bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymphoid and myeloid immune cell reconstitution after nicotinamide-expanded cord blood transplantation
Authors: de Koning Coco , Tao Weiyang , Lacna Amelia , van Veghel Karin , Horwitz Mitchell E. , Sanz Guillermo , Jagasia Madan H. , Wagner John E. , Stiff Patrick J. , Hanna Rabi , Cilloni Daniela , Valcárcel David , Peled Tony , Galamidi Cohen Einat , Goshen Uri , Pandit Aridaman , Lindemans Caroline A. , Jan Boelens Jaap , Nierkens Stefan 
Published: July 2021

AbstractOmidubicel (nicotinamide-expanded cord blood) is a potential alternative source for allogeneic hematopoietic cell transplantation (HCT) when an HLA-identical donor is lacking. A phase I/II trial with standalone omidubicel HCT showed rapid and robust neutrophil and platelet engraftment. In this study, we evaluated the immune reconstitution (IR) of patients receiving omidubicel grafts during the first 6 months post-transplant, as IR is critical for favorable outcomes of the procedure. Data was collected from the omidubicel phase I-II international, multicenter trial. The primary endpoint was the probability of achieving adequate CD4+ T-cell IR (CD4IR: > 50 × 106/L within 100 days). Secondary endpoints were the recovery of T-cells, natural killer (NK)-cells, B-cells, dendritic cells (DC), and monocytes as determined with multicolor flow cytometry. LOESS-regression curves and cumulative incidence plots were used for data description. Thirty-six omidubicel recipients (median 44; 13–63 years) were included, and IR data was available from 28 recipients. Of these patients, 90% achieved adequate CD4IR. Overall, IR was complete and consisted of T-cell, monocyte, DC, and notably fast NK- and B-cell reconstitution, compared to conventional grafts. Our data show that transplantation of adolescent and adult patients with omidubicel results in full and broad IR, which is comparable with IR after HCT with conventional graft sources.
An enzymatic activation of formaldehyde for nucleotide methylation
Authors: Bou-Nader Charles , Stull Frederick W. , Pecqueur Ludovic , Simon Philippe , Guérineau Vincent , Royant Antoine , Fontecave Marc , Lombard Murielle , Palfey Bruce A. , Hamdane Djemel 
Published: July 2021

AbstractFolate enzyme cofactors and their derivatives have the unique ability to provide a single carbon unit at different oxidation levels for the de novo synthesis of amino-acids, purines, or thymidylate, an essential DNA nucleotide. How these cofactors mediate methylene transfer is not fully settled yet, particularly with regard to how the methylene is transferred to the methylene acceptor. Here, we uncovered that the bacterial thymidylate synthase ThyX, which relies on both folate and flavin for activity, can also use a formaldehyde-shunt to directly synthesize thymidylate. Combining biochemical, spectroscopic and anaerobic crystallographic analyses, we showed that formaldehyde reacts with the reduced flavin coenzyme to form a carbinolamine intermediate used by ThyX for dUMP methylation. The crystallographic structure of this intermediate reveals how ThyX activates formaldehyde and uses it, with the assistance of active site residues, to methylate dUMP. Our results reveal that carbinolamine species promote methylene transfer and suggest that the use of a CH2O-shunt may be relevant in several other important folate-dependent reactions.
Invisible surfaces enabled by the coalescence of anti-reflection and wavefront controllability in ultrathin metasurfaces
Authors: Chu Hongchen , Zhang Haoyang , Zhang Yang , Peng Ruwen , Wang Mu , Hao Yang , Lai Yun 
Published: July 2021

AbstractReflection inherently occurs on the interfaces between different media. In order to perfectly manipulate waves on the interfaces, integration of antireflection function in metasurfaces is highly desired. In this work, we demonstrate an approach to realize exceptional metasurfaces that combine the two vital functionalities of antireflection and arbitrary phase manipulation in the deep subwavelength scale. Such ultrathin devices confer reflection-less transmission through impedance-mismatched interfaces with arbitrary wavefront shapes. Theoretically and experimentally, we demonstrate a three-layer antireflection metasurface that achieves an intriguing phenomenon: the simultaneous elimination of the reflection and refraction effects on a dielectric surface. Incident waves transmit straightly through the dielectric surface as if the surface turns invisible. We further demonstrate a wide variety of applications such as invisible curved surfaces, “cloaking” of dielectric objects, reflection-less negative refraction and flat axicons on dielectric-air interfaces, etc. The coalescence of antireflection and wavefront controllability in the deep subwavelength scale brings new opportunities for advanced interface optics with high efficiency and great flexibility.
Interplay of mechanics and chemistry governs wear of diamond-like carbon coatings interacting with ZDDP-additivated lubricants
Authors: Salinas Ruiz Valentin R. , Kuwahara Takuya , Galipaud Jules , Masenelli-Varlot Karine , Hassine Mohamed Ben , Héau Christophe , Stoll Melissa , Mayrhofer Leonhard , Moras Gianpietro , Martin Jean Michel , Moseler Michael , de Barros Bouchet Maria-Isabel 
Published: July 2021

AbstractFriction and wear reduction by diamond-like carbon (DLC) in automotive applications can be affected by zinc-dialkyldithiophosphate (ZDDP), which is widely used in engine oils. Our experiments show that DLC’s tribological behaviour in ZDDP-additivated oils can be optimised by tailoring its stiffness, surface nano-topography and hydrogen content. An optimal combination of ultralow friction and negligible wear is achieved using hydrogen-free tetrahedral amorphous carbon (ta-C) with moderate hardness. Softer coatings exhibit similarly low wear and thin ZDDP-derived patchy tribofilms but higher friction. Conversely, harder ta-Cs undergo severe wear and sub-surface sulphur contamination. Contact-mechanics and quantum-chemical simulations reveal that shear combined with the high local contact pressure caused by the contact stiffness and average surface slope of hard ta-Cs favour ZDDP fragmentation and sulphur release. In absence of hydrogen, this is followed by local surface cold welding and sub-surface mechanical mixing of sulphur resulting in a decrease of yield stress and wear.
Colonization of dermal arterioles by Neisseria meningitidis provides a safe haven from neutrophils
Authors: Manriquez Valeria , Nivoit Pierre , Urbina Tomas , Echenique-Rivera Hebert , Melican Keira , Fernandez-Gerlinger Marie-Paule , Flamant Patricia , Schmitt Taliah , Bruneval Patrick , Obino Dorian , Duménil Guillaume 
Published: July 2021

AbstractThe human pathogenNeisseria meningitidiscan cause meningitis and fatal systemic disease. The bacteria colonize blood vessels and rapidly cause vascular damage, despite a neutrophil-rich inflammatory infiltrate. Here, we use a humanized mouse model to show that vascular colonization leads to the recruitment of neutrophils, which partially reduce bacterial burden and vascular damage. This partial effect is due to the ability of bacteria to colonize capillaries, venules and arterioles, as observed in human samples. In venules, potent neutrophil recruitment allows efficient bacterial phagocytosis. In contrast, in infected capillaries and arterioles, adhesion molecules such as E-Selectin are not expressed on the endothelium, and intravascular neutrophil recruitment is minimal. Our results indicate that the colonization of capillaries and arterioles byN. meningitidiscreates an intravascular niche that precludes the action of neutrophils, resulting in immune escape and progression of the infection.
The apicoplast link to fever-survival and artemisinin-resistance in the malaria parasite
Authors: Zhang Min , Wang Chengqi , Oberstaller Jenna , Thomas Phaedra , Otto Thomas D. , Casandra Debora , Boyapalle Sandhya , Adapa Swamy R. , Xu Shulin , Button-Simons Katrina , Mayho Matthew , Rayner Julian C. , Ferdig Michael T. , Jiang Rays H. Y. , Adams John H. 
Published: July 2021

AbstractThe emergence and spread of Plasmodium falciparum parasites resistant to front-line antimalarial artemisinin-combination therapies (ACT) threatens to erase the considerable gains against the disease of the last decade. Here, we develop a large-scale phenotypic screening pipeline and use it to carry out a large-scale forward-genetic phenotype screen in P. falciparum to identify genes allowing parasites to survive febrile temperatures. Screening identifies more than 200 P. falciparum mutants with differential responses to increased temperature. These mutants are more likely to be sensitive to artemisinin derivatives as well as to heightened oxidative stress. Major processes critical for P. falciparum tolerance to febrile temperatures and artemisinin include highly essential, conserved pathways associated with protein-folding, heat shock and proteasome-mediated degradation, and unexpectedly, isoprenoid biosynthesis, which originated from the ancestral genome of the parasite’s algal endosymbiont-derived plastid, the apicoplast. Apicoplast-targeted genes in general are upregulated in response to heat shock, as are other Plasmodium genes with orthologs in plant and algal genomes. Plasmodium falciparum parasites appear to exploit their innate febrile-response mechanisms to mediate resistance to artemisinin. Both responses depend on endosymbiont-derived genes in the parasite’s genome, suggesting a link to the evolutionary origins of Plasmodium parasites in free-living ancestors.
Insulin signaling regulates longevity through protein phosphorylation in Caenorhabditis elegans
Authors: Li Wen-Jun , Wang Chen-Wei , Tao Li , Yan Yong-Hong , Zhang Mei-Jun , Liu Ze-Xian , Li Yu-Xin , Zhao Han-Qing , Li Xue-Mei , He Xian-Dong , Xue Yu , Dong Meng-Qiu 
Published: July 2021

AbstractInsulin/IGF-1 Signaling (IIS) is known to constrain longevity by inhibiting the transcription factor FOXO. How phosphorylation mediated by IIS kinases regulates lifespan beyond FOXO remains unclear. Here, we profile IIS-dependent phosphorylation changes in a large-scale quantitative phosphoproteomic analysis of wild-type and three IIS mutant Caenorhabditis elegans strains. We quantify more than 15,000 phosphosites and find that 476 of these are differentially phosphorylated in the long-lived daf-2/insulin receptor mutant. We develop a machine learning-based method to prioritize 25 potential lifespan-related phosphosites. We perform validations to show that AKT-1 pT492 inhibits DAF-16/FOXO and compensates the loss of daf-2 function, that EIF-2α pS49 potently inhibits protein synthesis and daf-2 longevity, and that reduced phosphorylation of multiple germline proteins apparently transmits reduced DAF-2 signaling to the soma. In addition, an analysis of kinases with enriched substrates detects that casein kinase 2 (CK2) subunits negatively regulate lifespan. Our study reveals detailed functional insights into longevity.
Imparting multi-functionality to covalent organic framework nanoparticles by the dual-ligand assistant encapsulation strategy
Authors: Chen Liang , Wang Wenxing , Tian Jia , Bu Fanxing , Zhao Tiancong , Liu Minchao , Lin Runfeng , Zhang Fan , Lee Myongsoo , Zhao Dongyuan , Li Xiaomin 
Published: July 2021

AbstractThe potential applications of covalent organic frameworks (COFs) can be further developed by encapsulating functional nanoparticles within the frameworks. However, the synthesis of monodispersed core@shell structured COF nanocomposites without agglomeration remains a significant challenge. Herein, we present a versatile dual-ligand assistant strategy for interfacial growth of COFs on the functional nanoparticles with abundant physicochemical properties. Regardless of the composition, geometry or surface properties of the core, the obtained core@shell structured nanocomposites with controllable shell-thickness are very uniform without agglomeration. The derived bowl-shape, yolk@shell, core@satellites@shell nanostructures can also be fabricated delicately. As a promising type of photosensitizer for photodynamic therapy (PDT), the porphyrin-based COFs were grown onto upconversion nanoparticles (UCNPs). With the assistance of the near-infrared (NIR) to visible optical property of UCNPs core and the intrinsic porosity of COF shell, the core@shell nanocomposites can be applied as a nanoplatform for NIR-activated PDT with deep tissue penetration and chemotherapeutic drug delivery.
Single pixel imaging at megahertz switching rates via cyclic Hadamard masks
Authors: Hahamovich Evgeny , Monin Sagi , Hazan Yoav , Rosenthal Amir 
Published: July 2021

AbstractOptical imaging is commonly performed with either a camera and wide-field illumination or with a single detector and a scanning collimated beam; unfortunately, these options do not exist at all wavelengths. Single-pixel imaging offers an alternative that can be performed with a single detector and wide-field illumination, potentially enabling imaging applications in which the detection and illumination technologies are immature. However, single-pixel imaging currently suffers from low imaging rates owing to its reliance on configurable spatial light modulators, generally limited to 22 kHz rates. We develop an approach for rapid single-pixel imaging which relies on cyclic patterns coded onto a spinning mask and demonstrate it for in vivo imaging of C. elegans worms. Spatial modulation rates of up to 2.4 MHz, imaging rates of up to 72 fps, and image-reconstruction times of down to 1.5 ms are reported, enabling real-time visualization of dynamic objects.
Plant mixture balances terrestrial ecosystem C:N:P stoichiometry
Authors: Chen Xinli , Chen Han Y. H. 
Published: July 2021

AbstractPlant and soil C:N:P ratios are of critical importance to productivity, food-web dynamics, and nutrient cycling in terrestrial ecosystems worldwide. Plant diversity continues to decline globally; however, its influence on terrestrial C:N:P ratios remains uncertain. By conducting a global meta-analysis of 2049 paired observations in plant species mixtures and monocultures from 169 sites, we show that, on average across all observations, the C:N:P ratios of plants, soils, soil microbial biomass and enzymes did not respond to species mixture nor to the species richness in mixtures. However, the mixture effect on soil microbial biomass C:N changed from positive to negative, and those on soil enzyme C:N and C:P shifted from negative to positive with increasing functional diversity in mixtures. Importantly, species mixture increased the C:N, C:P, N:P ratios of plants and soils when background soil C:N, C:P, and N:P were low, but decreased them when the respective background ratios were high. Our results demonstrate that plant mixtures can balance terrestrial plant and soil C:N:P ratios dependent on background soil C:N:P. Our findings highlight that plant diversity conservation does not only increase plant productivity, but also optimizes ecosystem stoichiometry for the diversity and productivity of today’s and future vegetation.
Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants
Authors: Ikegame Satoshi , Siddiquey Mohammed N. A. , Hung Chuan-Tien , Haas Griffin , Brambilla Luca , Oguntuyo Kasopefoluwa Y. , Kowdle Shreyas , Chiu Hsin-Ping , Stevens Christian S. , Vilardo Ariel Esteban , Edelstein Alexis , Perandones Claudia , Kamil Jeremy P. , Lee Benhur 
Published: July 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected at least 180 million people since its identification as the cause of the current COVID-19 pandemic. The rapid pace of vaccine development has resulted in multiple vaccines already in use worldwide. The contemporaneous emergence of SARS-CoV-2 ‘variants of concern’ (VOC) across diverse geographic locales underscores the need to monitor the efficacy of vaccines being administered globally. All WHO designated VOC carry spike (S) polymorphisms thought to enable escape from neutralizing antibodies. Here, we characterize the neutralizing activity of post-Sputnik V vaccination sera against the ensemble of S mutations present in alpha (B.1.1.7) and beta (B.1.351) VOC. Using de novo generated replication-competent vesicular stomatitis virus expressing various SARS-CoV-2-S in place of VSV-G (rcVSV-CoV2-S), coupled with a clonal 293T-ACE2 + TMPRSS2 + cell line optimized for highly efficient S-mediated infection, we determine that only 1 out of 12 post-vaccination serum samples shows effective neutralization (IC90) of rcVSV-CoV2-S: B.1.351 at full serum strength. The same set of sera efficiently neutralize S from B.1.1.7 and exhibit only moderately reduced activity against S carrying the E484K substitution alone. Taken together, our data suggest that control of some emergent SARS-CoV-2 variants may benefit from updated vaccines.
CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial
Authors: Spiegel Jay Y. , Patel Shabnum , Muffly Lori , Hossain Nasheed M. , Oak Jean , Baird John H. , Frank Matthew J. , Shiraz Parveen , Sahaf Bita , Craig Juliana , Iglesias Maria , Younes Sheren , Natkunam Yasodha , Ozawa Michael G. , Yang Eric , Tamaresis John , Chinnasamy Harshini , Ehlinger Zach , Reynolds Warren , Lynn Rachel , Rotiroti Maria Caterina , Gkitsas Nikolaos , Arai Sally , Johnston Laura , Lowsky Robert , Majzner Robbie G. , Meyer Everett , Negrin Robert S. , Rezvani Andrew R. , Sidana Surbhi , Shizuru Judith , Weng Wen-Kai , Mullins Chelsea , Jacob Allison , Kirsch Ilan , Bazzano Magali , Zhou Jing , Mackay Sean , Bornheimer Scott J. , Schultz Liora , Ramakrishna Sneha , Davis Kara L. , Kong Katherine A. , Shah Nirali N. , Qin Haiying , Fry Terry , Feldman Steven , Mackall Crystal L. , Miklos David B. 
Published: July 2021

AbstractDespite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Ten of 16 patients with large B cell lymphoma (LBCL) with progressive disease after CAR19 treatment had absent or low CD19. Lower surface CD19 density pretreatment was associated with progressive disease. To prevent relapse with CD19− or CD19lo disease, we tested a bispecific CAR targeting CD19 and/or CD22 (CD19-22.BB.z-CAR) in a phase I clinical trial (NCT03233854) of adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) and LBCL. The primary end points were manufacturing feasibility and safety with a secondary efficacy end point. Primary end points were met; 97% of products met protocol-specified dose and no dose-limiting toxicities occurred during dose escalation. In B-ALL (n = 17), 100% of patients responded with 88% minimal residual disease-negative complete remission (CR); in LBCL (n = 21), 62% of patients responded with 29% CR. Relapses were CD19−/lo in 50% (5 out of 10) of patients with B-ALL and 29% (4 out of 14) of patients with LBCL but were not associated with CD22−/lo disease. CD19/22-CAR products demonstrated reduced cytokine production when stimulated with CD22 versus CD19. Our results further implicate antigen loss as a major cause of CAR T cell resistance, highlight the challenge of engineering multi-specific CAR T cells with equivalent potency across targets and identify cytokine production as an important quality indicator for CAR T cell potency.
Mechanical activities of self-beating cardiomyocyte aggregates under mechanical compression
Authors: Nakano Ken , Nanri Naoya , Tsukamoto Yoshinari , Akashi Mitsuru 
Published: July 2021

AbstractSince the discovery of synchronous pulsations in cardiomyocytes (CMs), electrical communication between CMs has been emphasized; however, recent studies suggest the possibility of mechanical communication. Here, we demonstrate that spherical self-beating CM aggregates, termed cardiac spheroids (CSs), produce enhanced mechanical energy under mechanical compression and work cooperatively via mechanical communication. For single CSs between parallel plates, compression increased both beating frequency and beating energy. Contact mechanics revealed a scaling law on the beating energy, indicating that the most intensively stressed cells in the compressed CSs predominantly contributed to the performance of mechanical work against mechanical compression. For pairs of CSs between parallel plates, compression immediately caused synchronous beating with mechanical coupling. Compression tended to strengthen and stabilize the synchronous beating, although some irregularity and temporary arrest were observed. These results suggest that mechanical compression is an indispensable control parameter when evaluating the activities of CMs and their aggregates.
Comparative assessment of amino acids composition in two types of marine fish silage
Authors: Gauthankar Mukund , Khandeparker Rakhee , Shivaramu Mamatha S. , Salkar Komal , Sreepada Rayadurga Anantha , Paingankar Mandar 
Published: July 2021

AbstractFish silage is a brown liquefied product achieved by the action of enzymes when finely grounded whole/parts of either single or mixed fish types are subjected to acidification. This study made a comparative assessment of biochemical and nutritive properties, especially the amino acid composition in supernatant phase of formic acid silages prepared from two fish types, Indian mackerel (Rastrelliger kanagurta) and false travely (Lactarius lactarius) representing fat fish (FF, fat content > 5%) and lean fish (LF, fat content < 5%), respectively during 35 days of fermentation (DoF). Significantly higher content of total amino acid (TAA) and free amino acids (FAA) were recorded in FFS (TAA, 41.2 ± 0.03 mg/g; FAA, 31.3 ± 0.003 mg/g) compared to LFS (TAA, 35.8 ± 0.07 mg/g; FAA, 18.26 ± 0.003 mg/g; FAA, 31.3 ± 0.003 mg/g) (p < 0.05). At the end of 35 DoF, the concentrations of amino acids such as asparagine, histidine, isoleucine, valine, cysteine, serine, lysine and arginine were significantly higher in FFS as compared to LFS. The relative amino acid composition of FFS and LFS varied in accordance with DoF and the relationship was found to be highly significant (ANOVA, p < 0.00001). High concentrations of l-amino acids such as leucine, glutamic acid and arginine were recorded in both FFS and LFS. In conclusion, the analysis suggested that a fermentation period of 25–30 days showed a significant effect on the composition of amino acids in both types of ensilage compared to other fermentation periods (p < 0.05). Considering the role of amino acids in enhancing the plant growth and proliferation, the findings of the present study are quite useful.