bluuebunny/crossref_metadata_2025 huggingface dataset:
The Ownership of Data
Authors: Dosis Anastasios , Sand-Zantman Wilfried
Published: February 2022

We study the effects of property rights over the use of data on market outcomes. To do so, we consider a model in which a monopolistic firm offers a service to a set of heterogeneous users. The use of the service generates valuable data, but data monetization entails a privacy cost for users. A trade-off emerges between under-processing and over-monetization of data. We show that both the firm and users prefer the users (the firm) to own the rights for low (high) values of data. We further discuss the robustness of our results when allowing more possible contracts for the data owner and show that the main trade-off is robust to these extensions.
Blunt cardiac injury presenting as a left-sided coronary artery dissection
Authors: Park Alex , Principe Daniel R
Published: February 2022

The presentation of blunt cardiac injuries (BCIs) following thoracic trauma is extremely varied, classically affecting the right-sided chambers of the heart. In extremely rare cases, BCIs can affect the coronary arteries. Diagnosing a traumatic coronary dissection can be challenging, as not only is presentation highly variable, but dissections are often masked by concomitant injuries. Here, we present the unusual case of a patient presenting to the emergency department following blunt thoracic trauma from an automobile accident. He demonstrated diffuse S and T wave segment elevations on electrocardiogram, and coronary angiography was significant for occlusion of the apical left anterior descending artery and stenosis of the second obtuse marginal artery. The patient was diagnosed with a BCI causing a left-sided coronary artery dissection. This serves as an important reminder that BCIs can manifest in any part of the cardiac anatomy, and should be considered in any patient with a history of thoracic trauma.
The anchoring of long-term inflation expectations of consumers: insights from a new survey
Authors: Galati Gabriele , Moessner Richhild , van Rooij Maarten
Published: February 2022

We provide new evidence on the level and probability distribution of consumers’ long-term expectations of inflation in the euro area and the Netherlands, using a new monthly representative Dutch survey before and during the COVID-19 pandemic. We find that consumers’ expectations of euro area and Dutch inflation 10 years ahead have not been well anchored at the ECB’s inflation aim of below, but close to 2%. Median expectations have remained elevated above the European Central Bank's (ECB) inflation aim throughout the pandemic. Moreover, individual probability distributions show that expected probabilities of higher inflation (4% or higher) have continuously been larger than those of lower inflation (0% or lower). While policymakers are currently concerned about a possible de-anchoring of inflation expectations on the downside, our results suggest that from a consumer’s point of view de-anchoring of long-term inflation expectations is mainly due to expected high inflation rather than low inflation.
Exploring the basal topology of the heteronemertean tree of life: establishment of a new family, along with turbotaxonomy of Valenciniidae (Nemertea: Pilidiophora: Heteronemertea)
Authors: Kajihara Hiroshi , Abukawa Shushi , Chernyshev Alexei V
Published: February 2022

With about 480 known species, Pilidiophora (phylum Nemertea) has been regarded as consisting of Hubrechtiiformes (~20 spp.) and Heteronemertea (~460 spp.). Most (~87%) of the latter belong to Lineidae (> 400 spp.), while the systematics of non-lineid heteronemerteans remains largely untouched. To explore the phylogeny of non-hubrechtiiformid, non-lineid pilidiophorans, we performed multilocus molecular phylogenetic analyses with five genes (18S, 28S, H3, 16S and COI) from 41 newly sequenced specimens. Pilidiophora comprised Hubrechtellidae, Lineidae, Valenciniidae, the new family Eopilidiidae and a not formally named family-level heteronemertean taxon. Eopilidion misakiense gen. et sp. nov. is described from a specimen from Japan, but whether it belongs to Heteronemertea remains unclear. Apart from this new species, the following 11 new species of valenciniids are established, based on molecular sequences and external morphology (localities in parentheses): Baseodiscus giribeti sp. nov. (Panama), B. kakuii sp. nov. (Japan), B. komatsui sp. nov. (Japan), B. narusei sp. nov. (Japan), B. ohtsukai sp. nov. (Japan), B. paracelensis sp. nov. (Vietnam), B. profundus sp. nov. (Russian Far East), B. urgorrii sp. nov. (Spain), B. zebra sp. nov. (Japan), Oxypolella hiebertae sp. nov. (Vietnam) and Valencinura jambio sp. nov. (Japan).
Differences in Persistence Between Adult Learners Enrolled in Two Online RN-BSN Progression Tracks
Authors: Shroyer Ashley , Benders David , Smith Daniel J. , Hart Carolyn
Published: February 2022

The purpose of this quantitative, causal-comparative study was to examine if and to what extent differences exist for total Persistence Scale for Online Education-Nursing (PSOE-N) scores and mean persistence factor scores for adult learners enrolled in accelerated academic progression tracks (n = 18) compared with adult learners enrolled in traditional academic progression tracks (n = 26) in online RN-BSN completion programs. Total PSOE-N scores, mean perceived stress and support scores, and goal attachment scores were found to be statistically significantly different (p < .05) between participants enrolled in a traditional track compared with those enrolled in an accelerated track.
Atypical Pathogens Presenting With Pulmonary Consolidations Detected by Cell-Free DNA Next-Generation Sequencing in Patients With Hematologic Malignancies
Authors: Caldararo Mario , Algazaq Jumanah , Schmidt Elizabeth , Joanow Alexa , Mariano Amanda , Predmore Jacqueline , Politikos Ioannis , Cho Christina , Stein Eytan M. , Wen Xiaoyun , Travis William D. , Raible Kevin , Cintron Melvili , Babady N. Esther , Papanicolaou Genovefa , Lee Yeon Joo
Published: February 2022

Identification of pathogens with pulmonary presentation in patients with hematologic malignancies may be challenging because of diagnostic difficulty related to the underlying malignancy and limitations of conventional microbiologic methods. Herein, we present a case series of 3 patients with pulmonary consolidations due to Legionella bozemanae necrotizing pneumonia, Pneumocystis jirovecii pneumonia, and disseminated Scedosporium infection, who were diagnosed by microbial cell-free DNA next-generation sequencing. We observed that this new sequencing modality was in agreement with criterion standard diagnostics, posing a potential solution to the problem of limited capability in diagnosing infections in hematological malignancy patients.
Educational Interventions to Improve Graduating Nursing Students' Practice Readiness
Authors: Shatto Bobbi , Meyer Geralyn , Krieger Mary , Kreienkamp Maria Josefa , Kendall Ashley , Breitbach Nicole
Published: February 2022

Background:

For practice readiness, graduates need minimal competence in many areas. The American Association of Colleges of Nursing (AACN) identified 10 domains of competence.

Purpose:

The aim was to determine whether there is evidence of the objective assessment of learning in the senior year that aligns with the new AACN domains.

Methods:

A systematic literature review included English language, final year, baccalaureate program, and outcomes objectively measured. Master's and midwifery programs were excluded. Database searches by a reference librarian (March 24, 2020) in Scopus, CINAHL, Ovid MEDLINE, ERIC, and Web of Science resulted in 40 peer-reviewed articles. Samples ranged from 9 to 527. Three authors examined results ensuring rigor, decreasing bias, and categorizing articles into the AACN's 10 domains. MERSQI scoring was applied.

Results:

Six of the 10 domains were addressed in the literature. Many studies used investigator-developed tools with no validity or reliability.

Conclusions:

An emphasis on practice readiness means educators must be able to teach and measure critical behaviors.
Men in Nursing Academia
Authors: Hand Mark C. , Reid Ashley
Published: February 2022

Background:

Currently, there is a shortage of males holding faculty positions in schools of nursing. Minimal research has been conducted to address the shortage of male faculty.

Purpose:

The purpose of this study was to identify factors related to recruitment and retention of men in the faculty role.

Methods:

In this multisite descriptive design, 242 male faculty completed the electronic Nurse Educator Recruitment and Retention Survey.

Results:

Top strategies regarding attraction to the role were opportunity to work with students and to help shape the nursing profession, and nurse faculty role modeling. Top recruitment strategies were increased salaries, employee benefits, having discussions with students, and flexibility in working hours. Retention strategies reported were a positive work environment and support from administration.

Conclusion:

The factors identified from this study are essential for the recruitment and retention of men in faculty roles.
Nursing Students' Self-Efficacy in Immigrant Health
Authors: McDermott-Levy Ruth , Mariani Bette , Lupinacci Paul
Published: February 2022

Background:

The United States has the largest, most diverse immigrant population. Nurses will care for immigrant clients in all areas of nursing practice.

Purpose:

The purpose of this study was to determine nursing students' self-efficacy in working with immigrant clients following a service-learning experience.

Methods:

A pre-/posttest descriptive study was used to measure students' self-efficacy in cultural aspects of screening, providing health education, and assisting with health care access prior to and after a voluntary service-learning experience at a resettlement agency.

Results:

Statistical significance was found in overall scale score and in all 19 individual items except 2 related to working with (P = .21) and communicating with (P = .49) the health care team. Overall, pretest and posttest results revealed that students' self-efficacy working with immigrant clients was improved.

Conclusion:

Collaborating with an immigrant resettlement program to provide a structured immigrant health learning experience for prelicensure nursing students can improve self-efficacy in working with immigrant clients.
Surgical Complications and Hospital Costs in Robot-Assisted Versus Conventional Laparoscopic Hysterectomy With Concurrent Sacrocolpopexy: Analysis of the Nationwide Readmissions Database
Authors: Andiman Sarah E. , Bui Anthony H. , Ascher-Walsh Charles , Wright Jason D. , Xu Xiao
Published: February 2022

Objectives

Despite increasing use of robotic technology for minimally invasive hysterectomy with sacrocolpopexy, evidence supporting the benefits of these costly procedures remains inconclusive. This study aimed to compare differences in perioperative complications, 30-day readmissions, and costs between robot-assisted and conventional laparoscopic hysterectomy with concurrent sacrocolpopexy using a large national database.

Methods

Using the 2009–2015 Nationwide Readmissions Database and procedure codes, we identified patients who underwent a robot-assisted or conventional laparoscopic hysterectomy with sacrocolpopexy. We measured in-hospital perioperative complications using diagnosis and procedure codes and measured 30-day readmissions based on patient linkages across hospitalizations. Hospital costs were estimated using charges and cost-to-charge ratios. These outcomes were compared between robot-assisted and conventional laparoscopic procedures using bivariate and multivariable regression analysis.

Results

Our weighted sample included a total of 7,675 patients. Major perioperative complications occurred in 6.7% of robot-assisted and 11.2% of conventional laparoscopic procedures (unadjusted P < 0.001; adjusted odds ratio, 0.69; 95% confidence interval, 0.51–0.93; P = 0.02). Hospital costs were higher in robot-assisted than in conventional laparoscopic procedures (respective median costs, $16,367 vs $13,898; P < 0.001), with an adjusted cost ratio of 1.24 (95% confidence interval, 1.17–1.31; P < 0.001). The risk of 30-day readmission was similar between robot-assisted and conventional laparoscopic procedures.

Conclusions

Nationally representative data suggest that, in laparoscopic hysterectomy with sacrocolpopexy, the robot-assisted approach is associated with a lower risk of perioperative complications, despite higher costs, compared with the conventional one. The risk of 30-day readmission was similar between the robot-assisted and conventional laparoscopic approaches.
Pan-cancer association of DNA repair deficiencies with whole-genome mutational patterns
Authors: Sørensen Simon G. , Shrikhande Amruta , Poulsgaard Gustav A. , Christensen Mikkel H. , Bertl Johanna , Hoffmann Eva R. , Pedersen Jakob S.
Published: February 2022

DNA repair deficiencies in cancers may result in characteristic mutational patterns, as exemplified by deficiency of BRCA1/2 and efficacy prediction for PARP-inhibitors. We trained and evaluated predictive models for loss-of-function (LOF) of 145 individual DDR genes based on genome-wide mutational patterns, including structural variants, indels, and base-substitution signatures. We identified 24 genes whose deficiency could be predicted with good accuracy, including expected mutational patterns for BRCA1/2, MSH3/6, TP53, and CDK12 LOF variants. CDK12 is associated with tandem-duplications, and we here demonstrate that this association can accurately predict gene deficiency in prostate cancers (area under the ROC curve=0.97). Our novel associations include mono- or biallelic LOF variants of ATRX, IDH1, HERC2, CDKN2A, PTEN, and SMARCA4, and our systematic approach yielded a catalogue of predictive models, which may provide targets for further research and development of treatment, and potentially help guide therapy.
Replicating RNA platform enables rapid response to the SARS-CoV-2 Omicron variant and elicits enhanced protection in naïve hamsters compared to ancestral vaccine
Authors: Hawman David W. , Meade-White Kimberly , Clancy Chad , Archer Jacob , Hinkley Troy , Leventhal Shanna S. , Rao Deepashri , Stamper Allie , Lewis Matthew , Rosenke Rebecca , Krieger Kyle , Randall Samantha , Khandhar Amit P. , Hao Linhue , Hsiang Tien-Ying , Greninger Alexander L. , Gale Michael , Berglund Peter , Fuller Deborah Heydenburg , Rosenke Kyle , Feldmann Heinz , Erasmus Jesse H.
Published: February 2022

In late 2021, the SARS-CoV-2 Omicron (B.1.1.529) variant of concern (VoC) was reported with many mutations in the viral spike protein that were predicted to enhance transmissibility and allow viral escape of neutralizing antibodies. Within weeks of the first report of B.1.1.529, this VoC has rapidly spread throughout the world, replacing previously circulating strains of SARS-CoV-2 and leading to a resurgence in COVID-19 cases even in populations with high levels of vaccine- and infection-induced immunity. Initial studies have shown that B.1.1.529 is less sensitive to protective antibody conferred by previous infections and vaccines developed against earlier lineages of SARS-CoV-2. The ability of B.1.1.529 to spread even among vaccinated populations has led to a global public health demand for updated vaccines that can confer protection against B.1.1.529. We report here the rapid development of a replicating RNA vaccine expressing the B.1.1.529 spike and show that this B.1.1.529-targeted vaccine is immunogenic in mice and hamsters. Interestingly, we found that mice previously immunized with A.1-specific vaccines failed to elevate neutralizing antibody titers against B.1.1.529 following B.1.1.529-targeted boosting, suggesting pre-existing immunity may impact the efficacy of B.1.1.529-targeted boosters. Furthermore, we found that our B.1.1.529-targeted vaccine provides superior protection compared to the ancestral A.1-targeted vaccine in hamsters challenged with the B.1.1.529 VoC after a single dose of each vaccine.

One Sentence Summary

Rapidly developed RNA vaccine protects against SARS-CoV-2 Omicron variant
Widespread contribution of transposable elements to the rewiring of mammalian 3D genomes and gene regulation
Authors: Choudhary Mayank NK , Quaid Kara , Xing Xiaoyun , Schmidt Heather , Wang Ting
Published: February 2022

Transposable elements (TEs) are major contributors of genetic material in mammalian genomes. These often include binding sites for architectural proteins, including the multifarious master protein, CTCF. These TE-derived architectural protein binding sites shape the 3D genome by creating loops, domains, and compartments borders as well as RNA-DNA chromatin interactions, all of which play a role in the compact packaging of DNA in the nucleus and have the potential to facilitate regulatory function.

In this study, we explore the widespread contribution of TEs to mammalian 3D genomes by quantifying the extent to which they give rise to loops and domain border differences across various cell types and species using a variety of 3D genome mapping technologies. We show that specific (sub-)families of TEs have significantly contributed to lineage-specific 3D chromatin structures in specific mammals. In many cases, these loops have the potential to facilitate interaction between distant cis-regulatory elements and target genes, and domains have the potential to segregate chromatin state to impact gene expression in a lineage-specific and cell-type-specific manner. Backing our extensive conformation study cataloguing and computational analyses, we perform experimental validation using CRISPR-Cas9 to delete one such candidate TE and show disruption of species-specific 3D chromatin structure.

Taken together, we comprehensively quantify and selectively validate our finding that TEs contribute significantly to 3D genome organization and continuously shape it to affect gene regulation during the course of mammalian evolution over deep time.
A Spiking Neural Network Model of Rodent Head Direction calibrated with Landmark Free Learning
Authors: Stentiford Rachael , Knowles Thomas C. , Pearson Martin J.
Published: February 2022

Maintaining a stable estimate of head direction requires both self motion (ideothetic) information and environmental (allothetic) anchoring. In unfamiliar or dark environments ideothetic drive can maintain a rough estimate of heading but is subject to inaccuracy, visual information is required to stabilise the head direction estimate. When learning to associate visual scenes with head angle, animals do not have access to the ‘ground truth’ of their head direction, and must use egocentrically derived imprecise head direction estimates.

We use both discriminative and generative methods of visual processing to learn these associations without extracting explicit landmarks from a natural visual scene, finding all are sufficiently capable at providing corrective signal. Further, we present a spiking continuous attractor model of head direction (SNN), which when driven by ideothetic input is subject to drift. We show that head direction predictions made by the chosen model-free visual learning algorithms can correct for drift, even when trained on a small training set of estimated head angles self-generated by the SNN. We validate this model against experimental work by reproducing cue rotation experiments which demonstrate visual control of the head direction signal.
Binding of His-tagged fluorophores to lipid bilayers of giant vesicles†
Authors: Pramanik Shreya , Steinkühler Jan , Dimova Rumiana , Spatz Joachim , Lipowsky Reinhard
Published: February 2022

His-tagged molecules can be attached to lipid bilayers via certain anchor lipids, a method that has been widely used for the bio-functionalization of membranes and vesicles. To observe the membrane-bound molecules, it is useful to consider His-tagged molecules that are fluorescent as well. Here, we study two such molecules, green fluorescence protein (GFP) and green-fluorescent fluorescein isothiocyanate (FITC), both of which are tagged with a chain of six histidines (6H) that bind to the anchor lipids within the bilayers. The His-tag 6H is much smaller than the GFP molecule but somewhat larger than the FITC dye. The lipid bilayers form giant unilamellar vesicles (GUVs), the behavior of which can be directly observed in the optical microscope. We apply and compare three well-established preparation methods for GUVs: electroformation on platinum wire, polyvinyl alcohol (PVA) hydrogel swelling, and electroformation on indium tin oxide (ITO) glass. Microfluidics is used to expose the GUVs to a constant fluorophore concentration in the exterior solution. The brightness of membrane-bound 6H-GFP exceeds the brightness of membrane-bound 6H-FITC, in contrast to the quantum yields of the two fluorophores in solution. In fact, 6H-FITC is observed to be strongly quenched by the anchor lipids which bind the fluorophores via Ni2+ ions. For both 6H-GFP and 6H-FITC, the membrane fluorescence is measured as a function of the fluorophores’ molar concentration. The theoretical analysis of these data leads to the equilibrium dissociation constants Kd = 37.5 nM for 6H-GFP and Kd = 18.5 nM for 6H-FITC. We also observe a strong pH-dependence of the membrane fluorescence.
Why SARS-CoV-2 Omicron variant is milder? A single high-frequency mutation of structural envelope protein matters
Authors: Xia Bingqing , wang Yi , pan Xiaoyan , Cheng Xi , Ji Hongying , Zuo Xiaoli , Li Jia , Gao Zhaobing
Published: February 2022

SARS-CoV-2 Omicron variant is highly transmissible and extensive morbidity, which has raised concerns for antiviral therapy. In addition, the molecular basis for the attenuated pathogenicity and replication capacity of Omicron remains elusive. Here, we report for the first time that a high-frequency mutation T9I on 2-E of SARS-CoV-2 variant Omicron forms a non-selective ion channel with abolished calcium permeability and reduced acid sensitivity compared to the WT channel. In addition, T9I caused less cell death and a weaker cytokine production. The channel property changes might be responsible for the Omicron variant releases less efficiently and induces a comparatively lower level of cell damage in the infected cells. Our study gives valuable insights into key features of the Omicron variant, further supporting 2-E is a promising drug target against SARS-CoV-2 and providing critical information for the COVID-19 treatment.
Chronic alcohol intake regulates expression of SARS-CoV2 infection-relevant genes in an organ-specific manner
Authors: Friske Marion M. , Giannone Francesco , Senger Mona , Seitz Robin , Hansson Anita C. , Spanagel Rainer
Published: February 2022

Chronic alcohol consumption and alcohol use disorder (AUD) have a tremendous impact on the patient’s psychological and physiological health. There is some evidence that chronic alcohol consumption influences SARS-CoV2 infection risk, but the molecular mechanism is unknown. Here, we generated expression data of SARS-CoV2 infection relevant genes (Ace2, Tmprss2 and Mas) in different organs in rat models of chronic alcohol exposure and alcohol dependence. ACE2 and TMPRSS2 represent the virus entry point whereas Mas is activating the anti-inflammatory response once the cells are infected. Across three different chronic alcohol test conditions, we found a consistent upregulation of Ace2 in the lung, which is the most affected organ in Covid-19 patients. Other organs such as liver, ileum, kidney, heart, and the brain showed also up-regulation of Ace2 and Mas but in a less consistent manner across the different animal models, while Tmprss2 was unaffected in all conditions. We suggest that alcohol-induced up-regulation of Ace2 can lead to an elevated stochastic probability of cellular virus entry and may thus confer a molecular risk factor for a SARS-CoV2 infection.
Distinct silencer states determine epigenetic states of heterochromatin
Authors: Saxton Daniel S. , Rine Jasper
Published: February 2022

A remarkable property of heterochromatin is that a given heterochromatic locus can exhibit different transcriptional states in genetically identical cells. Studies demonstrate that epigenetic inheritance of the silenced state requires silencers and therefore cannot be driven by the inheritance of modified histones alone. To address these observations, we surveyed the chromatin architectures of strong and weak silencers in Saccharomyces. We found that strong silencers recruited Sir proteins and silenced the locus in all cells. Strikingly, weakening these silencers reduced Sir protein recruitment and stably silenced the locus in some cells; however, this silenced state could probabilistically convert to an expressed state that lacked Sir protein recruitment. Additionally, changes in the constellation of silencer-bound proteins or the concentration of a structural Sir protein modulated the probability that a locus existed in the silenced or expressed state. These findings argued that distinct states of silencers generate epigenetic states and regulate their dynamics.
Dynamically regulated Focal adhesions coordinate endothelial cell remodelling in developing vasculature
Authors: Chau Tevin CY. , Yordanov Teodor E. , Silva Jason A. da , Paterson Scott , Yap Alpha S. , Hogan Benjamin M. , Lagendijk Anne Karine
Published: February 2022

The assembly of a mature vascular network involves the coordinated control of cell shape changes to regulate morphogenesis of a complex vascular network. Cellular changes include a process of endothelial cell (EC) elongation which is essential for establishing appropriately sized lumens during vessel maturation1-3. However how EC elongation is dynamically regulated in vivo is not fully understood since live monitoring of this event can be challenging in animal models. Here, we utilise the live imaging capacity of the zebrafish to explore how integrin adhesion complexes, known as Focal Adhesions (FAs), control EC dynamics in live flow pressured vasculature. To do this, we generated a zebrafish mutant, deficient for the integrin adaptor protein Talin1. Notably, unlike the severe cardiovascular defects that arise in Talin1 knockout mice4, vasculogenesis still occurs normally talin1 mutants and cardiac output remains sufficient up to two days post fertilisation (dpf). This allowed us to uncouple primary roles for FAs in ECs during subsequent morphogenesis events, including angiogenesis and vessel remodelling, without interference of secondary effects that might occur due to systemic vessel failure or loss of blood flow. We further established a FA marker line, expressing endothelial Vinculin-eGFP, and demonstrated that FAs are lost in our talin1 mutants. This Vinculin transgene represents the first in vivo model to monitor endothelial FA dynamics. Loss of FAs in talin1 mutants, leads to compromised F-actin rearrangements, which perturb EC elongation and cell-cell junction linearisation during vessel remodelling. Chemical induction of actin polymerisation can restore these cellular phenotypes, suggesting a recovery of actin rearrangements that are sufficient to allow cell and junction shape changes. Together, we have identified that FAs are essential for active guidance of EC elongation and junction linearisation in flow pressured vessels. These observations can explain the severely compromised vessel beds, haemorrhage and vascular leakage that has been observed in mouse models that lack integrin signalling4-8.
Sentinel Cards Provide Practical SARS-CoV-2 Monitoring in School Settings
Authors: Cantú Victor J. , Sanders Karenina , Belda-Ferre Pedro , Salido Rodolfo A. , Tsai Rebecca , Austin Brett , Jordan William , Asudani Menka , Walster Amanda , Magallanes Celestine G , Valentine Holly D. , Majnoonian Araz , Wijaya Carrissa , Omaleki Vinton , Aigner Stefan , Baer Nathan A. , Betty Maryan , Castro-Martínez Anelizze , Cheung Willi , De Hoff Peter , Eisner Emily , Hakim Abbas , Lastrella Alma L. , Lawrence Elijah S. , Ngo Toan T. , Ostrander R. Tyler , Plascencia Ashley , Sathe Shashank , Smoot Elizabeth W. , Carlin Aaron F , Yeo Gene W , Laurent Louise C , Manlutac Anna Liza , Fielding-Miller Rebecca , Knight Rob
Published: February 2022

Accurate, high-resolution environmental monitoring of SARS-CoV-2 traces indoors through sentinel cards is a promising approach to help students safely return to in-person learning. Because SARS-CoV-2 RNA can persist for up to a week on several indoor surface types, there is a need for increased temporal resolution to determine whether consecutive surface positives arise from new infection events or continue to report past events. Cleaning sentinel cards after sampling would provide the needed resolution, but might interfere with assay performance. We tested the effect of three cleaning solutions (BZK wipes, wet wipes, RNase Away) at three different viral loads: "high" (4 x 104 GE/mL), "medium" (1 x 104 GE/mL), and "low" (2.5 x 103 GE/mL). RNAse Away, chosen as a positive control, was the most effective cleaning solution on all three viral loads. Wet wipes were found to be more effective than BZK wipes in the medium viral load condition. The low viral load condition was easily reset with all three cleaning solutions. These findings will enable temporal SARS-CoV-2 monitoring in indoor environments where transmission risk of the virus is high and the need to avoid individual-level sampling for privacy or compliance reasons exists.
An ancient endogenous DNA virus in the human genome
Authors: Barreat Jose Gabriel Nino , Katzourakis Aris
Published: February 2022

The genomes of eukaryotes preserve a striking diversity of ancient viruses in the form of endogenous viral elements (EVEs). Study of this genomic fossil record provides insights into the diversity, origin and evolution of viruses across geological timescales. In particular,Maverickshave emerged as one of the oldest groups of viruses infecting vertebrates (≥419 My). They have been found in the genomes of fish, amphibians and non-avian reptiles but had been overlooked in mammals. Thus, their evolutionary history and the causes of their demise in mammals remain puzzling questions. Here, we conduct a detailed evolutionary study of twoMaverick-like integrations found on human chromosomes 7 and 8. We performed a comparative analysis of the integrations and determined their orthology across placental mammals (Eutheria) via the syntenic arrangement of neighbouring genes. The integrations were absent at the orthologous sites in the genomes of marsupials and monotremes. These observations allowed us to reconstruct a time-calibrated phylogeny and infer the age of their most recent common ancestor at 268.61 (199.70–344.54) My. In addition, we estimate the age of the individual integrations at ~105 My which represent the oldest non-retroviral EVEs found in the human genome. Our findings suggest that activeMavericksexisted in the ancestors of modern mammals ~172 My ago (Jurassic Period) and potentially to the end of the Early Cretaceous. We hypothesiseMaverickscould have gone extinct in mammals from the evolution of an antiviral defence system or from reduced opportunities for transmission in terrestrial hosts.

Importance

The genomes of vertebrates preserve an enormous diversity of endogenous viral elements (remnants of ancient viruses that accumulate in host genomes over evolutionary time). Although retroviruses account for the vast majority of these elements, diverse DNA viruses have also been found and novel lineages are being described. Here we analyse two elements found in the human genome belonging to an ancient group of DNA viruses calledMavericks. We study their evolutionary history, finding that the elements are shared between humans and many different species of placental mammals. These observations suggest the elements inserted at least ~105 Mya in the most recent common ancestor of placentals. We further estimate the age of the viral ancestor around 268 My. Our results provide evidence for some of the oldest viral integrations in the human genome and insights into the ancient interactions of viruses with the ancestors of modern-day mammals.
Minilungs from hESCs to study the interaction ofStreptococcus pneumoniaewith the respiratory tract
Authors: González-Camacho Fernando , Rossi Suélen Andreia , Sempere Julio , de Lucas María Pilar , Rojas-Cabañeros José María , Taborda Carlos Pelleschi , Zaragoza Óscar , Yuste José , Zambrano Alberto
Published: February 2022

The new generation of organoids derived from human pluripotent stem cells holds a promising strategy for modeling host-bacteria interaction studies. Organoids recapitulate the composition, diversity of cell types and, to some extent, the functional features of the native organ. We have generated lung bud organoids derived from human embryonic stem cells to study the interaction ofStreptococcus pneumoniae(pneumococcus) with the alveolar epithelium. Invasive pneumococcal disease is an important health problem that may occur as a result of the spread of pneumococcus from the lower respiratory tract to sterile sites. We show here an efficient experimental approach to model the main events of the pneumococcal infection that occur in the human lung exploring bacterial adherence to the epithelium, internalization, and triggering of an innate response that includes the interaction with the surfactant and the expression of representative cytokines and chemokines. Thus, this model, based on human minilungs, can be used to study pneumococcal virulence factors, the pathogenesis of different serotypes and it will allow therapeutic interventions in a reliable human context.

IMPORTANCE

Streptococcus pneumoniaeis responsible for high morbidity and mortalities rates worldwide affecting mainly children and adults older than 65 years. Pneumococcus is also the most common etiologic agent of bacterial pneumonia, non-epidemic meningitis, and a frequent cause of bacterial sepsis. Although the advent of pneumococcal vaccines has decreased the burden of the diseases caused by pneumococcus, the emerging of antibiotic-resistant strains and non-vaccine types by serotype replacement, is worrisome. To study the biology of pneumococcus and to establish a reliable human model for pneumococcal pathogenesis, we have generated human minilungs from embryonic stem cells. The results show that these organoids can be used to model some events occurring during the interaction of pneumococcus with the lung such as adherence, internalization, and the initial alveolar innate response. This model also represents a great alternative to study virulence factors involved in pneumonia, drug screening, and other therapeutic interventions.
Ddp1 cooperates with Ppx1 to counter a stress response initiated by non-vacuolar polyphosphate
Authors: McCarthy Liam , Abramchuk Iryna , Wafy Gamal , Denoncourt Alix , Lavallée-Adam Mathieu , Downey Michael
Published: February 2022

In diverse cells from bacterial to mammalian species, inorganic phosphate is stored in long chains called polyphosphates (polyP). These near universal polymers, ranging from 3 to thousands of phosphate moieties in length, are associated with molecular functions including energy homeostasis, protein folding, and cell signaling. In many cell types, polyphosphate is concentrated in subcellular compartments or organelles. In the budding yeast S. cerevisiae, polyP synthesis by the membrane-bound VTC complex is coupled to its translocation into the lumen of the vacuole, a lysosome-related organelle, where it is stored at high concentrations. In contrast, ectopic expression of bacterial polyphosphate kinase, PPK, results in the toxic accumulation of polyP outside of the vacuole. In this study, we used label-free mass spectrometry to investigate the mechanisms underlying this toxicity. We find that PPK expression results in the activation of a stress response mediated in part by the Hog1 and Yak1 kinases, and Msn2/Msn4 transcription factors. This response is countered by the combined action of the Ddp1 and Ppx1 polyphosphatases that function together to counter polyP accumulation and downstream toxicity. In contrast, ectopic expression of previously proposed mammalian polyphosphatases did not impact PPK-mediated toxicity in this model, suggesting either that these enzymes do not function directly as polyphosphatases in vivo or that they require co-factors unique to higher eukaryotes. Our work provides a mechanistic explanation for why polyP accumulation outside of lysosome-related organelles is toxic. Further, it serves as a resource for exploring how polyP may impact conserved biological processes at a molecular level.
Gut commensal bacteria enhance pathogenesis of a tumorigenic murine retrovirus
Authors: Spring Jessica , Lara Sophie , Khan Aly A. , O’Grady Kelly , Wilks Jessica , Gurbuxani Sandeep , Erickson Steven , Fischbach Michael , Jacobson Amy , Chervonsky Alexander , Golovkina Tatyana
Published: February 2022

The influence of the microbiota on viral transmission and replication is well appreciated. However, its impact on retroviral pathogenesis outside of transmission/replication control remained unknown. Using Murine Leukemia Virus (MuLV), we found that some commensal bacteria promoted the development of leukemia induced by this retrovirus. The promotion of leukemia development by commensals was due to suppression of the adaptive immune response through upregulation of several negative regulators of immunity. These negative regulators included Serpinb9b and Rnf128, which are associated with a poor prognosis of some spontaneous human cancers. Upregulation of Serpinb9b was mediated by sensing of bacteria by NOD1/NOD2/RIPK2 pathway. This work describes a novel mechanism by which the microbiota enhances tumorigenesis within gut-distant organs and points at potential new targets for cancer therapy.
Molecular mechanics underlying flat-to-round membrane budding in live secretory cells
Authors: Shin Wonchul , Zucker Ben , Kundu Nidhi , Lee Sung Hoon , Shi Bo , Guo Xiaoli , Chan Chung Yu , Harrison Jonathan T. , Turechek Jaymie Moore , Hinshaw Jenny E. , Kozlov Michael M. , Wu Ling-Gang
Published: February 2022

Membrane budding entails forces to transform flat membrane into vesicles essential for cell survival. Accumulated studies have identified coat-proteins (e.g., clathrin) as potential budding factors. However, forces mediating many non-coated membrane buddings remain unclear. By visualizing proteins in mediating endocytic budding in live neuroendocrine cells, performing in vitro protein reconstitution and physical modelling, we discovered how non-coated-membrane budding is mediated: actin filaments and dynamin generate a pulling force transforming flat membrane into Λ-shape; subsequently, dynamin helices surround and constrict Λ-profile’s base, transforming Λ- to Ω-profile, and then constrict Ω-profile’s pore, converting Ω-profiles to vesicles. These mechanisms control budding speed, vesicle size and number, generating diverse endocytic modes differing in these parameters. Their impact is widespread beyond secretory cells, as the unexpectedly powerful functions of dynamin and actin, previously thought to mediate fission and overcome tension, respectively, may contribute to many dynamin/actin-dependent non- coated-membrane buddings, coated-membrane buddings, and other membrane remodelling processes.
Efficient combinatorial targeting of RNA transcripts in single cells with Cas13 RNA Perturb-seq
Authors: Wessels Hans-Hermann , Méndez-Mancilla Alejandro , Papalexi Efthymia , Mauck William M , Lu Lu , Morris John A. , Mimitou Eleni , Smibert Peter , Sanjana Neville E. , Satija Rahul
Published: February 2022

Pooled CRISPR screens coupled with single-cell RNA-sequencing have enabled systematic interrogation of gene function and regulatory networks. Here, we introduce Cas13 RNA Perturb-seq (CaRPool-seq) which leverages the RNA-targeting CRISPR/Cas13d system and enables efficient combinatorial perturbations alongside multimodal single-cell profiling. CaRPool-seq encodes multiple perturbations on a cleavable array which is associated with a detectable barcode sequence, allowing for the simultaneous targeting of multiple genes. We compared CaRPool-seq to existing Cas9-based methods, highlighting its unique strength to efficiently profile combinatorially perturbed cells. Finally, we apply CaRPool-seq to perform multiplexed combinatorial perturbations of myeloid differentiation regulators in an acute myeloid leukemia (AML) model system and identify extensive interactions between different chromatin regulators that can enhance or suppress AML differentiation phenotypes.
Presenilin and APP regulate synaptic kainate receptors
Authors: Barthet Gael , Moreira-de-Sá Ana , Zhang Pei , Castanheira Jorge , Gorlewicz Adam , Mulle Christophe
Published: February 2022

Kainate receptors (KARs) form a family of ionotropic glutamate receptors which regulate the activity of neuronal networks by both pre- and post-synaptic mechanisms. Their implication in pathologies is well documented for epilepsy. The higher prevalence of epileptic symptoms in Alzheimer disease (AD) patients questions the role of KARs in AD. Here we investigated whether the synaptic expression and function of KARs was impaired in mouse models of AD. We addressed this question by immunostaining and electrophysiology at synapses between mossy fibers and CA3 pyramidal cells, in which KARs are abundant and play a prominent physiological role. We observed a decrease of the immunostaining for GluK2 in the stratum lucidum in CA3, and of the amplitude of synaptic currents mediated by GluK2-containing KARs in an amyloid mouse model (APP/PS1) of AD. Interestingly, a similar phenotype was observed in CA3 pyramidal cells with a genetic deletion of either presenilin or APP/APLP2 as well as in organotypic cultures treated with γ-secretase inhibitors. Finally, the GluK2 protein interacts with full-length and C-terminal fragments of APP. Overall, our data suggest that APP stabilizes KARs at synapses, possibly through a trans-synaptic mechanism, and this interaction is under the control the γ-secretase proteolytic activity of presenilin.
Synthesis and crystal structure of poly[[di-μ3-tetrathioantimonato-tris[(cyclam)cobalt(II)]] acetonitrile disolvate dihydrate] (cyclam = 1,4,8,11-tetraazacyclotetradecane)
Authors: Näther Christian , Danker Felix , Bensch Wolfgang
Published: February 2022

Reaction of Co(ClO4)2·6H2O with cyclam (cyclam = 1,4,8,11-tetraazacyclotetradecane) and Na3SbS4·9H2O (Schlippesches salt) in a mixture of acetonitrile and water leads to the formation of crystals of the title compound with the composition {[Co3(SbS4)2(C10H24N4)3]·2CH3CN·2H2O}
n
or {[(Co-cyclam)3(SbS4)2]·2(acetonitrile)·2H2O}
n
. The crystal structure of the title compound consists of three crystallographically independent [Co-cyclam]2+ cations, which are located on centers of inversion, one [SbS4]3− anion, one water and one acetonitrile molecule that occupy general positions. The acetonitrile molecule is disordered over two orientations and was refined using a split model. The CoII cations are coordinated by four N atoms of the cyclam ligand and two trans-S atoms of the tetrathioantimonate anion within slightly distorted octahedra. The unique [SbS4]3− anion is coordinated to all three crystallographically independent CoII cations and this unit, with its symmetry-related counterparts, forms rings composed of six Co-cyclam cations and six tetrathioantimonate anions that are further condensed into layers. These layers are perfectly stacked onto each other so that channels are formed in which acetontrile solvate molecules that are hydrogen bonded to the anions are embedded. The water solvate molecules are located between the layers and are connected to the cyclam ligands and the [SbS4]3− anions via intermolecular N—H...O and O—H...S hydrogen bonding.
Ciprofloxacin salt and salt co-crystal with dihydroxybenzoic acids
Authors: Nugraha Yuda Prasetya , Sugiyama Haruki , Uekusa Hidehiro
Published: February 2022

The crystal structure of two multi-component crystals of ciprofloxacin [systematic name: 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)quinoline-3-carboxylic acid], a fluoroquinolone antibiotic, namely, ciprofloxacin 2,6-dihydroxybenzoate salt, C17H19FN3O3
+·C7H5O4
−, (I), and ciprofloxacin hydrochloride–3,5-dihydroxybenzoic–water (1/1/1), C17H19FN3O3
+·Cl−·C7H6O4·H2O, (II), were determined. In (I) and (II), the ciprofloxacin cations are connected via head-to-tail N—H...O hydrogen bonding. Both structures show an alternating layered arrangement between ciprofloxacin and dihydroxybenzoic acid.
Crystal structure and Hirshfeld surface analysis of 5-acetyl-2-amino-4-(4-bromophenyl)-6-oxo-1-phenyl-1,4,5,6-tetrahydropyridine-3-carbonitrile
Authors: Mamedov Ibrahim G. , Khrustalev Victor N. , Akkurt Mehmet , Novikov Anton P. , Asgarova Ayten R. , Aliyeva Khatira N. , Akobirshoeva Anzurat A.
Published: February 2022

The crystal structure of the title compound, C20H16BrN3O2, was determined using an inversion twin. Its asymmetric unit comprises two crystallographically independent molecules (A and B) being the stereoisomers. Both molecules are linked by pairs of N—H...O hydrogen bonds, forming a dimer with an R
2
2(16) ring motif. The dimers are connected by further N—H...O and N—H...N hydrogen bonds, forming chains along the c-axis direction·C—Br...π interactions between these chains contribute to the stabilization of the molecular packing. Hirshfeld surface analysis showed that the most important contributions to the crystal packing are from H...H, C...H/H...C, O...H/H...O, Br...H/H...Br and N...H/H...N interactions.
Coaching to prepare students for their school-to-work transition: conceptualizing core coaching competences
Authors: van der Baan Niels , Gast Inken , Gijselaers Wim , Beausaert Simon
Published: February 2022

Purpose

The present study proposes coaching as a pedagogical intervention to prepare students for transitioning to the labour market. Taking a competence-based approach, the proposed coaching practice aims to enhance students' employability competences to facilitate a smoother school-to-work transition. However, what transition coaching looks like remains largely unclear. Moreover, in competence-based education, teachers are expected to be highly skilled coaches, facilitating students' transition to the labour market. The present study aims to map the core competencies of a transition coach.

Design/methodology/approach

A qualitative design was adopted to map the core competences of a transition coach. Data were collected from two focus groups, consisting of coaches in higher education and in the workplace.

Findings

Results show that, to create the necessary support conditions, a coach creates a safe coaching environment and supports students in setting goals, guide them in the activities they undertake to attain these goals, and asks reflective questions. Moreover, the coach stimulates students' ownership by putting the student in the centre of the decision-making process. Furthermore, the results emphasize the importance of the coach's professional attitude and knowledge about the transition process and the labour market.

Practical implications

The article concludes with practical implications for novice transition coaches and teachers in higher education.

Originality/value

The present study adds to the agenda of graduate work readiness by proposing a coaching practice aimed at preparing students for their transition to the labour market.