bluuebunny/crossref_metadata_2025 huggingface dataset:
SaccuFlow – A High-throughput Analysis Platform to Investigate Bacterial Cell Wall Interactions
Authors: Apostolos Alexis J. , Ferraro Noel J. , Dalesandro Brianna E. , Pires Marcos M.
Published: April 2021

Bacterial cell walls are formidable barriers that protect bacterial cells against external insults and oppose internal turgor pressure. While cell wall composition is variable across species, peptidoglycan is the principal component of all cell walls. Peptidoglycan is a mesh-like scaffold composed of crosslinked strands that can be heavily decorated with anchored proteins. The biosynthesis and remodeling of peptidoglycan must be tightly regulated by cells because disruption to this biomacromolecule is lethal. This essentiality is exploited by the human innate immune system in resisting colonization and by a number of clinically relevant antibiotics that target peptidoglycan biosynthesis. Evaluation of molecules or proteins that interact with peptidoglycan can be a complicated and, typically, qualitative effort. We have developed a novel assay platform (SaccuFlow) that preserves the native structure of bacterial peptidoglycan and is compatible with high-throughput flow cytometry analysis. We show that the assay is facile and versatile as demonstrated by its compatibility with sacculi from Gram-positive bacteria, Gram-negative bacteria, and mycobacteria. Finally, we highlight the utility of this assay to assess the activity of sortase A fromStaphylococcus aureusagainst potential anti-virulence agents.
The allosteric activation of α7 nAChR by α-conotoxin MrIC is modified by mutations at the vestibular site
Authors: Gulsevin Alican , Papke Roger L. , Stokes Clare , Tran Hue N. T. , Jin Ai-Hua , Vetter Irina , Meiler Jens
Published: April 2021

α-conotoxins are 13-19 amino acid toxin peptides that bind various nicotinic acetylcholine receptor (nAChR) subtypes. α-conotoxin Mr1.7c (MrIC) is a 17 amino acid peptide that targets α7 nAChR. Although MrIC has no activating effect on α7 nAChR when applied by itself, it evokes a large response when co-applied with the type II positive allosteric modulator PNU-120596, which potentiates α7 nAChR response by recovering it from a desensitized state. Lack of standalone activity despite activation upon co-application with a positive allosteric modulator was previously observed for molecules that bind to an extracellular domain allosteric activation (AA) site at the vestibule of the receptor. We hypothesized that MrIC may activate α7 nAChR allosterically through this site. We ran voltage-clamp electrophysiology experiments and in silico peptide docking calculations to gather evidence in support of α7 nAChR activation by MrIC through the AA site. The experiments with the wild-type α7 nAChR supported an allosteric mode of action, which was confirmed by the increased MrIC + PNU-120596 responses of three α7 nAChR AA site mutants that were designed in silico to improve MrIC binding. Overall, our results shed light on allosteric activation of α7 nAChR by MrIC and suggest involvement of the AA site.

Significance Statement

α-conotoxin MrIC (MrIC) is an allosteric agonist of the α7 nicotinic acetylcholine receptor (nAChR). This mode of action is unique among α-conotoxins since these peptides typically act as orthosteric antagonists of nAChR. However, the mechanism of α7 nAChR activation by MrIC has been elusive so far. This work demonstrates that activation by MrIC is independent of the α7 nAChR orthosteric site and is related to a vestibular allosteric activation site at the extracellular domain of the receptor. Our experimental and computational studies identified the residues that play a role in allosteric activation and confirmed the utility of ensemble docking methods in understanding peptide – nAChR interactions, thus providing a basis for the design of peptides for allosteric modulation of nAChR.
A quantile integral linear model to quantify genetic effects on phenotypic variability
Authors: Miao Jiacheng , Lin Yupei , Wu Yuchang , Zheng Boyan , Schmitz Lauren L. , Fletcher Jason M. , Lu Qiongshi
Published: April 2021

Detecting genetic variants associated with the variance of complex traits, i.e. variance quantitative trait loci (vQTL), can provide crucial insights into the interplay between genes and environments and how they jointly shape human phenotypes in the population. We propose a quantile integral linear model (QUAIL) to estimate genetic effects on trait variability. Through extensive simulations and analyses of real data, we demonstrate that QUAIL provides computationally efficient and statistically powerful vQTL mapping that is robust to non-Gaussian phenotypes and confounding effects on phenotypic variability. Applied to UK Biobank (N=375,791), QUAIL identified 11 novel vQTL for body mass index (BMI). Top vQTL findings showed substantial enrichment for interactions with physical activities and sedentary behavior. Further, variance polygenic scores (vPGS) based on QUAIL effect estimates showed superior predictive performance on both population-level and within-individual BMI variability compared to existing approaches. Overall, QUAIL is a unified framework to quantify genetic effects on the phenotypic variability at both single-variant and vPGS levels. It addresses critical limitations in existing approaches and may have broad applications in future gene-environment interaction studies.
Towards guided mutagenesis: Gaussian process regression predicts MHC class II antigen mutant binding
Authors: Bell David R. , Chen Serena H.
Published: April 2021

Antigen-specific immunotherapies (ASI) require successful loading and presentation of antigen peptide into the major histocompatibility complex (MHC) binding cleft. One route of ASI design is to mutate native antigens for either stronger or weaker binding interaction to MHC. Exploring all possible mutations is costly both experimentally and computationally. To reduce experimental and computational expense, here we investigate the minimal amount of prior data required to accurately predict the relative binding affinity of point mutations for peptide-MHC class II (pMHCII) binding. Using data from different residue subsets, we interpolate pMHCII mutant binding affinities by Gaussian process (GP) regression of residue volume and hydrophobicity. We apply GP regression to an experimental dataset from the Immune Epitope Database, and theoretical datasets from NetMHCIIpan and Free Energy Perturbation calculations. We find that GP regression can predict binding affinities of 9 neutral residues from a 6-residue subset with an average R2coefficient of determination value of 0.62 ± 0.04 (±95% CI), average error of 0.09 ± 0.01 kcal/mol (±95% CI), and with an ROC AUC value of 0.92 for binary classification of enhanced or diminished binding affinity. Similarly, metrics increase to an R2value of 0.69 ± 0.04, average error of 0.07 ± 0.01 kcal/mol, and an ROC AUC value of 0.94 for predicting 7 neutral residues from an 8-residue subset. Our work finds that prediction is most accurate for neutral residues at anchor residue sites without register shift. This work holds relevance to predicting pMHCII binding and accelerating ASI design.
An mRNA SARS-CoV-2 vaccine employing Charge-Altering Releasable Transporters with a TLR-9 agonist induces neutralizing antibodies and T cell memory
Authors: Haabeth Ole A.W. , Lohmeyer Julian J.K. , Sallets Adrienne , Blake Timothy R. , Sagiv-Barfi Idit , Czerwinski Debra K. , McCarthy Blaine , Powell Abigail E. , Wender Paul A. , Waymouth Robert M. , Levy Ronald
Published: April 2021

The SARS-CoV-2 pandemic has necessitated the rapid development of prophylactic vaccines. Two mRNA vaccines have been approved for emergency use by the FDA and have demonstrated extraordinary effectiveness. The success of these mRNA vaccines establishes the speed of development and therapeutic potential of mRNA. These authorized vaccines encode full-length versions of the SARS-CoV-2 spike protein. They are formulated with Lipid Nanoparticle (LNP) delivery vehicles that have inherent immunostimulatory properties. Different vaccination strategies and alternative mRNA delivery vehicles would be desirable to ensure flexibility of future generations of SARS-CoV-2 vaccines and the development of mRNA vaccines in general.

Here, we report on the development of an alternative mRNA vaccine approach using a delivery vehicle called Charge-Altering Releasable Transporters (CARTs). Using these inherently nonimmunogenic vehicles we can tailor the vaccine immunogenicity by inclusion of co-formulated adjuvants such as oligodeoxynucleotides with CpG motifs (CpG-ODN). Mice vaccinated with the mRNA-CART vaccine developed therapeutically relevant levels of RBD-specific neutralizing antibodies in both the circulation and in the lung bronchial fluids. In addition, vaccination elicited strong and long lasting RBD-specific TH1 T cell responses including CD4+and CD8+T cell memory.
Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids
Authors: Liu Lizhong , Nemashkalo Anastasiia , Jung Ji Yoon , Chhabra Sapna , Guerra M. Cecilia , Heemserk Idse , Warmflash Aryeh
Published: April 2021

Morphogens are signaling molecules that convey positional information and dictate cell fates during development. Little is known about how morphogen gradients are created and interpreted during mammalian embryogenesis. Here we take advantage of a human gastruloid model to visualize endogenous Nodal protein in living cells. We show that Nodal is extremely short range so that Nodal protein is limited to the immediate neighborhood of source cells. Nodal activity spreads through a relay mechanism in which Nodal production induces neighboring cells to transcribe Nodal. We further show that the Nodal inhibitor Lefty, while biochemically capable of long-range diffusion, also acts locally to control the timing of Nodal spread and therefore of mesoderm differentiation during patterning. Our study establishes a novel paradigm for tissue patterning by an activator-inhibitor pair.
Drp1 SUMO/deSUMOylation by Senp5 isoforms influences ER tubulation and mitochondrial dynamics to regulate brain development
Authors: Yamada Seiya , Sato Ayaka , Akiyama Hiroki , Sakakibara Shin-ichi
Published: April 2021

Brain development is a highly orchestrated process requiring spatiotemporally regulated mitochondrial dynamics. Drp1, a key molecule in the mitochondrial fission machinery, undergoes various post-translational modifications including conjugation to the small ubiquitin-like modifier (SUMO). However, the functional significance of SUMOylation/deSUMOylation on Drp1 remains controversial. SUMO-specific protease 5 (Senp5L) catalyzes the deSUMOylation of Drp1. We revealed that a splicing variant of Senp5L, Senp5S, which lacks peptidase activity, prevents deSUMOylation of Drp1 by competing against other Senps. The altered SUMOylation level of Drp1 induced by Senp5L/5S affects Drp1 ubiquitination and tubulation of the endoplasmic reticulum (ER), thereby influencing mitochondrial morphology. A dynamic SUMOylation/deSUMOylation balance controls neuronal polarization and migration during the development of the cerebral cortex. These findings suggest a novel role of post translational modification, in which a deSUMOylation enzyme isoform competitively regulates mitochondrial dynamics and ER tubulation via Drp1 SUMOylation levels in a tightly controlled process of neuronal differentiation and corticogenesis.
Fast leaps between millisecond confinements govern Ase1 diffusion along microtubules
Authors: Bujak Łukasz , Holanová Kristýna , Marín Antonio García , Henrichs Verena , Barvík Ivan , Braun Marcus , Lánský Zdenĕk , Piliarik Marek
Published: April 2021

Diffusion is the most fundamental mode of protein translocation within cells. Confined diffusion of proteins along the electrostatic potential constituted by the surface of microtubules, although modeled meticulously in molecular dynamics simulations, has not been experimentally observed in real-time. Here, we used interferometric scattering microscopy to directly visualize the movement of the microtubule-associated protein Ase1 along the microtubule surface at nanometer and microsecond resolution. We resolved millisecond confinements of Ase1 and fast leaps between these positions of dwelling preferentially occurring along the microtubule protofilaments, revealing Ase1’s mode of diffusive translocation along the microtubule’s periodic surface. The derived interaction potential closely matches the tubulin-dimer periodicity and the distribution of the electrostatic potential on the microtubule lattice. We anticipate that mapping the interaction landscapes for different proteins on microtubules, finding plausible energetic barriers of different positioning and heights, will provide valuable insights into regulating the dynamics of essential cytoskeletal processes, such as intracellular cargo trafficking, cell division, and morphogenesis, all of which rely on diffusive translocation of proteins along microtubules.
Pore dynamics and asymmetric cargo loading in an encapsulin nanocompartment
Authors: Ross Jennifer , McIver Zak , Lambert Thomas , Piergentili Cecilia , Bird Jasmine Emma , Gallagher Kelly J. , Cruickshank Faye L. , James Patrick , Zarazúa-Arvizu Efrain , Horsfall Louise E. , Waldron Kevin J. , Wilson Marcus D. , Mackay C. Logan , Baslé Arnaud , Clarke David J. , Marles-Wright Jon
Published: April 2021

Encapsulins are protein nanocompartments that house various cargo enzymes, including a family of decameric ferritin-like proteins. Here, we study a recombinantHaliangium ochraceumencapsulin:encapsulated ferritin complex using electron cryo-microscopy and hydrogen/deuterium exchange mass spectrometry to gain insight into the structural relationship between the encapsulin shell and its protein cargo. An asymmetric single particle reconstruction reveals four encapsulated ferritin decamers in a tetrahedral arrangement within the encapsulin nanocompartment. This leads to a symmetry mismatch between the protein cargo and the icosahedral encapsulin shell. The encapsulated ferritin decamers are offset from the interior face of the encapsulin shell. Using HDX-MS, we observed dynamic behavior of the major five-fold pore in the encapsulin shell and show the pore opening via the movement of the encapsulin A-domain. These data will accelerate efforts to engineer the encapsulation of heterologous cargo proteins and to alter the permeability of the encapsulin shell via pore modifications.

Teaser

Cryo-EM and HDX-MS analysis of an encapsulin nanocompartment shows that the pores at the five-fold icosahedral vertex of the shell are flexible.
Parallel and sequential pathways of molecular recognition of a tandem-repeat protein and its intrinsically disordered binding partner
Authors: Smith Ben M. , Rowling Pamela J. E. , Dobson Chris M. , Itzhaki Laura S.
Published: April 2021

The Wnt signalling pathway plays an important role in cell proliferation, differentiation and fate decisions in embryonic development and in the maintenance of adult tissues, and the twelve Armadillo (ARM) repeat-containing protein β-catenin acts as the signal transducer in this pathway. Here we investigate the interaction between β-catenin and the intrinsically disordered transcription factor TCF7L2, comprising a very long nanomolar-affinity interface of approximately 4800 Å2that spans ten of the twelve ARM repeats of β-catenin. First, a fluorescence reporter system for the interaction was engineered and used to determine the kinetic rate constants for the association and dissociation. The association kinetics of TCF7L2 and β-catenin was monophasic and rapid (7.3 ± 0.1 ×107M-1s-1), whereas dissociation was biphasic and slow (5.7 ± 0.4 ×10−4s-1, 15.2 ± 2.8 ×10−4s-1). This reporter system was then combined with site-directed mutagenesis to investigate the striking variability in the conformation adopted by TCF7L2 in the three different crystal structures of the TCF7L2-β-catenin complex. We found that mutation of the N- and C-terminal subdomains of TCF7L2 that adopt relatively fixed conformations in the crystal structures has a large effect on the dissociation kinetics, whereas mutation of the labile sub-domain connecting them has negligible effect. These results point to a two-site avidity mechanism of binding with the linker region forming a “fuzzy” complex involving transient contacts that are not site-specific. Strikingly, two mutations in the N-terminal subdomain that have the largest effects on the dissociation kinetics showed two additional phases, indicating partial flux through an alternative dissociation pathway that is inaccessible to the wild type. The results presented here provide insights into the kinetics of molecular recognition of a long intrinsically disordered region with an elongated repeat-protein surface, a process found to involve parallel routes with sequential steps in each.
Public contributions to early detection of new invasive pests
Authors: Epanchin‐Niell Rebecca , Thompson Alexandra L. , Treakle Tyler
Published: April 2021

Early detection of new invasive pest incursions enables faster management responses and more successful outcomes. Formal surveillance programs—such as agency‐led pest detection surveys—are thus key components of domestic biosecurity programs for managing invasive species. Independent sources of pest detection, such as members of the public and farm operators, also contribute to early detection efforts, but their roles are less understood. To assess the relative contributions of different detection sources, we compiled a novel dataset comprising reported detections of new plant pests in the US from 2010 through 2018 and analyze when, where, how, and by whom pests were first detected. While accounting for uncertainties arising from data limitations, we find that agency‐led activities detected 32–56% of new pests, independent sources detected 27–60%, and research/extension detected 8–17%. We highlight the value of independent sources in detecting high impact pests, diverse pest types, and narrowly distributed pests—with contributions comparable with agency‐led surveys. However, in the US, independent sources detect a smaller proportion of new pests than in New Zealand. We suggest opportunities to further leverage independent pest detection sources, including by citizen science, landscaping contractors, and members of the public.
Relationship between work–family conflict and turnover intention in nurses: A meta‐analytic review
Authors: Yildiz Bora , Yildiz Harun , Ayaz Arda Ozlem
Published: April 2021

Aim

This meta‐analytic review aimed to synthesize and analyse studies that explored the relationship between nurses’ work–family conflicts and turnover intentions.

Design

This meta‐analytical review was conducted according to the Joanna Briggs Institute guidelines and PRISMA checklist.

Data Sources

A total of 191 (k = 14) publications published between 2005 and 2019 in English, including grey literature on turnover intention and work–family conflict, were retrieved from PubMed, PsycINFO, Web of Science, ProQuest and Scopus databases.

Review Methods

Studies on the relationship between work–family conflict and turnover intention were summarized.

Results

An overall effect size of r = .28 (N = 5781, 95% CI [0.23−0.33]) was obtained, indicating a moderate, positive and significant relationship between work–family conflict and turnover intention. The moderator analysis showed that individualism and long‐term orientation accounted for 90% of effect size heterogeneity of work–family conflict and turnover intention relationship.

Conclusion

Exploring the correlation between work–family conflict and turnover intention can provide guidelines and recommendations for the development of strategies to promote nurse retention and alleviate the nursing shortage. National culture, particularly individualism and long‐term orientation, were found to play a significant moderator role in this relationship. Cultures that are highly individualistic and have a long‐term orientation have a diminishing effect on the relationship between work–family conflict and turnover intention.

Impact

Work–family conflict and turnover intention are significantly correlated factors regardless of the studies’ cultural characteristics examined in this study. Policymakers and managers should consider this finding and develop strategies that provide a balance‐oriented work design to prevent nurse shortage.
The aesthetics of country music
Authors: Dyck John
Published: April 2021

Country music has not gotten much attention in philosophy. I introduce two philosophical issues that country music raises. First, country music is simple. Some people might think that its simplicity makes country music worse; I argue that simplicity is aesthetically valuable. The second issue is country music’s ideal of authenticity; fans and performers think that country should be real or genuine in a particular way. But country music scholars have debunked the idea that country authenticity gets at anything real; widespread ideas about country authenticity are rooted in a racist and fabricated picture of country music. In discussing these two issues, I highlight the importance of community in country music.
Large canopy and animal‐dispersed species facilitate natural regeneration in tropical forest restoration
Authors: Mendes Lara M. , César Ricardo G. , Uezu Alexandre , Beltrame Tiago P. , Rodriguez Luiz C. E. , Gomes Haroldo B. , Cullen Laury
Published: April 2021

Realizing the benefits of forest restoration requires that these ecosystems be maintained after the senescence of planted trees through facilitation of natural regeneration. We analyzed the effect of tree canopy cover, dispersal syndrome, deciduousness, and taxon in facilitating natural regeneration in tropical forest restoration planting. Canopy cover had additive positive effect on natural regeneration when combined with animal dispersal or evergreen trees. Animal dispersal had a positive effect on facilitating natural regeneration abundance, while evergreen species had a positive effect on natural regeneration richness only. Although variation within and among species was high, restoration practitioners could consider using species with these traits to facilitate natural regeneration and hence development of restoration plantings.
The Dilemma of Scale: competing imperatives for global restoration
Authors: Sigman Emily
Published: April 2021

Social–ecological restoration (SoER) embraces the nested interdependence of societies and ecosystems. An outpouring of SoER research has substantively shaped the global restoration agenda and will continue to play a critical role as the UN Decade on Ecosystem Restoration unfolds. In this article, I argue that global restoration ambitions are limited by two competing imperatives in SoER literature. The first imperative seeks to generalize restoration standards and metrics through rapid coordination and scaling. The second imperative seeks to upend problematic power dynamics, demanding social inclusivity and site specificity at levels that tend to resist scaling. Although these imperatives do not necessarily compete in theory, they often do in practice. Relying on a synthesis of key articles and expanding on the concept of “social‐ecological mismatches” (Cumming et al. 2006), I examine how the prevailing SoER research discourse creates a confounding landscape for restoration practitioners, who face what I term the “Dilemma of Scale.” I explore how this dilemma perpetuates systems of global inequality and inhibits efforts to effectively animate initiatives like the UN Decade on Ecosystem Restoration. I suggest that the Dilemma of Scale can be effectively mitigated by (1) identifying values that span both imperatives and work to decouple SoER projects from systems of exploitation and oppression and (2) expressly incorporating historical methods into SoER research and projects.
Vigencia de la teología latinoamericana de la liberación: a cinco décadas de su origen
Authors: Costadoat Jorge
Published: April 2021

En este artículo se da cuenta de aquello que perdura como novedoso de la teología latinoamericana de la liberación a cinco décadas de sus comienzos. El texto sitúa a esta teología en continuidad y como expresión de la recepción latinoamericana del Concilio Vaticano II. Los teólogos de la liberación han convenido en pensar que en Medellín, 1968, comenzó una apropiación creativa del Concilio, que consistió, en pocas palabras, en una opción por los pobres. El caso es que, si en los comienzos esta teología puso el énfasis en la necesidad de hacer cambios sociales y económicos estructurales en sociedades injustas, con el correr del tiempo ha descubierto la importancia de los pobres como sujetos de su reflexión y liberación. Ha sido muy significativo, en este sentido, descubrir el enorme valor de la lectura popular de la Biblia realizada en las comunidades eclesiales de base. Este artículo revisa, por lo mismo, el método de la teología de la liberación. Con el correr de los años se ha hecho necesario actualizar el planteamiento de Gustavo Gutiérrez para precisar lo esencial e incorporar el aporte, por ejemplo, de la teología feminista y de la teología india. Estas, bien distintas en cuanto a sus sujetos y temáticas, comparten sin embargo el ser teologías inductivas de colectivos que descubren su opresión. En una última sección, el artículo describe la que sería una novedad mayor, la concepción de la revelación. Varios teólogos no solo acogen el círculo hermenéutico de las teologías contextuales, sino que postulan que Dios continúa revelándose en el presente histórico con una Palabra nueva, la que se hace oír en el clamor de los pobres por su liberación.
Ultraprecision quantum sensing and measurement based on nonlinear hybrid optomechanical systems containing ultracold atoms or atomic Bose–Einstein condensate
Authors: Motazedifard Ali , Dalafi A. , Naderi M. H.
Published: April 2021

In this review, the authors study how a hybrid optomechanical system (OMS), in which a quantum micro- or nano-mechanical oscillator is coupled to the electromagnetic radiation pressure, consisting of an ensemble of ultracold atoms or an atomic Bose–Einstein condensate, can be used as an ultraprecision quantum sensor for measuring very weak signals. As is well-known in any precise quantum measurement, the competition between the shot noise and the backaction noise of measurement executes a limitation on the measurement precision which is the so-called standard quantum limit (SQL). In the case where the intensity of the signal is even lower than the SQL, one needs to perform an ultraprecision quantum sensing to beat the SQL. For this purpose, the authors review three important methods for surpassing the SQL in a hybrid OMS: (i) the backaction evading measurement of a quantum nondemolition variable of the system, (ii) the coherent quantum backaction noise cancelation, and (iii) the so-called parametric sensing, the simultaneous signal amplification, and added noise suppression below the SQL. Furthermore, the authors have shown in this article for the first time how the classical fluctuation of the driving laser phase, the so-called laser phase noise, affects the power spectrum of the output optical field in a standard OMS and induces an additional impression noise which makes the total system noise increase above the SQL. Also, for the first time in this review it has been shown that in the standard OMSs, it is impossible to amplify the signal while suppressing the noise below the SQL simultaneously.
Click evoked middle ear muscle reflex: Spectral and temporal aspects
Authors: Boothalingam Sriram , Goodman Shawn S.
Published: April 2021

This study describes a time series-based method of middle ear muscle reflex (MEMR) detection using bilateral clicks. Although many methods can detect changes in the otoacoustic emissions evoking stimulus to monitor the MEMR, they do not discriminate between true MEMR-mediated vs artifactual changes in the stimulus. We measured MEMR in 20 young clinically normal hearing individuals using 1-s-long click trains presented at six levels (65 to 95 dB peak-to-peak sound pressure level in 6 dB steps). Changes in the stimulus levels over the 1 s period were well-approximated by two-term exponential functions. The magnitude of ear canal pressure changes due to MEMR increased monotonically as a function of click level but non-monotonically with frequency when separated into 1/3 octave wide bands between 1 and 3.2 kHz. MEMR thresholds estimated using this method were lower than that obtained from a clinical tympanometer in ∼94% of the participants. A time series-based method, along with statistical tests, may provide additional confidence in detecting the MEMR. MEMR effects were smallest at 2 kHz, between 1 and 3.2 kHz, which may provide avenues for minimizing the MEMR influence while measuring other responses (e.g., the medial olivocochlear reflex).
Absolute abundance and preservation rate of
Tyrannosaurus rex
Authors: Marshall Charles R. , Latorre Daniel V. , Wilson Connor J. , Frank Tanner M. , Magoulick Katherine M. , Zimmt Joshua B. , Poust Ashley W.
Published: April 2021

Estimating dinosaur abundance

Estimating the abundance of a species is a common practice for extant species and can reveal many aspects of its ecology, evolution, and threat level. Estimating abundance for species that are extinct, especially those long extinct, is a much trickier endeavor. Marshall
et al.
used a relationship established between body size and population density in extant species to estimate traits such as density, distribution, total biomass, and species persistence for one of the best-known dinosaurs,
Tyrannosaurus rex
, revealing previously hidden aspects of its population ecology.

Science
, this issue p.
284
Ion-capture electrodialysis using multifunctional adsorptive membranes
Authors: Uliana Adam A. , Bui Ngoc T. , Kamcev Jovan , Taylor Mercedes K. , Urban Jeffrey J. , Long Jeffrey R.
Published: April 2021

One-step purification and desalination

The purification of water for drinking purposes can require multiple filtration steps and technologies to remove contaminants such as salts and heavy metals. Some contaminants could have value if recovered, but these are often discharged in the waste streams. Uliana
et al.
describe a general approach for the fabrication of robust, tunable, adsorptive membranes through the incorporation of porous aromatic framework (PAF) nanoparticles into ion exchange membranes such as those made from sulfonated polymers. Salts are removed using a series of cation and anion exchange membranes, and the PAF particles can be selected to capture specific target ions, such as those of copper, mercury, or iron. This allows for simultaneous desalination and decontamination of the water.

Science
, this issue p.
296
COVID-19 response: mitigating negative impacts on other areas of health
Authors: Hrynick Tabitha A , Ripoll Lorenzo Santiago , Carter Simone E
Published: April 2021

‘Vertical’ responses focused primarily on preventing and containing COVID-19 have been implemented in countries around the world with negative consequences for other health services, people’s access to and use of them, and associated health outcomes, especially in low-income and middle-income countries (LMICs). ‘Lockdowns’ and restrictive measures, especially, have complicated service provision and access, and disrupted key supply chains. Such interventions, alongside more traditional public health measures, interact with baseline health, health system, and social and economic vulnerabilities in LMICs to compound negative impacts. This analysis, based on a rapid evidence assessment by the Social Science in Humanitarian Action Platform in mid-2020, highlights the drivers and evidence of these impacts, emphasises the additional vulnerabilities experienced by marginalised social groups, and provides insight for governments, agencies, organisations and communities to implement more proportionate, appropriate, comprehensive and socially just responses that address COVID-19 in the context of and alongside other disease burdens. In the short term, there is an urgent need to monitor and mitigate impacts of pandemic responses on health service provision, access and use, including through embedding COVID-19 response within integrated health systems approaches. These efforts should also feed into longer-term strategies to strengthen health systems, expand universal healthcare coverage and attend to the social determinants of health—commitments, both existing and new—which governments, donors and international agencies must make and be held accountable to. Crucially, affected communities must be empowered to play a central role in identifying health priorities, allocating resources, and designing and delivering services.
Abnormal corneal properties in osteogenesis imperfecta and glaucoma: a case series
Authors: Doolan Emer , O’Brien Colm
Published: April 2021

Objective

We aimed to carry out ocular examination and genetic studies in a family in which some members are affected with osteogenesis imperfecta (OI) and primary open-angle glaucoma (POAG). We compared the corneal properties of affected and unaffected members (ie, cases and controls).

Methods

Eight family members from two generations, both affected and unaffected, were examined. Corneal hysteresis (CH), intraocular pressure (IOP) measured with Goldmann applanation tonometer, central corneal thickness (CCT) and cornea-corrected IOP (IOPcc) were recorded. Blood samples were obtained from seven family members, both affected and unaffected, and tested for a panel of genes associated with OI.

Results

Family members affected with OI (n=6) had a heterozygous splice site mutation in intron 26 of the COL1A1 gene. The family members affected with OI had reduced CCT (476.5±24.6 µm) and CH (7.9 ±1.4 mmHg) compared with the unaffected controls (CCT, 575.8±10.8 µm; CH, 12.3±0.8 mmHg). Two of the six patients affected with OI had a glaucoma diagnosis and were on topical therapy and under regular clinical review.

Conclusions

Patients affected with OI have a significant risk of developing POAG due to the effects of abnormal collagen on various ocular structures. Two of these effects which place them at risk are reduced CCT and CH. They should be screened and monitored for glaucoma from a young age, and the examination should include corneal biomechanical measurements and CCT to identify those most at risk. IOPcc may be a more accurate way to monitor IOP in the presence of abnormal corneal properties.
To prescribe or not to prescribe for paediatric sore throat: a retrospective cohort study comparing clinician-led antibiotic prescriptions to FeverPAIN and Centor scoring in a tertiary paediatric emergency department and a national review of practice
Authors: Malley Michael , Driver Katie , Costelloe Megan , Monaghan Isla , Jefferson Lucy , Poole Louise , Lewis Cliona , Salt Rachael , Marlow Robin
Published: April 2021

Background

Tonsillopharyngitis is a common presentation to paediatric emergency departments (PEDs). FeverPAIN (FP) and Centor scoring systems are recommended in the UK to help delineate bacterial aetiology, despite being primarily evidenced in adult populations. We investigate how the use of FP or Centor compares to actual clinician practice in guiding antibiotic prescription rates in PED. We establish current national practice in English PEDs.

Methods

We performed a retrospective cohort study of tonsillopharyngitis presentations to a tertiary PED in January–February 2020. Investigators retrospectively assigned each patient FP and Centor scores using documented symptoms. We compared antibiotic prescription rates guided by FP/Centor against the actual rate prescribed by clinicians, and assessed agreement between these strategies using kappa analysis. We contacted 153 English emergency departments to establish national practice.

Results

We identified 632 consecutive patients aged 6 months to 15 years. Actual clinician-prescribed antibiotics numbered 116 (18.4%). Prescriptions predicted by FP score numbered 124 (19.6%) and Centor 112 (17.7%). Kappa (K) analysis indicated only moderate agreement between clinician choice versus FP (K=0.434) and clinician choice versus Centor (K=0.476). This was similar for cohorts aged under and over 3 years.

National practice was reportedly heterogeneous, with 70 emergency departments (45.8%) not employing a specific system.

Conclusion

Current guidance is variably interpreted and inconsistently implemented in paediatric populations. FeverPAIN and Centor scoring systems may not rationalise antibiotics as much as previously reported compared with judicious clinician practice. Producing clear paediatric-specific national guidelines, especially for under-5s who are omitted from NICE sore throat guidance, may help further rationalise and standardise antibiotic use in paediatric tonsillopharyngitis.
Moral obligations in conducting stem cell-based therapy trials for autism spectrum disorder
Authors: Yeo-Teh Nicole Shu Ling , Tang Bor Luen
Published: April 2021

Unregulated patient treatments and approved clinical trials have been conducted with haematopoietic stem cells and mesenchymal stem cells for children with autism spectrum disorder (ASD). While the former direct-to-consumer practice is usually considered rogue and should be legally constrained, regulated clinical trials could also be ethically questionable. Here, we outline principal objections against these trials as they are currently conducted. Notably, these often lack a clear rationale for how transplanted cells may confer a therapeutic benefit in ASD, and thus, have ill-defined therapeutic outcomes. We posit that ambiguous and unsubstantiated descriptions of outcome from such clinical trials may nonetheless appeal to the lay public as being based on authentic scientific findings. These may further fuel caregivers of patients with ASD to pursue unregulated direct-to-consumer treatments, thus exposing them to unnecessary risks. There is, therefore, a moral obligation on the part of those regulating and conducting clinical trials of stem cell-based therapeutic for ASD minors to incorporate clear therapeutic targets, scientific rigour and reporting accuracy in their work. Any further stem cell-based trials for ASD unsupported by significant preclinical advances and particularly sound scientific hypothesis and aims would be ethically indefensible.
Nasal versus oronasal masks for home non-invasive ventilation in patients with chronic hypercapnia: a systematic review and individual participant data meta-analysis
Authors: Lebret Marius , Léotard Antoine , Pépin Jean Louis , Windisch Wolfram , Ekkernkamp Emelie , Pallero Mercedes , Sánchez-Quiroga M-Ángeles , Hart Nicholas , Kelly Julia L , Patout Maxime , Funk Georg Chistian , Duiverman Marieke L , Masa Juan F , Simonds Anita , Murphy Patrick Brian , Wijkstra Peter J , Dreher Michael , Storre Jan , Khouri Charles , Borel Jean-Christian
Published: April 2021

Background

The optimal interface for the delivery of home non-invasive ventilation (NIV) to treat chronic respiratory failure has not yet been determined. The aim of this individual participant data (IPD) meta-analysis was to compare the effect of nasal and oronasal masks on treatment efficacy and adherence in patients with COPD and obesity hypoventilation syndrome (OHS).

Methods

We searched Medline and Cochrane Central Register of Controlled Trials for prospective randomised controlled trials (RCTs) of at least 1 month’s duration, published between January 1994 and April 2019, that assessed NIV efficacy in patients with OHS and COPD. The main outcomes were diurnal PaCO2, PaO2 and NIV adherence (PROSPERO CRD42019132398).

Findings

Of 1576 articles identified, 34 RCTs met the inclusion criteria and IPD were obtained for 18. Ten RCTs were excluded because only one type of mask was used, or mask data were missing. Data from 8 RCTs, including 290 IPD, underwent meta-analysis. Oronasal masks were used in 86% of cases. There were no differences between oronasal and nasal masks for PaCO2 (0.61 mm Hg (95% CI −2.15 to 3.38); p=0.68), PaO2 (−0.00 mm Hg (95% CI −4.59 to 4.58); p=1) or NIV adherence (0·29 hour/day (95% CI −0.74 to 1.32); p=0.58). There was no interaction between the underlying pathology and the effect of mask type on any outcome.

Interpretation

Oronasal masks are the most used interface for the delivery of home NIV in patients with OHS and COPD; however, there is no difference in the efficacy or tolerance of oronasal or nasal masks.
Facile synthesis of pyrazole derivatives using reusable Fe3O4@MCM-41-SO3H
Authors: Sharifi Samanehsadat , Maghsoudlou Malek Taher , Hazeri Nourallah
Published: April 2021

In this research, Fe3O4-MCM-41-SO3H was synthesized as a magnetically reusable Lewis acid catalyst and used in the cyclization reaction of 3-acylcoumarins or 3-chromonecarboxylic acid with arylhydrazine derivatives for the synthesis of pyrazoles in high yields under solvent-free conditions and with a simple work-up process. Fe3O4-MCM-41-SO3H was characterized by Fourier transform infrared (FTIR), scanning electron microscopy (SEM), and X‐ray diffraction (XRD) analyses.
Wear evaluation and microstructure analysis of cryogenically treated AISI 440C bearing steel
Authors: Idayan A. , Elanchezhian C. , Vijaya Ramnath B. , Palanikumar K.
Published: April 2021

In this study, two types of cryogenic treatment [deep cryogenic treatment (−196 °C) and shallow cryogenic treatment (−80 °C)] were used to increase wear resistance in AISI 440C bearing steel. Out focus was to find a way to increase wear resistance via deep microstructural analyses, and also to correlate the microstructure with the wear characteristics of specimens subjected to deep cryogenic treatment, conventional heat treatment, or shallow cryogenic treatment. Microstructural examinations of the specimens were performed using scanning electron microscopy, energy dispersive analysis of X-rays, and X-ray diffraction to study the wear characteristics of AISI 440C bearing steel. The results show that the specimens subjected to deep cryogenic treatment have greater wear resistance than the specimens subjected to shallow cryogenic or conventional heat treatment. The wear mechanisms included the formation and delamination of white layers. The microstructure of the steel was altered by the heat treatment process: the precipitation characteristics of the secondary carbides were modified and the levels of retained austenite were reduced, which correlated with the wear characteristics, and were identified as the potential mechanisms behind the increased wear resistance of the bearing steels due to the deep cryogenic treatment.
Investigation of the fake reject cases with unqualified operational dimension based on the error compensation and tolerance compression
Authors: Ma Xiaosan , Jiao Feng , Feng Wenhui , Bie Wenbo , Chen Fan
Published: April 2021

A fake reject (FR) with unqualified operational dimension often occurs during part machining when the operational data do not coincide with the design data, which can lead to unnecessary waste. We investigated novel judgment and remedial measures for FR to enhance the product qualification rate. We first discuss the reasons for FRs that occur when the calculation for the operational tolerance of the dimension chain is too narrow when calculated using the worst-case scenario method for the process. Following that, we present a novel method for estimating FRs by calculating a new dimension chain. The operational dimension is treated as the concluding link. The actual deviations of the dimensions generated before the operational dimension are used to replace their upper and lower deviations. Finally, based on the error compensation relationship among the component links in the process dimension chain, we propose a novel remedial measure for FR via compressing the dimension tolerance in subsequent processing. We also calculated the dimension tolerance after tolerance compression. This results from this study contribute to the assessment and processing of FRs in part machining.
Orientation fluctuations in magnetotactic swimming
Authors: Smyk Sebastian , Telezki Vitali , Riepl Josef , Hayes Johannes , Klumpp Stefan
Published: April 2021

The fluctuations experienced by magnetic microswimmers in a magnetic field often have non-thermal contributions, in particular in the case of biological swimmers such as magnetotactic bacteria. Here we study a model for an active self-propelled particle subject to correlated internal noise as a model for the active, non-thermal noise contribution and determine the effect of the correlation time on the diffusion of the swimmer and on its orientation in a magnetic field. A description in terms of an effective temperature is possible, but has limitations.
Genistein Triggers Translocation of Estrogen Receptor-Alpha in Mitochondria to Induce Expressions of ATP Synthesis-Associated Genes and Improves Energy Production and Osteoblast Maturation
Authors: Wu Gong-Jhe , Cherng Yih-Giun , Chen Jui-Tai , Chang Chuen-Chau , Liu Shing-Hwa , Chen Ruei-Ming
Published: April 2021

Our previous study showed that estrogen can induce mitochondrial adenosine triphosphate (ATP) synthesis-associated gene expressions and osteoblast maturation. Genistein, a phytoestrogenic isoflavone that is widely found in various foods and traditional herb products, is beneficial for osteogenesis by selectively triggering estrogen receptor alpha (ER[Formula: see text] expression. In this study, we further investigated the mechanisms of genistein-induced energy production and osteoblast activation. Exposure of rat calvarial osteoblasts and human U-2 OS cells to genistein triggered osteoblast activation without affecting cell survival. Treatment with genistein time-dependently induced ER[Formula: see text] mRNA and protein expressions in rat calvarial osteoblasts. Analyses by confocal microscopy and immunoblotting showed that genistein stimulated translocation of ER[Formula: see text] from the cytoplasm to mitochondria. Subsequently, expressions of mitochondrial cytochrome c oxidase (COX) I and II mRNAs and proteins in primary rat osteoblasts were induced after exposure to genistein. Knocking-down ER[Formula: see text] concurrently inhibited genistein-induced COX I and II mRNA expressions. In addition, mitochondrial complex enzyme activities, the mitochondrial membrane potential, and cellular ATP levels in rat calvarial osteoblasts were time-dependently augmented by genistein. Suppressing ER[Formula: see text] expression instantaneously lowered genistein-induced enhancements of mitochondrial energy production and osteoblast activation. Effects of genistein on ER[Formula: see text] translocation, COX I and II mRNA expressions, ATP synthesis, and osteoblast activation were further confirmed in human U-2 OS cells. This study showed that genistein can stimulate energy production and consequent osteoblast activation via inducing ER[Formula: see text]-mediated mitochondrial ATP synthesis-linked gene expressions.
Effect of oxide layer and size on the vibration frequency of silicon nanobeams
Authors: Li Yanliang , Wang Jing
Published: April 2021

We studied the vibration frequencies of small double-clamped silicon nanobeams using a molecular dynamics method. The effects of cross-section area, size, and oxide layer were investigated through simulation. The results show that the vibration frequency decreases with increasing length, whereas it increases slightly with increasing cross-section area of the nanobeam. The existence and thickness of an oxide layer lead to increasing of the vibration frequency of silicon nanobeams.