bluuebunny/crossref_metadata_2025 huggingface dataset:
The validation of contemporary body composition methods in various races and ethnicities
Authors: Blue Malia N. M. , Hirsch Katie R. , Brewer Gabrielle J. , Cabre Hannah E. , Gould Lacey M. , Tinsley Grant M. , Ng Bennett K. , Ryan Eric D. , Padua Darin , Smith-Ryan Abbie E.
Published: February 2022

Few investigations have evaluated the validity of current body composition technology among racially and ethnically diverse populations. This study assessed the validity of common body composition methods in a multi-ethnic sample stratified by race and ethnicity. One hundred and ten individuals (55 % female, age: 26·5 (sd 6·9) years) identifying as Asian, African American/Black, Caucasian/White, Hispanic, Multi-racial and Native American were enrolled. Seven body composition models (dual-energy X-ray absorptiometry (DXA), air displacement plethysmography (ADP), two bioelectrical impedance devices (BIS, IB) and three multi-compartment models) were evaluated against a four-compartment criterion model by assessing total error (TE) and standard error of the estimate. For the total sample, measures of % fat and fat-free mass (FFM) from multi-compartment models were all excellent to ideal (% fat: TE = 0·94–2·37 %; FFM: TE = 0·72–1·78 kg) compared with the criterion. % fat measures were very good to excellent for DXA, ADP and IB (TE = 2·52–2·89 %) and fairly good for BIS (TE = 4·12 %). For FFM, single device estimates were good (BIS; TE = 3·12 kg) to ideal (DXA, ADP, IB; TE = 1·21–2·15 kg). Results did not vary meaningfully between each race and ethnicity, except BIS was not valid for African American/Black, Caucasian/White and Multi-racial participants for % fat (TE = 4·3–4·9 %). The multi-compartment models evaluated can be utilised in a multi-ethnic sample and in each individual race and ethnicity to obtain highly valid results for % fat and FFM. Estimates from DXA, ADP and IB were also valid. The BIS may demonstrate greater TE for all racial and ethnic cohorts and results should be interpreted cautiously.
Antiquity to Modernity: Mei Lanfang’s Preparatory and Presentational Strategies for his American and Soviet Visits
Authors: Feng Wei , Pi Ye
Published: February 2022

The Chinese actor Mei Lanfang and his retinue prepared several documents for his visits to the USA in 1930 and the USSR in 1935. Using these primary sources, this article explores the reasons why Mei presented traditional Chinese theatre differently in each context. One reason was winning popularity among specifically targeted audiences, as indicated by the carefully selected programmes, explanatory discourses, and illustrations from promotional materials. Through a comparative examination, this article argues that, for the American tour, Mei made traditional Chinese theatre an emblem of ancient Chinese art, while, for the Soviet tour, he endorsed the Soviet Union’s social and artistic enterprises, labelling traditional Chinese theatre a modern art. Both images, one static and the other dynamic, were authentic representations of the multifaceted contemporary Chinese theatre as it underwent modernization. Wei Feng received his PhD in Theatre Studies from Trinity College Dublin and teaches in the School of Foreign Languages and Literature at Shandong University. He is the author of Intercultural Aesthetics in Traditional Chinese Theatre: From 1978 to the Present (Palgrave Macmillan, 2020). Ye Pi (corresponding author) teaches in the School of Foreign Languages and Literature at Shandong University, specializing in Russian literature.
The recognition of a right to be rescued at sea in international law
Authors: Papachristodoulou Aphrodite
Published: February 2022

Current efforts to address the challenges faced by migrants at sea are not effective, as the attention is deflected to security measures for deterring people to leave their countries in the first place, rather than efforts to provide for an adequate search and rescue system which will preserve their rights and lives. This article puts an individual right to be rescued at sea on the legal map mindful of evolving migration challenges and the need to be responsive to human rights crises. By contextualizing philosophical theories that have shaped our understanding of the idea of human rights, it turns to examine the pathways in which rights on the horizon emerge and achieve full recognition. This article contends that irregular migration by sea necessitates normative change and activates an international dialogue on recognizing a right to be rescued at sea that will utmost challenge the boundaries of rights beyond national borders.
Existence and uniqueness of solutions to a flow and transport problem with degenerating coefficients
Authors: RAY NADJA , SCHULZ RAPHAEL
Published: February 2022

Structural changes of the pore space and clogging phenomena are inherent to many porous media applications. However, related analytical investigations remain challenging due to potentially vanishing coefficients in the respective systems of partial differential equations. In this research, we apply an appropriate scaling of the unknowns and work with porosity-weighted function spaces. This enables us to prove existence, uniqueness and non-negativity of weak solutions to a combined flow and transport problem with vanishing, but prescribed porosity field, permeability and diffusion.
Logistic Red Flags in Mass-Casualty Incidents and Disasters: A Problem-Based Approach
Authors: Gamberini Lorenzo , Imbriaco Guglielmo , Ingrassia Pier Luigi , Mazzoli Carlo Alberto , Badiali Stefano , Colombo Davide , Carenzo Luca , Flauto Alfonso , Tengattini Marco , Merlo Federico , Azzaretto Massimo , Monesi Alessandro , Candido Fernando , Coniglio Carlo , Gordini Giovanni , Della Corte Francesco
Published: February 2022

Background:

Mass-casualty incidents (MCIs) and disasters are characterized by a high heterogeneity of effects and may pose important logistic challenges that could hamper the emergency rescue operations.

The main objective of this study was to establish the most frequent logistic challenges (red flags) observed in a series of Italian disasters with a problem-based approach and to verify if the 80-20 rule of the Pareto principle is respected.

Methods:

A series of 138 major events from 1944 through 2020 with a Disaster Severity Score (DSS) ≥ four and five or more victims were analyzed for the presence of twelve pre-determined red flags.

A Pareto graph was built considering the most frequently observed red flags, and eventual correlations between the number of red flags and the components of the DSS were investigated.

Results:

Eight out of twelve red flags covered 80% of the events, therefore not respecting the 80-20 rule; the number of red flags showed a low positive correlation with most of the components of the DSS score. The Pareto analysis showed that potential hazards, casualty nest area > 2.5km2, number of victims over 50, evacuation noria over 20km, number of nests > five, need for extrication, complex access to victims, and complex nest development were the most frequently observed red flags.

Conclusions:

Logistic problems observed in MCIs and disaster scenarios do not follow the 80-20 Pareto rule; this demands for careful and early evaluation of different logistic red flags to appropriately tailor the rescue response.
A tunable bandpass filter with extended passband bandwitdh
Authors: Dong Gaoya , Li Shaosheng , Yang Xiaolong
Published: February 2022

An Nth-order tunable bandpass filter (BPF) structure with extended passband bandwidth has been proposed in this paper based on the novel tunable resonator and coupling structure. The designed tunable resonator is composed of two coupled lines and one varactor diode, while the presented tunable coupling structure is constructed by two cascaded transmission lines and one short-circuited varactor diode. Moreover, the even-(odd-) method and lumped-element equivalent circuit are employed to analyze the operating mechanisms of the designed Nth-order tunable BPF. Specifically, the frequency tuning range is determined by the characteristic impedance and electrical length of coupled line when the varactor diode is within the fixed tuning range. Then, the design procedure for the Nth-order tunable BPFs is proposed. To demonstrate the presented idea, the second- and third-order fully tunable BPFs have been designed and simulated. Finally, a second-order tunable BPF with the compact size of 0.03λg × 0.13λg has been fabricated and measured, and the measured center frequencies are ranging from 0.91 to 1.46 GHz with the passband bandwidths wider than 11.2%.
Hotspots in Psychology – 2022 Edition
Authors: Steinmetz Holger , Wedderhoff Nadine , Bošnjak Michael
Published: February 2022

Abstract. This editorial introduces the five articles included in the sixth “Hotspots in Psychology” of the Zeitschrift für Psychologie. With the new edition, the format enlarges it focus beyond meta-analyses and systematic reviews to new developments such as big data in psychology. The included five articles span a diverse array of topics, that is, the application of individual participants meta-analyses as a way to replicate studies, the role of the degree of anthropomorphism (“human-likeness”) in human-robot interactions, the challenge of multiple dependent effect sizes when conducting a meta-analytical structural equation model, the value of using log data of online platform as a way to predict learning outcomes, and the utility of a block-wise fit evaluation in structural equation models with many longitudinally measured variables. To promote the open science philosophy, the papers present supplemental material that can be accessed via the repository PsychArchives ( www.psycharchives.org ).
Transit Times and StorAge Selection Functions in Idealized Hillslopes With Steady Infiltration
Authors: Kim Minseok , Harman Ciaran J.
Published: February 2022

Spatially integrated transport models have been applied widely to model hydrologic transport. However, we lack simple and process‐based theoretical tools to predict the transport closures—transit time distributions (TTDs) and StorAge Selection (SAS) functions. This limits our ability to infer characteristics of hydrologic systems from tracer observations and to make first‐order estimates of SAS functions in catchments where no tracer data is available. Here we present a theoretical framework linking TTDs and SAS functions to hydraulic groundwater theory at the hillslope scale. For hillslopes where the saturated hydraulic conductivity declines exponentially with depth, analytical solutions for the closures are derived that can be used as hypotheses to test against data. In the simplest form, the hillslope SAS function resembles a uniform or exponential distribution (corresponding to flow pathways in the saturated zone) offset from zero by the storage in the unsaturated zone that does not contribute to discharge. The framework is validated against nine idealized virtual hillslopes constructed using a 2‐D Richards equation‐based model, and against data from tracer experiments in two artificial hillslopes. Modeled internal age, life expectancy, and transit time structures reproduce theoretical predictions. The experimental data also support the theory, though further work is needed to account for the effects of time‐variability. The shape and tailing of TTDs and their power spectra are discussed. The theoretical framework yields several dimensionless numbers that can be used to classify hillslope scale flow and transport dynamics and suggests distinct water age structures for high or low Hillslope number.
Precipitation and Lake Water Evaporation Recorded by Terrestrial and Aquatic n‐Alkane δ2H Isotopes in Lake Khar Nuur, Mongolia
Authors: Strobel Paul , Struck Julian , Bazarradnaa Enkhtuya , Zech Michael , Zech Roland , Bliedtner Marcel
Published: February 2022

The compound‐specific hydrogen isotopic composition (δ2H) of n‐alkanes is a valuable proxy to investigate hydrological conditions in lake sediments. While terrestrial n‐alkanes reflect the isotopic signal of the local precipitation, aquatic n‐alkanes incorporate the isotopic signal of the lake's water, which can be strongly modulated by evaporative enrichment. So far, the spatial distribution of the terrestrial and aquatic δ2H signal within lakes have not systematically been investigated. Here, we present compound‐specific δ2H results of terrestrial (δ2HC31) and aquatic (δ2HC23) n‐alkanes of surface sediment samples from Lake Khar Nuur, a semi‐arid and high‐altitude lake in the Mongolian Altai, and additionally investigate the δ2H signal of topsoils from the catchment. Our results show that the majority of the n‐alkane δ2H values from the catchment topsoils correspond well with modeled local growing season precipitation (JJAS). However, few samples in the northern catchment show more positive δ2H values possibly due to increased evapo(transpi)ration by southward exposition and shallower soils there. The only small variability of δ2HC31 in the surface sediments is in the range of most topsoils δ2H from the catchment, and thus, well reflects local growing season precipitation. δ2HC23 in surface sediment samples from the central and deepest parts of the lake, that is, the lake's sediment accumulation zones, shows distinctly more positive δ2HC23 values due to evaporative lake water enrichment. Consequently, Δaq‐terr, which is the isotopic offset between δ2HC23 and δ2HC31, indicates distinct lake water enrichment in the lake's accumulation zones and is a valuable proxy to investigate past hydrological changes.
Impacts of Road Deicing Application on Sodium and Chloride Concentrations in Philadelphia Region Drinking Water
Authors: Cruz Yuliza D. , Rossi Marissa L. , Goldsmith Steven T.
Published: February 2022

Historical application of roadway deicing agents (e.g., road salt and brines) has led to an increase in sodium and chloride concentrations in surface water over time. Numerous studies have explored the impacts of road salt on freshwater aquatic organisms such as amphibians and benthic macroinvertebrates; however, the public health risk associated with consuming drinking water with elevated sodium has been largely unexplored in the literature. Yet, sodium ingestion, primarily through diet, has been linked to adverse human health conditions, such as hypertension. This study documents weekly sodium and chloride concentrations in municipal tap water from three municipalities within the Philadelphia metropolitan area during winter 2018–2019 (November through March). A late winter peak in sodium and chloride concentrations was observed for all three municipalities immediately following successive snow events coupled with daily high temperatures above 0°C. Among municipalities, mean and peak sodium and chloride concentrations were associated with relatively higher development in upstream areas. Observed sodium concentrations ranged from 1 to 6.4x the USEPA recommended guideline of 20 mg/L for individuals restricted to a total sodium intake of 500 mg/day. Additionally, the contribution of sodium ingestion from water consumption to the recommended daily sodium intake limits for adults ranged from 3.5% to 18.8% for non‐restricted and 4.2%–33.3% for “low salt” (i.e., <1,500 mg/day) diets, respectively. The study results coupled with a records review for 40 U.S. municipalities in snow affected regions indicate the need for real‐time communication between water utilities and the general public regarding sodium exposure risk during winter months.
Characteristics of the Effective Scale Height in the Topside Ionosphere Extracted From Swarm A and Digisonde Observations: Preliminary Results
Authors: Belehaki A. , Tsagouri I. , Paouris E.
Published: February 2022

The ionospheric scale height is a key parameter that defines the shape of the electron density profile. Given that its direct calculation requires knowledge of the physical and chemical state of the plasma, the concept of the effective scale height was proposed to facilitate its application. It is defined as the scale height that fits the electron density profiles with the α‐Chapman function. Its main characteristics, including the diurnal and altitudinal variation are still under investigation. This paper focuses on the specification of its key characteristics at middle latitudes based on coincident Digisonde and Swarm A satellite data. Based on the assumption that the topside electron density profile is approximated with the α‐Chapman model of variable scale height, the effective scale height at the Swarm A altitude is calculated and compared with the effective scale height at . A general conclusion is that the topside effective scale height at ∼450 km exhibits a diurnal variation with highest values in the early morning and evening sectors, while at it gets its maximum values at noon. At night, the effective scale height tends to increase with altitude, however in the daytime, its behavior is more complex. On a local scale, evidence for connection between spread F irregularities and high variability in the topside effective scale height is reported. These preliminary results indicate the potential to further exploit Swarm and Digisonde data for the development of a model for the effective scale height, able to support realistic electron density reconstruction models.
Global Evaluation of the Noah‐MP Land Surface Model and Suggestions for Selecting Parameterization Schemes
Authors: Li Jianduo , Miao Chiyuan , Zhang Guo , Fang Yuan‐Hao , Shangguan Wei , Niu Guo‐Yue
Published: February 2022

This study examines the overall performance of the Noah with multiparameterization (Noah‐MP) land surface model in simulating key land‐atmosphere variables at a global scale and explores the feasibility of running Noah‐MP with regionally different combinations of parameterization schemes. We conducted Noah‐MP ensemble simulations and evaluated the annual means and seasonal cycles of the simulated latent heat flux, net radiation (RN), runoff, soil moisture, snow water equivalent, land surface temperature (LST), leaf area index (LAI), and gross primary productivity (GPP) against a wide variety of global products. The results show that the global patterns of the modeled annual means of these variables generally agree with those of the reference data sets. By evaluating the best simulations in the ensemble, we show that Noah‐MP performs very well in simulating global LST and RN but produces biases in annual mean LAI and GPP by more than 40% in most herbaceous regions. Overall, the main disagreements between Noah‐MP and the reference data sets occurred in the tropical, polar, high‐altitude, and hyperarid regions. This study also highlights the potential of land‐cover‐specific combinations of parameterization schemes to produce optimal modeling results over different land‐cover types. In addition, we strongly suggest the use of multi‐objective optimization of the key parameterizations and parameters to further improve the Noah‐MP's overall performance.
Tides, Topography, and Seagrass Cover Controls on the Spatial Distribution ofPinna nobilison a Coastal Lagoon Tidal Flat
Authors: Silvestri Sonia , Capra Veronica , Cucchiaro Sara , Pivato Mattia , Tarolli Paolo
Published: February 2022

In the last two decadesPinna nobilis, the largest bivalve mollusk endemic to the Mediterranean Sea, has recolonized the tidal flats of some coastal lagoons along the Italian Adriatic coast. In this study, we investigate the influence of tides on the spatial distribution and density of aP. nobilispopulation developing on a tidal flat of the Venice lagoon (NE Italy) by exploiting remote sensing technologies. Our results show that there is a threshold topographic elevation (about 0.5 m below mean sea level for the studied tidal flat) above which the number and duration of emersions become limiting factors ofP. nobilisabundance. Above this elevation, the population density decreases sharply. Densely populated areas tend to occur in tidal flat depressions, where the duration and frequency of emersions are low. We find, however, that the population density has large spatial variability in response to other factors, such as the seagrass percentage cover. The density of the shells increases with increasing seagrass percentage cover, and the denseP. nobilispopulation (0.8–2.68 N/m2) grows within theCymodocea nodosameadow that has a high seagrass percentage cover (>85%). However, within the seagrass meadow with the highest percentage cover, the bivalve preferentially colonizes the portion closest to the main channel, a possible source of nutrients. The shift toC. nodosa—dominated meadows in the Venice lagoon occurred during the last two decades has probably facilitated the observed colonization byP. nobilis. Our findings provide management information for protection and/or restoration ofP. nobilisin coastal lagoons.
Toward Reconciling Radiocarbon Production Rates With Carbon Cycle Changes of the Last 55,000 Years
Authors: Köhler Peter , Adolphi Florian , Butzin Martin , Muscheler Raimund
Published: February 2022

Since it is currently not understood how changes in 14C production rate (Q), and in the carbon cycle, can be combined to explain the reconstructed atmospheric Δ14C record, we discuss possible reasons for this knowledge gap. Reviewing the literature, we exclude that changes in the content of atoms in the atmosphere, which produce cosmogenic 14C after being hit by galactic cosmic rays, might be responsible for parts of the observed differences. When combining Q with carbon cycle changes, one needs to understand the changes in the atmospheric 14C inventory, which are partially counterintuitive. For example, during the Last Glacial Maximum, Δ14C was ∼400‰ higher compared with preindustrial times, but the 14C inventory was 10% smaller. Some pronounced changes in atmospheric Δ14C do not correspond to any significant changes in the atmospheric 14C inventory, since CO2 was changing simultaneously. Using two conceptually different models (BICYCLE‐SE and LSG‐OGCM), we derive hypothetical Qs by forcing the models with identical atmospheric CO2 and Δ14C data. Results are compared with the most recent data‐based estimates of Q derived from cosmogenic isotopes. Millennial‐scale climate change connected to the bipolar seesaw is missing in the applied models, which might explain some, but probably not all, of the apparent model‐data disagreement in Q. Furthermore, Q based on either data from marine sediments or ice cores contains offsets, suggesting an interpretation deficit in the current data‐based approaches.
Fecal microbiota transplantation ameliorates atherosclerosis in mice with C1q/TNF-related protein 9 genetic deficiency
Authors: Kim Eun Sil , Yoon Bo Hyun , Lee Seung Min , Choi Min , Kim Eun Hye , Lee Byong-Wook , Kim Sang-Yeob , Pack Chan-Gi , Sung Young Hoon , Baek In-Jeoung , Jung Chang Hee , Kim Tae-Bum , Jeong Jin-Yong , Ha Chang Hoon
Published: February 2022

Despite the strong influence of the gut microbiota on atherosclerosis, a causal relationship between atherosclerosis pathophysiology and gut microbiota is still unverified. This study was performed to determine the impact of the gut microbiota on the pathogenesis of atherosclerosis caused by genetic deficiency. To elucidate the influence of the gut microbiota on atherosclerosis pathogenesis, an atherosclerosis-prone mouse model (C1q/TNF-related protein 9-knockout (CTRP9-KO) mice) was generated. The gut microbial compositions of CTRP9-KO and WT control mice were compared. Fecal microbiota transplantation (FMT) was performed to confirm the association between gut microbial composition and the progression of atherosclerosis. FMT largely affected the gut microbiota in both CTRP9-KO and WT mice, and all transplanted mice acquired the gut microbiotas of the donor mice. Atherosclerotic lesions in the carotid arteries were decreased in transplanted CTRP9-KO mice compared to CTRP9-KO mice prior to transplantation. Conversely, WT mice transplanted with the gut microbiotas of CTRP9-KO mice showed the opposite effect as that of CTRP9-KO mice transplanted with the gut microbiotas of WT mice. Here, we show that CTRP9 gene deficiency is related to the distribution of the gut microbiota in subjects with atherosclerosis. Transplantation of WT microbiotas into CTRP9-KO mice protected against the progression of atherosclerosis. Conversely, the transplantation of CTRP9-KO microbiotas into WT mice promoted the progression of atherosclerosis. Treating atherosclerosis by restoring gut microbial homeostasis may be an effective therapeutic strategy.
ZNF32 promotes the self-renewal of colorectal cancer cells by regulating the LEPR-STAT3 signaling pathway
Authors: Li Jun , Li Xiaoan , Lan Lili , Sun Lin , Li Xuemei , Li Yaqi , Tian Yan , Zhang Tongqin , Zhou Yan , Mo Chunfen , Fu Xiangsheng
Published: February 2022

Due to the self-renewal characteristics and tumorigenic abilities of cancer stem cells (CSCs), CSCs have been demonstrated to play vital roles in carcinogenesis and antitumor therapy. Our previous report found that Krüppel-like family members (KLFs) and zinc finger protein 32 (ZNF32) play oncogenic roles in carcinogenesis. However, the roles and mechanism of ZNF32 in CSCs are still unknown. Our study demonstrated that ZNF32 was highly expressed in colorectal CSCs, which promoted their self-renewal capacity and tumorigenicity. Overexpression of ZNF32 in colorectal cancer (CRC) cells increased their self-renewal capacity. Furthermore, we identified the leptin receptor (LEPR) as the downstream target gene of ZNF32 and verified that the ZNF32-mediated regulation of CRC self-renewal is achieved via the LEPR- signal transducer and activator of transcription 3 (STAT3) pathway. Moreover, ZNF32 regulated the expression of SOX2, a core transcription factor in stem cells. Finally, we demonstrated that ZNF32 and LEPR were positively correlated in CRC tissues. ZNF32 expression was negatively correlated with the prognosis of CRC patients. Therefore, therapeutically targeting the ZNF32-LEPR-STAT3 pathway in the clinic is tempting.
DGKZ promotes TGFβ signaling pathway and metastasis in triple-negative breast cancer by suppressing lipid raft-dependent endocytosis of TGFβR2
Authors: Zhao Yuanyuan , Sun Hefen , Li Xuan , Liu Qiqi , Liu Yang , Hou Yifeng , Jin Wei
Published: February 2022

Diacylglycerol kinase ζ (DGKZ) is a diacylglycerol kinase that metabolizes diacylglycerol to yield phosphatidic acid, and its function in breast cancer progression remains unclear. In this study, via screening of a CRISPR-Cas9 knockout library containing lipid metabolic genes, DGKZ was identified as a potential prometastatic gene. We first confirmed that high DGKZ expression correlated with tumor progression and poor prognosis in patients. Next, knockout of DGKZ in triple-negative breast cancer cell lines were found to significantly inhibit metastatic behaviors in vitro and in vivo, whereas its overexpression increased the metastatic potential of cell lines. Mechanistic studies based on RNA sequencing and bioinformatic analysis indicated that DGKZ might regulate cell metastasis by promoting epithelial–mesenchymal transition via the transforming growth factor β (TGFβ) signaling pathway. Furthermore, we found that overexpression of DGKZ activated the TGFβ/TGFβR2/Smad3 signaling pathway by inhibiting the degradation of TGFβR2 through suppression of caveolin/lipid raft-dependent endocytosis. Moreover, the caveolin/lipid raft-dependent endocytosis of TGFβR2 was regulated by the metabolite phosphatidic acid, which might alter TGFβR2 partitioning in lipid rafts and nonlipid rafts by affecting the fluidity of the plasma membrane. These findings suggested that DGKZ is a novel promoter of metastasis and that it could be a potential prognostic indicator in patients with triple-negative breast cancer.
miR-582 negatively regulates pre-B cell proliferation and survival through targeting Hif1α and Rictor
Authors: Li Xinxin , Zhang Yufei , Zheng Minhua , Cao Xiuli , Guo Min , Gao Xiangyu , Han Hua
Published: February 2022

B cell development in bone marrow (BM) is a multi-staged process involving pro-B, pre-B, immature B, and mature B cells, among which pre-B cells undergo vigorous proliferation, differentiation, apoptosis, and gene rearrangement. While several signaling pathways participate in pre-B cell development have been clarified, detailed intrinsic mechanisms regulating pre-B cell proliferation and survival have not been fully understood. In the current study, we report that miR-582 regulates pre-B cell proliferation and survival. miR-582 is enriched in pre-B cells. Deletion of miR-582 in mice expanded the BM pre-B cell population in a cell-autonomous manner as shown by competitive BM transplantation. We show that forced miR-582 overexpression inhibited pre-B cell proliferation and survival, whereas downregulation of miR-582 by siRNA significantly promoted pre-B cell proliferation and survival in vitro. We identified that Hif1α and Rictor are authentic targets of miR-582 in pre-B cells as shown by reporter assays. Moreover, miR-582 overexpression reduced the expression of Hif1α and its downstream molecule Glut1, as well as Rictor and mTORC2 activity as shown by attenuated AKT and FoxO1 phosphorylation, while miR-582 knockdown showed opposite effects. miR-582 knockdown-induced increases in pre-B proliferation and survival was abrogated by Hif1α and Rictor inhibitors. Together, miR-582 functions as a negative regulator of pre-B cell proliferation and survival by simultaneously targeting Hif1α and mTORC2 signaling that regulates metabolism in early B cell development.
cFLIP downregulation is an early event required for endoplasmic reticulum stress-induced apoptosis in tumor cells
Authors: Mora-Molina Rocío , Stöhr Daniela , Rehm Markus , López-Rivas Abelardo
Published: February 2022

Protein misfolding or unfolding and the resulting endoplasmic reticulum (ER) stress frequently occur in highly proliferative tumors. How tumor cells escape cell death by apoptosis after chronic ER stress remains poorly understood. We have investigated in both two-dimensional (2D) cultures and multicellular tumor spheroids (MCTSs) the role of caspase-8 inhibitor cFLIP as a regulator of the balance between apoptosis and survival in colon cancer cells undergoing ER stress. We report that downregulation of cFLIP proteins levels is an early event upon treatment of 2D cultures of colon cancer cells with ER stress inducers, preceding TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) upregulation, caspase-8 activation, and apoptosis. Maintaining high cFLIP levels during ER stress by ectopic expression of cFLIP markedly inhibits ER stress-induced caspase-8 activation and apoptosis. Conversely, cFLIP knockdown by RNA interference significantly accelerates caspase-8 activation and apoptosis upon ER stress. Despite activation of the proapoptotic PERK branch of the unfolded protein response (UPR) and upregulation of TRAIL-R2, MCTSs are markedly more resistant to ER stress than 2D cultures of tumor cells. Resistance of MCTSs to ER stress-induced apoptosis correlates with sustained cFLIPLexpression. Interestingly, resistance to ER stress-induced apoptosis is abolished in MCTSs generated from cFLIPLknockdown tumor cells. Overall, our results suggest that controlling cFLIP levels in tumors is an adaptive strategy to prevent tumor cell’s demise in the unfavorable conditions of the tumor microenvironment.
TNF antagonist sensitizes synovial fibroblasts to ferroptotic cell death in collagen-induced arthritis mouse models
Authors: Wu Jiao , Feng Zhuan , Chen Liang , Li Yong , Bian Huijie , Geng Jiejie , Zheng Zhao-Hui , Fu Xianghui , Pei Zhuo , Qin Yifei , Yang Liu , Zhao Yilin , Wang Ke , Chen Ruo , He Qian , Nan Gang , Jiang Xuejun , Chen Zhi-Nan , Zhu Ping
Published: February 2022

Ferroptosis is a nonapoptotic cell death process that requires cellular iron and the accumulation of lipid peroxides. In progressive rheumatoid arthritis (RA), synovial fibroblasts proliferate abnormally in the presence of reactive oxygen species (ROS) and elevated lipid oxidation. Here we show, using a collagen-induced arthritis (CIA) mouse model, that imidazole ketone erastin (IKE), a ferroptosis inducer, decreases fibroblast numbers in the synovium. Data from single-cell RNA sequencing further identify two groups of fibroblasts that have distinct susceptibility to IKE-induced ferroptosis, with the ferroptosis-resistant fibroblasts associated with an increased TNF-related transcriptome. Mechanistically, TNF signaling promotes cystine uptake and biosynthesis of glutathione (GSH) to protect fibroblasts from ferroptosis. Lastly, low dose IKE together with etanercept, a TNF antagonist, induce ferroptosis in fibroblasts and attenuate arthritis progression in the CIA model. Our results thus imply that the combination of TNF inhibitors and ferroptosis inducers may serve as a potential candidate for RA therapy.
The toposiomerase IIIalpha-RMI1-RMI2 complex orients human Bloom’s syndrome helicase for efficient disruption of D-loops
Authors: Harami Gábor M. , Pálinkás János , Seol Yeonee , Kovács Zoltán J. , Gyimesi Máté , Harami-Papp Hajnalka , Neuman Keir C. , Kovács Mihály
Published: February 2022

Homologous recombination (HR) is a ubiquitous and efficient process that serves the repair of severe forms of DNA damage and the generation of genetic diversity during meiosis. HR can proceed via multiple pathways with different outcomes that may aid or impair genome stability and faithful inheritance, underscoring the importance of HR quality control. Human Bloom’s syndrome (BLM, RecQ family) helicase plays central roles in HR pathway selection and quality control via unexplored molecular mechanisms. Here we show that BLM’s multi-domain structural architecture supports a balance between stabilization and disruption of displacement loops (D-loops), early HR intermediates that are key targets for HR regulation. We find that this balance is markedly shifted toward efficient D-loop disruption by the presence of BLM’s interaction partners Topoisomerase IIIα-RMI1-RMI2, which have been shown to be involved in multiple steps of HR-based DNA repair. Our results point to a mechanism whereby BLM can differentially process D-loops and support HR control depending on cellular regulatory mechanisms.
Hydrodynamic manipulation of nano-objects by optically induced thermo-osmotic flows
Authors: Fränzl Martin , Cichos Frank
Published: February 2022

Manipulation of nano-objects at the microscale is of great technological importance for constructing new functional materials, manipulating tiny amounts of fluids, reconfiguring sensor systems, or detecting tiny concentrations of analytes in medical screening. Here, we show that hydrodynamic boundary flows enable the trapping and manipulation of nano-objects near surfaces. We trigger thermo-osmotic flows by modulating the van der Waals and double layer interactions at a gold-liquid interface with optically generated local temperature fields. The hydrodynamic flows, attractive van der Waals and repulsive double layer forces acting on the suspended nanoparticles enable precise nanoparticle positioning and guidance. A rapid multiplexing of flow fields permits the parallel manipulation of many nano-objects and the generation of complex flow fields. Our findings have direct implications for the field of plasmonic nanotweezers and other thermo-plasmonic trapping systems, paving the way for nanoscopic manipulation with boundary flows.
Highly selective cesium(I) capture under acidic conditions by a layered sulfide
Authors: Tang Jun-Hao , Jin Jian-Ce , Li Wei-An , Zeng Xi , Ma Wen , Li Ji-Long , Lv Tian-Tian , Peng Ying-Chen , Feng Mei-Ling , Huang Xiao-Ying
Published: February 2022

Radiocesium remediation is desirable for ecological protection, human health and sustainable development of nuclear energy. Effective capture of Cs+ from acidic solutions is still challenging, mainly due to the low stability of the adsorbing materials and the competitive adsorption of protons. Herein, the rapid and highly selective capture of Cs+ from strongly acidic solutions is achieved by a robust K+-directed layered metal sulfide KInSnS4 (InSnS-1) that exhibits excellent acid and radiation resistance. InSnS-1 possesses high adsorption capacity for Cs+ and can serve as the stationary phase in ion exchange columns to effectively remove Cs+ from neutral and acidic solutions. The adsorption of Cs+ and H3O+ is monitored by single-crystal structure analysis, and thus the underlying mechanism of selective Cs+ capture from acidic solutions is elucidated at the molecular level.
Reversible transition between the polar and antipolar phases and its implications for wake-up and fatigue in HfO2-based ferroelectric thin film
Authors: Cheng Yan , Gao Zhaomeng , Ye Kun Hee , Park Hyeon Woo , Zheng Yonghui , Zheng Yunzhe , Gao Jianfeng , Park Min Hyuk , Choi Jung-Hae , Xue Kan-Hao , Hwang Cheol Seong , Lyu Hangbing
Published: February 2022

Atomic-resolution Cs-corrected scanning transmission electron microscopy revealed local shifting of two oxygen positions (OI and OII) within the unit cells of a ferroelectric (Hf0.5Zr0.5)O2 thin film. A reversible transition between the polar Pbc21 and antipolar Pbca phases, where the crystal structures of the 180° domain wall of the Pbc21 phase and the unit cell structure of the Pbca phase were identical, was induced by applying appropriate cycling voltages. The critical field strength that determined whether the film would be woken up or fatigued was ~0.8 MV/cm, above or below which wake-up or fatigue was observed, respectively. Repeated cycling with sufficiently high voltages led to development of the interfacial nonpolar P42/nmc phase, which induced fatigue through the depolarizing field effect. The fatigued film could be rejuvenated by applying a slightly higher voltage, indicating that these transitions were reversible. These mechanisms are radically different from those of conventional ferroelectrics.
Internal Stark effect of single-molecule fluorescence
Authors: Vasilev Kirill , Doppagne Benjamin , Neuman Tomáš , Rosławska Anna , Bulou Hervé , Boeglin Alex , Scheurer Fabrice , Schull Guillaume
Published: February 2022

The optical properties of chromophores can be efficiently tuned by electrostatic fields generated in their close environment, a phenomenon that plays a central role for the optimization of complex functions within living organisms where it is known as internal Stark effect (ISE). Here, we realised an ISE experiment at the lowest possible scale, by monitoring the Stark shift generated by charges confined within a single chromophore on its emission energy. To this end, a scanning tunneling microscope (STM) functioning at cryogenic temperatures is used to sequentially remove the two central protons of a free-base phthalocyanine chromophore deposited on a NaCl-covered Ag(111) surface. STM-induced fluorescence measurements reveal spectral shifts that are associated to the electrostatic field generated by the internal charges remaining in the chromophores upon deprotonation.
Arabidopsis guard cell chloroplasts import cytosolic ATP for starch turnover and stomatal opening
Authors: Lim Shey-Li , Flütsch Sabrina , Liu Jinhong , Distefano Luca , Santelia Diana , Lim Boon Leong
Published: February 2022

Stomatal opening requires the provision of energy in the form of ATP for proton pumping across the guard cell (GC) plasma membrane and for associated metabolic rearrangements. The source of ATP for GCs is a matter of ongoing debate that is mainly fuelled by controversies around the ability of GC chloroplasts (GCCs) to perform photosynthesis. By imaging compartment-specific fluorescent ATP and NADPH sensor proteins in Arabidopsis, we show that GC photosynthesis is limited and mitochondria are the main source of ATP. Unlike mature mesophyll cell (MC) chloroplasts, which are impermeable to cytosolic ATP, GCCs import cytosolic ATP through NUCLEOTIDE TRANSPORTER (NTT) proteins. GCs from ntt mutants exhibit impaired abilities for starch biosynthesis and stomatal opening. Our work shows that GCs obtain ATP and carbohydrates via different routes from MCs, likely to compensate for the lower chlorophyll contents and limited photosynthesis of GCCs.
Cerebral microcirculation mapped by echo particle tracking velocimetry quantifies the intracranial pressure and detects ischemia
Authors: Zhang Zeng , Hwang Misun , Kilbaugh Todd J. , Sridharan Anush , Katz Joseph
Published: February 2022

Affecting 1.1‰ of infants, hydrocephalus involves abnormal accumulation of cerebrospinal fluid, resulting in elevated intracranial pressure (ICP). It is the leading cause for brain surgery in newborns, often causing long-term neurologic disabilities or even death. Since conventional invasive ICP monitoring is risky, early neurosurgical interventions could benefit from noninvasive techniques. Here we use clinical contrast-enhanced ultrasound (CEUS) imaging and intravascular microbubble tracking algorithms to map the cerebral blood flow in hydrocephalic pediatric porcine models. Regional microvascular perfusions are quantified by the cerebral microcirculation (CMC) parameter, which accounts for the concentration of micro-vessels and flow velocity in them. Combining CMC with hemodynamic parameters yields functional relationships between cortical micro-perfusion and ICP, with correlation coefficients exceeding 0.85. For cerebral ischemia cases, the nondimensionalized cortical micro-perfusion decreases by an order of magnitude when ICP exceeds 50% of the MAP. These findings suggest that CEUS-based CMC measurement is a plausible noninvasive method for assessing the ICP and detecting ischemia.
Circadian lipid and hepatic protein rhythms shift with a phase response curve different than melatonin
Authors: Kent Brianne A. , Rahman Shadab A. , St. Hilaire Melissa A. , Grant Leilah K. , Rüger Melanie , Czeisler Charles A. , Lockley Steven W.
Published: February 2022

While studies suggest that light and feeding patterns can reset circadian rhythms in various metabolites, whether these shifts follow a predictable pattern is unknown. We describe the first phase response curves (PRC) for lipids and hepatic proteins in response to combined light and food stimuli. The timing of plasma rhythms was assessed by constant routine before and after exposure to a combined 6.5-hour blue light exposure and standard meal schedule, which was systematically varied by ~20° between individuals. We find that the rhythms shift according to a PRC, with generally greater shifts for lipids and liver proteins than for melatonin. PRC timing varies relative to the stimulus, with albumin and triglyceride PRCs peaking at a time similar to melatonin whereas the cholesterol and high-density lipoprotein PRCs are offset by ~12 h. These data have important implications for treating circadian misalignment in shiftworkers who consume meals and are exposed to light around the clock.
Myeloid cell interferon responses correlate with clearance of SARS-CoV-2
Authors: Singh Dhiraj K. , Aladyeva Ekaterina , Das Shibali , Singh Bindu , Esaulova Ekaterina , Swain Amanda , Ahmed Mushtaq , Cole Journey , Moodley Chivonne , Mehra Smriti , Schlesinger Larry S. , Artyomov Maxim N. , Khader Shabaana A. , Kaushal Deepak
Published: February 2022

Emergence of mutant SARS-CoV-2 strains associated with an increased risk of COVID-19-related death necessitates better understanding of the early viral dynamics, host responses and immunopathology. Single cell RNAseq (scRNAseq) allows for the study of individual cells, uncovering heterogeneous and variable responses to environment, infection and inflammation. While studies have reported immune profiling using scRNAseq in terminal human COVID-19 patients, performing longitudinal immune cell dynamics in humans is challenging. Macaques are a suitable model of SARS-CoV-2 infection. Our longitudinal scRNAseq of bronchoalveolar lavage (BAL) cell suspensions from young rhesus macaques infected with SARS-CoV-2 (n = 6) demonstrates dynamic changes in transcriptional landscape 3 days post- SARS-CoV-2-infection (3dpi; peak viremia), relative to 14-17dpi (recovery phase) and pre-infection (baseline) showing accumulation of distinct populations of both macrophages and T-lymphocytes expressing strong interferon-driven inflammatory gene signature at 3dpi. Type I interferon response is induced in the plasmacytoid dendritic cells with appearance of a distinct HLADR+CD68+CD163+SIGLEC1+macrophage population exhibiting higher angiotensin-converting enzyme 2 (ACE2) expression. These macrophages are significantly enriched in the lungs of macaques at 3dpi and harbor SARS-CoV-2 while expressing a strong interferon-driven innate anti-viral gene signature. The accumulation of these responses correlated with decline in viremia and recovery.
The IGFBP3/TMEM219 pathway regulates beta cell homeostasis
Authors: D’Addio Francesca , Maestroni Anna , Assi Emma , Ben Nasr Moufida , Amabile Giovanni , Usuelli Vera , Loretelli Cristian , Bertuzzi Federico , Antonioli Barbara , Cardarelli Francesco , El Essawy Basset , Solini Anna , Gerling Ivan C. , Bianchi Cristina , Becchi Gabriella , Mazzucchelli Serena , Corradi Domenico , Fadini Gian Paolo , Foschi Diego , Markmann James F. , Orsi Emanuela , Škrha Jan , Camboni Maria Gabriella , Abdi Reza , James Shapiro A. M. , Folli Franco , Ludvigsson Johnny , Del Prato Stefano , Zuccotti Gianvincenzo , Fiorina Paolo
Published: February 2022

Loss of pancreatic beta cells is a central feature of type 1 (T1D) and type 2 (T2D) diabetes, but a therapeutic strategy to preserve beta cell mass remains to be established. Here we show that the death receptor TMEM219 is expressed on pancreatic beta cells and that signaling through its ligand insulin-like growth factor binding protein 3 (IGFBP3) leads to beta cell loss and dysfunction. Increased peripheral IGFBP3 was observed in established and at-risk T1D/T2D patients and was confirmed in T1D/T2D preclinical models, suggesting that dysfunctional IGFBP3/TMEM219 signaling is associated with abnormalities in beta cells homeostasis. In vitro and in vivo short-term IGFBP3/TMEM219 inhibition and TMEM219 genetic ablation preserved beta cells and prevented/delayed diabetes onset, while long-term IGFBP3/TMEM219 blockade allowed for beta cell expansion. Interestingly, in several patients’ cohorts restoration of appropriate IGFBP3 levels was associated with improved beta cell function. The IGFBP3/TMEM219 pathway is thus shown to be a physiological regulator of beta cell homeostasis and is also demonstrated to be disrupted in T1D/T2D. IGFBP3/TMEM219 targeting may therefore serve as a therapeutic option in diabetes.
Biophysical properties at patch scale shape the metabolism of biofilm landscapes
Authors: Depetris Anna , Tagliavini Giorgia , Peter Hannes , Kühl Michael , Holzner Markus , Battin Tom J.
Published: February 2022

Phototrophic biofilms form complex spatial patterns in streams and rivers, yet, how community patchiness, structure and function are coupled and contribute to larger-scale metabolism remains unkown. Here, we combined optical coherence tomography with automated O2 microprofiling and amplicon sequencing in a flume experiment to show how distinct community patches interact with the hydraulic environment and how this affects the internal distribution of oxygen. We used numerical simulations to derive rates of community photosynthetic activity and respiration at the patch scale and use the obtained parameter to upscale from individual patches to the larger biofilm landscape. Our biofilm landscape approach revealed evidence of parallels in the structure-function coupling between phototrophic biofilms and their streambed habitat.