bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic activity of combined inhibition of anti-apoptotic molecules in B-cell precursor ALL
Authors: Seyfried Felix , Stirnweiß Felix Uli , Niedermayer Alexandra , Enzenmüller Stefanie , Hörl Rebecca Louise , Münch Vera , Köhrer Stefan , Debatin Klaus-Michael , Meyer Lüder Hinrich 
Published: January 2022

AbstractTargeting BCL-2, a key regulator of survival in B-cell malignancies including precursor B-cell acute lymphoblastic leukemia, has become a promising treatment strategy. However, given the redundancy of anti-apoptotic BCL-2 family proteins (BCL-2, BCL-XL, MCL-1), single targeting may not be sufficient. When analyzing the effects of BH3-mimetics selectively targeting BCL-XL and MCL-1 alone or in combination with the BCL-2 inhibitor venetoclax, heterogeneous sensitivity to either of these inhibitors was found in ALL cell lines and in patient-derived xenografts. Interestingly, some venetoclax-resistant leukemias were sensitive to the MCL-1-selective antagonist S63845 and/or BCL-XL-selective A-1331852 suggesting functional mutual substitution. Consequently, co-inhibition of BCL-2 and MCL-1 or BCL-XL resulted in synergistic apoptosis induction. Functional analysis by BH3-profiling and analysis of protein complexes revealed that venetoclax-treated ALL cells are dependent on MCL-1 and BCL-XL, indicating that MCL-1 or BCL-XL provide an Achilles heel in BCL-2-inhibited cells. The effect of combining BCL-2 and MCL-1 inhibition by venetoclax and S63845 was evaluated in vivo and strongly enhanced anti-leukemia activity was found in a pre-clinical patient-derived xenograft model. Our study offers in-depth molecular analysis of mutual substitution of BCL-2 family proteins in acute lymphoblastic leukemia and provides targets for combination treatment in vivo and in ongoing clinical studies.
A magnetically enabled simulation of microgravity represses the auxin response during early seed germination on a microfluidic platform
Authors: Du Jing , Zeng Lin , Yu Zitong , Chen Sihui , Chen Xi , Zhang Yi , Yang Hui 
Published: January 2022

AbstractFor plants on Earth, the phytohormone auxin is essential for gravitropism-regulated seedling establishment and plant growth. However, little is known about auxin responses under microgravity conditions due to the lack of a tool that can provide an alteration of gravity. In this paper, a microfluidic negative magnetophoretic platform is developed to levitate Arabidopsis seeds in an equilibrium plane where the applied magnetic force compensates for gravitational acceleration. With the benefit of the microfluidic platform to simulate a microgravity environment on-chip, it is found that the auxin response is significantly repressed in levitated seeds. Simulated microgravity statistically interrupts auxin responses in embryos, even after chemical-mediated auxin alterations, illustrating that auxin is a critical factor that mediates the plant response to gravity alteration. Furthermore, pretreatment with an auxin transportation inhibitor (N-1-naphthylphthalamic acid) enables a decrease in the auxin response, which is no longer affected by simulated microgravity, demonstrating that polar auxin transportation plays a vital role in gravity-regulated auxin responses. The presented microfluidic platform provides simulated microgravity conditions in an easy-to-implement manner, helping to study and elucidate how plants correspond to diverse gravity conditions; in the future, this may be developed into a versatile tool for biological study on a variety of samples.
Integrated single-cell RNA sequencing analysis reveals distinct cellular and transcriptional modules associated with survival in lung cancer
Authors: Zhang Li , Zhang Yiming , Wang Chengdi , Yang Ying , Ni Yinyun , Wang Zhoufeng , Song Tingting , Yao Menglin , Liu Zhiqiang , Chao Ningning , Yang Yongfeng , Shao Jun , Li Zhidan , Zhou Ran , Chen Li , Zhang Dan , Zhao Yuancun , Liu Wei , Li Yupeng , He Ping , Lin Jing-wen , Wang Yuan , Zhang Kang , Chen Lu , Li Weimin 
Published: January 2022

AbstractLung adenocarcinoma (LUAD) and squamous carcinoma (LUSC) are two major subtypes of non-small cell lung cancer with distinct pathologic features and treatment paradigms. The heterogeneity can be attributed to genetic, transcriptional, and epigenetic parameters. Here, we established a multi-omics atlas, integrating 52 single-cell RNA sequencing and 2342 public bulk RNA sequencing. We investigated their differences in genetic amplification, cellular compositions, and expression modules. We revealed that LUAD and LUSC contained amplifications occurring selectively in subclusters of AT2 and basal cells, and had distinct cellular composition modules associated with poor survival of lung cancer. Malignant and stage-specific gene analyses further uncovered critical transcription factors and genes in tumor progression. Moreover, we identified subclusters with proliferating and differentiating properties in AT2 and basal cells. Overexpression assays of ten genes, including sub-cluster markers AQP5 and KPNA2, further indicated their functional roles, providing potential targets for early diagnosis and treatment in lung cancer.
NEK2 enhances malignancies of glioblastoma via NIK/NF-κB pathway
Authors: Xiang Jianyang , Alafate Wahafu , Wu Wei , Wang Yichang , Li Xiaodong , Xie Wanfu , Bai Xiaobin , Li Ruichun , Wang Maode , Wang Jia 
Published: January 2022

AbstractGlioblastoma (GBM) is one of the most lethal primary brain tumor with a poor median survival less than 15 months. Despite the development of the clinical strategies over the decades, the outcomes for GBM patients remain dismal due to the strong proliferation and invasion ability and the acquired resistance to radiotherapy and chemotherapy. Therefore, developing new biomarkers and therapeutic strategies targeting GBM is in urgent need. In this study, gene expression datasets and relevant clinical information were extracted from public cancers/glioma datasets, including TCGA, GRAVENDEEL, REMBRANDT, and GILL datasets. Differentially expressed genes were analyzed and NEK2 was picked as a candidate gene for subsequent validation. Human tissue samples and corresponding data were collected from our center and detected by immunohistochemistry analysis. Molecular biological assays and in vivo xenograft transplantation were performed to confirm the bioinformatic findings. High-throughput RNA sequencing, followed by KEGG analysis, GSEA analysis and GO analysis were conducted to identify potential signaling pathways related to NEK2 expression. Subsequent mechanism assays were used to verify the relationship between NEK2 and NF-κB signaling. Overall, we identified that NEK2 is significantly upregulated in GBM and the higher expression of NEK2 exhibited a poorer prognosis. Functionally, NEK2 knockdown attenuated cell proliferation, migration, invasion, and tumorigenesis of GBM while NEK2 overexpression promoted the GBM progression. Furthermore, High-throughput RNA sequencing and bioinformatics analysis indicated that NEK2 was positively related to the NF-κB signaling pathway in GBM. Mechanically, NEK2 activated the noncanonical NF-κB signaling pathway by phosphorylating NIK and increasing the activity and stability of NIK. In conclusion, NEK2 promoted the progression of GBM through activation of noncanonical NF-κB signaling, indicating that NEK2- NF-κB axis could be a potential drug target for GBM.
Real-space anisotropy of the superconducting gap in the charge-density wave material 2H-NbSe2
Authors: Sanna Antonio , Pellegrini Camilla , Liebhaber Eva , Rossnagel Kai , Franke Katharina J. , Gross E. K. U. 
Published: January 2022

AbstractWe present a scanning tunneling microscopy (STM) and ab-initio study of the anisotropic superconductivity of 2H-NbSe2 in the charge-density-wave (CDW) phase. Differential-conductance spectra show a clear double-peak structure, which is well reproduced by density functional theory simulations enabling full k- and real-space resolution of the superconducting gap. The hollow-centered (HC) and chalcogen-centered (CC) CDW patterns observed in the experiment are mapped onto separate van der Waals layers with different electronic properties. We identify the CC layer as the high-gap region responsible for the main STM peak. Remarkably, this region belongs to the same Fermi surface sheet that is broken by the CDW gap opening. Simulations reveal a highly anisotropic distribution of the superconducting gap within single Fermi sheets, setting aside the proposed scenario of a two-gap superconductivity. Our results point to a spatially localized competition between superconductivity and CDW involving the HC regions of the crystal.
Diverse classes of constraints enable broader applicability of a linear programming-based dynamic metabolic modeling framework
Authors: Lee Justin Y. , Styczynski Mark P. 
Published: January 2022

AbstractCurrent metabolic modeling tools suffer from a variety of limitations, from scalability to simplifying assumptions, that preclude their use in many applications. We recently created a modeling framework, Linear Kinetics-Dynamic Flux Balance Analysis (LK-DFBA), that addresses a key gap: capturing metabolite dynamics and regulation while retaining a potentially scalable linear programming structure. Key to this framework’s success are the linear kinetics and regulatory constraints imposed on the system. However, while the linearity of these constraints reduces computational complexity, it may not accurately capture the behavior of many biochemical systems. Here, we developed three new classes of LK-DFBA constraints to better model interactions between metabolites and the reactions they regulate. We tested these new approaches on several synthetic and biological systems, and also performed the first-ever comparison of LK-DFBA predictions to experimental data. We found that no single constraint approach was optimal across all systems examined, and systems with the same topological structure but different parameters were often best modeled by different types of constraints. However, we did find that when genetic perturbations were implemented in the systems, the optimal constraint approach typically remained the same as for the wild-type regardless of the model topology or parameterization, indicating that just a single wild-type dataset could allow identification of the ideal constraint to enable model predictivity for a given system. These results suggest that the availability of multiple constraint approaches will allow LK-DFBA to model a wider range of metabolic systems.
Maize stalk stiffness and strength are primarily determined by morphological factors
Authors: Stubbs Christopher J. , Larson Ryan , Cook Douglas D. 
Published: January 2022

AbstractThe maize (Zea mays) stem is a biological structure that must balance both biotic and structural load bearing duties. These competing requirements are particularly relevant in the design of new bioenergy crops. Although increased stem digestibility is typically associated with a lower structural strength and higher propensity for lodging, with the right balance between structural and biological activities it may be possible to design crops that are high-yielding and have digestible biomass. This study investigates the hypothesis that geometric factors are much more influential in determining structural strength than tissue properties. To study these influences, both physical and in silico experiments were used. First, maize stems were tested in three-point bending. Specimen-specific finite element models were created based on x-ray computed tomography scans. Models were validated by comparison with experimental data. Sensitivity analyses were used to assess the influence of structural parameters such as geometric and material properties. As hypothesized, geometry was found to have a much stronger influence on structural stability than material properties. This information reinforces the notion that deficiencies in tissue strength could be offset by manipulation of stalk morphology, thus allowing the creation of stalks which are both resilient and digestible.
Alleviating time poverty among the working poor: a pre-registered longitudinal field experiment
Authors: Whillans Ashley , West Colin 
Published: January 2022

Abstract
Poverty entails more than a scarcity of material resources—it also involves a shortage of time. To examine the causal benefits of reducing time poverty, we conducted a longitudinal field experiment over six consecutive weeks in an urban slum in Kenya with a sample of working mothers, a population who is especially likely to experience severe time poverty. Participants received vouchers for services designed to reduce their burden of unpaid labor. We compared the effect of these vouchers against equivalently valued unconditional cash transfers (UCTs) and a neutral control condition. In contrast to our pre-registered hypotheses, a pre-registered Bayesian ANCOVA indicated that the time-saving, UCT, and control conditions led to similar increases in subjective well-being, reductions in perceived stress, and decreases in relationship conflict (Cohen’s d’s ranged from 0.25 to 0.85 during the treatment weeks and from 0.21 to 0.36 at the endline). Exploratory analyses revealed that the time-saving vouchers and UCTs produced these benefits through distinct psychological pathways. We conclude by discussing the implications of these results for economic development initiatives.

Protocol registration
The Stage 1 protocol for this Registered Report was accepted in principle on 27/06/2019. The protocol, as accepted by Nature Human Behaviour, can be found at https://doi.org/10.6084/m9.figshare.c.4368455.
Experience-dependent learning of behavioral laterality in the scale-eating cichlid Perissodus microlepis occurs during the early developmental stage
Authors: Takeuchi Yuichi , Higuchi Yuna , Ikeya Koki , Tagami Masataka , Oda Yoichi 
Published: January 2022

AbstractBehavioral laterality—typically represented by human handedness—is widely observed among animals. However, how laterality is acquired during development remains largely unknown. Here, we examined the effect of behavioral experience on the acquisition of lateralized predation at different developmental stages of the scale-eating cichlid fish Perissodus microlepis. Naïve juvenile fish without previous scale-eating experience showed motivated attacks on prey goldfish and an innate attack side preference. Following short-term predation experience, naïve juveniles learned a pronounced lateralized attack using their slightly skewed mouth morphology, and improved the velocity and amplitude of body flexion to succeed in foraging scales during dominant-side attack. Naïve young fish, however, did not improve the dynamics of flexion movement, but progressively developed attack side preference and speed to approach the prey through predation experience. Thus, the cichlid learns different aspects of predation behavior at different developmental stages. In contrast, naïve adults lost the inherent laterality, and they neither developed the lateralized motions nor increased their success rate of predation, indicating that they missed appropriate learning opportunities for scale-eating skills. Therefore, we conclude that behavioral laterality of the cichlid fish requires the integration of genetic basis and behavioral experiences during early developmental stages, immediately after they start scale-eating.
Desertification risk fuels spatial polarization in ‘affected’ and ‘unaffected’ landscapes in Italy
Authors: Nickayin Samaneh Sadat , Coluzzi Rosa , Marucci Alvaro , Bianchini Leonardo , Salvati Luca , Cudlin Pavel , Imbrenda Vito 
Published: January 2022

AbstractSouthern Europe is a hotspot for desertification risk because of the intimate impact of soil deterioration, landscape transformations, rising human pressure, and climate change. In this context, large-scale empirical analyses linking landscape fragmentation with desertification risk assume that increasing levels of land vulnerability to degradation are associated with significant changes in landscape structure. Using a traditional approach of landscape ecology, this study evaluates the spatial structure of a simulated landscape based on different levels of vulnerability to land degradation using 15 metrics calculated at three time points (early-1960s, early-1990s, early-2010s) in Italy. While the (average) level of land vulnerability increased over time almost in all Italian regions, vulnerable landscapes demonstrated to be increasingly fragmented, as far as the number of homogeneous patches and mean patch size are concerned. The spatial balance in affected and unaffected areas—typically observed in the 1960s—was progressively replaced with an intrinsically disordered landscape, and this process was more intense in regions exposed to higher (and increasing) levels of land degradation. The spread of larger land patches exposed to intrinsic degradation brings to important consequences since (1) the rising number of hotspots may increase the probability of local-scale degradation processes, and (2) the buffering effect of neighbouring (unaffected) land can be less effective on bigger hotspots, promoting a downward spiral toward desertification.
Microscale drivers of summer CO2 fluxes in the Svalbard High Arctic tundra
Authors: Magnani Marta , Baneschi Ilaria , Giamberini Mariasilvia , Raco Brunella , Provenzale Antonello 
Published: January 2022

AbstractHigh-Arctic ecosystems are strongly affected by climate change, and it is still unclear whether they will become a carbon source or sink in the next few decades. In turn, such knowledge gaps on the drivers and the processes controlling CO2 fluxes and storage make future projections of the Arctic carbon budget a challenging goal. During summer 2019, we extensively measured CO2 fluxes at the soil–vegetation–atmosphere interface, together with basic meteoclimatic variables and ecological characteristics in the Bayelva river basin near Ny Ålesund, Spitzbergen, Svalbard (NO). By means of multi-regression models, we identified the main small-scale drivers of CO2 emission (Ecosystem Respiration, ER), and uptake (Gross Primary Production, GPP) in this tundra biome, showing that (i) at point scale, the temporal variability of fluxes is controlled by the classical drivers, i.e. air temperature and solar irradiance respectively for ER and GPP, (ii) at site scale, the heterogeneity of fractional vegetation cover, soil moisture and vegetation type acted as additional source of variability for both CO2 emissions and uptake. The assessment of the relative importance of such drivers in the multi-regression model contributes to a better understanding of the terrestrial carbon dioxide exchanges and of Critical Zone processes in the Arctic tundra.
Retinal microvasculature features in patients with Behcet’s disease: a systematic review and meta-analysis
Authors: Ji Kai-bao , Hu Zhe , Zhang Qing-lin , Mei Hai-feng , Xing Yi-qiao 
Published: January 2022

AbstractThis meta-analysis aimed to analyze retinal microvasculature features in eyes with Behçet’s disease (BD) using optical coherence tomography angiography (OCTA). Electronic databases, including PubMed, Web of Science, Embase, and Cochrane Library, were comprehensively searched for published studies comparing retinal microvasculature characteristics between eyes with BD and controls. Continuous variables were calculated using the mean difference (MD) with 95% confidence interval (CI). Review Manager software (version 5.30) was used to conduct statistical analysis. A total of 13 eligible studies involving 599 eyes with BD and 622 control eyes were included in the meta-analysis. The pooled results showed that the macular whole enface superficial and deep vessel density (VD) values measured by OCTA were significantly lower in eyes with BD than in control eyes (superficial VD: MD = − 3.05, P < 0.00001; deep VD: MD = − 4.05, P = 0.0004). The foveal superficial and deep VD values were also significantly lower in the BD group than in the control group (superficial VD: MD = − 1.50, P = 0.009; deep VD: MD = − 4.25, −  = 0.03). Similarly, the analysis revealed a significant reduction in the parafoveal superficial and deep VD in eyes with BD than in control eyes (superficial VD: MD =  − 3.68, P < 0.00001; deep VD: MD = − 4.95, P = 0.0007). In addition, the superficial and deep foveal avascular zones (FAZs) were significantly larger in patients with BD than in controls (superficial FAZ: MD = 0.06, P = 0.02; deep FAZ: MD = 0.12, P = 0.03). The present meta-analysis found that macular whole enface VD, foveal VD, and parafoveal VD were lower in eyes with BD, and the FAZ was larger in patients with BD. The findings suggest that OCTA can assist clinicians in diagnosing and monitoring the status of patients with BD.
Removal of lead from aqueous solutions using three biosorbents of aquatic origin with the emphasis on the affective factors
Authors: Rezaei Maryam , Pourang Nima , Moradi Ali Mashinchian 
Published: January 2022

AbstractThe biosorptive potentials of three aquatics-based biosorbents, including shells of a bivalve mollusk and scales of two fish species for Pb removal from aqueous solutions were evaluated, for the first time. A Box–Behnken design with the response surface methodology was used to investigate the effects of the seven important variables (contact time, temperature, initial concentration, dosage, size, salinity and pH) on the sorption capacity of the sorbents. Among the seven studied factors, the effects of biosorbent dosage, initial concentration and pH were significant for all the response variables, while biosorbent size was not significant for any of the responses. The initial concentration was the most influential factor. The presence of Pb ions on the surfaces of the biosorbents after the adsorption was clearly confirmed by the SEM–EDX and XRF analyses. The maximum sorption capacities of the biosorbents were comparable to the literature and the descending order was as follows: scales of Rutilus kutum and Oncorhynchus mykiss and the shells of Cerastoderma glaucum. The isotherm studies revealed Langmuir model applicability for the Pb adsorption by R. kutum and O. mykiss scales, while Freundlich model was fitted to the adsorption C. glaucum shells.
Spatiotemporal change analysis of long time series inland water in Sri Lanka based on remote sensing cloud computing
Authors: Li Jianfeng , Wang Jiawei , Yang Liangyan , Ye Huping 
Published: January 2022

AbstractSri Lanka is an important hub connecting Asia-Africa-Europe maritime routes. It receives abundant but uneven spatiotemporal distribution of rainfall and has evident seasonal water shortages. Monitoring water area changes in inland lakes and reservoirs plays an important role in guiding the development and utilisation of water resources. In this study, a rapid surface water extraction model based on the Google Earth Engine remote sensing cloud computing platform was constructed. By evaluating the optimal spectral water index method, the spatiotemporal variations of reservoirs and inland lakes in Sri Lanka were analysed. The results showed that Automated Water Extraction Index (AWEIsh) could accurately identify the water boundary with an overall accuracy of 99.14%, which was suitable for surface water extraction in Sri Lanka. The area of the Maduru Oya Reservoir showed an overall increasing trend based on small fluctuations from 1988 to 2018, and the monthly area of the reservoir fluctuated significantly in 2017. Thus, water resource management in the dry zone should focus more on seasonal regulation and control. From 1995 to 2015, the number and area of lakes and reservoirs in Sri Lanka increased to different degrees, mainly concentrated in arid provinces including Northern, North Central, and Western Provinces. Overall, the amount of surface water resources have increased.