bluuebunny/crossref_metadata_2025_split huggingface dataset:
An old model with new insights: endogenous retroviruses drive the evolvement toward ASD susceptibility and hijack transcription machinery during development
Authors: Lin Chia-Wen , Ellegood Jacob , Tamada Kota , Miura Ikuo , Konda Mikiko , Takeshita Kozue , Atarashi Koji , Lerch Jason P. , Wakana Shigeharu , McHugh Thomas J. , Takumi Toru 
Published: March 2023

AbstractThe BTBR T+Itpr3tf/J (BTBR/J) strain is one of the most valid models of idiopathic autism, serving as a potent forward genetics tool to dissect the complexity of autism. We found that a sister strain with an intact corpus callosum, BTBR TF/ArtRbrc (BTBR/R), showed more prominent autism core symptoms but moderate ultrasonic communication/normal hippocampus-dependent memory, which may mimic autism in the high functioning spectrum. Intriguingly, disturbed epigenetic silencing mechanism leads to hyperactive endogenous retrovirus (ERV), a mobile genetic element of ancient retroviral infection, which increases de novo copy number variation (CNV) formation in the two BTBR strains. This feature makes the BTBR strain a still evolving multiple-loci model toward higher ASD susceptibility. Furthermore, active ERV, analogous to virus infection, evades the integrated stress response (ISR) of host defense and hijacks the transcriptional machinery during embryonic development in the BTBR strains. These results suggest dual roles of ERV in the pathogenesis of ASD, driving host genome evolution at a long-term scale and managing cellular pathways in response to viral infection, which has immediate effects on embryonic development. The wild-type Draxin expression in BTBR/R also makes this substrain a more precise model to investigate the core etiology of autism without the interference of impaired forebrain bundles as in BTBR/J.
Emerging phagocytosis checkpoints in cancer immunotherapy
Authors: Liu Yu’e , Wang Yanjin , Yang Yanrong , Weng Linjun , Wu Qi , Zhang Jin , Zhao Pengcheng , Fang Lan , Shi Yufeng , Wang Ping 
Published: March 2023

AbstractCancer immunotherapy, mainly including immune checkpoints-targeted therapy and the adoptive transfer of engineered immune cells, has revolutionized the oncology landscape as it utilizes patients’ own immune systems in combating the cancer cells. Cancer cells escape immune surveillance by hijacking the corresponding inhibitory pathways via overexpressing checkpoint genes. Phagocytosis checkpoints, such as CD47, CD24, MHC-I, PD-L1, STC-1 and GD2, have emerged as essential checkpoints for cancer immunotherapy by functioning as “don’t eat me” signals or interacting with “eat me” signals to suppress immune responses. Phagocytosis checkpoints link innate immunity and adaptive immunity in cancer immunotherapy. Genetic ablation of these phagocytosis checkpoints, as well as blockade of their signaling pathways, robustly augments phagocytosis and reduces tumor size. Among all phagocytosis checkpoints, CD47 is the most thoroughly studied and has emerged as a rising star among targets for cancer treatment. CD47-targeting antibodies and inhibitors have been investigated in various preclinical and clinical trials. However, anemia and thrombocytopenia appear to be formidable challenges since CD47 is ubiquitously expressed on erythrocytes. Here, we review the reported phagocytosis checkpoints by discussing their mechanisms and functions in cancer immunotherapy, highlight clinical progress in targeting these checkpoints and discuss challenges and potential solutions to smooth the way for combination immunotherapeutic strategies that involve both innate and adaptive immune responses.
Non-canonical functions of SNAIL drive context-specific cancer progression
Authors: Paul Mariel C. , Schneeweis Christian , Falcomatà Chiara , Shan Chuan , Rossmeisl Daniel , Koutsouli Stella , Klement Christine , Zukowska Magdalena , Widholz Sebastian A. , Jesinghaus Moritz , Heuermann Konstanze K. , Engleitner Thomas , Seidler Barbara , Sleiman Katia , Steiger Katja , Tschurtschenthaler Markus , Walter Benjamin , Weidemann Sören A. , Pietsch Regina , Schnieke Angelika , Schmid Roland M. , Robles Maria S. , Andrieux Geoffroy , Boerries Melanie , Rad Roland , Schneider Günter , Saur Dieter 
Published: March 2023

AbstractSNAIL is a key transcriptional regulator in embryonic development and cancer. Its effects in physiology and disease are believed to be linked to its role as a master regulator of epithelial-to-mesenchymal transition (EMT). Here, we report EMT-independent oncogenic SNAIL functions in cancer. Using genetic models, we systematically interrogated SNAIL effects in various oncogenic backgrounds and tissue types. SNAIL-related phenotypes displayed remarkable tissue- and genetic context-dependencies, ranging from protective effects as observed in KRAS- or WNT-driven intestinal cancers, to dramatic acceleration of tumorigenesis, as shown in KRAS-induced pancreatic cancer. Unexpectedly, SNAIL-driven oncogenesis was not associated with E-cadherin downregulation or induction of an overt EMT program. Instead, we show that SNAIL induces bypass of senescence and cell cycle progression through p16INK4A-independent inactivation of the Retinoblastoma (RB)-restriction checkpoint. Collectively, our work identifies non-canonical EMT-independent functions of SNAIL and unravel its complex context-dependent role in cancer.
Engineering zero modes in transformable mechanical metamaterials
Authors: Hu Zhou , Wei Zhibo , Wang Kun , Chen Yan , Zhu Rui , Huang Guoliang , Hu Gengkai 
Published: March 2023

AbstractIn the field of flexible metamaterial design, harnessing zero modes plays a key part in enabling reconfigurable elastic properties of the metamaterial with unconventional characteristics. However, only quantitative enhancement of certain properties succeeds in most cases rather than qualitative transformation of the metamaterials’ states or/and functionalities, due to the lack of systematic designs on the corresponding zero modes. Here, we propose a 3D metamaterial with engineered zero modes, and experimentally demonstrate its transformable static and dynamic properties. All seven types of extremal metamaterials ranging from null-mode (solid state) to hexa-mode (near-gaseous state) are reported to be reversibly transformed from one state to another, which is verified by the 3D-printed Thermoplastic Polyurethanes prototypes. Tunable wave manipulations are further investigated in 1D-, 2D- and 3D-systems. Our work sheds lights on the design of flexible mechanical metamaterials, which can be potentially extended from the mechanical to the electro-magnetite, the thermal or other types.
Structural basis of peptide recognition and activation of endothelin receptors
Authors: Ji Yujie , Duan Jia , Yuan Qingning , He Xinheng , Yang Gong , Zhu Shengnan , Wu Kai , Hu Wen , Gao Tianyu , Cheng Xi , Jiang Hualiang , Eric Xu H. , Jiang Yi 
Published: March 2023

AbstractEndothelin system comprises three endogenous 21-amino-acid peptide ligands endothelin-1, -2, and -3 (ET-1/2/3), and two G protein-coupled receptor (GPCR) subtypes—endothelin receptor A (ETAR) and B (ETBR). Since ET-1, the first endothelin, was identified in 1988 as one of the most potent endothelial cell-derived vasoconstrictor peptides with long-lasting actions, the endothelin system has attracted extensive attention due to its critical role in vasoregulation and close relevance in cardiovascular-related diseases. Here we present three cryo-electron microscopy structures of ETAR and ETBR bound to ET-1 and ETBR bound to the selective peptide IRL1620. These structures reveal a highly conserved recognition mode of ET-1 and characterize the ligand selectivity by ETRs. They also present several conformation features of the active ETRs, thus revealing a specific activation mechanism. Together, these findings deepen our understanding of endothelin system regulation and offer an opportunity to design selective drugs targeting specific ETR subtypes.
Distinct roles of Arabidopsis ORC1 proteins in DNA replication and heterochromatic H3K27me1 deposition
Authors: Vergara Zaida , Gomez María S. , Desvoyes Bénédicte , Sequeira-Mendes Joana , Masoud Kinda , Costas Celina , Noir Sandra , Caro Elena , Mora-Gil Victoria , Genschik Pascal , Gutierrez Crisanto 
Published: March 2023

AbstractMost cellular proteins involved in genome replication are conserved in all eukaryotic lineages including yeast, plants and animals. However, the mechanisms controlling their availability during the cell cycle are less well defined. Here we show that the Arabidopsis genome encodes for two ORC1 proteins highly similar in amino acid sequence and that have partially overlapping expression domains but with distinct functions. The ancestralORC1bgene, present before the partial duplication of the Arabidopsis genome, has retained the canonical function in DNA replication. ORC1b is expressed in both proliferating and endoreplicating cells, accumulates during G1 and is rapidly degraded upon S-phase entry through the ubiquitin-proteasome pathway. In contrast, the duplicatedORC1agene has acquired a specialized function in heterochromatin biology. ORC1a is required for efficient deposition of the heterochromatic H3K27me1 mark by the ATXR5/6 histone methyltransferases. The distinct roles of the two ORC1 proteins may be a feature common to other organisms with duplicatedORC1genes and a major difference with animal cells.
Fully 3D-printed organic electrochemical transistors
Authors: Massetti Matteo , Zhang Silan , Harikesh Padinhare Cholakkal , Burtscher Bernhard , Diacci Chiara , Simon Daniel T. , Liu Xianjie , Fahlman Mats , Tu Deyu , Berggren Magnus , Fabiano Simone 
Published: March 2023

AbstractOrganic electrochemical transistors (OECTs) are being researched for various applications, ranging from sensors to logic gates and neuromorphic hardware. To meet the requirements of these diverse applications, the device fabrication process must be compatible with flexible and scalable digital techniques. Here, we report a direct-write additive process to fabricate fully 3D-printed OECTs, using 3D printable conducting, semiconducting, insulating, and electrolyte inks. These 3D-printed OECTs, which operate in the depletion mode, can be fabricated on flexible substrates, resulting in high mechanical and environmental stability. The 3D-printed OECTs have good dopamine biosensing capabilities (limit of detection down to 6 µM without metal gate electrodes) and show long-term (~1 h) synapse response, indicating their potential for various applications such as sensors and neuromorphic hardware. This manufacturing strategy is suitable for applications that require rapid design changes and digitally enabled direct-write techniques.
Deficiency of Perry syndrome-associated p150Glued in midbrain dopaminergic neurons leads to progressive neurodegeneration and endoplasmic reticulum abnormalities
Authors: Yu Jia , Yang Xuan , Zheng Jiayin , Sgobio Carmelo , Sun Lixin , Cai Huaibin 
Published: March 2023

AbstractMultiple missense mutations in p150Glued are linked to Perry syndrome (PS), a rare neurodegenerative disease pathologically characterized by loss of nigral dopaminergic (DAergic) neurons. Here we generated p150Glued conditional knockout (cKO) mice by deleting p150Glued in midbrain DAergic neurons. The young cKO mice displayed impaired motor coordination, dystrophic DAergic dendrites, swollen axon terminals, reduced striatal dopamine transporter (DAT), and dysregulated dopamine transmission. The aged cKO mice showed loss of DAergic neurons and axons, somatic accumulation of α-synuclein, and astrogliosis. Further mechanistic studies revealed that p150Glued deficiency in DAergic neurons led to the reorganization of endoplasmic reticulum (ER) in dystrophic dendrites, upregulation of ER tubule-shaping protein reticulon 3, accumulation of DAT in reorganized ERs, dysfunction of COPII-mediated ER export, activation of unfolded protein response, and exacerbation of ER stress-induced cell death. Our findings demonstrate the importance of p150Glued in controlling the structure and function of ER, which is critical for the survival and function of midbrain DAergic neurons in PS.
MFCSC: Novel method to calculate mismatch between functional and structural brain connectomes, and its application for detecting hemispheric functional specialisations
Authors: Civier Oren , Sourty Marion , Calamante Fernando 
Published: March 2023

AbstractWe introduce a novel connectomics method, MFCSC, that integrates information on structural connectivity (SC) from diffusion MRI tractography and functional connectivity (FC) from functional MRI, at individual subject level. The MFCSC method is based on the fact that SC only broadly predicts FC, and for each connection in the brain, the method calculates a value that quantifies the mismatch that often still exists between the two modalities. To capture underlying physiological properties, MFCSC minimises biases in SC and addresses challenges with the multimodal analysis, including by using a data-driven normalisation approach. We ran MFCSC on data from the Human Connectome Project and used the output to detect pairs of left and right unilateral connections that have distinct relationship between structure and function in each hemisphere; we suggest that this reflects cases of hemispheric functional specialisation. In conclusion, the MFCSC method provides new information on brain organisation that may not be inferred from an analysis that considers SC and FC separately.
In vivo multi-parameter mapping of the habenula using MRI
Authors: Milotta Giorgia , Green Isobel , Roiser Jonathan P. , Callaghan Martina F. 
Published: March 2023

AbstractThe habenula is a small, epithalamic brain structure situated between the mediodorsal thalamus and the third ventricle. It plays an important role in the reward circuitry of the brain and is implicated in psychiatric conditions, such as depression. The importance of the habenula for human cognition and mental health make it a key structure of interest for neuroimaging studies. However, few studies have characterised the physical properties of the human habenula using magnetic resonance imaging because its challenging visualisation in vivo, primarily due to its subcortical location and small size. To date, microstructural characterization of the habenula has focused on quantitative susceptibility mapping. In this work, we complement this previous characterisation with measures of longitudinal and effective transverse relaxation rates, proton density and magnetisation transfer saturation using a high-resolution quantitative multi-parametric mapping protocol at 3T, in a cohort of 26 healthy participants. The habenula had consistent boundaries across the various parameter maps and was most clearly visualised on the longitudinal relaxation rate maps. We have provided a quantitative multi-parametric characterisation that may be useful for future sequence optimisation to enhance visualisation of the habenula, and additionally provides reference values for future studies investigating pathological differences in habenula microstructure.
On electromagnetic head digitization in MEG and EEG
Authors: Jaiswal Amit , Nenonen Jukka , Parkkonen Lauri 
Published: March 2023

AbstractIn MEG and EEG studies, the accuracy of the head digitization impacts the co-registration between functional and structural data. The co-registration is one of the major factors that affect the spatial accuracy in MEG/EEG source imaging. Precisely digitized head-surface (scalp) points do not only improve the co-registration but can also deform a template MRI. Such an individualized-template MRI can be used for conductivity modeling in MEG/EEG source imaging if the individual’s structural MRI is unavailable. Electromagnetic tracking (EMT) systems (particularly Fastrak, Polhemus Inc., Colchester, VT, USA) have been the most common solution for digitization in MEG and EEG. However, they may occasionally suffer from ambient electromagnetic interference which makes it challenging to achieve (sub-)millimeter digitization accuracy. The current study—(i) evaluated the performance of the Fastrak EMT system under different conditions in MEG/EEG digitization, and (ii) explores the usability of two alternative EMT systems (Aurora, NDI, Waterloo, ON, Canada; Fastrak with a short-range transmitter) for digitization. Tracking fluctuation, digitization accuracy, and robustness of the systems were evaluated in several test cases using test frames and human head models. The performance of the two alternative systems was compared against the Fastrak system. The results showed that the Fastrak system is accurate and robust for MEG/EEG digitization if the recommended operating conditions are met. The Fastrak with the short-range transmitter shows comparatively higher digitization error if digitization is not carried out very close to the transmitter. The study also evinces that the Aurora system can be used for MEG/EEG digitization within a constrained range; however, some modifications would be required to make the system a practical and easy-to-use digitizer. Its real-time error estimation feature can potentially improve digitization accuracy.
Histone H3-wild type diffuse midline gliomas with H3K27me3 loss are a distinct entity with exclusive EGFR or ACVR1 mutation and differential methylation of homeobox genes
Authors: Ajuyah Pamela , Mayoh Chelsea , Lau Loretta M. S. , Barahona Paulette , Wong Marie , Chambers Hazel , Valdes-Mora Fatima , Senapati Akanksha , Gifford Andrew J. , D’Arcy Colleen , Hansford Jordan R. , Manoharan Neevika , Nicholls Wayne , Williams Molly M. , Wood Paul J. , Cowley Mark J. , Tyrrell Vanessa , Haber Michelle , Ekert Paul G. , Ziegler David S. , Khuong-Quang Dong-Anh 
Published: March 2023

AbstractDiffuse midline gliomas (DMG) harbouring H3K27M mutation are paediatric tumours with a dismal outcome. Recently, a new subtype of midline gliomas has been described with similar features to DMG, including loss of H3K27 trimethylation, but lacking the canonical H3K27M mutation (H3-WT). Here, we report a cohort of five H3-WT tumours profiled by whole-genome sequencing, RNA sequencing and DNA methylation profiling and combine their analysis with previously published cases. We show that these tumours have recurrent and mutually exclusive mutations in either ACVR1 or EGFR and are characterised by high expression of EZHIP associated to its promoter hypomethylation. Affected patients share a similar poor prognosis as patients with H3K27M DMG. Global molecular analysis of H3-WT and H3K27M DMG reveal distinct transcriptome and methylome profiles including differential methylation of homeobox genes involved in development and cellular differentiation. Patients have distinct clinical features, with a trend demonstrating ACVR1 mutations occurring in H3-WT tumours at an older age. This in-depth exploration of H3-WT tumours further characterises this novel DMG, H3K27-altered sub-group, characterised by a specific immunohistochemistry profile with H3K27me3 loss, wild-type H3K27M and positive EZHIP. It also gives new insights into the possible mechanism and pathway regulation in these tumours, potentially opening new therapeutic avenues for these tumours which have no known effective treatment.
This study has been retrospectively registered on clinicaltrial.gov on 8 November 2017 under the registration number NCT03336931 (https://clinicaltrials.gov/ct2/show/NCT03336931).
The efficiency of quantum teleportation with three-qubit entangled state in a noisy environment
Authors: Zhang Chang-Yue , Zheng Zhu-Jun , Fan Zhao-Bing , Ma Hai-Tao 
Published: March 2023

AbstractQuantum teleportation plays a significant role in the field of quantum communication. This paper investigates quantum teleportation through a noisy environment by using GHZ state and non-standard W state as quantum channels. We analyze the efficiency of quantum teleportation by solving analytically a master equation in Lindblad form. Following the quantum teleportation protocol, we obtain the fidelity of quantum teleportation as a function of evolution time. The calculation results show that the teleportation fidelity using non-standard W is higher in comparison to GHZ state at the same evolution time. Moreover, we consider the efficiency of teleportation with weak measurements and reverse quantum measurement under amplitude damping noise. Our analysis suggests that the teleportation fidelity using non-standard W is also more robust to noise than GHZ state in the same conditions. Interestingly, we found that weak measurement and its reverse operation have no positive effect on the efficiency of quantum teleportation by using GHZ and non-standard W state in the amplitude damping noise environment. In addition, we also demonstrate the efficiency of quantum teleportation can be improved by making minor modifications to the protocol.
Interaural time difference sensitivity under binaural cochlear implant stimulation persists at high pulse rates up to 900 pps
Authors: Buck Alexa N. , Buchholz Sarah , Schnupp Jan W. , Rosskothen-Kuhl Nicole 
Published: March 2023

AbstractSpatial hearing remains one of the major challenges for bilateral cochlear implant (biCI) users, and early deaf patients in particular are often completely insensitive to interaural time differences (ITDs) delivered through biCIs. One popular hypothesis is that this may be due to a lack of early binaural experience. However, we have recently shown that neonatally deafened rats fitted with biCIs in adulthood quickly learn to discriminate ITDs as well as their normal hearing litter mates, and perform an order of magnitude better than human biCI users. Our unique behaving biCI rat model allows us to investigate other possible limiting factors of prosthetic binaural hearing, such as the effect of stimulus pulse rate and envelope shape. Previous work has indicated that ITD sensitivity may decline substantially at the high pulse rates often used in clinical practice. We therefore measured behavioral ITD thresholds in neonatally deafened, adult implanted biCI rats to pulse trains of 50, 300, 900 and 1800 pulses per second (pps), with either rectangular or Hanning window envelopes. Our rats exhibited very high sensitivity to ITDs at pulse rates up to 900 pps for both envelope shapes, similar to those in common clinical use. However, ITD sensitivity declined to near zero at 1800 pps, for both Hanning and rectangular windowed pulse trains. Current clinical cochlear implant (CI) processors are often set to pulse rates ≥ 900 pps, but ITD sensitivity in human CI listeners has been reported to decline sharply above ~ 300 pps. Our results suggest that the relatively poor ITD sensitivity seen at > 300 pps in human CI users may not reflect the hard upper limit of biCI ITD performance in the mammalian auditory pathway. Perhaps with training or better CI strategies good binaural hearing may be achievable at pulse rates high enough to allow good sampling of speech envelopes while delivering usable ITDs.