bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Cas3-base editing tool for targetable in vivo mutagenesis
Authors: Zimmermann Anna , Prieto-Vivas Julian E. , Cautereels Charlotte , Gorkovskiy Anton , Steensels Jan , Van de Peer Yves , Verstrepen Kevin J. 
Published: June 2023

AbstractThe generation of genetic diversity via mutagenesis is routinely used for protein engineering and pathway optimization. Current technologies for random mutagenesis often target either the whole genome or relatively narrow windows. To bridge this gap, we developed CoMuTER (Confined Mutagenesis using a Type I-E CRISPR-Cas system), a tool that allows inducible and targetable, in vivo mutagenesis of genomic loci of up to 55 kilobases. CoMuTER employs the targetable helicase Cas3, signature enzyme of the class 1 type I-E CRISPR-Cas system, fused to a cytidine deaminase to unwind and mutate large stretches of DNA at once, including complete metabolic pathways. The tool increases the number of mutations in the target region 350-fold compared to the rest of the genome, with an average of 0.3 mutations per kilobase. We demonstrate the suitability of CoMuTER for pathway optimization by doubling the production of lycopene in Saccharomyces cerevisiae after a single round of mutagenesis.
Intranasal or airborne transmission-mediated delivery of an attenuated SARS-CoV-2 protects Syrian hamsters against new variants
Authors: Stauft Charles B. , Selvaraj Prabhuanand , D’Agnillo Felice , Meseda Clement A. , Liu Shufeng , Pedro Cyntia L. , Sangare Kotou , Lien Christopher Z. , Weir Jerry P. , Starost Matthew F. , Wang Tony T. 
Published: June 2023

AbstractDetection of secretory antibodies in the airway is highly desirable when evaluating mucosal protection by vaccines against a respiratory virus, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We show that intranasal delivery of an attenuated SARS-CoV-2 (Nsp1-K164A/H165A) induces both mucosal and systemic IgA and IgG in male Syrian hamsters. Interestingly, either direct intranasal immunization or airborne transmission-mediated delivery of Nsp1-K164A/H165A in Syrian hamsters offers protection against heterologous challenge with variants of concern (VOCs) including Delta, Omicron BA.1, BA.2.12.1 and BA.5. Vaccinated animals show significant reduction in both tissue viral loads and lung inflammation. Similarly attenuated viruses bearing BA.1 and BA.5 spike boost variant-specific neutralizing antibodies in male mice that were first vaccinated with modified vaccinia virus Ankara vectors (MVA) expressing full-length WA1/2020 Spike protein. Together, these results demonstrate that our attenuated virus may be a promising nasal vaccine candidate for boosting mucosal immunity against future SARS-CoV-2 VOCs.
Asymptomatic immunodeficiency-associated vaccine-derived poliovirus infections in two UK children
Authors: Singanayagam Anika , Klapsa Dimitra , Burton-Fanning Shirelle , Hand Julian , Wilton Thomas , Stephens Laura , Mate Ryan , Shillitoe Benjamin , Celma Cristina , Slatter Mary , Flood Terry , Gopal Robin , Martin Javier , Zambon Maria 
Published: June 2023

AbstractIncreasing detections of vaccine-derived poliovirus (VDPV) globally, including in countries previously declared polio free, is a public health emergency of international concern. Individuals with primary immunodeficiency (PID) can excrete polioviruses for prolonged periods, which could act as a source of cryptic transmission of viruses with potential to cause neurological disease. Here, we report on the detection of immunodeficiency-associated VDPVs (iVDPV) from two asymptomatic male PID children in the UK in 2019. The first child cleared poliovirus with increased doses of intravenous immunoglobulin, the second child following haematopoetic stem cell transplantation. We perform genetic and phenotypic characterisation of the infecting strains, demonstrating intra-host evolution and a neurovirulent phenotype in transgenic mice. Our findings highlight a pressing need to strengthen polio surveillance. Systematic collection of stool from asymptomatic PID patients who are at high risk for poliovirus excretion could improve the ability to detect and contain iVDPVs.
Spectral signatures of a unique charge density wave in Ta2NiSe7
Authors: Watson Matthew D. , Louat Alex , Cacho Cephise , Choi Sungkyun , Lee Young Hee , Neumann Michael , Kim Gideok 
Published: June 2023

AbstractCharge Density Waves (CDW) are commonly associated with the presence of near-Fermi level states which are separated from others, or “nested", by a wavector of q. Here we use Angle-Resolved Photo Emission Spectroscopy (ARPES) on the CDW material Ta2NiSe7 and identify a total absence of any plausible nesting of states at the primary CDW wavevector q. Nevertheless we observe spectral intensity on replicas of the hole-like valence bands, shifted by a wavevector of q, which appears with the CDW transition. In contrast, we find that there is a possible nesting at 2q, and associate the characters of these bands with the reported atomic modulations at 2q. Our comprehensive electronic structure perspective shows that the CDW-like transition of Ta2NiSe7 is unique, with the primary wavevector q being unrelated to any low-energy states, but suggests that the reported modulation at 2q, which would plausibly connect low-energy states, might be more important for the overall energetics of the problem.
Tuning magnetoelectricity in a mixed-anisotropy antiferromagnet
Authors: Fogh Ellen , Klemke Bastian , Reehuis Manfred , Bourges Philippe , Niedermayer Christof , Holm-Dahlin Sonja , Zaharko Oksana , Schefer Jürg , Kristensen Andreas B. , Sørensen Michael K. , Paeckel Sebastian , Pedersen Kasper S. , Hansen Rasmus E. , Pages Alexandre , Moerner Kimmie K. , Meucci Giulia , Soh Jian-Rui , Bombardi Alessandro , Vaknin David , Rønnow Henrik. M. , Syljuåsen Olav F. , Christensen Niels B. , Toft-Petersen Rasmus 
Published: June 2023

AbstractControl of magnetization and electric polarization is attractive in relation to tailoring materials for data storage and devices such as sensors or antennae. In magnetoelectric materials, these degrees of freedom are closely coupled, allowing polarization to be controlled by a magnetic field, and magnetization by an electric field, but the magnitude of the effect remains a challenge in the case of single-phase magnetoelectrics for applications. We demonstrate that the magnetoelectric properties of the mixed-anisotropy antiferromagnet LiNi1−xFexPO4 are profoundly affected by partial substitution of Ni2+ ions with Fe2+ on the transition metal site. This introduces random site-dependent single-ion anisotropy energies and causes a lowering of the magnetic symmetry of the system. In turn, magnetoelectric couplings that are symmetry-forbidden in the parent compounds, LiNiPO4 and LiFePO4, are unlocked and the dominant coupling is enhanced by almost two orders of magnitude. Our results demonstrate the potential of mixed-anisotropy magnets for tuning magnetoelectric properties.
Understanding unconventional magnetic order in a candidate axion insulator by resonant elastic x-ray scattering
Authors: Soh Jian-Rui , Bombardi Alessandro , Mila Frédéric , Rahn Marein C. , Prabhakaran Dharmalingam , Francoual Sonia , Rønnow Henrik M. , Boothroyd Andrew T. 
Published: June 2023

AbstractMagnetic topological insulators and semimetals are a class of crystalline solids whose properties are strongly influenced by the coupling between non-trivial electronic topology and magnetic spin configurations. Such materials can host exotic electromagnetic responses. Among these are topological insulators with certain types of antiferromagnetic order which are predicted to realize axion electrodynamics. Here we investigate the highly unusual helimagnetic phases recently reported in EuIn2As2, which has been identified as a candidate for an axion insulator. Using resonant elastic x-ray scattering we show that the two types of magnetic order observed in EuIn2As2 are spatially uniform phases with commensurate chiral magnetic structures, ruling out a possible phase-separation scenario, and we propose that entropy associated with low energy spin fluctuations plays a significant role in driving the phase transition between them. Our results establish that the magnetic order in EuIn2As2 satisfies the symmetry requirements for an axion insulator.
Co-translational binding of importins to nascent proteins
Authors: Seidel Maximilian , Romanov Natalie , Obarska-Kosinska Agnieszka , Becker Anja , Trevisan Doimo de Azevedo Nayara , Provaznik Jan , Nagaraja Sankarshana R. , Landry Jonathan J. M. , Benes Vladimir , Beck Martin 
Published: June 2023

AbstractVarious cellular quality control mechanisms support proteostasis. While, ribosome-associated chaperones prevent the misfolding of nascent chains during translation, importins were shown to prevent the aggregation of specific cargoes in a post-translational mechanism prior the import into the nucleoplasm. Here, we hypothesize that importins may already bind ribosome-associated cargo in a co-translational manner. We systematically measure the nascent chain association of all importins in Saccharomyces cerevisiae by selective ribosome profiling. We identify a subset of importins that bind to a wide range of nascent, often uncharacterized cargoes. This includes ribosomal proteins, chromatin remodelers and RNA binding proteins that are aggregation prone in the cytosol. We show that importins act consecutively with other ribosome-associated chaperones. Thus, the nuclear import system is directly intertwined with nascent chain folding and chaperoning.
Substantia nigral dopamine transporter uptake in dementia with Lewy bodies
Authors: Lee Young-gun , Jeon Seun , Baik Kyoungwon , Kang Sung Woo , Ye Byoung Seok 
Published: June 2023

AbstractNigrostriatal dopaminergic degeneration is a pathological hallmark of dementia with Lewy bodies (DLB). To identify the subregional dopamine transporter (DAT) uptake patterns that improve the diagnostic accuracy of DLB, we analyzed N-(3-[18F] fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl)-nortropane (FP-CIT) PET in 51 patients with DLB, in 36 patients with mild cognitive impairment with Lewy body (MCI-LB), and in 40 healthy controls (HCs). In addition to a high affinity for DAT, FP-CIT show a modest affinity to serotonin or norepinephrine transporters. Specific binding ratios (SBRs) of the nigrostriatal subregions were transformed to age-adjusted z-scores (zSBR) based on HCs. The diagnostic accuracy of subregional zSBRs were tested using receiver operating characteristic (ROC) curve analyses separately for MCI-LB and DLB versus HCs. Then, the effect of subregional zSBRs on the presence of clinical features and gray matter (GM) density were evaluated in all patients with MCI-LB or DLB as a group. ROC curve analyses showed that the diagnostic accuracy of DLB based on the zSBR of substantia nigra (area under the curve [AUC], 0.90) or those for MCI-LB (AUC, 0.87) were significantly higher than that based on the zSBR of posterior putamen for DLB (AUC, 0.72) or MCI-LB (AUC, 0.65). Lower zSBRs in nigrostriatal regions were associated with visual hallucination, severe parkinsonism, and cognitive dysfunction, while lower zSBR of substantia nigra was associated with widespread GM atrophy in DLB and MCI-LB patients. Taken together, our results suggest that evaluation of nigral DAT uptake may increase the diagnostic accuracy of DLB and MCI-LB than other striatal regions.
Ethnic inequality, multimorbidity and psychosis: can a syndemic framework resolve disputed evidence?
Authors: Zahid Uzma , Hosang Georgina M. , de Freitas Daniela Fonseca , Mooney Roisin , Bhui Kamaldeep 
Published: June 2023

AbstractSyndemic theory is described as population-level clustering or co-occurrence of health conditions in the context of shared aetiologies that interact and can act synergistically. These influences appear to act within specific places of high disadvantage. We suggest ethnic inequality in experiences and outcomes of multimorbidity, including psychosis, may be explained through a syndemic framework. We discuss the evidence for each component of syndemic theory in relation to psychosis, using psychosis and diabetes as an exemplar. Following this, we discuss the practical and theoretical adaptations to syndemic theory in order to apply it to psychosis, ethnic inequality and multimorbidity, with implications for research, policy, and practice.
Universal redirection of CAR T cells against solid tumours via membrane-inserted ligands for the CAR
Authors: Zhang Angela Q. , Hostetler Alexander , Chen Laura E. , Mukkamala Vainavi , Abraham Wuhbet , Padilla Lucia T. , Wolff Alexandra N. , Maiorino Laura , Backlund Coralie M. , Aung Aereas , Melo Mariane , Li Na , Wu Shengwei , Irvine Darrell J. 
Published: June 2023

AbstractThe effectiveness of chimaeric antigen receptor (CAR) T cell therapies for solid tumours is hindered by difficulties in the selection of an effective target antigen, owing to the heterogeneous expression of tumour antigens and to target antigen expression in healthy tissues. Here we show that T cells with a CAR specific for fluorescein isothiocyanate (FITC) can be directed against solid tumours via the intratumoural administration of a FITC-conjugated lipid–poly(ethylene)-glycol amphiphile that inserts itself into cell membranes. In syngeneic and human tumour xenografts in mice, ‘amphiphile tagging’ of tumour cells drove tumour regression via the proliferation and accumulation of FITC-specific CAR T cells in the tumours. In syngeneic tumours, the therapy induced the infiltration of host T cells, elicited endogenous tumour-specific T cell priming and led to activity against distal untreated tumours and to protection against tumour rechallenge. Membrane-inserting ligands for specific CARs may facilitate the development of adoptive cell therapies that work independently of antigen expression and of tissue of origin.
Resolving sepsis-induced immunoparalysis via trained immunity by targeting interleukin-4 to myeloid cells
Authors: Schrijver David P. , Röring Rutger J. , Deckers Jeroen , de Dreu Anne , Toner Yohana C. , Prevot Geoffrey , Priem Bram , Munitz Jazz , Nugraha Eveline G. , van Elsas Yuri , Azzun Anthony , Anbergen Tom , Groh Laszlo A. , Becker Anouk M. D. , Pérez-Medina Carlos , Oosterwijk Roderick S. , Novakovic Boris , Moorlag Simone J. C. F. M. , Jansen Aron , Pickkers Peter , Kox Matthijs , Beldman Thijs J. , Kluza Ewelina , van Leent Mandy M. T. , Teunissen Abraham J. P. , van der Meel Roy , Fayad Zahi A. , Joosten Leo A. B. , Fisher Edward A. , Merkx Maarten , Netea Mihai G. , Mulder Willem J. M. 
Published: June 2023

AbstractImmunoparalysis is a compensatory and persistent anti-inflammatory response to trauma, sepsis or another serious insult, which increases the risk of opportunistic infections, morbidity and mortality. Here, we show that in cultured primary human monocytes, interleukin-4 (IL4) inhibits acute inflammation, while simultaneously inducing a long-lasting innate immune memory named trained immunity. To take advantage of this paradoxical IL4 feature in vivo, we developed a fusion protein of apolipoprotein A1 (apoA1) and IL4, which integrates into a lipid nanoparticle. In mice and non-human primates, an intravenously injected apoA1-IL4-embedding nanoparticle targets myeloid-cell-rich haematopoietic organs, in particular, the spleen and bone marrow. We subsequently demonstrate that IL4 nanotherapy resolved immunoparalysis in mice with lipopolysaccharide-induced hyperinflammation, as well as in ex vivo human sepsis models and in experimental endotoxemia. Our findings support the translational development of nanoparticle formulations of apoA1-IL4 for the treatment of patients with sepsis at risk of immunoparalysis-induced complications.
Deep-learning-based blood pressure estimation using multi channel photoplethysmogram and finger pressure with attention mechanism
Authors: Kyung Jehyun , Yang Joon-Young , Choi Jeong-Hwan , Chang Joon-Hyuk , Bae Sangkon , Choi Jinwoo , Kim Younho 
Published: June 2023

AbstractRecently, several studies have proposed methods for measuring cuffless blood pressure (BP) using finger photoplethysmogram (PPG) signals. This study presents a new BP estimation system that measures PPG signals under progressive finger pressure, making the system relatively robust to errors caused by finger position when using the cuffless oscillometric method. To reduce errors caused by finger position, we developed a sensor that can simultaneously measure multi-channel PPG and force signals in a wide field of view (FOV). We propose a deep-learning-based algorithm that can learn to focus on the optimal PPG channel from multi channel PPG using an attention mechanism. The errors (ME ± STD) of the proposed multi channel system were 0.43±9.35 mmHg and 0.21 ± 7.72 mmHg for SBP and DBP, respectively. Through extensive experiments, we found a significant performance difference depending on the location of the PPG measurement in the BP estimation system using finger pressure.
Effects of an aerobic training program on liver functions in male athletes: a randomized controlled trial
Authors: Bari Mohd Arshad , MahmoodAlobaidi Mohammed Aiyad , Ansari Hena Ayub , Parrey Junaid Ahmad , Ajhar Arish , Nuhmani Shibili , Alghadir Ahmad H. , Khan Masood 
Published: June 2023

AbstractThe optimal functioning of the liver is essential for athletic performance. It is necessary to maintain the liver’s enzymes at an optimal level so that liver cells can be protected from inflammation or damage. This study investigated the effects of a 12-week aerobic exercise program on the liver function of adult athletes. A pretest–posttest experimental design was used. A total of thirty healthy male athletes (football players) aged 21 to 24 years were recruited for this study and randomly and equally divided into the experimental group (EG) and control group (CG). The CG did not participate in any special activities. The EG performed an aerobic training program consisting of several exercises for 12 weeks. Evaluation of all participants in both groups was carried out before and after the intervention by measuring the blood levels of Alkaline phosphate, AST/SGOT, ALT/SGPT, Bilirubin Total/indirect/direct, Albumin, Globulin, and Total protein using the standard methods by collecting blood samples. There was a significant decrease (p < 0.05) in Bilirubin and globulin levels in the EG after 12 weeks of aerobic training sessions. However, there was no significant difference in alkaline phosphate, AST/SGOT, ALT/SGPT Total protein, and Albumin (p > 0.05) between both groups post-treatment. The 12 weeks of aerobic training used in the study can potentially improve the liver function of adult athletes.
Relation of sedentary behaviour to physical function in phase I cardiac rehabilitation
Authors: Izawa Kazuhiro P. , Kanejima Yuji , Kitamura Masahiro , Ishihara Kodai , Ogura Asami , Kubo Ikko , Oka Koichiro , Nagashima Hitomi , Tawa Hideto , Matsumoto Daisuke , Shimizu Ikki 
Published: June 2023

AbstractIncreased sedentary behaviour (SB) is reportedly associated with mortality and morbidity in cardiovascular disease. However, its relation with physical function is not well understood in phase I cardiac rehabilitation (CR). This study aimed to investigate the rate of SB and the relation between SB and physical function among patients participating in phase I CR. This prospective multicentre cohort study enrolled patients participating in CR from October 2020 to July 2022. Patients with probable dementia and difficulty walking alone were excluded. We used sitting SB time as the index of SB and the Short Performance Physical Battery (SPPB) as the index of physical function at discharge. Patients were divided into the low SB group (< 480 min/day) or high SB group (≥ 480 min/day). We analysed and compared the two groups. The final analysis included 353 patients (mean age: 69.6 years, male: 75.6%), of whom 47.6% (168 of 353) were high SB patients. Total sitting SB time was higher in the high SB group versus the low SB group (733.6 ± 155.3 vs 246.4 ± 127.4 min/day, p < 0.001), and mean SPPB score was lower in the high SB group versus the low SB group (10.5 ± 2.4 vs 11.2 ± 1.6 points, p = 0.001). Multiple regression analysis identified SB as an explanatory variable for total SPPB score (p = 0.017). Patients with high SB had significantly lower SPPB scores than those with low SB. These findings underscore the importance of considering SB when improving physical function. Effective strategies to improve physical function can be developed that consider SB in phase I CR.
Potential for rupture before eruption at Campi Flegrei caldera, Southern Italy
Authors: Kilburn Christopher R. J. , Carlino Stefano , Danesi Stefania , Pino Nicola Alessandro 
Published: June 2023

AbstractVolcanoes reawakening after long repose must rupture the crust before magma can erupt. Rupture is preceded by repeatable variations in the rate of seismicity with ground movement, which trace the amount of applied stress that is released by local earthquakes. A rupturing sequence has been developing across four episodes of ground uplift at Italy’s Campi Flegrei caldera: in 1950-1952, 1969-1972, 1982-1984 and since 2004. We predicted in 2016 that the approach to rupture would continue after an additional uplift of 30-40 cm at the location of largest movement. We have updated our analysis with new data on changes in the numbers of local earthquakes with amounts of ground movement. Here we show that subsequent events have confirmed our prediction and that the unrest has been changing the structure of Campi Flegrei’s crust. The results provide new constraints for evaluating the volcano’s potential to erupt or to subside without eruption.
Caves demonstrate decrease in rainfall recharge of southwest Australian groundwater is unprecedented for the last 800 years
Authors: Priestley Stacey C. , Treble Pauline C. , Griffiths Alan D. , Baker Andy , Abram Nerilie J. , Meredith Karina T. 
Published: June 2023

AbstractBillions of people worldwide rely on groundwater. As rainfall in many regions in the future is projected to decrease, it is critical to understand the impacts of climate change on groundwater recharge. The groundwater recharge response to a sustained decrease in rainfall across southwest Australia that began in the late 1960s was examined in seven modern speleothems and drip waters from four caves. These show a pronounced increase or uptick in regional drip water and speleothem oxygen isotopic composition (δ18O) that is not driven by a change in rainfall δ18O values, but is in response to the shallow karst aquifers becoming disconnected from rainfall recharge due to regional drying. Our findings imply that rainfall recharge to groundwater may no longer be reliably occurring in this region, which is highly dependent on groundwater resources. Examination of the longer speleothem record shows that this situation is unprecedented over the last 800 years.