bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transformation of tenofovir into stable ProTide nanocrystals with long-acting pharmacokinetic profiles
Authors: Cobb Denise A. , Smith Nathan , Deodhar Suyash , Bade Aditya N. , Gautam Nagsen , Shetty Bhagya Laxmi Dyavar , McMillan JoEllyn , Alnouti Yazen , Cohen Samuel M. , Gendelman Howard E. , Edagwa Benson 
Published: September 2021

AbstractTreatment and prevention of human immunodeficiency virus type one (HIV-1) infection was transformed through widespread use of antiretroviral therapy (ART). However, ART has limitations in requiring life-long daily adherence. Such limitations have led to the creation of long-acting (LA) ART. While nucleoside reverse transcriptase inhibitors (NRTI) remain the ART backbone, to the best of our knowledge, none have been converted into LA agents. To these ends, we transformed tenofovir (TFV) into LA surfactant stabilized aqueous prodrug nanocrystals (referred to as NM1TFV and NM2TFV), enhancing intracellular drug uptake and retention. A single intramuscular injection of NM1TFV, NM2TFV, or a nanoformulated tenofovir alafenamide (NTAF) at 75 mg/kg TFV equivalents to Sprague Dawley rats sustains active TFV-diphosphate (TFV-DP) levels ≥ four times the 90% effective dose for two months. NM1TFV, NM2TFV and NTAF elicit TFV-DP levels of 11,276, 1,651, and 397 fmol/g in rectal tissue, respectively. These results are a significant step towards a LA TFV ProTide.
Vacuum-field-induced THz transport gap in a carbon nanotube quantum dot
Authors: Valmorra F. , Yoshida K. , Contamin L. C. , Messelot S. , Massabeau S. , Delbecq M. R. , Dartiailh M. C. , Desjardins M. M. , Cubaynes T. , Leghtas Z. , Hirakawa K. , Tignon J. , Dhillon S. , Balibar S. , Mangeney J. , Cottet A. , Kontos T. 
Published: September 2021

AbstractThe control of light-matter interaction at the most elementary level has become an important resource for quantum technologies. Implementing such interfaces in the THz range remains an outstanding problem. Here, we couple a single electron trapped in a carbon nanotube quantum dot to a THz resonator. The resulting light-matter interaction reaches the deep strong coupling regime that induces a THz energy gap in the carbon nanotube solely by the vacuum fluctuations of the THz resonator. This is directly confirmed by transport measurements. Such a phenomenon which is the exact counterpart of inhibition of spontaneous emission in atomic physics opens the path to the readout of non-classical states of light using electrical current. This would be a particularly useful resource and perspective for THz quantum optics.
Hecw controls oogenesis and neuronal homeostasis by promoting the liquid state of ribonucleoprotein particles
Authors: Fajner Valentina , Giavazzi Fabio , Sala Simona , Oldani Amanda , Martini Emanuele , Napoletano Francesco , Parazzoli Dario , Cesare Giuliana , Cerbino Roberto , Maspero Elena , Vaccari Thomas , Polo Simona 
Published: September 2021

AbstractSpecialised ribonucleoprotein (RNP) granules are a hallmark of polarized cells, like neurons and germ cells. Among their main functions is the spatial and temporal modulation of the activity of specific mRNA transcripts that allow specification of primary embryonic axes. While RNPs composition and role are well established, their regulation is poorly defined. Here, we demonstrate that Hecw, a newly identified Drosophila ubiquitin ligase, is a key modulator of RNPs in oogenesis and neurons. Hecw depletion leads to the formation of enlarged granules that transition from a liquid to a gel-like state. Loss of Hecw activity results in defective oogenesis, premature aging and climbing defects associated with neuronal loss. At the molecular level, reduced ubiquitination of the Fmrp impairs its translational repressor activity, resulting in altered Orb expression in nurse cells and Profilin in neurons.
Community and single cell analyses reveal complex predatory interactions between bacteria in high diversity systems
Authors: Cohen Yossi , Pasternak Zohar , Müller Susann , Hübschmann Thomas , Schattenberg Florian , Sivakala Kunjukrishnan Kamalakshi , Abed-Rabbo Alfred , Chatzinotas Antonis , Jurkevitch Edouard 
Published: September 2021

AbstractA fundamental question in community ecology is the role of predator–prey interactions in food-web stability and species coexistence. Although microbial microcosms offer powerful systems to investigate it, interrogating the environment is much more arduous. Here, we show in a 1-year survey that the obligate predators Bdellovibrio and like organisms (BALOs) can regulate prey populations, possibly in a density-dependent manner, in the naturally complex, species-rich environments of wastewater treatment plants. Abundant as well as rarer prey populations are affected, leading to an oscillating predatory landscape shifting at various temporal scales in which the total population remains stable. Shifts, along with differential prey range, explain co-existence of the numerous predators through niche partitioning. We validate these sequence-based findings using single-cell sorting combined with fluorescent hybridization and community sequencing. Our approach should be applicable for deciphering community interactions in other systems.
COVID-19 patients age, comorbidity profiles and clinical presentation related to the SARS-CoV-2 UK-variant spread in the Southeast of France
Authors: Courjon Johan , Contenti Julie , Demonchy Elisa , Levraut Jacques , Barbry Pascal , Rios Géraldine , Dellamonica Jean , Chirio David , Bonnefoy Caroline , Giordanengo Valérie , Carles Michel 
Published: September 2021

AbstractThe variant 20I/501Y.V1, associated to a higher risk of transmissibility, emerged in Nice city (Southeast of France, French Riviera) during January 2021. The pandemic has resumed late December 2020 in this area. A high incidence rate together with a fast turn-over of the main circulating variants, provided us the opportunity to analyze modifications in clinical profile and outcome traits. We performed an observational study in the University hospital of Nice from December 2020 to February 2021. We analyzed data of sequencing of SARS-CoV-2 from the sewage collector and PCR screening from all positive samples at the hospital. Then, we described the characteristics of all COVID-19 patients admitted in the emergency department (ED) (n = 1247) and those hospitalized in the infectious diseases ward or ICU (n = 232). The UK-variant was absent in this area in December, then increasingly spread in January representing 59% of the PCR screening performed mid-February. The rate of patients over 65 years admitted to the ED decreased from 63 to 50% (p = 0.001). The mean age of hospitalized patients in the infectious diseases ward decreased from 70.7 to 59.2 (p < 0.001) while the proportion of patients without comorbidity increased from 16 to 42% (p = 0.007). Spread of the UK-variant in the Southeast of France affects younger and healthier patients.
Effect of arbuscular mycorrhizal fungi on the physiological functioning of maize under zinc-deficient soils
Authors: Saboor Abdul , Ali Muhammad Arif , Danish Subhan , Ahmed Niaz , Fahad Shah , Datta Rahul , Ansari Mohammad Javed , Nasif Omaima , Rahman Muhammad Habib ur , Glick Bernard R. 
Published: September 2021

AbstractZinc (Zn) deficiency can severely inhibit plant growth, yield, and enzymatic activities. Zn plays a vital role in various enzymatic activities in plants. Arbuscular mycorrhizal fungi (AMF) play a crucial role in improving the plant’s Zn nutrition and mitigating Zn stress effects on plants. The current study was conducted to compare the response of inoculated and non-inoculated maize (YH 1898) in the presence of different levels of zinc under greenhouse conditions under a Zn deficient condition. There were two mycorrhizal levels (i.e., M + with mycorrhizae, M- without mycorrhizae) and five Zn levels (i.e., 0, 1.5, 3, 6, and 12 mg kg-1), with three replicates following completely randomized design. At the vegetative stage (before tillering), biochemical, physiological, and agronomic attributes were measured. The results showed that maize plants previously inoculated with AMF had higher gaseous exchange traits, i.e., a higher stomatal conductance rate, favoring an increased photosynthetic rate. Improvement in antioxidant enzyme activity was also observed in inoculated compared to non-inoculated maize plants. Moreover, AMF inoculation also played a beneficial role in nutrients availability and its uptake by plants. Higher Zn12 (12 mg Zn kg-1 soil) treatment accumulated a higher Zn concentration in soil, root, and shoot in AMF-inoculated than in non-inoculated maize plants. These results are consistent with mycorrhizal symbiosis beneficial role for maize physiological functioning in Zn deficient soil conditions. Additionally, AMF inoculation mitigated the stress conditions and assisted nutrient uptake by maize.
Direct visualization of the effect of DNA structure and ionic conditions on HU–DNA interactions
Authors: Lin Szu-Ning , Dame Remus T. , Wuite Gijs J. L. 
Published: September 2021

AbstractArchitectural DNA–binding proteins are involved in many important DNA transactions by virtue of their ability to change DNA conformation. Histone-like protein from E. coli strain U93, HU, is one of the most studied bacterial architectural DNA–binding proteins. Nevertheless, there is still a limited understanding of how the interactions between HU and DNA are affected by ionic conditions and the structure of DNA. Here, using optical tweezers in combination with fluorescent confocal imaging, we investigated how ionic conditions affect the interaction between HU and DNA. We directly visualized the binding and the diffusion of fluorescently labelled HU dimers on DNA. HU binds with high affinity and exhibits low mobility on the DNA in the absence of Mg2+; it moves 30-times faster and stays shorter on the DNA with 8 mM Mg2+ in solution. Additionally, we investigated the effect of DNA tension on HU–DNA complexes. On the one hand, our studies show that binding of HU enhances DNA helix stability. On the other hand, we note that the binding affinity of HU for DNA in the presence of Mg2+ increases at tensions above 50 pN, which we attribute to force-induced structural changes in the DNA. The observation that HU diffuses faster along DNA in presence of Mg2+ compared to without Mg2+ suggests that the free energy barrier for rotational diffusion along DNA is reduced, which can be interpreted in terms of reduced electrostatic interaction between HU and DNA, possibly coinciding with reduced DNA bending.
Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations
Authors: Xu Haijin , Isenmann Sandra , López-Hernández Tania , Estévez Raúl , Lukacs Gergely L. , Apaja Pirjo M. 
Published: September 2021

AbstractThe significance of crosstalks among constituents of plasma membrane protein clusters/complexes in cellular proteostasis and protein quality control (PQC) remains incompletely understood. Examining the glial (enriched) cell adhesion molecule (CAM), we demonstrate its chaperone-like role in the biosynthetic processing of the megalencephalic leukoencephalopathy with subcortical cyst 1 (MLC1)-heteromeric regulatory membrane protein complex, as well as the function of the GlialCAM/MLC1 signalling complex. We show that in the absence of GlialCAM, newly synthesized MLC1 molecules remain unfolded and are susceptible to polyubiquitination-dependent proteasomal degradation at the endoplasmic reticulum. At the plasma membrane, GlialCAM regulates the diffusional partitioning and endocytic dynamics of cluster members, including the ClC-2 chloride channel and MLC1. Impaired folding and/or expression of GlialCAM or MLC1 in the presence of diseases causing mutations, as well as plasma membrane tethering compromise the functional expression of the cluster, leading to compromised endo-lysosomal organellar identity. In addition, the enlarged endo-lysosomal compartments display accelerated acidification, ubiquitinated cargo-sorting and impaired endosomal recycling. Jointly, these observations indicate an essential and previously unrecognized role for CAM, where GliaCAM functions as a PQC factor for the MLC1 signalling complex biogenesis and possess a permissive role in the membrane dynamic and cargo sorting functions with implications in modulations of receptor signalling.
Copper-binding ligands in deep-sea pore waters of the Pacific Ocean and potential impacts of polymetallic nodule mining on the copper cycle
Authors: Paul Sophie A. L. , Zitoun Rebecca , Noowong Ann , Manirajah Mythili , Koschinsky Andrea 
Published: September 2021

AbstractThe release of potentially toxic metals, such as copper (Cu), into the water column is of concern during polymetallic nodule mining. The bioavailability and thus toxicity of Cu is strongly influenced by its speciation which is dominated by organic ligand (L) complexation in seawater, with L-complexes being considered less bioavailable than free Cu2+. The presence of CuL-complexes in deep-sea sediments has, however, not been systematically studied in the context of deep-sea mining. We thus analyzed the Cu-binding L concentration ([L]) in deep-sea pore waters of two polymetallic nodule provinces in the Pacific Ocean, the Peru Basin and the Clarion-Clipperton-Zone, using competitive ligand equilibration–adsorptive stripping voltammetry. The pore-water dissolved Cu concentration ([dCu]) ranged from 3 to 96 nM, generally exceeding bottom water concentrations (4–44 nM). Based on fitting results from ProMCC and Excel, Cu was predominantly complexed by L (3–313 nM) in bottom waters and undisturbed pore waters. We conclude that processes like deep-sea mining are unlikely to cause a release of toxic Cu2+ concentrations ([Cu2+]) to the seawater as > 99% Cu was organically complexed in pore waters and the [Cu2+] was < 6 pM for 8 of 9 samples. Moreover, the excess of L found especially in shallow pore waters implied that even with a Cu release through mining activities, Cu2+ likely remains beneath toxic thresholds.
Emerging of new bioartificial corticospinal motor synergies using a robotic additional thumb
Authors: Rossi Simone , Salvietti Gionata , Neri Francesco , Romanella Sara M. , Cinti Alessandra , Sinigaglia Corrado , Ulivelli Monica , Lisini Baldi Tommaso , Santarnecchi Emiliano , Prattichizzo Domenico 
Published: September 2021

AbstractIt is likely that when using an artificially augmented hand with six fingers, the natural five plus a robotic one, corticospinal motor synergies controlling grasping actions might be different. However, no direct neurophysiological evidence for this reasonable assumption is available yet. We used transcranial magnetic stimulation of the primary motor cortex to directly address this issue during motor imagery of objects’ grasping actions performed with or without the Soft Sixth Finger (SSF). The SSF is a wearable robotic additional thumb patented for helping patients with hand paresis and inherent loss of thumb opposition abilities. To this aim, we capitalized from the solid notion that neural circuits and mechanisms underlying motor imagery overlap those of physiological voluntary actions. After a few minutes of training, healthy humans wearing the SSF rapidly reshaped the pattern of corticospinal outputs towards forearm and hand muscles governing imagined grasping actions of different objects, suggesting the possibility that the extra finger might rapidly be encoded into the user’s body schema, which is integral part of the frontal-parietal grasping network. Such neural signatures might explain how the motor system of human beings is open to very quickly welcoming emerging augmentative bioartificial corticospinal grasping strategies. Such an ability might represent the functional substrate of a final common pathway the brain might count on towards new interactions with the surrounding objects within the peripersonal space. Findings provide a neurophysiological framework for implementing augmentative robotic tools in humans and for the exploitation of the SSF in conceptually new rehabilitation settings.
Deep saliency models learn low-, mid-, and high-level features to predict scene attention
Authors: Hayes Taylor R. , Henderson John M. 
Published: September 2021

AbstractDeep saliency models represent the current state-of-the-art for predicting where humans look in real-world scenes. However, for deep saliency models to inform cognitive theories of attention, we need to knowhowdeep saliency models prioritize different scene features to predict where people look. Here we open the black box of three prominent deep saliency models (MSI-Net, DeepGaze II, and SAM-ResNet) using an approach that models the association between attention, deep saliency model output, and low-, mid-, and high-level scene features. Specifically, we measured the association between each deep saliency model and low-level image saliency, mid-level contour symmetry and junctions, and high-level meaning by applying a mixed effects modeling approach to a large eye movement dataset. We found that all three deep saliency models were most strongly associated with high-level and low-level features, but exhibited qualitatively different feature weightings and interaction patterns. These findings suggest that prominent deep saliency models are primarily learning image features associated with high-level scene meaning and low-level image saliency and highlight the importance of moving beyond simply benchmarking performance.
Brick Strex: a robust device built of LEGO bricks for mechanical manipulation of cells
Authors: Mäntylä Elina , Ihalainen Teemu O. 
Published: September 2021

AbstractCellular forces, mechanics and other physical factors are important co-regulators of normal cell and tissue physiology. These cues are often misregulated in diseases such as cancer, where altered tissue mechanics contribute to the disease progression. Furthermore, intercellular tensile and compressive force-related signaling is highlighted in collective cell behavior during development. However, the mechanistic understanding on the role of physical forces in regulation of cellular physiology, including gene expression and signaling, is still lacking. This is partly because studies on the molecular mechanisms of force transmission require easily controllable experimental designs. These approaches should enable both easy mechanical manipulation of cells and, importantly, readouts ranging from microscopy imaging to biochemical assays. To achieve a robust solution for mechanical manipulation of cells, we developed devices built of LEGO bricks allowing manual, motorized and/or cyclic cell stretching and compression studies. By using these devices, we show that$$\upbeta$$β-catenin responds differentially to epithelial monolayer stretching and lateral compression, either localizing more to the cell nuclei or cell–cell junctions, respectively. In addition, we show that epithelial compression drives cytoplasmic retention and phosphorylation of transcription coregulator YAP1. We provide a complete part listing and video assembly instructions, allowing other researchers to build and use the devices in cellular mechanics-related studies.
Tunable X-ray dark-field imaging for sub-resolution feature size quantification in porous media
Authors: Blykers Benjamin K. , Organista Caori , Boone Matthieu N. , Kagias Matias , Marone Federica , Stampanoni Marco , Bultreys Tom , Cnudde Veerle , Aelterman Jan 
Published: September 2021

AbstractX-ray computed micro-tomography typically involves a trade-off between sample size and resolution, complicating the study at a micrometer scale of representative volumes of materials with broad feature size distributions (e.g. natural stones). X-ray dark-field tomography exploits scattering to probe sub-resolution features, promising to overcome this trade-off. In this work, we present a quantification method for sub-resolution feature sizes using dark-field tomograms obtained by tuning the autocorrelation length of a Talbot grating interferometer. Alumina particles with different nominal pore sizes (50 nm and 150 nm) were mixed and imaged at the TOMCAT beamline of the SLS synchrotron (PSI) at eighteen correlation lengths, covering the pore size range. The different particles cannot be distinguished by traditional absorption µCT due to their very similar density and the pores being unresolved at typical image resolutions. Nevertheless, by exploiting the scattering behavior of the samples, the proposed analysis method allowed to quantify the nominal pore sizes of individual particles. The robustness of this quantification was proven by reproducing the experiment with solid samples of alumina, and alumina particles that were kept separated. Our findings demonstrate the possibility to calibrate dark-field image analysis to quantify sub-resolution feature sizes, allowing multi-scale analyses of heterogeneous materials without subsampling.
Late stage 3 chronic kidney disease is an independent risk factor for sarcopenia, but not proteinuria
Authors: An Jung Nam , Kim Jwa-Kyung , Lee Hyung-Seok , Kim Sung Gyun , Kim Hyung Jik , Song Young Rim 
Published: September 2021

AbstractMost epidemiologic studies assessing the relationship between chronic kidney disease (CKD) and sarcopenia have been performed in dialysis patients. This study aimed to evaluate the relationship between estimated glomerular filtration rate (eGFR), proteinuria, and sarcopenia in patients with non-dialysis-dependent CKD. A total of 892 outpatients who did not show any rapid changes in renal function were enrolled in this observational cohort study. We measured the muscle mass using bioimpedance analysis and handgrip strength (HGS), and sarcopenia was defined as low HGS and low muscle mass. Sarcopenia was found in 28.1% of the patients and its prevalence decreased as the body mass index (BMI) increased; however, in patients with BMI ≥ 23 kg/m2, the prevalence did not increase with BMI. As eGFR decreased, the lean tissue index and HGS significantly decreased. However, the eGFR did not affect the fat tissue index. The risk of sarcopenia increased approximately 1.6 times in patients with eGFR < 45 mL/min/1.73 m2. However, proteinuria was not associated with sarcopenia. With a decrease in eGFR, the lean muscle mass and muscle strength decreased, and the prevalence of sarcopenia increased. In patients with late stage 3 CKD, further assessment of body composition and screening for sarcopenia may be needed.
Highly efficient CRISPR/Cas9 system in Plasmodium falciparum using Cas9-expressing parasites and a linear donor template
Authors: Nishi Tsubasa , Shinzawa Naoaki , Yuda Masao , Iwanaga Shiroh 
Published: September 2021

AbstractThe CRISPR/Cas9 system is a powerful genetic engineering technology for Plasmodium falciparum. We here report further improvement of the CRISPR/Cas9 system by combining the Cas9-expressing parasite with a liner donor template DNA. The Cas9-expressing parasite was generated by inserting the cas9 gene in the genome by double crossover recombination. The site-directed mutagenesis and the fusion of fluorescence protein was achieved within two weeks with high efficiency (> 85%), by transfecting the schizonts of the Cas9-expressing parasite with the liner donor template and the plasmid carrying the sgRNAs. Notably, there were neither off-target mutations in the resultant transgenic parasites nor unexpected recombination, that are the technical problems of the current CRISPR/Cas9 system. Furthermore, with our system, two genes on different chromosomes were successfully modified in single transfection. Because of its high efficiency and robustness, our improved CRISPR/Cas9 system will become a standard technique for genetic engineering of P. falciparum, which dramatically advances future studies of this parasite.