bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of viral integration reveals new insights of oncogenic mechanism in HBV-infected intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma
Authors: Zhao Linghao , Wang Yuyouye , Tian Tao , Rao Xinjie , Dong Wei , Zhang Jinmin , Yang Yuan , Tao Qifei , Peng Fang , Shen Chenhang , Wang Songbo , Liu Hui , Zeng Xi , Zhou Weiping
Published: September 2022

Background

Integration of HBV DNA into the human genome could progressively contribute to hepatocarcinogenesis. Both intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC) are known to be associated with HBV infection. However, the integration of HBV and mechanism of HBV-induced carcinogenesis in ICC and CHC remains unclear.

Methods

41 patients with ICC and 20 patients with CHC were recruited in the study. We conducted HIVID analysis on these 61 samples to identify HBV integration sites in both the tumor tissues and adjacent non-tumor liver tissues. To further explore the effect of HBV integration on gene alteration, we selected paired tumors and adjacent non-tumor liver tissues from 3 ICC and 4 CHC patients for RNA-seq and WGS.

Results

We detected 493 HBV integration sites in ICC patients, of which 417 were from tumor samples and 76 were from non-tumor samples. And 246 HBV integration sites were detected in CHC patients, of which 156 were located in the genome of tumor samples and 90 were in non-tumor samples. Recurrent HBV integration events were detected in ICC including TERT, ZMAT4, MET, ANKFN1, PLXNB2, and in CHC like TERT, ALKBH5. Together with our established data of HBV-infected hepatocellular carcinoma, we found that HBV preferentially integrates into the specific regions which may affect the gene expression and regulation in cells and involved in carcinogenesis. We further performed genomic and transcriptomic sequencing of three ICC and four CHC patients, and found that HBV fragments could integrate near some important oncogene like TERT, causing large-scale genome variations on nearby genomic sequences, and at the same time changing the expression level of the oncogenes.

Conclusion

Comparative analysis demonstrates numerous newly discovered mutational events in ICC and CHC resulting from HBV insertions in the host genome. Our study provides an in-depth biological and clinical insights into HBV-induced ICC and CHC.
Fenestrate bryozoan fauna from the Middle Devonian of the Eifel (western Rhenish Massif, Germany)
Authors: Ernst Andrej
Published: September 2022

Seven fenestrate bryozoans are described from the Middle Devonian of the Eifel. Three species were identified asProlixicella bifurcataErnst and Schroeder, 2007,Rectifenestella aculeata(Sandberger and Sandberger, 1856), andSpinofenestella antiqua(Goldfuss, 1826). Four species are described in open nomenclature:Rectifenestellasp. 1 and sp. 2,Ptyloporasp., andSpinofenestellasp. Analysis of the distribution of the fenestrate bryozoans from the Middle Devonian of the Eifel shows their relatively high level of endemism revealing some few connections to the Devonian of Europe and Asia. The studied association shows similarities to the contemporary fauna from Sauerland.
Comparison of Extraction Methods for the Detection of Tick-Borne Encephalitis Virus RNA in Goat Raw Milk and Cream Cheese
Authors: Müller Irene , Althof Nadine , Hoffmann Bernd , Klaus Christine , Schilling-Loeffler Katja , Falkenhagen Alexander , Johne Reimar
Published: September 2022

Infection with the tick-borne encephalitis virus (TBEV) can cause meningitis, meningoencephalitis and myelitis in humans. TBEV is an enveloped RNA virus of the family Flaviviridae, which is mostly transmitted via tick bites. However, transmission by consumption of virus-contaminated goat raw milk and goat raw milk products has also been described. Only a few methods have been reported for the detection of TBEV in food so far. Here, we compare different virus extraction methods for goat raw milk and goat raw milk cream cheese and subsequent detection of TBEV-RNA by RT-qPCR. Langat virus (LGTV), a naturally attenuated TBEV strain, was used for artificial contamination experiments. Mengovirus and the human coronavirus 229E were compared to assess their suitability to serve as internal process controls. Out of three tested extraction protocols for raw milk, sample centrifugation followed by direct RNA extraction from the aqueous interphase yielded the best results, with a recovery rate (RR) of 31.8 ± 4.9% for LGTV and a detection limit of 6.7 × 103 LGTV genome copies/ml. Out of two methods for cream cheese, treatment of the samples with TRI Reagent® and chloroform prior to RNA extraction showed the best RR of 4.7 ± 1.6% for LGTV and a detection limit of 9.4 × 104 LGTV genome copies/g. RRs of Mengovirus and LGTV were similar for both methods; therefore, Mengovirus is suggested as internal process control virus. The developed methods may be useful for screening or surveillance studies, as well as in outbreak investigations.
Shifting Baselines: Longitudinal Reductions in EEG Beta Band Power Characterize Resting Brain Activity with Intensive Meditation
Authors: Skwara Alea C. , King Brandon G. , Zanesco Anthony P. , Saron Clifford D.
Published: September 2022

Objectives

A core assumption of meditation training is that cognitive capacities developed during formal practice will transfer to other contexts or activities as expertise develops over time. This implies that meditation training might influence domain-general neurocognitive systems, the spontaneous activity of which should be reflected in the dynamics of the resting brain. Previous research has demonstrated that 3 months of meditation training led to reductions in EEG beta band power during mindfulness of breathing practice. The current study extends these findings to ask whether concomitant shifts in power are observed during 2 min of eyes closed rest, when participants are not explicitly engaged in formal meditation.

Methods

Experienced meditation practitioners were randomly assigned to practice 3 months of focused attention meditation in a residential retreat, or to serve as waitlist controls. The waitlist controls later completed their own 3-month retreat. Permutation-based cluster analysis of 88-channel resting EEG data was used to test for spectral changes in spontaneous brain activity over the course of the retreats.

Results

Longitudinal reductions in EEG power in the beta frequency range were identified and replicated across the two independent training periods. Less robust reductions were also observed in the high alpha frequency range, and in individual peak alpha frequency. These changes closely mirror those previously observed during formal mindfulness of breathing meditation practice.

Conclusions

These findings suggest that the neurocognitive effects of meditation training can extend beyond the bounds of formal practice, influencing the spontaneous activity of the resting brain. Rather than serving as an invariant baseline, resting states might carry meaningful training-related effects, blurring the line between state and trait change.
Unleashing the Potential of the TQM and Industry 4.0 to Achieve Sustainability Performance in the Context of a Developing Country
Authors: Saha Palash , Talapatra Subrata , Belal H. M. , Jackson Victoria
Published: September 2022

Business organizations may be able to improve their Sustainability Performance (SP) by adopting Total Quality Management (TQM) concepts combined with Industry 4.0 (I4.0) technologies. This research has developed a model to investigate the influence of TQM and I4.0 on SP. It also analyzes the mediating role of TQM in the relationship between I4.0 and SP. A survey was conducted among 240 respondents employed in ready-made garment (RMG) industries in Bangladesh. A Structural Equation Modelling (SEM) technique was used to analyze the collected data. Research findings show that both TQM and I4.0 technologies have a significant impact on the sustainable growth of the Bangladeshi RMG sector. Moreover, it is observed that TQM mediates the relationship between I4.0 and SP. The findings show that TQM helps to explain the relationship between I4.0 and sustainable performance. This study will provide a guideline for industrial executives on securing sustainability through the adoption of TQM concepts and I4.0 technologies. We are not aware of any additional studies that look at the possible link between TQM, I4.0, and SP, as well as the mediating role of TQM between I4.0 and SP.
One year of COVID-19 pandemic on patients with eating disorders, healthy sisters, and community women: evidence of psychological vulnerabilities
Authors: Meneguzzo Paolo , Sala Alessandra , Merlino Laura , Ceccato Enrico , Santonastaso Paolo
Published: September 2022

Purpose

The COVID-19 pandemic has been a psychological burden worldwide, especially for individuals with eating disorders (EDs). In addition, the healthy sisters of patients with EDs are known to present specific psychological vulnerabilities. This study evaluates differences between the general population, patients with EDs, and their healthy sisters.

Method

A group of 233 participants (91 patients with EDs, 57 of their healthy sisters and 85 community women) was enrolled in an online survey on general and specific psychopathology 1 year after the beginning of the COVID-19 pandemic. The survey examined associations between posttraumatic symptoms and depression, anxiety, obsessive–compulsiveness, interpersonal sensitivity, and eating-related concerns.

Results

Clinically relevant scores for posttraumatic disorders were found in patients with EDs. Healthy sisters scored similarly to patients for avoidance. Regression analysis showed specific associations between interpersonal sensitivity and posttraumatic symptomatology in patients and healthy sisters, but not in community women.

Conclusion

The psychological burden in patients with EDs is clinically relevant and linked to interpersonal sensitivity, obsessive–compulsiveness, and global symptom severity. Differences between patients, healthy sisters, and community women are discussed regarding vulnerability factors for EDs.

Level of evidence

Level III: evidence obtained from well-designed cohort or case–control analytic studies.
Only two Betchov homogeneity constraints exist for isotropic turbulence
Authors: Carbone Maurizio , Wilczek Michael
Published: September 2022

Statistically homogeneous flows obey exact kinematic relations. The Betchov homogeneity constraints (Betchov,J. Fluid Mech., vol. 1, 1956, pp. 497–504) for the average principal invariants of the velocity gradient are among the most well-known and extensively employed homogeneity relations. These homogeneity relations have far-reaching implications for the coupled dynamics of strain and vorticity, as well as for the turbulent energy cascade. Whether the Betchov homogeneity constraints are the only possible ones or whether additional homogeneity relations exist has not been proven yet. Here we show that the Betchov homogeneity constraints are the only homogeneity constraints for incompressible and statistically isotropic velocity gradient fields. Our analysis also applies to compressible/perceived velocity gradients, and it allows the derivation of homogeneity relations involving the velocity gradient and other dynamically relevant quantities, such as the pressure Hessian and viscous stresses.
An analytical blockage correction model for high-solidity turbines
Authors: Steiros K. , Bempedelis N. , Cicolin M.M.
Published: September 2022

A significant challenge in the experimental or computational characterisation of porous bodies and wind turbines is the correction of the obtained flow quantities for wall interference effects. Conventional corrective models are based on the Rankine–Froude theory, which is valid when the body solidity, or turbine induction factor, is sufficiently low. To resolve this issue, this work presents a new corrective model that builds on an extension of the Rankine–Froude theory, valid at arbitrary solidities, coupled with the method of mirror images to account for the existence of channel walls. The predictions of the new model are validated using laboratory and numerical experiments of porous plates and wind turbines. The results show that the new model performs equally as well as conventional ones when the solidity is low, but becomes increasingly more accurate as the latter grows.
A Markov jump process associated with the matrix-exponential distribution
Authors: Peralta Oscar
Published: September 2022

Let f be the density function associated to a matrix-exponential distribution of parameters
$(\boldsymbol{\alpha}, T,\boldsymbol{{s}})$
. By exponentially tilting f, we find a probabilistic interpretation which generalizes the one associated to phase-type distributions. More specifically, we show that for any sufficiently large
$\lambda\ge 0$
, the function
$x\mapsto \left(\int_0^\infty e^{-\lambda s}f(s)\textrm{d} s\right)^{-1}e^{-\lambda x}f(x)$
can be described in terms of a finite-state Markov jump process whose generator is tied to T. Finally, we show how to revert the exponential tilting in order to assign a probabilistic interpretation to f itself.
Returns to public investments in clean plant centers: A case study of leafroll virus-tested grapevines in support of cost-effective grape production systems
Authors: Li Jie , Troendle Jason , Gómez Miguel I. , Ifft Jennifer , Golino Deborah , Fuchs Marc
Published: September 2022

Viruses and related graft-transmissible pathogens cause diseases that cost the grape industry billions of dollars annually if left uncontrolled. The National Clean Plant Network (NCPN), a USDA Farm Bill program, is an organization of clean plant centers that produce and maintain virus-tested foundation vine stocks and distribute propagation material derived thereof to nurseries and growers to minimize the introduction of viruses and virus-like diseases into the vineyard. Foundation Plant Services (FPS) is the major NCPN-grapes center. We examined the economic impacts of public investments in FPS from 2006 to 2019. By focusing on grapevine leafroll disease, our analyses revealed a benefit-cost ratio ranging from 22:1 to 96:1, with a 5% and a 20% disease infection rates in commercial vineyards, respectively. A welfare analysis was consistent with grape growers and nurseries capturing most (64–98%) of the benefits from adopting clean planting material compared with winemakers and other actors in the downstream wine supply chain system. This study provided new insights into the returns to public investments in a clean plant center and documented strong financial incentives for higher adoption of clean vines derived from virus-tested stocks, while justifying continued support of NCPN centers from public and private sectors.
The New Politics of Judicial Appointments in Southern Africa
Authors: Brett Peter
Published: September 2022

Political scientists analyze the global rise of judicial appointment commissions as a response to judicialized politics. They argue that appointment processes have formalized to include more constituencies now affected by judicial decisions. This article presents evidence from Southern Africa confounding their expectations. In this region, formalization has social as well as political origins. Over the last two decades, the senior judiciary has suddenly become subject to the same demands for organizational accountability and descriptive representation that sociologists of other professions have been documenting for decades. Throughout the region, therefore, it has become increasingly difficult to defend opaque practices inherited from British (and South African) colonialism. Twenty years ago, Namibia, Botswana, Lesotho, and Swaziland/Eswatini all recruited most appellate judges from abroad through informal channels. In every country, this system has come under pressure from a variety of local sources. Yet those demanding reform have always been able to mobilize new international orthodoxies that require the judiciary to represent its society and make itself accountable to profane, external audiences. These new orthodoxies have acquired an unusual power in Southern Africa thanks to their embodiment in South Africa’s own post-apartheid transition, and long-standing moral imperatives to “localize” senior expatriate positions in postcolonial states.
Paleohistological inferences of thermometabolic regimes in Notosuchia (Pseudosuchia: Crocodylomorpha) revisited
Authors: Cubo Jorge , Aubier Paul , Faure-Brac Mathieu G. , Martet Gaspard , Pellarin Romain , Pelletan Idriss , Sena Mariana V. A.
Published: September 2022

Notosuchia is a group of mostly terrestrial crocodyliforms. The presence of a prominent crest overhanging the acetabulum, slender straight-shafted long bones with muscular insertions close to the joints, and a stable knee joint suggests that they had an erect posture. This stance has been proposed to be linked to endothermy, because it is present in mammals and birds and contributes to the efficiency of their respiratory systems. However, a bone paleohistological study unexpectedly suggested that Notosuchia were ectothermic organisms. The thermophysiological status of Notosuchia deserves further analysis, because the methodology of the previous study can be improved. First, it was based on a relationship between red blood cell size and bone vascular canal diameter tested using 14 extant tetrapod species. Here we present evidence for this relationship using a more comprehensive sample of extant tetrapods (31 species). Moreover, contrary to previous results, bone cross-sectional area appears to be a significant explanatory variable (in addition to vascular canal diameter). Second, red blood cell size estimations were performed using phylogenetic eigenvector maps, and this method excludes a fraction of the phylogenetic information. This is because it generates a high number of eigenvectors requiring a selection procedure to compile a subset of them to avoid model overfitting. Here we inferred the thermophysiology of Notosuchia using phylogenetic logistic regressions, a method that overcomes this problem by including all of the phylogenetic information and a sample of 46 tetrapods. These analyses suggest thatAraripesuchus wegeneri,Armadillosuchus arrudai,Baurusuchussp.,Iberosuchus macrodon, andStratiotosuchus maxhechtiwere ectothermic organisms.
The future of the Affective Neuroscience Personality Scales: A reflection on seven pressing matters
Authors: Montag Christian , Solms Mark , Stelzel Christine , Davis Kenneth L.
Published: September 2022

The Affective Neuroscience Personality Scales (ANPS) were designed to provide researchers in the mental sciences with an inventory to assess primary emotional systems according to Pankseppian Affective Neuroscience Theory (ANT). The original ANPS, providing researchers with such a tool, was published in 2003. In the present brief communication, about 20 years later, we reflect upon some pressing matters regarding the further development of the ANPS. We touch upon problems related to disentangling traits and states of the primary emotional systems with the currently available versions of the ANPS and upon its psychometric properties and its length. We reflect also on problems such as the large overlap between the SADNESS and FEAR dimensions, the disentangling of PANIC and GRIEF in the context of SADNESS, and the absence of a LUST scale. Lastly, we want to encourage scientists with the present brief communication to engage in further biological validation of the ANPS.
When Legal Fundamentalism Meets Political Justice: The Case of Poland
Authors: Koncewicz Tomasz Tadeusz
Published: September 2022

To Professor Martin Shapiro, With friendship, gratitude, and admiration

The ruling of 22 October 2020 concerning termination of pregnancy in Case K 1/20, handed down by the body once known as the Polish Constitutional Court, has devastated the legal and social landscape in Poland. The decision ruled as unconstitutional the provision that allowed medically assisted termination in cases where prenatal screening or other medical considerations indicated a high probability of a severe and irreversible abnormality or an incurable disease of the fetus. This analysis argues that the ruling is the most serious attempt to discredit and humiliate the Polish Constitution of 1997, and stands as the ultimate proof of weaponising judicial review. The argument will be made that if one wishes to understand the extent of the capture of independent institutions by the ruling majority, the ruling under consideration must be read and considered in the light of a more general context. Only by going beyond and contextualising it, can one grasp the extent to which the constitutional profile of a state has been altered by methods of unconstitutional capture. The analysis argues that once we contextualise the ruling and view it in a more systemic light, there are important systemic signposts that will help to explain how we arrived here and, more importantly, what is next. These signposts, in turn, contain a cautionary tale of the institutional fragility that is relevant for liberal democracies.
On Gregariousness
Authors: Costa Jonas Faria
Published: September 2022

There seems to be a difference between drinking coffee alone at home and drinking coffee in a café. Yet, drinking coffee in a café is not a joint action. It is an individual action done in a social environment. The café, with each person minding their own business next to others, is what I call a gregarious state of affairs. Gregariousness refers to the warmth of the social world. It is the difference between studying alone at home and studying in the library. This light form of sociality is precisely what we were deprived of during the coronavirus lockdowns. Gregariousness cannot be explained as interaction or coordination, and neither can it be grasped solely as a normative aspect of the environment. This is why gregariousness cannot be explained using the concepts of strategic equilibrium, shared planning agency, joint commitment, we-intention, or second-person standpoint. In this paper, I will also provide a prospective theory of gregariousness. The aim of this paper is not to provide a definitive theory of gregariousness, nor to demonstrate that other theories of joint action are incorrect, but rather to draw attention to this aspect of the social world that has been largely neglected.
Rethinking Acts of Conscience: Personal Integrity, Civility, and the Common Good
Authors: Garcia Ernesto V.
Published: September 2022

What should we think about ‘acts of conscience’, viz., cases where our personal judgments and public authority come into conflict such that principled resistance to the latter seems necessary? Philosophers mainly debate two issues: theAccommodation Question, i.e., ‘When, if ever, should public authority accommodate claims of conscience?’ and theJustification Question, i.e., ‘When, if ever, are we justified in engaging in acts of conscience – and why?’. By contrast, a third important topic – theConduct Question, i.e., ‘How should we act, morally speaking, when engaging in acts of conscience?’ – has been mostly neglected. This paper aims to offer concrete guidance for persons wishing to engage in acts of conscience in morally virtuous ways. I argue that such agents are subject to two basicprima facieduties: (i) duties to oneself related to demands of integrity and (ii) duties to others related to demands of civility. I explain both duties in detail, arguing with regard to (i), that in light of what I call ‘the paradox of conscience’, we need to rethink our views about both ‘conscience’ and ‘integrity’; and with regard to (ii), that, building upon Rawls’ ‘duty of civility’, we should embrace at least seven general principles for undertaking acts of conscience in a morally conscientious manner.
Digitale Phänotypisierung in der Psychologie – ein Quantensprung in der psychologischen Forschung?
Authors: Baumeister Harald , Garatva Patricia , Pryss Rüdiger , Ropinski Timo , Montag Christian
Published: September 2022

Zusammenfassung: Digitale Phänotypisierung stellt einen neuen, leistungsstarken Ansatz zur Realisierung psychodiagnostischer Aufgaben in vielen Bereichen der Psychologie und Medizin dar. Die Grundidee besteht aus der Nutzung digitaler Spuren aus dem Alltag, um deren Vorhersagekraft für verschiedenste Anwendungsmöglichkeiten zu überprüfen und zu nutzen. Voraussetzungen für eine erfolgreiche Umsetzung sind elaborierte Smart Sensing Ansätze sowie Big Data-basierte Extraktions- (Data Mining) und Machine Learning-basierte Analyseverfahren. Erste empirische Studien verdeutlichen das hohe Potential, aber auch die forschungsmethodischen sowie ethischen und rechtlichen Herausforderungen, um über korrelative Zufallsbefunde hinaus belastbare Befunde zu gewinnen. Hierbei müssen rechtliche und ethische Richtlinien sicherstellen, dass die Erkenntnisse in einer für Einzelne und die Gesellschaft als Ganzes wünschenswerten Weise genutzt werden. Für die Psychologie als Lehr- und Forschungsdomäne bieten sich durch Digitale Phänotypisierung vielfältige Möglichkeiten, die zum einen eine gelebte Zusammenarbeit verschiedener Fachbereiche und zum anderen auch curriculare Erweiterungen erfordern. Die vorliegende narrative Übersicht bietet eine theoretische, nicht-technische Einführung in das Forschungsfeld der Digitalen Phänotypisierung, mit ersten empirischen Befunden sowie einer Diskussion der Möglichkeiten und Grenzen sowie notwendigen Handlungsfeldern.
Lower Urban Humidity Moderates Outdoor Heat Stress
Authors: Chakraborty T. , Venter Z. S. , Qian Y. , Lee X.
Published: September 2022

Surface temperature is often used to examine heat exposure in multi‐city studies and for informing urban heat mitigation efforts due to scarcity of urban air temperature measurements. Cities also have lower relative humidity, traditionally not accounted for in large‐scale observational urban heat risk assessments. Here, using crowdsourced measurements from over 40,000 weather stations in ≈600 urban clusters in Europe, we show the moderating effect of this urbanization‐induced humidity reduction on outdoor heat stress during the 2019 heatwave. We demonstrate that daytime differences in heat index between urban clusters and their surroundings are weak, and associations of this urban‐rural difference with background climate, generally examined from the surface temperature perspective, are diminished due to moisture feedbacks. We also examine the spatial variability of surface temperature, air temperature, and heat index within these clusters—relevant for detecting hotspots and potential disparities in heat exposure—and find that surface temperature is a poor proxy for the intra‐urban distribution of heat index during daytime. Finally, urban vegetation shows much weaker (∼1/6th as strong) associations with heat index than with surface temperature, which has broad implications for optimizing urban heat stress mitigation strategies. These findings are valid for operational metrics of heat stress for shaded conditions (apparent temperature and humidex), thermodynamic proxies (wet‐bulb temperature), and empirical heat indices. Based on this large‐scale empirical evidence, surface temperature, used due to the lack of better alternatives, may not be suitable for accurately informing heat mitigation strategies within and across cities, necessitating more urban‐scale observations and better urban‐resolving models.
Sediment Release in the Benguela Upwelling System Dominates Trace Metal Input to the Shelf and Eastern South Atlantic Ocean
Authors: Liu Te , Krisch Stephan , Xie Ruifang C. , Hopwood Mark J. , Dengler Marcus , Achterberg Eric P.
Published: September 2022

Upwelling of subsurface waters injects macronutrients (fixed N, P, and Si) and micronutrient trace metals (TMs) into surface waters supporting elevated primary production in Eastern Boundary Upwelling Regions. The eastern South Atlantic features a highly productive shelf sea transitioning to a low productivity N‐Fe (co)limited open ocean. Whilst a gradient in most TM concentrations is expected in any off‐shelf transect, the factors controlling the magnitude of cross‐shelf TM fluxes are poorly constrained. Here, we present dissolved TM concentrations of Fe, Co, Mn, Cd, Ni, and Cu within the Benguela Upwelling System from the coastal section of the GEOTRACES GA08 cruise. Elevated dissolved Fe, Co, Mn, Cd, Ni, Cu and macronutrient concentrations were observed near shelf sediments. Benthic sources supplied 2.22 ± 0.99 μmol Fe m−2 day−1, 0.05 ± 0.03 μmol Co m−2 day−1, 0.28 ± 0.11 μmol Mn m−2 day−1 and were found to be the dominant source to shallow shelf waters compared to atmospheric depositions. Similarly, off‐shelf transfer was a more important source of TMs to the eastern South Atlantic Ocean compared to atmospheric deposition. Assessment of surface (shelf, upper 200 m) and subsurface (shelf edge, 200–500 m) fluxes of Fe and Co indicated TM fluxes from subsurface were 2–5 times larger than those from surface into the eastern South Atlantic Ocean. Under future conditions of increasing ocean deoxygenation, these fluxes may increase further, potentially contributing to a shift toward more extensive regional limitation of primary production by fixed N availability.
Using Principal Component Analysis of Satellite and Ground Magnetic Data to Model the Equatorial Electrojet and Derive Its Tidal Composition
Authors: Soares Gabriel , Yamazaki Yosuke , Morschhauser Achim , Matzka Jürgen , Pinheiro Katia J. , Stolle Claudia , Alken Patrick , Yoshikawa Akimasa , Hozumi Kornyanat , Kulkarni Atul , Supnithi Pornchai
Published: September 2022

The intensity of the equatorial electrojet (EEJ) shows temporal and spatial variability that is not yet fully understood nor accurately modeled. Atmospheric solar tides are among the main drivers of this variability but determining different tidal components and their respective time series is challenging. It requires good temporal and spatial coverage with observations, which, previously could only be achieved by accumulating data over many years. Here, we propose a new technique for modeling the EEJ based on principal component analysis (PCA) of a hybrid ground‐satellite geomagnetic data set. The proposed PCA‐based model (PCEEJ) represents the observed EEJ better than the climatological EEJM‐2 model, especially when there is good local time separation among the satellites involved. The amplitudes of various solar tidal modes are determined from PCEEJ based tidal equation fitting. This allows to evaluate interannual and intraannual changes of solar tidal signatures in the EEJ. On average, the obtained time series of migrating and nonmigrating tides agree with the average climatology available from earlier work. A comparison of tidal signatures in the EEJ with tides derived from neutral atmosphere temperature observations show a remarkable correlation for nonmigrating tides such as DE3, DE2, DE4, and SW4. The results indicate that it is possible to obtain a meaningful EEJ spectrum related to solar tides for a relatively short time interval of 70 days.
The Impact of Incremental Analysis Update on Regional Simulations for Typhoons
Authors: Ge Yangjinxi , Lei Lili , Whitaker Jeffrey S. , Tan Zhe‐Min
Published: September 2022

The analyses produced by intermittent data assimilation methods can be dynamically inconsistent and unbalanced. By gradually distributing the analysis increment along model integration, the incremental analysis update (IAU) is effective to combat the inconsistences and imbalances. Different implementations of IAU with time constant or time‐varying increments using different increment frequencies are systematically evaluated for regional simulations, especially for fast‐moving typhoons. Results show that experiments with IAU generally produce smaller forecast errors of temperature, specific humidity, and wind speed than experiment CTRL without initialization. Three‐dimensional IAUs (3DIAUs) with time‐constant increments have smaller errors than four‐dimensional IAUs (4DIAUs) with time‐varying increments interpolated from 3‐hr and hourly increments. Thus, for regional simulations, 3DIAU that imposes stronger filtering has advantages over 4DIAUs with different increment frequencies. For two typhoon cases, experiments with IAU obtain better intensity and structure of vortex than experiment CTRL; thus, the application of IAU can better retain the observation information and build the improved TC structure. But due to the displacement errors in priors and posteriors, the advantage of 4DIAU that considers the propagation of increment is limited compared to 3DIAU. As a trade‐off between the filtering and time‐varying increment, 4DIAU with 3‐hr increment that considers time‐varying increments compared to 3DIAU but imposes stronger filtering than 4DIAU with hourly increment could be preferred for TCs.
Preclinical investigation of artesunate as a therapeutic agent for hepatocellular carcinoma via impairment of glucosylceramidase-mediated autophagic degradation
Authors: Chen Wenjia , Ma Zhaochen , Yu Lingxiang , MAO Xia , Ma Nan , Guo Xiaodong , Yin Xiaoli , Jiang Funeng , Wang Qian , Wang Jigang , Fang Mingliang , Lin Na , Zhang Yanqiong
Published: September 2022

Artesunate (ART) has been indicated as a candidate drug for hepatocellular carcinoma (HCC). Glucosylceramidase (GBA) is required for autophagic degradation. Whether ART regulates autophagic flux by targeting GBA in HCC remains to be defined. Herein, our data demonstrated that the dramatic overexpression of GBA was significantly associated with aggressive progression and short overall survival times in HCC. Subsequent experiments revealed an association between autophagic activity and GBA expression in clinical HCC samples, tumor tissues from a rat model of inflammation-induced HCC and an orthotopic mouse model, and human HCC cell lines. Interestingly, probe labeling identified GBA as an ART target, which was further verified by both a glutathione-S-transferase pulldown assay and surface plasmon resonance analysis. The elevated protein expression of LC3B, the increased numbers of GFP-LC3B puncta and double-membrane vacuoles, and the enhanced expression of SQSTM1/p62 indicated that the degradation of autophagosomes in HCC cells was inhibited by ART treatment. Both the in vitro and in vivo data revealed that autophagosome accumulation through targeting of GBA was responsible for the anti-HCC effects of ART. In summary, this preclinical study identified GBA as one of the direct targets of ART, which may have promising potential to inhibit lysosomal autophagy for HCC therapy.
A non-canonical GABAergic pathway to the VTA promotes unconditioned freezing
Authors: Broussot Loïc , Contesse Thomas , Costa-Campos Renan , Glangetas Christelle , Royon Léa , Fofo Hugo , Lorivel Thomas , Georges François , Fernandez Sebastian P. , Barik Jacques
Published: September 2022

Freezing is a conserved defensive behaviour that constitutes a major stress-coping mechanism. Decades of research have demonstrated a role of the amygdala, periaqueductal grey and hypothalamus as core actuators of the control of fear responses, including freezing. However, the role that other modulatory sites provide to this hardwired scaffold is not known. Here, we show that freezing elicited by exposure to electrical foot shocks activates laterodorsal tegmentum (LDTg) GABAergic neurons projecting to the VTA, without altering the excitability of cholinergic and glutamatergic LDTg neurons. Selective chemogenetic silencing of this inhibitory projection, but not other LDTg neuronal subtypes, dampens freezing responses but does not prevent the formation of conditioned fear memories. Conversely, optogenetic-activation of LDTg GABA terminals within the VTA drives freezing responses and elicits bradycardia, a common hallmark of freezing. Notably, this aversive information is subsequently conveyed from the VTA to the amygdala via a discrete GABAergic pathway. Hence, we unveiled a circuit mechanism linking LDTg-VTA-amygdala regions, which holds potential translational relevance for pathological freezing states such as post-traumatic stress disorders, panic attacks and social phobias.
Diabetes downregulates the antimicrobial peptide psoriasin and increases E. coli burden in the urinary bladder
Authors: Mohanty Soumitra , Kamolvit Witchuda , Scheffschick Andrea , Björklund Anneli , Tovi Jonas , Espinosa Alexander , Brismar Kerstin , Nyström Thomas , Schröder Jens M. , Östenson Claes-Göran , Aspenström Pontus , Brauner Hanna , Brauner Annelie
Published: September 2022

Diabetes is known to increase susceptibility to infections, partly due to impaired granulocyte function and changes in the innate immunity. Here, we investigate the effect of diabetes, and high glucose on the expression of the antimicrobial peptide, psoriasin and the putative consequences for E. coli urinary tract infection. Blood, urine, and urine exfoliated cells from patients are studied. The influence of glucose and insulin is examined during hyperglycemic clamps in individuals with prediabetes and in euglycemic hyperinsulinemic clamped patients with type 1 diabetes. Important findings are confirmed in vivo in type 2 diabetic mice and verified in human uroepithelial cell lines. High glucose concentrations induce lower psoriasin levels and impair epithelial barrier function together with altering cell membrane proteins and cytoskeletal elements, resulting in increasing bacterial burden. Estradiol treatment restores the cellular function with increasing psoriasin and bacterial killing in uroepithelial cells, confirming its importance during urinary tract infection in hyperglycemia. In conclusion, our findings present the effects and underlying mechanisms of high glucose compromising innate immunity.
Insight into mode-of-action and structural determinants of the compstatin family of clinical complement inhibitors
Authors: Lamers Christina , Xue Xiaoguang , Smieško Martin , van Son Henri , Wagner Bea , Berger Nadja , Sfyroera Georgia , Gros Piet , Lambris John D. , Ricklin Daniel
Published: September 2022

With the addition of the compstatin-based complement C3 inhibitor pegcetacoplan, another class of complement targeted therapeutics have recently been approved. Moreover, compstatin derivatives with enhanced pharmacodynamic and pharmacokinetic profiles are in clinical development (e.g., Cp40/AMY-101). Despite this progress, the target binding and inhibitory modes of the compstatin family remain incompletely described. Here, we present the crystal structure of Cp40 complexed with its target C3b at 2.0-Å resolution. Structure-activity-relationship studies rationalize the picomolar affinity and long target residence achieved by lead optimization, and reveal a role for structural water in inhibitor binding. We provide explanations for the narrow species specificity of this drug class and demonstrate distinct target selection modes between clinical compstatin derivatives. Functional studies provide further insight into physiological complement activation and corroborate the mechanism of its compstatin-mediated inhibition. Our study may thereby guide the application of existing and development of next-generation compstatin analogs.
(NHC)Pd(II) hydride-catalyzed dehydroaromatization by olefin chain-walking isomerization and transfer-dehydrogenation
Authors: Chen Weihao , Chen Yang , Gu Xiao , Chen Zaizhu , Ho Chun-Yu
Published: September 2022

Transition-metal-catalyzed homogeneous dehydrogenation and isomerization are common organic molecular activation reactions. Palladium hydrides are good olefin isomerization catalysts but are usually short-lived species under redox-active dehydrogenation conditions. Here, we show that Pd-H in the presence of an N-heterocyclic carbene ligand and an alkene regulator enables transfer-dehydroaromatization, avoiding the homo-disproportionation pathway. The desired product is obtained with up to 99:1 selectivity, and the exo-to-endo olefin isomerization can be carried out in one pot. In contrast to previously reported methods that rely on the efficient removal of Pd-H, the approach reported herein benefits from the steric effects of the N-heterocyclic carbene and the choice of alkene to regulate the competing reactivity of allylic C‒H activation and hydropalladation. This method circumvents the challenges associated with tedious olefin separation and a low exo-to-endo olefin isomerization ratio and expands the scope to include challenging endo- and exo-cyclic olefins under mild, neutral, and oxidant-free conditions. Overall, herein, we provide a strategy to synthesize (hetero)aromatic compounds via chemoselective dehydrogenation of cyclic alkenes over ketones and the dehydrogenative Diels-Alder reaction of a cyclic enamine.
Many-body localization enables iterative quantum optimization
Authors: Wang Hanteng , Yeh Hsiu-Chung , Kamenev Alex
Published: September 2022

Many discrete optimization problems are exponentially hard due to the underlying glassy landscape. This means that the optimization cost exhibits multiple local minima separated by an extensive number of switched discrete variables. Quantum computation was coined to overcome this predicament, but so far had only a limited progress. Here we suggest a quantum approximate optimization algorithm which is based on a repetitive cycling around the tricritical point of the many-body localization (MBL) transition. Each cycle includes quantum melting of the glassy state through a first order transition with a subsequent reentrance through the second order MBL transition. Keeping the reentrance path sufficiently close to the tricritical point separating the first and second order transitions, allows one to systematically improve optimization outcomes. The running time of this algorithm scales algebraically with the system size and the required precision. The corresponding exponents are related to critical indexes of the continuous MBL transition.
Global soil profiles indicate depth-dependent soil carbon losses under a warmer climate
Authors: Wang Mingming , Guo Xiaowei , Zhang Shuai , Xiao Liujun , Mishra Umakant , Yang Yuanhe , Zhu Biao , Wang Guocheng , Mao Xiali , Qian Tian , Jiang Tong , Shi Zhou , Luo Zhongkui
Published: September 2022

Soil organic carbon (SOC) changes under future climate warming are difficult to quantify in situ. Here we apply an innovative approach combining space-for-time substitution with meta-analysis to SOC measurements in 113,013 soil profiles across the globe to estimate the effect of future climate warming on steady-state SOC stocks. We find that SOC stock will reduce by 6.0 ± 1.6% (mean±95% confidence interval), 4.8 ± 2.3% and 1.3 ± 4.0% at 0–0.3, 0.3–1 and 1–2 m soil depths, respectively, under 1 °C air warming, with additional 4.2%, 2.2% and 1.4% losses per every additional 1 °C warming, respectively. The largest proportional SOC losses occur in boreal forests. Existing SOC level is the predominant determinant of the spatial variability of SOC changes with higher percentage losses in SOC-rich soils. Our work demonstrates that warming induces more proportional SOC losses in topsoil than in subsoil, particularly from high-latitudinal SOC-rich systems.
Predicting demographics from meibography using deep learning
Authors: Wang Jiayun , Graham Andrew D. , Yu Stella X. , Lin Meng C.
Published: September 2022

This study introduces a deep learning approach to predicting demographic features from meibography images. A total of 689 meibography images with corresponding subject demographic data were used to develop a deep learning model for predicting gland morphology and demographics from images. The model achieved on average 77%, 76%, and 86% accuracies for predicting Meibomian gland morphological features, subject age, and ethnicity, respectively. The model was further analyzed to identify the most highly weighted gland morphological features used by the algorithm to predict demographic characteristics. The two most important gland morphological features for predicting age were the percent area of gland atrophy and the percentage of ghost glands. The two most important morphological features for predicting ethnicity were gland density and the percentage of ghost glands. The approach offers an alternative to traditional associative modeling to identify relationships between Meibomian gland morphological features and subject demographic characteristics. This deep learning methodology can currently predict demographic features from de-identified meibography images with better than 75% accuracy, a number which is highly likely to improve in future models using larger training datasets, which has significant implications for patient privacy in biomedical imaging.
Effects of silica soil amendment against Exserohilum rostratum, the fungal pathogen of rice brown spot disease in Peninsular Malaysia
Authors: Mahmad-Toher Ainu-Shahirah , Govender Nisha , Dorairaj Deivaseeno , Wong Mui-Yun
Published: September 2022

Rice brown spot (BS) exerts devastating agronomic effects on grain quality and overall productivity. In Peninsular Malaysia, BS disease incidence is fairly prevalent and little is known about the diversity of BS pathogens in the local granaries. Fifteen isolates from BS symptomatic rice plants were identified at five different rice granaries across Peninsular Malaysia. Based on the morphological and molecular analyses, two isolates were confirmed asBipolaris oryzaewhile the rest were identified asExserohilum rostratum. Phylogenetic tree analysis revealed that BS incidence in rice granaries in Peninsular Malaysia is caused by a pair of closely related fungal pathogens,E. rostratumandB. oryzae,with the former being more predominant. Cultural characterization ofE. rostratumisolate KT831962 showed the best growth and sporulation activity on corn meal agar plates incubated in complete darkness. The effects of calcium silicate (CaSiO3) and rice husk ash (RHA) soil amendment against MR219 and MR253 rice varieties were evaluated during rice-E. rostratuminteraction. Results showed that soil amelioration using CaSiO3and RHA singly and in combination with manganese (Mn) significantly reduced rice BS disease severity. The BS disease index was reduced significantly to less than 31.6% in the silicon-treated rice plants relative to the control plants at 41.2%. Likewise, the grain yield at the harvest stage showed significantly higher yield in the Si-treated rice plants in comparison to the control, non-Si treated rice plants. The findings highlight the potential of RHA agro-waste as Si fertilizer in a sustainable rice production system.
Glucocorticoid receptor activation reduces food intake independent of hyperglycemia in zebrafish
Authors: Nipu Niepukolie , Antomagesh Femilarani , Faught Erin , Vijayan Mathilakath M.
Published: September 2022

Chronic cortisol exposure suppresses food intake in fish, but the central mechanism(s) involved in appetite regulation are unclear. Stress and the associated increase in cortisol levels increase hepatic gluconeogenesis, leading to hyperglycemia. As hyperglycemia causes a reduction in food intake, we tested the hypothesis that cortisol-induced hyperglycemia suppresses feeding in zebrafish (Danio rerio). We first established that stress-independent hyperglycemia suppressed food intake, and this corresponded with a reduction in the phosphorylation of the nutrient sensor, AMP-activated protein kinase (AMPK) in the brain. Chronic cortisol exposure also led to hyperglycemia and reduced food intake, but the mechanisms were distinct. In cortisol-exposed fish, there were no changes in brain glucose uptake or AMPK phosphorylation. Also, the phosphorylation of Akt and mTOR was reduced along with an increase in redd1, suggesting an enhanced capacity for proteolysis. Loss of the glucocorticoid receptor did not rescue cortisol-mediated feeding suppression but did increase glucose uptake and abolished the changes seen in mTOR phosphorylation and redd1 transcript abundance. Taken together, our results indicate that GR activation enhances brain proteolysis, and the associated amino acids levels, and not hyperglycemia, maybe a key mediator of the feeding suppression in response to chronic cortisol stimulation in zebrafish.