bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual selection as race making
Authors: Sheldon Myrna Perez
Published: July 2021

Charles Darwin's theory of sexual selection, as described inThe Descent of Man, and Selection in Relation to Sex(1871), should be viewed as a significant transitional point in the modern expression of race. Unlike earlier race theorists, Darwin proposed that sexual reproduction was not merely a testing ground of racial character, but was itself a causal force that could create new races. His account of race was distinctly modern – viewing race not in terms of blood but as a collection of population-level characteristics. Recognizing this feature of Darwin's sexual-selection theory allows us to situate Darwin's work not solely within the history of evolutionary science, but also within the structures of racism that became the governing principles of modern nation states. In other words, sexual selection is an expression of Michel Foucault's biopolitics, in which political power is exercised by states not through the contracts of liberal governance but through the management of population-level phenomena. Furthermore, by contextualizing sexual selection in this theoretical framework, it becomes possible to more clearly emphasize the importance of race in the rise of modern biopolitics.
On the Epistemic Costs of Friendship: Against the Encroachment View
Authors: Rioux Catherine
Published: July 2021

I defend the thesis that friendship can constitutively require epistemic irrationality against a recent, forceful challenge, raised by proponents of moral and pragmatic encroachment. Defenders of the “encroachment strategy” argue that exemplary friends who are especially slow to believe that their friends have acted wrongly are simply sensitive to the high prudential or moral costs of falsely believing in their friends’ guilt. Drawing on psychological work on epistemic motivation (and in particular on the notion of “need for closure”), I propose a different picture of what friendship requires in the doxastic realm. I argue that contrary to what the encroachment strategy suggests, exemplary friends’ belief formation ought not be guided by a concern with accuracy or error avoidance, but instead by a need to avoid a “specific closure” – namely, a need to avoid concluding in their friends’ guilt. I propose that exemplary friendship often generates a defeasible, doxastic obligation to exemplify such a need, despite its inherent corrupting effects on exemplary friends’ epistemic faculties.
Rethinking the Value of Author Contribution Statements in Light of How Research Teams Respond to Retractions
Authors: Andersen Line Edslev , Wray K. Brad
Published: July 2021

The authorship policies of scientific journals often assume that in order to be able to properly place credit and responsibility for the content of a collaborative paper we should be able to distinguish the contributions of the various individuals involved. Hence, many journals have introduced a requirement for author contribution statements aimed at making it easier to place credit and responsibility on individual scientists. We argue that from a purely descriptive point of view the practices of collaborating scientists are at odds with the requirement for author contribution statements. We also argue that from a normative point of view the authorship policies may be unnecessary. Our arguments draw on an examination of 35 years of retraction notices in the journal Science.
Forgiveness and the Repairing of Epistemic Trust
Authors: Green Adam
Published: July 2021

The epistemic relevance of forgiveness has been neglected by both the discussion of forgiveness in moral psychology and by social epistemology generally. Moral psychology fails to account for the forgiveness of epistemic wrongs and for the way that wrongs in general have epistemic implications. Social epistemology, for its part, neglects the way that epistemic trust is not only conferred but repaired. In this essay, I show that the repair of epistemic trust through forgiveness is necessary to the economy of knowledge for fallible persons like us. Despite the fact that forgiveness is never included on lists of important intellectual virtues or epistemic activities, it is vital to our lives as social knowers. Likewise, an account of forgiveness that neglects its epistemic dimension is importantly incomplete.
A Note on Posttreatment Selection in Studying Racial Discrimination in Policing
Authors: ZHAO QINGYUAN , KEELE LUKE J , SMALL DYLAN S , JOFFE MARSHALL M
Published: July 2021

We discuss some causal estimands that are used to study racial discrimination in policing. A central challenge is that not all police–civilian encounters are recorded in administrative datasets and available to researchers. One possible solution is to consider the average causal effect of race conditional on the civilian already being detained by the police. We find that such an estimand can be quite different from the more familiar ones in causal inference and needs to be interpreted with caution. We propose using an estimand that is new for this context—the causal risk ratio, which has more transparent interpretation and requires weaker identification assumptions. We demonstrate this through a reanalysis of the NYPD Stop-and-Frisk dataset. Our reanalysis shows that the naive estimator that ignores the posttreatment selection in administrative records may severely underestimate the disparity in police violence between minorities and whites in these and similar data.
Ordering results for smallest claim amounts from two portfolios of risks with dependent heterogeneous exponentiated location-scale claims
Authors: Das Sangita , Kayal Suchandan , Balakrishnan N.
Published: July 2021

Let $\{Y_{1},\ldots ,Y_{n}\}$ be a collection of interdependent nonnegative random variables, with $Y_{i}$ having an exponentiated location-scale model with location parameter $\mu _i$, scale parameter $\delta _i$ and shape (skewness) parameter $\beta _i$, for $i\in \mathbb {I}_{n}=\{1,\ldots ,n\}$. Furthermore, let $\{L_1^{*},\ldots ,L_n^{*}\}$ be a set of independent Bernoulli random variables, independently of $Y_{i}$'s, with $E(L_{i}^{*})=p_{i}^{*}$, for $i\in \mathbb {I}_{n}.$ Under this setup, the portfolio of risks is the collection $\{T_{1}^{*}=L_{1}^{*}Y_{1},\ldots ,T_{n}^{*}=L_{n}^{*}Y_{n}\}$, wherein $T_{i}^{*}=L_{i}^{*}Y_{i}$ represents the $i$th claim amount. This article then presents several sufficient conditions, under which the smallest claim amounts are compared in terms of the usual stochastic and hazard rate orders. The comparison results are obtained when the dependence structure among the claim severities are modeled by (i) an Archimedean survival copula and (ii) a general survival copula. Several examples are also presented to illustrate the established results.
Multiple Cognitive and Behavioral Factors Link Association Between Brain Structure and Functional Impairment of Daily Instrumental Activities in Older Adults
Authors: Kwak Seyul , Park Su Mi , Jeon Yeong-Ju , Ko Hyunwoong , Oh Dae Jong , Lee Jun-Young
Published: July 2021

Objective:

Functional impairment in daily activity is a cornerstone in distinguishing the clinical progression of dementia. Multiple indicators based on neuroimaging and neuropsychological instruments are used to assess the levels of impairment and disease severity; however, it remains unclear how multivariate patterns of predictors uniquely predict the functional ability and how the relative importance of various predictors differs.

Method:

In this study, 881 older adults with subjective cognitive complaints, mild cognitive impairment (MCI), and dementia with Alzheimer’s type completed brain structural magnetic resonance imaging (MRI), neuropsychological assessment, and a survey of instrumental activities of daily living (IADL). We utilized the partial least square (PLS) method to identify latent components that are predictive of IADL.

Results:

The result showed distinct brain components (gray matter density of cerebellar, medial temporal, subcortical, limbic, and default network regions) and cognitive–behavioral components (general cognitive abilities, processing speed, and executive function, episodic memory, and neuropsychiatric symptoms) were predictive of IADL. Subsequent path analysis showed that the effect of brain structural components on IADL was largely mediated by cognitive and behavioral components. When comparing hierarchical regression models, the brain structural measures minimally added the explanatory power of cognitive and behavioral measures on IADL.

Conclusion:

Our finding suggests that cerebellar structure and orbitofrontal cortex, alongside with medial temporal lobe, play an important role in the maintenance of functional status in older adults with or without dementia. Moreover, the significance of brain structural volume affects real-life functional activities via disruptions in multiple cognitive and behavioral functions.
Making Sense of the Arbitrator's Ruling in DS 316, EC and Certain Member States – Measures Affecting Trade in Large Civil Aircraft (Article 22.6-EC): A Jigsaw Puzzle with (at Least) a Couple Missing Pieces
Authors: Mavroidis Petros C. , Saggi Kamal
Published: July 2021

‘The US won a $7.5 Billion award from the World Trade Organization against the European Union, who has for many years treated the USA very badly on Trade due to Tariffs, Trade Barriers, and more. This case going on for years, a nice victory’, tweeted President Trump on 3 October 2019. The United States (US) won not only the highest amount of retaliation ever adjudicated in the history of the WTO but also an ongoing right to retaliate on an annual basis until such time as the EU had complied by either removing the subsidies it granted Airbus or somehow neutralizing their adverse effects on Boeing. In light of the facts of the case, this ruling has two major shortcomings. First, in sharp contrast with the statutory language and practice until now, the Arbitrator effectively introduced a permanent liability rule into the WTO system through the backdoor. Second, given the way the decision and the associated award has been written, it is simply impossible for the EU to comply because (a) the contested subsidies are no longer in existence and (b) no guidance has been provided on how the EU might go about removing their adverse effects on Boeing if it sought to achieve compliance. Thus, in all likelihood, the EU is saddled with a ruling that obligates it to cough up an annual sum of $7.5 billion USD for an indefinite time period.
Placental insufficiency induces a sexually dimorphic response in the expression of cardiac growth and metabolic signalling molecules upon exposure to a postnatal western diet in guinea pigs
Authors: Darby Jack R.T. , Chiu Jacky , Regnault Timothy R.H. , Morrison Janna L.
Published: July 2021

There is a strong relationship between low birth weight (LBW) and an increased risk of developing cardiovascular disease (CVD). In postnatal life, LBW offspring are becoming more commonly exposed to the additional independent CVD risk factors, such as an obesogenic diet. However, how an already detrimentally programmed LBW myocardium responds to a secondary insult, such as an obesogenic diet (western diet; WD), during postnatal life is ill defined. Herein, we aimed to determine in a pre-clinical guinea pig model of CVD, both the independent and interactive effects of LBW and a postnatal WD on the molecular pathways that regulate cardiac growth and metabolism. Uterine artery ablation was used to induce placental insufficiency (PI) in pregnant guinea pigs to generate LBW offspring. Normal birth weight (NBW) and LBW offspring were weaned onto either a Control diet or WD. At ˜145 days after birth (young adulthood), male and female offspring were humanely killed, the heart weighed and left ventricle tissue collected. The mRNA expression of signalling molecules involved in a pathological hypertrophic and fibrotic response was increased in the myocardium of LBW male, but not female offspring, fed a WD as was the mRNA expression of transcription factors involved in fatty acid oxidation. The mRNA expression of glucose transporters was downregulated by LBW and WD in male, but not female hearts. This study has highlighted a sexually dimorphic cardiac pathological hypertrophic and fibrotic response to the secondary insult of postnatal WD consumption in LBW offspring.
Vietnam's Military and Political Challenges in Cambodia and the Early Rise of Cambodia's Strongman, Hun Sen, 1977–79
Authors: Path Kosal , Nhem Boraden
Published: July 2021

Much has been written about Cambodia's strongman, Prime Minister Hun Sen, who has been in power since 1985. Yet, the history of Hun Sen's early rise to a position of power in the Vietnam-initiated Cambodian revolution after June 1977 remains murky. Relying on Vietnamese and Cambodian archival documents, memoirs and interviews with former veterans of Unit 125 as well as Hun Sen's speeches and personal recollection of his historic journey to Vietnam on 20 June 1977, we make a two-fold argument. First, Hanoi's decision to establish an anti-Pol Pot Cambodian revolution in southern Vietnam to take over Cambodia—after toppling Democratic Kampuchea—was part of Hanoi's strategic plan to handle a double challenge: (1) to avoid being branded as an invader and (2) to establish a capable and friendly regime in Cambodia after the war. This provided an opportunity for a young Khmer Rouge defector, Hun Sen, to change his fortune by quickly earning the Vietnamese military leadership's trust and confidence based on his competence to organize and command the first army unit of the new Cambodian revolution, i.e. Unit 125. Second, as lucky as he was to flee across the heavily militarized border into Vietnam unharmed, Hun Sen's early rise to power is attributed to his survivalist instinct combined with shrewd strategic thinking.
Recent Trends in SST, Chl‐a, Productivity and Wind Stress in Upwelling and Open Ocean Areas in the Upper Eastern North Atlantic Subtropical Gyre
Authors: Siemer J. P. , Machín F. , González‐Vega A. , Arrieta J. M. , Gutiérrez‐Guerra M. A. , Pérez‐Hernández M. D. , Vélez‐Belchí P. , Hernández‐Guerra A. , Fraile‐Nuez E.
Published: July 2021

The global upper ocean has been warming during the last decades accompanied with a chlorophyll‐a (Chl‐a) and productivity decrease. Whereas subtropical gyres show similar trends, Eastern Boundary Upwelling Systems are thought to increase in productivity due to increased trade winds. This study analyzes recent trends in sea surface temperature (SST), Chl‐a, net primary production (NPP) and meridional wind stress in the Eastern North Atlantic subtropical gyre (NASE) in order to examine if the global trends can be detected in open ocean and upwelling areas and how the ocean biota responds. Satellite data of such variables of the last 15–40 years were analyzed to calculate mean trends in upwelling areas in the Canary upwelling system and open ocean areas around the Azores, Madeira and the Canary Islands. Our results show significant warming in the area with a maximum of 2.7°C per century for the Azores. Moreover, a general decreasing trend for Chl‐a and NPP seems to be more evident in the permanent upwelling areas, which will be responsible for a loss of 0.13% of the global NPP per century. Our results also highlight a significant expansion of the oceanic desert area of 10% with an increase in unproductive days of up to 84 days in the last 20 years. The competitive relationship of stratification and wind stress in the Canary upwelling system might be a more plausible explanation for the decrease in Chl‐a and NPP in upwelling areas linked to the increase in upwelling favorable wind stress and the surface warming.
Quantifying the effects of hydrogen on carbon assimilation in a seafloor microbial community associated with ultramafic rocks
Authors: Coskun Ömer K , Vuillemin Aurèle , Schubotz Florence , Klein Frieder , Sichel Susanna E , Eisenreich Wolfgang , Orsi William D
Published: July 2021

Thermodynamic models predict that H2 is energetically favorable for seafloor microbial life, but how H2 affects anabolic processes in seafloor-associated communities is poorly understood. Here, we used quantitative 13C DNA stable isotope probing (qSIP) to quantify the effect of H2 on carbon assimilation by microbial taxa synthesizing 13C-labeled DNA that are associated with partially serpentinized peridotite rocks from the equatorial Mid-Atlantic Ridge. The rock-hosted seafloor community was an order of magnitude more diverse compared to the seawater community directly above the rocks. With added H2, peridotite-associated taxa increased assimilation of 13C-bicarbonate and 13C-acetate into 16S rRNA genes of operational taxonomic units by 146% (±29%) and 55% (±34%), respectively, which correlated with enrichment of H2-oxidizing NiFe-hydrogenases encoded in peridotite-associated metagenomes. The effect of H2 on anabolism was phylogenetically organized, with taxa affiliated with Atribacteria, Nitrospira, and Thaumarchaeota exhibiting the most significant increases in 13C-substrate assimilation in the presence of H2. In SIP incubations with added H2, an order of magnitude higher number of peridotite rock-associated taxa assimilated 13C-bicarbonate, 13C-acetate, and 13C-formate compared to taxa that were not associated with peridotites. Collectively, these findings indicate that the unique geochemical nature of the peridotite-hosted ecosystem has selected for H2-metabolizing, rock-associated taxa that can increase anabolism under high H2 concentrations. Because ultramafic rocks are widespread in slow-, and ultraslow-spreading oceanic lithosphere, continental margins, and subduction zones where H2 is formed in copious amounts, the link between H2 and carbon assimilation demonstrated here may be widespread within these geological settings.
Distinct motivations to seek out information in healthy individuals and problem gamblers
Authors: Dezza Irene Cogliati , Noel Xavier , Cleeremans Axel , Yu Angela J.
Published: July 2021

As massive amounts of information are becoming available to people, understanding the mechanisms underlying information-seeking is more pertinent today than ever. In this study, we investigate the underlying motivations to seek out information in healthy and addicted individuals. We developed a novel decision-making task and a novel computational model which allows dissociating the relative contribution of two motivating factors to seek out information: a desire for novelty and a general desire for knowledge. To investigate whether/how the motivations to seek out information vary between healthy and addicted individuals, in addition to healthy controls we included a sample of individuals with gambling disorder—a form of addiction without the confound of substance consumption and characterized by compulsive gambling. Our results indicate that healthy subjects and problem gamblers adopt distinct information-seeking “modes”. Healthy information-seeking behavior was mostly motivated by a desire for novelty. Problem gamblers, on the contrary, displayed reduced novelty-seeking and an increased desire for accumulating knowledge compared to healthy controls. Our findings not only shed new light on the motivations driving healthy and addicted individuals to seek out information, but they also have important implications for the treatment and diagnosis of behavioral addiction.
BH3-only protein expression determines hepatocellular carcinoma response to sorafenib-based treatment
Authors: Busche Stephanie , John Katharina , Wandrer Franziska , Vondran Florian W. R. , Lehmann Ulrich , Wedemeyer Heiner , Essmann Frank , Schulze-Osthoff Klaus , Bantel Heike
Published: July 2021

Hepatocellular carcinoma (HCC) represents a global health challenge with limited therapeutic options. Anti-angiogenic immune checkpoint inhibitor-based combination therapy has been introduced for progressed HCC, but improves survival only in a subset of HCC patients. Tyrosine-kinase inhibitors (TKI) such as sorafenib represent an alternative treatment option but have only modest efficacy. Using different HCC cell lines and HCC tissues from various patients reflecting HCC heterogeneity, we investigated whether the sorafenib response could be enhanced by combination with pro-apoptotic agents, such as TNF-related apoptosis-inducing ligand (TRAIL) or the BH3-mimetic ABT-737, which target the death receptor and mitochondrial pathway of apoptosis, respectively. We found that both agents could enhance sorafenib-induced cell death which was, however, dependent on specific BH3-only proteins. TRAIL augmented sorafenib-induced cell death only in NOXA-expressing HCC cells, whereas ABT-737 enhanced the sorafenib response also in NOXA-deficient cells. ABT-737, however, failed to augment sorafenib cytotoxicity in the absence of BIM, even when NOXA was strongly expressed. In the presence of NOXA, BIM-deficient HCC cells could be in turn strongly sensitized for cell death induction by the combination of sorafenib with TRAIL. Accordingly, HCC tissues sensitive to apoptosis induction by sorafenib and TRAIL revealed enhanced NOXA expression compared to HCC tissues resistant to this treatment combination. Thus, our results suggest that BH3-only protein expression determines the treatment response of HCC to different sorafenib-based drug combinations. Individual profiling of BH3-only protein expression might therefore assist patient stratification to certain TKI-based HCC therapies.
HO-1 nuclear accumulation and interaction with NPM1 protect against stress-induced endothelial senescence independent of its enzymatic activity
Authors: Luo Wenwei , Li Jingyan , Li Ziqing , Lin Tong , Zhang Lili , Yang Wanqi , Mai Yanqi , Liu Ruiming , Chen Meiting , Dai Chunmei , Yang Hanwei , Lu Jing , Li Hong , Guan Guimei , Huang Min , Liu Peiqing , Li Zhuoming
Published: July 2021

Heme oxygenase-1 (HO-1) has attracted accumulating attention for its antioxidant enzymatic activity. However, the exact regulatory role of its non-enzymatic activity in the cardiovascular system remains unaddressed. Here, we show that HO-1 was accumulated in the nuclei of stress-induced senescent endothelial cells, and conferred protection against endothelial senescence independent of its enzymatic activity. Overexpression of ΔHO-1, a truncated HO-1 without transmembrane segment (TMS), inhibited H2O2-induced endothelial senescence. Overexpression of ΔHO-1H25A, the catalytically inactive form of ΔHO-1, also exhibited anti-senescent effect. In addition, infection of recombinant adenovirus encoding ΔHO-1 with three nuclear localization sequences (NLS), alleviated endothelial senescence induced by knockdown of endogenous HO-1 by CRISPR/Cas9. Moreover, repression of HO-1 nuclear translocation by silencing of signal peptide peptidase (SPP), which is responsible for enzymatic cleavage of the TMS of HO-1, exacerbated endothelial senescence. Mechanistically, nuclear HO-1 interacted with NPM1 N-terminal portion, prevented NPM1 translocation from nucleolus to nucleoplasm, thus disrupted NPM1/p53/MDM2 interactions and inhibited p53 activation by NPM1, finally resisted endothelial senescence. This study provides a novel understanding of HO-1 as a promising therapeutic strategy for vascular senescence-related cardiovascular diseases.
Generation of non-stabilized alkyl radicals from thianthrenium salts for C–B and C–C bond formation
Authors: Chen Cheng , Wang Zheng-Jun , Lu Hongjian , Zhao Yue , Shi Zhuangzhi
Published: July 2021

Sulfonium salts bearing a positively charged sulfur atom with three organic substituents have intrigued chemists for more than a century for their unusual structures and high chemical reactivity. These compounds are known to undergo facile single-electron reduction to emerge as a valuable and alternative source of aryl radicals for organic synthesis. However, the generation of non-stabilized alkyl radicals from sulfonium salts has been a challenge for several decades. Here we report the treatment of S-(alkyl) thianthrenium salts to generate non-stabilized alkyl radicals as key intermediates granting the controlled and selective outcome of the ensuing reactions under mild photoredox conditions. The value of these reagents has been demonstrated through the efficient construction of alkylboronates and other transformations, including heteroarylation, alkylation, alkenylation, and alkynylation. The developed method is practical, and provides the opportunity to convert C–OH bond to C–B and C–C bonds.
BiPOLES is an optogenetic tool developed for bidirectional dual-color control of neurons
Authors: Vierock Johannes , Rodriguez-Rozada Silvia , Dieter Alexander , Pieper Florian , Sims Ruth , Tenedini Federico , Bergs Amelie C. F. , Bendifallah Imane , Zhou Fangmin , Zeitzschel Nadja , Ahlbeck Joachim , Augustin Sandra , Sauter Kathrin , Papagiakoumou Eirini , Gottschalk Alexander , Soba Peter , Emiliani Valentina , Engel Andreas K. , Hegemann Peter , Wiegert J. Simon
Published: July 2021

Optogenetic manipulation of neuronal activity through excitatory and inhibitory opsins has become an indispensable experimental strategy in neuroscience research. For many applications bidirectional control of neuronal activity allowing both excitation and inhibition of the same neurons in a single experiment is desired. This requires low spectral overlap between the excitatory and inhibitory opsin, matched photocurrent amplitudes and a fixed expression ratio. Moreover, independent activation of two distinct neuronal populations with different optogenetic actuators is still challenging due to blue-light sensitivity of all opsins. Here we report BiPOLES, an optogenetic tool for potent neuronal excitation and inhibition with light of two different wavelengths. BiPOLES enables sensitive, reliable dual-color neuronal spiking and silencing with single- or two-photon excitation, optical tuning of the membrane voltage, and independent optogenetic control of two neuronal populations using a second, blue-light sensitive opsin. The utility of BiPOLES is demonstrated in worms, flies, mice and ferrets.
Neural attentional-filter mechanisms of listening success in middle-aged and older individuals
Authors: Tune Sarah , Alavash Mohsen , Fiedler Lorenz , Obleser Jonas
Published: July 2021

Successful listening crucially depends on intact attentional filters that separate relevant from irrelevant information. Research into their neurobiological implementation has focused on two potential auditory filter strategies: the lateralization of alpha power and selective neural speech tracking. However, the functional interplay of the two neural filter strategies and their potency to index listening success in an ageing population remains unclear. Using electroencephalography and a dual-talker task in a representative sample of listeners (N = 155; age=39–80 years), we here demonstrate an often-missed link from single-trial behavioural outcomes back to trial-by-trial changes in neural attentional filtering. First, we observe preserved attentional–cue-driven modulation of both neural filters across chronological age and hearing levels. Second, neural filter states vary independently of one another, demonstrating complementary neurobiological solutions of spatial selective attention. Stronger neural speech tracking but not alpha lateralization boosts trial-to-trial behavioural performance. Our results highlight the translational potential of neural speech tracking as an individualized neural marker of adaptive listening behaviour.
Bottleneck size and selection level reproducibly impact evolution of antibiotic resistance
Authors: Mahrt Niels , Tietze Alexandra , Künzel Sven , Franzenburg Sören , Barbosa Camilo , Jansen Gunther , Schulenburg Hinrich
Published: July 2021

During antibiotic treatment, the evolution of bacterial pathogens is fundamentally affected by bottlenecks and varying selection levels imposed by the drugs. Bottlenecks—that is, reductions in bacterial population size—lead to an increased influence of random effects (genetic drift) during bacterial evolution, and varying antibiotic concentrations during treatment may favour distinct resistance variants. Both aspects influence the process of bacterial evolution during antibiotic therapy and thereby treatment outcome. Surprisingly, the joint influence of these interconnected factors on the evolution of antibiotic resistance remains largely unexplored. Here we combine evolution experiments with genomic and genetic analyses to demonstrate that bottleneck size and antibiotic-induced selection reproducibly impact the evolutionary path to resistance in pathogenic Pseudomonas aeruginosa, one of the most problematic opportunistic human pathogens. Resistance is favoured—expectedly—under high antibiotic selection and weak bottlenecks, but—unexpectedly—also under low antibiotic selection and severe bottlenecks. The latter is likely to result from a reduced probability of losing favourable variants through drift under weak selection. Moreover, the absence of high resistance under low selection and weak bottlenecks is caused by the spread of low-resistance variants with high competitive fitness under these conditions. We conclude that bottlenecks, in combination with drug-induced selection, are currently neglected key determinants of pathogen evolution and outcome of antibiotic treatment.
Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination
Authors: Schmidt Tina , Klemis Verena , Schub David , Mihm Janine , Hielscher Franziska , Marx Stefanie , Abu-Omar Amina , Ziegler Laura , Guckelmus Candida , Urschel Rebecca , Schneitler Sophie , Becker Sören L. , Gärtner Barbara C. , Sester Urban , Sester Martina
Published: July 2021

Heterologous priming with the ChAdOx1 nCoV-19 vector vaccine followed by boosting with a messenger RNA vaccine (BNT162b2 or mRNA-1273) is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available. In this observational study we show that, in healthy adult individuals (n = 96), the heterologous vaccine regimen induced spike-specific IgG, neutralizing antibodies and spike-specific CD4 T cells, the levels of which which were significantly higher than after homologous vector vaccine boost (n = 55) and higher or comparable in magnitude to homologous mRNA vaccine regimens (n = 62). Moreover, spike-specific CD8 T cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Spike-specific T cells were predominantly polyfunctional with largely overlapping cytokine-producing phenotypes in all three regimens. Recipients of both the homologous vector regimen and the heterologous vector/mRNA combination reported greater reactogenicity following the priming vector vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA boosting. Taken together, heterologous vector/mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profiles.
Effect of substitution on the superconducting phase of transition metal dichalcogenide Nb(Se$$_{x}$$S$$_{1-x}$$)$$_{2}$$ van der Waals layered structure
Authors: Tsuppayakorn-aek Prutthipong , Pluengphon Prayoonsak , Phansuke Piya , Inceesungvorn Burapat , Busayaporn Wutthikrai , Kaewtubtim Pungtip , Bovornratanaraks Thiti
Published: July 2021

By means of first-principles cluster expansion, anisotropic superconductivity in the transition metal dichalcogenide Nb(Se$$_{x}$$

x

S$$_{1-x}$$

1
-
x

)$$_{2}$$

2

forming a van der Waals (vdW) layered structure is observed theoretically. We show that the Nb(Se$$_{0.5}$$

0.5

S$$_{0.5}$$

0.5

)$$_{2}$$

2

vdW-layered structure exhibits minimum ground-state energy. The Pnnm structure is more thermodynamically stable when compared to the 2H–NbSe$$_{2}$$

2

and 2H–NbS$$_{2}$$

2

structures. The characteristics of its phonon dispersions confirm its dynamical stability. According to electronic properties, i.e., electronic band structure, density of states, and Fermi surface indicate metallicity of Nb(Se$$_{0.5}$$

0.5

S$$_{0.5}$$

0.5

)$$_{2}$$

2

. The corresponding superconductivity is then investigated through the Eliashberg spectral function, which gives rise to a superconducting transition temperature of 14.5 K. This proposes a remarkable improvement of superconductivity in this transition metal dichalcogenide.
Extracellular NLRP3 inflammasome particles are internalized by human coronary artery smooth muscle cells and induce pro-atherogenic effects
Authors: Gaul Susanne , Schaeffer Karen Marie , Opitz Lena , Maeder Christina , Kogel Alexander , Uhlmann Luisa , Kalwa Hermann , Wagner Ulf , Haas Jan , Behzadi Amirhossein , Pelegrin Pablo , Boeckel Jes-Niels , Laufs Ulrich
Published: July 2021

Inflammation driven by intracellular activation of the NLRP3 inflammasome is involved in the pathogenesis of a variety of diseases including vascular pathologies. Inflammasome specks are released into the extracellular compartment from disrupting pyroptotic cells. The potential uptake and function of extracellular NLRP3 inflammasomes in human coronary artery smooth muscle cells (HCASMC) are unknown. Fluorescently labeled NLRP3 inflammasome particles were isolated from a mutant NLRP3-YFP cell line and used to treat primary HCASMC for 4 and 24 h. Fluorescent and expressional analyses showed that extracellular NLRP3-YFP particles are internalized into HCASMC, where they remain active and stimulate intracellular caspase-1 (1.9-fold) and IL-1β (1.5-fold) activation without inducing pyroptotic cell death. Transcriptomic analysis revealed increased expression level of pro-inflammatory adhesion molecules (ICAM1, CADM1), NLRP3 and genes involved in cytoskleleton organization. The NLRP3-YFP particle-induced gene expression was not dependent on NLRP3 and caspase-1 activation. Instead, the effects were partly abrogated by blocking NFκB activation. Genes, upregulated by extracellular NLRP3 were validated in human carotid artery atheromatous plaques. Extracellular NLRP3-YFP inflammasome particles promoted the secretion of pro-atherogenic and inflammatory cytokines such as CCL2/MCP1, CXCL1 and IL-17E, and increased HCASMC migration (1.8-fold) and extracellular matrix production, such as fibronectin (5.8-fold) which was dependent on NFκB and NLRP3 activation. Extracellular NLRP3 inflammasome particles are internalized into human coronary artery smooth muscle cells where they induce pro-inflammatory and pro-atherogenic effects representing a novel mechanism of cell-cell communication and perpetuation of inflammation in atherosclerosis. Therefore, extracellular NLRP3 inflammasomes may be useful to improve the diagnosis of inflammatory diseases and the development of novel anti-inflammatory therapeutic strategies.
Relationship between abnormalities detected by magnetic resonance imaging and knee symptoms in early knee osteoarthritis
Authors: Ota Seiya , Sasaki Eiji , Sasaki Shizuka , Chiba Daisuke , Kimura Yuka , Yamamoto Yuji , Kumagai Mika , Ando Masataka , Tsuda Eiichi , Ishibashi Yasuyuki
Published: July 2021

We investigated the prevalence of magnetic resonance imaging (MRI) findings and their relationship with knee symptoms in women without radiographic evidence of knee osteoarthritis (KOA). This cross-sectional cohort study included 359 Japanese women without radiographic evidence of KOA (Kellgren‒Lawrence grade < 2). All participants underwent T2-weighted fat-suppressed MRI of their knees. Structural abnormalities (cartilage damage, bone marrow lesions [BMLs], subchondral cysts, bone attrition, osteophytes, meniscal lesions, and synovitis) were scored according to the whole-organ MRI score method. Knee symptoms were evaluated using the Knee Injury and Osteoarthritis Outcome Score. Participants were divided into early and non-KOA groups based on early KOA classification criteria. Logistic regression analysis was performed to evaluate the relationship between MRI abnormalities and knee symptoms. Cartilage damage was the most common abnormality (43.5%). The prevalences of cartilage damage, BMLs, subchondral cysts, bone attrition, meniscal lesions, and synovitis were higher in patients with early KOA than in those without. Synovitis (odds ratio [OR] 2.254, P = 0.002) and meniscal lesions (OR 1.479, P = 0.031) were positively associated with the presence of early KOA. Synovitis was most strongly associated with knee pain and might be a therapeutic target in patients with early KOA.
Unveiling the Nottingham Inversion Instability during the thermo-field emission from refractory metal micro-protrusions
Authors: Mofakhami Darius , Seznec Benjamin , Minea Tiberiu , Landfried Romaric , Testé Philippe , Dessante Philippe
Published: July 2021

The electron emission by micro-protrusions has been studied for over a century, but the complete explanation of the unstable behaviors and their origin remains an open issue. These systems often evolve towards vacuum breakdown, which makes experimental studies of instabilities very difficult. Modeling studies are therefore necessary. In our model, refractory metals have shown the most striking results for discontinuities or jumps recorded on the electron emitted current under high applied voltages. Herein, we provide evidence on the mechanisms responsible for the initiation of a thermal instability during the field emission from refractory metal micro-protrusions. A jump in the emission current at steady state is found beyond a threshold electric field, and it is correlated to a similar jump in temperature. These jumps are related to a transient runaway of the resistive heating that occurs after the Nottingham flux inversion. That causes the hottest region to move beneath the apex, and generates an emerging heat reflux towards the emitting surface. Two additional conditions are required to initiate the runaway. The emitter geometry must ensure a large emission area and the thermal conductivity must be high enough at high temperatures so that the heat reflux can significantly compete with the heat diffusion towards the thermostat. The whole phenomenon, that we propose to call the Nottingham Inversion Instability, can explain unexpected thermal failures and breakdowns observed with field emitters.
Honey bee queen health is unaffected by contact exposure to pesticides commonly found in beeswax
Authors: McAfee Alison , Milone Joseph P , Metz Bradley , McDermott Erin , Foster Leonard J , Tarpy David R
Published: July 2021

Honey bee queen health is crucial for colony health and productivity, and pesticides have been previously associated with queen loss and premature supersedure. Prior research has investigated the effects of indirect pesticide exposure on queens via workers, as well as direct effects on queens during development. However, as adults, queens are in constant contact with wax as they walk on comb and lay eggs; therefore, direct pesticide contact with adult queens is a relevant but seldom investigated exposure route. Here, we conducted laboratory and field experiments to investigate the impacts of topical pesticide exposure on adult queens. We tested six pesticides commonly found in wax: coumaphos, tau-fluvalinate, atrazine, 2,4-DMPF, chlorpyriphos, chlorothalonil, and a cocktail of all six, each administered at 1, 4, 8, 16, and 32 times the concentrations typically found in wax. We found no effect of any treatment on queen mass, sperm viability, or fat body protein expression. In a field trial testing queen topical exposure of a pesticide cocktail, we found no impact on egg-laying pattern, queen mass, emergence mass of daughter workers, and no proteins in the spermathecal fluid were differentially expressed. These experiments consistently show that pesticides commonly found in wax have no direct impact on queen performance, reproduction, or quality metrics at the doses tested. We suggest that previously reported associations between high levels of pesticide residues in wax and queen failure are most likely driven by indirect effects of worker exposure (either through wax or other hive products) on queen care or queen perception.
FDG-PET predicts bone invasion and prognosis in patients with oral squamous cell carcinoma
Authors: Lin Nan-Chin , Su I-Hsien , Hsu Jui-Ting , Tsai Kuo-Yang , Chen Michael Y. C.
Published: July 2021

18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) is widely used for tumor staging. This study sought to determine the relationship of preoperative primary tumor SUVmax (tSUVmax) with the clinicopathological features of patients with OSCC and to compare the prognostic ability of tSUVmax with that of other recurrence factors. Data of 340 patients with OSCC who were diagnosed, treated, and followed up at the Changhua Christian Hospital were retrospectively analyzed. Only patients with OSCC arising from gingiva, palate, floor of the mouth, and retromolar trigone and those who had received preoperative FDG-PET within 2 weeks before surgery were included. tSUVmax value > 9.2 was the strong predictor of bone invasion (area under the receiver operating characteristic curve, 0.844). tSUVmax value > 7.2 showed a strong association with advanced pathological T stage and recurrence factors and was associated with poor survival; tSUVmax > 7.2 showed stronger predictive power for poor disease-free survival (DFS) than pT stage and the other recurrence factors related to primary tumor. FDG-PET can be a useful supplement to contrast-enhanced computed tomography or contrast-enhanced magnetic resonance imaging for diagnosing bone invasion by OSCC. The tSUVmax value was an independent predictor of DFS in this study.
Clinical outcomes of hospitalized COVID-19 patients with renal injury: a multi-hospital observational study from Wuhan
Authors: Chen Kehong , Lei Yu , He Yani , Xiao Fei , Yu Yan , Lai Xiaodong , Liu Yang , Wang Jiang , Dai Huanzi
Published: July 2021

Renal injury is common in patients with coronavirus disease 2019 (COVID‐19). We aimed to determine the relationship of estimated glomerular filtration rate (eGFR) and acute kidney injury (AKI) with the characteristics, progression, and prognosis of COVID-19 in-patients. We retrospectively reviewed 1851 COVID-19 patients admitted to 3 hospitals in Wuhan, China. Clinical, laboratory, radiological, treatment, complication, and outcome data were analyzed. Patients were stratified according to levels of eGFR (≥ 90 vs. 60–89 vs. < 60 mL/min/1.73 m2). The risk of reaching the composite endpoint—intensive care unit admission, invasive ventilation, or death—was compared. On admission, 25.5% patients had renal impairment (eGFR < 90 mL/min/1.73 m2), but only 2.6% patients had chronic kidney disease (CKD). The overall in-hospital AKI incidence was 6.7%. Severe illness and comorbidities (hypertension, diabetes, CKD, and cardiovascular/cerebrovascular diseases) were more common among patients with low eGFR (< 90 mL/min/1.73 m2). Despite the more frequent use of intensive oxygen therapy, continuous blood purification, and glucocorticoid treatment, the prognosis of these patients was unsatisfactory, with the incidence of the composite endpoint (15.4% vs. 19.6% vs. 54.5%; P = 0.000) and complications (AKI, respiratory failure, cardiac injury, coagulation disorders, sepsis, etc.) increasing with decreasing eGFR. Kaplan–Meier survival analysis revealed that patients with eGFR < 90 mL/min/1.73 m2 or AKI had significantly escalated risks of reaching the composite endpoint. Multivariate regression analysis showed that renal insufficiency (eGFR < 60 mL/min/1.73 m2) on admission and in-hospital AKI independently predicted poor prognosis among COVID-19 in-patients. And renal impairment on admission was a greater predictor of poor prognosis in non-elderly patients than that in elderly patients. Early and continuous renal-function monitoring and early AKI diagnosis are necessary to predict and prevent the progression of COVID-19.
Madrepora oculata forms large frameworks in hypoxic waters off Angola (SE Atlantic)
Authors: Orejas Covadonga , Wienberg Claudia , Titschack Jürgen , Tamborrino Leonardo , Freiwald André , Hebbeln Dierk
Published: July 2021

This study aims to map the occurrence and distribution of Madrepora oculata and to quantify density and colony sizes across recently discovered coral mounds off Angola. Despite the fact that the Angolan populations of M. oculata thrive under extreme hypoxic conditions within the local oxygen minimum zone, they reveal colonies with remarkable heights of up to 1250 mm—which are the tallest colonies ever recorded for this species—and average densities of 0.53 ± 0.37 (SD) colonies m−2. This is particularly noteworthy as these values are comparable to those documented in areas without any oxygen constraints. The results of this study show that the distribution pattern documented for M. oculata appear to be linked to the specific regional environmental conditions off Angola, which have been recorded in the direct vicinity of the thriving coral community. Additionally, an estimated average colony age of 95 ± 76 (SD) years (total estimated age range: 16–369 years) indicates relatively old M. oculata populations colonizing the Angolan coral mounds. Finally, the characteristics of the Angolan populations are benchmarked and discussed in the light of the existing knowledge on M. oculata gained from the North Atlantic and Mediterranean Sea.
Leukocytes with chromosome Y loss have reduced abundance of the cell surface immunoprotein CD99
Authors: Mattisson Jonas , Danielsson Marcus , Hammond Maria , Davies Hanna , Gallant Caroline J. , Nordlund Jessica , Raine Amanda , Edén Malin , Kilander Lena , Ingelsson Martin , Dumanski Jan P. , Halvardson Jonatan , Forsberg Lars A.
Published: July 2021

Mosaic loss of chromosome Y (LOY) in immune cells is a male-specific mutation associated with increased risk for morbidity and mortality. TheCD99gene, positioned in the pseudoautosomal regions of chromosomes X and Y, encodes a cell surface protein essential for several key properties of leukocytes and immune system functions. Here we used CITE-seq for simultaneous quantification ofCD99derived mRNA and cell surface CD99 protein abundance in relation to LOY in single cells. The abundance of CD99 molecules was lower on the surfaces of LOY cells compared with cells without this aneuploidy in all six types of leukocytes studied, while the abundance of CD proteins encoded by genes located on autosomal chromosomes were independent from LOY. These results connect LOY in single cells with immune related cellular properties at the protein level, providing mechanistic insight regarding disease vulnerability in men affected with mosaic chromosome Y loss in blood leukocytes.
The isotopic niche of Atlantic, biting marine mammals and its relationship to skull morphology and body size
Authors: Drago Massimiliano , Signaroli Marco , Valdivia Meica , González Enrique M. , Borrell Asunción , Aguilar Alex , Cardona Luis
Published: July 2021

Understanding the trophic niches of marine apex predators is necessary to understand interactions between species and to achieve sustainable, ecosystem-based fisheries management. Here, we review the stable carbon and nitrogen isotope ratios for biting marine mammals inhabiting the Atlantic Ocean to test the hypothesis that the relative position of each species within the isospace is rather invariant and that common and predictable patterns of resource partitioning exists because of constrains imposed by body size and skull morphology. Furthermore, we analyze in detail two species-rich communities to test the hypotheses that marine mammals are gape limited and that trophic position increases with gape size. The isotopic niches of species were highly consistent across regions and the topology of the community within the isospace was well conserved across the Atlantic Ocean. Furthermore, pinnipeds exhibited a much lower diversity of isotopic niches than odontocetes. Results also revealed body size as a poor predictor of the isotopic niche, a modest role of skull morphology in determining it, no evidence of gape limitation and little overlap in the isotopic niche of sympatric species. The overall evidence suggests limited trophic flexibility for most species and low ecological redundancy, which should be considered for ecosystem-based fisheries management.