bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparative study of receptor interactions between SARS-CoV and SARS-CoV-2 from molecular modeling
Authors: Lai Hien T. T. , Nguyen Ly H. , Phan Anh D. , Kranjc Agata , Nguyen Toan T. , Nguyen-Manh Duc
Published: September 2022

The pandemic of COVID-19 severe acute respiratory syndrome, which was fatal for millions of people worldwide, triggered the race to understand in detail the molecular mechanisms of this disease. In this work, the differences of interactions between the SARS-CoV/SARS-CoV-2 Receptor binding domain (RBD) and the human Angiotensin Converting Enzyme 2 (ACE2) receptor were studied usingin silicotools. Our results show that SARS-CoV-2 RBD is more stable and forms more interactions with ACE2 than SARS-CoV. At its interface, three stable binding patterns are observed and named red-K31, green-K353 and blue-M82 according to the central ACE2 binding residue. In SARS-CoV instead, only the first two binding patches are persistently formed during the MD simulation. Our MM/GBSA calculations indicate the binding free energy difference of about 2.5 kcal/molbetween SARS-CoV-2 and SARS-CoV which is compatible with the experiments. The binding free energy decomposition points out that SARS-CoV-2 RBD–ACE2 interactions of the red-K31 ($$-23.5~\pm ~0.2~kcal/mol$$-23.5±0.2kcal/mol) and blue-M82 ($$-9.1~\pm ~0.1~kcal/mol$$-9.1±0.1kcal/mol) patterns contribute more to the binding affinity than in SARS-CoV ($$-1.8~\pm ~0.02~kcal/mol$$-1.8±0.02kcal/molfor red-K31), while the contribution of the green-K353 pattern is very similar in the two strains ($$-17.8~\pm ~0.2~kcal/mol$$-17.8±0.2kcal/moland$$-22.7~\pm ~0.1~kcal/mol$$-22.7±0.1kcal/molfor SARS-CoV-2 and SARS-CoV, respectively). Five groups of mutations draw our attention at the RBD–ACE2 binding interface, among them, the mutation –PPA469-471/GVEG482-485 has the most important and favorable impact on SARS-CoV-2 binding to the ACE2 receptor. These results, highlighting the molecular differences in the binding between the two viruses, contribute to the common knowledge about the new corona virus and to the development of appropriate antiviral treatments, addressing the necessity of ongoing pandemics.
Combined retention of large living and dead trees can improve provision of tree-related microhabitats in Central European montane forests
Authors: Spînu Andreea Petronela , Asbeck Thomas , Bauhus Jürgen
Published: September 2022

Retention of habitat trees is a common biodiversity conservation practice in continuous cover forests of temperate Europe. Commonly, living habitat trees are selected on the basis of their tree-related microhabitats (TreMs) such as cavities or crown deadwood. Owing to the increasing frequency and intensity of climate change-related disturbances, habitat trees in particular are expected to experience increased mortality rates. This may impact the long-term provisioning of TreMs. Here, we compared the TreM occurrence on living and dead trees to investigate whether dead trees support more and other TreMs than living trees. We also hypothesized that a combination of living and dead trees results in the most diverse stand-level TreM composition. We surveyed the TreM composition of living and dead habitat trees in 133 one-hectare plots in the Black Forest region managed according to a continuous cover approach. We fitted generalized linear mixed models to identify the main predictors of TreM occurrence to predict their abundance and richness. Tree identity (as a combination of species and vitality status) and diameter were the main drivers of TreM abundance and richness, which were highest on dead Abies alba. Even though dead A. alba and Picea abies supported TreM numbers similar to those provided by large living trees, their TreM composition was significantly different. This suggests that dead trees cannot substitute the habitat functions of living habitat trees, but they can complement them to increase the overall stand-level TreM diversity, in particular through decayed, large snags.
Comparing Reading Comprehension of Narrative and Expository Texts Based on the Direct and Inferential Mediation Model
Authors: Härtig Hendrik , Bernholt Sascha , Fraser Nicole , Cromley Jennifer G. , Retelsdorf Jan
Published: September 2022

Reading comprehension is an essential skill for learning in general and in science classes. Problems with reading comprehension might hinder students’ participation in learning science. Text in science includes specific language features that distinguishes it from narrative text, so should reading instruction be part of teaching science? The direct and inferential mediation (DIME) model of reading comprehension subsumes factors that influence reading comprehension. It was tested separately regarding narrative text as well as expository text in English; however, both have not been tested by directly comparing them to each other. In this study, we investigated to what degree general reading comprehension of narrative text is directly comparable to topic-specific reading comprehension of science text. Hence, first the applicability of the DIME model of reading comprehension in another language (i.e. German) was tested. Second, a general reading comprehension model was directly compared to a topic-specific model for reading comprehension of science text. Participants across the two studies were 704 German Grade 8 students who completed measures of comprehension and the DIME predictor variables. Results of two path analyses indicate the general applicability of the model for another language and additionally for both genres. However, some differences are highlighted that may be of importance in future science-specific studies as well as for teaching science.
Strengthening mechanisms and wear behavior of electrodeposited Ni–SiC nanocomposite coatings
Authors: Pinate S. , Ghassemali E. , Zanella C.
Published: September 2022

The present paper describes the study of the synergism between the matrix microstructure and reinforcement phase in electrodeposited nanocomposite coatings. Adding hard nanoparticles into the metallic matrix leads to hardening of the coating. The effects of particle load, size and dispersion on hardening as well as their influence on metal microstructure refinement were studied. The relative contributions of strengthening factors in Ni/nano-SiC composites, namely, Hall–Petch strengthening, Orowan strengthening, enhanced dislocation density and particles incorporation, were evaluated. The production of various coatings under different stirring conditions and powders resulted in dissimilarities in the incorporation of particles. The Hall–Petch relationship for pure nickel was determined using samples produced under different current densities. Additionally, the grain refinement resulting from the particle codeposition and agitation mode were identified as influential factors in grain-size strengthening. Dislocation density strengthening was significant in electrodeposits produced using ultrasonic agitation, while it was negligible in layers produced under other conditions. Particles codeposition affected the magnitude of Orowan strengthening, resulting in cases where strengthening was negligible despite the presence of particles. The sum of contributions and the modified Clyne methods were used to calculate the hardness of the composites based on the contribution of each strengthening factor, and the calculation results were in good agreement with experimental data. The wear behavior of the composites was analyzed by pin-on-disk measurements, and the results correlated with the strengthening mechanisms. Particle size, dispersion and content increased the strengthening effects as well as the hardness and wear resistance of the coatings.

Graphical abstract
Elasmobranchs from Indonesian Waters: Feeding Ecology and Trypanorhynch Cestode Fauna Composition to Support Efforts in Shark and Ray Conservation
Authors: Kleinertz S. , Yulianto I. , Kurschat C. , Koepper S. , Simeon B. M. , Klimpel S. , Theisen S. , Unger P. , Retnoningtyas H. , Neitemeier-Duventester X. , Barton D. P. , Damriyasa I. M. , Palm H. W.
Published: September 2022

Purpose

The stomachs and spiral valves of sharks and rays were examined for their trypanorhynch (Cestoda) parasite fauna and dietary items to infer feeding ecology. In Indonesia, sharks and rays have been experiencing increasing awareness and conservation in the recent years due to high fisheries activities and to avoid future species extinction.

Methods

The samples were collected in 2009 from two different sampling sites at the southern coasts of Java and Bali in Indonesia. The parasite fauna was studied for 41 elasmobranch fishes. Amongst these, three shark species, Carcharhinus sorrah, Carcharhinus sp. I and Squalus megalops and seven ray species, Brevitrygon heterura, B. cf. heterura, Gymnura zonura, Maculabatis gerrardi, Mobula kuhlii, Neotrygon cauruleopuncatata and Rhinobatos penggali were studied. Four additional specimens, belonging to the shark species Carcharhinus sp. II and Mustelus cf. manazo and the ray species Maculabatis gerrardi were studied from the waters of South Bali.

Results

Analyses of the feeding ecology of the ray M. gerrardi revealed distinct differences between both sampling sites, indicating the presence of ecological differences between the geographically independent regions. A total of 11 different trypanorhynch species/taxa belonging to the five families Eutetrarhynchidae (5), Gilquiniidae (1), Lacistorhynchidae (1), Pterobothriidae (1) and Tentaculariidae (3) were found. Ten trypanorhynch species from Penyu Bay and four species from South Bali could be identified. Two taxa that might represent new species were collected: Dollfusiella sp. from Brevitrygon heterura and Prochristianella sp. from Maculabatis gerrardi.

Conclusions

The present paper gives insights in using the trypanorhynch cestode community in combination with feeding ecology analyses to support conservation of elasmobranchs in Indonesian waters.
Existence of solutions of discrete fractional problem coupled to mixed fractional boundary conditions
Authors: Bourguiba Rim , Cabada Alberto , Kalthoum Wanassi Om
Published: September 2022

In this paper, we introduce a two-point nonlinear boundary value problem for a finite fractional difference equation. An associated Green’s function is constructed as a series of functions and some of its properties are obtained. Some existence results are deduced from fixed point theory and lower and upper solutions.
The Social Activity of Polish Migrants in the Republic of Ireland from the Perspective of Their Religiosity
Authors: Sadlon Wojciech
Published: September 2022

Background

This article is focused on social activity of Polish migrants in the Republic of Ireland in the context of change in their religiosity after coming to Ireland.

Purpose

This research applies statistical methods to the study of the impact of change in religiosity going beyond answering the question of whether migration is a disruptive event that either alienates immigrants from religious practices or, instead, ‘theologizes’ them.

Methods

It statistically verifies the correlation between social activity and change in religiosity and linear regression models of Polish migrants in Ireland and presents the results of a survey on Polish migrants in Ireland based on Respondent-Driven Sampling conducted in 2018 and 2019 (n = 520).

Results

The results highlight that the process of change in religiosity has two different patterns. The first one concerns both migrants who declare ‘no degree of religious change’ in themselves and these who affirm ‘a decline’ in their religious attitudes. The second mode of religious change concerns a minority of Polish migrants who declare themselves to have experienced a religious revival in Ireland. This group who feel themselves to have undergone a religious revival is socially active and participates in local activities in Ireland. The linear regression analysis demonstrates that a statistically significant relationship exists between social activity and especially prayer when controlling for demographic characteristics.

Conclusions and Implications

Migration not only deconstructs religiosity but, for the group of Polish migrants studied, it was accompanied by religious renewal and social activism. Statistical methods should take into account the fact that religiosity is not a deterministic characteristic of individuals but rather as pertaining to the individual's independent properties and capable of exerting autonomous influences’.
Updates in Hypersensitivity Pneumonitis: A Narrative Review
Authors: Anwar Javeria , Kong Wing Tai , Balakrishnan Bathmapriya
Published: September 2022

Purpose of Review

Hypersensitivity pneumonitis (HP) is an immune-mediated disease triggered by a known or unknown antigen. While reversible in the early stages of disease, progression toward irreversible pulmonary fibrosis may occur. This narrative review summarizes recent publications highlighting a methodical approach toward the diagnosis, classification, and management of fibrotic and nonfibrotic HP.

Recent Findings

Establishing the diagnosis of HP is often challenging given its variable clinical course, extensive inciting agents, and overlapping features with other interstitial lung diseases. Recently, HP has been re-classified into nonfibrotic and fibrotic subtypes based on radiographic and histopathological features. Chronic fibrotic HP is associated with significant functional impairment and increased mortality. In addition to antigen avoidance, immunosuppression is the cornerstone of management in nonfibrotic HP. Antifibrotic agents have emerged as a therapeutic option in halting the progression of chronic fibrotic HP.

The combination of clinical, radiographical, and histopathological data will assist in increasing the diagnostic certainty of HP. The new dichotomization of HP is thought to provide better prognostication for patients. This review provides clinicians with a current and evidence-based approach toward the management of patients with HP.
Exploring the Perceived Relevance of University Mathematics Studies by First-Semester Teaching Students
Authors: Büdenbender-Kuklinski Christiane , Hochmuth Reinhard , Liebendörfer Michael
Published: September 2022

As earlier research results suggest that many mathematics teaching students criticize a missing relevance in their studies, we explore explanations and interrelationships of their relevance assessments. We aim at finding out how one could support the students in attributing relevance to their study programs. A two-fold model for relevance assessments in mathematics teacher education is proposed, consisting of relevance content and relevance reasons. We investigate students' relevance perceptions of mathematical topics and of topics’ complexities, as well as their rating of individual and societal/ vocational relevance reasons, all in relation to their perception of the relevance of their overall program of study. Contrary to earlier research findings, our results suggest that mathematics teaching students already do attribute relevance to many content areas and that a preparation for the teaching profession is not the only reason for them to assign relevance. There also seem to be many students who would attribute relevance if they could develop as individuals and pursue their interests. We suggest that giving students opportunities to set individual priorities in their studies could hence support their relevance assessments. As low relevance assessments seem to be connected to students’ motivational problems, students might profit from motivational support, as well.
Alternative Performance Measures: A Structured Literature Review of Research in Academic and Professional Journals
Authors: Herr Sascha B. , Lorson Peter , Pilhofer Jochen
Published: September 2022

For more than two decades, the reporting of so-called ‘alternative performance measures’ (APMs) has been a common phenomenon in external financial reporting. APMs are voluntarily disclosed and generally unaudited performance measures. Typically, APMs modify earnings measures calculated in accordance with generally accepted accounting principles (GAAP) by (subjectively) adjusting certain earnings components. In the academic literature, with the information motive on the one hand and the motive of (adversarial) investor influence on the other hand, two alternative explanations for the voluntary reporting of alternative performance measures are discussed, which are difficult, if not impossible, for external stakeholders to disentangle. Taking into account the recent developments in more than 250 published articles in the last decade, this paper critically reviews a wide range of literature from the United States (U.S.), Europe and, to a less extent, Australia/Asia. In particular, we analyse a comprehensive sample of more than 400 research papers published in academic and professional journals as well as other publications which are important in the academic discourse. The purpose of this paper is to identify relevant research gaps that provide starting points for future research. For this purpose, our methodological approach strictly follows structured literature review (SLR) methodology in order to minimise researcher idiosyncrasies. Thus, our SLR facilitates a decided derivation of research gaps based on a reliable and valid analytical framework which has been deductively derived from previous research.
Die chronische Pankreatitis
Authors: Steiner Emanuel , Maieron Andreas
Published: September 2022

Bei der chronischen Pankreatitis handelt es sich um eine entzündliche, fibrosierende Erkrankung mit progredientem Verlust der exokrinen und endokrinen Funktion.

Im Verlauf ist sie zusätzlich durch Alterationen des Gangsystems, im Sinn von Kalzifizierungen und Stenosen, sowie durch das Auftreten von Pseudozysten und Pankreasgangsteinen charakterisiert.

Die exokrine und endokrine Insuffizienz zusammen mit einem komplexen Schmerzsyndrom führen dabei zu einer massiven Einschränkung der Lebensqualität. Schmerzexazerbationen sind hierbei meist auf akute Entzündungsschübe, eine Obstruktion des Pankreasgangs (bzw. Gallengangs) und lokale Komplikationen, wie Pseudozysten, zurückzuführen.

Ziel ist eine frühe Diagnose und Reduktion der Risikofaktoren (Alkohol und Nikotin), um einen Progress der Erkrankung anzuhalten. Weiterhin ist eine adäquate Schmerztherapie (WHO-Stufenschema) und eine Substitution der exokrinen und endokrinen Insuffizienz mit Optimierung der Nährstoffversorgung zum Erhalt der Lebensqualität und Prävention einer katabolen Stoffwechsellage notwendig.

Bei fehlender Schmerzkontrolle, genauso wie bei Verdacht auf Komplikationen der chronischen Pankreatitis, sollte die Zuweisung in ein Zentrum für Pankreaserkrankung erfolgen. Hier besteht die Möglichkeit, im multidisziplinären Setting eine etwaige Therapieeskalation (medikamentös/endoskopisch/chirurgisch) zu evaluieren und umzusetzen.
Bayesian finite-population inference with spatially correlated measurements
Authors: Chan-Golston Alec , Banerjee Sudipto , Belin Thomas R. , Roth Sarah E. , Prelip Michael L.
Published: September 2022

Community-based public health interventions often rely on representative, spatially referenced outcome data to draw conclusions about a finite population. To estimate finite-population parameters, we are posed with two challenges: to correctly account for spatial association among the sampled and nonsampled participants and to correctly model missingness in key covariates, which may be also spatially associated. To accomplish this, we take inspiration from the preferential sampling literature and develop a general Bayesian framework that can specifically account for preferential non-response. This framework is first applied to three missing data scenarios in a simulation study. It is then used to account for missing data patterns seen in reported annual household income in a corner-store intervention project. Through this, we are able to construct finite-population estimates of the percent of income spent on fruits and vegetables. Such a framework provides a flexible way to account for spatial association and complex missing data structures in finite populations.
Microbial degradation of polyethylene terephthalate: a systematic review
Authors: Benavides Fernández Cesar David , Guzmán Castillo Michelly Paola , Quijano Pérez Silvia Andrea , Carvajal Rodríguez Lida Vivian
Published: September 2022

Plastic pollution levels have increased rapidly in recent years, due to the accumulation of plastic waste, including polyethylene terephthalate (PET). Both high production and the lack of efficient methods for disposal and recycling affect diverse aquatic and terrestrial ecosystems owing to the high accumulation rates of plastics. Traditional chemical and physical degradation techniques have caused adverse effects on the environment; hence, the use of microorganisms for plastic degradation has gained importance recently. This systematic review was conducted for evaluating the reported findings about PET degradation by wild and genetically modified microorganisms to make them available for future work and to contribute to the eventual implementation of an alternative, an effective, and environmentally friendly method for the management of plastic waste such as PET. Both wild and genetically modified microorganisms with the metabolic potential to degrade this polymer were identified, in addition to the enzymes and genes used for genetic modification. The most prevalent wild-type PET-degrading microorganisms were bacteria (56.3%, 36 genera), followed by fungi (32.4%, 30 genera), microalgae (1.4%; 1 genus, namelySpirulinasp.), and invertebrate associated microbiota (2.8%). Among fungi and bacteria, the most prevalent genera wereAspergillussp. andBacillussp., respectively. About genetically modified microorganisms, 50 strains ofEscherichia coli, most of them expressing PETase enzyme, have been used. We emphasize the pressing need for implementing biological techniques for PET waste management on a commercial scale, using consortia of microorganisms. We present this work in five sections: an Introduction that highlights the importance of PET biodegradation as an effective and sustainable alternative, a section on Materials and methods that summarizes how the search for articles and manuscripts in different databases was done, and another Results section where we present the works found on the subject, a final part of Discussion and analysis of the literature found and finally we present a Conclusion and prospects.
Facial identity protection using deep learning technologies: an application in affective computing
Authors: Mase Jimiama M. , Leesakul Natalie , Figueredo Grazziela P. , Torres Mercedes Torres
Published: September 2022

Automatic prediction of human attributions of valence and arousal using facial recognition technologies can improve human–computer and human–robot interaction. However, data protection has become an issue of great concern in affect recognition using facial images, as the facial identities of people (i.e. recognising who a person is) could be exposed in the process. For instance, malicious individuals could exploit facial images of users to assume their identities and infiltrate biometric authentication systems. Possible solutions to protect the facial identity of users are to: (1) extract anonymised facial features in users’ local machines, namely action units (AU) of facial images, discard their facial images and send the AUs to the developer for processing, and (2) employ a federated learning approach i.e. process users’ facial images in their local machines and only send their locally trained models back to the developer’s machine for augmenting the final model. In this paper, we implement and compare the performance of these privacy-preserving strategies for affect recognition. Results on the popular RECOLA affective datasets show promising affect recognition performance in adopting a federated learning approach to protect users’ identities, with Concordance Correlation Coefficient of 0.426 for valence and 0.390 for arousal.
An urban infrastructure assessment system built on geo-tagged images and machine learning
Authors: Zhang Ding , Yi Hongdu , Chen Yang , Jiang Nan , Shao Jinxin , Liu Liu
Published: September 2022

In modern era, the maintenance of public infrastructure often takes up a large share of financial budget for a city. The management of these urban assets is supported by a frequently updated inventory reflecting facility conditions. Traditional methods relying on inspection staff or sensors are faced with two main challenges: comprehensive and standardized data collection; quick and automatic assessment process. In this technical note, we introduce a unified method for condition assessment, purely based on street views and machine learning to develop perception quantification models with pairwise labeling datasets. In this way, the two problems could be solved with automatic and scalable processes, updatable algorithms, and affordable costs The method has been tested in the city of Ulaanbaatar, in which a benchmark covering the assessment of eight types of urban infrastructure (roadway, road curbs, road markings, road signs, sidewalks, catch basins, guardrails, and manholes) is demonstrated.
Hybrid Hydrogels Based on Methacrylate-Functionalized Gelatin (GelMA) and Synthetic Polymers
Authors: Liang J. , Dijkstra P. J. , Poot A. A. , Grijpma D. W.
Published: September 2022

This review on hybrid hydrogels prepared from methacrylated gelatin (GelMA) and synthetic polymers presents their advantageous properties and potential applications in biomedical engineering. It describes the preparation of the different types of frequently used hybrid hydrogel networks: co-networks, interpenetrating networks (IPNs), and semi-interpenetrating networks (semi-IPNs) and gives an overview of the different methods of preparing biomedical devices from these materials.
Black Shakespeare
Authors: Smith Ian
Published: September 2022

Race may dominate everyday speech, media headlines and public policy, yet still questions of racialized blackness and whiteness in Shakespeare are resisted. In his compelling new book Ian Smith addresses the influence of systemic whiteness on the interpretation of Shakespeare's plays. This far-reaching study shows that significant parts of Shakespeare's texts have been elided, misconstrued or otherwise rendered invisible by readers who have ignored the presence of race in early modern England. Bringing the Black American intellectual tradition into fruitful dialogue with European thought, this urgent interdisciplinary work offers a deep, revealing and incisive analysis of individual plays, including Othello, The Merchant of Venice and Hamlet. Demonstrating how racial illiteracy inhibits critical practice, Ian Smith provides a necessary anti-racist alternative that will transform the way you read Shakespeare.
Violent and Nonviolent Ethnic Resistance
Authors: Clarke Killian
Published: September 2022

Why do ethnic minorities who have been cut out of power choose, in some contexts, to take up arms and, in other contexts, to take to the streets? This question might seem an obvious one to ask, and yet it has rarely been posed in quite these terms – in large part because ethnic politics research has concentrated far more on violent resistance than its nonviolent alternative. We have reams of pages on the roots of ethnic insurgency, violent secessionism, and ethnic civil war but far less on why and how marginalized ethnic groups might mobilize using unarmed strategies of civil resistance. Manuel Vogt’s impressive new book makes this point well – and offers a succinct and parsimonious explanation to answer the question of why an ethnic group might choose one path over another.
Extension of the Electron Density Enhancement From Middle to High Latitudes Observed by Swarm‐A in Summer of the Southern Hemisphere
Authors: Wang Jin , Sun Yang‐Yi , Yu Tao , Chen Gang , Ye Hailun , Yan Xiangxiang , Yang Na , Qi Yifan
Published: September 2022

The major causal mechanism for the eastward contraction of the electron density (Ne) enhancement associated with the southern Midlatitude Summer Nighttime Anomaly (MSNA) was attributed to the thermospheric neutral wind at the middle geomagnetic latitude in the fixed local time coordinate. In the study, the Ne and horizontal cross‐track ion drifts observed by the Swarm‐A satellite at 462 km altitude show that the horizontal drifts can drive the Ne enhancement of the southern MSNA in the local summer of the Southern Hemisphere. Both the eastward and westward ion drifts transport the enhancement from the middle to the high geomagnetic latitudes, which results in the enhancement evolving at all the longitudes in the whole day.
Contributions of External Forcing to the Decadal Decline of the South Asian High
Authors: Zhang Dapeng , Huang Yanyan , Zhou Botao , Wang Huijun
Published: September 2022

The South Asian high (SAH) experienced a decadal weakening in the late 1970s under global warming. Based on an evaluation of the historical runs from CMIP6 models, we quantitatively assessed the contributions of different external forcing using “good” models that reasonably simulated the decadal decline of the SAH. All‐forcing runs yielded the weakened SAH after the late 1970s, albeit the decadal decline was underestimated by most models. Compared to the insignificant contributions of greenhouse gas and natural forcing, anthropogenic aerosol played a dominant role in the decadal decline of the SAH. The increased aerosol likely drove a cooling surface over the Tibetan Plateau (TP) and East China via its effect on radiation. Consequently, the weakened heat source over the TP and associated thermodynamic effects over East China would have driven a cooling of eddy temperature and cyclonic anomalies in the upper troposphere, respectively, thereby causing the decline of the SAH.
Radium Inputs Into the Arctic Ocean From Rivers: A Basin‐Wide Estimate
Authors: Bullock Emma J. , Kipp Lauren , Moore Willard , Brown Kristina , Mann Paul J. , Vonk Jorien E. , Zimov Nikita , Charette Matthew A.
Published: September 2022

Radium isotopes have been used to trace nutrient, carbon, and trace metal fluxes inputs from ocean margins. However, these approaches require a full accounting of radium sources to the coastal ocean including rivers. Here, we aim to quantify river radium inputs into the Arctic Ocean for the first time for 226Ra and to refine the estimates for 228Ra. Using new and existing data, we find that the estimated combined (dissolved plus desorbed) annual 226Ra and 228Ra fluxes to the Arctic Ocean are [7.0–9.4] × 1014 dpm y−1 and [15–18] × 1014 dpm y−1, respectively. Of these totals, 44% and 60% of the river 226Ra and 228Ra, respectively are from suspended sediment desorption, which were estimated from laboratory incubation experiments. Using Ra isotope data from 20 major rivers around the world, we derived global annual 226Ra and 228Ra fluxes of [7.4–17] × 1015 and [15–27] × 1015 dpm y−1, respectively. As climate change spurs rapid Arctic warming, hydrological cycles are intensifying and coastal ice cover and permafrost are diminishing. These river radium inputs to the Arctic Ocean will serve as a valuable baseline as we attempt to understand the changes that warming temperatures are having on fluxes of biogeochemically important elements to the Arctic coastal zone.
UHRF1 overexpression promotes osteosarcoma metastasis through altered exosome production and AMPK/SEMA3E suppression
Authors: Wu Stephanie C. , Kim Ahhyun , Gu Yijun , Martinez Daniel I. , Zocchi Loredana , Chen Claire C. , Lopez Jocelyne , Salcido Kelsey , Singh Sarah , Wu Jie , Nael Ali , Benavente Claudia A.
Published: September 2022

Loss-of-function mutations at the retinoblastoma (RB1) gene are associated with increased mortality, metastasis, and poor therapeutic outcome in several cancers, including osteosarcoma. However, the mechanism(s) through which RB1 loss worsens clinical outcome remains understudied. Ubiquitin-like with PHD and Ring Finger domains 1 (UHRF1) has been identified as a critical downstream effector of the RB/E2F signaling pathway that is overexpressed in various cancers. Here, we determined the role and regulatory mechanisms of UHRF1 in rendering osteosarcoma cells more aggressive. Higher UHRF1 expression correlated with malignancy in osteosarcoma cell lines, clinical samples, and genetically engineered mouse models. Gain- and loss-of-function assays revealed that UHRF1 has cell-intrinsic and extrinsic functions promoting cell proliferation, migration, invasion, angiogenesis, and metastasis. UHRF1 overexpression induced angiogenesis by suppressing AMPK activation and Semaphorin 3E (SEMA3E) expression. Further, UHRF1-mediated migration and metastasis resulted, at least in part, through altered expression of extracellular vesicles and their cargo, including urokinase-type plasminogen activator (uPA). Novel osteosarcoma genetically engineered mouse models confirmed that knocking out Uhrf1 considerably decreased metastasis and reversed the poorer survival associated with Rb1 loss. This presents a new mechanistic insight into RB1 loss-associated poor prognosis and novel oncogenic roles of UHRF1 in the regulation of angiogenesis and exosome secretion, both critical for osteosarcoma metastasis. This provides substantial support for targeting UHRF1 or its downstream effectors as novel therapeutic options to improve current treatment for osteosarcoma.
The mutational signatures of formalin fixation on the human genome
Authors: Guo Qingli , Lakatos Eszter , Bakir Ibrahim Al , Curtius Kit , Graham Trevor A. , Mustonen Ville
Published: September 2022

Clinical archives of patient material near-exclusively consist of formalin-fixed and paraffin-embedded (FFPE) blocks. The ability to precisely characterise mutational signatures from FFPE-derived DNA has tremendous translational potential. However, sequencing of DNA derived from FFPE material is known to be riddled with artefacts. Here we derive genome-wide mutational signatures caused by formalin fixation. We show that the FFPE-signature is highly similar to signature 30 (the signature of Base Excision Repair deficiency due to NTHL1 mutations), and chemical repair of DNA lesions leads to a signature highly similar to signature 1 (clock-like signature due to spontaneous deamination of methylcytosine). We demonstrate that using uncorrected mutational catalogues of FFPE samples leads to major mis-assignment of signature activities. To correct for this, we introduce FFPEsig, a computational algorithm to rectify the formalin-induced artefacts in the mutational catalogue. We demonstrate that FFPEsig enables accurate mutational signature analysis both in simulated and whole-genome sequenced FFPE cancer samples. FFPEsig thus provides an opportunity to unlock additional clinical potential of archival patient tissues.
Substrate multiplexed protein engineering facilitates promiscuous biocatalytic synthesis
Authors: McDonald Allwin D. , Higgins Peyton M. , Buller Andrew R.
Published: September 2022

Enzymes with high activity are readily produced through protein engineering, but intentionally and efficiently engineering enzymes for an expanded substrate scope is a contemporary challenge. One approach to address this challenge is Substrate Multiplexed Screening (SUMS), where enzyme activity is measured on competing substrates. SUMS has long been used to rigorously quantitate native enzyme specificity, primarily for in vivo settings. SUMS has more recently found sporadic use as a protein engineering approach but has not been widely adopted by the field, despite its potential utility. Here, we develop principles of how to design and interpret SUMS assays to guide protein engineering. This rich information enables improving activity with multiple substrates simultaneously, identifies enzyme variants with altered scope, and indicates potential mutational hot-spots as sites for further engineering. These advances leverage common laboratory equipment and represent a highly accessible and customizable method for enzyme engineering.
Dissecting the role of the human microbiome in COVID-19 via metagenome-assembled genomes
Authors: Ke Shanlin , Weiss Scott T. , Liu Yang-Yu
Published: September 2022

Coronavirus disease 2019 (COVID-19), primarily a respiratory disease caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is often accompanied by gastrointestinal symptoms. However, little is known about the relation between the human microbiome and COVID-19, largely due to the fact that most previous studies fail to provide high taxonomic resolution to identify microbes that likely interact with SARS-CoV-2 infection. Here we used whole-metagenome shotgun sequencing data together with assembly and binning strategies to reconstruct metagenome-assembled genomes (MAGs) from 514 COVID-19 related nasopharyngeal and fecal samples in six independent cohorts. We reconstructed a total of 11,584 medium-and high-quality microbial MAGs and obtained 5403 non-redundant MAGs (nrMAGs) with strain-level resolution. We found that there is a significant reduction of strain richness for many species in the gut microbiome of COVID-19 patients. The gut microbiome signatures can accurately distinguish COVID-19 cases from healthy controls and predict the progression of COVID-19. Moreover, we identified a set of nrMAGs with a putative causal role in the clinical manifestations of COVID-19 and revealed their functional pathways that potentially interact with SARS-CoV-2 infection. Finally, we demonstrated that the main findings of our study can be largely validated in three independent cohorts. The presented results highlight the importance of incorporating the human gut microbiome in our understanding of SARS-CoV-2 infection and disease progression.
Metagenomic and metatranscriptomic insights into sulfate-reducing bacteria in a revegetated acidic mine wasteland
Authors: Li Jin-tian , Jia Pu , Wang Xiao-juan , Ou Shu-ning , Yang Tao-tao , Feng Shi-wei , Lu Jing-li , Fang Zhou , Liu Jun , Liao Bin , Shu Wen-sheng , Liang Jie-Liang
Published: September 2022

The widespread occurrence of sulfate-reducing microorganisms (SRMs) in temporarily oxic/hypoxic aquatic environments indicates an intriguing possibility that SRMs can prevail in constantly oxic/hypoxic terrestrial sulfate-rich environments. However, little attention has been given to this possibility, leading to an incomplete understanding of microorganisms driving the terrestrial part of the global sulfur (S) cycle. In this study, genome-centric metagenomics and metatranscriptomics were employed to explore the diversity, metabolic potential, and gene expression profile of SRMs in a revegetated acidic mine wasteland under constantly oxic/hypoxic conditions. We recovered 16 medium- to high-quality metagenome-assembled genomes (MAGs) containing reductive dsrAB. Among them, 12 and four MAGs belonged to Acidobacteria and Deltaproteobacteria, respectively, harboring three new SRM genera. Comparative genomic analysis based on seven high-quality MAGs (completeness >90% and contamination <10%; including six acidobacterial and one deltaproteobacterial) and genomes of three additional cultured model species showed that Acidobacteria-related SRMs had more genes encoding glycoside hydrolases, oxygen-tolerant hydrogenases, and cytochrome c oxidases than Deltaproteobacteria-related SRMs. The opposite pattern was observed for genes encoding superoxide reductases and thioredoxin peroxidases. Using VirSorter, viral genome sequences were found in five of the 16 MAGs and in all three cultured model species. These prophages encoded enzymes involved in glycoside hydrolysis and antioxidation in their hosts. Moreover, metatranscriptomic analysis revealed that 15 of the 16 SRMs reported here were active in situ. An acidobacterial MAG containing a prophage dominated the SRM transcripts, expressing a large number of genes involved in its response to oxidative stress and competition for organic matter.
Practical tips in bronchiectasis for Primary Care
Authors: Martinez-Garcia Miguel Angel , Garcia-Ortega Alberto , Oscullo Grace
Published: September 2022

Bronchiectasis is the third most common chronic inflammatory airway disease, after chronic obstructive pulmonary disease (COPD) and asthma with a prevalence clearly underestimated probably because of its clinical similitudes with other chronic airway diseases. Bronchiectasis can be caused by a dozen of pulmonary and extra-pulmonary diseases and a variable number and severity of exacerbations can appear throughout its natural history, usually with an infectious profile. The dilation of the airway and the inflammation/infection is their radiological and pathophysiological hallmarks. Primary Care should play an important play in many aspects of the bronchiectasis assessment. In this article, we will try to offer a series of important concepts and practical tips on some key aspects of the diagnosis and management of bronchiectasis in Primary Care: clinical suspicion, diagnostic methods, severity assessment, overlap with asthma and COPD and microbiological and therapeutic aspects.
Composable end-to-end security of Gaussian quantum networks with untrusted relays
Authors: Ghalaii Masoud , Papanastasiou Panagiotis , Pirandola Stefano
Published: September 2022

Gaussian networks are fundamental objects in network information theory. Here many senders and receivers are connected by physically motivated Gaussian channels, while auxiliary Gaussian components, such as Gaussian relays, are entailed. Whilst the theoretical backbone of classical Gaussian networks is well established, the quantum analog is yet immature. Here, we theoretically tackle composable security of arbitrary Gaussian quantum networks, with generally untrusted nodes, in the finite-size regime. We put forward a general methodology for parameter estimation, which is only based on the data shared by the remote end-users. Taking a chain of identical quantum links as an example, we further demonstrate our study. Additionally, we find that the key rate of a quantum amplifier-assisted chain can ideally beat the fundamental repeaterless limit with practical block sizes. However, this objective is practically questioned leading the way to future network/chain designs.
Development of an attenuated vaccine against Koi Herpesvirus Disease (KHVD) suitable for oral administration and immersion
Authors: Klafack Sandro , Schröder Lars , Jin Yeonhwa , Lenk Matthias , Lee Pei-Yu , Fuchs Walter , Avarre Jean-Christophe , Bergmann Sven M.
Published: September 2022

Since the end of the1990ies,Cyprinid herpesvirus 3(also known as koi herpesvirus, KHV) has caused mass mortality events of koi and common carp all over the globe. This induced a high economic impact, since the KHV disease cannot be cured up to now, but only prevented by vaccination. Unfortunately, there is only one commercial vaccine available which is not approved in most countries. Therefore, there is an urgent need for new, safe and available vaccines. In this study, a live attenuated vaccine virus was generated by cell culture passages of virulent KHV, and shown to protect carp or koi after immersion or oral application against wild type challenge. An advantage of boost immunization was demonstrated, especially after oral application. Vaccination induced no or mild clinical signs and protecting antibodies have been measured. Additionally, the vaccine virus allowed differentiation of infected from vaccinated animals (DIVA) by PCR. The attenuation of the newly generated vaccine was tracked down to a partial deletion of open reading frame 150. This was confirmed by the generation of engineered ORF150 deletion mutants of wild-type KHV which exhibited a similar attenuation in vivo.
Rational attenuation of RNA viruses with zinc finger antiviral protein
Authors: Gonçalves-Carneiro Daniel , Mastrocola Emily , Lei Xiao , DaSilva Justin , Chan Yoke Fun , Bieniasz Paul D.
Published: September 2022

Attenuation of a virulent virus is a proven approach for generating vaccines but can be unpredictable. For example, synonymous recoding of viral genomes can attenuate replication but sometimes results in pleiotropic effects that confound rational vaccine design. To enable specific, conditional attenuation of viruses, we examined target RNA features that enable zinc finger antiviral protein (ZAP) function. ZAP recognized CpG dinucleotides and targeted CpG-rich RNAs for depletion, but RNA features such as CpG numbers, spacing and surrounding nucleotide composition that enable specific modulation by ZAP were undefined. Using synonymously mutated HIV-1 genomes, we defined several sequence features that govern ZAP sensitivity and enable stable attenuation. We applied rules derived from experiments with HIV-1 to engineer a mutant enterovirus A71 genome whose attenuation was stable and strictly ZAP-dependent, both in cell culture and in mice. The conditionally attenuated enterovirus A71 mutant elicited neutralizing antibodies that were protective against wild-type enterovirus A71 infection and disease in mice. ZAP sensitivity can thus be readily applied for the rational design of conditionally attenuated viral vaccines.
Impact of embryonic manipulations on core body temperature dynamics and survival in broilers exposed to cyclic heat stress
Authors: Ncho Chris Major , Goel Akshat , Gupta Vaishali , Jeong Chae-Mi , Choi Yang-Ho
Published: September 2022

Ambient temperature-associated stress has been shown to affect the normal physiological functions of birds. The recent literature indicated that both, embryonic thermal manipulation (ETM) and in ovo feeding (IOF) of γ-aminobutyric acid (GABA) can mitigate the deleterious effects of heat stress (HS) in young broiler chicks. Therefore, this study intended to assess the effects of cyclic HS (32 ± 1 °C, 4 h/day from day 29 to 35) on rectal temperatures (RTs) and survival in broiler chickens after ETM and in IOF of GABA. A total of 275 RT data points and survival data were collected from chicks assigned to the following five treatments: chicks hatched from control eggs (CON); chicks hatched from control eggs but exposed to HS (CON + HS); chicks hatched from eggs injected at 17.5 days of incubation with 0.6 mL of 10% GABA and exposed to HS (G10 + HS); chicks hatched from thermally manipulated eggs (39.6 °C, 6 h/day from embryonic days 10 to 18) and exposed to HS (TM + HS); chicks hatched from eggs that received both previous treatments during incubation and exposed to HS (G10 + TM + HS). Under thermoneutral conditions, RTs increased quadratically from 39.9 ± 0.2 °C at hatching to 41.4 ± 0.1 °C at 8 days of age. When exposed to cyclic HS during the last week of rearing, the birds’ RTs tended to decrease at the end of the heat stress challenge (from 43.0 ± 0.2 °C on day 29 to 42.4 ± 0.1 °C on day 35). A stepwise Cox regression indicated that treatment was predictive of birds’ survival. Hazard ratios (HR) and their confidence intervals (CI) were calculated to assess the likelihood of death during the trial. The birds, belonging to the G10 + TM + HS group, were less likely to die under HS (HR 0.11, 95% CI 0.02 to 0.91, P = 0.041) compared to the CON + HS birds. Taken together, the combination of ETM and GABA IOF may help mitigate the drawbacks of cyclic HS by improving the survival of broilers.