bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional regulation and chromatin dynamics at DNA double-strand breaks
Authors: Min Sunwoo , Ji Jae-Hoon , Heo Yungyeong , Cho Hyeseong 
Published: October 2022

AbstractIn eukaryotic cells, DNA damage can occur at any time and at any chromatin locus, including loci at which active transcription is taking place. DNA double-strand breaks affect chromatin integrity and elicit a DNA damage response to facilitate repair of the DNA lesion. Actively transcribed genes near DNA lesions are transiently suppressed by crosstalk between DNA damage response factors and polycomb repressive complexes. Epigenetic modulation of the chromatin environment also contributes to efficient DNA damage response signaling and transcriptional repression. On the other hand, RNA transcripts produced in the G1 phase, as well as the active chromatin context of the lesion, appear to drive homologous recombination repair. Here, we discuss how the ISWI family of chromatin remodeling factors coordinates the DNA damage response and transcriptional repression, especially in transcriptionally active regions, highlighting the direct modulation of the epigenetic environment.
Formation and fluorescent mechanism of red emissive carbon dots from o-phenylenediamine and catechol system
Authors: Li Pengfei , Xue Shanshan , Sun Lu , Zong Xupeng , An Li , Qu Dan , Wang Xiayan , Sun Zaicheng 
Published: October 2022

AbstractCarbon dots (CDs) as the advancing fluorescent carbon nanomaterial have superior potential and prospective. However, the ambiguous photoluminescence (PL) mechanism and intricate structure-function relationship become the greatest hindrances in the development and applications of CDs. Herein, red emissive CDs were synthesized in high yield from o-phenylenediamine (oPD) and catechol (CAT). The PL mechanism of the CDs is considered as the molecular state fluorophores because 5,14-dihydroquinoxalino[2,3-b] phenazine (DHQP) is separated and exhibits the same PL properties and behavior as the CDs. These include the peak position and shape of the PL emission and PL excitation and the emission dependence on pH and solvent polarity. Both of them display close PL lifetime decays. Based on these, we deduce that DHQP is the fluorophore of the red emissive CDs and the PL mechanism of CDs is similar to DHQP. During the PL emission of CDs, the electron of the molecule state can transfer to CDs. The formation process of DHQP is further confirmed by the reaction intermediates (phthalazine, dimers) and oPD. These findings provide insights into the PL mechanism of this type of CDs and may guide the further development of tunable CDs for tailored properties.
Addictive and other mental disorders: a call for a standardized definition of dual disorders
Authors: Szerman Nestor , Torrens Marta , Maldonado Rafael , Balhara Yatan Pal Singh , Salom Caroline , Maremmani Icro , Sher Leo , Didia-Attas Javier , Chen Jun , Baler Ruben ,   World Association on Dual Disorders (WADD)
Published: October 2022

AbstractThe persistent difficulty in conceptualizing the relationship between addictive and other mental disorders stands out among the many challenges faced by the field of Psychiatry. The different philosophies and schools of thought about, and the sheer complexity of these highly prevalent clinical conditions make progress inherently difficult, not to mention the profusion of competing and sometimes contradictory terms that unnecessarily exacerbate the challenge. The lack of a standardized term adds confusion, fuels stigma, and contributes to a “wrong door syndrome” that captures the difficulty of not only diagnosing but also treating addictive and other mental disorders in an integrated manner. The World Association on Dual Disorders (WADD) proposes the adoption of the term “Dual Disorder” which, while still arbitrary, would help harmonize various clinical and research efforts by rallying around a single, more accurate, and less stigmatizing designation.
c-Mpl-del, a c-Mpl alternative splicing isoform, promotes AMKL progression and chemoresistance
Authors: Li Fei , Xiong Yuanyan , Yang Mo , Chen Peiling , Zhang Jingkai , Wang Qiong , Xu Miao , Wang Yiming , He Zuyong , Zhao Xin , Huang Junyu , Gu Xiaoqiong , Zhang Li , Sun Rui , Sun Xunsha , Li Jingyao , Ou Jinxin , Xu Ting , Huang Xueying , Cao Yange , Xu Xiaohong Ruby , Karakas Danielle , Li June , Ni Heyu , Zhang Qing 
Published: October 2022

AbstractAcute megakaryocytic leukemia (AMKL) is a clinically heterogeneous subtype of acute myeloid leukemia characterized by unrestricted megakaryoblast proliferation and poor prognosis. Thrombopoietin receptor c-Mpl is a primary regulator of megakaryopoeisis and a potent mitogenic receptor. Aberrant c-Mpl signaling has been implicated in a myriad of myeloid proliferative disorders, some of which can lead to AMKL, however, the role of c-Mpl in AMKL progression remains largely unexplored. Here, we identified increased expression of a c-Mpl alternative splicing isoform, c-Mpl-del, in AMKL patients. We found that c-Mpl-del expression was associated with enhanced AMKL cell proliferation and chemoresistance, and decreased survival in xenografted mice, while c-Mpl-del knockdown attenuated proliferation and restored apoptosis. Interestingly, we observed that c-Mpl-del exhibits preferential utilization of phosphorylated c-Mpl-del C-terminus Y607 and biased activation of PI3K/AKT pathway, which culminated in upregulation of GATA1 and downregulation of DDIT3-related apoptotic responses conducive to AMKL chemoresistance and proliferation. Thus, this study elucidates the critical roles of c-Mpl alternative splicing in AMKL progression and drug resistance, which may have important diagnostic and therapeutic implications for leukemia accelerated by c-Mpl-del overexpression.
Conserved signalling components coordinate epidermal patterning and cuticle deposition in barley
Authors: Liu Linsan , Jose Sarah B. , Campoli Chiara , Bayer Micha M. , Sánchez-Diaz Miguel A. , McAllister Trisha , Zhou Yichun , Eskan Mhmoud , Milne Linda , Schreiber Miriam , Batstone Thomas , Bull Ian D. , Ramsay Luke , von Wettstein-Knowles Penny , Waugh Robbie , Hetherington Alistair M. , McKim Sarah M. 
Published: October 2022

AbstractFaced with terrestrial threats, land plants seal their aerial surfaces with a lipid-rich cuticle. To breathe, plants interrupt their cuticles with adjustable epidermal pores, called stomata, that regulate gas exchange, and develop other specialised epidermal cells such as defensive hairs. Mechanisms coordinating epidermal features remain poorly understood. Addressing this, we studied two loci whose allelic variation causes both cuticular wax-deficiency and misarranged stomata in barley, identifying the underlying genes,Cer-g/HvYDA1, encoding a YODA-like (YDA) MAPKKK, andCer-s/HvBRX-Solo, encoding a single BREVIS-RADIX (BRX) domain protein. Both genes control cuticular integrity, the spacing and identity of epidermal cells, and barley’s distinctive epicuticular wax blooms, as well as stomatal patterning in elevated CO2conditions. Genetic analyses revealed epistatic and modifying relationships betweenHvYDA1andHvBRX-Solo, intimating that their products participate in interacting pathway(s) linking epidermal patterning with cuticular properties in barley. This may represent a mechanism for coordinating multiple adaptive features of the land plant epidermis in a cultivated cereal.
Continuous biomarker monitoring with single molecule resolution by measuring free particle motion
Authors: Buskermolen Alissa D. , Lin Yu-Ting , van Smeden Laura , van Haaften Rik B. , Yan Junhong , Sergelen Khulan , de Jong Arthur M. , Prins Menno W. J. 
Published: October 2022

AbstractThere is a need for sensing technologies that can continuously monitor concentration levels of critical biomolecules in applications such as patient care, fundamental biological research, biotechnology and food industry, as well as the environment. However, it is fundamentally difficult to develop measurement technologies that are not only sensitive and specific, but also allow monitoring over a broad concentration range and over long timespans. Here we describe a continuous biomolecular sensing methodology based on the free diffusion of biofunctionalized particles hovering over a sensor surface. The method records digital events due to single-molecule interactions and enables biomarker monitoring at picomolar to micromolar concentrations without consuming any reagents. We demonstrate the affinity-based sensing methodology for DNA-based sandwich and competition assays, and for an antibody-based cortisol assay. Additionally, the sensor can be dried, facilitating storage over weeks while maintaining its sensitivity. We foresee that this will enable the development of continuous monitoring sensors for applications in fundamental research, for studies on organs on a chip, for the monitoring of patients in critical care, and for the monitoring of industrial processes and bioreactors as well as ecological systems.
Solvent-free protic liquid enabling batteries operation at an ultra-wide temperature range
Authors: Liao Mochou , Ji Xiao , Cao Yongjie , Xu Jie , Qiu Xuan , Xie Yihua , Wang Fei , Wang Chunsheng , Xia Yongyao 
Published: October 2022

AbstractNowadays, electrolytes for commercial batteries are mostly liquid solutions composed of solvent and salt to migrate the ions. However, solvents of the electrolyte bring several inherent limitations, either the electrochemical window, working temperature, volatility or flammability. Herein, we report polyphosphoric acid as a solvent-free protic liquid electrolyte, which excludes the demerits of solvent and exhibits unprecedented superiorities, including nonflammability, wider electrochemical stability window (>2.5 V) than aqueous electrolyte, low volatility and wide working temperature range (>400 °C). The proton conductive electrolyte enables MoO3/LiVPO4F rocking-chair battery to operate well in a wide temperature range from 0 °C to 250 °C and deliver a high power density of 4975 W kg−1 at a high temperature of 100 °C. The solvent-free electrolyte could provide a viable route for the stable and safe batteries working under harsh conditions, opening up a route towards designing wide-temperature electrolytes.
Caldesmon controls stress fiber force-balance through dynamic cross-linking of myosin II and actin-tropomyosin filaments
Authors: Kokate Shrikant B. , Ciuba Katarzyna , Tran Vivien D. , Kumari Reena , Tojkander Sari , Engel Ulrike , Kogan Konstantin , Kumar Sanjay , Lappalainen Pekka 
Published: October 2022

AbstractContractile actomyosin bundles are key force-producing and mechanosensing elements in muscle and non-muscle tissues. Whereas the organization of muscle myofibrils and mechanism regulating their contractility are relatively well-established, the principles by which myosin-II activity and force-balance are regulated in non-muscle cells have remained elusive. We show that Caldesmon, an important component of smooth muscle and non-muscle cell actomyosin bundles, is an elongated protein that functions as a dynamic cross-linker between myosin-II and tropomyosin-actin filaments. Depletion of Caldesmon results in aberrant lateral movement of myosin-II filaments along actin bundles, leading to irregular myosin distribution within stress fibers. This manifests as defects in stress fiber network organization and contractility, and accompanied problems in cell morphogenesis, migration, invasion, and mechanosensing. These results identify Caldesmon as critical factor that ensures regular myosin-II spacing within non-muscle cell actomyosin bundles, and reveal how stress fiber networks are controlled through dynamic cross-linking of tropomyosin-actin and myosin filaments.
Reducing Akt2 in retinal pigment epithelial cells causes a compensatory increase in Akt1 and attenuates diabetic retinopathy
Authors: Liu Haitao , Stepicheva Nadezda A. , Ghosh Sayan , Shang Peng , Chowdhury Olivia , Daley Rachel A. , Yazdankhah Meysam , Gupta Urvi , Hose Stacey L. , Valapala Mallika , Fitting Christopher Scott , Strizhakova Anastasia , Shan Yang , Feenstra Derrick , Sahel José-Alain , Jayagopal Ashwath , Handa James T. , Zigler J. Samuel , Fort Patrice E. , Sodhi Akrit , Sinha Debasish 
Published: October 2022

AbstractThe retinal pigment epithelium (RPE) plays an important role in the development of diabetic retinopathy (DR), a leading cause of blindness worldwide. Here we set out to explore the role of Akt2 signaling—integral to both RPE homeostasis and glucose metabolism—to DR. Using human tissue and genetically manipulated mice (including RPE-specific conditional knockout (cKO) and knock-in (KI) mice), we investigate whether Akts in the RPE influences DR in models of diabetic eye disease. We found that Akt1 and Akt2 activities were reciprocally regulated in the RPE of DR donor tissue and diabetic mice. Akt2 cKO attenuated diabetes-induced retinal abnormalities through a compensatory upregulation of phospho-Akt1 leading to an inhibition of vascular injury, inflammatory cytokine release, and infiltration of immune cells mediated by the GSK3β/NF-κB signaling pathway; overexpression of Akt2 has no effect. We propose that targeting Akt1 activity in the RPE may be a novel therapy for treating DR.
Guidance landscapes unveiled by quantitative proteomics to control reinnervation in adult visual system
Authors: Vilallongue Noemie , Schaeffer Julia , Hesse Anne-Marie , Delpech Céline , Blot Béatrice , Paccard Antoine , Plissonnier Elise , Excoffier Blandine , Couté Yohann , Belin Stephane , Nawabi Homaira 
Published: October 2022

AbstractIn the injured adult central nervous system (CNS), activation of pro-growth molecular pathways in neurons leads to long-distance regeneration. However, most regenerative fibers display guidance defects, which prevent reinnervation and functional recovery. Therefore, the molecular characterization of the proper target regions of regenerative axons is essential to uncover the modalities of adult reinnervation. In this study, we use mass spectrometry (MS)-based quantitative proteomics to address the proteomes of major nuclei of the adult visual system. These analyses reveal that guidance-associated molecules are expressed in adult visual targets. Moreover, we show that bilateral optic nerve injury modulates the expression of specific proteins. In contrast, the expression of guidance molecules remains steady. Finally, we show that regenerative axons are able to respond to guidance cues ex vivo, suggesting that these molecules possibly interfere with brain target reinnervation in adult. Using a long-distance regeneration model, we further demonstrate that the silencing of specific guidance signaling leads to rerouting of regenerative axons in vivo. Altogether, our results suggest ways to modulate axon guidance of regenerative neurons to achieve circuit repair in adult.
The Hippo pathway links adipocyte plasticity to adipose tissue fibrosis
Authors: Shen Hongyu , Huang Xun , Zhao Yiheng , Wu Dongmei , Xue Kaili , Yao Jingfei , Wang Yushuang , Tang Nan , Qiu Yifu 
Published: October 2022

AbstractFibrosis disrupts adipose tissue (AT) homeostasis and exacerbates metabolic dysfunction upon chronic caloric excess. The molecular mechanisms linking adipocyte plasticity to AT fibrosis are largely unknown. Here we show that the Hippo pathway is coupled with TGFβ signaling to orchestrate a cellular and/or functional shift of adipocytes from energy storage to extracellular matrix (ECM) remodeling in AT fibrosis. We found that Lats1/2-knockout adipocytes could dedifferentiate into DPP4+ progenitor cells and convert to DPP4− myofibroblasts upon TGFβ stimulation. On the other hand, Hippo pathway inhibition during obesity impaired adipocyte identity while promoted ECM remodeling activity of adipocytes. Macrophages recruited by CCL2 produced TGFβ to accelerate AT fibrosis. YAP and TAZ, the Hippo downstream effectors, enhanced SMAD2 stability to promote fibrotic responses. Importantly, inhibition of YAP/TAZ activity in obese mice markedly relieved AT fibrosis and improved metabolic homeostasis. Together, our findings identify the Hippo pathway as a molecular switch in the initiation and development of AT fibrosis, implying it as a therapeutic target.
[2]-Ladderanes as isosteres for meta-substituted aromatic rings and rigidified cyclohexanes
Authors: Epplin Rachel C. , Paul Shashwati , Herter Loïc , Salome Christophe , Hancock Erin N. , Larrow Jay F. , Baum Erich W. , Dunstan David R. , Ginsburg-Moraff Carol , Fessard Thomas C. , Brown M. Kevin 
Published: October 2022

AbstractAromatic ring isosteres and rigidified saturated hydrocarbons are important motifs to enable drug discovery. Herein we disclose [2]-ladderanes as a class of meta-substituted aromatic ring isosteres and rigidified cyclohexanes. A straightforward synthesis of the building blocks is presented along with representative derivatization. Preliminary studies reveal that the [2]-ladderanes offer similar metabolic and physicochemical properties thus establishing this class of molecules as interesting motifs.
Recommender system for discovery of inorganic compounds
Authors: Hayashi Hiroyuki , Seko Atsuto , Tanaka Isao 
Published: October 2022

AbstractA recommender system based on experimental databases is useful for the efficient discovery of inorganic compounds. Here, we review studies on the discovery of as-yet-unknown compounds using recommender systems. The first method used compositional descriptors made up of elemental features. Chemical compositions registered in the inorganic crystal structure database (ICSD) were supplied to machine learning for binary classification. The other method did not use any descriptors, but a tensor decomposition technique was adopted. The predictive performance for currently unknown chemically relevant compositions (CRCs) was determined by examining their presence in other databases. According to the recommendation, synthesis experiments of two pseudo-ternary compounds with currently unknown structures were successful. Finally, a synthesis-condition recommender system was constructed by machine learning of a parallel experimental data-set collected in-house using a polymerized complex method. Recommendation scores for unexperimented conditions were then evaluated. Synthesis experiments under the targeted conditions found two yet-unknown pseudo-binary oxides.
A systematic review of brain morphometry related to deep brain stimulation outcome in Parkinson’s disease
Authors: Wang Fengting , Lai Yijie , Pan Yixin , Li Hongyang , Liu Qimin , Sun Bomin 
Published: October 2022

AbstractWhile the efficacy of deep brain stimulation (DBS) is well-established in Parkinson’s Disease (PD), the benefit of DBS varies across patients. Using imaging features for outcome prediction offers potential in improving effectiveness, whereas the value of presurgical brain morphometry, derived from the routinely used imaging modality in surgical planning, remains under-explored. This review provides a comprehensive investigation of links between DBS outcomes and brain morphometry features in PD. We systematically searched PubMed and Embase databases and retrieved 793 articles, of which 25 met inclusion criteria and were reviewed in detail. A majority of studies (24/25), including 1253 of 1316 patients, focused on the outcome of DBS targeting the subthalamic nucleus (STN), while five studies included 57 patients receiving globus pallidus internus (GPi) DBS. Accumulated evidence showed that the atrophy of motor cortex and thalamus were associated with poor motor improvement, other structures such as the lateral-occipital cortex and anterior cingulate were also reported to correlated with motor outcome. Regarding non-motor outcomes, decreased volume of the hippocampus was reported to correlate with poor cognitive outcomes. Structures such as the thalamus, nucleus accumbens, and nucleus of basalis of Meynert were also reported to correlate with cognitive functions. Caudal middle frontal cortex was reported to have an impact on postsurgical psychiatric changes. Collectively, the findings of this review emphasize the utility of brain morphometry in outcome prediction of DBS for PD. Future efforts are needed to validate the findings and demonstrate the feasibility of brain morphometry in larger cohorts.
Longitudinal bioluminescence imaging to monitor breast tumor growth and treatment response using the chick chorioallantoic membrane model
Authors: Javed Sumreen , Soukhtehzari Sepideh , Fernandes Nazarine , Williams Karla C. 
Published: October 2022

AbstractThe development of successful treatment regimens for breast cancer requires strong pre-clinical data generated in physiologically relevant pre-clinical models. Here we report the development of the chick embryo chorioallantoic membrane (CAM) model to study tumor growth and angiogenesis using breast cancer cell lines. MDA-MB-231 and MCF7 tumor cell lines were engrafted onto the chick embryo CAM to study tumor growth and treatment response. Tumor growth was evaluated through bioluminescence imaging and a significant increase in tumor size and vascularization was found over a 9-day period. We then evaluated the impact of anti-angiogenic drugs, axitinib and bevacizumab, on tumor growth and angiogenesis. Drug treatment significantly reduced tumor vascularization and size. Overall, our findings demonstrate that the chick embryo CAM is a clinically relevant model to monitor therapeutic response in breast cancer and can be used as a platform for drug screening to evaluate not only gross changes in tumor burden but physiological processes such as angiogenesis.
Ultrafast laser filament-induced fluorescence for detecting uranium stress in Chlamydomonas reinhardtii
Authors: Finney Lauren A. , Skrodzki Patrick J. , Peskosky Nicholas , Burger Milos , Nees John , Krushelnick Karl , Jovanovic Igor 
Published: October 2022

AbstractPlants and other photosynthetic organisms have been suggested as potential pervasive biosensors for nuclear nonproliferation monitoring. We demonstrate that ultrafast laser filament-induced fluorescence of chlorophyll in the green alga Chlamydomonas reinhardtii is a promising method for remote, in-field detection of stress from exposure to nuclear materials. This method holds an advantage over broad-area surveillance, such as solar-induced fluorescence monitoring, when targeting excitation of a specific plant would improve the detectability, for example when local biota density is low. After exposing C. reinhardtii to uranium, we find that the concentration of chlorophyll a, chlorophyll fluorescence lifetime, and carotenoid content increase. The increased fluorescence lifetime signifies a decrease in non-photochemical quenching. The simultaneous increase in carotenoid content implies oxidative stress, further confirmed by the production of radical oxygen species evidence in the steady-state absorption spectrum. This is potentially a unique signature of uranium, as previous work finds that heavy metal stress generally increases non-photochemical quenching. We identify the temporal profile of the chlorophyll fluorescence to be a distinguishing feature between uranium-exposed and unexposed algae. Discrimination of uranium-exposed samples is possible at a distance of $$\sim $$
∼
35 m with a single laser shot and a modest collection system, as determined through a combination of experiment and simulation of distance-scaled uncertainty in discriminating the temporal profiles. Illustrating the potential for remote detection, detection over 125 m would require 100 laser shots, commensurate with the detection time on the order of 1 s.