bluuebunny/crossref_metadata_2025 huggingface dataset:
Whey protein concentrate ameliorates the methotrexate-induced liver and kidney damage
Authors: Tufan Elif , Sivas Güzin Göksun , Gürel-Gökmen Begüm , Yılmaz-Karaoğlu Sümeyye , Dursun Ercan , Çalışkan-Ak Esin , Muhan Aleyna , Özbeyli Dilek , Şener Göksel , Tunali-Akbay Tuğba
Published: March 2023

Methotrexate (MTX) is a cytotoxic immunosuppressant that is widely used in the treatment of tumours, rheumatoid arthritis and psoriasis. This study aims to evaluate the effects of whey proteins on MTX-induced liver and kidney damage by focusing on oxidant–antioxidant systems and eating habits. The study was conducted in four groups of thirty Sprague–Dawley rats (control, control + whey protein concentrate (WPC), MTX, MTX + WPC). A single dose of 20 mg/kg MTX was administered intraperitoneally to the MTX groups. Control and MTX groups were given 2 g/kg WPC by oral gavage every day for 10 d. At the end of day 10, blood samples were drawn and liver and kidney tissues were removed. MTX administration increased the lipid peroxidation level and decreased glutathione level, superoxide dismutase and glutathione-S-transferase activities in the liver and kidney. Administration of WPC significantly reduced the damage caused by MTX in the liver and kidney. While a decrease in serum urea level and an increase in serum creatinine level were detected in the MTX group, WPC administration reversed these results up to control group levels. Administration of WPC to the MTX group significantly reversed the histopathological damage scores of the liver and kidney. WPC administration ameliorated the MTX-induced oxidative damage in the liver and kidney tissues due to its antioxidant properties. Liver and kidney damage can be prevented by using whey proteins as a nutraceutical in MTX therapy. In conclusion, whey proteins demonstrated a protective effect against MTX-induced liver and kidney damage.
‘Great Northern Wilderness’-style environmentalism: Nature preservation and the legacies of Mao-era land reclamation in China’s northeast borderland
Authors: Fromm Martin T.
Published: March 2023

One of the epic national narratives of modernization and development in China is the story of Beidahuang (‘Great Northern Wilderness’) in the country’s northeast. The term ‘Beidahuang’ refers originally to state-sponsored campaigns, starting in the 1950s, that involved the enlistment of tens of thousands of People’s Liberation Army soldiers, educated youth, and Communist Party cadres. Their task was to transform the vast northeast ‘wasteland’ into productive farmland that would feed the nation while securing the nation’s borders with Russia. This article examines the significance of Beidahuang as a feature of the environmental discourse in China’s northeast borderlands, focusing on the first decade of the twenty-first century when the Chinese state was establishing more systematic measures for addressing environmental concerns. In the context of the northeast borderland, the massive deforestation that resulted from the socialist campaigns to transform ‘wasteland’ into productive farmland has left a controversial legacy for regional elites grappling with the Party leadership’s turn towards environmental conservation as an emerging political priority. This article suggests that the ongoing importance of the ‘Great Northern Wilderness’ in the Chinese cultural imagination has shaped the ways in which regional elites frame environmental issues in relation to economic development, nationalism, and border relations with Russia.
Axial ratio beamwidth enhancement of a low-profile circularly polarized antenna using defected ground structures
Authors: Ray Mrityunjoy Kumar , Mandal Kaushik , Moloudian Gholamhosein , Lalbakhsh Ali
Published: March 2023

This article explores the possibilities of incorporating a defected ground structure (DGS) for widening the 3 dB axial ratio beamwidth (ARBW) of a simple low-profile planar circularly polarized (CP) antenna. Two pairs of DGSs are etched symmetrically along the diagonals of the ground plane to overcome the limited 3 dB ARBW performance of a crossed-slotted circular-shaped planar CP antenna. Here, one pair of DGSs is orthogonal to another pair of DGSs. The distance between the pairs of DGSs plays a key role in enhancing the 3 dB ARBW by 40.62%. A gap of 0.18λ0 is considered between the DGSs to maintain the symmetrical electric field distribution in the substrate. It also helps to reduce orthogonal current components and provides uniformly distributed patch surface currents. These phenomena collectively help the proposed CP antenna to exhibit right-handed circular polarization radiation with the 3 dB ARBW of 186° and 188° in the E-plane and H-plane, respectively. The measured results yield impedance bandwidth (S11 ≤ −10 dB) of 2.6% (2.283–2.342 GHz), CP bandwidth of 0.9% (2.294–2.315 GHz), gain higher than 4.8 dBic, and total antenna efficiency more than 64% across the entire CP band.
Temporal Trends of Racial and Socioeconomic Disparities in Population Exposures to Upstream Oil and Gas Development in California
Authors: González David J. X. , Morton Claire M. , Hill Lee Ann L. , Michanowicz Drew R. , Rossi Robert J. , Shonkoff Seth B. C. , Casey Joan A. , Morello‐Frosch Rachel
Published: March 2023

People living near oil and gas development are exposed to multiple environmental stressors that pose health risks. Some studies suggest these risks are higher for racially and socioeconomically marginalized people, which may be partly attributable to disparities in exposures. We examined whether racially and socioeconomically marginalized people in California are disproportionately exposed to oil and gas wells and associated hazards. We longitudinally assessed exposure to wells during three time periods (2005–2009, 2010–2014, and 2015–2019) using sociodemographic data at the census block group‐level. For each block group and time period, we assessed exposure to new, active, retired, and plugged wells, and cumulative production volume. We calculated risk ratios to determine whether marginalized people disproportionately resided near wells (within 1 km). Averaged across the three time periods, we estimated that 1.1 million Californians (3.0%) lived within 1 km of active wells. Nearly 9 million Californians (22.9%) lived within 1 km of plugged wells. The proportion of Black residents near active wells was 42%–49% higher than the proportion of Black residents across California, and the proportion of Hispanic residents near active wells was 4%–13% higher than their statewide proportion. Disparities were greatest in areas with the highest oil and gas production, where the proportion of Black residents was 105%–139% higher than statewide. Socioeconomically marginalized residents also had disproportionately high exposure to wells. Though oil and gas production has declined in California, marginalized communities persistently had disproportionately high exposure to wells, potentially contributing to health disparities.
An Analytical Method to Estimate Groundwater Depletion of an Aquitard Due To Variable Drawdowns in Adjacent Aquifers
Authors: Li Zhaofeng , Li Hao , Xiao Xianxuan , Illman Walter A. , Wang Ruizhe , Zhang Qiang
Published: March 2023

Computing aquitard depletion, which is often overlooked, is of great significance for the assessment of groundwater resources and land subsidence. The issue is viewed as troublesome because of the additional computational burden, the poorly known hydrogeological parameters of the aquitard, and the lack of drawdown history in pumped aquifers. In this study, an analytical solution is derived to describe the drawdown variation in a nonlinear‐consolidated aquitard under the condition of variable drawdowns in adjacent aquifers. Based on the analytical solution, we study the characteristics of groundwater dynamics and water balance under the conditions of linearly increasing drawdown of aquifers in adjacent aquifers. In addition, we put forward a method to calculate the depletion and hydrogeological parameters of an aquitard corresponding to variable drawdowns in adjacent aquifers, applicable even when historical drawdown data are lacking. The accuracy of the method is generally very good, but results improve when the drawdown history of pumped aquifers is divided into more periods for estimation. Groundwater depletion of the aquitard increases with increasing compression index, coefficient of consolidation, thickness of aquitard, rate of drawdown change in the adjacent aquifer, while decreasing with initial void ratio, and initial effective stress. The proposed approach is demonstrated at a field site in Shanghai city of China, and it would help for the effective management of groundwater resources and estimation of the global transfer from groundwater to surface water.
ABL1 kinase as a tumor suppressor in AML1-ETO and NUP98-PMX1 leukemias
Authors: Golovine Konstantin , Abalakov Gleb , Lian Zhaorui , Chatla Srinivas , Karami Adam , Chitrala Kumaraswamy Naidu , Madzo Jozef , Nieborowska-Skorska Margaret , Huang Jian , Skorski Tomasz
Published: March 2023

Deletion of ABL1 was detected in a cohort of hematologic malignancies carrying AML1-ETO and NUP98 fusion proteins. Abl1−/− murine hematopoietic cells transduced with AML1-ETO and NUP98-PMX1 gained proliferation advantage when compared to Abl1 + /+ counterparts. Conversely, overexpression and pharmacological stimulation of ABL1 kinase resulted in reduced proliferation. To pinpoint mechanisms facilitating the transformation of ABL1-deficient cells, Abl1 was knocked down in 32Dcl3-Abl1ko cells by CRISPR/Cas9 followed by the challenge of growth factor withdrawal. 32Dcl3-Abl1ko cells but not 32Dcl3-Abl1wt cells generated growth factor-independent clones. RNA-seq implicated PI3K signaling as one of the dominant mechanisms contributing to growth factor independence in 32Dcl3-Abl1ko cells. PI3K inhibitor buparlisib exerted selective activity against Lin-cKit+ NUP98-PMX1;Abl1−/− cells when compared to the Abl1 + /+ counterparts. Since the role of ABL1 in DNA damage response (DDR) is well established, we also tested the inhibitors of ATM (ATMi), ATR (ATRi) and DNA-PKcs (DNA-PKi). AML1-ETO;Abl1−/− and NUP98-PMX1;Abl1−/− cells were hypersensitive to DNA-PKi and ATRi, respectively, when compared to Abl1 + /+ counterparts. Moreover, ABL1 kinase inhibitor enhanced the sensitivity to PI3K, DNA-PKcs and ATR inhibitors. In conclusion, we showed that ABL1 kinase plays a tumor suppressor role in hematological malignancies induced by AML1-ETO and NUP98-PMX1 and modulates the response to PI3K and/or DDR inhibitors.
Long-term risks of invasive cervical cancer following HPV infection: follow-up of two screening cohorts in Manchester
Authors: Gilham Clare , Sargent Alexandra , Crosbie Emma J. , Peto Julian
Published: March 2023

Background

Long-term follow-up of large cohorts is needed to determine the effects of HPV and screening on CIN3 (grade 3 cervical intraepithelial neoplasia) and ICC (invasive cervical cancer).

Methods

Women were recruited when attending for routine cervical screening in Greater Manchester, UK: 1987–93 for the Manchester Cohort (MC: 47,625 women) and 2001–03 for the ARTISTIC Cohort (AC: 24,496 women). Both were followed through national registration for cancer incidence and mortality to 2020.

Results

Risk patterns following HPV infection differed for CIN3 and ICC. Risk of ICC in the MC rises for 30 years following a single positive HPV test, reaching 2.5% (95% CI: 1.3–4.5%). A similar pattern was seen in the AC, but the risks of cancer were approximately halved. CIN3 was diagnosed much sooner in the AC due to more efficient cytology. More sensitive HPV testing was able to better predict future risk.

Conclusion

The sensitivity of HPV testing and cytology influences the CIN3 detection rate. Sensitive HPV testing enables effective risk stratification. Increased risk of ICC is observed 15–30 years after HPV infection. Women testing HPV + should be followed until their infection clears. Discharging women from screening programmes whilst they remain HPV + may not be safe, even if cytology and colposcopy tests are normal.
Diamagnetic mechanism of critical current non-reciprocity in multilayered superconductors
Authors: Sundaresh Ananthesh , Väyrynen Jukka I. , Lyanda-Geller Yuli , Rokhinson Leonid P.
Published: March 2023

The suggestion that non-reciprocal critical current (NRC) may be an intrinsic property of non-centrosymmetric superconductors has generated renewed theoretical and experimental interest motivated by an analogy with the non-reciprocal resistivity due to the magnetochiral effect in uniform materials with broken spatial and time-reversal symmetry. Theoretically it has been understood that terms linear in the Cooper pair momentum do not contribute to NRC, although the role of higher-order terms remains unclear. In this work we show that critical current non-reciprocity is a generic property of multilayered superconductor structures in the presence of magnetic field-generated diamagnetic currents. In the regime of an intermediate coupling between the layers, the Josephson vortices are predicted to form at high fields and currents. Experimentally, we report the observation of NRC in nanowires fabricated from InAs/Al heterostructures. The effect is independent of the crystallographic orientation of the wire, ruling out an intrinsic origin of NRC. Non-monotonic NRC evolution with magnetic field is consistent with the generation of diamagnetic currents and formation of the Josephson vortices. This extrinsic NRC mechanism can be used to design novel devices for superconducting circuits.
Antigen discrimination by T cells relies on size-constrained microvillar contact
Authors: Jenkins Edward , Körbel Markus , O’Brien-Ball Caitlin , McColl James , Chen Kevin Y. , Kotowski Mateusz , Humphrey Jane , Lippert Anna H. , Brouwer Heather , Santos Ana Mafalda , Lee Steven F. , Davis Simon J. , Klenerman David
Published: March 2023

T cells use finger-like protrusions called ‘microvilli’ to interrogate their targets, but why they do so is unknown. To form contacts, T cells must overcome the highly charged, barrier-like layer of large molecules forming a target cell’s glycocalyx. Here, T cells are observed to use microvilli to breach a model glycocalyx barrier, forming numerous small (<0.5 μm diameter) contacts each of which is stabilized by the small adhesive protein CD2 expressed by the T cell, and excludes large proteins including CD45, allowing sensitive, antigen dependent TCR signaling. In the absence of the glycocalyx or when microvillar contact-size is increased by enhancing CD2 expression, strong signaling occurs that is no longer antigen dependent. Our observations suggest that, modulated by the opposing effects of the target cell glycocalyx and small adhesive proteins, the use of microvilli equips T cells with the ability to effect discriminatory receptor signaling.
IMC-Denoise: a content aware denoising pipeline to enhance Imaging Mass Cytometry
Authors: Lu Peng , Oetjen Karolyn A. , Bender Diane E. , Ruzinova Marianna B. , Fisher Daniel A. C. , Shim Kevin G. , Pachynski Russell K. , Brennen W. Nathaniel , Oh Stephen T. , Link Daniel C. , Thorek Daniel L. J.
Published: March 2023

Imaging Mass Cytometry (IMC) is an emerging multiplexed imaging technology for analyzing complex microenvironments using more than 40 molecularly-specific channels. However, this modality has unique data processing requirements, particularly for patient tissue specimens where signal-to-noise ratios for markers can be low, despite optimization, and pixel intensity artifacts can deteriorate image quality and downstream analysis. Here we demonstrate an automated content-aware pipeline, IMC-Denoise, to restore IMC images deploying a differential intensity map-based restoration (DIMR) algorithm for removing hot pixels and a self-supervised deep learning algorithm for shot noise image filtering (DeepSNiF). IMC-Denoise outperforms existing methods for adaptive hot pixel and background noise removal, with significant image quality improvement in modeled data and datasets from multiple pathologies. This includes in technically challenging human bone marrow; we achieve noise level reduction of 87% for a 5.6-fold higher contrast-to-noise ratio, and more accurate background noise removal with approximately 2 × improved F1 score. Our approach enhances manual gating and automated phenotyping with cell-scale downstream analyses. Verified by manual annotations, spatial and density analysis for targeted cell groups reveal subtle but significant differences of cell populations in diseased bone marrow. We anticipate that IMC-Denoise will provide similar benefits across mass cytometric applications to more deeply characterize complex tissue microenvironments.
Higher-order interactions shape collective dynamics differently in hypergraphs and simplicial complexes
Authors: Zhang Yuanzhao , Lucas Maxime , Battiston Federico
Published: March 2023

Higher-order networks have emerged as a powerful framework to model complex systems and their collective behavior. Going beyond pairwise interactions, they encode structured relations among arbitrary numbers of units through representations such as simplicial complexes and hypergraphs. So far, the choice between simplicial complexes and hypergraphs has often been motivated by technical convenience. Here, using synchronization as an example, we demonstrate that the effects of higher-order interactions are highly representation-dependent. In particular, higher-order interactions typically enhance synchronization in hypergraphs but have the opposite effect in simplicial complexes. We provide theoretical insight by linking the synchronizability of different hypergraph structures to (generalized) degree heterogeneity and cross-order degree correlation, which in turn influence a wide range of dynamical processes from contagion to diffusion. Our findings reveal the hidden impact of higher-order representations on collective dynamics, highlighting the importance of choosing appropriate representations when studying systems with nonpairwise interactions.
Predictability of fossil fuel CO2 from air quality emissions
Authors: Miyazaki Kazuyuki , Bowman Kevin
Published: March 2023

Quantifying the coevolution of greenhouse gases and air quality pollutants can provide insight into underlying anthropogenic processes enabling predictions of their emission trajectories. Here, we classify the dynamics of historic emissions in terms of a modified Environmental Kuznets Curve (MEKC), which postulates the coevolution of fossil fuel CO2(FFCO2) and NOx emissions as a function of macroeconomic development. The MEKC broadly captures the historic FFCO2-NOxdynamical regimes for countries including the US, China, and India as well as IPCC scenarios. Given these dynamics, we find the predictive skill of FFCO2 given NOxemissions constrained by satellite data is less than 2% error at one-year lags for many countries and less than 10% for 4-year lags. The proposed framework in conjunction with an increasing satellite constellation provides valuable guidance to near-term emission scenario development and evaluation at time-scales relevant to international assessments such as the Global Stocktake.
Continuous ammonia electrosynthesis using physically interlocked bipolar membrane at 1000 mA cm−2
Authors: Xu Ziang , Wan Lei , Liao Yiwen , Pang Maobin , Xu Qin , Wang Peican , Wang Baoguo
Published: March 2023

Electrosynthesis of ammonia from nitrate reduction receives extensive attention recently for its relatively mild conditions and clean energy requirements, while most existed electrochemical strategies can only deliver a low yield rate and short duration for the lack of stable ion exchange membranes at high current density. Here, a bipolar membrane nitrate reduction process is proposed to achieve ionic balance, and increasing water dissociation sites is delivered by constructing a three-dimensional physically interlocked interface for the bipolar membrane. This design simultaneously boosts ionic transfer and interfacial stability compared to traditional ones, successfully reducing transmembrane voltage to 1.13 V at up to current density of 1000 mA cm−2. By combining a Co three-dimensional nanoarray cathode designed for large current and low concentration utilizations, a continuous and high yield bipolar membrane reactor for NH3 electrosynthesis realized a stable electrolysis at 1000 mA cm−2 for over 100 h, Faradaic efficiency of 86.2% and maximum yield rate of 68.4 mg h−1 cm−2 with merely 2000 ppm NO3- alkaline electrolyte. These results show promising potential for artificial nitrogen cycling in the near future.
FTD-tau S320F mutation stabilizes local structure and allosterically promotes amyloid motif-dependent aggregation
Authors: Chen Dailu , Bali Sofia , Singh Ruhar , Wosztyl Aleksandra , Mullapudi Vishruth , Vaquer-Alicea Jaime , Jayan Parvathy , Melhem Shamiram , Seelaar Harro , van Swieten John C. , Diamond Marc I. , Joachimiak Lukasz A.
Published: March 2023

Amyloid deposition of the microtubule-associated protein tau is associated with neurodegenerative diseases. In frontotemporal dementia with abnormal tau (FTD-tau), missense mutations in tau enhance its aggregation propensity. Here we describe the structural mechanism for how an FTD-tau S320F mutation drives spontaneous aggregation, integrating data from in vitro, in silico and cellular experiments. We find that S320F stabilizes a local hydrophobic cluster which allosterically exposes the 306VQIVYK311 amyloid motif; identify a suppressor mutation that destabilizes S320F-based hydrophobic clustering reversing the phenotype in vitro and in cells; and computationally engineer spontaneously aggregating tau sequences through optimizing nonpolar clusters surrounding the S320 position. We uncover a mechanism for regulating tau aggregation which balances local nonpolar contacts with long-range interactions that sequester amyloid motifs. Understanding this process may permit control of tau aggregation into structural polymorphs to aid the design of reagents targeting disease-specific tau conformations.
Impact of small farmers' access to improved seeds and deforestation in DR Congo
Authors: Bernard Tanguy , Lambert Sylvie , Macours Karen , Vinez Margaux
Published: March 2023

Since the 1960s, the increased availability of modern seed varieties in developing countries has had large positive effects on households’ well-being. However, the effect of related land use changes on deforestation and biodiversity is ambiguous. This study examines this question through a randomized control trial in a remote area in the Congo Basin rainforest with weak input and output markets. Using plot-level data on land conversion combined with remote sensing data, we find that promotion of modern seed varieties did not lead to an increase in overall deforestation by small farmers. However, farmers cleared more primary forest and less secondary forest. We attribute this to the increased demand for nitrogen required by the use of some modern seed varieties, and to the lack of alternative sources of soil nutrients, which induced farmers to shift towards cultivation of land cleared in primary forest. Unless combined with interventions to maintain soil fertility, policies to promote modern seed varieties may come at the cost of important losses in biodiversity.
Purkinje cell dopaminergic inputs to astrocytes regulate cerebellar-dependent behavior
Authors: Li Chang , Saliba Natalie B. , Martin Hannah , Losurdo Nicole A. , Kolahdouzan Kian , Siddiqui Riyan , Medeiros Destynie , Li Wei
Published: March 2023

Dopamine has a significant role in motor and cognitive function. The dopaminergic pathways originating from the midbrain have received the most attention; however, the relevance of the cerebellar dopaminergic system is largely undiscovered. Here, we show that the major cerebellar astrocyte type Bergmann glial cells express D1 receptors. Dopamine can be synthesized in Purkinje cells by cytochrome P450 and released in an activity-dependent fashion. We demonstrate that activation of D1 receptors induces membrane depolarization and Ca2+release from the internal store. These astrocytic activities in turn modify Purkinje cell output by altering its excitatory and inhibitory synaptic input. Lastly, we show that conditional knockout of D1 receptors in Bergmann glial cells results in decreased locomotor activity and impaired social activity. These results contribute to the understanding of the molecular, cellular, and circuit mechanisms underlying dopamine function in the cerebellum, revealing a critical role for the cerebellar dopaminergic system in motor and social behavior.
STING agonist-loaded, CD47/PD-L1-targeting nanoparticles potentiate antitumor immunity and radiotherapy for glioblastoma
Authors: Zhang Peng , Rashidi Aida , Zhao Junfei , Silvers Caylee , Wang Hanxiang , Castro Brandyn , Ellingwood Abby , Han Yu , Lopez-Rosas Aurora , Zannikou Markella , Dmello Crismita , Levine Rebecca , Xiao Ting , Cordero Alex , Sonabend Adam M. , Balyasnikova Irina V. , Lee-Chang Catalina , Miska Jason , Lesniak Maciej S.
Published: March 2023

As a key component of the standard of care for glioblastoma, radiotherapy induces several immune resistance mechanisms, such as upregulation of CD47 and PD-L1. Here, leveraging these radiotherapy-elicited processes, we generate a bridging-lipid nanoparticle (B-LNP) that engages tumor-associated myeloid cells (TAMCs) to glioblastoma cells via anti-CD47/PD-L1 dual ligation. We show that the engager B-LNPs block CD47 and PD-L1 and promote TAMC phagocytic activity. To enhance subsequent T cell recruitment and antitumor responses after tumor engulfment, the B-LNP was encapsulated with diABZI, a non-nucleotidyl agonist for stimulator of interferon genes. In vivo treatment with diABZI-loaded B-LNPs induced a transcriptomic and metabolic switch in TAMCs, turning these immunosuppressive cells into antitumor effectors, which induced T cell infiltration and activation in brain tumors. In preclinical murine models, B-LNP/diABZI administration synergized with radiotherapy to promote brain tumor regression and induce immunological memory against glioma. In summary, our study describes a nanotechnology-based approach that hijacks irradiation-triggered immune checkpoint molecules to boost potent and long-lasting antitumor immunity against glioblastoma.
Multimaterial 3D printed self-locking thick-panel origami metamaterials
Authors: Ye Haitao , Liu Qingjiang , Cheng Jianxiang , Li Honggeng , Jian Bingcong , Wang Rong , Sun Zechu , Lu Yang , Ge Qi
Published: March 2023

Thick-panel origami has shown great potential in engineering applications. However, the thick-panel origami created by current design methods cannot be readily adopted to structural applications due to the inefficient manufacturing methods. Here, we report a design and manufacturing strategy for creating thick-panel origami structures with excellent foldability and capability of withstanding cyclic loading. We directly print thick-panel origami through a single fused deposition modeling (FDM) multimaterial 3D printer following a wrapping-based fabrication strategy where the rigid panels are wrapped and connected by highly stretchable soft parts. Through stacking two thick-panel origami panels into a predetermined configuration, we develop a 3D self-locking thick-panel origami structure that deforms by following a push-to-pull mode enabling the origami structure to support a load over 11000 times of its own weight and sustain more than 100 cycles of 40% compressive strain. After optimizing geometric parameters through a self-built theoretical model, we demonstrate that the mechanical response of the self-locking thick-panel origami structure is highly programmable, and such multi-layer origami structure can have a substantially improved impact energy absorption for various structural applications.
Highly-sensitive label-free deep profiling of N-glycans released from biomedically-relevant samples
Authors: Marie Anne-Lise , Ray Somak , Ivanov Alexander R.
Published: March 2023

Alterations of protein glycosylation can serve as sensitive and specific disease biomarkers. Labeling procedures for improved separation and detectability of oligosaccharides have several drawbacks, including incomplete derivatization, side-products, noticeable desialylation/defucosylation, sample loss, and interference with downstream analyses. Here, we develop a label-free workflow based on high sensitivity capillary zone electrophoresis-mass spectrometry (CZE-MS) for profiling of native underivatized released N-glycans. Our workflow provides a >45-fold increase in signal intensity compared to the conventional CZE-MS approaches used for N-glycan analysis. Qualitative and quantitative N-glycan profiling of purified human serum IgG, bovine serum fetuin, bovine pancreas ribonuclease B, blood-derived extracellular vesicle isolates, and total plasma results in the detection of >250, >400, >150, >310, and >520 N-glycans, respectively, using injected amounts equivalent to <25 ng of model protein and nL-levels of plasma-derived samples. Compared to reported results for biological samples of similar amounts and complexity, the number of identified N-glycans is increased up to ~15-fold, enabling highly sensitive analysis of sample amounts as low as sub-0.2 nL of plasma volume equivalents. Furthermore, highly sialylated N-glycans are identified and structurally characterized, and untreated sialic acid-linkage isomers are resolved in a single CZE-MS analysis.
Emergence of flexible kesterite solar cells: progress and perspectives
Authors: Li Jianjun , Sun Kaiwen , Yuan Xiaojie , Huang Jialiang , Green Martin A. , Hao Xiaojing
Published: March 2023

Flexible photovoltaics have been and will be increasingly in demand in modern and future society in various applications. Searching for ideal flexible photovoltaic technologies that can perfectly meet these expanding demands has long been an active branch of photovoltaic research. Flexible kesterite Cu2ZnSn(S,Se)4 (CZTSSe) has emerged in recent years owning to its great potential to be an abundant, low-cost, stable, and high-efficiency ‘green’ photovoltaic material that can be widely deployed with the lowest detrimental environmental impact. Here, we review the recent progress with flexible kesterite solar cells in thin-film and monograin technologies, discuss the key challenges and strategies associated with the flexible substrates, and finally provide the future perspectives on further pushing the efficiency toward commercial-competitive levels.
Combination Ad26.RSV.preF/preF protein vaccine induces superior protective immunity compared with individual vaccine components in preclinical models
Authors: Saeland Eirikur , van der Fits Leslie , Bolder Renske , Heemskerk-van der Meer Marjolein , Drijver Joke , van Polanen Yolinda , Vaneman Cornelis , Tettero Lisanne , Cox Freek , Serroyen Jan , Jorgensen Matthew J. , Langedijk Johannes P. M. , Schuitemaker Hanneke , Callendret Benoit , Zahn Roland C.
Published: March 2023

Respiratory syncytial virus (RSV) is a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously shown that a prefusion (preF) conformation-stabilized RSV F protein antigen and an adenoviral vector encoding RSV preF protein (Ad26.RSV.preF) are immunogenic and protective in animals when administered as single components. Here, we evaluated a combination of the 2 components, administered as a single injection. Strong induction of both humoral and cellular responses was shown in RSV-naïve and pre-exposed mice and pre-exposed African green monkeys (AGMs). Both components of the combination vaccine contributed to humoral immune responses, while the Ad26.RSV.preF component was the main contributor to cellular immune responses in both mice and AGMs. Immunization with the combination elicited superior protection against RSV A2 challenge in cotton rats. These results demonstrate the advantage of a combination vaccine and support further clinical development.
Real-time detection of ammonium in soil pore water
Authors: Yupiter Rotem , Arnon Shlomi , Yeshno Elad , Visoly-Fisher Iris , Dahan Ofer
Published: March 2023

The development of technologies for continuous measurement of nitrogen forms in the soil is essential for optimizing the application of fertilizers in agriculture and preventing water-resource pollution. However, there is no effective commercial technology available for continuous monitoring of ammonium species in soil pore water. This work investigates an approach for real-time measurement of ammonium in soil water using near-infrared transmission spectroscopy and partial least squares regression (PLSR) for spectral analysis. The PLSR model was trained using soil pore water collected from various soils spiked with ammonium to achieve a wide concentration range. The monitoring approach was then validated through transport experiments in a soil column. The results demonstrated capabilities for real-time tracking of the temporal variation in soil ammonium concentration and potential utilization in agronomical or environmental sensing.
How autoreactive thymocytes differentiate into regulatory versus effector CD4+ T cells after avoiding clonal deletion
Authors: Tai Xuguang , Indart Alyssa , Rojano Mirelle , Guo Jie , Apenes Nicolai , Kadakia Tejas , Craveiro Marco , Alag Amala , Etzensperger Ruth , Badr Mohamed Elsherif , Zhang Flora , Zhang Zhongmei , Mu Jie , Guinter Terry , Crossman Assiatu , Granger Larry , Sharrow Susan , Zhou Xuyu , Singer Alfred
Published: March 2023

Thymocytes bearing autoreactive T cell receptors (TCRs) are agonist-signaled by TCR/co-stimulatory molecules to either undergo clonal deletion or to differentiate into specialized regulatory T (Treg) or effector T (Teff) CD4+ cells. How these different fates are achieved during development remains poorly understood. We now document that deletion and differentiation are agonist-signaled at different times during thymic selection and that Treg and Teff cells both arise after clonal deletion as alternative lineage fates of agonist-signaled CD4+CD25+ precursors. Disruption of agonist signaling induces CD4+CD25+ precursors to initiate Foxp3 expression and become Treg cells, whereas persistent agonist signaling induces CD4+CD25+ precursors to become IL-2+ Teff cells. Notably, we discovered that transforming growth factor-β induces Foxp3 expression and promotes Treg cell development by disrupting weaker agonist signals and that Foxp3 expression is not induced by IL-2 except under non-physiological in vivo conditions. Thus, TCR signaling disruption versus persistence is a general mechanism of lineage fate determination in the thymus that directs development of agonist-signaled autoreactive thymocytes.
High-resolution calibrated and validated Synthetic Aperture Radar Ocean surface wind data around Australia
Authors: Khan Salman , Young Ian , Ribal Agustinus , Hemer Mark
Published: March 2023

The dataset consists of ocean surface wind speed and direction at 10 m height and 1 km spatial resolution around the wider Australian coastal areas, spanning 4 years (2017 to 2021) of measurements from Sentinel-1 A and B imaging Synthetic Aperture Radar (SAR) platforms. The winds have been derived using a consistent SAR wind retrieval algorithm, processing the full Sentinel-1 archive in this region. The data are appropriately quality controlled, flagged, and archived as NetCDF files representing SAR wind field maps aligned with satellite along-track direction. The data have been calibrated against Metop-A/B Scatterometer buoy-calibrated, wind measurements and examined for potential changes in calibration over the duration of the data. The calibrated data are further validated by comparisons against independent Altimeter (Cryosat-2, Jason-2, Jason-3, and SARAL) wind speeds. Several methods for data access are also listed. The database is potentially useful for offshore industries (oil and gas, fisheries, shipping, offshore wind energy), public recreational activities (fishing, sailing, surfing), and protection and management of coasts and natural habitats.
Geosmin suppresses defensive behaviour and elicits unusual neural responses in honey bees
Authors: Scarano Florencia , Deivarajan Suresh Mukilan , Tiraboschi Ettore , Cabirol Amélie , Nouvian Morgane , Nowotny Thomas , Haase Albrecht
Published: March 2023

Geosmin is an odorant produced by bacteria in moist soil. It has been found to be extraordinarily relevant to some insects, but the reasons for this are not yet fully understood. Here we report the first tests of the effect of geosmin on honey bees. A stinging assay showed that the defensive behaviour elicited by the bee’s alarm pheromone component isoamyl acetate (IAA) is strongly suppressed by geosmin. Surprisingly, the suppression is, however, only present at very low geosmin concentrations, and disappears at higher concentrations. We investigated the underlying mechanisms at the level of the olfactory receptor neurons by means of electroantennography, finding the responses to mixtures of geosmin and IAA to be lower than to pure IAA, suggesting an interaction of both compounds at the olfactory receptor level. Calcium imaging of the antennal lobe (AL) revealed that neuronal responses to geosmin decreased with increasing concentration, correlating well with the observed behaviour. Computational modelling of odour transduction and coding in the AL suggests that a broader activation of olfactory receptor types by geosmin in combination with lateral inhibition could lead to the observed non-monotonic increasing–decreasing responses to geosmin and thus underlie the specificity of the behavioural response to low geosmin concentrations.
Functional sugar-free chewing gum infused with spices bolsters antioxidant capacity and phenolic content of saliva
Authors: Crowe-White Kristi M. , Jung Seung Eun , Bragg Anna , Senkus Katelyn E.
Published: March 2023

Oral and vascular diseases are seemingly disparate conditions, yet individuals with poor oral health are at increased risk for cardiovascular events. Spice-derived bioactive polyphenols with antioxidant functionality may attenuate mechanisms linking the diseases, namely oxidative stress and inflammation. Acknowledging that novel approaches to increase antioxidant intake are warranted, the purpose of this study was to evaluate the influence of two functional sugar-free gums infused with spices on antioxidant capacity and phenolic content of saliva using the oxygen radical absorbance capacity and Folin-Ciocalteu assays, respectively. Unstimulated followed by stimulated saliva was collected according to a validated method across a prescribed five minute chewing period. Both gums significantly increased hydrophilic, lipophilic, and total antioxidant capacity of saliva (p < 0.05) yet to varying extents. Phenolic content of saliva was significantly higher (p < 0.001) post-chew for both gums. Results suggest spices infused into sugar-free chewing gum bolster the antioxidant capacity of saliva, thereby promoting oral health. Research evaluating the sublingual absorption of spice-derived antioxidants in functional gums and their influence on systemic oxidative stress is warranted.
Investigating livestock management in the early Neolithic archaeological site of Cabecicos Negros (Almería, Spain) from the organic residue analysis in pottery
Authors: Tarifa-Mateo N. , Saña M. , Clop X. , Rosell-Melé A. , Camalich-Massieu M. D. , Martín-Socas D.
Published: March 2023

This paper seeks to reconstruct the management of food resources in the early Neolithic site of Cabecicos Negros in southeastern Spain. For this purpose, we have studied 29 potsherds from Cabecicos Negros (Andalusia, Spain). Applying the methods of gas chromatography and mass spectrometry we were able to recompose the daily use of the sherds related to the consumption and storage of food products. Among the results obtained in this work, we were able to show new evidence of the exploitation of dairy products in the south of the Iberian Peninsula, as well as provide information on the exploitation and management of the early domestic animals herds. To improve the archaeological results obtained, isotopic results were compared with a modern reference of 53 fat samples from the adipose tissue of domestic pigs and wild boars.
Growth and characterization of thorium-doped calcium fluoride single crystals
Authors: Beeks Kjeld , Sikorsky Tomas , Rosecker Veronika , Pressler Martin , Schaden Fabian , Werban David , Hosseini Niyusha , Rudischer Lukas , Schneider Felix , Berwian Patrick , Friedrich Jochen , Hainz Dieter , Welch Jan , Sterba Johannes H. , Kazakov Georgy , Schumm Thorsten
Published: March 2023

We have grown $$^{232}$$

232

Th:CaF$$_2$$

2

and $$^{229}$$

229

Th:CaF$$_2$$

2

single crystals for investigations on the VUV laser-accessible first nuclear excited state of $$^{229}$$

229

Th, with the aim of building a solid-state nuclear clock. To reach high doping concentrations despite the extreme scarcity (and radioactivity) of $$^{229}$$

229

Th, we have scaled down the crystal volume by a factor 100 compared to established commercial or scientific growth processes. We use the vertical gradient freeze method on 3.2 mm diameter seed single crystals with a 2 mm drilled pocket, filled with a co-precipitated CaF$$_2$$

2

:ThF$$_4$$

4

:PbF$$_2$$

2

powder in order to grow single crystals. Concentrations of $$4\cdot 10^{19}$$

4
·

10
19

 cm$$^{-3}$$

-
3

have been realized with $$^{232}$$

232

Th with good (> 10%) VUV transmission. However, the intrinsic radioactivity of $$^{229}$$

229

Th drives radio-induced dissociation during growth and radiation damage after solidification. Both lead to a degradation of VUV transmission, currently limiting the $$^{229}$$

229

Th concentration to $$<5\times 10^{17}$$

<
5
×

10
17

 cm$$^{-3}$$

-
3

.
Circulating tumor DNA in molecular assessment feasibly predicts early progression of pancreatic cancer that cannot be identified via initial imaging
Authors: Watanabe Fumiaki , Suzuki Koichi , Aizawa Hidetoshi , Endo Yuhei , Takayama Yuji , Kakizawa Nao , Kato Takaharu , Noda Hiroshi , Rikiyama Toshiki
Published: March 2023

Molecular assessment using circulating tumor DNA (ctDNA) has not been well-defined. We recruited 61 pancreatic cancer (PC) patients who underwent initial computed tomography (CT) imaging study during first-line chemotherapy. Initial molecular assessment was performed using droplet digital PCR and defined as the change in KRAS-mutated ctDNA before and after treatments, which was classified into five categories: mNT, molecular negative; mCR, complete response; mPR, partial response; mSD, stable disease; mPD, progressive disease. Of 61 patients, 14 diagnosed with PD after initial CT imaging showed significantly worse therapeutic outcomes than 47 patients with disease control. In these 47 patients, initial molecular assessment exhibited significant differences in therapeutic outcomes between patients with and without ctDNA (mPD + mSD vs. mCR + mNT; 13.2 M vs. 21.7 M, P = 0.0029) but no difference between those with mPD and mSD + mCR + mNT, suggesting that the presence of ctDNA had more impact on the therapeutic outcomes than change in its number. Multivariate analysis revealed that it was the only independent prognostic factor (P = 0.0405). The presence of ctDNA in initial molecular assessment predicted early tumor progression and identified PC patients more likely to benefit from chemotherapy.
Embryo morphokinetics derived from fresh and vitrified bovine oocytes predict blastocyst development and nuclear abnormalities
Authors: Angel-Velez Daniel , De Coster Tine , Azari-Dolatabad Nima , Fernández-Montoro Andrea , Benedetti Camilla , Pavani Krishna , Van Soom Ann , Bogado Pascottini Osvaldo , Smits Katrien
Published: March 2023

Embryo development is a dynamic process and critical stages may go unnoticed with the use of traditional morphologic assessments, especially the timing of embryonic divisions and aberrant zygotic cleavage patterns. Bovine embryo development is impaired after oocyte vitrification, but little is known about the underlying morphokinetic behavior. Here, bovine zygotes from fresh (n = 708) and vitrified oocytes (n = 182) were monitored by time-lapse imaging and the timing and nature of early blastomere divisions were modeled to find associations with blastocyst development at day 8. The predictive potential of morphokinetic parameters was analyzed by logistic regression and receiver operating characteristic curve analysis to determine optimal cut-off values. Lag-phase was highly correlated with embryo development. Remarkably, 100% of zygotes that reached the blastocyst stage showed a lag-phase. Fast first cleavage increased the chance of blastocyst development to 30% with a cut-off of 32 h and 22 min. Aberrant zygotic cleavage events, including multipolar division, unequal blastomere sizes, and membrane ruffling resulted in decreased blastocyst development. Multipolar division leads to uneven blastomeres, which was associated with anuclear and multinuclear blastomeres, indicating genome segregation errors. Moreover, we described for the first time morphokinetics of embryos derived from vitrified bovine oocytes. Vitrification severely affected blastocyst development, although lower cryoprotectant concentration in equilibration solutions seems to be less detrimental for embryo yield. Impaired development was linked to slow cleavages, lower lag-phase incidence, and increased early embryonic arrest. Typically, less than 15% of the embryos produced from vitrified oocytes reached more than eight cells. Interestingly, the rate of abnormal first cleavage events was not affected by oocyte vitrification. In conclusion, time to first cleavage, the presence of a lag-phase, and the absence of aberrant zygotic cleavage were the best predictors of bovine blastocyst development for both fresh and vitrified oocytes.
High-precision measurements of the hyperfine structure of cobalt ions in the deep ultraviolet range
Authors: Koszorús Á. , Block M. , Campbell P. , Cheal B. , de Groote R. P. , Gins W. , Moore I. D. , Ortiz-Cortes A. , Raggio A. , Warbinek J.
Published: March 2023

High-precision hyperfine structure measurements were performed on stable, singly-charged $$^{59}$$

59

Co ions at the IGISOL facility in Jyväskylä, Finland using the collinear laser spectroscopy technique. A newly installed light collection setup enabled the study of transitions in the 230 nm wavelength range from low-lying states below 6000 cm$$^{-1}$$

-
1

. We report a 100-fold improvement on the precision of the hyperfine A parameters, and furthermore present newly measured hyperfine B paramaters.
Integrative transcriptomic and metabolomic analysis reveals alterations in energy metabolism and mitochondrial functionality in broiler chickens with wooden breast
Authors: Wang Ziqing , Brannick Erin , Abasht Behnam
Published: March 2023

This integrative study of transcriptomics and metabolomics aimed to improve our understanding of Wooden Breast myopathy (WB). Breast muscle samples from 8 WB affected and 8 unaffected male broiler chickens of 47 days of age were harvested for metabolite profiling. Among these 16 samples, 5 affected and 6 unaffected also underwent gene expression profiling. The Joint Pathway Analysis was applied on 119 metabolites and 3444 genes exhibiting differential abundance or expression between WB affected and unaffected chickens. Mitochondrial dysfunctions in WB was suggested by higher levels of monoacylglycerols and down-regulated genes involved in lipid production, fatty acid beta oxidation, and oxidative phosphorylation. Lower levels of carnosine and anserine, along with down-regulated carnosine synthase 1 suggested decreased carnosine synthesis and hence impaired antioxidant capacity in WB. Additionally, Weighted Gene Co-expression Network Analysis results indicated that abundance of inosine monophosphate, significantly lower in WB muscle, was correlated with mRNA expression levels of numerous genes related to focal adhesion, extracellular matrix and intercellular signaling, implying its function in connecting and possibly regulating multiple key biological pathways. Overall, this study showed not only the consistency between transcript and metabolite profiles, but also the potential in gaining further insights from analyzing multi-omics data.