bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure and dynamics of SARS-CoV-2 proofreading exoribonuclease ExoN
Authors: Moeller Nicholas H. , Shi Ke , Demir Özlem , Belica Christopher , Banerjee Surajit , Yin Lulu , Durfee Cameron , Amaro Rommie E. , Aihara Hideki
Published: February 2022

Significance

SARS-CoV-2 nonstructural protein 14 (nsp14) exoribonuclease (ExoN) plays important roles in the proofreading during viral RNA synthesis and the evasion of host immune responses. We used X-ray crystallography, molecular dynamics simulations, and biochemical assays to investigate the structure, dynamics, and RNA-binding mechanisms of nsp14-ExoN and how its activity is regulated by another viral protein, nsp10. We also demonstrated that nsp14-ExoN can collaborate with the viral RNA polymerase to enable RNA synthesis in the presence of a chain-terminating drug, biochemically recapitulating the proofreading process. Our studies provide mechanistic insights into the functions of a key viral enzyme and a basis for future development of chemical inhibitors.
Glacial isostatic adjustment directed incision of the Channeled Scabland by Ice Age megafloods
Authors: Pico Tamara , David Scott R. , Larsen Isaac J. , Mix Alan C. , Lehnigk Karin , Lamb Michael P.
Published: February 2022

Significance

The glacial Lake Missoula outburst floods are among the largest known floods on Earth. Dozens of these floods scoured the landscapes of eastern Washington during the last Ice Age, from 18 to 15.5 thousand years ago, forming what is known as the Channeled Scabland. We explored how changes in topography due to the solid Earth’s response to ice sheet loading and unloading influenced the history of megaflood routing over the Channeled Scabland. We found that deformation of Earth’s crust played an important role in directing the erosion of the Channeled Scabland.
Molecular parallelism in signaling function across different sexually selected ornaments in a warbler
Authors: Sly Nicholas D. , Freeman-Gallant Corey R. , Henschen Amberleigh E. , Minias Piotr , Whittingham Linda A. , Dunn Peter O.
Published: February 2022

Significance

Ornaments are thought to signal the genetic quality of males to females choosing mates, but the qualities they signal and why they sometimes vary between populations are poorly understood. Here, we show, within a single warbler species, that two plumage ornaments signal similar aspects of male quality (e.g., immunity and oxidative balance) at the level of genetic functions, even though the ornament preferred by females differs between populations, involves different body parts, and is produced by different pigments (melanins and carotenoids). This parallelism at the functional level provides the flexibility for different types of ornaments to be used as signals of similar aspects of male quality, allowing for switches in female preferences between ornaments and potentially facilitating divergence and speciation.
Regional dialect leveling in Mandarin Chinese
Authors: Li Aini
Published: February 2022

This paper studies the variation that stems from language contact between the suffix ‑tou, a locative marker in the Chengdu dialect spoken in Southwest China, and its standard Chinese counterpart ‑mian. The data are drawn from sociolinguistic interviews with 40 native speakers of the Chengdu dialect. It is shown that the standard Chinese form ‑mianhas outnumbered ‑touin terms of occurrence, suggesting a change in progress over apparent time that essentially involves a dialect leveling that results from language standardization and contact-induced convergence. Meanwhile, the two variants undergo certain stylistic reallocation and begin to serve new socio-stylistic roles. To our knowledge, this is the first study that systematically investigates the variation of Chinese locatives.
Formulaic time buyers for young foreign language learners
Authors: Gheitasi Parvin , Enever Janet
Published: February 2022

Multiword units of language, known as formulaic sequences, are pervasive and essential in communication (Wray, 2008). Although issues related to formulaicity have been under investigation in a
number of research studies (e.g. Conklin & Schmitt, 2008; Wood, 2006), the present study is different in investigating the functions of formulaic sequences in the
oral language production of young learners in the context of English as a foreign language. A class of 11 students (aged 9 to 11)
was observed and video recorded for 16 sessions (90 minutes per session). Following transcription of selected speech samples,
formulaic sequences were identified based on pre-established criteria. Analysis enabled categorisation of a range of functions for
formulaic sequences in learners’ oral language production. Results revealed evidence that formulaic sequences performed a variety
of roles in the learners’ language production. These sequences helped young language learners to improve their fluency, to
economize effort on processing and also to buy time for processing. A significant novel finding of this study was evidence that
language users might introduce dis-fluency in the production of their sequences in order to buy time for further processing.
Tuning the morphology of 2D transition metal chalcogenides via oxidizing conditions
Authors: Yao Bing , Li Rongsheng , Zhang Chenxi , Zhou Zhenjia , Fu Zihao , Huang Xianlei , Yuan Guowen , Xu Jie , Gao Libo
Published: February 2022

Two-dimensional transition metal chalcogenides (TMCs) are emerging as an intriguing platform to realize nascent properties in condensed matter physics, materials science and device engineering. Controllable growing of TMCs becomes increasingly important, especially for the layer number, doping, and morphology. Here, we successfully tune the morphology of MoS2, MoSe2, WS2 and WSe2, from homogenous films to individual single crystalline grains only via changing the oxidizing growth conditions. The oxidization degrees are determined by the oxygen that adsorbed on substrates and the oxygen concentrations in reaction gas together. We find the homogenous films are easily formed under the reductive conditions, triangular grains prefer the weak oxidizing conditions, and medium oxidizing conditions bring in dendritic grains with higher oxygen doping and inhomogenous photoluminescence intensities from edge to interior regions shown in the dendritic grains. These growth rules under different oxidizing conditions are easily generalized to other TMCs, which also show potential for growing specific TMCs with designed oxygen doping levels.
Ultradiscrete analogue of the van der Pol equation
Authors: Isojima Shin , Suzuki Seiichiro
Published: February 2022

Ultradiscretization with parity variables (pUD) is a method of constructing a conditional piecewise linear equation which approximates a given difference equation. Its application is not limited to subtraction-free equation, being different from the traditional ultradiscretization. In this paper, the procedure of pUD is applied to the van der Pol equation, which is a non-integrable system, and it is studied how the procedure works. The behavior of the ultradiscrete solution is understood by summarizing in transition diagrams, and some periodic solutions are found.
Quasi-graphs, zero entropy and measures with discrete spectrum
Authors: Li Jian , Oprocha Piotr , Zhang Guohua
Published: February 2022

In this paper, we study dynamics of maps on quasi-graphs and characterise their invariant measures. In particular, we prove that every invariant measure of a quasi-graph map with zero topological entropy has discrete spectrum. Additionally, we obtain an analog of Llibre–Misiurewicz’s result relating positive topological entropy with existence of topological horseshoes. We also study dynamics on dendrites and show that if a continuous map on a dendrite whose set of all endpoints is closed and has only finitely many accumulation points, has zero topological entropy, then every invariant measure supported on an orbit closure has discrete spectrum.
Direct x-ray detection using thin-film pentacene Schottky diodes
Authors: Lakshmi Vineela V. , Praveen P.A. , Kanagasekaran T. , Kumar C Nitish , Narasimha Murty N.V.L.
Published: February 2022

Direct x-ray detectors using thermally evaporated pentacene
thin-films are fabricated in Schottky and coplanar configurations
and are analysed for low x-ray dose rates. In both configurations,
the x-ray induced photocurrent is found to be five orders of
magnitude greater than the theoretically evaluated threshold value
that may reflect possible internal gain mechanism. Coplanar
detectors showed unstable x-ray photocurrent characteristics; on the
other hand, Schottky photodiode structure showed stable response and
thus allowed to proceed for x-ray sensitivity
measurements. Pentacene-based Schottky detector presented a decent
volume sensitivity of 162.3 μC/mGy/cm3. The high x-ray
sensitivity of pentacene Schottky detector can be due to the
complete depletion of the thin-film at the operating reverse bias,
revealed by transfer characteristics of fabricated pentacene
MESFET. Such a reasonably good x-ray photoconversion in low-Z
organic semiconducting materials uncovers the possibility of
implementing them in x-ray medical dosimetry applications and in
wearable electronic technology.
Untapped potential: leak reduction is the most cost-effective urban water management tool
Authors: Rupiper Amanda , Weill Joakim , Bruno Ellen , Jessoe Katrina , Loge Frank
Published: February 2022

Providing sufficient, safe, and reliable drinking water is a growing challenge as water supplies become more scarce and uncertain. Meanwhile, water utilities in the United States lose approximately 17% of their delivered water to leaks each year. Using data from over 800 utilities across four U.S. states, California, Georgia, Tennessee, and Texas, we characterize the heterogeneity in water losses across the U.S., develop a model to assess the economically efficient level of losses, and use this model to compare the net benefits of several proposed water loss regulations and modeling approaches. Combining economic and engineering principles, our model shows that for the median utility, it is economically efficient to reduce water losses by 34.7%, or 100 acre-feet (AF) per year. The median cost of water savings from leak management is $277/AF, which falls well below the cost of traditional water management tools. However, the optimal level of water losses strongly depends on utility-specific characteristics, leading to large differences in the potential for cost-effective leak reduction across utilities. We show that water loss management can lead to water savings that generate net economic benefits, but only if management approaches incorporate economic and engineering principles.
ENSO modulation of summertime tropospheric ozone over China
Authors: Yang Yang , Li Mengyun , Wang Hailong , Li Huimin , Wang Pinya , Li Ke , Gao Meng , Liao Hong
Published: February 2022

Ozone (O3) is one of the most critical pollutants affecting air quality in China in recent years. In this study, different impacts of the El Niño–Southern Oscillation (ENSO) warm/cold phases on summertime tropospheric O3 over China are examined based on model simulations, ground measurements, and reanalysis data. Summertime surface O3 concentrations in China show a positive correlation with ENSO index during years 1990–2019, with the largest increases by 20% over southern China in El Niño (warm phase) relative to La Niña (cold phase) years. The ENSO modulation extends to the middle and even upper troposphere. Our analysis indicates that O3 flux convergence associated with weakened southerlies is the primary reason for the increase in tropospheric O3 over southern China. In addition, the O3 increase during El Niño years is mainly from domestic emissions in China. This study highlights the potential significance of ENSO in modulating tropospheric O3 concentrations in China, with great implications for O3 pollution mitigation.
A family of fourth-order superintegrable systems with rational potentials related to Painlevé VI
Authors: Marquette I , Post S , Ritter L
Published: February 2022

We discuss a family of Hamiltonians given by particular rational extensions of the singular oscillator in two-dimensions. The wave functions of these Hamiltonians can be expressed in terms of products of Laguerre and exceptional Jacobi polynomials. We show that these systems are superintegrable and admit an integral of motion that is of fourth-order. As such systems have been classified, we see that these potentials satisfy a non-linear equation related to Painlevé VI. We begin by demonstrating the process with the simpler example of rational extensions of the harmonic oscillator and use the classification of third-order superintegrable systems to connect these families with the known solutions of Painlevé IV associated with Hermite polynomials.
A Systematic Review on the Current Trend in Nonsurgical Aesthetic Training for Knowledge, Skill, and Professional Identity Formation
Authors: Kumar Narendra , Parsa Ali Davod , Rahman Eqram
Published: February 2022

Background

Non-surgical aesthetics is a rapidly growing healthcare domain and lacks pedagogically sound education and training programs. The trainee physicians often participate in short courses which are outside of the scope of an existing postgraduate training program to acquire the necessary knowledge and procedural skills. However, such training programs lack values and interests that shape critical thinking and holistic decision-making, often referred to as professional identity.

Objectives

This systematic review aims to analyze current trends in non-surgical aesthetic clinical education to form knowledge, skills, and professional identity.

Methods

A detailed literature search was conducted in electronic databases—PubMed, Cochrane, Centre for Reviews and Dissemination, and Google Scholar—for relevant studies published between January 2010 and December 2020, with an update in September 2021.

Results

Fifty-five articles were identified through electronic searches, among which 40 were selected following a review of the abstracts. Sixteen articles were identified as the best evidence for the detailed and iterative review based on their relevance and fit to the inclusion criteria. Unfortunately, none of the included studies designed their questionnaire based on the Kirkpatrick Model, which is best known for analyzing and evaluating the results of training and educational programs.

Conclusions

This systematic review provides valuable insight into graduate professional identity formation and graduates’ readiness for independent clinical practice. Therefore, particular consideration should be given to incorporating these triggers when developing evidence-based postgraduate curricula for non-surgical aesthetics.
Synthesis and biological evaluation of cajaninstilbene acid and amorfrutins A-D as cytotoxic agents against human pancreatic carcinoma PANC-1 cells
Authors: Fujita Tadafumi , Lin Jianyu , Kimishima Atsushi , Arai Masayoshi , Takikawa Hirosato , Ogura Yusuke
Published: February 2022

A concise synthesis of cajaninstilbene acid was achieved in 7 steps from (E)-3,5-dimethoxystilbene in 8.6% overall yield via the Claisen rearrangement of an aryl reverse-prenyl ether as the key step. Cytotoxic activities against human pancreatic carcinoma PANC-1 cells of cajaninstilbene acid and amorfrutins A-D were also evaluated.
Shape-dependent leaf manipulation in the leaf rolling weevil Phymatapoderus pavens (Coleoptera: Attelabidae)
Authors: Higuchi Yumiko , Kawakita Atsushi
Published: February 2022

Plant leaves are utilized by various shelter-building insects. Some insects are constrained in their host plant use by the difficulty in modifying leaves into shelters, while others may cope through different construction methods. Here, we show that the leaf-rolling weevil Phymatapoderus pavens (Coleoptera, Attelabidae) constructs two types of leaf rolⅼ on Boehmeria silvestrii (Urticaceae) according to the shape of the leaf. Female weevils make leaf rolls using the whole leaf when the leaf is small and weakly lobed, whereas they use only one of the lateral lobes when the leaf is large and deeply lobed. Both types were found within a population and each functioned as a site for the growth of offspring. Weevils bite the leaf veins differently when constructing each of these leaf rolls, suggesting that the leaf roll type is determined before the leaf is rolled. Compared with another leaf-rolling weevil species, Apoderus praecellens (Coleoptera, Attelabidae), which makes leaf rolls on similarly lobed leaves of Isodon umbrosus var. hakusanensis (Lamiaceae), P. pavens utilizes a wider range of leaf shapes because these weevils are able to construct leaf rolls on the lateral lobes of the leaves. Differences in leaf-rolling behaviour, leaf venation pattern, and the relative size of weevils and leaves are factors affecting the results.
Attractiveness of floral traits to diverse pollinators in zygomorphic flowers of Isodon trichocarpus (Lamiaceae)
Authors: Itagaki Tomoyuki , Hoshi Kouta , Aoyagi Blue Yuta , Sakai Satoki
Published: February 2022

When the abundance and the composition of pollinators are unpredictable, exploitation of a diverse assemblage of pollinators is important for plant reproduction. To examine the role of floral traits in attracting diverse pollinators, we performed a field study using the zygomorphic flowers of Isodon trichocarpus. We investigated variation in floral traits among flowers and seasonal variation in pollinator assemblage and determined whether pollinator behaviour is linked to floral traits. We compared pollinator diversity among flowers by flower-based rarefaction and extrapolation. Pollinator diversity increased with span of corolla opening. The number of bumble bee visits increased with upper lip height. During the flowering period, there were only 2 days when all pollinator groups (wasps, bumble bees, small bees and hoverflies) were observed, and there were 4 days when only one group was observed. Thus, the degree of generalization was not similar for all flowers because pollinator visits differed according to floral traits and some pollinator groups were observed in only part of the flowering season. Our results show that floral form increased attractiveness to diverse pollinators and that different flower traits were associated with different pollinator visits. Thus, pollinator assemblage in this species is related to floral traits.
All for one: changes in mitochondrial morphology and activity during syncytial oogenesis
Authors: Urbisz Anna Z , Chajec Łukasz , Małota Karol , Student Sebastian , Sawadro Marta K , Śliwińska Małgorzata A , Świątek Piotr
Published: February 2022

The syncytial groups of germ cells (germ-line cysts) forming in ovaries of clitellate annelids are an attractive model to study mitochondrial stage-specific changes. Using transmission electron microscopy, serial block-face scanning electron microscopy, and fluorescent microscopy, we analyzed the mitochondria distribution and morphology and the state of membrane potential in female cysts in Enchytraeus albidus. We visualized in 3D at the ultrastructural level mitochondria in cysts at successive stages: 2-celled, 4-celled, 16-celled cysts, and cyst in advanced oogenesis. We found that mitochondria form extensive aggregates—they are fused and connected into large and branched mitochondrial networks. The most extensive networks are formed with up to 10 000 fused mitochondria, whereas individual organelles represent up to 2% of the total mitochondrial volume. We classify such a morphology of mitochondria as a dynamic hyperfusion state and suggest that this can maintain their high activity and intensify the process of cellular respiration within the syncytial cysts. We found some individual mitochondria undergoing degradation, which implies that damaged mitochondria are removed from networks for their final elimination. As growing oocytes were shown to possess less active mitochondria than the nurse cells, the high activity of mitochondria in the nurse cells and their dynamic hyperfusion state are attributed to serve the needs of the growing oocyte. In addition, we measured by calorimetry the total antioxidant capacity of germ-line cysts in comparison with somatic tissue, and it suggests that antioxidative defense systems, together with mitochondrial networks, can effectively protect germ-line mitochondria from damage.
From temporal to spatial topography: hierarchy of neural dynamics in higher- and lower-order networks shapes their complexity
Authors: Golesorkhi Mehrshad , Gomez-Pilar Javier , Çatal Yasir , Tumati Shankar , Yagoub Mustapha C E , Stamatakis Emanuel A , Northoff Georg
Published: February 2022

The brain shows a topographical hierarchy along the lines of lower- and higher-order networks. The exact temporal dynamics characterization of this lower-higher-order topography at rest and its impact on task states remains unclear, though. Using 2 functional magnetic resonance imaging data sets, we investigate lower- and higher-order networks in terms of the signal compressibility, operationalized by Lempel–Ziv complexity (LZC). As we assume that this degree of complexity is related to the slow–fast frequency balance, we also compute the median frequency (MF), an estimation of frequency distribution. We demonstrate (i) topographical differences at rest between higher- and lower-order networks, showing lower LZC and MF in the former; (ii) task-related and task-specific changes in LZC and MF in both lower- and higher-order networks; (iii) hierarchical relationship between LZC and MF, as MF at rest correlates with LZC rest–task change along the lines of lower- and higher-order networks; and (iv) causal and nonlinear relation between LZC at rest and LZC during task, with MF at rest acting as mediator. Together, results show that the topographical hierarchy of lower- and higher-order networks converges with their temporal hierarchy, with these neural dynamics at rest shaping their range of complexity during task states in a nonlinear way.
Reproduction Numbers of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants: A Systematic Review and Meta-analysis
Authors: Du Zhanwei , Liu Caifen , Wang Chunyu , Xu Lingfeng , Xu Mingda , Wang Lin , Bai Yuan , Xu Xiaoke , Lau Eric H Y , Wu Peng , Cowling Benjamin J
Published: February 2022

The coronavirus disease 2019 (COVID-19) pandemic continues to pose substantial risks to public health, worsened by the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that may have a higher transmissibility and reduce vaccine effectiveness. We conducted a systematic review and meta-analysis on reproduction numbers of SARS-CoV-2 variants and provided pooled estimates for each variant.
Effect of water management on microbial diversity and composition in an Italian rice field system
Authors: Hester Eric R , Vaksmaa Annika , Valè Giampiero , Monaco Stefano , Jetten Mike S M , Lüke Claudia
Published: February 2022

Traditional rice cultivation consumes up to 2500 L of water per kg yield and new strategies such as the ‘Alternate Wetting and Drying’ (AWD) might be promising water-saving alternatives. However, they might have large impacts on the soil microbiology. In this study, we compared the bacterial and archaeal communities in experimental field plots, cultivated under continuously flooding (CF) and AWD management, by high-throughput sequencing of the 16S rRNA gene. We analysed alpha and beta diversity in bulk soil and on plant roots, in plots cultivated with two different rice cultivars. The strongest difference was found between soil and root communities. Beside others, the anaerobic methanotroph Methanoperedens was abundant in soil, however, we detected a considerable number of ANME-2a-2b on plant roots. Furthermore, root communities were significantly affected by the water management: Differential abundance analysis revealed the enrichment of aerobic and potentially plant-growth-promoting bacteria under AWD treatment, such as Sphingomonadaceae and Rhizobiaceae (both Alphaproteobacteria), and Bacteroidetes families. Microorganisms with an overall anaerobic lifestyle, such as various Delta- and Epsilonproteobacteria, and Firmicutes were depleted. Our study indicates that the bulk soil communities seem overall well adapted and more resistant to changes in the water treatment, whereas the root microbiota seems more vulnerable.
Clonal hematopoiesis as a pitfall in germline variant interpretation in the context of Mendelian disorders
Authors: Brunet Theresa , Berutti Riccardo , Dill Veronika , Hecker Judith S , Choukair Daniela , Andres Stephanie , Deschauer Marcus , Diehl-Schmid Janine , Krenn Martin , Eckstein Gertrud , Graf Elisabeth , Gasser Thomas , Strom Tim M , Hoefele Julia , Götze Katharina S , Meitinger Thomas , Wagner Matias
Published: February 2022

Clonal hematopoiesis because of somatic mutations in hematopoietic stem/progenitor cells is an age-related phenomenon and commonly observed when sequencing blood DNA in elderly individuals. Several genes that are implicated in clonal hematopoiesis are also associated with Mendelian disorders when mutated in the germline, potentially leading to variant misinterpretation. We performed a literature search to identify genes associated with age-related clonal hematopoiesis followed by an OMIM query to identify the subset of genes in which germline variants are associated with Mendelian disorders. We retrospectively screened for diagnostic cases in which the presence of age-related clonal hematopoiesis confounded exome sequencing data interpretation. We found 58 genes in which somatic mutations are implicated in clonal hematopoiesis, while germline variants in the same genes are associated with Mendelian (mostly neurodevelopmental) disorders. Using five selected cases of individuals with suspected monogenic disorders, we illustrate how clonal hematopoiesis in either variant databases or exome sequencing datasets poses a pitfall, potentially leading to variant misclassification and erroneous conclusions regarding gene–disease associations.
Duration of Humoral Immunity and Cross-Neutralizing Activity Against the Alpha, Beta, and Delta Variants After Wild-Type Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Prospective Cohort Study
Authors: Noh Ji Yun , Yang Jeong Sun , Hwang Soon Young , Hyun Hakjun , Seong Hye , Gu Yoon Jin , Yoon Soo Young , Cheong Hee Jin , Kim Woo Joo , Park Woo Jung , Kim Jun Won , Lee Joo Yeon , Song Joon Young
Published: February 2022

A prospective cohort study was conducted for adults with a diagnosis of with coronavirus disease 2019 (COVID-19). Convalescent blood samples were obtained 4, 6, and 11 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The seropositivity of anti-spike antibody was maintained in all patients (100%) until 11 months after COVID-19 diagnosis. Neutralizing antibody levels against wild-type SARS-CoV-2 gradually decreased but remained positive in >50% of patients 11 months after diagnosis: in 98.5% (67 of 68) at 4 months, 86.8% (46 of 53) at 6 months, and 58.8% (40 of 68) at 11 months. However, cross-neutralizing activity against the Beta and Delta variants was attenuated 2.53-fold and 2.93-fold, respectively, compared with the wild-type strain.
Morbidity of Respiratory Syncytial Virus (RSV) Infections: RSV Compared With Severe Acute Respiratory Syndrome Coronavirus 2 Infections in Children Aged 0–4 Years in Cologne, Germany
Authors: Meyer Meike , Ruebsteck Esra , Eifinger Frank , Klein Florian , Oberthuer André , van Koningsbruggen-Rietschel Silke , Huenseler Christoph , Weber Lutz Thorsten
Published: February 2022

The aim of this retrospective analysis was to provide information on how infections with respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) differ in symptoms, clinical course, outcome, and utilization of hospital care. We investigated 748 polymerase chain reaction results from symptomatic children aged 0–4 years in Cologne, Germany. One hundred sixty-nine patients tested positive for RSV (22.6%) and 24 children for SARS-CoV-2 (3.2%). Symptomatic patients with RSV infection were hospitalized significantly longer. RSV-positive patients needed oxygen supplementation significantly more often as well as high-flow therapy. With regard to care efforts, RSV-infected patients put higher pressure on the hospital and utilized more hospital resources.
Invasive Pneumococcal Disease Clusters Disproportionally Impact Persons Experiencing Homelessness, Injecting Drug Users, and the Western United States
Authors: Beall Bernard , Chochua Sopio , Li Zhongya , Tran Theresa , Varghese Jasmine , McGee Lesley , Li Yuan , Metcalf Benjamin J
Published: February 2022

Background

Invasive pneumococcal disease (IPD) isolates forming genomic clusters can reflect rapid disease transmission between vulnerable individuals.

Methods

We performed whole genome sequencing of 2820 IPD isolates recovered during 2019 through Centers for Disease Control and Prevention’s Active Bacterial Core surveillance to provide strain information (serotypes, resistance, genotypes), and 2778 of these genomes were analyzed to detect highly related genomic clusters.

Results

Isolates from persons experiencing homelessness (PEH) were more often within genomic clusters than those from persons not experiencing homelessness (PNEH) (105/198 [53.0%] vs 592/2551 [23.2%]; P < .001). The 4 western sites accounted for 33.4% (929/2778) of isolates subjected to cluster analysis yet accounted for 48.7% (343/705) of clustering isolates (P < .001) and 75.8% (150/198) of isolates recovered from PEH (P < .001). Serotypes most frequent among PEH were (in rank order) 12F, 4, 3, 9N, 8, 20, and 22F, all of which were among the 10 serotypes exhibiting the highest proportions of clustering isolates among all cases. These serotypes accounted for 44.9% (1265/2820) of all IPD cases and are included within available vaccines.

Conclusions

We identified serotype-specific and geographic differences in IPD transmission. We show the vulnerability of PEH within different regions to rapidly spreading IPD transmission networks representing several pneumococcal serotypes included in available vaccines.
Limiting factors for milk production in dairy cows: perspectives from physiology and nutrition
Authors: Gross Josef J
Published: February 2022

Milk production in dairy cows increases worldwide since many decades. With rising milk yields, however, potential limiting factors are increasingly discussed. Particularly, the availability of glucose and amino acids is crucial to maintain milk production as well as animal health. Limitations arise from feed sources, the rumen and digestive tract, tissue mobilization, intermediary metabolism and transport, and the uptake of circulating nutrients by the lactating mammary gland. The limiting character can change depending on the stage of lactation. Although physiological boundaries are prevalent throughout the gestation–lactation cycle, limitations are aggravated during the early lactation period when high milk production is accompanied by low feed intake and high mobilization of body reserves. The knowledge about physiological constraints may help to improve animal health and make milk production more sustainably. The scope of this review is to address contemporary factors related to production limits in dairy cows from a physiological perspective. Besides acknowledged physiological constraints, selected environmental and management-related factors affecting animal performance and physiology will be discussed. Potential solutions and strategies to overcome or to alleviate these constraints can only be presented briefly. Instead, they are thought to address existing shortcomings and to identify possibilities for optimization. Despite a scientific-based view on physiological limits, we should keep in mind that only healthy animals could use their genetic capacity and produce high amounts of milk.
Antibiotics Alter the Expression of Genes Related to Behavioral Development in Honey Bees (Hymenoptera: Apidae)
Authors: Ortiz-Alvarado Yarira , Giray Tugrul
Published: February 2022

Honey bees, as many species of social insects, display a division of labor among colony members based on behavioral specializations related to age. Adult worker honey bees perform a series of tasks in the hive when they are young (such as brood care or nursing) and at ca. 2–3 wk of age, shift to foraging for nectar and pollen outside the hive. The transition to foraging involves changes in metabolism and neuroendocrine activities. These changes are associated with a suite of developmental genes. It was recently demonstrated that antibiotics influence behavioral development by accelerating or delaying the onset of foraging depending on timing of antibiotic exposure. To understand the mechanisms of these changes, we conducted a study on the effects of antibiotics on expression of candidate genes known to regulate behavioral development. We demonstrate a delay in the typical changes in gene expression over the lifetime of the individuals that were exposed to antibiotics during immature stage and adulthood. Additionally, we show an acceleration in the typical changes in gene expression on individuals that were expose to antibiotics only during immature stage. These results show that timing of antibiotic exposure alter the typical regulation of behavioral development by metabolic and neuroendocrine processes.
Explaining deep learning of galaxy morphology with saliency mapping
Authors: Bhambra Prabh , Joachimi Benjamin , Lahav Ofer
Published: February 2022

We successfully demonstrate the use of explainable artificial intelligence (XAI) techniques on astronomical data sets in the context of measuring galactic bar lengths. The method consists of training convolutional neural networks on human classified data from Galaxy Zoo in order to predict general galaxy morphologies, and then using SmoothGrad (a saliency mapping technique) to extract the bar for measurement by a bespoke algorithm. We contrast this to another method of using a convolutional neural network to directly predict galaxy bar lengths. These methods achieved correlation coefficients of 0.76 and 0.59, and root mean squared errors of 1.69 and 2.10 respective to human measurements. We conclude that XAI methods outperform conventional deep learning in this case, which could be reasonably explained by the larger data sets available when training the models. We suggest that our XAI method can be used to extract other galactic features (such as the bulge-to-disc ratio) without needing to collect new data sets or train new models. We also suggest that these techniques can be used to refine deep learning models as well as identify and eliminate bias within training data sets.
An observational synthesis of the Taurid meteor complex
Authors: Egal A , Brown P G , Wiegert P , Kipreos Y
Published: February 2022

We provide an overview of the observational properties of the four major Taurid showers, namely the Northern and Southern Taurids (#017 NTA and #002 STA), the β Taurids (#173 BTA), and the ζ Perseids (#172 ZPE). Analysing more than two decades of meteor observations from visual, optical, and radar measurements, we present the Taurids average activity, annual variations in strength, radiant drift, and orbital variations as a function of solar longitude and particle size. The Taurid showers are detected over several weeks in the spring and autumn, but their annual activity level is generally low (less than 15 visual meteors per hour). We find the STA to be pre-dominant in autumn, while its twin, the ZPE, dominates over the BTA in spring. Due to their long duration, the position of each shower’s radiant and orbital elements are variable with time. Optical measurements have previously recorded enhanced STA activity and increased fireball rates caused by the return of a swarm of meteoroids trapped in the 7:2 mean motion resonance with Jupiter. However, we find no presence of the swarm in radar data, suggesting that small meteoroids are removed from the resonance faster than fireball-producing meteoroids. We also find the STA to be enriched in smaller particles early in their activity period. The differences we identify in our analysis between the showers at different particle sizes provide strong observational constraints to future dynamical modelling of the Taurid Meteoroid Complex.
Acceleration and cooling of the corona during X-ray flares from the Seyfert galaxy I Zw 1
Authors: Wilkins D R , Gallo L C , Costantini E , Brandt W N , Blandford R D
Published: February 2022

We report on X-ray flares that were observed from the active galactic nucleus I Zwicky 1 (I Zw 1) in 2020 January by the NuSTAR and XMM-Newton observatories. The X-ray spectrum is well-described by a model comprised of the continuum emission from the corona and its reflection from the accretion disc around a rapidly spinning (a > 0.94) black hole. In order to model the broadband spectrum, it is necessary to account for the variation in ionization across the disc. Analysis of the X-ray spectrum in time periods before, during and after the flares reveals the underlying changes to the corona associated with the flaring. During the flares, the reflection fraction drops significantly, consistent with the acceleration of the corona away from the accretion disc. We find the first evidence that during the X-ray flares, the temperature drops from $140_{-20}^{+100}$ keV before to $45_{-9}^{+40}$ keV during the flares. The profile of the iron K line reveals the emissivity profile of the accretion disc, showing it to be illuminated by a compact corona extending no more than $7_{-2}^{+4}$ rg over the disc before the flares, but with tentative evidence that the corona expands as it is accelerated during the flares. Once the flares subsided, the corona had collapsed to a radius of $6_{-2}^{+2}$ rg. The rapid time-scale of the flares suggests that they arise within the black hole magnetosphere rather than in the accretion disc, and the variation of the corona is consistent with the continuum arising from the Comptonization of seed photons from the disc.
Cdc48Ufd1/Npl4 segregase removes mislocalized centromeric histone H3 variant CENP-A from non-centromeric chromatin
Authors: Ohkuni Kentaro , Gliford Loran , Au Wei-Chun , Suva Evelyn , Kaiser Peter , Basrai Munira A
Published: February 2022

Restricting the localization of CENP-A (Cse4 in Saccharomyces cerevisiae) to centromeres prevents chromosomal instability (CIN). Mislocalization of overexpressed CENP-A to non-centromeric chromatin contributes to CIN in budding and fission yeasts, flies, and humans. Overexpression and mislocalization of CENP-A is observed in cancers and is associated with increased invasiveness. Mechanisms that remove mislocalized CENP-A and target it for degradation have not been defined. Here, we report that Cdc48 and its cofactors Ufd1 and Npl4 facilitate the removal of mislocalized Cse4 from non-centromeric chromatin. Defects in removal of mislocalized Cse4 contribute to lethality of overexpressed Cse4 in cdc48,ufd1 andnpl4 mutants. High levels of polyubiquitinated Cse4 and mislocalization of Cse4 are observed in cdc48-3, ufd1-2 and npl4-1mutants even under normal physiological conditions, thereby defining polyubiquitinated Cse4 as the substrate of the ubiquitin directed segregase Cdc48Ufd1/Npl4. Accordingly, Npl4, the ubiquitin binding receptor, associates with mislocalized Cse4, and this interaction is dependent on Psh1-mediated polyubiquitination of Cse4. In summary, we provide the first evidence for a mechanism that facilitates the removal of polyubiquitinated and mislocalized Cse4 from non-centromeric chromatin. Given the conservation of Cdc48Ufd1/Npl4 in humans, it is likely that defects in such pathways may contribute to CIN in human cancers.
The Burkholderia cenocepacia iron starvation σ factor, OrbS, possesses an on-board iron sensor
Authors: Butt Aaron T , Banyard Christopher D , Haldipurkar Sayali S , Agnoli Kirsty , Mohsin Muslim I , Vitovski Srdjan , Paleja Ameya , Tang Yingzhi , Lomax Rebecca , Ye Fuzhou , Green Jeffrey , Thomas Mark S
Published: February 2022

Burkholderia cenocepacia is an opportunistic pathogen that causes severe infections of the cystic fibrosis (CF) lung. To acquire iron, B. cenocepacia secretes the Fe(III)-binding compound, ornibactin. Genes for synthesis and utilisation of ornibactin are served by the iron starvation (IS) extracytoplasmic function (ECF) σ factor, OrbS. Transcription of orbS is regulated in response to the prevailing iron concentration by the ferric uptake regulator (Fur), such that orbS expression is repressed under iron-sufficient conditions. Here we show that, in addition to Fur-mediated regulation of orbS, the OrbS protein itself responds to intracellular iron availability. Substitution of cysteine residues in the C-terminal region of OrbS diminished the ability to respond to Fe(II) in vivo. Accordingly, whilst Fe(II) impaired transcription from and recognition of OrbS-dependent promoters in vitro by inhibiting the binding of OrbS to core RNA polymerase (RNAP), the cysteine-substituted OrbS variant was less responsive to Fe(II). Thus, the cysteine residues within the C-terminal region of OrbS contribute to an iron-sensing motif that serves as an on-board ‘anti-σ factor’ in the presence of Fe(II). A model to account for the presence two regulators (Fur and OrbS) that respond to the same intracellular Fe(II) signal to control ornibactin synthesis and utilisation is discussed.
Summarizing internal dynamics boosts differential analysis and functional interpretation of super enhancers
Authors: Liu Xiang , Zhao Bo , Shaw Timothy I , Fridley Brooke L , Duckett Derek R , Tan Aik Choon , Teng Mingxiang
Published: February 2022

Super enhancers (SEs) are broad enhancer domains usually containing multiple constituent enhancers that hold elevated activities in gene regulation. Disruption in one or more constituent enhancers causes aberrant SE activities that lead to gene dysregulation in diseases. To quantify SE aberrations, differential analysis is performed to compare SE activities between cell conditions. The state-of-art strategy in estimating differential SEs relies on overall activities and neglect the changes in length and structure of SEs. Here, we propose a novel computational method to identify differential SEs by weighting the combinatorial effects of constituent-enhancer activities and locations (i.e. internal dynamics). In addition to overall activity changes, our method identified four novel classes of differential SEs with distinct enhancer structural alterations. We demonstrate that these structure alterations hold distinct regulatory impact, such as regulating different number of genes and modulating gene expression with different strengths, highlighting the differentiated regulatory roles of these unexplored SE features. When compared to the existing method, our method showed improved identification of differential SEs that were linked to better discernment of cell-type-specific SE activity and functional interpretation.
Isolated Pulmonary Emergomycosis in an Immunocompetent Patient in Alberta, Canada
Authors: Mah Jordan , Bakker Andrea , Tseng Calvin , Lafay-Cousin Lucie , Kuhn Susan , Brundler Marie-Anne , Lisboa Luiz F
Published: February 2022

Emergomyces canadensis pulmonary infection was incidentally diagnosed in an asymptomatic patient suspected to have metastatic osteosarcoma. Molecular diagnosis was imperative to fungal identification given overlapping histopathological features with histoplasmosis. This report documents a case of isolated pulmonary emergomycosis in an otherwise immunocompetent patient while discussing diagnostic and management pitfalls of this emerging and underdiagnosed infection.
Efficacy of Noncarbapenem β-Lactams Compared to Carbapenems for Extended-Spectrum β-Lactamase–Producing Enterobacterales Urinary Tract Infections
Authors: Anderson Daniel T , Albrecht Benjamin , Jones K Ashley , Jacob Jesse T , Sexton Mary Elizabeth , Wiley Zanthia , Dube William C , Lee Benjamin , Suchindran Sujit
Published: February 2022

Background

Extended-spectrum β-lactamase (ESBL)–producing Enterobacterales are frequent causes of urinary tract infections (UTIs). Severe infections caused by ESBL Enterobacterales are often treated with carbapenems, but optimal treatment for less severe infections such as UTIs is unclear.

Methods

This retrospective cohort study included patients admitted to 4 hospitals in an academic healthcare system with an ESBL UTI treated with either a noncarbapenem β-lactam (NCBL) or a carbapenem for at least 48 hours from 1 April 2014 to 30 April 2018. Those who received an NCBL were compared to those receiving a carbapenem, with a primary outcome of hospital length of stay (LOS) and secondary outcomes of clinical and microbiological response, days until transition to oral therapy, rate of relapsed infection, and rate of secondary infections with a multidrug-resistant organism.

Results

Characteristics were similar among patients who received carbapenems (n = 321) and NCBLs (n = 171). There was no difference in LOS for the NCBL group compared to the carbapenem group (13 days vs 15 days, P = .66). The NCBL group had higher rates of microbiologic eradication (98% vs 92%, P = .002), shorter time to transition to oral therapy (5 days vs 9 days, P < .001), shorter overall durations of therapy (7 days vs 10 days, P < .001), and lower rates of relapsed infections (5% vs 42%, P = .0003).

Conclusions

Patients treated with NCBLs had similar LOS, higher rates of culture clearance, and shorter durations of antibiotic therapy compared to patients treated with carbapenems, suggesting that treatment for ESBL UTIs should not be selected solely based on phenotypic resistance.
Costs and Prescribing Patterns of Anthelmintics in the United States Military: A Retrospective Analysis
Authors: Lindrose Alyssa R , Fraser Jamie A , Hickey Patrick W , Mitre Edward
Published: February 2022

Background

Recent price increases in medications used to treat helminth infections have had demonstrated impacts on Medicaid and immigrant patient populations. Helminth infections are common within the US military; however, anthelmintic prescribing patterns and costs have not yet been investigated in this patient population.

Methods

We conducted a retrospective analysis of pharmaceutical data from the Military Health System Data Repository between fiscal years 2012 and 2019. Prescription information, including costs and demographics, were abstracted for all anthelmintic medications as well as associated helminth diagnostic codes within 30 days of the prescription dispensing date.

Results

On average, there were 10 871 anthelmintic medications prescribed per year, for a total of 86 697 during the study period. Ivermectin and albendazole were each prescribed >34 000 times. There were 15 498 mebendazole prescriptions and 1327 praziquantel prescriptions. The total cost of all anthelmintic prescriptions was $16 018 381. Annual costs for anthelmintic medications increased 16-fold during the study period, up to nearly $5 000 000 in fiscal year 2019, primarily driven by price increases in albendazole and mebendazole. Albendazole prescriptions accounted for $12 282 891 of total costs (76.7%), though only 39.1% of total prescriptions. The most common diagnosis associated with albendazole and mebendazole prescriptions was enterobiasis.

Conclusions

Price increases in anthelmintic medications have significantly impacted the costs borne by the US government for treating parasitic infections. There are a substantial number of anthelmintic prescriptions in the US military health care system annually, suggesting a higher number of helminth infections than previously thought.