bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating Dam Water Release Strategies for Migrating Adult Salmon Using Computational Fluid Dynamic Modeling and Biotelemetry
Authors: Li Pengcheng , Zhang Wenming , Burnett Nicholas J. , Zhu David Z. , Casselman Matthew , Hinch Scott G.
Published: July 2021

Hydrodynamics in dam tailraces can influence the swimming behavior and survival of fish, and yet there have been few studies that have linked the movement patterns of fish to encountered flow patterns. In this study, we examined the flow field downstream of Seton Dam in British Columbia, Canada using acoustic Doppler current profilers (ADCPs), and computational fluid dynamic (CFD) modeling of two dam water release scenarios to understand their impacts on the swim speed and behavior of upriver‐migrating adult sockeye salmon (Oncorhynchus nerka). Forty‐five sockeye salmon were tagged with acoustic transmitters and tracked to understand their movement patterns, swim speed, residence time in the dam tailrace, and postdam passage survival. The water release scenarios produced contrasting tailrace hydrodynamics and altered the behavior of migrating sockeye salmon. Tagged fish avoided areas of high velocity (>2.4 m/s or four body lengths/s, twice their critical swim speed), high Reynolds shear stress (>21 Pa), and high turbulence kinetic energy (>0.12 m2 s−2) in the dam tailrace. Excessive use of anaerobic metabolism, together with high water shear stress adjacent to and downstream of the fishway entrance, were thought to be the main cause for low postdam passage survival of sockeye salmon. Additional dam water release strategies were assessed with the CFD model to target releases that improve the migration conditions for sockeye salmon. Our study highlights the importance of pairing hydraulic and ecological information to better understand and improve the migration conditions for wild fish.
Onshore Thermokarst Primes Subsea Permafrost Degradation
Authors: Angelopoulos Michael , Overduin Pier P. , Jenrich Maren , Nitze Ingmar , Günther Frank , Strauss Jens , Westermann Sebastian , Schirrmeister Lutz , Kholodov Alexander , Krautblatter Michael , Grigoriev Mikhail N. , Grosse Guido
Published: July 2021

The response of permafrost to marine submergence can vary between ice‐rich late Pleistocene deposits and the thermokarst basins that thawed out during the Holocene. We hypothesize that inundated Alases offshore thaw faster than submerged Yedoma. To test this hypothesis, we estimated depths to the top of ice‐bearing permafrost offshore of the Bykovsky Peninsula in northeastern Siberia using electrical resistivity surveys. The surveys traversed submerged lagoon deposits, drained and refrozen Alas deposits, and undisturbed Yedoma from the coastline to 373 m offshore. While the permafrost degradation rates of the submerged Yedoma were in the range of similar sites, the submerged Alas permafrost degradation rates were up to 170 faster. Remote sensing analyses suggest that 54 of lagoons wider than 500 m along northeast Siberian and northwest American coasts originated in thermokarst basins. Given the abundance of thermokarst basins and lakes along parts of the Arctic coastline, their effect on subsea permafrost degradation must be similarly prevalent.
A Strain‐Model Based InSAR Time Series Method and Its Application to The Geysers Geothermal Field, California
Authors: Liu Jihong , Hu Jun , Bürgmann Roland , Li Zhiwei , Sun Qian , Ma Zhangfeng
Published: July 2021

A new time series interferometric synthetic aperture radar method is presented based on a strain model. Traditionally, the interferometric phases are optimized based only on a constant set of statistically homogeneous points throughout the observing period, and thus the decorrelated phase cannot be well recovered and possible incoherent (or coherent) phases are (are not) used to optimize the target phase. In the proposed method, a strain model, representing the geophysical relationship of spatially adjacent points' deformations, is employed to optimize the interferometric phases interferogram‐by‐interferogram. The unwrapped phase time series can be estimated from the wrapped interferograms based on the linear iterative weighted least squares method, which is simple and can effectively suppress the decorrelation noise. Both simulations and analysis of data over The Geysers geothermal field (TG), California are conducted, validating that the proposed method can reduce the decorrelations and simultaneously preserve the deformation signals. The displacement results of TG from 2007–2011 L‐band ascending ALOS‐1 data and 2015–2020 C‐band ascending/descending Sentinel‐1 data reveal that (a) the displacement rate of TG is decreasing from 2007–2011 to 2015–2020, and (b) temporally variable displacement signals in addition to steady displacement can be observed from 2015 to 2020 for both the east‐west and the vertical components.
Transport of Heat by Hydrothermal Circulation in a Young Rift Setting: Observations From the Auka and JaichMaa Ja'ag' Vent Field in the Pescadero Basin, Southern Gulf of California
Authors: Negrete‐Aranda Raquel , Neumann Florian , Contreras Juan , Harris Robert N. , Spelz Ronald M. , Zierenberg Robert , Caress David W.
Published: July 2021

Heat flow measurements collected throughout the Auka and JaichMaa Ja'ag' hydrothermal vent fields in the central graben of the Southern Pescadero Basin, southern Gulf of California, indicate upflow of hydrothermal fluids associated with rifting dissipate heat in excess of 10 W/m2 around faults that have a few kilometers in length. Paradoxically, longer faults do not show signs of venting. Heat flow anomalies slowly decay to background values of ∼2 W/m2 at distances of ∼1 km from these faults following an inverse square‐root distance law. We develop a near‐fault model of heat transport in steady state for the Auka vent field based on the fundamental Green's function solution of the heat equation. The model includes the effects of circulation in fracture networks, and the lateral seepage of geothermal brines to surrounding hemipelagic sediments. We use an optimal fitting method to estimate the reservoir depth, permeability, and circulation rate. Independently derived constraints for the model, indicate the heat source is at a depth of ∼5.7 km; from the model, permeability and flow rates in the fracture system are ∼10−14 m2 and 10−6 m/s, respectively, and ∼10−16 m2 and 10−8 m/s in the basin aquitards, respectively. Model results point to the importance of fault scaling laws in controlling sediment‐hosted vent fields and slow circulation throughout low permeability sediments in controlling the brine's chemistry. Although the fault model seems appropriate and straightforward for the Pescadero vents, it does seem to be the exception to the other known sediment‐hosted vent fields in the Pacific.
Socioeconomic position and body composition in childhood in high- and middle-income countries: a systematic review and narrative synthesis
Authors: Bridger Staatz Charis , Kelly Yvonne , Lacey Rebecca E. , Blodgett Joanna M. , George Anitha , Arnot Megan , Walker Emma , Hardy Rebecca
Published: July 2021

Background

The relation between socioeconomic position (SEP) and obesity measured by body mass index (BMI), a measure of weight for height, has been extensively reviewed in children, showing consistent associations between disadvantaged SEP and higher BMI in high-income countries (HICs) and lower BMI in middle-income countries (MICs). Fat mass (FM), a more accurate measure of adiposity, and fat-free mass (FFM) are not captured by BMI, but have been shown to track from childhood to adulthood, and be important for cardiovascular health and functional outcomes in later life. It is not clear whether body composition is associated with SEP. We systematically reviewed the association between SEP and body composition in childhood.

Methods

A systematic review was carried out following PRISMA guidelines. The protocol was pre-registered with PROSPERO (CRD42019119937). Original studies in the English language, which examined the association between SEP and body composition in childhood, were included. An electronic search of three databases was conducted. Two independent reviewers carried out screening, data extraction and quality assessment. Due to heterogeneity in results, a narrative synthesis was conducted. Heterogeneity in findings according to SEP, sex, body composition measure and country income level was investigated.

Results

50 papers were included, the majority from HICs. No papers were from low-income countries. Disadvantage in childhood was associated with greater FM and lower FFM in HICs, but with lower FM and lower FFM in MICs. When measures of FFM indexed to height were used there was no evidence of associations with SEP. In HICs, more studies reported associations between disadvantaged SEP and higher FM among girls comparative to boys.

Conclusions

Inequalities in FM are evident in HICs and, in the opposite direction, in MICs and follow similar trends to inequalities for BMI. Inequalities in height are likely important in understanding inequalities in FFM.
Determination of the embedded electronic states at nanoscale interface via surface-sensitive photoemission spectroscopy
Authors: Wang Hui-Qiong , Xu Jiayi , Lin Xiaoyuan , Li Yaping , Kang Junyong , Zheng Jin-Cheng
Published: July 2021

The fabrication of small-scale electronics usually involves the integration of different functional materials. The electronic states at the nanoscale interface plays an important role in the device performance and the exotic interface physics. Photoemission spectroscopy is a powerful technique to probe electronic structures of valence band. However, this is a surface-sensitive technique that is usually considered not suitable for the probing of buried interface states, due to the limitation of electron-mean-free path. This article reviews several approaches that have been used to extend the surface-sensitive techniques to investigate the buried interface states, which include hard X-ray photoemission spectroscopy, resonant soft X-ray angle-resolved photoemission spectroscopy and thickness-dependent photoemission spectroscopy. Especially, a quantitative modeling method is introduced to extract the buried interface states based on the film thickness-dependent photoemission spectra obtained from an integrated experimental system equipped with in-situ growth and photoemission techniques. This quantitative modeling method shall be helpful to further understand the interfacial electronic states between functional materials and determine the interface layers.
Ammonia-oxidizing archaea possess a wide range of cellular ammonia affinities
Authors: Jung Man-Young , Sedlacek Christopher J , Kits K Dimitri , Mueller Anna J , Rhee Sung-Keun , Hink Linda , Nicol Graeme W , Bayer Barbara , Lehtovirta-Morley Laura , Wright Chloe , de la Torre Jose R , Herbold Craig W , Pjevac Petra , Daims Holger , Wagner Michael
Published: July 2021

Nitrification, the oxidation of ammonia to nitrate, is an essential process in the biogeochemical nitrogen cycle. The first step of nitrification, ammonia oxidation, is performed by three, often co-occurring guilds of chemolithoautotrophs: ammonia-oxidizing bacteria (AOB), archaea (AOA), and complete ammonia oxidizers (comammox). Substrate kinetics are considered to be a major niche-differentiating factor between these guilds, but few AOA strains have been kinetically characterized. Here, the ammonia oxidation kinetic properties of 12 AOA representing all major cultivated phylogenetic lineages were determined using microrespirometry. Members of the genus Nitrosocosmicus have the lowest affinity for both ammonia and total ammonium of any characterized AOA, and these values are similar to previously determined ammonia and total ammonium affinities of AOB. This contrasts previous assumptions that all AOA possess much higher substrate affinities than their comammox or AOB counterparts. The substrate affinity of ammonia oxidizers correlated with their cell surface area to volume ratios. In addition, kinetic measurements across a range of pH values supports the hypothesis that—like for AOB—ammonia and not ammonium is the substrate for the ammonia monooxygenase enzyme of AOA and comammox. Together, these data will facilitate predictions and interpretation of ammonia oxidizer community structures and provide a robust basis for establishing testable hypotheses on competition between AOB, AOA, and comammox.
Efficacy and tolerability of Janus kinase inhibitors in myelofibrosis: a systematic review and network meta-analysis
Authors: Sureau Léa , Orvain Corentin , Ianotto Jean-Christophe , Ugo Valérie , Kiladjian Jean-Jacques , Luque Paz Damien , Riou Jérémie
Published: July 2021

Myelofibrosis is a myeloproliferative neoplasm associated with constitutional symptoms, increasing splenomegaly, and worsening cytopenias. Janus kinase (JAK) inhibitors have been used for the treatment of myelofibrosis for several years, but there is a lack of comparative information between those treatments. A systematic review and network meta-analysis was performed on randomized controlled trials in patients with myelofibrosis receiving JAK inhibitor or placebo or control. Primary outcomes were efficacy on spleen volume reduction and total symptom score reduction. Additional analyses were conducted on anemia and thrombopenia events. Seven studies were included in the network meta-analysis including 1953 patients randomly assigned to four JAK inhibitors—ruxolitinib, fedratinib, pacritinib, momelotinib—or control. In first-line therapy, momelotinib and fedratinib were associated with comparable efficacy to ruxolitinib, and with less toxicity on erythrocytes and platelets, respectively. Pacritinib was less effective on splenomegaly than ruxolitinib as a first-line treatment but seemed effective in second line, after ruxolitinib exposure. Fedratinib and ruxolitinib that are FDA approved in myelofibrosis have both confirmed being valuable option to treat splenomegaly and constitutional symptoms, and their slightly different tolerance-profiles can guide therapeutic choice for first-line treatment, according to patient profile. Momelotinib could be another option especially due to its positive effect on anemia.
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

Omidubicel (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

Folate 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

Reflection 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

Friction 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

The 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

The 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

Insulin/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

The 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

Optical 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

Plant 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

Severe 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

Despite 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

Since 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

Fish 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.
Cortical silent period reflects individual differences in action stopping performance
Authors: Paci Mario , Di Cosmo Giulio , Perrucci Mauro Gianni , Ferri Francesca , Costantini Marcello
Published: July 2021

Inhibitory control is the ability to suppress inappropriate movements and unwanted actions, allowing to regulate impulses and responses. This ability can be measured ﻿via the Stop Signal Task, which provides a temporal index of response inhibition, namely the stop signal reaction time (SSRT). At the neural level, Transcranial Magnetic Stimulation (TMS) allows to investigate motor inhibition within the primary motor cortex (M1), such as the cortical silent period (CSP) which is an index of GABAB-mediated intracortical inhibition within M1. Although there is strong evidence that intracortical inhibition varies during action stopping, it is still not clear whether differences in the neurophysiological markers of intracortical inhibition contribute to behavioral differences in actual inhibitory capacities. Hence, here we explored the relationship between intracortical inhibition within M1 and behavioral response inhibition. GABABergic-mediated inhibition in M1 was determined by the duration of CSP, while behavioral inhibition was assessed by the SSRT. We found a significant positive correlation between CSP’s duration and SSRT, namely that individuals with greater levels of GABABergic-mediated inhibition seem to perform overall worse in inhibiting behavioral responses. These results support the assumption that individual differences in intracortical inhibition are mirrored by individual differences in action stopping abilities.
Outer retina dysfunction and choriocapillaris impairment in type 1 diabetes
Authors: Parravano M. , Ziccardi L. , Borrelli E. , Costanzo E. , Frontoni S. , Picconi F. , Parisi V. , Sacconi R. , Di Renzo A. , Varano M. , Querques G.
Published: July 2021

To study the outer retina morpho-functional characteristics and the choriocapillaris (CC) features in type 1 diabetic (T1D) patients, with and without signs of diabetic retinopathy (NPDR and NoDR). Twenty-five NPDR and 18 NoDR eyes were imaged by Optical Coherence Tomography Angiography. Ellipsoid zone (EZ) “normalized” reflectivity and CC perfusion density parameters, as flow deficits number (FDn), flow deficit average area (FDa) and flow deficit percentage (FD%), were analysed. Multifocal electroretinogram (mfERG) response amplitude densities (RADs) were measured. Mean EZ “normalized” reflectivity, CC FDn and FD% values, were similar (p > 0.05) in both groups, FDa was significant greater (p > 0.05) in NPDR compared with NoDR eyes. MfERG-RADs were similar in both groups. NPDR eyes showed a significant (p < 0.05) linear correlation between RADs and both, CC FDa and FD%. The EZ “normalized” reflectivity was negatively correlated with CC FD% in NoDR eyes. In NPDR T1D eyes a significant relationship between abnormal outer retina functional responses and CC impairment was observed, while in NoDR eyes the photoreceptor reflectivity was correlated to CC abnormalities. The outer retina dysfunction in NPDR correlated to CC drop-out let hypothesize that the outer retinal elements are functionally impaired in proportion to the CC vascular supply deficit.
The association of atherosclerotic cardiovascular disease and statin use with inflammation and treatment outcomes in tuberculosis
Authors: Chidambaram Vignesh , Ruelas Castillo Jennie , Kumar Amudha , Wei Justin , Wang Siqing , Majella Marie Gilbert , Gupte Akshay , Wang Jann-Yuan , Karakousis Petros C.
Published: July 2021

Tuberculosis (TB) and atherosclerotic cardiovascular disease (ASCVD) have a close epidemiological and pathogenetic overlap. Thus, it becomes essential to understand the relationship between ASCVD and TB outcomes. From our retrospective cohort on drug-susceptible TB patients at the National Taiwan University Hospital, we assessed the association of pre-existing ASCVD (coronary artery disease (CAD) and atherothrombotic stroke (ATS)) with 9-month all-cause and infection-related mortality and the extent of mediation by systemic inflammatory markers. We determined the effect of pre-existing ASCVD on 2-month sputum microbiological status. Among ASCVD patients, we assessed the association of statin use on mortality. Nine-month all-cause mortality was higher in CAD patients with prior acute myocardial infarction (CAD+AMI+) (adjusted HR 2.01, 95%CI 1.38–3.00) and ATS patients (aHR 2.79, 95%CI 1.92–4.07) and similarly, for infection-related mortality was higher in CAD+AMI+ (aHR 1.95, 95%CI 1.17–3.24) and ATS (aHR 2.04, 95%CI 1.19–3.46) after adjusting for confounding factors. Pre-existing CAD (AMI- or AMI+) or ATS did not change sputum culture conversion or sputum smear AFB positivity at 2 months. The CAD+AMI+ group had significantly higher levels of CRP at TB diagnosis in the multivariable linear regression analysis (Adjusted B(SE) 1.24(0.62)). CRP mediated 66% (P = 0.048) and 25% (P = 0.033) of the association all-cause mortality with CAD+AMI− and CAD+AMI+, respectively. In summary, patients with ASCVD have higher hazards of 9-month all-cause and infection-related mortality, with elevated serum inflammation mediating one to three-quarters of this association when adjusted for confounders. Statin use was associated with lower all-cause mortality among patients with ASCVD.
S494 O-glycosylation site on the SARS-CoV-2 RBD affects the virus affinity to ACE2 and its infectivity; a molecular dynamics study
Authors: Rahnama Shadi , Azimzadeh Irani Maryam , Amininasab Mehriar , Ejtehadi Mohammad Reza
Published: July 2021

SARS-CoV-2 is a strain of Coronavirus family that caused the ongoing pandemic of COVID-19. Several studies showed that the glycosylation of virus spike (S) protein and the Angiotensin-Converting Enzyme 2 (ACE2) receptor on the host cell is critical for the virus infectivity. Molecular Dynamics (MD) simulations were used to explore the role of a novel mutated O-glycosylation site (D494S) on the Receptor Binding Domain (RBD) of S protein. This site was suggested as a key mediator of virus-host interaction. By exploring the dynamics of three O-glycosylated models and the control systems of unglcosylated S4944 and S494D complexes, it was shown that the decoration of S494 with elongated O-glycans results in stabilized interactions on the direct RBD-ACE2. Calculation of the distances between RBD and two major H1, H2 helices of ACE2 and the interacting pairs of amino acids in the interface showed that the elongated O-glycan maintains these interactions by forming several polar contacts with the neighbouring residues while it would not interfere in the direct binding interface. Relative binding free energy of RBD-ACE2 is also more favorable in the O-glycosylated models with longer glycans. The increase of RBD binding affinity to ACE2 depends on the size of attached O-glycan. By increasing the size of O-glycan, the RBD-ACE2 binding affinity will increase. Hence, this crucial factor must be taken into account for any further inhibitory approaches towards RBD-ACE2 interaction.
A modified age-structured SIR model for COVID-19 type viruses
Authors: Ram Vishaal , Schaposnik Laura P.
Published: July 2021

We present a modified age-structured SIR model based on known patterns of social contact and distancing measures within Washington, USA. We find that population age-distribution has a significant effect on disease spread and mortality rate, and contribute to the efficacy of age-specific contact and treatment measures. We consider the effect of relaxing restrictions across less vulnerable age-brackets, comparing results across selected groups of varying population parameters. Moreover, we analyze the mitigating effects of vaccinations and examine the effectiveness of age-targeted distributions. Lastly, we explore how our model can applied to other states to reflect social-distancing policy based on different parameters and metrics.
Lower peripheral blood Toll-like receptor 3 expression is associated with an unfavorable outcome in severe COVID-19 patients
Authors: Menezes Maria Clara Saad , Veiga Alicia Dudy Müller , Martins de Lima Thais , Kunimi Kubo Ariga Suely , Vieira Barbeiro Hermes , de Lucena Moreira Claudia , Pinto Agnes Araujo Sardinha , Brandao Rodrigo Antonio , Marchini Julio Flavio , Alencar Julio Cesar , Marino Lucas Oliveira , Gomez Luz Marina , Olsen Saraiva Camara Niels , Souza Heraldo P.
Published: July 2021

The role of innate immunity in COVID-19 is not completely understood. Therefore, this study explored the impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection on the expression of Pattern Recognition Receptors (PRRs) in peripheral blood cells and their correlated cytokines. Seventy-nine patients with severe COVID-19 on admission, according to World Health Organization (WHO) classification, were divided into two groups: patients who needed mechanical ventilation and/or deceased (SEVERE, n = 50) and patients who used supplementary oxygen but not mechanical ventilation and survived (MILD, n = 29); a control group (CONTROL, n = 17) was also enrolled. In the peripheral blood, gene expression (mRNA) of Toll-like receptors (TLRs) 3, 4, 7, 8, and 9, retinoic-acid inducible gene I (RIGI), NOD-like receptor family pyrin domain containing 3 (NLRP3), interferon alpha (IFN-α), interferon beta (IFN-β), interferon gamma (IFN-γ), interferon lambda (IFN-λ), pro-interleukin(IL)-1β (pro-IL-1β), and IL-18 was determined on admission, between 5–9 days, and between 10–15 days. Circulating cytokines in plasma were also measured. When compared to the COVID-19 MILD group, the COVID-19 SEVERE group had lower expression of TLR3 and overexpression of TLR4.
Socio-emotional and motor engagement during musical activities in older adults with major neurocognitive impairment
Authors: Hobeika Lise , Ghilain Matthieu , Schiaratura Loris , Lesaffre Micheline , Huvent-Grelle Dominique , Puisieux François , Samson Séverine
Published: July 2021

Although music therapy may engender clinical benefits in patients with neurodegenerative disease, the impacts of social and musical factors of such activities on socio-emotional and motor engagements are poorly understood. To address this issue, non-verbal behaviors of 97 patients with or without major cognitive impairment (CI) were assessed when listening to music or a metronome in front of a musician who was present physically (live) or virtually (video). Socio-emotional engagement was quantified as emotional facial expression production and gaze direction. Motor engagement was quantified as overall body motion and the production of rhythmic movements. In both groups, positive facial expressions were more frequent and rhythmic motor activities lasted longer with music than with a metronome, and during a live performance rather than a video performance. Relative to patients without CI, patients with CI moved less with music, expressed fewer emotions, and spent less time looking at the musician in the video condition and in the metronome condition. The relative reductions in motor and socio-emotional engagements in patients with CI might be markers of disease progression. However, the presence of a live partner induces older adults to engage emotionally and physically in musical activities emphasizing the relevance of using live performance as motivational levers during music therapy.