bluuebunny/crossref_metadata_2025 huggingface dataset:
The Lifetimes of Plasma Structures at High Latitudes
Authors: Ivarsen Magnus F. , Jin Yaqi , Spicher Andres , Miloch Wojciech , Clausen Lasse B. N.
Published: January 2021

We present an investigation of polar cap plasma structure lifetimes. We analyze both simulated data from ionospheric models (International Reference Ionosphere model and Mass Spectrometer Incoherent Scatter model) and in situ data from the Swarm satellite mission (the 16 Hz Advanced Plasma Density dataset). We find that the theoretical prediction that E‐region conductance is a predictor of F‐region polar cap plasma structure lifetimes is indeed supported by both in situ‐based observations and by ionospheric models. In situ plasma structure lifetimes correlate well with the ratio of F‐ to E‐region conductance. We present explicit predictions of small scale (∼1 km) structure lifetimes, which range from less than 1 h during local summer to around 3 h during local winter. We highlight a large discrepancy between the observational and theoretical scale‐dependency of decay due to diffusion.
Pressure‐Driven Poiseuille Flow Inherited From Mesozoic Mantle Circulation Led to the Eocene Separation of Australia and Antarctica
Authors: Stotz I. L. , Tassara A. , Iaffaldano G.
Published: January 2021

The separation between Australia and Antarctica occurred during the final stages of the break‐up of Pangea. Reconstructions of the rifting of the Australian plate away from Antarctica show fast spreading rates since Mid‐Eocene (45 Ma). These reconstructions can be used to understand and quantify the forces driving the Australia/Antarctica separation, and to test hypotheses on mechanisms that may be of shallow (i.e., lithosphere) or deep (i.e., mantle) origin. Analytical calculations indicate that plate‐boundary forces are highly unlikely to be a plausible candidate to explain such a separation. Thus, we use a recently developed global coupled models of mantle and lithosphere dynamics, here we show that this event, whose kinematics are reproduced in our models within the bounds of the reconstruction uncertainties, owes to a significant degree to the pressure‐driven asthenospheric Poiseuille flow associated with the mantle buoyancy field inherited from viscous circulation history throughout the Mesozoic. On the contrary, in simulations when such a buoyancy field is replaced by another one resulting from a random distribution of mantle temperature–thus not representative of Earth’s mantle circulation history–the rapid northward motion of Australia does not occur. Similarly, suppressing contemporaneous plate‐boundary processes (i.e., subduction of the Pacific ridge at the Aleutians and healing of the India‐Australia ridge) from our models does not have a noticeable effect on the Australia‐Antarctica kinematics. Thus, a pressure‐driven Poiseuille mantle flow must be considered, at least in this example and possible elsewhere, as a main driver of plate tectonics.
High‐Resolution Surveys of Phytoplankton‐Derived Polyunsaturated Aldehydes at Frontal Zones Outside a Eutrophic Estuary
Authors: Wu Zhengchao , Li Qian P. , Dong Yuan , Xu Jie , Luo Lin
Published: January 2021

In this study, we report high‐resolution spatiotemporal distributions of particulate polyunsaturated aldehyde (pPUA) and dissolved polyunsaturated aldehyde (dPUA) across a frontal system outside the Pearl River Estuary of the northern South China Sea (NSCS) by synthesizing field data collected during the summers of 2015, 2016, and 2019. High levels of pPUA (up to 40 nM) in the surface waters were related to intense phytoplankton blooms at the frontal zone dominated by PUA‐producing diatoms. We found phytoplankton chlorophyll‐a negatively correlated with the heptadienal percentage but positively correlated with the octadienal percentage in pPUA at the surface frontal zone, consistent with a cross‐front shift of the dominant PUA‐producing diatoms from Skeletonema costatum to Thalassiosira minima. Also, pPUA was significantly correlated with chlorophyll‐a in the surface boundary but with turbidity in the bottom boundary of the front during the cross‐front transect, indicating a biological source of surface pPUA but a sedimentary source of bottom pPUA (likely from the resuspended PUA precursors). At the frontal zone, a fast decrease of dPUA with depths below the mixed layer could be a result of enhanced mixing by the intruded bottom seawater. In summary, we reveal the complex distributions of pPUA and dPUA in the frontal system outside a eutrophic estuary, including both its surface and the bottom boundary layers. We further discuss the ecological and biogeochemical implications of the unique PUA distributional patterns on the NSCS shelf‐sea.
A spatially resolved brain region- and cell type-specific isoform atlas of the postnatal mouse brain
Authors: Joglekar Anoushka , Prjibelski Andrey , Mahfouz Ahmed , Collier Paul , Lin Susan , Schlusche Anna Katharina , Marrocco Jordan , Williams Stephen R. , Haase Bettina , Hayes Ashley , Chew Jennifer G. , Weisenfeld Neil I. , Wong Man Ying , Stein Alexander N. , Hardwick Simon A. , Hunt Toby , Wang Qi , Dieterich Christoph , Bent Zachary , Fedrigo Olivier , Sloan Steven A. , Risso Davide , Jarvis Erich D. , Flicek Paul , Luo Wenjie , Pitt Geoffrey S. , Frankish Adam , Smit August B. , Ross M. Elizabeth , Tilgner Hagen U.
Published: January 2021

Splicing varies across brain regions, but the single-cell resolution of regional variation is unclear. We present a single-cell investigation of differential isoform expression (DIE) between brain regions using single-cell long-read sequencing in mouse hippocampus and prefrontal cortex in 45 cell types at postnatal day 7 (www.isoformAtlas.com). Isoform tests for DIE show better performance than exon tests. We detect hundreds of DIE events traceable to cell types, often corresponding to functionally distinct protein isoforms. Mostly, one cell type is responsible for brain-region specific DIE. However, for fewer genes, multiple cell types influence DIE. Thus, regional identity can, although rarely, override cell-type specificity. Cell types indigenous to one anatomic structure display distinctive DIE, e.g. the choroid plexus epithelium manifests distinct transcription-start-site usage. Spatial transcriptomics and long-read sequencing yield a spatially resolved splicing map. Our methods quantify isoform expression with cell-type and spatial resolution and it contributes to further our understanding of how the brain integrates molecular and cellular complexity.
Interstitial boron-doped mesoporous semiconductor oxides for ultratransparent energy storage
Authors: Zhi Jian , Zhou Min , Zhang Zhen , Reiser Oliver , Huang Fuqiang
Published: January 2021

Realizing transparent and energy-dense supercapacitor is highly challenging, as there is a trade-off between energy storing capability and transparency in the active material film. We report here that interstitial boron-doped mesoporous semiconductor oxide shows exceptional electrochemical capacitance which rivals other pseudocapacitive materials, while maintaining its transparent characteristic. This improvement is credited to the robust redox reactions at interstitial boron-associated defects that transform inert semiconductor oxides into an electrochemically active material without affecting its transparency. By precisely tuning the level of doping, the pseudocapacitive reactivity of these materials is optimized, resulting in a volumetric capacitance up to 1172 F cm−3. Attributing to such efficient charge storage utilization on the active film, the fabricated transparent supercapacitor delivers a maximum areal energy density of 1.36 × 10−3 mWh cm−2 that is close to those of conventional pseudocapacitive materials, with nearly 100% capacitance retention after 15000 cycles and ultrahigh transparency (up to 85% transmittance at 550 nm). In addition, this device shows excellent durability and flexibility with multiple optional outputs, demonstrating the potential as a transparent energy supply in planar electronics.
The multi-photon induced Fano effect
Authors: Litvinenko K. L. , Le Nguyen H. , Redlich B. , Pidgeon C. R. , Abrosimov N. V. , Andreev Y. , Huang Zhiming , Murdin B. N.
Published: January 2021

The ordinary Fano effect occurs in many-electron atoms and requires an autoionizing state. With such a state, photo-ionization may proceed via pathways that interfere, and the characteristic asymmetric resonance structures appear in the continuum. Here we demonstrate that Fano structure may also be induced without need of auto-ionization, by dressing the continuum with an ordinary bound state in any atom by a coupling laser. Using multi-photon processes gives complete, ultra-fast control over the interference. We show that a line-shape indexqnear unity (maximum asymmetry) may be produced in hydrogenic silicon donors with a relatively weak beam. Since the Fano lineshape has both constructive and destructive interference, the laser control opens the possibility of state-selective detection with enhancement on one side of resonance and invisibility on the other. We discuss a variety of atomic and molecular spectroscopies, and in the case of silicon donors we provide a calculation for a qubit readout application.
Crossover between the adiabatic and nonadiabatic electron transfer limits in the Landau-Zener model
Authors: Zhu Guang Yuan , Qin Yi , Meng Miao , Mallick Suman , Gao Hang , Chen Xiaoli , Cheng Tao , Tan Ying Ning , Xiao Xuan , Han Mei Juan , Sun Mei Fang , Liu Chun Y.
Published: January 2021

The semiclassical models of nonadiabatic transition were proposed first by Landau and Zener in 1932, and have been widely used in the study of electron transfer (ET); however, experimental demonstration of the Landau-Zener formula remains challenging to observe. Herein, employing the Hush-Marcus theory, thermal ET in mixed-valence complexes {[Mo2]-(ph)n-[Mo2]}+(n = 1–3) has been investigated, spanning the nonadiabatic throughout the adiabatic limit, by analysis of the intervalence transition absorbances. Evidently, the Landau-Zener formula is valid in the adiabatic regime in a broader range of conditions than the theoretical limitation known as the narrow avoided-crossing. The intermediate system is identified with an overall transition probability (κel) of ∼0.5, which is contributed by the single and the first multiple passage. This study shows that in the intermediate regime, the ET kinetic results derived from the adiabatic and nonadiabatic formalisms are nearly identical, in accordance with the Landau-Zener model. The obtained insights help to understand and control the ET processes in biological and chemical systems.
Epidermal progenitors suppress GRHL3-mediated differentiation through intronic polyadenylation promoted by CPSF-HNRNPA3 collaboration
Authors: Chen Xin , Lloyd Sarah M. , Kweon Junghun , Gamalong Giovanni M. , Bao Xiaomin
Published: January 2021

In self-renewing somatic tissue such as skin epidermis, terminal differentiation genes must be suppressed in progenitors to sustain regenerative capacity. Here we show that hundreds of intronic polyadenylation (IpA) sites are differentially used during keratinocyte differentiation, which is accompanied by downregulation of the Cleavage and Polyadenylation Specificity Factor (CPSF) complex. Sustained CPSF expression in undifferentiated keratinocytes requires the contribution from the transcription factor MYC. In keratinocytes cultured in undifferentiation condition, CSPF knockdown induces premature differentiation and partially affects dynamically used IpA sites. These sites include an IpA site located in the first intron of the differentiation activator GRHL3. CRISPR knockout of GRHL3 IpA increased full-length GRHL3 mRNA expression. Using a targeted genetic screen, we identify that HNRNPA3 interacts with CPSF and enhances GRHL3 IpA. Our data suggest a model where the interaction between CPSF and RNA-binding proteins, such as HNRNPA3, promotes site-specific IpA and suppresses premature differentiation in progenitors.
Genomic epidemiology of SARS-CoV-2 reveals multiple lineages and early spread of SARS-CoV-2 infections in Lombardy, Italy
Authors: Alteri Claudia , Cento Valeria , Piralla Antonio , Costabile Valentino , Tallarita Monica , Colagrossi Luna , Renica Silvia , Giardina Federica , Novazzi Federica , Gaiarsa Stefano , Matarazzo Elisa , Antonello Maria , Vismara Chiara , Fumagalli Roberto , Epis Oscar Massimiliano , Puoti Massimo , Perno Carlo Federico , Baldanti Fausto
Published: January 2021

From February to April 2020, Lombardy (Italy) reported the highest numbers of SARS-CoV-2 cases worldwide. By analyzing 346 whole SARS-CoV-2 genomes, we demonstrate the presence of seven viral lineages in Lombardy, frequently sustained by local transmission chains and at least two likely to have originated in Italy. Six single nucleotide polymorphisms (five of them non-synonymous) characterized the SARS-CoV-2 sequences, none of them affecting N-glycosylation sites. The seven lineages, and the presence of local transmission clusters within three of them, revealed that sustained community transmission was underway before the first COVID-19 case had been detected in Lombardy.
Recruitment of upper-limb motoneurons with epidural electrical stimulation of the cervical spinal cord
Authors: Greiner Nathan , Barra Beatrice , Schiavone Giuseppe , Lorach Henri , James Nicholas , Conti Sara , Kaeser Melanie , Fallegger Florian , Borgognon Simon , Lacour Stéphanie , Bloch Jocelyne , Courtine Grégoire , Capogrosso Marco
Published: January 2021

Epidural electrical stimulation (EES) of lumbosacral sensorimotor circuits improves leg motor control in animals and humans with spinal cord injury (SCI). Upper-limb motor control involves similar circuits, located in the cervical spinal cord, suggesting that EES could also improve arm and hand movements after quadriplegia. However, the ability of cervical EES to selectively modulate specific upper-limb motor nuclei remains unclear. Here, we combined a computational model of the cervical spinal cord with experiments in macaque monkeys to explore the mechanisms of upper-limb motoneuron recruitment with EES and characterize the selectivity of cervical interfaces. We show that lateral electrodes produce a segmental recruitment of arm motoneurons mediated by the direct activation of sensory afferents, and that muscle responses to EES are modulated during movement. Intraoperative recordings suggested similar properties in humans at rest. These modelling and experimental results can be applied for the development of neurotechnologies designed for the improvement of arm and hand control in humans with quadriplegia.
Degradation of complex arabinoxylans by human colonic Bacteroidetes
Authors: Pereira Gabriel V. , Abdel-Hamid Ahmed M. , Dutta Soumajit , D’Alessandro-Gabazza Corina N. , Wefers Daniel , Farris Jacob A. , Bajaj Shiv , Wawrzak Zdzislaw , Atomi Haruyuki , Mackie Roderick I. , Gabazza Esteban C. , Shukla Diwakar , Koropatkin Nicole M. , Cann Isaac
Published: January 2021

Some Bacteroidetes and other human colonic bacteria can degrade arabinoxylans, common polysaccharides found in dietary fiber. Previous work has identified gene clusters (polysaccharide-utilization loci, PULs) for degradation of simple arabinoxylans. However, the degradation of complex arabinoxylans (containing side chains such as ferulic acid, a phenolic compound) is poorly understood. Here, we identify a PUL that encodes multiple esterases for degradation of complex arabinoxylans inBacteroidesspecies. The PUL is specifically upregulated in the presence of complex arabinoxylans. We characterize some of the esterases biochemically and structurally, and show that they release ferulic acid from complex arabinoxylans. Growth of four different colonic Bacteroidetes members, includingBacteroides intestinalis, on complex arabinoxylans results in accumulation of ferulic acid, a compound known to have antioxidative and immunomodulatory properties.
A real-world longitudinal study of anemia management in non-dialysis-dependent chronic kidney disease patients: a multinational analysis of CKDopps
Authors: Lopes Marcelo Barreto , Tu Charlotte , Zee Jarcy , Guedes Murilo , Pisoni Ronald L. , Robinson Bruce M. , Foote Bryce , Hedman Katarina , James Glen , Lopes Antonio Alberto , Massy Ziad , Reichel Helmut , Sloand James , Waechter Sandra , Wong Michelle M. Y. , Pecoits-Filho Roberto
Published: January 2021

Previously lacking in the literature, we describe longitudinal patterns of anemia prescriptions for non-dialysis-dependent chronic kidney disease (NDD-CKD) patients under nephrologist care. We analyzed data from 2818 Stage 3-5 NDD-CKD patients from Brazil, Germany, and the US, naïve to anemia medications (oral iron, intravenous [IV] iron, or erythropoiesis stimulating agent [ESA]) at enrollment in the CKDopps. We report the cumulative incidence function (CIF) of medication initiation stratified by baseline characteristics. Even in patients with hemoglobin (Hb) < 10 g/dL, the CIF at 12 months for any anemia medication was 40%, and 28% for ESAs. Patients with TSAT < 20% had a CIF of 26% and 6% for oral and IV iron, respectively. Heart failure was associated with earlier initiation of anemia medications. IV iron was prescribed to < 10% of patients with iron deficiency. Only 40% of patients with Hb < 10 g/dL received any anemia medication within a year. Discontinuation of anemia treatment was very common. Anemia treatment is initiated in a limited number of NDD-CKD patients, even in those with guideline-based indications to treat. Hemoglobin trajectory and a history of heart failure appear to guide treatment start. These results support the concept that anemia is sub-optimally managed among NDD-CKD patients in the real-world setting.
2D materials coated on etched optical fibers as humidity sensor
Authors: Owji Erfan , Mokhtari Hossein , Ostovari Fatemeh , Darazereshki Behnam , Shakiba Nazanin
Published: January 2021

In this investigation, etched-fibers are coated by 2D layers such as Molybdenum disulfide (MoS2), Molybdenum diselenide (MoSe2) and composition of graphene and graphene oxide (G/GO) to modify humidity sensing. The relative differentiation of attenuations (RDA) in presence of relative humidity (RH) is measured by Optical Loss Test Set at two standard-wavelengths-telecommunication (1310 nm and 1550 nm). Results show that the etched single-mode fiber (ESMF) coated with G/GO has relatively high and one by one function for RDA versus RH (more than 30%). Also, its sensitivity and variance are reasonable. The MoSe2 based sensor is applicable at humidity below 30% because of higher RDA. However, it is not useful at humidity more than 30% due to the absence of one by one function for RDA versus RH. Besides, ESMF coated with MoS2 has indistinctive behavior and is not useful as a humidity sensor.
Mechanistic basis of breast cancer resistance protein inhibition by new indeno[1,2-b]indoles
Authors: Kita Diogo Henrique , Guragossian Nathalie , Zattoni Ingrid Fatima , Moure Vivian Rotuno , Rego Fabiane Gomes de Moraes , Lusvarghi Sabrina , Moulenat Thomas , Belhani Billel , Picheth Geraldo , Bouacida Sofiane , Bouaziz Zouhair , Marminon Christelle , Berredjem Malika , Jose Joachim , Gonçalves Marcos Brown , Ambudkar Suresh V. , Valdameri Glaucio , Le Borgne Marc
Published: January 2021

The ATP-binding cassette transporter ABCG2 mediates the efflux of several chemotherapeutic drugs, contributing to the development of multidrug resistance (MDR) in many cancers. The most promising strategy to overcome ABCG2-mediated MDR is the use of specific inhibitors. Despite many efforts, the identification of new potent and specific ABCG2 inhibitors remains urgent. In this study, a structural optimization of indeno[1,2-b]indole was performed and a new generation of 18 compounds was synthesized and tested as ABCG2 inhibitors. Most compounds showed ABCG2 inhibition with IC50 values below 0.5 µM. The ratio between cytotoxicity (IG50) and ABCG2 inhibition potency (IC50) was used to identify the best inhibitors. In addition, it was observed that some indeno[1,2-b]indole derivatives produced complete inhibition, while others only partially inhibited the transport function of ABCG2. All indeno[1,2-b]indole derivatives are not transported by ABCG2, and even the partial inhibitors are able to fully chemosensitize cancer cells overexpressing ABCG2. The high affinity of these indeno[1,2-b]indole derivatives was confirmed by the strong stimulatory effect on ABCG2 ATPase activity. These compounds did not affect the binding of conformation-sensitive antibody 5D3 binding, but stabilized the protein structure, as revealed by the thermostabilization assay. Finally, a docking study showed the indeno[1,2-b]indole derivatives share the same binding site as the substrate estrone-3-sulfate.
Effects of knee osteoarthritis severity on inter-joint coordination and gait variability as measured by hip-knee cyclograms
Authors: Park Jae Hyeon , Lee Hyojin , Cho Jae-sung , Kim Inyoung , Lee Jongshill , Jang Seong Ho
Published: January 2021

Inter-joint coordination and gait variability in knee osteoarthritis (KOA) has not been well investigated. Hip-knee cyclograms can visualize the relationship between the hip and knee joint simultaneously. The aim of this study was to elucidate differences in inter-joint coordination and gait variability with respect to KOA severity using hip-knee cyclograms. Fifty participants with KOA (early KOA, n = 20; advanced KOA, n = 30) and 26 participants (≥ 50 years) without KOA were recruited. We analyzed inter-joint coordination by hip-knee cyclogram parameters including range of motion (RoM), center of mass (CoM), perimeter, and area. Gait variability was assessed by the coefficient of variance (CV) of hip-knee cyclogram parameters. Knee RoM was significantly reduced and total perimeter tended to be decreased with KOA progression. KOA patients (both early and advanced) had reduced stance phase perimeter, swing phase area, and total area than controls. Reduced knee CoM and swing phase perimeter were observed only in advanced KOA. Both KOA groups had a greater CV for CoM, knee RoM, perimeter (stance phase, swing phase and total) and swing phase area than the controls. Increased CV of hip RoM was only observed in advanced KOA. These results demonstrate that hip-knee cyclograms can provide insights into KOA patient gait.
Impact of genetic variants on major bleeding after percutaneous coronary intervention based on a prospective multicenter registry
Authors: Cha Jung-Joon , Joo Hyung Joon , Park Jae Hyoung , Hong Soon Jun , Ahn Tae Hoon , Kim Byeong-Keuk , Shin WonYong , Ahn Sung Gyun , Yoon JungHan , Kim Yong Hoon , Cho Yun-Hyeong , Kang Woong Chol , Kim Weon , Lim Young-Hyo , Gwon HyeonCheol , Choi WoongGil , Lim Do-Sun
Published: January 2021

Although dual antiplatelet therapy is essential for patients who undergo percutaneous coronary interventions, the risk of bleeding remains an unsolved problem, and there is limited information on the potential relationship between genetic variants and major bleeding. We analyzed the correlations between four major single nucleotide polymorphisms (CYP2C19, ABCB1, PON1, and P2Y12 G52T polymorphisms) and clinical outcomes in 4489 patients from a prospective multicenter registry. The primary endpoint was major bleeding, defined as a Bleeding Academic Research Consortium ≥ 3 bleeding event. The allelic frequencies of ABCB1, PON1, and both individual and combined CYP2C19 variants did not differ significantly between patient groups with and without major bleeding. However, the allelic frequency of the P2Y12 variant differed significantly between the two groups. Focusing on the P2Y12 G52T variant, patients in the TT group had a significantly higher rate of major bleeding (6.4%; adjusted hazard ratio [HR] 2.51; 95% confidence interval [CI] 1.08–5.84; p = 0.033) than patients in the other groups (GG [2.9%] or GT [1.9%]). Therefore, the TT variant of the P2Y12 G52T polymorphism may be an independent predictor of major bleeding.

Trial registration: NCT02707445 (https://clinicaltrials.gov/ct2/show/NCT02707445?term=02707445&draw=2&rank=1).
Direct detection of SARS-CoV-2 using non-commercial RT-LAMP reagents on heat-inactivated samples
Authors: Alekseenko Alisa , Barrett Donal , Pareja-Sanchez Yerma , Howard Rebecca J. , Strandback Emilia , Ampah-Korsah Henry , Rovšnik Urška , Zuniga-Veliz Silvia , Klenov Alexander , Malloo Jayshna , Ye Shenglong , Liu Xiyang , Reinius Björn , Elsässer Simon J. , Nyman Tomas , Sandh Gustaf , Yin Xiushan , Pelechano Vicent
Published: January 2021

RT-LAMP detection of SARS-CoV-2 has been shown to be a valuable approach to scale up COVID-19 diagnostics and thus contribute to limiting the spread of the disease. Here we present the optimization of highly cost-effective in-house produced enzymes, and we benchmark their performance against commercial alternatives. We explore the compatibility between multiple DNA polymerases with high strand-displacement activity and thermostable reverse transcriptases required for RT-LAMP. We optimize reaction conditions and demonstrate their applicability using both synthetic RNA and clinical patient samples. Finally, we validate the optimized RT-LAMP assay for the detection of SARS-CoV-2 in unextracted heat-inactivated nasopharyngeal samples from 184 patients. We anticipate that optimized and affordable reagents for RT-LAMP will facilitate the expansion of SARS-CoV-2 testing globally, especially in sites and settings where the need for large scale testing cannot be met by commercial alternatives.
Chronic exposure of humans to high level natural background radiation leads to robust expression of protective stress response proteins
Authors: Nishad S. , Chauhan Pankaj Kumar , Sowdhamini R. , Ghosh Anu
Published: January 2021

Understanding exposures to low doses of ionizing radiation are relevant since most environmental, diagnostic radiology and occupational exposures lie in this region. However, the molecular mechanisms that drive cellular responses at these doses, and the subsequent health outcomes, remain unclear. A local monazite-rich high level natural radiation area (HLNRA) in the state of Kerala on the south-west coast of Indian subcontinent show radiation doses extending from ≤ 1 to ≥ 45 mGy/y and thus, serve as a model resource to understand low dose mechanisms directly on healthy humans. We performed quantitative discovery proteomics based on multiplexed isobaric tags (iTRAQ) coupled with LC–MS/MS on human peripheral blood mononuclear cells from HLNRA individuals. Several proteins involved in diverse biological processes such as DNA repair, RNA processing, chromatin modifications and cytoskeletal organization showed distinct expression in HLNRA individuals, suggestive of both recovery and adaptation to low dose radiation. In protein–protein interaction (PPI) networks, YWHAZ (14-3-3ζ) emerged as the top-most hub protein that may direct phosphorylation driven pro-survival cellular processes against radiation stress. PPI networks also identified an integral role for the cytoskeletal protein ACTB, signaling protein PRKACA; and the molecular chaperone HSPA8. The data will allow better integration of radiation biology and epidemiology for risk assessment [Data are available via ProteomeXchange with identifier PXD022380].
Lactobacillus rhamnosus attenuates bone loss and maintains bone health by skewing Treg-Th17 cell balance in Ovx mice
Authors: Sapra Leena , Dar Hamid Y. , Bhardwaj Asha , Pandey Amit , Kumari Surbhi , Azam Zaffar , Upmanyu Vishu , Anwar Aleena , Shukla Prashant , Mishra Pradyumna K. , Saini Chaman , Verma Bhupendra , Srivastava Rupesh K.
Published: January 2021

Osteoporosis is a systemic-skeletal disorder characterized by enhanced fragility of bones leading to increased rates of fractures and morbidity in large number of populations. Probiotics are known to be involved in management of various-inflammatory diseases including osteoporosis. But no study till date had delineated the immunomodulatory potential of Lactobacillus rhamnosus (LR) in bone-health. In the present study, we examined the effect of probiotic-LR on bone-health in ovariectomy (Ovx) induced postmenopausal mice model. In the present study, we for the first time report that LR inhibits osteoclastogenesis and modulates differentiation of Treg-Th17 cells under in vitro conditions. We further observed that LR attenuates bone loss under in vivo conditions in Ovx mice. Both the cortical and trabecular bone-content of Ovx+LR treated group was significantly higher than Ovx-group. Remarkably, the percentage of osteoclastogenic CD4+Rorγt+Th17 cells at distinct immunological sites such as BM, spleen, LN and PP were significantly reduced, whereas the percentage of anti-osteoclastogenic CD4+Foxp3+Tregs and CD8+Foxp3+Tregs were significantly enhanced in LR-treated group thereby resulting in inhibition of bone loss. The osteoprotective role of LR was further supported by serum cytokine data with a significant reduction in osteoclastogenic cytokines (IL-6, IL-17 and TNF-α) along with enhancement in anti-osteoclastogenic cytokines (IL-4, IL-10, IFN-γ) in LR treated-group. Altogether, the present study for the first time establishes the osteoprotective role of LR on bone health, thus highlighting the immunomodulatory potential of LR in the treatment and management of various bone related diseases including osteoporosis.
Silicon attenuates calcium deficiency by increasing ascorbic acid content, growth and quality of cabbage leaves
Authors: da Silva Dalila Lopes , de Mello Prado Renato , Tenesaca Luis Felipe Lata , da Silva José Lucas Farias , Mattiuz Ben-Hur
Published: January 2021

Calcium (Ca) deficiency in cabbage plants induces oxidative damage, hampering growth and decreasing quality, however, it is hypothesized that silicon (Si) added to the nutrient solution may alleviate crop losses. Therefore, this study aims at evaluating whether silicon supplied in the nutrient solution reduces, in fact, the calcium deficiency effects on cabbage plants. In a greenhouse, cabbage plants were grown using nutrient solutions with Ca sufficiency and Ca deficiency (5 mM) without and with added silicon (2.5 mM), arranged as a 2 × 2 factorial in randomized blocks, with five replications. At 91 days after transplanting, the plants were harvested for biological evaluations. In the treatment without added Si, Ca deficiency promoted oxidative stress, low antioxidant content, decreased dry matter, and lower quality leaf. On the other hand, added Si attenuated Ca deficiency in cabbage by decreasing cell extravasation while increasing both ascorbic acid content and fresh and dry matter, providing firmer leaves due to diminished leaf water loss after harvesting. We highlighted the agronomic importance of Si added to the nutrient solution, especially in crops at risk of Ca deficiency.
Projecting health-ageing trajectories in Europe using a dynamic microsimulation model
Authors: Marois Guillaume , Aktas Arda
Published: January 2021

The extent of the challenges and opportunities that population ageing presents depends heavily on the population’s health. Hence, for the development of appropriate strategies that enable countries to adopt the emerging demographic and epidemiological realities, information on future health trajectories of elderly population is a natural requirement. This study presents an innovative methodological framework for projecting the health of individuals using a dynamic microsimulation model that considers interactions between sociodemographic characteristics, health, mortality, bio-medical and behavioral risk factors. The model developed, called ATHLOS-Mic, is used to project the health of cohorts born before 1960 for the period 2015–2060 for selected European Countries using SHARE data to illustrate the possible effects of some selected risk factors and education on future health trajectories. Results show that, driven by a better educational attainment, each generation will be healthier than the previous one at same age. Also, we see that, on average, an individual of our base population will live about 18 more years since the start of the projection period, but only 5 years in good health. Finally, we find that a scenario that removes the effect of having a low level of education on individual health has the largest impact on the projected average health, the average number of years lived per person, and the average number of years lived in good health.
The relationships between microbiota and the amino acids and organic acids in commercial vegetable pickle fermented in rice-bran beds
Authors: Sawada Kazunori , Koyano Hitoshi , Yamamoto Nozomi , Yamada Takuji
Published: January 2021

The microbial community during fermented vegetable production has a large impact on the quality of the final products. Lactic acid bacteria have been well-studied in such processes, but knowledge about the roles of non-lactic acid bacteria is limited. This study aimed to provide useful knowledge about the relationships between the microbiota, including non-lactic acid bacteria, and metabolites in commercial pickle production by investigating Japanese pickles fermented in rice-bran. The samples were provided by six manufacturers, divided into two groups depending on the production conditions. The microbiological content of these samples was investigated by high-throughput sequencing, and metabolites were assessed by liquid chromatography-mass spectrometry and enzymatic assay. The data suggest that Halomonas, halophilic Gram-negative bacteria, can increase glutamic acid content during the pickling process under selective conditions for bacterial growth. In contrast, in less selective conditions, the microbiota consumed glutamic acid. Our results indicate that the glutamic acid content in fermented pickle is influenced by the microbiota, rather than by externally added glutamic acid. Our data suggest that both lactic acid bacteria and non-lactic acid bacteria are positive key factors in the mechanism of commercial vegetable fermentation and affect the quality of pickles.
Nanoporous gold nanoleaf as tunable metamaterial
Authors: Rout Sangeeta , Qi Zhen , Biener Monika M. , Courtwright Devon , Adrien Jakeem C. , Mills Ezekiel , Shahabuddin Mohammad , Noginova Natalia , Noginov Mikhail A.
Published: January 2021

We have studied optical properties of single-layer and multi-fold nanoporous gold leaf (NPGL) metamaterials and observed highly unusual transmission spectra composed of two well-resolved peaks. We explain this phenomenon in terms of a surface plasmon absorption band positioned on the top of a broader transmission band, the latter being characteristic of both homogeneous “solid” and inhomogeneous “diluted” Au films. The transmission spectra of NPGL metamaterials were shown to be controlled by external dielectric environments, e.g. water and applied voltage in an electrochemical cell. This paves the road to numerous functionalities of the studied tunable and active metamaterials, including control of spontaneous emission, energy transfer and many others.
Multifocal stimulation of the cerebro-cerebellar loop during the acquisition of a novel motor skill
Authors: Wessel Maximilian J. , Park Chang-hyun , Beanato Elena , Cuttaz Estelle A. , Timmermann Jan E. , Schulz Robert , Morishita Takuya , Koch Philipp J. , Hummel Friedhelm C.
Published: January 2021

Transcranial direct current stimulation (tDCS)-based interventions for augmenting motor learning are gaining interest in systems neuroscience and clinical research. Current approaches focus largely on monofocal motorcortical stimulation. Innovative stimulation protocols, accounting for motor learning related brain network interactions also, may further enhance effect sizes. Here, we tested different stimulation approaches targeting the cerebro-cerebellar loop. Forty young, healthy participants trained a fine motor skill with concurrent tDCS in four sessions over two days, testing the following conditions: (1) monofocal motorcortical, (2) sham, (3) monofocal cerebellar, or (4) sequential multifocal motorcortico-cerebellar stimulation in a double-blind, parallel design. Skill retention was assessed after circa 10 and 20 days. Furthermore, potential underlying mechanisms were studied, applying paired-pulse transcranial magnetic stimulation and multimodal magnetic resonance imaging-based techniques. Multisession motorcortical stimulation facilitated skill acquisition, when compared with sham. The data failed to reveal beneficial effects of monofocal cerebellar or additive effects of sequential multifocal motorcortico-cerebellar stimulation. Multimodal multiple linear regression modelling identified baseline task performance and structural integrity of the bilateral superior cerebellar peduncle as the most influential predictors for training success. Multisession application of motorcortical tDCS in several daily sessions may further boost motor training efficiency. This has potential implications for future rehabilitation trials.
Bleaching of leaf litter accelerates the decomposition of recalcitrant components and mobilization of nitrogen in a subtropical forest
Authors: Osono Takashi , Hiradate Syuntaro , Hobara Satoru
Published: January 2021

Selective removal of lignin and other recalcitrant compounds, collectively registered as acid-unhyrolyzable residue (AUR), results in bleaching of leaf litter, but the importance of bleaching in decomposition processes on forest soil has not been fully evaluated. The aims of this study were to elucidate the occurrence of bleached area in decomposing leaf litter and to compare chemical composition between bleached and nonbleached portions in a subtropical forest in Japan. Field incubation of leaf litter was performed over an 18-month period with the litterbag method. The decomposition processes during the first 9 month were characterized by the relatively rapid mass loss and increase of bleached area, whereas the mass loss was slowed down and the bleached area decreased thereafter. Mass loss of leaf tissues was faster and AUR content was lower in bleached than in nonbleached portions, indicating the acceleration of mass loss in bleached leaf tissues by the selective decomposition of recalcitrant compounds. The decrease in carbonyl-C in the bleached portions was associated with the increase of extractable nitrogen. The results suggest that the bleaching plays a dominant role in the transformation and turnover of organic compounds and nitrogen in decomposing leaf litter.
Prediction of coronary heart disease incidence in a general male population by circulating non-coding small RNA sRNY1-5p in a nested case–control study
Authors: Costa Vera L. , Ruidavets Jean-Bernard , Bongard Vanina , Perret Bertrand , Repetto Emanuela , Stathopoulou Maria G. , Serra Fabrizio , Benahmed Mohamed , Mauduit Claire , Grandjean Valerie , Ferrières Jean , Martinez Laurent O. , Trabucchi Michele
Published: January 2021

During the development of atherosclerotic lesion, s-RNYs (small RNAs of about 24/34 nucleotides) are derived by the processing of long Ro-associated non-coding RNAs (RNYs) in macrophages. The levels of serum s-RNYs have been found significantly upregulated in patients with coronary heart disease (CHD) compared to age-matched CHD-free individuals. The present study aimed to examine the predictive value of serum s-RNYs for CHD events in the general male population. Within the frame of nested-case–control study, the GENES study, we measured the absolute expression of a RNY-derived small RNA, the s-RNY1-5p, in the serum of individuals (without CHD at baseline) who encountered a CHD event within 12 years of follow-up (n = 30) (Cases) and compared them to individuals who remained event-free (Controls) (n = 30). The expression of s-RNY1-5p in serum was significantly upregulated in Cases compared to Controls (p = 0.027). The proportion of CHD event-free was significantly higher among individuals with serum s-RNY1-5p below the median value (631 molecules/mL). In a multivariable model adjusted for age, smoking, hypertension, diabetes and dyslipidemia, the risk of CHD events increased more than fourfold in individuals with serum s-RNY1-5p above the median value (HR, 4.36; 95% CI 1.22–15.60). A positive association with CHD events was also observed when considering s-RNY1-5p as a continuous variable (p = 0.022). Based on our results, we conclude that serum s-RNY1-5p is an independent predictor of CHD events in a general male population and might be a relevant biomarker for early detection of cardiovascular diseases.
Enlarged adipocytes from subcutaneous vs. visceral adipose tissue differentially contribute to metabolic dysfunction and atherogenic risk of patients with obesity
Authors: Suárez-Cuenca Juan Antonio , De La Peña-Sosa Gustavo , De La Vega-Moreno Karen , Banderas-Lares Diana Zaineff , Salamanca-García Moisés , Martínez-Hernández José Enrique , Vera-Gómez Eduardo , Hernández-Patricio Alejandro , Zamora-Alemán Carlos Ramiro , Domínguez-Pérez Gabriela Alexandra , Ruíz-Hernández Atzín Suá , Gutiérrez-Buendía Juan Ariel , Melchor-López Alberto , Ortíz-Fernández Moisés , Montoya-Ramírez Jesús , Gaytán-Fuentes Omar Felipe , Toríz-Ortíz Angélica , Osorio-Valero Mario , Orozco-Vázquez Julita , Alcaráz-Estrada Sofía Lizeth , Rodríguez-Arellano Martha Eunice , Maldonado-Arriaga Brenda , Pérez-Cabeza de Vaca Rebeca , Escamilla-Tilch Mónica , Pineda-Juárez Juan Antonio , Téllez-González Mario Antonio , García Silvia , Mondragón-Terán Paul
Published: January 2021

Morphological characteristics and source of adipose tissue as well as adipokines may increase cardiometabolic risk. This study aimed to explore whether adipose tissue characteristics may impact metabolic and atherogenic risks. Subcutaneous Adipose Tissue (SAT), Visceral Adipose Tissue (VAT) and peripheral blood were obtained from obese patients submitted to bariatric surgery. Adipose tissue (morphometry), plasma adiponectin, TNF-α, resistin (multiplexing) and biochemical chemistry were analyzed; as well as endothelial dysfunction (Flow Mediated Dilation, FMD) and atherogenesis (Carotid Intima Media Thickness, CIMT). Subgroups divided by adipocyte size and source were compared; as well as correlation and multivariate analysis. Sixty patients 36.6% males, aged 44 years-old, BMI 46.7 kg/m2 were included. SAT’s adipocytes showed a lower range of size expandability than VAT’s adipocytes. Independent from their source, larger adipocytes were associated with higher glucose, lower adiponectin and higher CIMT. Particularly, larger adipocytes from SAT were associated with higher blood pressure, lower insulin and HDL-cholesterol; and showed positive correlation with glucose, HbA1c, systolic/diastolic values, and negatively correlated with insulin and adiponectin. VAT’s larger adipocytes particularly associated with lower resistin and lower FMD values. Gender and Diabetes Mellitus significantly impacted the relation of adipocyte size/source with the metabolic and atherogenic risk. Multivariable analysis suggested hypertension-resistin-HbA1c interactions associated with SAT’s larger adipocytes; whereas potential insulin-adiponectin associations were observed for VAT’s larger adipocytes. Adipocyte morphology and source are differentially related with cardiometabolic and atherogenic risk in population with obesity, which are potentially affected by gender and Diabetes Mellitus.
Influence of water washing treatment on Ulva prolifera-derived biochar properties and sorption characteristics of ofloxacin
Authors: Yang Chenghu , Miao Shichao , Li Tiejun
Published: January 2021

The influences of water washing treatment on the properties of Ulva prolifera-derived biochar (U.P-biochar) and its sorption characteristics of ofloxacin (OFL) were investigated. The results showed that the water washing treatment significantly changed the physiochemical structures of U.P-biochars, and improved the sorption capacity of OFL. The sorption capacity of OFL by U.P-biochar was closely dependent on pyrolysis temperature (200–600 °C) and equilibrium solution pH (3–11). Different sorption mechanisms (e.g. cation exchange, electrostatic attraction, H-bond and cationic–π and π–π interactions) were dominant for specific U.P-biochars under various pH regions (acidic, neutral and alkaline). Moreover, the unwashed and washed U.P-biochars prepared at 200 °C (BC200 and BCW200) showed a higher sorption capacity of OFL at pH = 7. The two-compartment first-order model provided an appropriate description of the sorption kinetics of OFL by BC200 and BCW200 (R2 > 0.98), which revealed that the contribution ratios between the fast and slow sorption compartments (ffast/fslow, 1.55 for BC200 and 1.25 for BCW200) reduced after water washing treatment of U.P-biochar. The values of n for the Freundlich model were less than 1, which demonstrated that the sorption of OFL by BC200 and BCW200 was favourable and nonlinear. Also, the sorption of OFL by BC200 and BCW200 increased with an increase in solution temperature and the sorption process was spontaneous and endothermic. This study provides valuable information for being a primary consideration in the production and application of U.P-biochar.
Tumor infiltrating lymphocyte clusters are associated with response to immune checkpoint inhibition in BRAF V600E/K mutated malignant melanomas
Authors: Klein Sebastian , Mauch Cornelia , Brinker Klaus , Noh Ka-Won , Knez Sonja , Büttner Reinhard , Quaas Alexander , Helbig Doris
Published: January 2021

Patients with metastasized malignant melanomas (MM) are regularly treated with immune checkpoint inhibitors (CPI). Within our study, we evaluated the predictive value of tumor infiltrating lymphocyte (TIL) clusters in primary MM and its association to molecular subtypes to predict response to CPI treatment. A cohort of 90 MM patients who received CPI treatment were collected from a single center, as well as a validation cohort of 351 patients from the TCGA database (SKCM) who received standard of care. A deep-convolutional-neural network (U-Net) was trained to detect viable tumor areas on H&E whole-slide-images, following a quantitative detection of TILs with help of a separate additional neural network. The number of TIL clusters was associated with response to CPI in 90 MM patients (AUC = 0.6), even more pronounced within the sub-cohort of BRAF V600E/K-mutated MM patients (AUC = 0.7, n = 32). Interestingly, the TIL clusters in NRAS-mutated as well as wildtype MM (BRAF-wt, NRAS-wt) tumors, did not demonstrate a predictive value of CPI response (AUC = 0.5, n = 25). Moreover, PD-L1 expression had a limited predictive value within our cohort. In parallel, within an independent cohort of MM patients (TCGA, n = 351), the number of TIL clusters was associated with improved survival in BRAF V600E/K mutated MM (p < 0.0001, n = 164) but neither in NRAS-mutated (55.7 months vs. 63.0 months, respectively, p = 0.590, n = 85) nor BRAF/NRAS-wildtype MM patients (52.4 months vs. 47.4 months, respectively, p = 0.581, n = 104). While TILs in MM have been associated with improved survival, we show—for the first time—that TIL clusters are associated with response to immunotherapy in BRAF V600E/K mutated MM.