bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transglutaminase 2 promotes tumorigenicity of colon cancer cells by inactivation of the tumor suppressor p53
Authors: Malkomes Patrizia , Lunger Ilaria , Oppermann Elsie , Abou-El-Ardat Khalil , Oellerich Thomas , Günther Stefan , Canbulat Can , Bothur Sabrina , Schnütgen Frank , Yu Weijia , Wingert Susanne , Haetscher Nadine , Catapano Claudia , Dietz Marina S. , Heilemann Mike , Kvasnicka Hans-Michael , Holzer Katharina , Serve Hubert , Bechstein Wolf Otto , Rieger Michael A. 
Published: June 2021

AbstractDespite a high clinical need for the treatment of colorectal carcinoma (CRC) as the second leading cause of cancer-related deaths, targeted therapies are still limited. The multifunctional enzyme Transglutaminase 2 (TGM2), which harbors transamidation and GTPase activity, has been implicated in the development and progression of different types of human cancers. However, the mechanism and role of TGM2 in colorectal cancer are poorly understood. Here, we present TGM2 as a promising drug target.In primary patient material of CRC patients, we detected an increased expression and enzymatic activity of TGM2 in colon cancer tissue in comparison to matched normal colon mucosa cells. The genetic ablation of TGM2 in CRC cell lines using shRNAs or CRISPR/Cas9 inhibited cell expansion and tumorsphere formation. In vivo, tumor initiation and growth were reduced upon genetic knockdown of TGM2 in xenotransplantations. TGM2 ablation led to the induction of Caspase-3-driven apoptosis in CRC cells. Functional rescue experiments with TGM2 variants revealed that the transamidation activity is critical for the pro-survival function of TGM2. Transcriptomic and protein–protein interaction analyses applying various methods including super-resolution and time-lapse microscopy showed that TGM2 directly binds to the tumor suppressor p53, leading to its inactivation and escape of apoptosis induction.We demonstrate here that TGM2 is an essential survival factor in CRC, highlighting the therapeutic potential of TGM2 inhibitors in CRC patients with high TGM2 expression. The inactivation of p53 by TGM2 binding indicates a general anti-apoptotic function, which may be relevant in cancers beyond CRC.
Detection of acute ventilatory problems via magnetic induction in a newborn animal model
Authors: Behr Sabrina C. , Platen Christopher , Vetter Pascal , Heussen Nicole , Leonhardt Steffen , Orlikowsky Thorsten , Heimann Konrad 
Published: June 2021

AbstractBackgroundMagnetic induction measurement (MIM) is a noninvasive method for the contactless registration of respiration in newborn piglets by using measurement coils positioned at the bottom of an incubator. Acute pulmonary problems may be determinants of poor neurological and psychomotor outcomes in preterm infants. The current study tested the detection of pulmonary ventilation disorders via MIM in 11 newborn piglets.MethodsSix measurement coils determined changes in magnetic induction, depending on the ventilation of the lung, in comparison with flow resistance. Contactless registration of induced acute pulmonary ventilation disorders (apnea, atelectasis, pneumothorax, and aspiration) was detected by MIM.ResultsAll pathologies except aspiration were detected by MIM. Significant changes occurred after induction of apnea (three coils), malposition of the tube (one coil), and pneumothorax (three coils) (p ≤ 0.05). No significant changes occurred after induction of aspiration (p = 0.12).ConclusionsMIM seems to have some potential to detect acute ventilation disorders in newborn piglets. The location of the measurement coil related to the animal’s position plays a critical role in this process. In addition to an early detection of acute pulmonary problems, potential information pointing to a therapeutic intervention, for example, inhalations or medical respiratory analepsis, may be conceivable with MIM in the future.ImpactMIM seems to be a method in which noncontact ventilation disorders of premature and mature infants can be detected.This study is an extension of the experimental setup to obtain preliminary evidence for detection of respiratory activity in neonatal piglets. For the first time, MIM is used to register acute ventilation problems of neonates.The possibility of an early detection of acute ventilation problems via MIM may provide an opportunity to receive patient-side information for therapeutical interventions like inhalations or medical respiratory analepsis.
G-MDSCs promote aging-related cardiac fibrosis by activating myofibroblasts and preventing senescence
Authors: Sun Shu-Ning , Ni Shi-Hao , Li Yue , Liu Xin , Deng Jian-Ping , Chen Zi-Xin , Li Huan , Feng Wen-Jun , Huang Yu-Sheng , Li Da-Nian , Xian Shao-Xiang , Yang Zhong-Qi , Wang Ling-Jun , Lu Lu 
Published: June 2021

AbstractAging is one of the most prominent risk factors for heart failure. Myeloid-derived suppressor cells (MDSCs) accumulate in aged tissue and have been confirmed to be associated with various aging-related diseases. However, the role of MDSCs in the aging heart remains unknown. Through RNA-seq and biochemical approaches, we found that granulocytic MDSCs (G-MDSCs) accumulated significantly in the aging heart compared with monocytic MDSCs (M-MDSCs). Therefore, we explored the effects of G-MDSCs on the aging heart. We found that the adoptive transfer of G-MDSCs of aging mice to young hearts resulted in cardiac diastolic dysfunction by inducing cardiac fibrosis, similar to that in aging hearts. S100A8/A9 derived from G-MDSCs induced inflammatory phenotypes and increased the osteopontin (OPN) level in fibroblasts. The upregulation of fibroblast growth factor 2 (FGF2) expression in fibroblasts mediated by G-MDSCs promoted antisenescence and antiapoptotic phenotypes of fibroblasts. SOX9 is the downstream gene of FGF2 and is required for FGF2-mediated and G-MDSC-mediated profibrotic effects. Interestingly, both FGF2 levels and SOX9 levels were upregulated in fibroblasts but not in G-MDSCs and were independent of S100A8/9. Therefore, a novel FGF2-SOX9 signaling axis that regulates fibroblast self-renewal and antiapoptotic phenotypes was identified. Our study revealed the mechanism by which G-MDSCs promote cardiac fibrosis via the secretion of S100A8/A9 and the regulation of FGF2-SOX9 signaling in fibroblasts during aging.
Genome-wide copy number variation analysis of hepatitis B infection in a Japanese population
Authors: Kikuchi Masataka , Kobayashi Kaori , Nishida Nao , Sawai Hiromi , Sugiyama Masaya , Mizokami Masashi , Tokunaga Katsushi , Nakaya Akihiro 
Published: June 2021

AbstractGenome-wide association studies have been performed to identify common genetic variants associated with hepatitis B (HB). However, little is known about copy number variations (CNVs) in HB. In this study, we performed a genome-wide CNV analysis between 1830 healthy controls and 1031 patients with HB infection after quality control. Using signal calling by the Axiom Analysis Suite and CNV detection by PennCNV software, we obtained a total of 4494 CNVs across all individuals. The genes with CNVs that were found only in the HB patients were associated with the immune system, such as antigen processing. A gene-level CNV association test revealed statistically significant CNVs in the contactin 6 (CNTN6) gene. Moreover, we also performed gene-level CNV association tests in disease subgroups, including hepatocellular carcinoma patients, liver cirrhosis patients, and HBV carriers, including asymptomatic carriers and patients with HBV-derived chronic hepatitis. Our findings from germline cells suggested that patient-specific CNVs may be inherent genetic risk factors for HB.
Aβ receptors specifically recognize molecular features displayed by fibril ends and neurotoxic oligomers
Authors: Amin Ladan , Harris David A. 
Published: June 2021

AbstractSeveral cell-surface receptors for neurotoxic forms of amyloid-β (Aβ) have been described, but their molecular interactions with Aβ assemblies and their relative contributions to mediating Alzheimer’s disease pathology have remained uncertain. Here, we used super-resolution microscopy to directly visualize Aβ-receptor interactions at the nanometer scale. We report that one documented Aβ receptor, PrPC, specifically inhibits the polymerization of Aβ fibrils by binding to the rapidly growing end of each fibril, thereby blocking polarized elongation at that end. PrPC binds neurotoxic oligomers and protofibrils in a similar fashion, suggesting that it may recognize a common, end-specific, structural motif on all of these assemblies. Finally, two other Aβ receptors, FcγRIIb and LilrB2, affect Aβ fibril growth in a manner similar to PrPC. Our results suggest that receptors may trap Aβ oligomers and protofibrils on the neuronal surface by binding to a common molecular determinant on these assemblies, thereby initiating a neurotoxic signal.
Nucleoside-modified VEGFC mRNA induces organ-specific lymphatic growth and reverses experimental lymphedema
Authors: Szőke Dániel , Kovács Gábor , Kemecsei Éva , Bálint László , Szoták-Ajtay Kitti , Aradi Petra , Styevkóné Dinnyés Andrea , Mui Barbara L. , Tam Ying K. , Madden Thomas D. , Karikó Katalin , Kataru Raghu P. , Hope Michael J. , Weissman Drew , Mehrara Babak J. , Pardi Norbert , Jakus Zoltán 
Published: June 2021

AbstractLack or dysfunction of the lymphatics leads to secondary lymphedema formation that seriously reduces the function of the affected organs and results in degradation of quality of life. Currently, there is no definitive treatment option for lymphedema. Here, we utilized nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNPs) encoding murine Vascular Endothelial Growth Factor C (VEGFC) to stimulate lymphatic growth and function and reduce experimental lymphedema in mouse models. We demonstrated that administration of a single low-dose of VEGFC mRNA-LNPs induced durable, organ-specific lymphatic growth and formation of a functional lymphatic network. Importantly, VEGFC mRNA-LNP treatment reversed experimental lymphedema by restoring lymphatic function without inducing any obvious adverse events. Collectively, we present a novel application of the nucleoside-modified mRNA-LNP platform, describe a model for identifying the organ-specific physiological and pathophysiological roles of the lymphatics, and propose an efficient and safe treatment option that may serve as a novel therapeutic tool to reduce lymphedema.
Molecular evidence of SARS-CoV-2 in New York before the first pandemic wave
Authors: Hernandez Matthew M. , Gonzalez-Reiche Ana S. , Alshammary Hala , Fabre Shelcie , Khan Zenab , van De Guchte Adriana , Obla Ajay , Ellis Ethan , Sullivan Mitchell J. , Tan Jessica , Alburquerque Bremy , Soto Juan , Wang Ching-Yi , Sridhar Shwetha Hara , Wang Ying-Chih , Smith Melissa , Sebra Robert , Paniz-Mondolfi Alberto E. , Gitman Melissa R. , Nowak Michael D. , Cordon-Cardo Carlos , Luksza Marta , Krammer Florian , van Bakel Harm , Simon Viviana , Sordillo Emilia Mia 
Published: June 2021

AbstractNumerous reports document the spread of SARS-CoV-2, but there is limited information on its introduction before the identification of a local case. This may lead to incorrect assumptions when modeling viral origins and transmission. Here, we utilize a sample pooling strategy to screen for previously undetected SARS-CoV-2 in de-identified, respiratory pathogen-negative nasopharyngeal specimens from 3,040 patients across the Mount Sinai Health System in New York. The patients had been previously evaluated for respiratory symptoms or influenza-like illness during the first 10 weeks of 2020. We identify SARS-CoV-2 RNA from specimens collected as early as 25 January 2020, and complete SARS-CoV-2 genome sequences from multiple pools of samples collected between late February and early March, documenting an increase prior to the later surge. Our results provide evidence of sporadic SARS-CoV-2 infections a full month before both the first officially documented case and emergence of New York as a COVID-19 epicenter in March 2020.
Clostridioides difficile specific DNA adenine methyltransferase CamA squeezes and flips adenine out of DNA helix
Authors: Zhou Jujun , Horton John R. , Blumenthal Robert M. , Zhang Xing , Cheng Xiaodong 
Published: June 2021

AbstractClostridioides difficile infections are an urgent medical problem. The newly discovered C.difficileadenine methyltransferase A (CamA) is specified by all C. difficile genomes sequenced to date (>300), but is rare among other bacteria. CamA is an orphan methyltransferase, unassociated with a restriction endonuclease. CamA-mediated methylation at CAAAAA is required for normal sporulation, biofilm formation, and intestinal colonization by C. difficile. We characterized CamA kinetic parameters, and determined its structure bound to DNA containing the recognition sequence. CamA contains an N-terminal domain for catalyzing methyl transfer, and a C-terminal DNA recognition domain. Major and minor groove DNA contacts in the recognition site involve base-specific hydrogen bonds, van der Waals contacts and the Watson-Crick pairing of a rearranged A:T base pair. These provide sufficient sequence discrimination to ensure high specificity. Finally, the surprisingly weak binding of the methyl donor S-adenosyl-l-methionine (SAM) might provide avenues for inhibiting CamA activity using SAM analogs.
MOGONET integrates multi-omics data using graph convolutional networks allowing patient classification and biomarker identification
Authors: Wang Tongxin , Shao Wei , Huang Zhi , Tang Haixu , Zhang Jie , Ding Zhengming , Huang Kun 
Published: June 2021

AbstractTo fully utilize the advances in omics technologies and achieve a more comprehensive understanding of human diseases, novel computational methods are required for integrative analysis of multiple types of omics data. Here, we present a novel multi-omics integrative method named Multi-Omics Graph cOnvolutional NETworks (MOGONET) for biomedical classification. MOGONET jointly explores omics-specific learning and cross-omics correlation learning for effective multi-omics data classification. We demonstrate that MOGONET outperforms other state-of-the-art supervised multi-omics integrative analysis approaches from different biomedical classification applications using mRNA expression data, DNA methylation data, and microRNA expression data. Furthermore, MOGONET can identify important biomarkers from different omics data types related to the investigated biomedical problems.
Two decades of neuroscience publication trends in Africa
Authors: Maina M. B. , Ahmad U. , Ibrahim H. A. , Hamidu S. K. , Nasr F. E. , Salihu A. T. , Abushouk A. I. , Abdurrazak M. , Awadelkareem M. A. , Amin A. , Imam A. , Akinrinade I. D. , Yakubu A. H. , Azeez I. A. , Mohammed Y. G. , Adamu A. A. , Ibrahim H. B. , Bukar A. M. , Yaro A. U. , Goni B. W. , Prieto-Godino L. L. , Baden T. 
Published: June 2021

AbstractNeuroscience research in Africa remains sparse. Devising new policies to boost Africa’s neuroscience landscape is imperative, but these must be based on accurate data on research outputs which is largely lacking. Such data must reflect the heterogeneity of research environments across the continent’s 54 countries. Here, we analyse neuroscience publications affiliated with African institutions between 1996 and 2017. Of 12,326 PubMed indexed publications, 5,219 show clear evidence that the work was performed in Africa and led by African-based researchers - on average ~5 per country and year. From here, we extract information on journals and citations, funding, international coauthorships and techniques used. For reference, we also extract the same metrics from 220 randomly selected publications each from the UK, USA, Australia, Japan and Brazil. Our dataset provides insights into the current state of African neuroscience research in a global context.
Deep learning connects DNA traces to transcription to reveal predictive features beyond enhancer–promoter contact
Authors: Rajpurkar Aparna R. , Mateo Leslie J. , Murphy Sedona E. , Boettiger Alistair N. 
Published: June 2021

AbstractChromatin architecture plays an important role in gene regulation. Recent advances in super-resolution microscopy have made it possible to measure chromatin 3D structure and transcription in thousands of single cells. However, leveraging these complex data sets with a computationally unbiased method has been challenging. Here, we present a deep learning-based approach to better understand to what degree chromatin structure relates to transcriptional state of individual cells. Furthermore, we explore methods to “unpack the black box” to determine in an unbiased manner which structural features of chromatin regulation are most important for gene expression state. We apply this approach to an Optical Reconstruction of Chromatin Architecture dataset of the Bithorax gene cluster inDrosophilaand show it outperforms previous contact-focused methods in predicting expression state from 3D structure. We find the structural information is distributed across the domain, overlapping and extending beyond domains identified by prior genetic analyses. Individual enhancer-promoter interactions are a minor contributor to predictions of activity.
Saturated free fatty acids and association with memory formation
Authors: Wallis Tristan P. , Venkatesh Bharat G. , Narayana Vinod K. , Kvaskoff David , Ho Alan , Sullivan Robert K. , Windels François , Sah Pankaj , Meunier Frédéric A. 
Published: June 2021

AbstractPolyunsaturated free fatty acids (FFAs) such as arachidonic acid, released by phospholipase activity on membrane phospholipids, have long been considered beneficial for learning and memory and are known modulators of neurotransmission and synaptic plasticity. However, the precise nature of other FFA and phospholipid changes in specific areas of the brain during learning is unknown. Here, using a targeted lipidomics approach to characterise FFAs and phospholipids across the rat brain, we demonstrated that the highest concentrations of these analytes were found in areas of the brain classically involved in fear learning and memory, such as the amygdala. Auditory fear conditioning led to an increase in saturated (particularly myristic and palmitic acids) and to a lesser extent unsaturated FFAs (predominantly arachidonic acid) in the amygdala and prefrontal cortex. Both fear conditioning and changes in FFA required activation of NMDA receptors. These results suggest a role for saturated FFAs in memory acquisition.
Mechanistic data-driven prediction of as-built mechanical properties in metal additive manufacturing
Authors: Xie Xiaoyu , Bennett Jennifer , Saha Sourav , Lu Ye , Cao Jian , Liu Wing Kam , Gan Zhengtao 
Published: June 2021

AbstractMetal additive manufacturing provides remarkable flexibility in geometry and component design, but localized heating/cooling heterogeneity leads to spatial variations of as-built mechanical properties, significantly complicating the materials design process. To this end, we develop a mechanistic data-driven framework integrating wavelet transforms and convolutional neural networks to predict location-dependent mechanical properties over fabricated parts based on process-induced temperature sequences, i.e., thermal histories. The framework enables multiresolution analysis and importance analysis to reveal dominant mechanistic features underlying the additive manufacturing process, such as critical temperature ranges and fundamental thermal frequencies. We systematically compare the developed approach with other machine learning methods. The results demonstrate that the developed approach achieves reasonably good predictive capability using a small amount of noisy experimental data. It provides a concrete foundation for a revolutionary methodology that predicts spatial and temporal evolution of mechanical properties leveraging domain-specific knowledge and cutting-edge machine and deep learning technologies.
Trends in the hyperfine interactions of magnetic adatoms on thin insulating layers
Authors: Shehada Sufyan , dos Santos Dias Manuel , Guimarães Filipe Souza Mendes , Abusaa Muayad , Lounis Samir 
Published: June 2021

AbstractNuclear spins are among the potential candidates prospected for quantum information technology. A recent breakthrough enabled to atomically resolve their interaction with the electron spin, the so-called hyperfine interaction, within individual atoms utilizing scanning tunneling microscopy (STM). Intriguingly, this was only realized for a few species put on a two-layers thick MgO. Here, we systematically quantify from first-principles the hyperfine interactions of the whole series of 3d transition adatoms deposited on various thicknesses of MgO, NaF, NaCl, h–BN, and Cu2N films. We identify the adatom-substrate complexes with the largest hyperfine interactions and unveil the main trends and exceptions. We reveal the core mechanisms at play, such as the interplay of the local bonding geometry and the chemical nature of the thin films, which trigger transitions between high- and low-spin states accompanied with subtle internal rearrangements of the magnetic electrons. By providing a general map of hyperfine interactions, our work has immediate implications in future STM investigations aiming at detecting and realizing quantum concepts hinging on nuclear spins.
Full daylight quantum-key-distribution at 1550 nm enabled by integrated silicon photonics
Authors: Avesani M. , Calderaro L. , Schiavon M. , Stanco A. , Agnesi C. , Santamato A. , Zahidy M. , Scriminich A. , Foletto G. , Contestabile G. , Chiesa M. , Rotta D. , Artiglia M. , Montanaro A. , Romagnoli M. , Sorianello V. , Vedovato F. , Vallone G. , Villoresi P. 
Published: June 2021

AbstractThe future envisaged global-scale quantum-communication network will comprise various nodes interconnected via optical fibers or free-space channels, depending on the link distance. The free-space segment of such a network should guarantee certain key requirements, such as daytime operation and the compatibility with the complementary telecom-based fiber infrastructure. In addition, space-to-ground links will require the capability of designing light and compact quantum devices to be placed in orbit. For these reasons, investigating available solutions matching all the above requirements is still necessary. Here we present a full prototype for daylight quantum key distribution at 1550 nm exploiting an integrated silicon-photonics chip as state encoder. We tested our prototype in the urban area of Padua (Italy) over a 145 m-long free-space link, obtaining a quantum bit error rate around 0.5% and an averaged secret key rate of 30 kbps during a whole sunny day (from 11:00 to 20:00). The developed chip represents a cost-effective solution for portable free-space transmitters and a promising resource to design quantum optical payloads for future satellite missions.