bluuebunny/crossref_metadata_2025_split huggingface dataset:
TEFM variants impair mitochondrial transcription causing childhood-onset neurological disease
Authors: Van Haute Lindsey , O’Connor Emily , Díaz-Maldonado Héctor , Munro Benjamin , Polavarapu Kiran , Hock Daniella H. , Arunachal Gautham , Athanasiou-Fragkouli Alkyoni , Bardhan Mainak , Barth Magalie , Bonneau Dominique , Brunetti-Pierri Nicola , Cappuccio Gerarda , Caruana Nikeisha J. , Dominik Natalia , Goel Himanshu , Helman Guy , Houlden Henry , Lenaers Guy , Mention Karine , Murphy David , Nandeesh Bevinahalli , Olimpio Catarina , Powell Christopher A. , Preethish-Kumar Veeramani , Procaccio Vincent , Rius Rocio , Rebelo-Guiomar Pedro , Simons Cas , Vengalil Seena , Zaki Maha S. , Ziegler Alban , Thorburn David R. , Stroud David A. , Maroofian Reza , Christodoulou John , Gustafsson Claes , Nalini Atchayaram , Lochmüller Hanns , Minczuk Michal , Horvath Rita 
Published: February 2023

AbstractMutations in the mitochondrial or nuclear genomes are associated with a diverse group of human disorders characterized by impaired mitochondrial respiration. Within this group, an increasing number of mutations have been identified in nuclear genes involved in mitochondrial RNA biology. The TEFM gene encodes the mitochondrial transcription elongation factor responsible for enhancing the processivity of mitochondrial RNA polymerase, POLRMT. We report for the first time that TEFM variants are associated with mitochondrial respiratory chain deficiency and a wide range of clinical presentations including mitochondrial myopathy with a treatable neuromuscular transmission defect. Mechanistically, we show muscle and primary fibroblasts from the affected individuals have reduced levels of promoter distal mitochondrial RNA transcripts. Finally, tefm knockdown in zebrafish embryos resulted in neuromuscular junction abnormalities and abnormal mitochondrial function, strengthening the genotype-phenotype correlation. Our study highlights that TEFM regulates mitochondrial transcription elongation and its defect results in variable, tissue-specific neurological and neuromuscular symptoms.
Low-dimensional encoding of decisions in parietal cortex reflects long-term training history
Authors: Latimer Kenneth W. , Freedman David J. 
Published: February 2023

AbstractNeurons in parietal cortex exhibit task-related activity during decision-making tasks. However, it remains unclear how long-term training to perform different tasks over months or even years shapes neural computations and representations. We examine lateral intraparietal area (LIP) responses during a visual motion delayed-match-to-category task. We consider two pairs of male macaque monkeys with different training histories: one trained only on the categorization task, and another first trained to perform fine motion-direction discrimination (i.e., pretrained). We introduce a novel analytical approach—generalized multilinear models—to quantify low-dimensional, task-relevant components in population activity. During the categorization task, we found stronger cosine-like motion-direction tuning in the pretrained monkeys than in the category-only monkeys, and that the pretrained monkeys’ performance depended more heavily on fine discrimination between sample and test stimuli. These results suggest that sensory representations in LIP depend on the sequence of tasks that the animals have learned, underscoring the importance of considering training history in studies with complex behavioral tasks.
Gene-encoding DNA origami for mammalian cell expression
Authors: Kretzmann Jessica A. , Liedl Anna , Monferrer Alba , Mykhailiuk Volodymyr , Beerkens Samuel , Dietz Hendrik 
Published: February 2023

AbstractDNA origami may enable more versatile gene delivery applications through its ability to create custom nanoscale objects with specific targeting, cell-invading, and intracellular effector functionalities. Toward this goal here we describe the expression of genes folded in DNA origami objects delivered to mammalian cells. Genes readily express from custom-sequence single-strand scaffolds folded within DNA origami objects, provided that the objects can denature in the cell. We demonstrate enhanced gene expression efficiency by including and tuning multiple functional sequences and structures, including virus-inspired inverted-terminal repeat-like (ITR) hairpin motifs upstream or flanking the expression cassette. We describe gene-encoding DNA origami bricks that assemble into multimeric objects to enable stoichiometrically controlled co-delivery and expression of multiple genes in the same cells. Our work provides a framework for exploiting DNA origami for gene delivery applications.
An optogenetic toolkit for light-inducible antibiotic resistance
Authors: Sheets Michael B. , Tague Nathan , Dunlop Mary J. 
Published: February 2023

AbstractAntibiotics are a key control mechanism for synthetic biology and microbiology. Resistance genes are used to select desired cells and regulate bacterial populations, however their use to-date has been largely static. Precise spatiotemporal control of antibiotic resistance could enable a wide variety of applications that require dynamic control of susceptibility and survival. Here, we use light-inducible Cre recombinase to activate expression of drug resistance genes in Escherichia coli. We demonstrate light-activated resistance to four antibiotics: carbenicillin, kanamycin, chloramphenicol, and tetracycline. Cells exposed to blue light survive in the presence of lethal antibiotic concentrations, while those kept in the dark do not. To optimize resistance induction, we vary promoter, ribosome binding site, and enzyme variant strength using chromosome and plasmid-based constructs. We then link inducible resistance to expression of a heterologous fatty acid enzyme to increase production of octanoic acid. These optogenetic resistance tools pave the way for spatiotemporal control of cell survival.
PHGDH arginine methylation by PRMT1 promotes serine synthesis and represents a therapeutic vulnerability in hepatocellular carcinoma
Authors: Wang Kui , Luo Li , Fu Shuyue , Wang Mao , Wang Zihao , Dong Lixia , Wu Xingyun , Dai Lunzhi , Peng Yong , Shen Guobo , Chen Hai-Ning , Nice Edouard Collins , Wei Xiawei , Huang Canhua 
Published: February 2023

AbstractSerine synthesis is crucial for tumor growth and survival, but its regulatory mechanism in cancer remains elusive. Here, using integrative metabolomics and transcriptomics analyses, we show a heterogeneity between metabolite and transcript profiles. Specifically, the level of serine in hepatocellular carcinoma (HCC) tissues is increased, whereas the expression of phosphoglycerate dehydrogenase (PHGDH), the first rate-limiting enzyme in serine biosynthesis pathway, is markedly downregulated. Interestingly, the increased serine level is obtained by enhanced PHGDH catalytic activity due to protein arginine methyltransferase 1 (PRMT1)-mediated methylation of PHGDH at arginine 236. PRMT1-mediated PHGDH methylation and activation potentiates serine synthesis, ameliorates oxidative stress, and promotes HCC growth in vitro and in vivo. Furthermore, PRMT1-mediated PHGDH methylation correlates with PHGDH hyperactivation and serine accumulation in human HCC tissues, and is predictive of poor prognosis of HCC patients. Notably, blocking PHGDH methylation with a TAT-tagged nonmethylated peptide inhibits serine synthesis and restrains HCC growth in an HCC patient-derived xenograft (PDX) model and subcutaneous HCC cell-derived xenograft model. Overall, our findings reveal a regulatory mechanism of PHGDH activity and serine synthesis, and suggest PHGDH methylation as a potential therapeutic vulnerability in HCC.
The phonon thermal Hall angle in black phosphorus
Authors: Li Xiaokang , Machida Yo , Subedi Alaska , Zhu Zengwei , Li Liang , Behnia Kamran 
Published: February 2023

AbstractThe origin of phonon thermal Hall Effect (THE) observed in a variety of insulators is yet to be identified. Here, we report on the observation of a thermal Hall conductivity in a non-magnetic elemental insulator, with an amplitude exceeding what has been previously observed. In black phosphorus (BP), the longitudinal (κii), and the transverse, κij, thermal conductivities peak at the same temperature and at this peak temperature, the κij/κjj/B is ≈ 10−4−10−3 T−1. Both these features are shared by other insulators displaying THE, despite an absolute amplitude spreading over three orders of magnitude. The absence of correlation between the thermal Hall angle and the phonon mean-free-path imposes a severe constraint for theoretical scenarios of THE. We show that in BP a longitudinal and a transverse acoustic phonon mode anti-cross, facilitating wave-like transport across modes. The anisotropic charge distribution surrounding atomic bonds can pave the way for coupling between phonons and the magnetic field.
Structure of human NaV1.6 channel reveals Na+ selectivity and pore blockade by 4,9-anhydro-tetrodotoxin
Authors: Li Yue , Yuan Tian , Huang Bo , Zhou Feng , Peng Chao , Li Xiaojing , Qiu Yunlong , Yang Bei , Zhao Yan , Huang Zhuo , Jiang Daohua 
Published: February 2023

AbstractThe sodium channel NaV1.6 is widely expressed in neurons of the central and peripheral nervous systems, which plays a critical role in regulating neuronal excitability. Dysfunction of NaV1.6 has been linked to epileptic encephalopathy, intellectual disability and movement disorders. Here we present cryo-EM structures of human NaV1.6/β1/β2 alone and complexed with a guanidinium neurotoxin 4,9-anhydro-tetrodotoxin (4,9-ah-TTX), revealing molecular mechanism of NaV1.6 inhibition by the blocker. The apo-form structure reveals two potential Na+ binding sites within the selectivity filter, suggesting a possible mechanism for Na+ selectivity and conductance. In the 4,9-ah-TTX bound structure, 4,9-ah-TTX binds to a pocket similar to the tetrodotoxin (TTX) binding site, which occupies the Na+ binding sites and completely blocks the channel. Molecular dynamics simulation results show that subtle conformational differences in the selectivity filter affect the affinity of TTX analogues. Taken together, our results provide important insights into NaV1.6 structure, ion conductance, and inhibition.
Monocular metasurface camera for passive single-shot 4D imaging
Authors: Shen Zicheng , Zhao Feng , Jin Chunqi , Wang Shuai , Cao Liangcai , Yang Yuanmu 
Published: February 2023

AbstractIt is a grand challenge for an imaging system to simultaneously obtain multi-dimensional light field information, such as depth and polarization, of a scene for the accurate perception of the physical world. However, such a task would conventionally require bulky optical components, time-domain multiplexing, and active laser illumination. Here, we experimentally demonstrate a compact monocular camera equipped with a single-layer metalens that can capture a 4D image, including 2D all-in-focus intensity, depth, and polarization of a target scene in a single shot under ambient illumination conditions. The metalens is optimized to have a conjugate pair of polarization-decoupled rotating single-helix point-spread functions that are strongly dependent on the depth of the target object. Combined with a straightforward, physically interpretable image retrieval algorithm, the camera can simultaneously perform high-accuracy depth sensing and high-fidelity polarization imaging over an extended depth of field for both static and dynamic scenes in both indoor and outdoor environments. Such a compact multi-dimensional imaging system could enable new applications in diverse areas ranging from machine vision to microscopy.
Flexible magnetoelectric complex oxide heterostructures on muscovite for proximity sensor
Authors: Wang Yong-Jyun , Chen Jia-Wei , Lai Yu-Hong , Shao Pao-Wen , Bitla Yugandhar , Chen Yi-Chun , Chu Ying-Hao 
Published: February 2023

AbstractIn modern technology, recent advances in multi-functional devices are rapidly developed for the diverse demands of human beings. Meanwhile, durability and adaptability to extreme environmental conditions are also required. In this study, a flexible magnetoelectric (ME) heterostructure based on CoFe2O4/Pb(Zr,Ti)O3 composite thin film on muscovite is presented, with two geometries of the constituents, namely laminar heterostructure, and vertical nanostructure, adopted for the comparison. On the other hand, credited to the mechanical flexibility of muscovite, the impact of flexibility on ME properties is also discussed with a series of bending tests. Moreover, the ME response sustains for 10,000 times bending without significant decrease, validating the mechanical durability of this heterostructure on muscovite. With these advantages, a flexible proximity sensor based on this heterostructure is demonstrated for motion detection. It is expected to offer a pathway for creating the next-generational flexible devices, showing potential for future practical application.
Immunogenicity and protective efficacy of GBP510/AS03 vaccine against SARS-CoV-2 delta challenge in rhesus macaques
Authors: Jacob-Dolan Catherine , Yu Jingyou , McMahan Katherine , Giffin Victoria , Chandrashekar Abishek , Martinot Amanda J. , Anioke Tochi , Powers Olivia C. , Hall Kevin , Hope David , Miller Jessica , Hachmann Nichole P. , Chung Benjamin , Gardner Sarah , Sellers Daniel , Barrett Julia , Lewis Mark G. , Andersen Hanne , Kleanthous Harry , Seo Ki-Woen , Lee Su Jeen , Park Yong Wook , Kim Hun , Barouch Dan H. 
Published: February 2023

AbstractDespite the availability of several effective SARS-CoV-2 vaccines, additional vaccines will be required for optimal global vaccination. In this study, we investigate the immunogenicity and protective efficacy of the GBP510 protein subunit vaccine adjuvanted with AS03, which has recently been authorized for marketing in South Korea under the trade name SKYCovioneTM. The antigen in GBP510/AS03 is a two-part recombinant nanoparticle, which displays 60 receptor binding domain (RBD) proteins of SARS-CoV-2 Spike on its surface. In this study we show that GBP510/AS03 induced robust immune responses in rhesus macaques and protected against a high-dose SARS-CoV-2 Delta challenge. We vaccinated macaques with two or three doses of GBP510/AS03 matched to the ancestral Wuhan strain of SARS-CoV-2 or with two doses of GBP510/AS03 matched to the ancestral strain and one dose matched to the Beta strain. Following the challenge with Delta, the vaccinated macaques rapidly controlled the virus in bronchoalveolar lavage and nasal swabs. Binding and neutralizing antibody responses prior to challenge correlated with protection against viral replication postchallenge. These data are consistent with data with this vaccine from the phase 3 clinical trial.
Intranasal multivalent adenoviral-vectored vaccine protects against replicating and dormant M.tb in conventional and humanized mice
Authors: Afkhami Sam , D’Agostino Michael R. , Vaseghi-Shanjani Maryam , Lepard Madeleine , Yang Jack X. , Lai Rocky , Choi Margaret Wa Yan , Chacon Alexis , Zganiacz Anna , Franken Kees L. M. C. , Ertl Hildegund C. , Ottenhoff Tom H. M. , Jeyanathan Mangalakumari , Gillgrass Amy , Xing Zhou 
Published: February 2023

AbstractViral-vectored vaccines are highly amenable for respiratory mucosal delivery as a means of inducing much-needed mucosal immunity at the point of pathogen entry. Unfortunately, current monovalent viral-vectored tuberculosis (TB) vaccine candidates have failed to demonstrate satisfactory clinical protective efficacy. As such, there is a need to develop next-generation viral-vectored TB vaccine strategies which incorporate both vaccine antigen design and delivery route. In this study, we have developed a trivalent chimpanzee adenoviral-vectored vaccine to provide protective immunity against pulmonary TB through targeting antigens linked to the three different growth phases (acute/chronic/dormancy) of Mycobacterium tuberculosis (M.tb) by expressing an acute replication-associated antigen, Ag85A, a chronically expressed virulence-associated antigen, TB10.4, and a dormancy/resuscitation-associated antigen, RpfB. Single-dose respiratory mucosal immunization with our trivalent vaccine induced robust, sustained tissue-resident multifunctional CD4+ and CD8+ T-cell responses within the lung tissues and airways, which were further quantitatively and qualitatively improved following boosting of subcutaneously BCG-primed hosts. Prophylactic and therapeutic immunization with this multivalent trivalent vaccine in conventional BALB/c mice provided significant protection against not only actively replicating M.tb bacilli but also dormant, non-replicating persisters. Importantly, when used as a booster, it also provided marked protection in the highly susceptible C3HeB/FeJ mice, and a single respiratory mucosal inoculation was capable of significant protection in a humanized mouse model. Our findings indicate the great potential of this next-generation TB vaccine strategy and support its further clinical development for both prophylactic and therapeutic applications.
A large-scale dataset for end-to-end table recognition in the wild
Authors: Yang Fan , Hu Lei , Liu Xinwu , Huang Shuangping , Gu Zhenghui 
Published: February 2023

AbstractTable recognition (TR) is one of the research hotspots in pattern recognition, which aims to extract information from tables in an image. Common table recognition tasks include table detection (TD), table structure recognition (TSR) and table content recognition (TCR). TD is to locate tables in the image, TCR recognizes text content, and TSR recognizes spatial & ontology (logical) structure. Currently, the end-to-end TR in real scenarios, accomplishing the three sub-tasks simultaneously, is yet an unexplored research area. One major factor that inhibits researchers is the lack of a benchmark dataset. To this end, we propose a new large-scale dataset named Table Recognition Set (TabRecSet) with diverse table forms sourcing from multiple scenarios in the wild, providing complete annotation dedicated to end-to-end TR research. It is the largest and first bi-lingual dataset for end-to-end TR, with 38.1 K tables in which 20.4 K are in English and 17.7 K are in Chinese. The samples have diverse forms, such as the border-complete and -incomplete table, regular and irregular table (rotated, distorted, etc.). The scenarios are multiple in the wild, varying from scanned to camera-taken images, documents to Excel tables, educational test papers to financial invoices. The annotations are complete, consisting of the table body spatial annotation, cell spatial & logical annotation and text content for TD, TSR and TCR, respectively. The spatial annotation utilizes the polygon instead of the bounding box or quadrilateral adopted by most datasets. The polygon spatial annotation is more suitable for irregular tables that are common in wild scenarios. Additionally, we propose a visualized and interactive annotation tool named TableMe to improve the efficiency and quality of table annotation.
On the identification of internal solitary waves from moored observations in the northern South China Sea
Authors: Gong Qinglong , Chen Liang , Diao Yina , Xiong Xuejun , Sun Jilin , Lv Xianqing 
Published: February 2023

AbstractBased on the temperature data recorded by a mooring system deployed in the northern South China Sea (SCS), this study compares the traditional methods of identifying and extracting internal solitary waves (ISWs): the whole water column isotherm (WCI) method and the single isotherm (SI) method, and proposes a novel method: the temperature superposition (TS) method. Results indicate that the TS method identifies the most ISWs, followed by the WCI method, and the SI method identifies the fewest. When the ISW amplitudes are smaller than 60 m, the TS method can identify the most ISWs. When the ISW amplitudes are greater than 60 m, the number of ISWs identified by the three methods is the same. The TS method removes the internal tides, takes into account the temperature of all depth layers, and amplifies the signal of ISWs to a certain extent, so as to effectively identify ISWs.
Impact of reboxetine plus oxybutynin treatment for obstructive sleep apnea on cardiovascular autonomic modulation
Authors: Perger Elisa , Castiglioni Paolo , Faini Andrea , Soranna Davide , Zambon Antonella , Rosa Debora , Vicini Stefano , Meriggi Paolo , Pini Laura , Baratto Claudia , Caravita Sergio , Azarbarzin Ali , Parati Gianfranco , Lombardi Carolina 
Published: February 2023

AbstractThe combination of noradrenergic (reboxetine) plus antimuscarinic (oxybutynin) drugs (reb-oxy) reduced obstructive sleep apnea (OSA) severity but no data are available on its effects on cardiac autonomic modulation. We sought to evaluate the impact of 1-week reb-oxy treatment on cardiovascular autonomic control in OSA patients. OSA patients were randomized to a double-blind, crossover trial comparing 4 mg reboxetine plus 5 mg oxybutynin to a placebo for OSA treatment. Heart rate (HR) variability (HRV), ambulatory blood pressure (BP) monitoring (ABPM) over 24 h baseline and after treatment were performed. Baroreflex sensitivity was tested over beat-to-beat BP recordings. 16 subjects with (median [interquartile range]) age 57 [51–61] years and body mass index 30 [26–36]kg/m2 completed the study. The median nocturnal HR was 65 [60–69] bpm at baseline and increased to 69 [64–77] bpm on reb-oxy vs 66 [59–70] bpm on placebo (p = 0.02). The mean 24 h HR from ABPM was not different among treatment groups. Reb-oxy administration was not associated with any modification in HRV or BP. Reb-oxy increased the baroreflex sensitivity and did not induce orthostatic hypotension. In conclusion, administration of reb-oxy did not induce clinically relevant sympathetic overactivity over 1-week and, together with a reduction in OSA severity, it improved the baroreflex function.
Implementation of a free water protocol at a long term acute care hospital
Authors: Gaidos Stefanie , Hrdlicka Henry C. , Corbett John 
Published: February 2023

AbstractThis feasibility study aimed to trial a Free Water Protocol (FWP) for patients with thin liquid dysphagia in the Long-Term Acute Care Hospital (LTACH) setting. Patients with dysphagia are often prescribed thickened liquids to avoid or mitigate aspiration. While this clinical intervention can minimize the risk of aspiration pneumonia (PNA), it is generally not well received by patients. As such, the goal of this study was to determine if patients who knowingly aspirate thin liquids can safely tolerate thin liquid water, and if so, to what degree of benefit. The study assessed for adverse events, fluid intake, hydration status, quality of life, and overall swallow function outcomes. These measurements were taken over a 7 day trial period using inventories, lab work, clinical judgment, and observation. Ten participants were enrolled in this study with 9 having sufficient data for analysis (n = 9). No adverse events related to the FWP were observed, and patients saw improved total fluid intake (P = 0.0074), swallow-related quality of life (P = 0.0273), and overall swallow function (P = 0.0002). The results in this feasibility study allowed for the hospital wide implementation of the FWP and laid out the groundwork for future studies looking at longitudinal effects of a FWP.