bluuebunny/crossref_metadata_2025 huggingface dataset:
Clandestine nanoelectromechanical tags for identification and authentication
Authors: Rassay Sushant , Ramezani Mehrdad , Shomaji Sumaiya , Bhunia Swarup , Tabrizian Roozbeh
Published: November 2020

The realization of truly unclonable identification and authentication tags is the key factor in protecting the global economy from an ever-increasing number of counterfeit attacks. Here, we report on the demonstration of nanoscale tags that exploit the electromechanical spectral signature as a fingerprint that is characterized by inherent randomness in fabrication processing. Benefiting from their ultraminiaturized size and transparent constituents, these clandestine nanoelectromechanical tags provide substantial immunity to physical tampering and cloning. Adaptive algorithms are developed for digital translation of the spectral signature into binary fingerprints. A large set of tags fabricated in the same batch is used to estimate the entropy of the corresponding fingerprints with high accuracy. The tags are also examined under repetitive measurements and temperature variations to verify the consistency of the fingerprints. These experiments highlight the potential of clandestine nanoelectromechanical tags for the realization of secure identification and authentication methodologies applicable to a wide range of products and consumer goods.
ASH2L drives proliferation and sensitivity to bleomycin and other genotoxins in Hodgkin’s lymphoma and testicular cancer cells
Authors: Constantin Daniel , Widmann Christian
Published: November 2020

It is of clinical importance to identify biomarkers predicting the efficacy of DNA damaging drugs (genotoxins) so that nonresponders are not unduly exposed to the deleterious effects of otherwise inefficient drugs. Here, we initially focused on the bleomycin genotoxin because of the limited information about the genes implicated in the sensitivity or resistance to this compound. Using a whole-genome CRISPR/Cas9 gene knockout approach, we identified ASH2L, a core component of the H3K4 methyl transferase complex, as a protein required for bleomycin sensitivity in L1236 Hodgkin lymphoma. Knocking down ASH2L in these cells and in the NT2D1 testicular cancer cell line rendered them resistant to bleomycin, etoposide, and cisplatin but did not affect their sensitivity toward ATM or ATR inhibitors. ASH2L knockdown decreased cell proliferation and facilitated DNA repair via homologous recombination and nonhomologous end-joining mechanisms. Data from the Tumor Cancer Genome Atlas indicate that patients with testicular cancer carrying alterations in the ASH2L gene are more likely to relapse than patients with unaltered ASH2L genes. The cell models we have used are derived from cancers currently treated either partially (Hodgkin’s lymphoma), or entirely (testicular cancer) with genotoxins. For such cancers, ASH2L levels could be used as a biomarker to predict the response to genotoxins. In situations where tumors are expressing low levels of ASH2L, which may allow them to resist genotoxic treatment, the use of ATR or ATM inhibitors may be more efficacious as our data indicate that ASH2L knockdown does not affect sensitivity to these inhibitors.
Differential guest location by host dynamics enhances propylene/propane separation in a metal-organic framework
Authors: Antypov Dmytro , Shkurenko Aleksander , Bhatt Prashant M. , Belmabkhout Youssef , Adil Karim , Cadiau Amandine , Suyetin Mikhail , Eddaoudi Mohamed , Rosseinsky Matthew J. , Dyer Matthew S.
Published: November 2020

Energy-efficient approaches to propylene/propane separation such as molecular sieving are of considerable importance for the petrochemical industry. The metal organic framework NbOFFIVE-1-Ni adsorbs propylene but not propane at room temperature and atmospheric pressure, whereas the isostructural SIFSIX-3-Ni does not exclude propane under the same conditions. The static dimensions of the pore openings of both materials are too small to admit either guest, signalling the importance of host dynamics for guest entrance to and transport through the channels. We use ab initio calculations together with crystallographic and adsorption data to show that the dynamics of the two framework-forming units, polyatomic anions and pyrazines, govern both diffusion and separation. The guest diffusion occurs by opening of the flexible window formed by four pyrazines. In NbOFFIVE-1-Ni, (NbOF5)2− anion reorientation locates propane away from the window, which enhances propylene/propane separation.
Probing the ionic defect landscape in halide perovskite solar cells
Authors: Reichert Sebastian , An Qingzhi , Woo Young-Won , Walsh Aron , Vaynzof Yana , Deibel Carsten
Published: November 2020

Point defects in metal halide perovskites play a critical role in determining their properties and optoelectronic performance; however, many open questions remain unanswered. In this work, we apply impedance spectroscopy and deep-level transient spectroscopy to characterize the ionic defect landscape in methylammonium lead triiodide (MAPbI3) perovskites in which defects were purposely introduced by fractionally changing the precursor stoichiometry. Our results highlight the profound influence of defects on the electronic landscape, exemplified by their impact on the device built-in potential, and consequently, the open-circuit voltage. Even low ion densities can have an impact on the electronic landscape when both cations and anions are considered as mobile. Moreover, we find that all measured ionic defects fulfil the Meyer–Neldel rule with a characteristic energy connected to the underlying ion hopping process. These findings support a general categorization of defects in halide perovskite compounds.
Integration of daytime radiative cooling and solar heating for year-round energy saving in buildings
Authors: Li Xiuqiang , Sun Bowen , Sui Chenxi , Nandi Ankita , Fang Haoming , Peng Yucan , Tan Gang , Hsu Po-Chun
Published: November 2020

The heating and cooling energy consumption of buildings accounts for about 15% of national total energy consumption in the United States. In response to this challenge, many promising technologies with minimum carbon footprint have been proposed. However, most of the approaches are static and monofunctional, which can only reduce building energy consumption in certain conditions and climate zones. Here, we demonstrate a dual-mode device with electrostatically-controlled thermal contact conductance, which can achieve up to 71.6 W/m2 of cooling power density and up to 643.4 W/m2 of heating power density (over 93% of solar energy utilized) because of the suppression of thermal contact resistance and the engineering of surface morphology and optical property. Building energy simulation shows our dual-mode device, if widely deployed in the United States, can save 19.2% heating and cooling energy, which is 1.7 times higher than cooling-only and 2.2 times higher than heating-only approaches.
An original infection model identifies host lipoprotein import as a route for blood-brain barrier crossing
Authors: Benmimoun Billel , Papastefanaki Florentia , Périchon Bruno , Segklia Katerina , Roby Nicolas , Miriagou Vivi , Schmitt Christine , Dramsi Shaynoor , Matsas Rebecca , Spéder Pauline
Published: November 2020

Pathogens able to cross the blood-brain barrier (BBB) induce long-term neurological sequelae and death. Understanding how neurotropic pathogens bypass this strong physiological barrier is a prerequisite to devise therapeutic strategies. Here we propose an innovative model of infection in the developing Drosophila brain, combining whole brain explants with in vivo systemic infection. We find that several mammalian pathogens are able to cross the Drosophila BBB, including Group B Streptococcus (GBS). Amongst GBS surface components, lipoproteins, and in particular the B leucine-rich Blr, are important for BBB crossing and virulence in Drosophila. Further, we identify (V)LDL receptor LpR2, expressed in the BBB, as a host receptor for Blr, allowing GBS translocation through endocytosis. Finally, we show that Blr is required for BBB crossing and pathogenicity in a murine model of infection. Our results demonstrate the potential of Drosophila for studying BBB crossing by pathogens and identify a new mechanism by which pathogens exploit the machinery of host barriers to generate brain infection.
Valley interference and spin exchange at the atomic scale in silicon
Authors: Voisin B. , Bocquel J. , Tankasala A. , Usman M. , Salfi J. , Rahman R. , Simmons M. Y. , Hollenberg L. C. L. , Rogge S.
Published: November 2020

Tunneling is a fundamental quantum process with no classical equivalent, which can compete with Coulomb interactions to give rise to complex phenomena. Phosphorus dopants in silicon can be placed with atomic precision to address the different regimes arising from this competition. However, they exploit wavefunctions relying on crystal band symmetries, which tunneling interactions are inherently sensitive to. Here we directly image lattice-aperiodic valley interference between coupled atoms in silicon using scanning tunneling microscopy. Our atomistic analysis unveils the role of envelope anisotropy, valley interference and dopant placement on the Heisenberg spin exchange interaction. We find that the exchange can become immune to valley interference by engineering in-plane dopant placement along specific crystallographic directions. A vacuum-like behaviour is recovered, where the exchange is maximised to the overlap between the donor orbitals, and pair-to-pair variations limited to a factor of less than 10 considering the accuracy in dopant positioning. This robustness remains over a large range of distances, from the strongly Coulomb interacting regime relevant for high-fidelity quantum computation to strongly coupled donor arrays of interest for quantum simulation in silicon.
Diverse crystal size effects in covalent organic frameworks
Authors: Ma Tianqiong , Wei Lei , Liang Lin , Yin Shawn , Xu Le , Niu Jing , Xue Huadong , Wang Xiaoge , Sun Junliang , Zhang Yue-Biao , Wang Wei
Published: November 2020

Crystal size effect is of vital importance in materials science by exerting significant influence on various properties of materials and furthermore their functions. Crystal size effect of covalent organic frameworks (COFs) has never been reported because their controllable synthesis is difficult, despite their promising properties have been exhibited in many aspects. Here, we report the diverse crystal size effects of two representative COFs based on the successful realization of crystal-size-controlled synthesis. For LZU-111 with rigid spiral channels, size effect reflects in pore surface area by influencing the pore integrity, while for flexible COF-300 with straight channels, crystal size controls structural flexibility by altering the number of repeating units, which eventually changes sorption selectivity. With the understanding and insight of the structure-property correlation not only at microscale but also at mesoscale for COFs, this research will push the COF field step forward to a significant advancement in practical applications.
MINPP1 prevents intracellular accumulation of the chelator inositol hexakisphosphate and is mutated in Pontocerebellar Hypoplasia
Authors: Ucuncu Ekin , Rajamani Karthyayani , Wilson Miranda S. C. , Medina-Cano Daniel , Altin Nami , David Pierre , Barcia Giulia , Lefort Nathalie , Banal Céline , Vasilache-Dangles Marie-Thérèse , Pitelet Gaële , Lorino Elsa , Rabasse Nathalie , Bieth Eric , Zaki Maha S. , Topcu Meral , Sonmez Fatma Mujgan , Musaev Damir , Stanley Valentina , Bole-Feysot Christine , Nitschké Patrick , Munnich Arnold , Bahi-Buisson Nadia , Fossoud Catherine , Giuliano Fabienne , Colleaux Laurence , Burglen Lydie , Gleeson Joseph G. , Boddaert Nathalie , Saiardi Adolfo , Cantagrel Vincent
Published: November 2020

Inositol polyphosphates are vital metabolic and secondary messengers, involved in diverse cellular functions. Therefore, tight regulation of inositol polyphosphate metabolism is essential for proper cell physiology. Here, we describe an early-onset neurodegenerative syndrome caused by loss-of-function mutations in the multiple inositol-polyphosphate phosphatase 1 gene (MINPP1). Patients are found to have a distinct type of Pontocerebellar Hypoplasia with typical basal ganglia involvement on neuroimaging. We find that patient-derived and genome edited MINPP1−/− induced stem cells exhibit an inefficient neuronal differentiation combined with an increased cell death. MINPP1 deficiency results in an intracellular imbalance of the inositol polyphosphate metabolism. This metabolic defect is characterized by an accumulation of highly phosphorylated inositols, mostly inositol hexakisphosphate (IP6), detected in HEK293 cells, fibroblasts, iPSCs and differentiating neurons lacking MINPP1. In mutant cells, higher IP6 level is expected to be associated with an increased chelation of intracellular cations, such as iron or calcium, resulting in decreased levels of available ions. These data suggest the involvement of IP6-mediated chelation on Pontocerebellar Hypoplasia disease pathology and thereby highlight the critical role of MINPP1 in the regulation of human brain development and homeostasis.
Enhanced dispersion stability of gold nanoparticles by the physisorption of cyclic poly(ethylene glycol)
Authors: Wang Yubo , Quinsaat Jose Enrico Q. , Ono Tomoko , Maeki Masatoshi , Tokeshi Manabu , Isono Takuya , Tajima Kenji , Satoh Toshifumi , Sato Shin-ichiro , Miura Yutaka , Yamamoto Takuya
Published: November 2020

Nano-sized metal particles are attracting much interest in industrial and biomedical applications due to the recent progress and development of nanotechnology, and the surface-modifications by appropriate polymers are key techniques to stably express their characteristics. Herein, we applied cyclic poly(ethylene glycol) (c-PEG), having no chemical inhomogeneity, to provide a polymer topology-dependent stabilization for the surface-modification of gold nanoparticles (AuNPs) through physisorption. By simply mixing c-PEG, but not linear counterparts, enables AuNPs to maintain dispersibility through freezing, lyophilization, or heating. Surprisingly, c-PEG endowed AuNPs with even better dispersion stability than thiolated PEG (HS–PEG–OMe). The stronger affinity of c-PEG was confirmed by DLS, ζ-potential, and FT-IR. Furthermore, the c-PEG system exhibited prolonged blood circulation and enhanced tumor accumulation in mice. Our data suggests that c-PEG induces physisorption on AuNPs, supplying sufficient stability toward bio-medical applications, and would be an alternative approach to the gold–sulfur chemisorption.
CCL7 recruits cDC1 to promote antitumor immunity and facilitate checkpoint immunotherapy to non-small cell lung cancer
Authors: Zhang Man , Yang Wei , Wang Peng , Deng Yu , Dong Yu-Ting , Liu Fang-Fang , Huang Rui , Zhang Peng , Duan Ya-Qi , Liu Xin-Dong , Lin Dandan , Chu Qian , Zhong Bo
Published: November 2020

The efficacy of checkpoint immunotherapy to non-small cell lung cancer (NSCLC) largely depends on the tumor microenvironment (TME). Here, we demonstrate that CCL7 facilitates anti-PD-1 therapy for the KrasLSL−G12D/+Tp53fl/fl (KP) and the KrasLSL−G12D/+Lkb1fl/fl (KL) NSCLC mouse models by recruiting conventional DC 1 (cDC1) into the TME to promote T cell expansion. CCL7 exhibits high expression in NSCLC tumor tissues and is positively correlated with the infiltration of cDC1 in the TME and the overall survival of NSCLC patients. CCL7 deficiency impairs the infiltration of cDC1 in the TME and the subsequent expansion of CD8+ and CD4+ T cells in bronchial draining lymph nodes and TME, thereby promoting tumor development in the KP mouse model. Administration of CCL7 into lungs alone or in combination with anti-PD-1 significantly inhibits tumor development and prolongs the survival of KP and KL mice. These findings suggest that CCL7 potentially serves as a biomarker and adjuvant for checkpoint immunotherapy of NSCLC.
An investigation of irreproducibility in maximum likelihood phylogenetic inference
Authors: Shen Xing-Xing , Li Yuanning , Hittinger Chris Todd , Chen Xue-xin , Rokas Antonis
Published: November 2020

Phylogenetic trees are essential for studying biology, but their reproducibility under identical parameter settings remains unexplored. Here, we find that 3515 (18.11%) IQ-TREE-inferred and 1813 (9.34%) RAxML-NG-inferred maximum likelihood (ML) gene trees are topologically irreproducible when executing two replicates (Run1 and Run2) for each of 19,414 gene alignments in 15 animal, plant, and fungal phylogenomic datasets. Notably, coalescent-based ASTRAL species phylogenies inferred from Run1 and Run2 sets of individual gene trees are topologically irreproducible for 9/15 phylogenomic datasets, whereas concatenation-based phylogenies inferred twice from the same supermatrix are reproducible. Our simulations further show that irreproducible phylogenies are more likely to be incorrect than reproducible phylogenies. These results suggest that a considerable fraction of single-gene ML trees may be irreproducible. Increasing reproducibility in ML inference will benefit from providing analyses’ log files, which contain typically reported parameters (e.g., program, substitution model, number of tree searches) but also typically unreported ones (e.g., random starting seed number, number of threads, processor type).
Structural and functional characterization of M. tuberculosis sedoheptulose- 7-phosphate isomerase, a critical enzyme involved in lipopolysaccharide biosynthetic pathway
Authors: Karan Sumita , Pratap Bhanu , Yadav Shiv Pratap , Ashish FNU , Saxena Ajay K.
Published: November 2020

M. tuberculosis GmhA enzyme catalyzes the isomerization of D-sedoheptulose 7-phosphate into D-glycero-D-α-manno-heptose-7-phosphate in GDP-D-glycero-α-D-manno-heptose biosynthetic pathway. The D-glycero-α-D-manno-heptose is a major constituent of lipopolysaccharide and contributes to virulence and antibiotic resistance to mycobacteria. In current study, we have performed the structural and biochemical analysis of M. tuberculosis GmhA, the first enzyme involved in D-sedoheptulose 7-phosphate isomerization in GDP-D-α-D-heptose biosynthetic pathway. The MtbGmhA enzyme exits as tetramer and small angle X-ray scattering analysis also yielded tetrameric envelope in solution. The MtbGmhA enzyme binds to D-sedoheptulose 7-phosphate with Km ~ 0.31 ± 0.06 mM−1 and coverts it to D-glycero-D-α-manno-heptose-7-phosphate with catalytic efficiency (kcat/Km) ~ 1.45 mM−1 s−1. The residues involved in D-sedoheptulose 7-phosphate and Zn2+ binding were identified using modeled MtbGmhA + D-sedoheptulose 7-phosphate + Zn2+ structure. To understand the role in catalysis, six site directed mutants of MtbGmhA were generated, which showed significant decrease in catalytic activity. The circular dichroism analysis showed ~ 46% α-helix, ~ 19% β-sheet and ~ 35% random coil structures of MtbGmhA enzyme and melting temperature ~ 53.5 °C. Small angle X-ray scattering analysis showed the tetrameric envelope, which fitted well with modeled MtbGmhA tetramer in closed conformation. The MtbGmhA dynamics involved in D-sedoheptulose 7-phosphate and Zn2+ binding was identified using dynamics simulation and showed enhanced stability in presence of these ligands. Our biochemical data and structural knowledge have provided insight into mechanism of action of MtbGmhA enzyme, which can be targeted for novel antibiotics development against M. tuberculosis.
Brief high fat high sugar diet results in altered energy and fat metabolism during pregnancy in mice
Authors: Pennington Kathleen A. , Dong Yuanlin , Ruano Simone Hernandez , van der Walt Nicola , Sangi-Haghpeykar Haleh , Yallampalli Chandrasekhar
Published: November 2020

During pregnancy several maternal adaptations occur in order to support the growing fetus which are further exacerbated by gestational diabetes mellitus (GDM). Previously we developed a mouse model of GDM, however we did not evaluate alterations to energy and fat metabolism. We have also shown that alterations in lipid metabolism are mediated by adrenomedullin (ADM) in normal and GDM pregnancies. Our objectives were: (1) evaluate energy and fat homeostasis in our GDM mouse model and (2) determine if ADM may play a role in these changes. Female mice were placed on either control (P-CD) or high fat, high sucrose diet (P-HFHS) 1 week prior to and throughout pregnancy. Mice were placed into comprehensive lab animal monitoring system (CLAMS) chambers throughout pregnancy. Visceral adipose tissue (VAT) was collected at d17.5 of pregnancy for analysis. Energy Expenditure was significantly increased (p < 0.05) in P-HFHS dams compared to all other groups. VAT ex-vivo lipolysis was increased (p < 0.05) in P-HFHS compared to P-CD dams. VAT gene expression of ADM receptors Crlr, Ramp2, and Ramp3 was increased (p < 0.05) in P-HFHS dams. ADM dose dependently increased ex vivo lipolysis. This data further validates our animal model of GDM and is usefulness in investigating the pathophysiology of GDM.
Phylogenetic comparison of egg transparency in ascidians by hyperspectral imaging
Authors: Shito Takumi T. , Hasegawa Naohiro , Oka Kotaro , Hotta Kohji
Published: November 2020

The transparency of animals is an important biological feature. Ascidian eggs have various degrees of transparency, but this characteristic has not yet been measured quantitatively and comprehensively. In this study, we established a method for evaluating the transparency of eggs to first characterize the transparency of ascidian eggs across different species and to infer a phylogenetic relationship among multiple taxa in the class Ascidiacea. We measured the transmittance of 199 eggs from 21 individuals using a hyperspectral camera. The spectrum of the visual range of wavelengths (400–760 nm) varied among individuals and we calculated each average transmittance of the visual range as bio-transparency. When combined with phylogenetic analysis based on the nuclear 18S rRNA and the mitochondrial cytochrome c oxidase subunit I gene sequences, the bio-transparencies of 13 species were derived from four different families: Ascidiidae, Cionidae, Pyuridae, and Styelidae. The bio-transparency varied 10–90% and likely evolved independently in each family. Ascidiella aspersa showed extremely high (88.0 ± 1.6%) bio-transparency in eggs that was maintained in the “invisible” larva. In addition, it was indicated that species of the Ascidiidae family may have a phylogenetic constraint of egg transparency.
A possible precursor prior to the Lushan earthquake from GPS observations in the southern Longmenshan
Authors: Wang Qixin , Xu Xiwei , Jiang Zaisen , Suppe John
Published: November 2020

Global Positioning System (GPS) stations installed in and around the epicenter of the Lushan earthquake (Mw 6.7), which occurred almost 5 years after the 2008 Wenchuan earthquake, recorded preseismic deformation corresponding to the Lushan earthquake within the southern Longmenshan thrust belt. A half-space dislocation model is used to simulate the theoretical values of the postseismic displacements caused by the 2008 Wenchuan earthquake, and after transforming the reference frame and filtering the GPS displacement time series, the theoretical and observed GPS values are compared to identify the geodetic anomaly preceding the Lushan earthquake. The abnormal extent of this geodetic anomaly decreases with increasing epicentral distance for each GPS site. This geodetic signal reflects preslip along a locked section of the 2013 seismogenic fault, which caused the accumulation of elastic strain energy until the faulting strength was overcome, thereby generating the Lushan earthquake. Hence, this anomaly might be used as an observable and identifiable precursor to forecast an impending earthquake within a period of less than two and half years before its occurrence.
A chromatographic approach to development of 5-aminosalicylate/folic acid fixed-dose combinations for treatment of Crohn’s disease and ulcerative colitis
Authors: Jeličić Mario-Livio , Brusač Edvin , Klarić Daniela Amidžić , Nigović Biljana , Turk Nikša , Mornar Ana
Published: November 2020

Medication adherence is an important factor in inflammatory bowel disease therapy, which includes regular supplementation of malabsorbed vitamins. Absorption of folic acid is limited due to the damaging of the gastrointestinal tract, which can increase the chances to develop megaloblastic anaemia and colorectal cancer. In this work, 5-aminosalicylates (mesalazine, balsalazide, sulfasalazine and olsalazine) and folic acid were characterized regarding their pharmacokinetic related properties (hydrophobicity, phospholipid and plasma protein binding) using the biomimetic chromatographic approach. Despite the high binding percentage of 5-aminosalicylates for human serum albumin (> 61.44%), results have shown that folic acid binding to human serum albumin protein is far greater (69.40%) compared to α1-acid-glycoprotein (3.45%). Frontal analysis and zonal elution studies were conducted to provide an insight into the binding of folic acid to human serum albumin and potential competition with 5-aminosalicylates. The analytical method for the simultaneous determination of assay in proposed fixed-dose combinations was developed and validated according to ICH Q2 (R1) and FDA method validation guidelines. Separation of all compounds was achieved within 16 min with satisfactory resolution (Rs > 3.67) using the XBridge Phenyl column (150 × 4.6 mm, 3.5 µm). High linearity (r > 0.9997) and precision (RSD < 2.29%) was obtained, whilst all recoveries were within the regulatory defined range by British (100.0 ± 5.0%) and United States Pharmacopeia (100.0 ± 10.0%).
Optimal photon pairs for quantum communication protocols
Authors: Lasota Mikołaj , Kolenderski Piotr
Published: November 2020

We theoretically investigate the problem of finding optimal characteristics of photon pairs, produced in the spontaneous parametric down-conversion (SPDC) process, for fiber-based quantum communication protocols. By using the accessible setup parameters, the pump pulse duration and the extended phase-matching function width, we minimize the temporal width of SPDC photons within the general scenario. This allows one to perform more effectively the temporal filtering procedure, which aims at reducing the noise acquired by the measurement devices. Moreover, we compare the obtained results with the achievable parameter values for SPDC sources based on $$\beta$$
β
-Barium Borate crystal. We also investigate the influence of non-zero detection timing jitter. Finally, we apply our optimization strategy to a simple quantum key distribution scheme to show that the full optimization of an SPDC source can potentially extend the maximal security distance by several tens of kilometres, which is around 30% more as compared to previous approaches.
Bundling of cellulose microfibrils in native and polyethylene glycol-containing wood cell walls revealed by small-angle neutron scattering
Authors: Penttilä Paavo A. , Altgen Michael , Awais Muhammad , Österberg Monika , Rautkari Lauri , Schweins Ralf
Published: November 2020

Wood and other plant-based resources provide abundant, renewable raw materials for a variety of applications. Nevertheless, their utilization would greatly benefit from more efficient and accurate methods to characterize the detailed nanoscale architecture of plant cell walls. Non-invasive techniques such as neutron and X-ray scattering hold a promise for elucidating the hierarchical cell wall structure and any changes in its morphology, but their use is hindered by challenges in interpreting the experimental data. We used small-angle neutron scattering in combination with contrast variation by poly(ethylene glycol) (PEG) to identify the scattering contribution from cellulose microfibril bundles in native wood cell walls. Using this method, mean diameters for the microfibril bundles from 12 to 19 nm were determined, without the necessity of cutting, drying or freezing the cell wall. The packing distance of the individual microfibrils inside the bundles can be obtained from the same data. This finding opens up possibilities for further utilization of small-angle scattering in characterizing the plant cell wall nanostructure and its response to chemical, physical and biological modifications or even in situ treatments. Moreover, our results give new insights into the interaction between PEG and the wood nanostructure, which may be helpful for preservation of archaeological woods.
Specific capture and whole-genome phylogeography of Dolphin morbillivirus
Authors: Cerutti Francesco , Giorda Federica , Grattarola Carla , Mignone Walter , Beltramo Chiara , Keck Nicolas , Lorusso Alessio , Di Francesco Gabriella , Di Renzo Ludovica , Di Guardo Giovanni , Goria Mariella , Masoero Loretta , Acutis Pier Luigi , Casalone Cristina , Peletto Simone
Published: November 2020

Dolphin morbillivirus (DMV) is considered an emerging threat having caused several epidemics worldwide. Only few DMV genomes are publicly available. Here, we report the use of target enrichment directly from cetacean tissues to obtain novel DMV genome sequences, with sequence comparison and phylodynamic analysis. RNA from 15 tissue samples of cetaceans stranded along the Italian and French coasts (2008–2017) was purified and processed using custom probes (by bait hybridization) for target enrichment and sequenced on Illumina MiSeq. Data were mapped against the reference genome, and the novel sequences were aligned to the available genome sequences. The alignment was then used for phylogenetic and phylogeographic analysis using MrBayes and BEAST. We herein report that target enrichment by specific capture may be a successful strategy for whole-genome sequencing of DMV directly from field samples. By this strategy, 14 complete and one partially complete genomes were obtained, with reads mapping to the virus up to 98% and coverage up to 7800X. The phylogenetic tree well discriminated the Mediterranean and the NE-Atlantic strains, circulating in the Mediterranean Sea and causing two different epidemics (2008–2015 and 2014–2017, respectively), with a limited time overlap of the two strains, sharing a common ancestor approximately in 1998.
Stability of the timing of food intake at daily and monthly timescales in young adults
Authors: McHill Andrew W. , Hilditch Cassie J. , Fischer Dorothee , Czeisler Charles A. , Garaulet Marta , Scheer Frank A. J. L. , Klerman Elizabeth B.
Published: November 2020

Cross-sectional observations have shown that the timing of eating may be important for health-related outcomes. Here we examined the stability of eating timing, using both clock hour and relative circadian time, across one semester (n = 14) at daily and monthly time-scales. At three time points ~ 1 month apart, circadian phase was determined during an overnight in-laboratory visit and eating was photographically recorded for one week to assess timing and composition. Day-to-day stability was measured using the Composite Phase Deviation (deviation from a perfectly regular pattern) and intraclass correlation coefficients (ICC) were used to determine individual stability across months (weekly average compared across months). Day-to-day clock timing of caloric events had poor stability within individuals (~ 3-h variation; ICC = 0.12–0.34). The timing of eating was stable across months (~ 1-h variation, ICCs ranging from 0.54–0.63), but less stable across months when measured relative to circadian timing (ICC = 0.33–0.41). Our findings suggest that though day-to-day variability in the timing of eating has poor stability, the timing of eating measured for a week is stable across months within individuals. This indicates two relevant timescales: a monthly timescale with more stability in eating timing than a daily timescale. Thus, a single day’s food documentation may not represent habitual (longer timescale) patterns.
Familial risks between giant cell arteritis and Takayasu arteritis and other autoimmune diseases in the population of Sweden
Authors: Thomsen Hauke , Li Xinjun , Sundquist Kristina , Sundquist Jan , Försti Asta , Hemminki Kari
Published: November 2020

Giant cell arteritis (GCA, also called temporal arteritis) is a rare and Takayasu arteritis (TA) is an even rarer autoimmune disease (AID), both of which present with inflammatory vasculitis of large and medium size arteries. The risk factors are largely undefined but disease susceptibility has been associated with human leukocyte antigen locus. Population-level familial risk is not known. In the present nation-wide study we describe familial risk for GCA and for GCA and TA with any other AID based on the Swedish hospital diagnoses up to years 2012. Family relationships were obtained from the Multigeneration Register. Familial standardized incidence ratios (SIRs) were calculated for offspring whose parents or siblings were diagnosed with GCA, TA or any other AID. The number of GCA patients in the offspring generation was 4695, compared to 209 TA patients; for both, familial patients accounted for 1% of all patients. The familial risk for GCA was 2.14, 2.40 for women and non-significant for men. GCA was associated with 10 other AIDs and TA was associated with 6 other AIDs; both shared associations with polymyalgia rheumatica and rheumatoid arthritis. The results showed that family history is a risk factor for GCA. Significant familial associations of both GCA and TA with such a number of other AIDs provide evidence for polyautoimmunity among these diseases.
Regulators of TNFα mediated insulin resistance elucidated by quantitative proteomics
Authors: Mohallem Rodrigo , Aryal Uma K.
Published: November 2020

Obesity is a growing epidemic worldwide and is a major risk factor for several chronic diseases, including diabetes, kidney disease, heart disease, and cancer. Obesity often leads to type 2 diabetes mellitus, via the increased production of proinflammatory cytokines such as tumor necrosis factor-α (TNFα). Our study combines different proteomic techniques to investigate the changes in the global proteome, secretome and phosphoproteome of adipocytes under chronic inflammation condition, as well as fundamental cross-talks between different cellular pathways regulated by chronic TNFα exposure. Our results show that many key regulator proteins of the canonical and non-canonical NF-κB pathways, such as Nfkb2, and its downstream effectors, including Csf-1 and Lgals3bp, directly involved in leukocyte migration and invasion, were significantly upregulated at the intra and extracellular proteomes suggesting the progression of inflammation. Our data provides evidence of several key proteins that play a role in the development of insulin resistance.
Lokiarchaeota archaeon schizorhodopsin-2 (LaSzR2) is an inward proton pump displaying a characteristic feature of acid-induced spectral blue-shift
Authors: Kojima Keiichi , Yoshizawa Susumu , Hasegawa Masumi , Nakama Masaki , Kurihara Marie , Kikukawa Takashi , Sudo Yuki
Published: November 2020

The photoreactive protein rhodopsin is widespread in microorganisms and has a variety of photobiological functions. Recently, a novel phylogenetically distinctive group named ‘schizorhodopsin (SzR)’ has been identified as an inward proton pump. We performed functional and spectroscopic studies on an uncharacterised schizorhodopsin from the phylum Lokiarchaeota archaeon. The protein, LaSzR2, having an all-trans-retinal chromophore, showed inward proton pump activity with an absorption maximum at 549 nm. The pH titration experiments revealed that the protonated Schiff base of the retinal chromophore (Lys188, pKa = 12.3) is stabilised by the deprotonated counterion (presumably Asp184, pKa = 3.7). The flash-photolysis experiments revealed the presence of two photointermediates, K and M. A proton was released and uptaken from bulk solution upon the formation and decay of the M intermediate. During the M-decay, the Schiff base was reprotonated by the proton from a proton donating residue (presumably Asp172). These properties were compared with other inward (SzRs and xenorhodopsins, XeRs) and outward proton pumps. Notably, LaSzR2 showed acid-induced spectral ‘blue-shift’ due to the protonation of the counterion, whereas outward proton pumps showed opposite shifts (red-shifts). Thus, we can distinguish between inward and outward proton pumps by the direction of the acid-induced spectral shift.
Working memory updating of emotional stimuli predicts emotional intelligence in females
Authors: Orzechowski Jarosław , Śmieja Magdalena , Lewczuk Karol , Nęcka Edward
Published: November 2020

Preliminary evidence concerning emotional intelligence (EI) and working memory (WM) showed that the relationship between them is dependent on the emotional content (‘hot’ or ‘cool’) of tasks involving WM. In this paper, we continue investigating the relationship between EI and WM, focusing on a crucial function of WM, i.e., the efficacy of updating its content. WM updating shows substantial correlations with general fluid intelligence (gF) and seems to be a significant predictor of cognitive performance and achievement. We assume that if updating is important for a wide range of higher-order processes, updating emotional content in WM could be essential for emotionally intelligent behavior. To test this hypothesis, we constructed two parallel versions of a task that requires WM updating: one with neutral and the other with emotional stimuli. In addition, performance-based measures of both gF and EI were used in the research. Using the structural equation approach, we sought to demonstrate that gF is dependent on the efficiency of WM updating for both emotional and neutral stimuli, whereas EI might depend only on the updating efficacy in the emotional context. The results are discussed in terms of the domain specificity of EI and the domain generality of gF. The main constraint of the study is its limited sample size (n = 123 for intelligence measures, n = 69 for WM updating tasks). Moreover, the study was based on a female sample; thus, the conclusions can be extrapolated only to women.
USP24 stabilizes bromodomain containing proteins to promote lung cancer malignancy
Authors: Wang Shao-An , Young Ming-Jer , Jeng Wen-Yih , Liu Chia-Yu , Hung Jan-Jong
Published: November 2020

Bromodomain (BRD)-containing proteins are important for chromatin remodeling to regulate gene expression. In this study, we found that the deubiquitinase USP24 interacted with BRD through its C-terminus increased the levels of most BRD-containing proteins through increasing their protein stability by the removal of ubiquitin from Lys391/Lys400 of the BRD. In addition, we found that USP24 and BRG1 could regulate each other through regulating the protein stability and the transcriptional activity, respectively, of the other, suggesting that the levels of USP24 and BRG1 are regulated to form a positive feedback loop in cancer progression. Loss of the interaction motif of USP24 eliminated the ability of USP24 to stabilize BRD-containing proteins and abolished the effect of USP24 on cancer progression, including its inhibition of cancer cell proliferation and promotion of cancer cell migration, suggesting that the interaction between USP24 and the BRD is important for USP24-mediated effects on cancer progression. The targeting of BRD-containing proteins has been developed as a strategy for cancer therapy. Based on our study, targeting USP24 to inhibit the levels of BRD-containing proteins may inhibit cancer progression.
Lysine demethylase 7a regulates murine anterior-posterior development by modulating the transcription of Hox gene cluster
Authors: Higashijima Yoshiki , Nagai Nao , Yamamoto Masamichi , Kitazawa Taro , Kawamura Yumiko K. , Taguchi Akashi , Nakada Natsuko , Nangaku Masaomi , Furukawa Tetsushi , Aburatani Hiroyuki , Kurihara Hiroki , Wada Youichiro , Kanki Yasuharu
Published: November 2020

Temporal and spatial colinear expression of the Hox genes determines the specification of positional identities during vertebrate development. Post-translational modifications of histones contribute to transcriptional regulation. Lysine demethylase 7A (Kdm7a) demethylates lysine 9 or 27 di-methylation of histone H3 (H3K9me2, H3K27me2) and participates in the transcriptional activation of developmental genes. However, the role of Kdm7a during mouse embryonic development remains to be elucidated. Herein, we show that Kdm7a−/− mouse exhibits an anterior homeotic transformation of the axial skeleton, including an increased number of presacral elements. Importantly, posterior Hox genes (caudally from Hox9) are specifically downregulated in the Kdm7a−/− embryo, which correlates with increased levels of H3K9me2, not H3K27me2. These observations suggest that Kdm7a controls the transcription of posterior Hox genes, likely via its demethylating activity, and thereby regulating the murine anterior-posterior development. Such epigenetic regulatory mechanisms may be harnessed for proper control of coordinate body patterning in vertebrates.
Phosphate-assisted efficient oxygen evolution over finely dispersed cobalt particles supported on graphene
Authors: Zeng Feng , Li Jialin , Hofmann Jan P. , Bisswanger Timo , Stampfer Christoph , Hartmann Heinrich , Besmehn Astrid , Palkovits Stefan , Palkovits Regina
Published: November 2020

Finely dispersed cobalt particles supported on graphene activated by phosphate boosting highly efficient and stable oxygen evolution.
Current concepts in robotic total hip arthroplasty
Authors: Kouyoumdjian Pascal , Mansour Jad , Assi Chahine , Caton Jacques , Lustig Sebastien , Coulomb Remy
Published: November 2020

Introduction:Total hip replacement provides mostly fair functional and clinical results. Many factors play an essential role in hip stability and long-term outcomes. Surgical positioning remains fundamental for obtaining accurate implant fit and prevent hip dislocation or impingement. Different categories of robotic assistance have been established throughout the previous years and all of the technologies target accuracy and reliability to reduce complications, and enhance clinical outcomes.Materials and methods: An overview is proposed over the principles of robotic assistance in hip arthroplasty surgery. Accuracy, reliability, management of the bone stock, clinical outcomes, constraints and limits of this technology are reported, based on recent literature.Results: Potential advantages regarding pre-operative planning accuracy, cup positioning, maintenance of the center of rotation, preservation of an adequate bone stock nay clinical short- and mid-term outcomes are balanced with some reported disadvantages and limits like hip anatomical specificity, cost-effectiveness, engineering dependence.Discussion: The use of robotic-assisted THA presents clear and evident benefits related to accurate implant positioning and maintenance of a minimal bone while allowing. For some authors, an early improvement in functional results and patient’s recovery. This technology demonstrated a shorter surgical time and a short learning curve required to optimize its use and this technology presents promising outcomes and results and potential use in routine clinical application but its limitation of use is still present especially the cost of the robot, the need for the presence of an engineer during the surgery, its availability of use in all hospitals as well as the difficulty presented in dysplastic or dysmorphic hip joints.
Therapeutisches Drug Monitoring von Antiinfektiva bei Intensivpatienten – für welche Arzneistoffe und wie?
Authors: König Christina , Kluge Stefan , Wicha Sebastian G.
Published: November 2020

Was ist neu?

Prinzip des therapeutischen Drug Monitorings Für immer mehr Antiinfektiva gibt es Erkenntnisse zur Expositions-Wirkungs-Beziehung, die im therapeutischen Drug Monitoring (TDM) genutzt werden können. Dabei spielt die Schätzung der AUC (area under the curve) eine wichtige Rolle. Eine spezielle Pharmakokinetik-Software hilft in der Praxis, die Schätzung der AUC auch anhand weniger Proben zu ermöglichen.

Für welche Arzneistoffe wird ein therapeutisches Drug Monitoring empfohlen? Neben dem vielfach bereits etablierten TDM für Aminoglykoside (Amikacin, Gentamicin und Tobramycin) und Glykopeptide (Vancomycin, Teicoplanin) empfiehlt ein fachübergreifendes Expertengremium bei Intensivpatienten ein TDM für Betalaktame, Linezolid und Voriconazol. Neuerungen gibt es auch bei Vancomycin, bei dem vom häufig praktizierten „Talspiegel“-TDM zum in klinischen Studien überlegenen AUC-basierten TDM übergegangen werden soll.
Adipositas-Chirurgie – eine sichere Option bei Risiko-Patienten mit irreversibler Organ-Dysfunktion
Authors: Moulla Yusef , Lange Undine Gabriele , Mehdorn Matthias , Blüher Matthias , van Bömmel Florian , Pietsch Uta-Carolin , Buchloh Dorina , Dietrich Arne
Published: November 2020

Einleitung Adipositas-Chirurgie ist weltweit etabliert und sicher durchführbar. Mit steigender Expertise werden auch zunehmend Risikopatienten operiert, die z.B. bei Organdysfunktion zu adipös für eine geplante Organtransplantation sind.

Patienten und Methoden In dem Zeitraum 1/13 bis 6/9 wurden 653 Patienten an unserem Zentrum adipositaschirurgisch versorgt. Die Daten wurden retrospektiv ausgewertet und es fanden sich unter den 653 Patienten 34 Patienten mit dialysepflichtiger Niereninsuffizienz, hochgradiger Herzinsuffizienz (linksventrikuläre Ejektionsfraktion < 30 %) oder Leberzirrhose (Child-Pugh-Stadium A und B). Das Minimum-Follow-up beträgt 12 Monate.

Ergebnisse Bei 5 der 34 Patienten (14,7 %) kam es zu einem komplizierten Verlauf. Folgende Komplikationen traten auf: 3x Wundheilungsstörung mit konservativer Therapie, 1x subkutane Nachblutung bei einem Patienten mit LVAD (konservative Therapie) und 1 Shunt-Verschluss, der operativ revidiert wurde.

Schlussfolgerung Adipositaschirurgische Eingriffe sind auch bei Risikopatienten mit geringer Morbidität und Mortalität durchführbar.
Metabolische Chirurgie, mehr als nur Typ-2-Diabetes
Authors: Rühle Annika , Boskovic Andrea , Billeter Adrian T. , Schwarz Anne-Catherine , Müller-Stich Beat P.
Published: November 2020

Die Prävalenzen von Adipositas und metabolischen Erkrankungen wie Diabetes mellitus Typ 2 (DM2), Nicht-alkoholischer Fettlebererkrankung (NAFLD), arterieller Hypertonie (aHT) oder Obstruktiver Schlafapnoe (OSAS) steigen. Die Adipositas-Chirurgie ist nicht nur hinsichtlich des Gewichtsverlustes der konservativen Therapie überlegen, sondern zeigt ebenfalls positive Effekte auf metabolische Erkrankungen. Die meisten Daten finden sich für den DM2, hier kommt es unabhängig vom Gewichtsverlust zu einer besseren glykämischen Kontrolle, Verbesserung mikro- und makrovaskulärer Komplikationen wie der diabetischen Nephropathie oder Polyneuropathie und Reduktion der Mortalität. Bei Patienten mit NAFLD zeigen sich sowohl laborchemisch als auch histologisch Befundverbesserungen bis hin zur Regredienz fibrotischer Veränderungen. Die antihypertensive Medikation kann nach metabolischem Eingriff nachhaltig reduziert oder gar sistiert werden, gleiches
gilt für die medikamentöse Therapie der Dyslipidämie. Patienten mit diabetischer Nephropathie oder auch Adipositas-assoziierter Albuminurie profitieren von einer Erholung der Nierenfunktion und Reduktion der Dialysepflichtigkeit. Auch das OSAS, eine häufige Erkrankung adipöser Patienten mit Erhöhung des kardiovaskulären Risikos, zeigt postoperativ eine Befundverbesserung. Diese beginnt sogar schon bevor es zu einem relevanten Gewichtsverlust kommt, welcher zusätzlich die Atemmechanik erleichtert.

Interessanterweise zeigen sich die beschriebenen Effekte nicht nur bei adipösen, sondern auch bei normalgewichtigen Patienten. Der DM2 stellt daher bereits in bestimmten Fällen beim normalgewichtigen Patienten eine Indikation zur metabolischen Chirurgie dar. Eine Anpassung der Leitlinien hinsichtlich anderer metabolischer Erkrankungen steht trotz zunehmender hochklassiger Evidenz diesbezüglich noch aus.