bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preparation of cationized albumin nanoparticles loaded indirubin by high pressure hemogenizer
Authors: Nekounam Houra , Dinarvand Rassoul , Khademi Rahele , Karimi Roya , Arzani Hossein , Mahmoodi Narges , Hasanzadeh Elham , Kamali Morteza , Khosravani Masood 
Published: May 2021

AbstractIndirubin can be applied as an anti-cancer drug for inhibition of brain tumors. However, its performance is reduced due to hydrophobicity. In this study, we synthesized cationic human serum albumin (CHSA) nanoparticle by a new hybrid approach for improvement the surface chemistry of albumin and investigate the amount of indirubin loaded CHSA nanoparticle. In this study, the generated mechanical force from a high-pressure homogenizer (HPH) was used to make nanoparticles with a certain size with narrow polydispersity. The results indicated that the size of indirubin loaded CHSA nanoparticles were 130 nm and their zeta potential were +9. Besides, the encapsulation efficiency and drug loading capacity were found to be 85% and 5.8 %, respectively. To the best to our knowledge, this is the first time that indirubin has been used in albumin nanoparticles. In this study, indirubin loaded CHSA nanoparticles was shown can be a potential candidate for drug delivery in the treatment of glioblastoma. Moreover, the cationized form allows the chemical agent to be transmitted to the brain.
Reduced cortico-muscular beta coupling in Parkinson’s disease predicts motor impairment
Authors: Zokaei Nahid , Quinn Andrew J , Hu Michele T , Husain Masud , van Ede Freek , Nobre Anna Christina 
Published: May 2021

AbstractLong-range communication through the motor system is thought to be facilitated by phase coupling between neural activity in the 15-30 Hz beta range. During periods of sustained muscle contraction (grip), such coupling is manifest between motor cortex and the contralateral forearm muscles – measured as the cortico-muscular coherence (CMC). We examined alterations in CMC in individuals with Parkinson’s disease (PD), while equating grip strength between individuals with PD (off their medication) and healthy control participants. We show a marked reduction in beta CMC in the PD group, even though the grip strength was comparable between the two groups. Moreover, the reduced CMC was related to motor symptoms, so that individuals with lower CMC also displayed worse motor symptoms. These findings highlight the CMC as a simple, effective, and clinically relevant neural marker of PD pathology, with the potential to aid monitoring of disease progression and the efficacy of novel treatments for PD.
Compositional data analysis of microbiome and any-omics datasets: a revalidation of the additive logratio transformation
Authors: Greenacre Michael , Martínez-Álvaro Marina , Blasco Agustín 
Published: May 2021

BackgroundMicrobiome and omics datasets are, by their intrinsic biological nature, of high dimensionality, characterized by counts of large numbers of components (microbial genes, operational taxonomic units, RNA transcripts, etc…). These data are generally regarded as compositional since the total number of counts identified within a sample are irrelevant. The central concept in compositional data analysis is the logratio transformation, the simplest being the additive logratios with respect to a fixed reference component. A full set of additive logratios is not isometric in the sense of reproducing the geometry of all pairwise logratios exactly, but their lack of isometry can be measured by the Procrustes correlation. The reference component can be chosen to maximize the Procrustes correlation between the additive logratio geometry and the exact logratio geometry, and for high-dimensional data there are many potential references. As a secondary criterion, minimizing the variance of the reference component’s log-transformed relative abundance values makes the subsequent interpretation of the logratios even easier. Finally, it is preferable that the reference component not be a rare component but well populated, and substantive biological reasons might also guide the choice if several reference candidates are identified. Results: On each of three high-dimensional datasets the additive logratio transformation was performed, using references that were identified according to the abovementioned criteria. For each dataset the compositional data structure was successfully reproduced, that is the additive logratios were very close to being isometric. The Procrustes correlations achieved for these datasets were 0.9991, 0.9977 and 0.9997, respectively. In the third case, where the objective was to distinguish between three groups of samples, the approximation was made to the restricted logratio space of the between-group variance. Conclusions: We show that for high-dimensional compositional data additive logratios can provide a valid choice as transformed variables that are (1) subcompositionally coherent, (2) explaining 100% of the total logratio variance and (3) coming measurably very close to being isometric, that is approximating almost perfectly the exact logratio geometry. The interpretation of additive logratios is simple and, when the variance of the log-transformed reference is very low, it is made even simpler since each additive logratio can be identified with a corresponding compositional component.
The autophagy initiating kinase ULK1 is required for pancreatic cancer cell growth and survival
Authors: Brun Sonja N. , Sancar Gencer , Lumibao Jan , Limpert Allison S. , Ren Huiyu , Ianniciello Angela , Tiriac Herve , Downes Michael , Engle Danielle D. , Evans Ronald M. , Cosford Nicholas D.P. , Shaw Reuben J. 
Published: May 2021

AbstractAmongst cancer subtypes, pancreatic ductal adenocarcinoma (PDA) has been demonstrated to be most sensitive to autophagy inhibition, which may be due to unique metabolic rewiring in these cells. The serine/threonine kinase ULK1 forms the catalytic center of a complex mediating the first biochemical step of autophagy. ULK1 directly recieves signals from mTORC1 and AMPK to trigger autophagy under stress and nutrient poor conditions. Studies in genetic engineered mouse models of cancer have revealed that deletion of core downstream autophagy genes (ATG5, ATG7) at the time of tumor iniation leads to a profound block in tumor progression leading to the development of autophagy inhibitors as cancer therapeutics. However, most preclinical studies and all clinical studies have relied on non-specific lysomotropic agents such as chloroquine and its derivatives, whose toxicity and off-target issues preclude further clinical development and which do not represent the impact of solely biochemically disrupting the autophagy pathway. Furthermore, druggable targets in the core autophagy pathway are quite limited, with ULK1 and ULK2 representing the only protein kinases in the pathway. Here we explore the genetic requirement for ULK1 and ULK2 in human PDA cancer cell lines and xenografts, and take advantage of new small molecule ULK1 inhibitors to demonstrate that ULK inhibition can overcome autophagy induction triggered by PDA therapeutics including chemotherapy and MEK inhibition. Finally we show that ULK inhibitors increase MHC Class I in PDA cells, suggestion a potential therapeutic avenue for such agents in combination with checkpoint immunotherapy.
The Unconventional Self-Cleavage of Selenoprotein K
Authors: Cheng Rujin , Liu Jun , Forstner Martin B. , Woodward George , Heppard Elmer , Hoffmann Peter R. , Rozovsky Sharon 
Published: May 2021

AbstractThrough known association with other proteins, human selenoprotein K (selenok) is currently implicated in the palmitoylation of proteins, degradation of misfolded proteins, innate immune response, and the life cycle of SARS-CoV-2 virus. However, neither the catalytic function of selenok’s selenocysteine (Sec), which, curiously, resides in an intrinsically disordered protein segment nor selenok’s specific role in these pathways are known to date. This report casts these questions in a new light as it describes that selenok is able -both in vitro and in vivo- to cleave some of its own peptide bonds. The cleavages not only release selenok segments that contain its reactive Sec, but as the specific cleavage sites were identified, they proved to cluster tightly near sites through which selenok interacts with protein partners. Furthermore, it is shown that selenok’s cleavage activity is neither restricted to itself nor promiscuous but selectively extends to at least one of its protein partners. Together, selenok’s cleavage ability and its features have all hallmarks of a regulatory mechanism that could play a central role in selenok’s associations with other proteins and its cellular functions overall.
Beyond BOLD: Evidence for diffusion fMRI contrast in the human brain distinct from neurovascular response
Authors: Olszowy Wiktor , Diao Yujian , Jelescu Ileana O. 
Published: May 2021

AbstractFunctional Magnetic Resonance Imaging (fMRI) is an essential method to measure brain activity non-invasively. While fMRI almost systematically relies on the blood oxygenation level-dependent (BOLD) contrast, there is an increasing interest in alternative methods that would not rely on neurovascular coupling. A promising but controversial such alternative is diffusion fMRI (dfMRI), which relies instead on dynamic fluctuations in apparent diffusion coefficient (ADC) due to microstructural changes underlying neuronal activity, i.e. neuromorphological coupling. However, it is unclear whether genuine dfMRI contrast, distinct from BOLD contamination, can be detected in the human brain in physiological conditions. Here, we present the first dfMRI study in humans attempting to minimize BOLD contamination sources and comparing functional responses at two field strengths (3T and 7T). Our study benefits from unprecedented high spatio-temporal resolution, harnesses novel denoising strategies and examines characteristics of not only task but also resting-state dfMRI. We report task-induced decrease in ADC with temporal and spatial features distinct from the BOLD response and yielding more specific activation maps. Furthermore, we report dfMRI resting-state functional connectivity which, compared to its BOLD counterpart, is essentially free from physiological artifacts and preserves positive correlations but preferentially suppresses anti-correlations, which are likely of vascular origin. A careful acquisition and processing design thus enable the detection of genuine dfMRI contrast on clinical MRI systems. As opposed to BOLD, diffusion functional contrast could be particularly well suited for low-field MRI.
A Novel Non-Invasive Epithelial Ovarian Cancer Mouse Model Of Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Authors: Alali Zahraa , Horowitz Max P. , Chau Danielle , Trestan Lexie , Hao Jing , Qi Peng , Esakov Emily L. , DeBernardo Robert L. , Yu Jennifer S. , Reizes Ofer 
Published: May 2021

ABSTRACTBackgroundHyperthermic intraperitoneal chemotherapy (HIPEC) in combination with interval cytoreductive surgery increases the overall survival of epithelial ovarian cancer (EOC) patients with advanced disease. Despite its proven benefits, the mechanism by which HIPEC extends overall survival remains unknown and current strategies to optimize HIPEC are therefore limited. A major challenge is the lack of a robust and streamlined model to investigate the mechanisms underlying HIPEC efficacy.ObjectiveTo introduce a novel murine model that can be used to enhance our understanding of HIPEC therapy.MethodID8-luc, an EOC mouse cell line, is inoculated into immunocompetent C57BL/6J mice intraperitoneally. Once tumor is detected by In Vivo Imaging System (IVIS), cisplatin (5 mg/kg) is injected intraperitoneally and superficial hyperthermia of 40°C is applied to the animal’s abdomen and pelvis using an FDA-approved hyperthermia unit (BSD500) for 20 minutes. To validate the model, four treatment conditions were tested: cisplatin and hyperthermia, cisplatin and normothermia, vehicle and hyperthermia, and vehicle and normothermia. Tumor growth was assessed over the course of treatment using IVIS optical spectrum.ResultsTumor growth in mice treated with hyperthermic cisplatin was significantly suppressed compared to mice treated with normothermic cisplatin (p < 0.05). No significant differences in tumor growth were observed in the hyperthermic vehicle and normothermic vehicle groups.ConclusionsWe developed an innovative noninvasive mouse model of HIPEC. Similar to patients with advanced ovarian cancer who are treated with HIPEC at the time of interval cytoreductive surgery, our model demonstrates that hyperthermia enhances the inhibitory effect of cisplatin on intraperitoneal tumor growth. Development of this murine model provides an opportunity to elucidate the mechanisms underlying HIPEC and offer an opportunity to test adjunct treatments in a pre-clinical setting to enhance the utility of HIPEC.
Distance-guided protein folding based on generalized descent direction
Authors: Wang Liujing , Liu Jun , Xia Yuhao , Xu Jiakang , Zhou Xiaogen , Zhang Guijun 
Published: May 2021

AbstractAdvances in the prediction of the inter-residue distance for a protein sequence have increased the accuracy to predict the correct folds of proteins with distance information. Here, we propose a distance-guided protein folding algorithm based on generalized descent direction, named GDDfold, which achieves effective structural perturbation and potential minimization in two stages. In the global stage, random-based direction is designed using evolutionary knowledge, which guides conformation population to cross potential barriers and explore conformational space rapidly in a large range. In the local stage, locally rugged potential landscape can be explored with the aid of conjugate-based direction integrated into a specific search strategy, which can improve exploitation ability. GDDfold is tested on 347 proteins of a benchmark set, 24 FM targets of CASP13 and 20 FM targets of CASP14. Results show that GDDfold correctly folds (TM-score ≥ 0.5) 316 out of 347 proteins, where 65 proteins have TM-scores that are greater than 0.8, and significantly outperforms Rosetta-dist (distance-assisted fragment assembly method) and L-BFGSfold (distance geometry optimization method). On CASP FM targets, GDDfold is comparable with five state-of-the-art methods, namely, Quark, RaptorX, Rosetta, MULTICOM and trRosetta in the CASP 13 and 14 server groups.
Differentiation of cortical brain organoids and optic nerve-like structures from retinal confluent cultures of pluripotent stem cells
Authors: Fernando Milan , Lee Scott , Wark Jesse R. , Xiao Di , Kim Hani J. , Smith Grady C. , Wong Ted , Teber Erdahl T. , Ali Robin R. , Yang Pengyi , Graham Mark E. , Gonzalez-Cordero Anai 
Published: May 2021

AbstractAdvances in the study of neurological conditions have been possible due to induced pluripotent stem cell technologies and the generation of neural cell types and organoids. Numerous studies have described the generation of neural ectoderm-derived retinal and brain structures from pluripotent stem cells. However, the field is still troubled by technical challenges, including high culture costs and organoid-to-organoid variability. Here, we describe a simple and economical protocol that reproducibly gives rise to the neural retina and cortical brain regions from confluent cultures of stem cells. The spontaneously generated cortical organoids were isolated and cultured in suspension conditions for maturation and are transcriptionally comparable to organoids generated by other methods and to human foetal cortex. Furthermore, these organoids show spontaneous functional network activity with proteomic analysis and electron microscopy demonstrating the presence of synaptic components and maturity. The generation of retinal and brain organoids in close proximity also enabled their mutual isolation. Further culture of this complex organoid system demonstrated the formation of optic nerve-like structures connecting retinal and brain organoids, which might facilitate the investigation of the mechanisms of neurological diseases of the eye and brain.
Dissecting the Cellular Landscape and Transcriptome Network in Viral Myocarditis by Single-Cell RNA Sequencing
Authors: Lasrado Ninaad , Borcherding Nicholas , Arumugam Rajkumar , Starr Timothy K. , Reddy Jay 
Published: May 2021

AbstractMyocarditis induced with Coxsackievirus B3 (CVB3) is commonly employed to study viral pathogenesis in mice. Although infectious virus is cleared after the acute phase, affected animals chronically develop the features of dilated cardiomyopathy, which may involve the mediation of immune and non-immune cells. To dissect this complexity, we performed single-cell RNA sequencing on heart cells obtained from healthy and myocarditic mice, leading us to note that myocarditic mice had significantly higher proportions of myeloid cells, CD4 and CD8 T cells, and fibroblasts, whereas NK cells, ILCs and B cells were low. While the transcriptome profiles of myeloid cells revealed detection of monocytes and macrophages of M2 phenotype with pathways important in immune metabolism and inflammation, T cells consisted of Th17 cells, CTLs, and Treg cells with transcriptome signatures critical for cytotoxic functions. Although fibroblasts detected in myocarditic mice were phenotypically heterogeneous, their transcriptomes played roles in fibrosis and regulation of inflammation and immune responses. Additionally, analysis of intercellular communication networks revealed unique interactions and signaling pathways in the cardiac cellulome, whereas myeloid cells and T cells in myocarditic mice revealed uniquely upregulated transcription factors modulating cardiac remodeling functions. Taken together, our data suggest that M2 cells, T cells, and fibroblasts may cooperatively or independently participate in the pathogenesis of viral myocarditis.
Assessment of exposure to ionizing radiation in Chernobyl tree frogs (Hyla orientalis)
Authors: Burraco Pablo , Car Clément , Bonzom Jean-Marc , Orizaola Germán 
Published: May 2021

AbstractIonizing radiation can damage organic molecules, causing detrimental effects on human and wildlife health. The accident at the Chernobyl nuclear power plant (1986) represents the largest release of radioactive material to the environment. An accurate estimation of the current exposure to radiation in wildlife, often reduced to ambient dose rate assessments, is crucial to understand the long-term impact of radiation on living organisms. Here, we present an evaluation of the sources and variation of current exposure to radiation in breeding Eastern tree frogs (Hyla orientalis) males living in the Chernobyl Exclusion Zone. Total dose rates inH. orientaliswere highly variable, although generally below widely used thresholds considered harmful for animal health. Internal exposure was the main source of absorbed dose rate (81% on average), with90Sr being the main contributor (78% of total dose rate, on average). These results highlight the importance of assessing both internal and external exposure levels in order to perform a robust evaluation of the exposure to radiation in wildlife. Further studies incorporating life-history, ecological, and evolutionary traits are needed to fully evaluate the effects that these exposure levels can have in amphibians and other taxa inhabiting radio-contaminated environments.
A close-to-native structure of the synaptonemal complex
Authors: Ortiz Rosario , Echeverría Olga M. , Masich Sergej , Höög Christer , Hernández-Hernández Abrahan 
Published: May 2021

AbstractGenetic variability in sexually reproducing organisms results from an exchange of genetic material between homologous chromosomes. The genetic exchange mechanism is dependent on the synaptonemal complex (SC), a protein structure localized between the homologous chromosomes. Current structural models of the SC are based on electron microscopy, super resolution, and expansion microscopy studies using chemical fixatives and sample dehydration of gonads, which are methodologies known to produce structural artifacts. We have developed a novel electron microscopy sample-preparation approach where pachytene cells are isolated from mouse testis by FACS, followed by cryo-fixation and cryo-substitution to achieve visualization of a close-to-native structure of the SC. We found that the central region of the SC was wider than previously recognized, and the transverse filaments more densely packed in the central region. Furthermore, we identified a structure nucleating the central element of the SC.
Firms’ performance during the COVID-19 outbreak: international evidence from 13 countries
Authors: Golubeva Olga 
Published: May 2021

PurposeThe purpose of this paper is to explore the impact of firm-, finance- and country-specific indicators to the performance of companies under the COVID-19 outbreak.Design/methodology/approachThe study uses a regression performance model for enterprises during the COVID-19 crisis. The investigation is based upon a data set of 5,730 firms from 13 countries collected by the World Bank through enterprise surveys. The author combined the analysis of traditional performance measurements with the testing of relatively novel variables.FindingsThis study confirms the significance of multiple factors for company performance: sector, size, participation in exports and market demand for firms’ products. Robust financing solutions during the coronavirus pandemic period include equity contributions, followed by firms’ cash balances and debt. Support by a government, however, has not yet been confirmed as a significant source of finance. This paper also suggests the importance of country-specific factors for the performance of enterprises, including the level of economic development and the corporate governance infrastructure.Practical implicationsThe research outcomes might assist regulatory bodies, policymakers and companies in their formulation of public and corporate governance strategies concerning future emergency preparedness and responses.Originality/valueThis paper is among the first empirical studies in the management realm that addresses the impact of COVID-19 on company performance, with cross-national empirical data.
A multi-objective approach to determining the usefulness of papers in academic search
Authors: Khalid Shah , Wu Shengli , Zhang Fang 
Published: May 2021

PurposeHow to provide the most useful papers for searchers is a key issue for academic search engines. A lot of research has been carried out to address this problem. However, when evaluating the effectiveness of an academic search engine, most of the previous investigations assume that the only concern of the user is the relevancy of the paper to the query. The authors believe that the usefulness of a paper is determined not only by its relevance to the query but also by other aspects including its publication age and impact in the research community. This is vital, especially when a large number of papers are relevant to the query.Design/methodology/approachThis paper proposes a group of metrics to measure the usefulness of a ranked list of papers. When defining these metrics, three factors, including relevance, publication age and impact, are considered at the same time. To accommodate this, the authors propose a framework to rank papers by a combination of their relevance, publication age and impact scores.FindingsThe framework is evaluated with the ACL (Association for Computational Linguistics Anthology Network) dataset. It demonstrates that the proposed ranking algorithm is effective for improving usefulness when two or three aspects of academic papers are considered at the same time, while the relevance of the retrieved papers is slightly down compared with the relevance-only retrieval.Originality/valueTo the best of the authors’ knowledge, the proposed multi-objective academic search framework is the first of its kind that is proposed and evaluated with a group of new evaluation metrics.