bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computer vision meets microfluidics: a label-free method for high-throughput cell analysis
Authors: Zhou Shizheng , Chen Bingbing , Fu Edgar S. , Yan Hong 
Published: September 2023

AbstractIn this paper, we review the integration of microfluidic chips and computer vision, which has great potential to advance research in the life sciences and biology, particularly in the analysis of cell imaging data. Microfluidic chips enable the generation of large amounts of visual data at the single-cell level, while computer vision techniques can rapidly process and analyze these data to extract valuable information about cellular health and function. One of the key advantages of this integrative approach is that it allows for noninvasive and low-damage cellular characterization, which is important for studying delicate or fragile microbial cells. The use of microfluidic chips provides a highly controlled environment for cell growth and manipulation, minimizes experimental variability and improves the accuracy of data analysis. Computer vision can be used to recognize and analyze target species within heterogeneous microbial populations, which is important for understanding the physiological status of cells in complex biological systems. As hardware and artificial intelligence algorithms continue to improve, computer vision is expected to become an increasingly powerful tool for in situ cell analysis. The use of microelectromechanical devices in combination with microfluidic chips and computer vision could enable the development of label-free, automatic, low-cost, and fast cellular information recognition and the high-throughput analysis of cellular responses to different compounds, for broad applications in fields such as drug discovery, diagnostics, and personalized medicine.
AIFM2 promotes hepatocellular carcinoma metastasis by enhancing mitochondrial biogenesis through activation of SIRT1/PGC-1α signaling
Authors: Guo Sanxing , Li Fengying , Liang Yixuan , Zheng Yufei , Mo Yingyi , Zhao Deyao , Jiang Zhixiong , Cui Mengmeng , Qi Lixia , Chen Jiaxing , Wan Lixin , Chen Guoyong , Wei Sidong , Yang Qi , Liu Junqi 
Published: September 2023

AbstractAIFM2 is a crucial NADH oxidase involved in the regulation of cytosolic NAD+. However, the role of AIFM2 in the progression of human cancers remains largely unexplored. Here, we elucidated the clinical implications, biological functions, and molecular mechanisms of AIFM2 in hepatocellular carcinoma (HCC). We found that AIFM2 is significantly upregulated in HCC, which is most probably caused by DNA hypomethylation and downregulation of miR-150-5p. High expression of AIFM2 is markedly associated with poor survival in patients with HCC. Knockdown of AIFM2 significantly impaired, while forced expression of AIFM2 enhanced the metastasis of HCC both in vitro and in vivo. Mechanistically, increased mitochondrial biogenesis and oxidative phosphorylation by activation of SIRT1/PGC-1α signaling contributed to the promotion of metastasis by AIFM2 in HCC. In conclusion, AIFM2 upregulation plays a crucial role in the promotion of HCC metastasis by activating SIRT1/PGC-1α signaling, which strongly suggests that AIFM2 could be targeted for the treatment of HCC.
U2AF1 pathogenic variants in myeloid neoplasms and precursor states: distribution of co-mutations and prognostic heterogeneity
Authors: Badar Talha , Vanegas Yenny A. Moreno , Nanaa Ahmad , Foran James M. , Al-Kali Aref , Mangaonkar Abhishek , Murthy Hemant , Alkhateeb Hassan B. , Viswanatha David , He Rong , Shah Mithun , Yi Cecilia Arana , Litzow Mark R. , Gangat Naseema , Tefferi Ayalew , Patnaik Mrinal M. 
Published: September 2023

AbstractWe have previously recognized the genotypic and prognostic heterogeneity of U2AF1 mutations (MT) in myelofibrosis (MF) and myelodysplastic syndromes (MDS). In the current study, we considered 179 U2AF1-mutated patients with clonal cytopenia of undetermined significance (CCUS; n = 22), MDS (n = 108), MDS/acute myeloid leukemia (AML; n = 18) and AML (n = 31). U2AF1 variants included S34 (60%), Q157 (35%), and others (5%): corresponding mutational frequencies were 45%, 55%, and 0% in CCUS; 57%, 39%, and 4% in MDS; 61%, 33%, and 6% in MDS/AML; and 55%, 35% and 10% in AML (P = 0.17, 0.36 and 0.09), respectively. Concurrent mutations included ASXL1 (37%), BCOR (19%), RUNX1 (14%), TET2 (15%), DNMT3A (10%), NRAS/KRAS (8%), TP53 (8%), JAK2 (5.5%) and SETBP1 (5%). The two most frequent U2AF1 MT were S34F (n = 97) and Q157P (n = 46); concurrent MT were more likely to be seen with the latter (91% vs 74%; P = 0.01) and abnormal karyotype with the former (70% vs 62%; P = 0.05). U2AF1 S34F MT clustered with BCOR (P = 0.04) and Q157P MT with ASXL1 (P = 0.01) and TP53 (P = 0.03). The median overall survival (OS) in months was significantly worse in AML (14.2) vs MDS/AML (27.3) vs MDS (33.7; P = 0.001); the latter had similar OS with CCUS (30.0). In morphologically high-risk disease (n = 49), defined by ≥10% blood or bone marrow blasts (i.e., AML or MDS/AML), median OS was 14.2 with Q157P vs 37.1 months in the presence of S34F (P = 0.008); transplant-adjusted multivariable analysis confirmed the detrimental impact of Q157P (P = 0.01) on survival and also identified JAK2 MT as an additional risk factor (P = 0.02). OS was favorably affected by allogeneic hematopoietic stem cell transplantation (HR: 0.16, 95% CI; 0.04-0.61, P = 0.007). The current study defines the prevalence and co-mutational profiles of U2AF1 pathogenic variants in AML, MDS/AML, MDS, and CCUS, and suggests prognostic heterogeneity in patients with ≥10% blasts.
A new vulnerability to BET inhibition due to enhanced autophagy in BRCA2 deficient pancreatic cancer
Authors: Lee EunJung , Archasappawat Suyakarn , Ji Keely , Pena Jocelyn , Fernandez-Vega Virneliz , Gangaraju Ritika , Beesabathuni Nitin Sai , Kim Martin Jean , Tian Qi , Shah Priya S. , Scampavia Louis , Spicer Timothy P. , Hwang Chang-Il 
Published: September 2023

AbstractPancreatic cancer is one of the deadliest diseases in human malignancies. Among total pancreatic cancer patients, ~10% of patients are categorized as familial pancreatic cancer (FPC) patients, carrying germline mutations of the genes involved in DNA repair pathways (e.g., BRCA2). Personalized medicine approaches tailored toward patients’ mutations would improve patients’ outcome. To identify novel vulnerabilities of BRCA2-deficient pancreatic cancer, we generated isogenic Brca2-deficient murine pancreatic cancer cell lines and performed high-throughput drug screens. High-throughput drug screening revealed that Brca2-deficient cells are sensitive to Bromodomain and Extraterminal Motif (BET) inhibitors, suggesting that BET inhibition might be a potential therapeutic approach. We found that BRCA2 deficiency increased autophagic flux, which was further enhanced by BET inhibition in Brca2-deficient pancreatic cancer cells, resulting in autophagy-dependent cell death. Our data suggests that BET inhibition can be a novel therapeutic strategy for BRCA2-deficient pancreatic cancer.
Priority areas to protect mangroves and maximise ecosystem services
Authors: Dabalà Alvise , Dahdouh-Guebas Farid , Dunn Daniel C. , Everett Jason D. , Lovelock Catherine E. , Hanson Jeffrey O. , Buenafe Kristine Camille V. , Neubert Sandra , Richardson Anthony J. 
Published: September 2023

AbstractAnthropogenic activities threaten global biodiversity and ecosystem services. Yet, area-based conservation efforts typically target biodiversity protection whilst minimising conflict with economic activities, failing to consider ecosystem services. Here we identify priority areas that maximise both the protection of mangrove biodiversity and their ecosystem services. We reveal that despite 13.5% of the mangrove distribution being currently strictly protected, all mangrove species are not adequately represented and many areas that provide disproportionally large ecosystem services are missed. Optimising the placement of future conservation efforts to protect 30% of global mangroves potentially safeguards an additional 16.3 billion USD of coastal property value, 6.1 million people, 1173.1 Tg C, and 50.7 million fisher days yr−1. Our findings suggest that there is a pressing need for including ecosystem services in protected area design and that strategic prioritisation and coordination of mangrove conservation could provide substantial benefits to human wellbeing.
Kapitza-resistance-like exciton dynamics in atomically flat MoSe2-WSe2 lateral heterojunction
Authors: Lamsaadi Hassan , Beret Dorian , Paradisanos Ioannis , Renucci Pierre , Lagarde Delphine , Marie Xavier , Urbaszek Bernhard , Gan Ziyang , George Antony , Watanabe Kenji , Taniguchi Takashi , Turchanin Andrey , Lombez Laurent , Combe Nicolas , Paillard Vincent , Poumirol Jean-Marie 
Published: September 2023

AbstractBeing able to control the neutral excitonic flux is a mandatory step for the development of future room-temperature two-dimensional excitonic devices. Semiconducting Monolayer Transition Metal Dichalcogenides (TMD-ML) with extremely robust and mobile excitons are highly attractive in this regard. However, generating an efficient and controlled exciton transport over long distances is a very challenging task. Here we demonstrate that an atomically sharp TMD-ML lateral heterostructure (MoSe2-WSe2) transforms the isotropic exciton diffusion into a unidirectional excitonic flow through the junction. Using tip-enhanced photoluminescence spectroscopy (TEPL) and a modified exciton transfer model, we show a discontinuity of the exciton density distribution on each side of the interface. We introduce the concept of exciton Kapitza resistance, by analogy with the interfacial thermal resistance referred to as Kapitza resistance. By comparing different heterostructures with or without top hexagonal boron nitride (hBN) layer, we deduce that the transport properties can be controlled, over distances far greater than the junction width, by the exciton density through near-field engineering and/or laser power density. This work provides a new approach for controlling the neutral exciton flow, which is key toward the conception of excitonic devices.
The TNFR Wengen regulates the FGF pathway by an unconventional mechanism
Authors: Letizia Annalisa , Espinàs Maria Lluisa , Giannios Panagiotis , Llimargas Marta 
Published: September 2023

AbstractUnveiling the molecular mechanisms of receptor activation has led to much understanding of development as well as the identification of important drug targets. We use the Drosophila tracheal system to study the activity of two families of widely used and conserved receptors, the TNFRs and the RTK-FGFRs. Breathless, an FGFR, controls the program of differentiation of the tracheal terminal cells in response to ligand activation. Here we identify a role for Wengen, a TNFR, in repressing the terminal cell program by regulating the MAPK pathway downstream of Breathless. We find that Wengen acts independently of both its canonical ligand and downstream pathway genes. Wengen does not stably localise at the membrane and is instead internalised—a trafficking that seems essential for activity. We show that Breathless and Wengen colocalise in intracellular vesicles and form a complex. Furthermore, Wengen regulates Breathless accumulation, possibly regulating Breathless trafficking and degradation. We propose that, in the tracheal context, Wengen interacts with Breathless to regulate its activity, and suggest that such unconventional mechanism, involving binding by TNFRs to unrelated proteins, may be a general strategy of TNFRs.
Anomalous spin current anisotropy in a noncollinear antiferromagnet
Authors: Cao Cuimei , Chen Shiwei , Xiao Rui-Chun , Zhu Zengtai , Yu Guoqiang , Wang Yangping , Qiu Xuepeng , Liu Liang , Zhao Tieyang , Shao Ding-Fu , Xu Yang , Chen Jingsheng , Zhan Qingfeng 
Published: September 2023

AbstractCubic materials host high crystal symmetry and hence are not expected to support anisotropy in transport phenomena. In contrast to this common expectation, here we report an anomalous anisotropy of spin current can emerge in the (001) film of Mn3Pt, a noncollinear antiferromagnetic spin source with face-centered cubic structure. Such spin current anisotropy originates from the intertwined time reversal-odd ($${{{{{\mathscr{T}}}}}}$$
T
-odd) and time reversal-even ($${{{{{\mathscr{T}}}}}}$$
T
-even) spin Hall effects. Based on symmetry analyses and experimental characterizations of the current-induced spin torques in Mn3Pt-based heterostructures, we find that the spin current generated by Mn3Pt (001) exhibits exotic dependences on the current direction for all the spin components, deviating from that in conventional cubic systems. We also demonstrate that such an anisotropic spin current can be used to realize low-power spintronic applications such as the efficient field-free switching of the perpendicular magnetizations.
Structural basis of the activation of TRPV5 channels by long-chain acyl-Coenzyme-A
Authors: Lee Bo-Hyun , De Jesús Pérez José J. , Moiseenkova-Bell Vera , Rohacs Tibor 
Published: September 2023

AbstractLong-chain acyl-coenzyme A (LC-CoA) is a crucial metabolic intermediate that plays important cellular regulatory roles, including activation and inhibition of ion channels. The structural basis of ion channel regulation by LC-CoA is not known. Transient receptor potential vanilloid 5 and 6 (TRPV5 and TRPV6) are epithelial calcium-selective ion channels. Here, we demonstrate that LC-CoA activates TRPV5 and TRPV6 in inside-out patches, and both exogenously supplied and endogenously produced LC-CoA can substitute for the natural ligand phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) in maintaining channel activity in intact cells. Utilizing cryo-electron microscopy, we determined the structure of LC-CoA-bound TRPV5, revealing an open configuration with LC-CoA occupying the same binding site as PI(4,5)P2 in previous studies. This is consistent with our finding that PI(4,5)P2 could not further activate the channels in the presence of LC-CoA. Our data provide molecular insights into ion channel regulation by a metabolic signaling molecule.
pH-gated nanoparticles selectively regulate lysosomal function of tumour-associated macrophages for cancer immunotherapy
Authors: Tang Mingmei , Chen Binlong , Xia Heming , Pan Meijie , Zhao Ruiyang , Zhou Jiayi , Yin Qingqing , Wan Fangjie , Yan Yue , Fu Chuanxun , Zhong Lijun , Zhang Qiang , Wang Yiguang 
Published: September 2023

AbstractTumour-associated macrophages (TAMs), as one of the most abundant tumour-infiltrating immune cells, play a pivotal role in tumour antigen clearance and immune suppression. M2-like TAMs present a heightened lysosomal acidity and protease activity, limiting an effective antigen cross-presentation. How to selectively reprogram M2-like TAMs to reinvigorate anti-tumour immune responses is challenging. Here, we report a pH-gated nanoadjuvant (PGN) that selectively targets the lysosomes of M2-like TAMs in tumours rather than the corresponding organelles from macrophages in healthy tissues. Enabled by the PGN nanotechnology, M2-like TAMs are specifically switched to a M1-like phenotype with attenuated lysosomal acidity and cathepsin activity for improved antigen cross-presentation, thus eliciting adaptive immune response and sustained tumour regression in tumour-bearing female mice. Our findings provide insights into how to specifically regulate lysosomal function of TAMs for efficient cancer immunotherapy.
Rapid design of top-performing metal-organic frameworks with qualitative representations of building blocks
Authors: Comlek Yigitcan , Pham Thang Duc , Snurr Randall Q. , Chen Wei 
Published: September 2023

AbstractData-driven materials design often encounters challenges where systems possess qualitative (categorical) information. Specifically, representing Metal-organic frameworks (MOFs) through different building blocks poses a challenge for designers to incorporate qualitative information into design optimization, and leads to a combinatorial challenge, with large number of MOFs that could be explored. In this work, we integrated Latent Variable Gaussian Process (LVGP) and Multi-Objective Batch-Bayesian Optimization (MOBBO) to identify top-performing MOFs adaptively, autonomously, and efficiently. We showcased that our method (i) requires no specific physical descriptors and only uses building blocks that construct the MOFs for global optimization through qualitative representations, (ii) is application and property independent, and (iii) provides an interpretable model of building blocks with physical justification. By searching only ~1% of the design space, LVGP-MOBBO identified all MOFs on the Pareto front and 97% of the 50 top-performing designs for the CO2 working capacity and CO2/N2 selectivity properties.
Effect of nitrogen content on corrosion behavior of high-nitrogen austenitic stainless steel
Authors: Gao Fengyin , Qiao Yanxin , Chen Jian , Yang Lanlan , Zhou Huiling , Zheng Zhibin , Zhang Lianmin 
Published: September 2023

AbstractA series of electrochemical tests combined with the techniques of scanning electron microscopy (SEM), electron backscatter diffraction (EBSD) and X-ray photoelectron spectroscopy (XPS) were used to study the effect of nitrogen content on the composition, structure and protectiveness of passive films, which were formed on the surfaces of high-nitrogen austenitic stainless steels (HNSS) in 0.5 mol/L NaCl solution. The results showed that the HNSS with higher nitrogen content had a larger proportion of low-angle grain boundaries, and it also had a lower corrosion current density in 0.5 mol/L NaCl solution and thus a lower corrosion rate. The existence of a larger proportion of stable oxides (e.g., Cr2O3) in the passive films facilitates the passivation/repassivation process and contributes to the high corrosion resistance of HNSS.
Uncovering the neurophysiology of mood, motivation and behavioral symptoms in Parkinson’s disease through intracranial recordings
Authors: Ricciardi Lucia , Apps Matthew , Little Simon 
Published: September 2023

AbstractNeuropsychiatric mood and motivation symptoms (depression, anxiety, apathy, impulse control disorders) in Parkinson’s disease (PD) are highly disabling, difficult to treat and exacerbated by current medications and deep brain stimulation therapies. High-resolution intracranial recording techniques have the potential to undercover the network dysfunction and cognitive processes that drive these symptoms, towards a principled re-tuning of circuits. We highlight intracranial recording as a valuable tool for mapping and desegregating neural networks and their contribution to mood, motivation and behavioral symptoms, via the ability to dissect multiplexed overlapping spatial and temporal neural components. This technique can be powerfully combined with behavioral paradigms and emerging computational techniques to model underlying latent behavioral states. We review the literature of intracranial recording studies investigating mood, motivation and behavioral symptomatology with reference to 1) emotional processing, 2) executive control 3) subjective valuation (reward & cost evaluation) 4) motor control and 5) learning and updating. This reveals associations between different frequency specific network activities and underlying cognitive processes of reward decision making and action control. If validated, these signals represent potential computational biomarkers of motivational and behavioural states and could lead to principled therapy development for mood, motivation and behavioral symptoms in PD.
Graph-based analysis of EEG for schizotypy classification applying flicker Ganzfeld stimulation
Authors: Zandbagleh Ahmad , Mirzakuchaki Sattar , Daliri Mohammad Reza , Sumich Alexander , Anderson John D. , Sanei Saeid 
Published: September 2023

AbstractGanzfeld conditions induce alterations in brain function and pseudo-hallucinatory experiences, particularly in people with high positive schizotypy. The current study uses graph-based parameters to investigate and classify brain networks under Ganzfeld conditions as a function of positive schizotypy. Participants from the general population (14 high schizotypy (HS), 29 low schizotypy (LS)) had an electroencephalography assessment during Ganzfeld conditions, with varying visual activation (8 frequencies of random light flicker) and soundscape-induced mood (neutral, serenity, and anxiety). Weighted functional networks were computed in six frequency sub-bands (delta, theta, alpha-low, alpha-high, beta, and gamma) as a function of light-flicker frequency and mood. The brain network was analyzed using graph theory parameters, including clustering coefficient (CC), strength, and global efficiency (GE). It was found that the LS groups had higher CC and strength than the HS groups, especially in bilateral temporal and frontotemporal brain regions. Moreover, some decreases in CC and strength measures were found in LS groups among occipital and parieto-occipital brain regions. LS groups also had significantly higher GE in all Ganzfeld conditions compared to the HS groups. The random under-sampling boosting (RUSBoost) algorithm achieved the best classification performance with an accuracy of 95.34%, specificity of 96.55%, and sensitivity of 92.85% during an anxiety-induction Ganzfeld condition. This is the first exploration of the relationship between brain functional state changes under Ganzfeld conditions in individuals who vary in positive schizotypy. The accuracy of graph-based parameters in classifying brain states as a function of schizotypy is shown, particularly for brain activity during anxiety induction, and should be investigated in psychosis.
Defining E3 ligase–substrate relationships through multiplex CRISPR screening
Authors: Timms Richard T. , Mena Elijah L. , Leng Yumei , Li Mamie Z. , Tchasovnikarova Iva A. , Koren Itay , Elledge Stephen J. 
Published: September 2023

AbstractSpecificity within the ubiquitin–proteasome system is primarily achieved through E3 ubiquitin ligases, but for many E3s their substrates—and in particular the molecular features (degrons) that they recognize—remain largely unknown. Current approaches for assigning E3s to their cognate substrates are tedious and low throughput. Here we developed a multiplex CRISPR screening platform to assign E3 ligases to their cognate substrates at scale. A proof-of-principle multiplex screen successfully performed ~100 CRISPR screens in a single experiment, refining known C-degron pathways and identifying an additional pathway through which Cul2FEM1B targets C-terminal proline. Further, by identifying substrates for Cul1FBXO38, Cul2APPBP2, Cul3GAN, Cul3KLHL8, Cul3KLHL9/13 and Cul3KLHL15, we demonstrate that the approach is compatible with pools of full-length protein substrates of varying stabilities and, when combined with site-saturation mutagenesis, can assign E3 ligases to their cognate degron motifs. Thus, multiplex CRISPR screening will accelerate our understanding of how specificity is achieved within the ubiquitin–proteasome system.