abdul , Mishra Gyan Prakash , Sen Kaushik , Smita Shuchi , Minz Aliva P , Biswas Viplov Kumar , Tripathy Archana , Senapati Shanti Bhushan , Gupta Bhawna , Orbea Hans Acha , Raghav Sunil Kumar
Published: March 2021

Dendritic cell (DC) fine-tunes inflammatory versus tolerogenic responses to protect from immune-pathology. However, the role of co-regulators in maintaining this balance is unexplored. NCoR1-mediated repression of DC immune-tolerance has been recently reported. Here we found that depletion of NCoR1 paralog SMRT (NCoR2) enhanced cDC1 activation and expression of IL-6, IL-12 and IL-23 while concomitantly decreasing IL-10 expression/secretion. Consequently, co-cultured CD4+and CD8+T-cells depicted enhanced Th1/Th17 frequency and cytotoxicity, respectively. Comparative genomic and transcriptomic analysis demonstrated differential regulation of IL-10 by SMRT and NCoR1. SMRT depletion represses mTOR-STAT3-IL10 signaling in cDC1 by downregulating NR4A1. Besides,NfkbiaandSocs3were down-regulated inNcor2(Smrt) knockdown cDC1, supporting increased production of inflammatory cytokines. Moreover, studies in mice showed, adoptive transfer of SMRT knockdown cDC1 in OVA-DTH induced footpad inflammation led to increased Th1/Th17 and reduced tumor burden after B16 melanoma injection by enhancing oncolytic CD8+T-cell frequency, respectively. We also depicted decreasedNcor2expression in Rheumatoid Arthritis, a Th1/Th17 disease.
Information flows from hippocampus to auditory cortex during replay of verbal working memory items
Authors: Dimakopoulos Vasileios , Mégevand Pierre , Stieglitz Lennart , Imbach Lukas , Sarnthein Johannes
Published: March 2021

The maintenance of items in working memory relies on a widespread network of cortical areas and hippocampus where synchronization between electrophysiological recordings reflects functional coupling.

We investigated the direction of information flow between auditory cortex and hippocampus while participants heard and then mentally replayed strings of letters in working memory by activating their phonological loop. We recorded LFP from the hippocampus, reconstructed beamforming sources of scalp EEG, and - additionally in 3 participants – recorded from subdural cortical electrodes. When analyzing Granger causality, the information flow was from auditory cortex to hippocampus with a peak in the 4-8 Hz range while participants heard the letters. This flow was subsequently reversed during maintenance while participants maintained the letters in memory. The functional interaction between hippocampus and the cortex and the reversal of information flow provide a physiological basis for the encoding of memory items and their active replay during maintenance.
A PX-BAR protein Mvp1/SNX8 and a dynamin-like GTPase Vps1 drive endosomal recycling
Authors: Suzuki Sho W. , Oishi Akihiko , Nikulin Nadia , Jorgensen Jeff R. , Baile Matthew G. , Emr Scott D.
Published: March 2021

Membrane protein recycling systems are essential for maintenance of the endosome-lysosome system. In yeast, retromer and Snx4 coat complexes are recruited to the endosomal surface where they recognize cargos. They sort cargo and deform the membrane into recycling tubules that bud from the endosome and target to the Golgi. Here, we reveal that the SNX-BAR protein, Mvp1, mediates an endosomal recycling pathway which is mechanistically distinct from the retromer and Snx4 pathways. Mvp1 deforms the endosomal membrane and sorts cargos containing a specific sorting motif into a membrane tubule. Subsequently, Mvp1 recruits the dynamin-like GTPase Vps1 to catalyze membrane scission and release of the recycling tubule. Similarly, SNX8, the human homolog of Mvp1, which has been also implicated in Alzheimer’s disease, mediates formation of an endosomal recycling tubule. Thus, we present evidence for a novel endosomal retrieval pathway that is conserved from yeast to humans.

In Brief

PX-BAR Mvp1 and dynamin-like GTPase Vps1 drive retromer independent endosomal recycling.

Highlights

Retromer- and Snx4-independent endosomal recycling pathway discovered

SNX-BAR Mvp1 and dynamin-like GTPase Vps1 mediate cargo sorting into recycling tubules/vesicles in the absence of retromer function

Mvp1 together with retromer and Snx4 complexes contribute to proper endosome function

Mvp1 mediated recycling is evolutionary conserved from yeast to humans

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Dosage sensitivity in Pumilio1-related phenotypes reflects distinct disease mechanisms
Authors: Botta Salvatore , de Prisco Nicola , Chemiakine Alexei , Cabaj Maximilian , Patel Purvi , Doron-Mandel Ella , Treadway Colton J. , Jovanovic Marko , Brown Nicholas G. , Soni Rajesh K. , Gennarino Vincenzo A.
Published: March 2021

Mutations in the RNA-binding protein (RBP) Pumilio1 (PUM1) can cause dramatically different phenotypes. We previously noted that phenotypic severity tracked with protein dosage: a mild mutation that reduces PUM1 levels by 25% causes late-onset ataxia, whereas PUM1 haploinsufficiency causes developmental delay and seizures. Why this difference in expression should cause such different phenotypes has been unclear: PUM1 targets are de-repressed to equal degrees in both cases, and the more severe mutation does not hinder PUM1’s RNA-binding ability. We therefore developed a PUM1 interactome in the murine brain. We find that mild PUM1 loss de-represses PUM1-specific targets, but PUM1 haploinsufficiency disrupts several interactors and regulation of their targets. We validated these phenomena in patient-derived cell lines and show that normalizing PUM1 levels restores interactors and their targets to proper levels. We therefore propose that dosage sensitivity does not necessarily reflect a linear change in protein abundance but can involve distinct mechanisms. Studying the interactors of RBPsin vivowill be necessary to understand their functions in neurological diseases.
Reevaluating claims of ecological speciation inHalichoeres bivittatus
Authors: Warren Dan L. , Eytan Ron I. , Dornburg Alex , Iglesias Teresa L. , Brandley Matthew C. , Wainwright Peter C.
Published: March 2021

Understanding the role of ecological processes in speciation has become one of the most active areas of research in marine population biology in recent decades. The traditional view was that allopatry was the primary driver of speciation in marine taxa, but the geography of the marine environment and the dispersal capabilities of many marine organisms render this view somewhat questionable. One of the earliest and most highly cited empirical examples of ecological speciation with gene flow in marine fishes is that of the slippery dick wrasse,Halichoeres bivittatus. Evidence for this cryptic or incipient speciation event was primarily in the form of a deep north-south divergence in a single mitochondrial locus, combined with a finding that these two haplotypes were associated with different habitat types in the Florida Keys and Bermuda, where they overlap. Here we examine habitat assortment in the Florida Keys using a broader sampling of populations and habitat types than were available for the original study, and find no evidence to support the claim that haplotype frequencies differ between habitat types, and little evidence to support any differences between populations. These results severely undermine claims of ecological speciation with gene flow inHalichoeres bivittatus. We argue that future claims of this type should be supported by multiple lines of evidence that illuminate potential mechanisms and allow researchers to rule out alternative explanations for spatial patterns of genetic differences.
Qualification of the UniBw protection concept in different rooms of the Obermenzinger high school
Authors: Kähler Christian J. , Fuchs Thomas , Hain Rainer
Published: March 2021

Current research has shown that SARS-CoV-2 is transmitted via airborne particles. These particles are generated when infected persons exhale and they spread throughout the room, resulting in a high concentration and thus a high risk of infection of non-infected persons. One way to reduce the concentration of particles is to filter them using mobile room air cleaners, which can be easily set up and reduce the concentration of viruses or keep them at a low level. Since many studies are conducted in generic rooms, the question of the cleaning performance of such room air cleaners in real rooms arises. In order to investigate this, measurements of the effectiveness were carried out in a total of 4 different rooms of the “Obermenzinger Gymnasium” (Obermenzinger high school) in Munich. It can be shown that good effects of the room air cleaners are achieved even under realistic conditions. Even Plexiglas screens, which serve as protection against direct infection, have no negative influence.
Modelling, prediction and design of national COVID-19 lockdowns by stringency and duration
Authors: Mellone Alberto , Gong Zilong , Scarciotti Giordano
Published: March 2021

The implementation of lockdowns has been a key policy to curb the spread of COVID-19 and to keep under control the number of infections. However, quantitatively predicting in advance the effects of lockdowns based on their stringency and duration is a complex task, in turn making it difficult for governments to design effective strategies to stop the disease. Leveraging a novel mathematical “hybrid” approach, we propose a new epidemic model that is able to predict the future number of active cases and deaths when lockdowns with different stringency levels or durations are enforced. The key observation is that lockdown-induced modifications of social habits may not be captured by traditional mean-field compartmental models because these models assume uniformity of social interactions among the population, which fails during lockdown. Our model is able to capture the abrupt social habit changes caused by lockdowns. The results are validated on the data of Israel and Germany by predicting past lockdowns and providing predictions in alternative lockdown scenarios (different stringency and duration). The findings show that our model can effectively support the design of lockdown strategies by stringency and duration, and quantitatively forecast the course of the epidemic during lockdown.
Novel aluminophosphate Na6[Al3P5O20] with the original microporous crystal structure established in the study of a pseudomerohedric microtwin
Authors: Yakubovich Olga V. , Kiriukhina Galina V. , Volkov Anatoliy S. , Dimitrova Olga V. , Borovikova Elena Yu.
Published: March 2021

The synthesis and characterization of a new aluminophosphate, Na6[Al3P5O20], obtained as single crystals in the same experiment together with Cl-sodalite, Na8[Al6Si6O24]Cl2, is reported. Na6[Al3P5O20], with a strongly pseudo-orthorhombic lattice, is described by the monoclinic crystal structure established in the study of a pseudomerohedric microtwin. The design of Na6[Al3P5O20] can be interpreted as an alternative to sodalite, with a monoclinic (pseudo-orthorhombic) 2×4×1 super-structure and unit-cell parameters multiples of those of sodalite: a ≃ 2a
s, b ≃ 4b
s and c ≃ c
s. The triperiodic framework is built by AlO6, AlO4 and PO4 polyhedra having vertex-bridging contacts. While all the oxygen vertices of the Al-centred octahedra and tetrahedra are shared with phosphate groups, some of the PO4 tetrahedra remain `pendant', e.g. containing vertices not shared with other polyhedra of the aluminophosphate construction. Na atoms occupy framework channels and cavities surrounded by eight-, six- and four-membered windows with maximal effective pore widths of 4.86 × 3.24 and 4.31 × 3.18 Å. The generalized framework density is equal to 19.8, which means that the compound may be classified as a microporous zeolite. The Na6[Al3P5O20] crystal structure is discussed as being formed from octahedral rods arranged in two perpendicular directions, similar to the rods elongated in one direction in the NASICON-type compounds, which have been intensively investigated as promising materials for batteries. Analogous properties can be expected for phases with a modified composition of the Na6Al3P5O20 topology, where the Al atoms at the centres of octahedra are replaced by Fe, V or Cr.
BCG and COVID-19: correlation or causality or neither?
Authors: Chiba Manoj Dayal , Verachia Abdullah
Published: March 2021

Learning outcomes

The learning outcome is to understand the difference between correlation and causation.

Case overview/synopsis

The case is set during the period of the COVID-19 pandemic, globally a search for effective treatments were underway. An initial forerunner that was being considered was Bacille Calmette-Guerin (BCG), given its effectiveness in the treatment of tuberculosis and other pulmonary-related infections. While there were a lack of randomised controlled trials, initial data from publicly related secondary data sources indicated that, in countries with BCG inoculation policies, the severity of the spread and mortality of COVID-19 was muted. The case is centered around the available information on BCG and COVID-19.

Complexity academic level

Post-graduate students learning statistics as part of a degree programme. The case assumes no prior statistics knowledge and therefore is aimed at teaching the difference between correlation and causation.

Subject code

CSS 7: Management Science

Supplementary materials

Teaching Notes are available for educators only.
Motivational foundations of identifying and exploiting entrepreneurial opportunities
Authors: Maran Thomas K. , Bachmann Anna K. , Mohr Christine , Ravet-Brown Theo , Vogelauer Lukas , Furtner Marco
Published: March 2021

Purpose

Motivation can serve as the engine that turns intention into action, and, as such, is indispensable in the early phase of the entrepreneurial process, where opportunity recognition and exploitation are key. However, research in this area has so far shed a selective spotlight on specific facets of entrepreneurial motivation, whereas the consideration of basic motives has been widely neglected. Hence, the purpose of this paper is to illuminate the basic motivational foundations of one core aspect of entrepreneurial behavior, namely opportunity recognition.

Design/methodology/approach

The study examined how motivation influences the process of recognizing and exploiting entrepreneurial opportunities in a sample of 312 managing directors and managing partners of small and medium-sized enterprises. Opportunity recognition and exploitation were assessed by two different measures: one evaluating the objective number of recognized and realized business opportunities, the other assessing the perceived proficiency in identifying and exploiting entrepreneurial opportunities. Implicit and explicit facets of basic motivation were measured using a comprehensive assessment of human needs.

Findings

Findings show that entrepreneurs' achievement motive is an important driver in both the identification and exploitation of opportunity. The power motive affects the perceived ability to exploit business opportunities. Interestingly, the explicit affiliation motive showed an inhibitory effect on the perceived ability of opportunity identification, whereas implicit affiliation motive is affecting the number of recognized and realized business opportunities positively.

Originality/value

This research clearly highlights the preeminence of basic motivational factors in explaining individual early-stage entrepreneurial behavior, making them a prime target for training interventions.
The antecedents of construction project change: an analysis of design and build procurement application
Authors: Smith Jessica , Edwards David John , Martek Igor , Chileshe Nicholas , Hayhow Susan , Roberts Chris J.
Published: March 2021

Purpose

This study aims to excoriate, define and delineate the main drivers of “change” in commercial construction projects and generate guidelines on how to minimise exposure to the associated adverse effects upon project stakeholders.

Design/methodology/approach

The research adopts mixed doctrines through a combination of epistemological lenses, embracing two primary philosophical stances: interpretivism, to identify the primary drivers of change based on a systematic literature review and a post-positivist, inductive approach to analyse the results of change within a Joint Contracts Tribunal (JCT) Design and Build (D&B) construction project case study.

Findings

The causal nexus of change during the construction phase is assessed and delineated; the key affecting factors are thematically grouped under headings: extent and severity; time in relation to implementing; instigating party; individual(s) responsible for managing the change; reason for the change; available resource; recoverable or non-recoverable; contract/project type; and type of client. Following this, the effects of change on key elements of the project are encapsulated and recommendations for adaptations which may provide improved experiences are offered.

Originality/value

The study tackles the common issue of managing the deleterious effects of change on commercial construction projects, defining management techniques to minimise stakeholder tribulation.
Minority shareholder treatment surrounding the Dell MBO
Authors: Kruse Timothy A.
Published: March 2021

Purpose

This paper is a clinical examination of the October 2013 Management Buyout of Dell Inc. by founder Michael Dell and Silver Lake Partners for a total consideration of $13.88 per share. The proposed transaction was targeted by shareholders unhappy with the deal price and voting framework. Various shareholders went on to file an appraisal suit. Examining these events yields insights into shareholder rights issues in a major transaction.

Design/methodology/approach

The paper examines events surrounding the acquisition including the negotiation process, go-shop period, shareholder activist demands for a higher price, shareholder voting and the subsequent appraisal trial and appeal.

Findings

Despite suggesting Dell's board fulfilled its fiduciary duties, Delaware Vice Chancellor Travis Laster awarded petitioning shareholders $17.62 per share, a 27% premium to the final deal consideration. This article draws on Laster's decision and research examining topics raised by the surrounding events to argue minority shareholder interests were not sufficiently protected.

Research limitations/implications

The Dell transaction represents only one data point. Moreover, Vice Chancellor Laster's decision was reversed on appeal.

Originality/value

Nevertheless, the paper discusses the nuances surrounding many issues of interest to practitioners involving large going private transactions. It could also be used to illustrate many “real world” perspectives in an advanced corporate finance or mergers and acquisitions class.
Nurses burnout, resilience and its association with safety culture: a cross sectional study
Authors: Majrabi Mohammed A. , Hasan Abd Alhadi , Alasmee Nofaa
Published: March 2021

Purpose

The purpose of this study was to assess burnout, resilience and the association with safety culture in nurses working in mental health institutions in Jazan government Hospital.

Design/methodology/approach

A cross-sectional survey using convenience sampling, with 119 nurses from the Jazan hospital between June and August 2018 was used.

Findings

The results of this study showed that 45.6% of the participants experienced a high level of emotional exhaustion, 36.5% reported a high level of depersonalisation and 15.9% reported high personal achievement. The high level of burnout and its dimensions have a negative effect on patient safety and resilience.

Originality/value

It is particularly important to assess burnout among mental health nurses, resilience and its association with safety culture. Although this study will add to a small body of knowledge, it will also be able to provide policymakers with evidence as how best to reduce burnout among nurses delivering mental health care in Saudi Arabia.
‘Making Black More Beautiful’: Black Women and the Cosmetics Industry in the Post‐Civil Rights Era
Authors: Baird Melissa L.
Published: March 2021

This article explores how the ‘Black is Beautiful’ movement transformed attitudes towards beauty standards within black communities and how the cosmetics industry tried to capitalise on these shifts in their marketing strategies. It charts how redefined beauty standards generated a proliferation of cosmetics companies and products exclusively for black women, and their success attracted widespread attention from across the industry. However, this article demonstrates that while the cosmetics industry removed certain racialised barriers to mainstream American beauty culture, the commodification of the language and imagery of “Black is Beautiful” in cosmetics advertising often reinforced gendered expectations as well as heightening tensions within black communities in regard to colourism and business ownership.
B‐cell capacity for differentiation changes with age
Authors: Xie Xuanxiao , Shrimpton Jennifer , Doody Gina M. , Conaghan Philip G. , Ponchel Frederique
Published: March 2021

Background

Age‐related immune deficiencies are thought to be responsible for increased susceptibility to infection in older adults, with alterations in lymphocyte populations becoming more prevalent over time. The loss of humoral immunity in ageing was attributed to the diminished numbers of B cells and the reduced ability to generate immunoglobulin.

Aims

To compare the intrinsic B‐cell capacity for differentiation into mature plasma cells (PCs), between young and old donors, using in vitro assays, providing either effective T‐cell help or activation via TLR engagement.

Methods

B cells were isolated from healthy individuals, in younger (30–38 years) and older (60–64 years) donors. An in vitro model system of B‐cell differentiation was used, analysing 5 differentiation markers by flow cytometry, under T‐dependent (TD: CD40/BCR stimulation) or T‐independent (TI: TLR7/BCR activation) conditions. Antibody secretion was measured by ELISA and gene expression using qPCR.

Results

TI and TD differentiation resulted in effective proliferation of B cells followed by their differentiation into PC. B‐cell‐executed TI differentiation was faster, all differentiation marker and genes being expressed earlier than under TD differentiation (day 6), although generating less viable cells and lower antibody levels (day 13). Age‐related differences in B‐cell capacity for differentiation were minimal in TD differentiation. In contrast, in TI differentiation age significantly affected proliferation, viability, differentiation, antibody secretion and gene expression, older donors being more efficient.

Conclusion

Altogether, B‐cell differentiation into PC appeared similar between age groups when provided with T‐cell help, in contrast to TI differentiation, where multiple age‐related changes suggest better capacities in older donors. These new findings may help explain the emergence of autoantibodies in ageing.
Defining a safe corridor for trans‐iliac pin placement in cats
Authors: Garcia‐Pertierra S , Meeson RL , Yeung BCY , Bedford G , Pead MJ
Published: March 2021

Objective

To identify whether a theoretical predictable safe corridor is available in cats for placement of trans‐iliac pins without the use of fluoroscopy.

Methods

Twenty‐one cats with straight orthogonal normal pelvic radiographs were included. Two start points were evaluated: a midpoint and a dorsal point. The midpoint was defined as midway between the dorsal lamina of the sacral vertebral canal and the cranial dorsal iliac spine. The dorsal start point was 2 mm ventral to the cranial dorsal iliac spine. The pin was assumed to be driven at 90 degrees to the lateral face of the ilium, and considered surgeon accuracy was ±4 degrees from the perpendicular. The angular range and the distance between the iliac wings from the ventrodorsal radiograph were used to calculate the possible cross‐sectional area and pin exit location if driven from one iliac wing to the other. The corridor was then evaluated for repeatability in six randomly selected cats.

Results

Vertebral foramina penetration risk was identified in some cats when using a 1.6 and 2 mm‐diameter pin using the mid‐iliac wing start point. The dorsal start point decreased the available pin placement area but reduced the risk of entering the hazardous zone for all pin sizes up to 2 mm.

Conclusion and Relevance

A theoretical defined safe corridor is available for trans‐iliac pin placement in cats between 2.0 and 5.5 kg. A 1.2‐mm pin is the safest if using the mid‐iliac wing start point. A more dorsal start point can accommodate up to a 2.0‐mm pin if correctly aligned to the sacrum.