bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of current genetic testing reports in German-speaking countries with regard to secondary use and future electronic implementation
Authors: Radke Teja Falk , Patton Simon J. , Pantazoglou Elisabeth , Sass Julian , Thun Sylvia
Published: February 2020

Modern diagnostic methods (next-generation sequencing) are one of the current hopes with regard to a personalised medicine. By applying detailed genetic analysis, it is possible to not only improve the prediction of potential risks (as, e.g., concerning hereditary breast cancer) but also the precision of therapy by targeting it to a specific genetic variant. However, there is no international standard for creating, structuring and/or transferring the results of a genetic test report. This type of test report often contains large amounts of complex information, and a standardised and consistent structure would offer potential benefits to all. These include reduced expenditure of time (due to the elimination of information-conversion steps), improved safety (due to a reduction in the occurrence of transmission errors, misunderstanding or misinterpretation of content) and improved clinical information gathering (by the respective linkage to scientific data and literature). Especially in regard to secondary use, a standardised (electronic) format would improve the suitability of these data in retrospective studies and basic research. In this study, we analysed the format and content of 96 genetic testing reports (germline and somatic) from Germany, Switzerland and Austria. Based on these results, we summarised and discussed potentially critical data that were demonstrated to be reported inconsistently, and propose a baseline structure for reporting that would also ease future electronic conversion.
Enhancing neuronal chloride extrusion rescues α2/α3 GABAA-mediated analgesia in neuropathic pain
Authors: Lorenzo Louis-Etienne , Godin Antoine G. , Ferrini Francesco , Bachand Karine , Plasencia-Fernandez Isabel , Labrecque Simon , Girard Alexandre A. , Boudreau Dominic , Kianicka Irenej , Gagnon Martin , Doyon Nicolas , Ribeiro-da-Silva Alfredo , De Koninck Yves
Published: February 2020

Spinal disinhibition has been hypothesized to underlie pain hypersensitivity in neuropathic pain. Apparently contradictory mechanisms have been reported, raising questions on the best target to produce analgesia. Here, we show that nerve injury is associated with a reduction in the number of inhibitory synapses in the spinal dorsal horn. Paradoxically, this is accompanied by a BDNF-TrkB-mediated upregulation of synaptic GABAARs and by an α1-to-α2GABAAR subunit switch, providing a mechanistic rationale for the analgesic action of the α2,3GABAAR benzodiazepine-site ligand L838,417 after nerve injury. Yet, we demonstrate that impaired Cl- extrusion underlies the failure of L838,417 to induce analgesia at high doses due to a resulting collapse in Cl- gradient, dramatically limiting the benzodiazepine therapeutic window. In turn, enhancing KCC2 activity not only potentiated L838,417-induced analgesia, it rescued its analgesic potential at high doses, revealing a novel strategy for analgesia in pathological pain, by combined targeting of the appropriate GABAAR-subtypes and restoring Cl- homeostasis.
Benchmarking tomographic acquisition schemes for high-resolution structural biology
Authors: Turoňová Beata , Hagen Wim J. H. , Obr Martin , Mosalaganti Shyamal , Beugelink J. Wouter , Zimmerli Christian E. , Kräusslich Hans-Georg , Beck Martin
Published: February 2020

Cryo electron tomography with subsequent subtomogram averaging is a powerful technique to structurally analyze macromolecular complexes in their native context. Although close to atomic resolution in principle can be obtained, it is not clear how individual experimental parameters contribute to the attainable resolution. Here, we have used immature HIV-1 lattice as a benchmarking sample to optimize the attainable resolution for subtomogram averaging. We systematically tested various experimental parameters such as the order of projections, different angular increments and the use of the Volta phase plate. We find that although any of the prominently used acquisition schemes is sufficient to obtain subnanometer resolution, dose-symmetric acquisition provides considerably better outcome. We discuss our findings in order to provide guidance for data acquisition. Our data is publicly available and might be used to further develop processing routines.
Macrophages employ quorum licensing to regulate collective activation
Authors: Muldoon Joseph J. , Chuang Yishan , Bagheri Neda , Leonard Joshua N.
Published: February 2020

Macrophage-initiated inflammation is tightly regulated to eliminate threats such as infections while suppressing harmful immune activation. However, individual cells’ signaling responses to pro-inflammatory cues are heterogeneous, with subpopulations emerging with high or low activation states. Here, we use single-cell tracking and dynamical modeling to develop and validate a revised model for lipopolysaccharide (LPS)-induced macrophage activation that invokes a mechanism we term quorum licensing. The results show that bimodal phenotypic partitioning of macrophages is primed during the resting state, dependent on cumulative history of cell density, predicted by extrinsic noise in transcription factor expression, and independent of canonical LPS-induced intercellular feedback in the tumor necrosis factor (TNF) response. Our analysis shows how this density-dependent coupling produces a nonlinear effect on collective TNF production. We speculate that by linking macrophage density to activation, this mechanism could amplify local responses to threats and prevent false alarms.
A case report of multiple primary prostate tumors with differential drug sensitivity
Authors: Wilkinson Scott , Harmon Stephanie A. , Terrigino Nicholas T. , Karzai Fatima , Pinto Peter A. , Madan Ravi A. , VanderWeele David J. , Lake Ross , Atway Rayann , Bright John R. , Carrabba Nicole V. , Trostel Shana Y. , Lis Rosina T. , Chun Guinevere , Gulley James L. , Merino Maria J. , Choyke Peter L. , Ye Huihui , Dahut William L. , Turkbey Baris , Sowalsky Adam G.
Published: February 2020

Localized prostate cancers are genetically variable and frequently multifocal, comprising spatially distinct regions with multiple independently-evolving clones. To date there is no understanding of whether this variability can influence management decisions for patients with prostate tumors. Here, we present a single case from a clinical trial of neoadjuvant intense androgen deprivation therapy. A patient was diagnosed with a large semi-contiguous tumor by imaging, histologically composed of a large Gleason score 9 tumor with an adjacent Gleason score 7 nodule. DNA sequencing demonstrates these are two independent tumors, as only the Gleason 9 tumor harbors single-copy losses ofPTENandTP53. ThePTEN/TP53-deficient tumor demonstrates treatment resistance, selecting for subclones with mutations to the remaining copies ofPTENandTP53, while the Gleason 7PTEN-intact tumor is almost entirely ablated. These findings indicate that spatiogenetic variability is a major confounder for personalized treatment of patients with prostate cancer.
Inference and effects of barcode multiplets in droplet-based single-cell assays
Authors: Lareau Caleb A. , Ma Sai , Duarte Fabiana M. , Buenrostro Jason D.
Published: February 2020

A widespread assumption for single-cell analyses specifies that one cell’s nucleic acids are predominantly captured by one oligonucleotide barcode. Here, we show that ~13–21% of cell barcodes from the 10x Chromium scATAC-seq assay may have been derived from a droplet with more than one oligonucleotide sequence, which we call “barcode multiplets”. We demonstrate that barcode multiplets can be derived from at least two different sources. First, we confirm that approximately 4% of droplets from the 10x platform may contain multiple beads. Additionally, we find that approximately 5% of beads may contain detectable levels of multiple oligonucleotide barcodes. We show that this artifact can confound single-cell analyses, including the interpretation of clonal diversity and proliferation of intra-tumor lymphocytes. Overall, our work provides a conceptual and computational framework to identify and assess the impacts of barcode multiplets in single-cell data.
Cross-talks of glycosylphosphatidylinositol biosynthesis with glycosphingolipid biosynthesis and ER-associated degradation
Authors: Wang Yicheng , Maeda Yusuke , Liu Yi-Shi , Takada Yoko , Ninomiya Akinori , Hirata Tetsuya , Fujita Morihisa , Murakami Yoshiko , Kinoshita Taroh
Published: February 2020

Glycosylphosphatidylinositol (GPI)-anchored proteins and glycosphingolipids interact with each other in the mammalian plasma membranes, forming dynamic microdomains. How their interaction starts in the cells has been unclear. Here, based on a genome-wide CRISPR-Cas9 genetic screen for genes required for GPI side-chain modification by galactose in the Golgi apparatus, we report that β1,3-galactosyltransferase 4 (B3GALT4), the previously characterized GM1 ganglioside synthase, additionally functions in transferring galactose to the N-acetylgalactosamine side-chain of GPI. Furthermore, B3GALT4 requires lactosylceramide for the efficient GPI side-chain galactosylation. Thus, our work demonstrates previously unexpected functional relationships between GPI-anchored proteins and glycosphingolipids in the Golgi. Through the same screening, we also show that GPI biosynthesis in the endoplasmic reticulum (ER) is severely suppressed by ER-associated degradation to prevent GPI accumulation when the transfer of synthesized GPI to proteins is defective. Our data demonstrates cross-talks of GPI biosynthesis with glycosphingolipid biosynthesis and the ER quality control system.
Optical inter-site spin transfer probed by energy and spin-resolved transient absorption spectroscopy
Authors: Willems Felix , von Korff Schmising Clemens , Strüber Christian , Schick Daniel , Engel Dieter W. , Dewhurst J. K. , Elliott Peter , Sharma Sangeeta , Eisebitt Stefan
Published: February 2020

Optically driven spin transport is the fastest and most efficient process to manipulate macroscopic magnetization as it does not rely on secondary mechanisms to dissipate angular momentum. In the present work, we show that such an optical inter-site spin transfer (OISTR) from Pt to Co emerges as a dominant mechanism governing the ultrafast magnetization dynamics of a CoPt alloy. To demonstrate this, we perform a joint theoretical and experimental investigation to determine the transient changes of the helicity dependent absorption in the extreme ultraviolet spectral range. We show that the helicity dependent absorption is directly related to changes of the transient spin-split density of states, allowing us to link the origin of OISTR to the available minority states above the Fermi level. This makes OISTR a general phenomenon in optical manipulation of multi-component magnetic systems.
Benchmark performance of low-cost Sb2Se3 photocathodes for unassisted solar overall water splitting
Authors: Yang Wooseok , Kim Jin Hyun , Hutter Oliver S. , Phillips Laurie J. , Tan Jeiwan , Park Jaemin , Lee Hyungsoo , Major Jonathan D. , Lee Jae Sung , Moon Jooho
Published: February 2020

Determining cost-effective semiconductors exhibiting desirable properties for commercial photoelectrochemical water splitting remains a challenge. Herein, we report a Sb2Se3 semiconductor that satisfies most requirements for an ideal high-performance photoelectrode, including a small band gap and favourable cost, optoelectronic properties, processability, and photocorrosion stability. Strong anisotropy, a major issue for Sb2Se3, is resolved by suppressing growth kinetics via close space sublimation to obtain high-quality compact thin films with favourable crystallographic orientation. The Sb2Se3 photocathode exhibits a high photocurrent density of almost 30 mA cm−2 at 0 V against the reversible hydrogen electrode, the highest value so far. We demonstrate unassisted solar overall water splitting by combining the optimised Sb2Se3 photocathode with a BiVO4 photoanode, achieving a solar-to-hydrogen efficiency of 1.5% with stability over 10 h under simulated 1 sun conditions employing a broad range of solar fluxes. Low-cost Sb2Se3 can thus be an attractive breakthrough material for commercial solar fuel production.
Ultra-long carrier lifetime in neutral graphene-hBN van der Waals heterostructures under mid-infrared illumination
Authors: Huang P. , Riccardi E. , Messelot S. , Graef H. , Valmorra F. , Tignon J. , Taniguchi T. , Watanabe K. , Dhillon S. , Plaçais B. , Ferreira R. , Mangeney J.
Published: February 2020

Graphene/hBN heterostructures are promising active materials for devices in the THz domain, such as emitters and photodetectors based on interband transitions. Their performance requires long carrier lifetimes. However, carrier recombination processes in graphene possess sub-picosecond characteristic times for large non-equilibrium carrier densities at high energy. An additional channel has been recently demonstrated in graphene/hBN heterostructures by emission of hBN hyperbolic phonon polaritons (HPhP) with picosecond decay time. Here, we report on carrier lifetimes in graphene/hBN Zener-Klein transistors of ~30 ps for photoexcited carriers at low density and energy, using mid-infrared photoconductivity measurements. We further demonstrate the switching of carrier lifetime from ~30 ps (attributed to interband Auger) down to a few picoseconds upon ignition of HPhP relaxation at finite bias and/or with infrared excitation power. Our study opens interesting perspectives to exploit graphene/hBN heterostructures for THz lasing and highly sensitive THz photodetection as well as for phonon polariton optics.
Topochemical synthesis of different polymorphs of polymers as a paradigm for tuning properties of polymers
Authors: Mohanrao Raja , Hema Kuntrapakam , Sureshan Kana M.
Published: February 2020

Different packing is a mechanism through which nature can produce materials of different properties from the same basic units. There is great interest in constructing different forms of the same polymer by utilising different packing. Common solution-synthesized polymers are amorphous and their post-synthesis crystallization into different topologies is almost impossible. Here we show solid-state polymerization of different reactive polymorphs of a monomer pre-organized in different topologies. Trimorphs of a dipeptide monomer pack in a head-to-tail fashion, placing the azide and alkyne of adjacent monomers in proximity. On heating, these crystals undergo a topochemical azide-alkyne cycloaddition reaction yielding triazole-linked polymer in three different crystalline states; one with antiparallel arrangement of polymer chains, another with parallelly oriented chains, and a third form containing a 1:1 blend of two different conformers aligned in parallel. This approach of exploiting different polymorphs of a monomer for topochemical polymerization to yield polymorphs of polymers is promising for future research.
Measurement properties from the Brazilian Portuguese version of the QUIP-RS
Authors: Guerra Daniela Freitas , Lemos Silva Ana Elisa , Paz Thiago da Silva Rocha , Filho Leandro Nogueira S. , Vasconcellos Luiz Felipe , de Britto Vera Lucia Santos , Allodi Silvana , Weintraub Daniel , Swarowsky Alessandra , Correa Clynton Lourenço
Published: February 2020

Parkinson’s disease (PD) has numerous motor and non-motor symptoms. Among non-motor manifestations impulse control disorders (ICDs) stand out. ICDs include compulsions for gambling, shopping, eating, and sexual behavior, and “related disorders” such as hobbyism, simple motor activities, and dopamine dysregulation syndrome. There is no rating scale translated and adapted transculturally into Brazilian Portuguese language. Therefore, we cross-culturally adapted and investigated the measurement properties of the Brazilian version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease-Rating Scale (QUIP-RS). Fifty-three patients participated in the study. Inter-evaluator and test–retest (patient and health professional) reliabilities (intraclass correlation coefficient) were all excellent (0.93, 0.93, and 0.99). The internal consistency was high (α = 0.92). The Minimal detectable change (MDC) value was 5.8 (patient) and 2.3 (health professional) points. There was a floor, but no ceiling, effect. In summary, the Brazilian version of the QUIP-RS has high reliability and content validity.
Strong local moment antiferromagnetic spin fluctuations in V-doped LiFeAs
Authors: Xu Zhuang , Dai Guangyang , Li Yu , Yin Zhiping , Rong Yan , Tian Long , Liu Panpan , Wang Hui , Xing Lingyi , Wei Yuan , Kajimoto Ryoichi , Ikeuchi Kazuhiko , Abernathy D. L. , Wang Xiancheng , Jin Changqing , Lu Xingye , Tan Guotai , Dai Pengcheng
Published: February 2020

We use neutron scattering to study Vanadium (hole)-doped LiFe1−xVxAs. In the undoped state, LiFeAs exhibits superconductivity at Tc = 18 K and transverse incommensurate spin excitations similar to electron overdoped iron pnictides. Upon Vanadium doping to form LiFe0.955V0.045, the transverse incommensurate spin excitations in LiFeAs transform into longitudinally elongated ones in a similar fashion to that of potassium (hole)-doped Ba0.7K0.3Fe2As2 but with dramatically enhanced magnetic scattering and elimination of superconductivity. This is different from the suppression of the overall magnetic excitations in hole-doped BaFe2As2 and the enhancement of superconductivity near optimal hole doping. These results are consistent with density function theory plus dynamic mean field theory calculations, suggesting that Vanadium doping in LiFeAs may induce an enlarged effective magnetic moment Seff with a spin crossover ground state arising from the inter-orbital scattering of itinerant electrons.
Molecular dynamics trajectories for 630 coarse-grained drug-membrane permeations
Authors: Hoffmann Christian , Centi Alessia , Menichetti Roberto , Bereau Tristan
Published: February 2020

The permeation of small-molecule drugs across a phospholipid membrane bears much interest both in the pharmaceutical sciences and in physical chemistry. Connecting the chemistry of the drug and the lipids to the resulting thermodynamic properties remains of immediate importance. Here we report molecular dynamics (MD) simulation trajectories using the coarse-grained (CG) Martini force field. A wide, representative coverage of chemistry is provided: across solutes—exhaustively enumerating all 105 CG dimers—and across six phospholipids. For each combination, umbrella-sampling simulations provide detailed structural information of the solute at all depths from the bilayer midplane to bulk water, allowing a precise reconstruction of the potential of mean force. Overall, the present database contains trajectories from 15,120 MD simulations. This database may serve the further identification of structure-property relationships between compound chemistry and drug permeability.
Enhanced homologous recombination by the modulation of targeting vector ends
Authors: Hirotsune Shinji , Kiyonari Hiroshi , Jin Mingyue , Kumamoto Kanako , Yoshida Kayo , Shinohara Miki , Watanabe Hitomi , Wynshaw-Boris Anthony , Matsuzaki Fumio
Published: February 2020

The field of genome editing was founded on the establishment of methods, such as the clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated protein (CRISPR/Cas) system, used to target DNA double-strand breaks (DSBs). However, the efficiency of genome editing also largely depends on the endogenous cellular repair machinery. Here, we report that the specific modulation of targeting vectors to provide 3′ overhangs at both ends increased the efficiency of homology-directed repair (HDR) in embryonic stem cells. We applied the modulated targeting vectors to produce homologous recombinant mice directly by pronuclear injection, but the frequency of HDR was low. Furthermore, we combined our method with the CRISPR/Cas9 system, resulting in a significant increase in HDR frequency. Thus, our HDR-based method, enhanced homologous recombination for genome targeting (eHOT), is a new and powerful method for genome engineering.
Risk factors and clinical correlates of neoplastic transformation in gastric hyperplastic polyps in Chinese patients
Authors: Hu Haiyi , Zhang Qian , Chen Guangyong , Pritchard D. Mark , Zhang Shutian
Published: February 2020

Gastric hyperplastic polyps (GHPs) have a potential risk of neoplastic transformation, but the responsible mechanisms have not yet been established. We conducted a study involving 55 patients (33 female) who had undergone endoscopic or surgical resection of GHPs. We compared 16 patients who had GHPs showing neoplastic transformation with 39 patients who had non-neoplastic GHPs. We analyzed differences in serology, gastroscopic manifestations and pathology between the two groups in order to establish risk factors that may be associated with neoplastic transformation. The mean age of the cohort was 61.73 ± 9.024 years. The prevalence of positive serum gastric parietal cell antibody (PCA) was 61.8%. 30 of the GHPs with neoplastic formation had a “strawberry-like” appearance with erosions of polyps (P = 0.000). A history of anaemia was a risk factor for GHPs which demonstrated neoplastic transformation (odds ratio [OR], 3.729; 95% confidence interval [CI], 1.099–12.649; P = 0.035). Although the differences were not significant, our data showed higher prevalences of positive serum PCA (P = 0.057), hypergastrinemia (P = 0.062) and female gender (P = 0.146) in the GHP patients who had neoplastic transformation. Multiple polyps in the corpus (P = 0.024) occurred more frequently in serum PCA positive patients. Hypergastrinemia occurred more frequently in Helicobacter pylori negative patients and of these 20/22 patients had a positive PCA (P = 0.007). GHPs are associated with autoimmune metaplastic atrophic gastritis (AMAG). AMAG is probably one of the risk factors for GHPs to undergo neoplastic transformation.
Author Correction: Novel Bead-Based Epitope Assay is a sensitive and reliable tool for profiling epitope-specific antibody repertoire in food allergy
Authors: Suprun Maria , Getts Robert , Raghunathan Rohit , Grishina Galina , Witmer Marc , Gimenez Gustavo , Sampson Hugh A. , Suárez-Fariñas Mayte
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Budgerigars adopt robust, but idiosyncratic flight paths
Authors: Karmaker Debajyoti , Groening Julia , Wilson Michael , Schiffner Ingo , Srinivasan Mandyam V.
Published: February 2020

We have investigated the paths taken by Budgerigars while flying in a tunnel. The flight trajectories of nine Budgerigars (Melopsittacus undulatus) were reconstructed in 3D from high speed stereo videography of their flights in an obstacle-free tunnel. Individual birds displayed highly idiosyncratic flight trajectories that were consistent from flight to flight over the course of several months. We then investigated the robustness of each bird’s trajectory by interposing a disk-shaped obstacle in its preferred flight path. We found that each bird continued to fly along its preferred trajectory up to a point very close to the obstacle before veering over the obstacle rapidly, making a minimal deviation to avoid a collision, and subsequently returning to its original path. Thus, Budgerigars show a high propensity to stick to their individual, preferred flight paths even when confronted with a clearly visible obstacle, and do not adopt a substantially different, unobstructed route. The robust preference for idiosyncratic flight paths, and the tendency to pass obstacles by flying above them, provide new insights into the strategies that underpin obstacle avoidance in birds. We believe that this is the first carefully controlled study of the behaviour of birds in response to a newly introduced obstacle in their flight path. The insights from the study could also have implications for conservation efforts to mitigate collisions of birds with man-made obstacles.
Computational modelling of wet adhesive mussel foot proteins (Bivalvia): Insights into the evolutionary convolution in diverse perspectives
Authors: Anand P. P. , Vardhanan Y. Shibu
Published: February 2020

Underwater adhesion in mussels (Bivalvia) is an extreme adaptation to achieve robust and firm wet adhesion in the freshwater/brackish/ocean, which biochemically shaped through millions of years. The protein-based adhesion has huge prospective in various fields like industry, medical, etc. Currently, no comprehensive records related to the systematic documentation of structural and functional properties of Mussel foot proteins (Mfps). In this study, we identified the nine species of bivalves in which the complete sequence of at least one adhesive protein is known. The insilico characterization revealed the specific physio-chemical structural and functional characters of each Mfps. The evolutionary analyses of selected bivalves are mainly based on Mfps, Mitogenome, and TimeTree. The outcome of the works has great applications for designing biomimetic materials in future.
Paternal leakage of mitochondrial DNA and maternal inheritance of heteroplasmy in Drosophila hybrids
Authors: Polovina Eirini-Slavka , Parakatselaki Maria-Eleni , Ladoukakis Emmanuel D.
Published: February 2020

Mitochondrial DNA (mtDNA) is maternally transmitted in animals and therefore, individuals are expected to have a single mtDNA haplotype (homoplasmy). Yet, heteroplasmic individuals have been observed in a large number of animal species. Heteroplasmy may emerge as a result of somatic mtDNA mutations, paternal leakage during fertilization or be inherited from a heteroplasmic mother. Understanding the causes of heteroplasmy could shed light into the evolution of mtDNA inheritance. In this study we examined heteroplasmy in progeny from heterospecific crosses of Drosophila for two consecutive generations. We studied the generation of heteroplasmy from paternal leakage and the maternal transmission of heteroplasmy. Our data reveal non-random patterns in the emergence and transmission of heteroplasmy and suggest that heteroplasmy depends on the family of origin.
Dynamic Tracking Algorithm for Time-Varying Neuronal Network Connectivity using Wide-Field Optical Image Video Sequences
Authors: Renteria Carlos , Liu Yuan-Zhi , Chaney Eric J. , Barkalifa Ronit , Sengupta Parijat , Boppart Stephen A.
Published: February 2020

Propagation of signals between neurons and brain regions provides information about the functional properties of neural networks, and thus information transfer. Advances in optical imaging and statistical analyses of acquired optical signals have yielded various metrics for inferring neural connectivity, and hence for mapping signal intercorrelation. However, a single coefficient is traditionally derived to classify the connection strength between two cells, ignoring the fact that neural systems are inherently time-variant systems. To overcome these limitations, we utilized a time-varying Pearson’s correlation coefficient, spike-sorting, wavelet transform, and wavelet coherence of calcium transients from DIV 12–15 hippocampal neurons from GCaMP6s mice after applying various concentrations of glutamate. Results provide a comprehensive overview of resulting firing patterns, network connectivity, signal directionality, and network properties. Together, these metrics provide a more comprehensive and robust method of analyzing transient neural signals, and enable future investigations for tracking the effects of different stimuli on network properties.
Contact Nonlinear Acoustic Diode
Authors: Huang Yao , Wang Xiaoyu , Gong Xun , Wu Haodong , Zhang Dong , Zhang De
Published: February 2020

Nonlinear implementations of acoustic diodes are inherently nonreciprocal and have received continuous attention from the beginning of the research boom for acoustic diodes. However, all the reported nonlinear schemes usually have the shortcomings such as low transmission ratio, action threshold, lack of stability and cumbersome setups. In the present design, we take advantage of extraordinarily large contact acoustic nonlinearity which is several orders of magnitude stronger than material nonlinearity. It is theoretically found that the spectra of the transmitted wave depend on the contact time. It is proven experimentally that the contact nonlinearity can be tamed by adjusting the driving amplitude, the static stress and the elastic constants of the materials. In order to build a compact acoustic diode, a sub-wavelength filter with a sandwich structure is designed. The total length of the acoustic diode is only three eighths of the incident wavelength. The amplitude-dependent behavior of the device exhibits similarities with electronic diodes. A more than 50% transmission ratio is obtained. A robust, stable, compact, highly efficient and solid-state acoustic diode is realized.
Female mouse tears contain an anti-aggression pheromone
Authors: Cavaliere Rosa Maria , Silvotti Lucia , Percudani Riccardo , Tirindelli Roberto
Published: February 2020

Tears contain pheromones that trigger specific behavioral responses. In the mouse, male tear fluid is involved in long and short-term effects such as the receptive behavior and pregnancy block in females and the aggression in males. In contrast, pup tears exert an inhibitory effect on male mating behavior, also promoting sexual rejection in females. In the rat, a male lacrimal protein acts as an intraspecific and heterospecific signal enhancing sexual behavior in females and evoking avoidance behavior in mouse. However, behavioral effects of female tears on male behavior have yet to be described. Here, we report that female lacrimal fluid of different mouse strains contains a relatively small and involatile factor that abolishes inter-male aggression switching it into a copulatory behavior. The production of this molecule by the lacrimal glands is not affected by the estrous cycle but it is sensitive to ovariectomy, thus suggesting a control mediated by hormones. Moreover, this lacrimal anti-aggression pheromone modulates the activity of the lateral habenula, a brain area responsible for the valence of the aggressive interactions.
The anti-tumoral potential of the saporin-based uPAR-targeting chimera ATF-SAP
Authors: Zuppone S. , Assalini C. , Minici C. , Bertagnoli S. , Branduardi P. , Degano M. , Fabbrini M. S. , Montorsi F. , Salonia A. , Vago R.
Published: February 2020

The development of personalized therapies represents an urgent need owing to the high rate of cancer recurrence and systemic toxicity of conventional drugs. So far, targeted toxins have shown promising results as potential therapeutic compounds. Specifically, toxins conjugated to antibodies or fused to growth factors/enzymes have been largely demonstrated to selectively address and kill cancer cells. We investigated the anti-tumor potential of a chimeric recombinant fusion protein formed by the Ribosome Inactivating Protein saporin (SAP) and the amino-terminal fragment (ATF) of the urokinase-type plasminogen activator (uPA), whose receptor has been shown to be over-expressed on the surface of aggressive tumors. ATF-SAP was recombinantly produced by the P. pastoris yeast and its activity was assessed on a panel of bladder and breast cancer cell lines. ATF-SAP resulted to be highly active in vitro, as nano-molar concentrations were sufficient to impair viability on tumor cell lines. In contrast to untargeted toxins, the chimeric fusion protein displayed a significantly improved toxic effect in uPAR-expressing cells, demonstrating that the selective activity was due to the presence of the targeting moiety. Fibroblasts were not sensitive to ATF-SAP despite uPAR expression, indicating that cell-specific receptor-mediated internalization pathway(s) might be considered. The in vivo anti-tumor effect of the chimera was shown in a bladder cancer xenograft model. Current findings indicate ATF-SAP as a suitable anti-tumoral therapeutic option to cope with cancer aggressiveness, as a single treatment or in combination with traditional therapeutic approaches, to appropriately address the intra- and inter- tumor heterogeneity.
The earliest farmers of northwest China exploited grain-fed pheasants not chickens
Authors: Barton Loukas , Bingham Brittany , Sankaranarayanan Krithivasan , Monroe Cara , Thomas Ariane , Kemp Brian M.
Published: February 2020

Though chickens (Gallus gallus domesticus) are globally ubiquitous today, the timing, location, and manner of their domestication is contentious. Until recently, archaeologists placed the origin of the domestic chicken in northern China, perhaps as early as 8,000 years ago. Such evidence however complicates our understanding of how the chicken was domesticated because its wild progenitor – the red jungle fowl (Gallus gallus) – lives in tropical ecosystems and does not exist in northern China today or in the recent past. Increasingly, multiple lines of evidence suggest that many of the archaeological bird remains underlying this northern origins hypothesis have been misidentified. Here we analyze the mitochondrial DNA of some of the earliest purported chickens from the Dadiwan site in northern China and conclude that they are pheasants (Phasianus colchicus). Curiously, stable isotope values from the same birds reveal that their diet was heavy in agricultural products (namely millet), meaning that they lived adjacent to or among some of the earliest farming communities in East Asia. We suggest that the exploitation of these baited birds was an important adaptation for early farmers in China’s arid north, and that management practices like these likely played a role in the domestication of animals – including the chicken – in similar contexts throughout the region.
Assessing the progression of systemic sclerosis by monitoring the tissue optic axis using PS-OCT
Authors: Adams David C. , Szabari Margit V. , Lagares David , McCrossan Andrew F. , Hariri Lida P. , Tager Andrew M. , Suter Melissa J.
Published: February 2020

The clinical assessment of fibrosis is critical to the diagnosis and management of patients with systemic sclerosis. Current clinical standards for patient assessment is to use skin fibrosis as an indicator of organ involvement, though this approach is highly subjective and relies on manual palpation. The development of a new method for accurately quantifying collagen content may therefore significantly improve the accuracy of the traditional skin score in patients with systemic sclerosis and may additionally aid in the monitoring of anti-fibrotic therapies in clinical practice. Polarization-sensitive optical coherence tomography (PS-OCT) is a high-speed volumetric imaging modality that can be used to assess birefringent tissues including collagen. In this work we demonstrate a novel computational approach using PS-OCT for the assessment of fibrosis. This approach, based on the measured distribution of optic axis values associated with a given volume of collagen orientation, characterizes fibrotic changes independently from the depth of the region of interest in the tissue. This approach has the potential to accurately quantify collagen content and orientation faster and more robustly compared to traditional PS-OCT metrics. We investigate the viability of this approach for assessing the development of fibrosis in a bleomycin induced skin fibrosis mouse model.
Individual variation in the attribution of incentive salience to social cues
Authors: Fitzpatrick Christopher J. , Morrow Jonathan D.
Published: February 2020

Research on the attribution of incentive salience to drug cues has furthered our understanding of drug self-administration in animals and addiction in humans. The influence of social cues on drug-seeking behavior has garnered attention recently, but few studies have investigated how social cues gain incentive-motivational value. In the present study, a Pavlovian conditioned approach (PCA) procedure was used to identify rats that are more (sign-trackers; STs) or less (goal-trackers; GTs) prone to attribute incentive salience to food reward cues. In Experiment 1, a novel procedure employed social ‘peers’ to compare the tendency of STs and GTs to attribute incentive salience to social reward cues as well as form a social-conditioned place preference. In Experiment 2, social behavior of STs and GTs was compared using social interaction and choice tests. Finally, in Experiment 3, levels of plasma oxytocin were measured in STs and GTs seven days after the last PCA training session, because oxytocin is known to modulate the mesolimbic reward system and social behavior. Compared to GTs, STs attributed more incentive salience to social-related cues and exhibited prosocial behaviors (e.g., social-conditioned place preference, increased social interaction, and social novelty-seeking). No group differences were observed in plasma oxytocin levels. Taken together, these experiments demonstrate individual variation in the attribution of incentive salience to both food- and social-related cues, which has important implications for the pathophysiology of addiction.
Pyrocatechol, a component of coffee, suppresses LPS-induced inflammatory responses by inhibiting NF-κB and activating Nrf2
Authors: Funakoshi-Tago Megumi , Nonaka Yusuke , Tago Kenji , Takeda Mika , Ishihara Yuma , Sakai Ami , Matsutaka Mari , Kobata Kenji , Tamura Hiroomi
Published: February 2020

Coffee is a complex mixture of many bioactive compounds possessing anti-inflammatory properties. However, the mechanisms by which coffee exerts anti-inflammatory effects remains unclear and the active ingredients have not yet been identified. In this study, we found that coffee extract at more than 2.5%(v/v) significantly inhibited LPS-induced inflammatory responses in RAW264.7 cells and that anti-inflammatory activity of coffee required the roasting process. Interestingly, we identified pyrocatechol, a degradation product derived from chlorogenic acid during roasting, as the active ingredient exhibiting anti-inflammatory activity in coffee. HPLC analysis showed that 124 μM pyrocatechol was included in 100% (v/v) roasted coffee. A treatment with 5%(v/v) coffee extract and more than 2.5 μM pyrocatechol inhibited the LPS-induced activation of NF-κB and also significantly activated Nrf2, which acts as a negative regulator in LPS-induced inflammation. Furthermore, intake of 60% (v/v) coffee extract and 74.4 μM pyrocatechol, which is the concentration equal to contained in 60% (v/v) coffee, markedly inhibited the LPS-induced inflammatory responses in mice. Collectively, these results demonstrated that pyrocatechol, which was formed by the roasting of coffee green beans, is one of the ingredients contributing to the anti-inflammatory activity of coffee.
Comb-locked frequency-swept synthesizer for high precision broadband spectroscopy
Authors: Gotti Riccardo , Puppe Thomas , Mayzlin Yuriy , Robinson-Tait Julian , Wójtewicz Szymon , Gatti Davide , Alsaif Bidoor , Lamperti Marco , Laporta Paolo , Rohde Felix , Wilk Rafal , Leisching Patrick , Kaenders Wilhelm G. , Marangoni Marco
Published: February 2020

Frequency combs have made optical metrology accessible to hundreds of laboratories worldwide and they have set new benchmarks in multi-species trace gas sensing for environmental, industrial and medical applications. However, current comb spectrometers privilege either frequency precision and sensitivity through interposition of a cw probe laser with limited tuning range, or spectral coverage and measurement time using the comb itself as an ultra-broadband probe. We overcome this restriction by introducing a comb-locked frequency-swept optical synthesizer that allows a continuous-wave laser to be swept in seconds over spectral ranges of several terahertz while remaining phase locked to an underlying frequency comb. This offers a unique degree of versatility, as the synthesizer can be either repeatedly scanned over a single absorption line to achieve ultimate precision and sensitivity, or swept in seconds over an entire rovibrational band to capture multiple species. The spectrometer enables us to determine line center frequencies with an absolute uncertainty of 30 kHz and at the same time to collect absorption spectra over more than 3 THz with state-of-the-art sensitivity of a few 10−10 cm−1. Beyond precision broadband spectroscopy, the proposed synthesizer is an extremely promising tool to force a breakthrough in terahertz metrology and coherent laser ranging.
MicroRNAs regulate innate immunity against uropathogenic and commensal-like Escherichia coli infections in the surrogate insect model Galleria mellonella
Authors: Mukherjee Krishnendu , Amsel Daniel , Kalsy Miriam , Billion Andre , Dobrindt Ulrich , Vilcinskas Andreas
Published: February 2020

Uropathogenic Escherichia coli (UPEC) strains cause symptomatic urinary tract infections in humans whereas commensal-like E. coli strains in the urinary bladder cause long-term asymptomatic bacteriuria (ABU). We previously reported that UPEC and ABU strains differentially regulate key DNA methylation and histone acetylation components in the surrogate insect host Galleria mellonella to epigenetically modulate innate immunity-related gene expression, which in turn controls bacterial growth. In this follow-up study, we infected G. mellonella larvae with UPEC strain CFT073 or ABU strain 83972 to identify differences in the expression of microRNAs (miRNAs), a class of non-coding RNAs that regulate gene expression at the post-transcriptional level. Our small RNA sequencing analysis showed that UPEC and ABU infections caused significant changes in the abundance of miRNAs in the larvae, and highlighted the differential expression of 147 conserved miRNAs and 95 novel miRNA candidates. We annotated the G. mellonella genome sequence to investigate the miRNA-regulated expression of genes encoding antimicrobial peptides, signaling proteins, and enzymatic regulators of DNA methylation and histone acetylation in infected larvae. Our results indicate that miRNAs play a role in the epigenetic reprograming of innate immunity in G. mellonella larvae to distinguish between pathogenic and commensal strains of E. coli.
A record of seafloor methane seepage across the last 150 million years
Authors: Oppo D. , De Siena L. , Kemp D. B.
Published: February 2020

Seafloor methane seepage is a significant source of carbon in the marine environment. The processes and temporal patterns of seafloor methane seepage over multi-million-year time scales are still poorly understood. The microbial oxidation of methane can store carbon in sediments through precipitation of carbonate minerals, thus providing a record of past methane emission. In this study, we compiled data on methane-derived carbonates to build a proxy time series of methane emission over the last 150 My and statistically compared it with the main hypothesised geological controllers of methane emission. We quantitatively demonstrate that variations in sea level and organic carbon burial are the dominant controls on methane leakage since the Early Cretaceous. Sea level controls methane seepage variations by imposing smooth trends on timescales in the order of tens of My. Organic carbon burial is affected by the same cyclicities, and instantaneously controls methane release because of the geologically rapid generation of biogenic methane. Both the identified fundamental (26–27 My) and higher (12 My) cyclicities relate to global phenomena. Temporal correlation analysis supports the evidence that modern expansion of hypoxic areas and its effect on organic carbon burial may lead to higher seawater methane concentrations over the coming centuries.
Demonstration of electron focusing using electronic lenses in low-dimensional system
Authors: Yan Chengyu , Pepper Michael , See Patrick , Farrer Ian , Ritchie David , Griffiths Jonathan
Published: February 2020

We report an all-electric integrable electron focusing lens in n-type GaAs. It is shown that a pronounced focusing peak takes place when the focal point aligns with an on-chip detector. The intensity and full width half maximum (FWHM) of the focusing peak are associated with the collimation of injected electrons. To demonstrate the reported focusing lens can be a useful tool, we investigate the characteristic of an asymmetrically gate biased quantum point contact with the assistance of a focusing lens. A correlation between the occurrence of conductance anomaly in low conductance regime and increase in FWHM of focusing peak is observed. The correlation is likely due to the electron-electron interaction. The reported electron focusing lens is essential for a more advanced electron optics device.
Linear and nonlinear optical probing of various excitons in 2D inorganic-organic hybrid structures
Authors: Adnan Mohammad , Baumberg Jeremy J. , Vijaya Prakash G
Published: February 2020

Nonlinear optical properties, such as two-(or multi-) photon absorption (2PA), are of special interest for technologically important applications in fast optical switching, in vivo imaging and so on. Highly intense infrared ultrashort pulses probe deep into samples and reveal several underlying structural perturbations (inter-layer distortions, intra-layer crumpling) and also provide information about new excited states and their relaxation. Naturally self-assembled inorganic-organic multiple quantum wells (IO-MQWs) show utility from room-temperature exciton emission features (binding energies ~200–250 meV). These Mott type excitons are highly sensitive to the self-assembly process, inorganic network distortions, thickness and inter-layer distortions of these soft two-dimensional (2D) and weak van der Waal layered hybrids. We demonstrate strong room-temperature nonlinear excitation intensity dependent two-photon absorption induced exciton photoluminescence (2PA-PL) from these IO-MQWs, excited by infrared femtosecond laser pulses. Strongly confined excitons show distinctly different one- and two-photon excited photoluminescence energies: from free-excitons (2.41 eV) coupled to the perfectly aligned MQWs and from energy down-shifted excitons (2.33 eV) that originate from the locally crumpled layered architecture. High intensity femtosecond induced PL from one-photon absorption (1PA-PL) suggests saturation of absorption and exciton-exciton annihilation, with typical reduction in PL radiative relaxation times from 270 ps to 190 ps upon increasing excitation intensities. From a wide range of IR excitation tuning, the origin of 2PA-PL excitation is suggested to arise from exciton dark states which extend below the bandgap. Observed two-photon absorption coefficients (β ~75 cm/GW) and two-photon excitation cross-sections (η2σ2 ~ 110GM), further support the evidence for 2PA excitation origin. Both 1PA- and 2PA-PL spatial mappings over large areas of single crystal platelets demonstrate the co-existence of both free and deep-level crumpled excitons with some traces of defect-induced trap state emission. We conclude that the two-photon absorption induced PL is highly sensitive to the self-assembly process of few to many mono layers, the crystal packing and deep level defects. This study paves a way to tailor the nonlinear properties of many 2D material classes. Our results thus open new avenues for exploring fundamental phenomena and novel optoelectronic applications using layered inorganic-organic and other metal organic frameworks.