bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential interactions between metal-based phenanthroline drugs and the unfolded protein response endoplasmic reticulum stress pathway
Authors: O’Leary Tadhg , McCarron Pauraic , Devereux Michael , Meaney Steve
Published: September 2022

The unfolded protein response has recently been implicated as a mechanism by which 1,10-phenanthroline-containing coordination compounds trigger cell death. We explored the interaction of two such compounds—one containing copper and one containing manganese—with endoplasmic reticulum (ER) stress. Pretreatment with anisomycin significantly enhanced the cytotoxic activity of both metal-based compounds in A2780, but only the copper-based compound in A549 cells. The effects of pretreatment with tunicamycin were dependent on the nature of the metal center in the compounds. In A2780 cells, the cytotoxic action of the copper compound was reduced by tunicamycin only at high concentration. In contrast, in A549 cells the efficacy of the manganese compound cells was reduced at all tested concentrations. Intriguingly, some impact of free 1,10-phenanthroline was also observed in A549 cells. These results are discussed in the context of the emerging evidence that the ER plays a role in the cytotoxic action of 1,10-phenanthroline-based compounds.
Identifying barriers to compliance with a universal inpatient protocol for Staphylococcus aureus nasal decolonization with povidone-iodine
Authors: Stern Rebecca A. , Harris Bryan D. , DeVault Mary , Talbot Thomas R.
Published: September 2022

Academic hospital nurses were surveyed to assess adherence barriers to a universal povidone-iodine nasal decolonization protocol to prevent Staphylococcus aureus infection. Low training rates, inadequate supplies, documentation and tracking challenges, patient refusal, and burnout contributed to suboptimal adherence. Prioritizing education is essential but alone is insufficient for successful protocol adoption.
EXPANDING THE REALS BY CONTINUOUS FUNCTIONS ADDS NO COMPUTATIONAL POWER
Authors: ANDREWS URI , KNIGHT JULIA F. , KUYPER RUTGER , MILLER JOSEPH S. , SOSKOVA MARIYA I.
Published: September 2022

We study the relative computational power of structures related to the ordered field of reals, specifically using the notion of generic Muchnik reducibility. We show that any expansion of the reals by a continuous function has no more computing power than the reals, answering a question of Igusa, Knight, and Schweber [7]. On the other hand, we show that there is a certain Borel expansion of the reals that is strictly more powerful than the reals and such that any Borel quotient of the reals reduces to it.
The civic district of Sala (Chellah – Rabat, Morocco): shaping and perceiving monuments under the Roman Empire
Authors: Camporeale Stefano , Mugnai Niccolò , Pansini Rossella
Published: September 2022

This article investigates the development of urbanism and architecture at the site of Sala (Chellah), from the end of the first century BC to the latter half of the second century AD. By looking at the transformations in the town's civic centre from the Mauretanian to Roman imperial period, the aim is to assess how the layout and function of public spaces and buildings were reshaped to respond to new ideas of monumentality. A range of research methodologies are applied to address this question, including architectural, archival, and archaeological analyses, as well as the use of 3D digital modelling. The case study of Sala is of particular importance, as it shows how certain pre-Roman monuments were kept in use within new public contexts, and how imperial-style, urban and architectural features were introduced in the town as part of trends that can be recognized across North Africa and the Roman Empire more broadly.
Partisanship in times of crisis: evidence from Italy
Authors: Bankert Alexa , Del Ponte Alessandro , Huddy Leonie
Published: September 2022

There is a continuing debate over the political importance and durability of partisan attachments in European multi-party systems. Drawing on a nationally representative five-wave panel, we provide a longitudinal test of the power of partisanship in Italy over the course of the tumultuous 2013 national elections. We find that a strong partisan affiliation measured as a social identity two years prior to the election promoted system stability by increasing support for the in-party and inhibiting electoral support for the insurgent Five Star Movement (M5S). In contrast, non-partisans, especially highly educated ones, were more likely than partisans to vote for M5S. Our results illustrate the role of partisanship in stabilizing multi-party systems amid crisis.
Added sugar intake and its forms and sources in relation to risk of non-alcoholic fatty liver disease: results from the Tianjin Chronic Low-grade Systemic Inflammation and Health cohort study
Authors: Zhang Shunming , Li Huiping , Meng Ge , Zhang Qing , Liu Li , Wu Hongmei , Gu Yeqing , Zhang Tingjing , Wang Xuena , Zhang Juanjuan , Dong Jun , Zheng Xiaoxi , Cao Zhixia , Zhang Xu , Dong Xinrong , Sun Shaomei , Wang Xing , Zhou Ming , Jia Qiyu , Song Kun ,   the China Cohort Consortium, Borné Yan , Sonestedt Emily , Qi Lu , Niu Kaijun
Published: September 2022

It has been suggested that added sugar intake is associated with non-alcoholic fatty liver disease (NAFLD). However, previous studies only focused on sugar-sweetened beverages; the evidence for associations with total added sugars and their sources is scarce. This study aimed to examine the associations of total added sugars, their physical forms (liquid v. solid) and food sources with risk of NAFLD among adults in Tianjin, China. We used data from 15 538 participants, free of NAFLD, other liver diseases, CVD, cancer or diabetes at baseline (2013–2018 years). Added sugar intake was estimated from a validated 100-item FFQ. NAFLD was diagnosed by ultrasonography after exclusion of other causes of liver diseases. Multivariable Cox proportional hazards models were fitted to calculate hazard ratios (HR) and corresponding 95 % CI for NAFLD risk with added sugar intake. During a median follow-up of 4·2 years, 3476 incident NAFLD cases were documented. After adjusting for age, sex, BMI and its change from baseline to follow-up, lifestyle factors, personal and family medical history and overall diet quality, the multivariable HR of NAFLD risk were 1·18 (95 % CI 1·06, 1·32) for total added sugars, 1·20 (95 % CI 1·08, 1·33) for liquid added sugars and 0·96 (95 % CI 0·86, 1·07) for solid added sugars when comparing the highest quartiles of intake with the lowest quartiles of intake. In this prospective cohort of Chinese adults, higher intakes of total added sugars and liquid added sugars, but not solid added sugars, were associated with a higher risk of NAFLD.
Facial ridge management in canal wall down tympanoplasty for middle-ear cholesteatoma
Authors: Capriotti V , Dal Cin E , Gatto A , Boscolo-Rizzo P , Danesi G , Tirelli G
Published: September 2022

Objective

To estimate whether leaving a high facial ridge during canal wall down tympanoplasty increases the risk of residual cholesteatoma.

Methods

In this retrospective case review, 321 patients treated with primary canal wall down tympanoplasty for middle-ear cholesteatoma were divided into a completely lowered facial ridge group and a non-completely lowered facial ridge group. Factors affecting facial ridge management, residual disease rate and disease-free survival were analysed.

Results

Residual disease rates were 10.8 per cent in the non-completely lowered facial ridge group and 16.6 per cent in the completely lowered facial ridge group (p = 0.15). Localisation at sinus tympani, mesotympanum or supratubal recess, pre-operative extracranial complications, and destroyed ossicular chain or fixed platina were associated with a completely lowered facial ridge. Residual disease rates and disease-free survival did not significantly differ between the groups.

Conclusion

Facial ridge can be managed according to cholesteatoma extension. The facial ridge can be maintained high if the cholesteatoma does not involve sinus tympani, mesotympanum or supratubal recess, without increasing the risk of residual disease.
Identity-based subgroups and information exchange in adversarial policy networks
Authors: Lee Jeongyoon , Huang Kun
Published: September 2022

While information exchange is essential in the policy process, little is known about how divergent subgroups filter actors’ technical and political information exchange, blocking learning processes. Guided by social identity, group entitativity, and self-categorisation theories, we introduce the concept and measurement of identity-based subgroups referring to informal clusters shaped by the self-referent perception of similarities among actors. The identity-based subgroup is recognised as a precursor for coalition building in a policy subsystem but received inadequate attention in the research on Advocacy Coalition Framework. We examine how divergent identity-based subgroups moderate the links between relational embeddedness and technical/political information exchanges in an adversarial fracking policy network in New York. Our quadratic assignment procedure multiple regression indicated that, despite trust, policy actors from different identity-based subgroups are less likely to share technical and political information in the network. When two actors’ identity-based subgroups are different, competition is more likely associated with lower technical information exchange in the network. These findings extend research on information exchange in adversarial policy subsystems.
From POW to Cold War DP: A Global Microhistory of Former Yugoslav Soldiers in Occupied Germany, 1946–48
Authors: Höschler Christian
Published: September 2022

There are still many historical blind spots in research on Europe's displaced persons (DPs) after the Second World War. In particular, there are relatively few studies that link microhistorical perspectives on repatriation and resettlement with global contexts. This essay addresses this gap, in empirical as well as methodological terms, by focusing on a group of DPs that hitherto has received little attention from scholars: former members of the Royal Yugoslav Army, whom the Nazis had taken to Germany as prisoners of war (POWs). Classified as DPs after 1945, they lived in camps administered by the United Nations Relief and Rehabilitation Administration (UNRRA) and the International Refugee Organization (IRO). Under the circumstances, they continued to maintain military-like routines and fiercely refused repatriation. This was partly an expression of loyalty to the exiled Yugoslav king, Peter II. But it also mirrored the fears of DPs about—and resistance to the idea of—being returned to their homeland in the context of the early Cold War. Using the example of a DP camp in Bad Aibling (Upper Bavaria), this article connects Yugoslav DPs, Allied DP politics, and the interests of Tito's government, as well as the interventions of international relief agencies. It shows how some DPs adroitly subverted the international logic of DP self-governance as promoted by UNRRA. A global microhistory approach thus reveals how local actors and sites are shaped by, but also foundationally constitutive of, global regimes of migrational self-governance.
Taiwan and the “One-China Principle” in the Age of COVID-19: Assessing the Determinants and Limits of Chinese Influence
Authors: Kastner Scott L. , Wang Guan , Pearson Margaret M. , Phillips-Alvarez Laura , Yinusa Joseph
Published: September 2022

During the current global COVID-19 crisis Taiwan has portrayed itself as both an example for other countries to follow and as a country willing to assist others in their own efforts with the virus. Taiwan has also renewed efforts to participate in the World Health Organization (WHO), an organisation from which it is currently excluded. Although some countries have supported Taiwan's efforts to participate in the WHO or have praised its COVID-19 response, others have been silent or even critical, sometimes citing commitments to a “one China policy.” In this paper, we use newly collected data to explore cross-national variation in support for Taiwan during the current pandemic. We find that a country's level of economic development and security ties with the US are strongly correlated with support for Taiwan while a country's economic ties to China is a less consistent predictor.
The Diplomatic Campaign Against the Short-Lived 1968 Berlin Olympic Bid
Authors: Dichter Heather L.
Published: September 2022

In 1963 the West Berlin mayor proposed a joint bid from West and East Berlin to host the 1968 Olympic Games. West Germany's closest allies sought to persuade the West German and Berlin governments to stop the bid, which both supported but had largely kept secret from their allies. This episode demonstrates not only the significance which foreign ministries have long attributed to international sport, but also their clear involvement to actively end another country's Olympic aspirations because of the diplomatic ramifications, particularly the potential to challenge the four-power control of Berlin, and their own self-serving interests in hosting the same event.
A Kantian Account of Trauma
Authors: Varden Helga
Published: September 2022

In our societies today, the prevalence of serious, untreated trauma means that we cannot reliably expect to receive or give unconditional love, understood as love which functions within a normative framework to protect each and all of us as having dignity. Serious, untreated trauma makes unconditional love (so understood) unreliable because each time the pattern of the psychological damage (trauma) is triggered in the traumatized person, in the wrongdoers or in the bystanders, their behaviour easily becomes self- and other-numbing, destructive and moralizing in an irrational and often self-deceived attempt to preserve or defend themselves or others against forces felt as threatening even though they are not. It is also common for someone who lives in societal conditions where it is impossible to avoid patterned, traumatizing behaviour to experience the emotional temptation to give up on the possibility of a better future for oneself, one’s loved ones or one’s community within the larger community or the state. For some, this is experienced as a draw towards suicide, while others experience it as a serious temptation to give up on working together with the good forces in society. This article seeks to continue Charles Mills’ work on radicalizing Kant by sketching a Kantian account of trauma and thereby develop philosophical resources that can help us fight historical oppression and violence.
VOLATILITY SWAPS VALUATION UNDER A MODIFIED RISK-NEUTRALIZED HESTON MODEL WITH A STOCHASTIC LONG-RUN VARIANCE LEVEL
Authors: HE XIN-JIANG , LIN SHA
Published: September 2022

We consider the pricing of discretely sampled volatility swaps under a modified Heston model, whose risk-neutralized volatility process contains a stochastic long-run variance level. We derive an analytical forward characteristic function under this model, which has never been presented in the literature before. Based on this, we further obtain an analytical pricing formula for volatility swaps which can guarantee the computational accuracy and efficiency. We also demonstrate the significant impact of the introduced stochastic long-run variance level on volatility swap prices with synthetic as well as calibrated parameters.
SIMPLY CONNECTED MANIFOLDS WITH LARGE HOMOTOPY STABLE CLASSES
Authors: CONWAY ANTHONY , CROWLEY DIARMUID , POWELL MARK , SIXT JOERG
Published: September 2022

For every$k \geq 2$and$n \geq 2$, we constructnpairwise homotopically inequivalent simply connected, closed$4k$-dimensional manifolds, all of which are stably diffeomorphic to one another. Each of these manifolds has hyperbolic intersection form and is stably parallelisable. In dimension four, we exhibit an analogous phenomenon for spin$^{c}$structures on$S^2 \times S^2$. For$m\geq 1$, we also provide similar$(4m-1)$-connected$8m$-dimensional examples, where the number of homotopy types in a stable diffeomorphism class is related to the order of the image of the stableJ-homomorphism$\pi _{4m-1}(SO) \to \pi ^s_{4m-1}$.
Compact, broadband, and thin corrugated U-shaped patch-constituted MIMO antennas for airborne UAV applications
Authors: Jain Kapil , Kushwah Vivek Singh
Published: September 2022

The major component for the effective functioning of airborne unmanned aerial vehicles (UAVs) is an antenna. The unified integration of an antenna with UAVs without disturbing the other components of UAVs, compact size, thin, and wideband antennas are preferred. Based on these prerequisites, a low-profile and a wideband antenna is presented for autonomous UAVs for C-band applications. The antenna is designed on an extremely thin substrate of size 0.01λ0 without compromising the antenna's broad bandwidth. The antenna structure comprises a corrugated U-shaped patch, a few parasitic patches along with the partial ground. Initially, only a single mode was excited using a U-shaped patch, then further on introducing a few more parasitic patches along with corrugations in a U-shaped patch other modes were also coupled leading to enhancement in the bandwidth of the antenna. The proposed antenna along with a 2 × 2 quad-port multiple input, multiple output (MIMO) antenna is designed and fabricated. The measured results are found to be in good agreement with the simulated results. A broad bandwidth of 74.5% (4.1–9.0 GHz) with 5.02 dBi peak gain at 6.6 GHz is exhibited by the fabricated MIMO antenna. Thus, the designed antenna proves to be an effective candidate for UAV-based C-band applications.
Effect of degree of water stress on growth and fecundity of velvetleaf (Abutilon theophrasti) using soil moisture sensors
Authors: Mausbach Jasmine , Irmak Suat , Chahal Parminder , Sarangi Debalin , Jhala Amit J.
Published: September 2022

Velvetleaf (Abutilon theophrasti Medik.) is a troublesome broadleaf weed that competes with crops for resources such as soil moisture. Water stress can affect the ability of weed species to grow and produce seeds. The objective of this study was to determine the effect of degree of water stress on the growth and fecundity of A. threophrasti using soil moisture sensors under greenhouse conditions. Abutilon threophrasti seeds collected from a corn (Zea mays L.)–soybean [Glycine max (L.) Merr.] field were grown in silty clay loam soil, and plants were maintained at 100%, 75%, 50%, and 25% soil field capacity (FC) corresponding to no, light, moderate, and high water-stress conditions, respectively. Water was added daily to pots based on soil moisture levels detected by a Meter Group 5TM sensor to maintain the desired water-stress level required by treatment. Plants maintained at 100% FC had the maximum number of leaves (28 leaves plant−1), followed by 21 and 15 leaves plant−1 at 75% and 50% FC, respectively. Abutilon threophrasti at 100% and 75% FC achieved maximum plant height (108 to 123 cm) compared with 83 cm at 50% FC. Abutilon threophrasti maintained at 75% FC had the greatest growth index (79,907 cm3) followed by 72,197 cm3 at 100% FC and 64,256 cm3 at 50% FC. Seed production was similar at 100%, 75%, and 50% FC (288 to 453 seeds plant−1) compared with 2 seeds plant−1 at 25% FC. This is because the majority of plants maintained at 25% FC did not survive more than 77 d after transplanting. Seed germination was 96% to 100% at 100%, 75%, and 50% FC compared with 20% germination at 25% FC. Abutilon threophrasti can survive ≥50% FC continuous water-stress conditions, although with reduced leaf number, plant height, and growth index compared with 75% and 100% FC.
Insights on Multistage Rock Avalanche Behavior From Runout Modeling Constrained by Seismic Inversions
Authors: Mitchell A. , Allstadt K. E. , George D. , Aaron J. , McDougall S. , Moore J. , Menounos B.
Published: September 2022

Inversion of low‐frequency regional seismic records to solve for a time series of bulk forces exerted on the earth by a landslide (a force‐time function) is increasingly being used to infer volumes and dynamics of large, highly energetic landslides, such as rock avalanches and flowslides, and to provide calibration information on event dynamics and volumes for numerical landslide runout models. Much of the work to date using landslide runout modeling constrained by seismic data has focused on using single‐phase models with frictional or velocity‐weakening rheologies. Awareness of multistage landslide initiations is increasing, with discrete failures separated in time contributing to the final impact of an event. Our work utilizes a method for incorporating seismic data as a calibration constraint for landslide runout models, considering variable rheologies and different initiation conditions. This study presents a systematic examination of multiple rheologies and initiation conditions, and shows how these factors affect the force‐time function derived from the landslide runout model. Our work confirms that, while rheology and fragmenting or initially coherent initiations affect the force‐time function, multiple collapses separated by tens of seconds have the greatest impact on the shape and amplitude. We apply this method to the analysis of three real rock avalanches to better constrain plausible initiation conditions and rheology parameters using both seismic and field data. This study provides insights on how assumptions about the initiation dynamics of the source zone and the runout model definition can aid in the interpretation of seismic inversions for multistage rock avalanches.
Tectonic Subsidence Modeling of Diachronous Transition From Backarc to Retroarc Basin Development and Uplift During Cordilleran Orogenesis, Patagonian‐Fuegian Andes
Authors: VanderLeest Rebecca A. , Fosdick Julie C. , Malkowski Matthew A. , Romans Brian W. , Ghiglione Matías C. , Schwartz Theresa M. , Sickmann Zachary T.
Published: September 2022

Backstripped tectonic basin subsidence histories are critical for interpreting phases of lithospheric deformation and paleoenvironmental change from the stratigraphic record. This study presents new subsidence modeling of the Rocas Verdes Backarc Basin (RVB) and Magallanes‐Austral retroarc foreland basin (MAB) of southernmost South America to evaluate along‐strike changes in tectonic subsidence related to the Late Jurassic through Miocene history of the Southern Andes. We compiled composite stratigraphic sections for seven basin localities that span 47°–54°S from published sedimentological records of paleoenvironment, paleobathymetry, and geochronology. Modeling results resolve regional trends in basin tectonic subsidence, uplift, and sedimentation rate that influenced the depositional environment during five broad phases of RVB‐MAB development: (a) Late Jurassic tectonic subsidence and basin deepening associated with rift‐related backarc extension that postdated regional diachronous rift‐related magmatism. (b) Southward younging of Early to Late Cretaceous pronounced acceleration in tectonic subsidence interpreted as the initiation of flexural loading and development of the MAB foreland basin system. (c) Late Cretaceous (ca. 85–70 Ma) tectonic uplift within the central foredeep ∼49° to 52°S, coeval with a shift from slope to shelf deposition at these latitudes. (d) A protracted period of low‐magnitude basin uplift and relative tectonic quiescence during the Paleogene, with the exception of southernmost localities; and (e) Synchronous latest Oligocene‐early Miocene tectonic subsidence linked to basin deepening and transgression across the northern and central basin sectors. Backstripped tectonic subsidence analysis corroborates existing interpretations for orogenic development in the RVB‐MAB and sheds new light on complex polyphase basin histories where extension precedes convergence.
Coupled Atmosphere–Ocean Variations on Timescales of Days Observed in the Western Tropical Pacific Warm Pool During Mid‐March 2020
Authors: Nagano Akira , Geng Biao , Richards Kelvin J. , Cronin Meghan F. , Taniguchi Kyoko , Katsumata Masaki , Ueki Iwao
Published: September 2022

From 11 to 12 March 2020, we observed atmosphere and ocean variations during a temporal warming of the western tropical Pacific warm pool and the associated active convection on the equator by the R/V Mirai and unmanned surface vehicles, known as Wave Gliders. The warming, which extended the warm pool eastward at a speed of approximately 2.9 m s−1, was found to be caused mainly by high sensitivity of the temperature of the thin mixed layer to shortwave and longwave radiation flux. During the warming, westward‐propagating inertia‐gravity wave disturbances in addition to intensified northerly wind intermittently enhanced turbulent latent heat release into the atmosphere (>150 W m−2), leading to heavy rainfall from midnight to morning, so‐called diurnal dancing, in the eastern region of the warm pool. The strong air–sea coupling was related to the zonal wind variation trapped near the sea level, which caused their convergences, also intensified atmospheric convection. Subsequently (13–14 March), due to the atmospheric density stratification and wind speed changes, atmospheric disturbances radiated upward and ceased to be coupled with the ocean.
Sediment Accumulation and Carbon Burial in Four Hadal Trench Systems
Authors: Oguri Kazumasa , Masqué Pere , Zabel Matthias , Stewart Heather A. , MacKinnon Gillian , Rowden Ashley A. , Berg Peter , Wenzhöfer Frank , Glud Ronnie N.
Published: September 2022

Hadal trenches are considered to act as depocenters for organic material, although pathways for the material transport and deposition rates are poorly constrained. Here we assess focusing, deposition and accumulation of material and organic carbon in four hadal trench systems underlying different surface ocean productivities; the eutrophic Atacama and Kuril‐Kamchatka trenches, the mesotrophic Kermadec trench and the oligotrophic Mariana Trench. The study is based on the distributions of naturally occurring 210Pbex, 137Cs and total organic carbon from recovered sediment cores and by applying previously quantified benthic mineralization rates. Periods of steady deposition and discreet mass‐wasting deposits were identified from the profiles and the latter were associated with historic recorded seismic events in the respective regions. During periods without mass wasting, the estimated focusing factors along trench axes were elevated, suggesting more or less continuous downslope focusing of material toward the interior of the trenches. The estimated organic carbon deposition rates during these periods exhibited extensive site‐specific variability, but were generally similar to values encountered at much shallower settings such as continental slopes and margins. Organic carbon deposition rates during periods of steady deposition were not mirrored by surface ocean productivity, but appeared confounded by local bathymetry. The inclusion of deposition mediated by mass‐wasting events enhanced the sediment and organic carbon accumulations for the past ∼150 years by up to a factor of ∼4. Thus, due to intensified downslope material focusing and infrequent mass‐wasting events, hadal trenches are important sites for deposition and sequestration of organic carbon in the deep sea.
Epigenetic aging and perceived psychological stress in old age
Authors: Vetter Valentin Max , Drewelies Johanna , Sommerer Yasmine , Kalies Christian Humberto , Regitz-Zagrosek Vera , Bertram Lars , Gerstorf Denis , Demuth Ilja
Published: September 2022

Adverse effects of psychological stress on physical and mental health, especially in older age, are well documented. How perceived stress relates to the epigenetic clock measure, DNA methylation age acceleration (DNAmAA), is less well understood and existing studies reported inconsistent results. DNAmAA was estimated from five epigenetic clocks (7-CpG, Horvath’s, Hannum’s, PhenoAge and GrimAge DNAmAA). Cohen’s Perceived Stress Scale (PSS) was used as marker of psychological stress. We analyzed data from 1,100 Berlin Aging Study II (BASE-II) participants assessed as part of the GendAge study (mean age = 75.6 years, SD = 3.8 years, 52.1% women). In a first step, we replicated well-established associations of perceived stress with morbidity, frailty, and symptoms of depression in the BASE-II cohort studied here. In a second step, we did not find any statistically significant association of perceived stress with any of the five epigenetic clocks in multiple linear regression analyses that adjusted for covariates. Although the body of literature suggests an association between higher DNAmAA and stress or trauma during early childhood, the current study found no evidence for an association of perception of stress with DNAmAA in older people. We discuss possible reasons for the lack of associations and highlight directions for future research.
Ferroptotic MSCs protect mice against sepsis via promoting macrophage efferocytosis
Authors: Pan Yuchen , Li Jingman , Wang Jiali , Jiang Qi , Yang Jingjing , Dou Huan , Liang Huaping , Li Kuanyu , Hou Yayi
Published: September 2022

The therapeutic effect of mesenchymal stem cells (MSCs) on sepsis has been well-known. However, a comprehensive understanding of the relationship between MSCs and macrophages remains elusive. Superparamagnetic iron oxide (SPIO) is one of the most commonly used tracers for MSCs. Our previous study has shown that SPIO enhanced the therapeutic effect of MSCs in a macrophage-dependent manner. However, the fate of SPIO-labeled MSCs (MSCSPIO) after infusion remains unknown and the direct interaction between MSCSPIO and macrophages remains unclear. Mice were injected intravenously with MSCSPIO at 2 h after Escherichia coli infection and sacrificed at different times to investigate their distribution and therapeutic effect. We found that MSCSPIO homed to lungs rapidly after infusion and then trapped in livers for more than 10 days. Only a few MSCSPIO homed to the spleen and there was no MSCSPIO detectable in the brain, heart, kidney, colon, and uterus. MSCSPIO tended to stay longer in injured organs compared with healthy organs and played a long-term protective role in sepsis. The mRNA expression profiles between MSCs and MSCSPIO were rather different, genes related to lipid metabolism, inflammation, and oxidative stress were changed. The levels of ROS and lipid peroxide were elevated in MSCSPIO, which confirmed that SPIO-induced ferroptosis in MSCSPIO. Ferroptosis of MSCSPIO induced by SPIO enhanced the efferocytosis of macrophages and thus enhanced the protective effect on septic mice, while the benefits were impaired after MSCSPIO were treated with Ferrostatin-1 (Fer-1) or Liproxtatin-1 (Lip-1), the inhibitors of ferroptosis. SPIO-induced ferroptosis in MSCs contributes to better therapeutic effects in sepsis by enhancing the efferocytosis of macrophages. Our data showed the efficacy and advantage of MSCSPIO as a therapeutic tool and the cell states exert different curative effects on sepsis.
A dual Keap1 and p47phox inhibitor Ginsenoside Rb1 ameliorates high glucose/ox-LDL-induced endothelial cell injury and atherosclerosis
Authors: Wang Zi-Chao , Niu Kai-Ming , Wu Yu-Jie , Du Kai-Rui , Qi Lian-Wen , Zhou Ye-Bo , Sun Hai-Jian
Published: September 2022

Oxidative stress is a vital contributor to the development and progression of diabetes-accelerated atherosclerosis. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a well-known molecule that participates in cellular defense against oxidative stress. Utilizing luciferase reporter assay from 379 natural products, we reported here that Ginsenoside Rb1 played a dual role in inhibiting Kelch-like ECH-associated protein 1 (Keap1) and p47phox luciferase reporter activities. In endothelial cells (ECs), Rb1 pretreatment enhanced cell viability, reduced oxidative stress, inflammation, endothelial-mesenchymal transition (EndMT), and apoptosis, as well as ameliorated mitochondrial quality following oxidized low-density lipoprotein (ox-LDL) plus high glucose (HG) challenge. Rb1 directly bound to Keap1 and promoted its ubiquitination and proteasomal degradation dependent on lysine residues (K108, K323, and K551) by recruiting the E3 ligase synovial apoptosis inhibitor 1 (SYVN1), leading to Nrf2 dissociation from Keap1, Nrf2 nuclear translocation, Nrf2/PGC-1α complex formation. We further identified that Rb1 could bind to p47phox and reduce its phosphorylation and membrane translocation, thereby disrupting the assembly of the NOX2 complex. Importantly, Rb1-mediated preservation of cytoplasmic p47phox stabilized and contributed to Nrf2 activation. Additionally, we revealed that Rb1 reduced aortic atherosclerotic plaque formation along with reductions in oxidative stress and inflammatory response in streptozotocin (STZ)-induced ApoE−/− mice, but not in ApoE−/− mice with deficiency of Nrf2 and PGC-1α. Collectively, we demonstrated that Rb1, which directly targeted Keap1 and p47phox in ECs, may be an attractive candidate for the treatment of atherosclerosis in diabetes.
Tracking 21st century anthropogenic and natural carbon fluxes through model-data integration
Authors: Bultan Selma , Nabel Julia E. M. S. , Hartung Kerstin , Ganzenmüller Raphael , Xu Liang , Saatchi Sassan , Pongratz Julia
Published: September 2022

Monitoring the implementation of emission commitments under the Paris agreement relies on accurate estimates of terrestrial carbon fluxes. Here, we assimilate a 21st century observation-based time series of woody vegetation carbon densities into a bookkeeping model (BKM). This approach allows us to disentangle the observation-based carbon fluxes by terrestrial woody vegetation into anthropogenic and environmental contributions. Estimated emissions (from land-use and land cover changes) between 2000 and 2019 amount to 1.4 PgC yr−1, reducing the difference to other carbon cycle model estimates by up to 88% compared to previous estimates with the BKM (without the data assimilation). Our estimates suggest that the global woody vegetation carbon sink due to environmental processes (1.5 PgC yr−1) is weaker and more susceptible to interannual variations and extreme events than estimated by state-of-the-art process-based carbon cycle models. These findings highlight the need to advance model-data integration to improve estimates of the terrestrial carbon cycle under the Global Stocktake.
Classical center-surround receptive fields facilitate novel object detection in retinal bipolar cells
Authors: Gaynes John A. , Budoff Samuel A. , Grybko Michael J. , Hunt Joshua B. , Poleg-Polsky Alon
Published: September 2022

Antagonistic interactions between center and surround receptive field (RF) components lie at the heart of the computations performed in the visual system. Circularly symmetric center-surround RFs are thought to enhance responses to spatial contrasts (i.e., edges), but how visual edges affect motion processing is unclear. Here, we addressed this question in retinal bipolar cells, the first visual neuron with classic center-surround interactions. We found that bipolar glutamate release emphasizes objects that emerge in the RF; their responses to continuous motion are smaller, slower, and cannot be predicted by signals elicited by stationary stimuli. In our hands, the alteration in signal dynamics induced by novel objects was more pronounced than edge enhancement and could be explained by priming of RF surround during continuous motion. These findings echo the salience of human visual perception and demonstrate an unappreciated capacity of the center-surround architecture to facilitate novel object detection and dynamic signal representation.
Center-surround interactions underlie bipolar cell motion sensitivity in the mouse retina
Authors: Strauss Sarah , Korympidou Maria M. , Ran Yanli , Franke Katrin , Schubert Timm , Baden Tom , Berens Philipp , Euler Thomas , Vlasits Anna L.
Published: September 2022

Motion sensing is a critical aspect of vision. We studied the representation of motion in mouse retinal bipolar cells and found that some bipolar cells are radially direction selective, preferring the origin of small object motion trajectories. Using a glutamate sensor, we directly observed bipolar cells synaptic output and found that there are radial direction selective and non-selective bipolar cell types, the majority being selective, and that radial direction selectivity relies on properties of the center-surround receptive field. We used these bipolar cell receptive fields along with connectomics to design biophysical models of downstream cells. The models and additional experiments demonstrated that bipolar cells pass radial direction selective excitation to starburst amacrine cells, which contributes to their directional tuning. As bipolar cells provide excitation to most amacrine and ganglion cells, their radial direction selectivity may contribute to motion processing throughout the visual system.
Circulating multimeric immune complexes contribute to immunopathology in COVID-19
Authors: Ankerhold Jakob , Giese Sebastian , Kolb Philipp , Maul-Pavicic Andrea , Voll Reinhard E. , Göppert Nathalie , Ciminski Kevin , Kreutz Clemens , Lother Achim , Salzer Ulrich , Bildl Wolfgang , Welsink Tim , Morgenthaler Nils G. , Grawitz Andrea Busse , Emmerich Florian , Steinmann Daniel , Huzly Daniela , Schwemmle Martin , Hengel Hartmut , Falcone Valeria
Published: September 2022

A dysregulated immune response with high levels of SARS-CoV-2 specific IgG antibodies characterizes patients with severe or critical COVID-19. Although a robust IgG response is considered to be protective, excessive triggering of activating Fc-gamma-receptors (FcγRs) could be detrimental and cause immunopathology. Here, we document excessive FcγRIIIA/CD16A activation in patients developing severe or critical COVID-19 but not in those with mild disease. We identify two independent ligands mediating extreme FcγRIIIA/CD16A activation. Soluble circulating IgG immune complexes (sICs) are detected in about 80% of patients with severe and critical COVID-19 at levels comparable to active systemic lupus erythematosus (SLE) disease. FcγRIIIA/CD16A activation is further enhanced by afucosylation of SARS-CoV-2 specific IgG. Utilizing cell-based reporter systems we provide evidence that sICs can be formed prior to a specific humoral response against SARS-CoV-2. Our data suggest a cycle of immunopathology driven by an early formation of sICs in predisposed patients. These findings suggest a reason for the seemingly paradoxical findings of high antiviral IgG responses and systemic immune dysregulation in severe COVID-19. The involvement of circulating sICs in the promotion of immunopathology in predisposed patients opens new possibilities for intervention strategies to mitigate critical COVID-19 progression.
McaA and McaB control the dynamic positioning of a bacterial magnetic organelle
Authors: Wan Juan , Monteil Caroline L. , Taoka Azuma , Ernie Gabriel , Park Kieop , Amor Matthieu , Taylor-Cornejo Elias , Lefevre Christopher T. , Komeili Arash
Published: September 2022

Magnetotactic bacteria are a diverse group of microorganisms that use intracellular chains of ferrimagnetic nanocrystals, produced within magnetosome organelles, to align and navigate along the geomagnetic field. Several conserved genes for magnetosome formation have been described, but the mechanisms leading to distinct species-specific magnetosome chain configurations remain unclear. Here, we show that the fragmented nature of magnetosome chains in Magnetospirillum magneticum AMB-1 is controlled by genes mcaA and mcaB. McaA recognizes the positive curvature of the inner cell membrane, while McaB localizes to magnetosomes. Along with the MamK actin-like cytoskeleton, McaA and McaB create space for addition of new magnetosomes in between pre-existing magnetosomes. Phylogenetic analyses suggest that McaA and McaB homologs are widespread among magnetotactic bacteria and may represent an ancient strategy for magnetosome positioning.
Modeling tissue-specific breakpoint proximity of structural variations from whole-genomes to identify cancer drivers
Authors: Martinez-Fundichely Alexander , Dixon Austin , Khurana Ekta
Published: September 2022

Structural variations (SVs) in cancer cells often impact large genomic regions with functional consequences. However, identification of SVs under positive selection is a challenging task because little is known about the genomic features related to the background breakpoint distribution in different cancers. We report a method that uses a generalized additive model to investigate the breakpoint proximity curves from 2,382 whole-genomes of 32 cancer types. We find that a multivariate model, which includes linear and nonlinear partial contributions of various tissue-specific features and their interaction terms, can explain up to 57% of the observed deviance of breakpoint proximity. In particular, three-dimensional genomic features such as topologically associating domains (TADs), TAD-boundaries and their interaction with other features show significant contributions. The model is validated by identification of known cancer genes and revealed putative drivers in cancers different than those with previous evidence of positive selection.
Redβ177 annealase structure reveals details of oligomerization and λ Red-mediated homologous DNA recombination
Authors: Newing Timothy P. , Brewster Jodi L. , Fitschen Lucy J. , Bouwer James C. , Johnston Nikolas P. , Yu Haibo , Tolun Gökhan
Published: September 2022

The Redβ protein of the bacteriophage λ red recombination system is a model annealase which catalyzes single-strand annealing homologous DNA recombination. Here we present the structure of a helical oligomeric annealing intermediate of Redβ, consisting of N-terminal residues 1-177 bound to two complementary 27mer oligonucleotides, determined via cryogenic electron microscopy (cryo-EM) to a final resolution of 3.3 Å. The structure reveals a continuous binding groove which positions and stabilizes complementary DNA strands in a planar orientation to facilitate base pairing via a network of hydrogen bonding. Definition of the inter-subunit interface provides a structural basis for the propensity of Redβ to oligomerize into functionally significant long helical filaments, a trait shared by most annealases. Our cryo-EM structure and molecular dynamics simulations suggest that residues 133-138 form a flexible loop which modulates access to the binding groove. More than half a century after its discovery, this combination of structural and computational observations has allowed us to propose molecular mechanisms for the actions of the model annealase Redβ, a defining member of the Redβ/RecT protein family.
Airway basal cells show a dedifferentiated KRT17highPhenotype and promote fibrosis in idiopathic pulmonary fibrosis
Authors: Jaeger Benedikt , Schupp Jonas Christian , Plappert Linda , Terwolbeck Oliver , Artysh Nataliia , Kayser Gian , Engelhard Peggy , Adams Taylor Sterling , Zweigerdt Robert , Kempf Henning , Lienenklaus Stefan , Garrels Wiebke , Nazarenko Irina , Jonigk Danny , Wygrecka Malgorzata , Klatt Denise , Schambach Axel , Kaminski Naftali , Prasse Antje
Published: September 2022

Idiopathic pulmonary fibrosis (IPF) is a fatal disease with limited treatment options. In this study, we focus on the properties of airway basal cells (ABC) obtained from patients with IPF (IPF-ABC). Single cell RNA sequencing (scRNAseq) of bronchial brushes revealed extensive reprogramming of IPF-ABC towards a KRT17high PTENlow dedifferentiated cell type. In the 3D organoid model, compared to ABC obtained from healthy volunteers, IPF-ABC give rise to more bronchospheres, de novo bronchial structures resembling lung developmental processes, induce fibroblast proliferation and extracellular matrix deposition in co-culture. Intratracheal application of IPF-ABC into minimally injured lungs of Rag2−/− or NRG mice causes severe fibrosis, remodeling of the alveolar compartment, and formation of honeycomb cyst-like structures. Connectivity MAP analysis of scRNAseq of bronchial brushings suggested that gene expression changes in IPF-ABC can be reversed by SRC inhibition. After demonstrating enhanced SRC expression and activity in these cells, and in IPF lungs, we tested the effects of saracatinib, a potent SRC inhibitor previously studied in humans. We demonstrate that saracatinib modified in-vitro and in-vivo the profibrotic changes observed in our 3D culture system and novel mouse xenograft model.
Battery-free wireless imaging of underwater environments
Authors: Afzal Sayed Saad , Akbar Waleed , Rodriguez Osvy , Doumet Mario , Ha Unsoo , Ghaffarivardavagh Reza , Adib Fadel
Published: September 2022

Imaging underwater environments is of great importance to marine sciences, sustainability, climatology, defense, robotics, geology, space exploration, and food security. Despite advances in underwater imaging, most of the ocean and marine organisms remain unobserved and undiscovered. Existing methods for underwater imaging are unsuitable for scalable, long-term, in situ observations because they require tethering for power and communication. Here we describe underwater backscatter imaging, a method for scalable, real-time wireless imaging of underwater environments using fully-submerged battery-free cameras. The cameras power up from harvested acoustic energy, capture color images using ultra-low-power active illumination and a monochrome image sensor, and communicate wirelessly at net-zero-power via acoustic backscatter. We demonstrate wireless battery-free imaging of animals, plants, pollutants, and localization tags in enclosed and open-water environments. The method’s self-sustaining nature makes it desirable for massive, continuous, and long-term ocean deployments with many applications including marine life discovery, submarine surveillance, and underwater climate change monitoring.
Structural insights into molecular mechanism for N6-adenosine methylation by MT-A70 family methyltransferase METTL4
Authors: Luo Qiang , Mo Jiezhen , Chen Hao , Hu Zetao , Wang Baihui , Wu Jiabing , Liang Ziyu , Xie Wenhao , Du Kangxi , Peng Maolin , Li Yingping , Li Tianyang , Zhang Yangyi , Shi Xiaoyan , Shen Wen-Hui , Shi Yang , Dong Aiwu , Wang Hailin , Ma Jinbiao
Published: September 2022

METTL4 belongs to a subclade of MT-A70 family members of methyltransferase (MTase) proteins shown to mediate N6-adenosine methylation for both RNA and DNA in diverse eukaryotes. Here, we report that Arabidopsis METTL4 functions as U2 snRNA MTase for N6−2’-O-dimethyladenosine (m6Am) in vivo that regulates flowering time, and specifically catalyzes N6-methylation of 2’-O-methyladenosine (Am) within a single-stranded RNA in vitro. The apo structures of full-length Arabidopsis METTL4 bound to S-adenosyl-L-methionine (SAM) and the complex structure with an Am-containing RNA substrate, combined with mutagenesis and in vitro enzymatic assays, uncover a preformed L-shaped, positively-charged cavity surrounded by four loops for substrate binding and a catalytic center composed of conserved residues for specific Am nucleotide recognition and N6-methylation activity. Structural comparison of METTL4 with the mRNA m6A enzyme METTL3/METTL14 heterodimer and modeling analysis suggest a catalytic mechanism for N6-adenosine methylation by METTL4, which may be shared among MT-A70 family members.