bluuebunny/crossref_metadata_2025 huggingface dataset:
Ancient human genome-wide data from a 3000-year interval in the Caucasus corresponds with eco-geographic regions
Authors: Wang Chuan-Chao , Reinhold Sabine , Kalmykov Alexey , Wissgott Antje , Brandt Guido , Jeong Choongwon , Cheronet Olivia , Ferry Matthew , Harney Eadaoin , Keating Denise , Mallick Swapan , Rohland Nadin , Stewardson Kristin , Kantorovich Anatoly R. , Maslov Vladimir E. , Petrenko Vladimira G. , Erlikh Vladimir R. , Atabiev Biaslan Ch. , Magomedov Rabadan G. , Kohl Philipp L. , Alt Kurt W. , Pichler Sandra L. , Gerling Claudia , Meller Harald , Vardanyan Benik , Yeganyan Larisa , Rezepkin Alexey D. , Mariaschk Dirk , Berezina Natalia , Gresky Julia , Fuchs Katharina , Knipper Corina , Schiffels Stephan , Balanovska Elena , Balanovsky Oleg , Mathieson Iain , Higham Thomas , Berezin Yakov B. , Buzhilova Alexandra , Trifonov Viktor , Pinhasi Ron , Belinskij Andrej B. , Reich David , Hansen Svend , Krause Johannes , Haak Wolfgang
Published: February 2019

Archaeogenetic studies have described the formation of Eurasian ‘steppe ancestry’ as a mixture of Eastern and Caucasus hunter-gatherers. However, it remains unclear when and where this ancestry arose and whether it was related to a horizon of cultural innovations in the 4th millennium BCE that subsequently facilitated the advance of pastoral societies in Eurasia. Here we generated genome-wide SNP data from 45 prehistoric individuals along a 3000-year temporal transect in the North Caucasus. We observe a genetic separation between the groups of the Caucasus and those of the adjacent steppe. The northern Caucasus groups are genetically similar to contemporaneous populations south of it, suggesting human movement across the mountain range during the Bronze Age. The steppe groups from Yamnaya and subsequent pastoralist cultures show evidence for previously undetected farmer-related ancestry from different contact zones, while Steppe Maykop individuals harbour additional Upper Palaeolithic Siberian and Native American related ancestry.
Physical principles of retroviral integration in the human genome
Authors: Michieletto D. , Lusic M. , Marenduzzo D. , Orlandini E.
Published: February 2019

Certain retroviruses, including HIV, insert their DNA in a non-random fraction of the host genome via poorly understood selection mechanisms. Here, we develop a biophysical model for retroviral integration as stochastic and quasi-equilibrium topological reconnections between polymers. We discover that physical effects, such as DNA accessibility and elasticity, play important and universal roles in this process. Our simulations predict that integration is favoured within nucleosomal and flexible DNA, in line with experiments, and that these biases arise due to competing energy barriers associated with DNA deformations. By considering a long chromosomal region in human T-cells during interphase, we discover that at these larger scales integration sites are predominantly determined by chromatin accessibility. Finally, we propose and solve a reaction-diffusion problem that recapitulates the distribution of HIV hot-spots within T-cells. With few generic assumptions, our model can rationalise experimental observations and identifies previously unappreciated physical contributions to retroviral integration site selection.
Higher energy and safer sodium ion batteries via an electrochemically made disordered Na3V2(PO4)2F3 material
Authors: Yan Guochun , Mariyappan Sathiya , Rousse Gwenaelle , Jacquet Quentin , Deschamps Michael , David Renald , Mirvaux Boris , Freeland John William , Tarascon Jean-Marie
Published: February 2019

The growing need to store an increasing amount of renewable energy in a sustainable way has rekindled interest for sodium-ion battery technology, owing to the natural abundance of sodium. Presently, sodium-ion batteries based on Na3V2(PO4)2F3/C are the subject of intense research focused on improving the energy density by harnessing the third sodium, which has so far been reported to be electrochemically inaccessible. Here, we are able to trigger the activity of the third sodium electrochemically via the formation of a disordered NaxV2(PO4)2F3 phase of tetragonal symmetry (I4/mmm space group). This phase can reversibly uptake 3 sodium ions per formula unit over the 1 to 4.8 V voltage range, with the last one being re-inserted at 1.6 V vs Na+/Na0. We track the sodium-driven structural/charge compensation mechanism associated to the new phase and find that it remains disordered on cycling while its average vanadium oxidation state varies from 3 to 4.5. Full sodium-ion cells based on this phase as positive electrode and carbon as negative electrode show a 10–20% increase in the overall energy density.
Patterned human microvascular grafts enable rapid vascularization and increase perfusion in infarcted rat hearts
Authors: Redd Meredith A. , Zeinstra Nicole , Qin Wan , Wei Wei , Martinson Amy , Wang Yuliang , Wang Ruikang K. , Murry Charles E. , Zheng Ying
Published: February 2019

Vascularization and efficient perfusion are long-standing challenges in cardiac tissue engineering. Here we report engineered perfusable microvascular constructs, wherein human embryonic stem cell-derived endothelial cells (hESC-ECs) are seeded both into patterned microchannels and the surrounding collagen matrix. In vitro, the hESC-ECs lining the luminal walls readily sprout and anastomose with de novo-formed endothelial tubes in the matrix under flow. When implanted on infarcted rat hearts, the perfusable microvessel grafts integrate with coronary vasculature to a greater degree than non-perfusable self-assembled constructs at 5 days post-implantation. Optical microangiography imaging reveal that perfusable grafts have 6-fold greater vascular density, 2.5-fold higher vascular velocities and >20-fold higher volumetric perfusion rates. Implantation of perfusable grafts containing additional hESC-derived cardiomyocytes show higher cardiomyocyte and vascular density. Thus, pre-patterned vascular networks enhance vascular remodeling and accelerate coronary perfusion, potentially supporting cardiac tissues after implantation. These findings should facilitate the next generation of cardiac tissue engineering design.
Engineer chimeric Cas9 to expand PAM recognition based on evolutionary information
Authors: Ma Dacheng , Xu Zhimeng , Zhang Zhaoyu , Chen Xi , Zeng Xiangzhi , Zhang Yiyang , Deng Tingyue , Ren Mengfei , Sun Zheng , Jiang Rui , Xie Zhen
Published: February 2019

Although Cas9 nucleases are remarkably diverse in microorganisms, the range of genomic sequences targetable by a CRISPR/Cas9 system is restricted by the requirement of a short protospacer adjacent motif (PAM) at the target site. Here, we generate a group of chimeric Cas9 (cCas9) variants by replacing the key region in the PAM interaction (PI) domain of Staphylococcus aureus Cas9 (SaCas9) with the corresponding region in a panel of SaCas9 orthologs. By using a functional assay at target sites with different nucleotide recombinations at PAM position 3–6, we identify several cCas9 variants with expanded recognition capability at NNVRRN, NNVACT, NNVATG, NNVATT, NNVGCT, NNVGTG, and NNVGTT PAM sequences. In summary, we provide a panel of cCas9 variants accessible up to 1/4 of all the possible genomic targets in mammalian cells.
Topological non-Hermitian origin of surface Maxwell waves
Authors: Bliokh Konstantin Y. , Leykam Daniel , Lein Max , Nori Franco
Published: February 2019

Maxwell electromagnetism, describing the wave properties of light, was formulated 150 years ago. More than 60 years ago it was shown that interfaces between optical media (including dielectrics, metals, negative-index materials) can support surface electromagnetic waves, which now play crucial roles in plasmonics, metamaterials, and nano-photonics. Here we show that surface Maxwell waves at interfaces between homogeneous isotropic media described by real permittivities and permeabilities have a topological origin explained by the bulk-boundary correspondence. Importantly, the topological classification is determined by the helicity operator, which is generically non-Hermitian even in lossless optical media. The corresponding topological invariant, which determines the number of surface modes, is a $${\Bbb Z}_4$$

Z

4

number (or a pair of $${\Bbb Z}_2$$

Z

2

numbers) describing the winding of the complex helicity spectrum across the interface. Our theory provides a new twist and insights for several areas of wave physics: Maxwell electromagnetism, topological quantum states, non-Hermitian wave physics, and metamaterials.
Robust lasing modes in coupled colloidal quantum dot microdisk pairs using a non-Hermitian exceptional point
Authors: Lafalce Evan , Zeng Qingji , Lin Chun Hao , Smith Marcus J. , Malak Sidney T. , Jung Jaehan , Yoon Young Jun , Lin Zhiqun , Tsukruk Vladimir V. , Vardeny Z. Valy
Published: February 2019

Evanescently coupled pairs of microdisk lasers have emerged as a useful platform for studying the non-Hermitian physics of exceptional points. It remains an open question how scalable and versatile such phenomena can be when carried over to other designs. Here we have studied the effect of gain/loss modulation in an evanescently coupled pair of microdisk optical resonators fabricated from solution-processed colloidal quantum dots. The emission spectra of these structures are sensitive to small imperfections, which cause frequency-splitting of the whispering gallery modes. Despite this inherent disorder, we found that when spatially modulating the optical pump to vary the gain differential between the coupled microdisks, the coupling drives the split parasitic intra-cavity modes into coalescence at an exceptional point of the resulting three-mode system. This unusual behavior is rationalized via a Hamiltonian that incorporates the intra-cavity coupling as well as the anisotropic inter-cavity coupling between modes in the microdisk pair.
A cell-free platform for the prenylation of natural products and application to cannabinoid production
Authors: Valliere Meaghan A. , Korman Tyler P. , Woodall Nicholas B. , Khitrov Gregory A. , Taylor Robert E. , Baker David , Bowie James U.
Published: February 2019

Prenylation of natural compounds adds structural diversity, alters biological activity, and enhances therapeutic potential. Because prenylated compounds often have a low natural abundance, alternative production methods are needed. Metabolic engineering enables natural product biosynthesis from inexpensive biomass, but is limited by the complexity of secondary metabolite pathways, intermediate and product toxicities, and substrate accessibility. Alternatively, enzyme catalyzed prenyl transfer provides excellent regio- and stereo-specificity, but requires expensive isoprenyl pyrophosphate substrates. Here we develop a flexible cell-free enzymatic prenylating system that generates isoprenyl pyrophosphate substrates from glucose to prenylate an array of natural products. The system provides an efficient route to cannabinoid precursors cannabigerolic acid (CBGA) and cannabigerovarinic acid (CBGVA) at >1 g/L, and a single enzymatic step converts the precursors into cannabidiolic acid (CBDA) and cannabidivarinic acid (CBDVA). Cell-free methods may provide a powerful alternative to metabolic engineering for chemicals that are hard to produce in living organisms.
Single-cell RNA sequencing reveals midbrain dopamine neuron diversity emerging during mouse brain development
Authors: Tiklová Katarína , Björklund Åsa K. , Lahti Laura , Fiorenzano Alessandro , Nolbrant Sara , Gillberg Linda , Volakakis Nikolaos , Yokota Chika , Hilscher Markus M. , Hauling Thomas , Holmström Fredrik , Joodmardi Eliza , Nilsson Mats , Parmar Malin , Perlmann Thomas
Published: February 2019

Midbrain dopamine (mDA) neurons constitute a heterogenous group of cells that have been intensely studied, not least because their degeneration causes major symptoms in Parkinson’s disease. Understanding the diversity of mDA neurons – previously well characterized anatomically – requires a systematic molecular classification at the genome-wide gene expression level. Here, we use single cell RNA sequencing of isolated mouse neurons expressing the transcription factor Pitx3, a marker for mDA neurons. Analyses include cells isolated during development up until adulthood and the results are validated by histological characterization of newly identified markers. This identifies seven neuron subgroups divided in two major branches of developing Pitx3-expressing neurons. Five of them express dopaminergic markers, while two express glutamatergic and GABAergic markers, respectively. Analysis also indicate evolutionary conservation of diversity in humans. This comprehensive molecular characterization will provide a valuable resource for elucidating mDA neuron subgroup development and function in the mammalian brain.
Catalytic enantioselective oxidative coupling of saturated ethers with carboxylic acid derivatives
Authors: Wang Gang , Xin Xiaodong , Wang Zehua , Lu Gang , Ma Yudao , Liu Lei
Published: February 2019

Catalytic enantioselective C–C bond forming process through cross-dehydrogenative coupling represents a promising synthetic strategy, but it remains a long-standing challenge in chemistry. Here, we report a formal catalytic enantioselective cross-dehydrogenative coupling of saturated ethers with diverse carboxylic acid derivatives involving an initial oxidative acetal formation, followed by nickel(II)-catalyzed asymmetric alkylation. The one-pot, general, and modular method exhibits wide compatibility of a broad range of saturated ethers not only including prevalent tetrahydrofuran and tetrahydropyran, but also including medium- and large-sized cyclic moieties and acyclic ones with excellent enantioselectivity and functional group tolerance. The application in the rapid preparation of biologically active molecules that are difficult to access with existing methods is also demonstrated.
Engineered microbial biofuel production and recovery under supercritical carbon dioxide
Authors: Boock Jason T. , Freedman Adam J. E. , Tompsett Geoffrey A. , Muse Sarah K. , Allen Audrey J. , Jackson Luke A. , Castro-Dominguez Bernardo , Timko Michael T. , Prather Kristala L. J. , Thompson Janelle R.
Published: February 2019

Culture contamination, end-product toxicity, and energy efficient product recovery are long-standing bioprocess challenges. To solve these problems, we propose a high-pressure fermentation strategy, coupled with in situ extraction using the abundant and renewable solvent supercritical carbon dioxide (scCO2), which is also known for its broad microbial lethality. Towards this goal, we report the domestication and engineering of a scCO2-tolerant strain ofBacillus megaterium, previously isolated from formation waters from the McElmo Dome CO2field, to produce branched alcohols that have potential use as biofuels. After establishing induced-expression under scCO2, isobutanol production from 2-ketoisovalerate is observed with greater than 40% yield with co-produced isopentanol. Finally, we present a process model to compare the energy required for our process to other in situ extraction methods, such as gas stripping, finding scCO2extraction to be potentially competitive, if not superior.
Non-equilibrium crystallization pathways of manganese oxides in aqueous solution
Authors: Sun Wenhao , Kitchaev Daniil A. , Kramer Denis , Ceder Gerbrand
Published: February 2019

Aqueous precipitation of transition metal oxides often proceeds through non-equilibrium phases, whose appearance cannot be anticipated from traditional phase diagrams. Without a precise understanding of which metastable phases form, or their lifetimes, targeted synthesis of specific metal oxides can become a trial-and-error process. Here, we construct a theoretical framework to reveal the nanoscale and metastable energy landscapes of Pourbaix (E-pH) diagrams, providing quantitative insights into the size–dependent thermodynamics of metastable oxide nucleation and growth in water. By combining this framework with classical nucleation theory, we interrogate how solution conditions influence the multistage oxidation pathways of manganese oxides. We calculate that even within the same stability region of a Pourbaix diagram, subtle variations in pH and redox potential can redirect a non-equilibrium crystallization pathway through different metastable intermediates. Our theoretical framework offers a predictive platform to navigate through the thermodynamic and kinetic energy landscape towards the rational synthesis of target materials.
Virus-specific memory T cells populate tumors and can be repurposed for tumor immunotherapy
Authors: Rosato Pamela C. , Wijeyesinghe Sathi , Stolley J. Michael , Nelson Christine E. , Davis Rachel L. , Manlove Luke S. , Pennell Christopher A. , Blazar Bruce R. , Chen Clark C. , Geller Melissa A. , Vezys Vaiva , Masopust David
Published: February 2019

The immunosuppressive tumor microenvironment limits the success of current immunotherapies. The host retains memory T cells specific for previous infections throughout the entire body that are capable of executing potent and immediate immunostimulatory functions. Here we show that virus-specific memory T cells extend their surveillance to mouse and human tumors. Reactivating these antiviral T cells can arrest growth of checkpoint blockade-resistant and poorly immunogenic tumors in mice after injecting adjuvant-free non-replicating viral peptides into tumors. Peptide mimics a viral reinfection event to memory CD8+ T cells, triggering antigen presentation and cytotoxic pathways within the tumor, activating dendritic cells and natural killer cells, and recruiting the adaptive immune system. Viral peptide treatment of ex vivo human tumors recapitulates immune activation gene expression profiles observed in mice. Lastly, peptide therapy renders resistant mouse tumors susceptible to PD-L1 blockade. Thus, re-stimulating known antiviral immunity may provide a unique therapeutic approach for cancer immunotherapy.
Immune modulation of liver sinusoidal endothelial cells by melittin nanoparticles suppresses liver metastasis
Authors: Yu Xiang , Chen Lu , Liu Jianqiao , Dai Bolei , Xu Guoqiang , Shen Guanxin , Luo Qingming , Zhang Zhihong
Published: February 2019

Liver sinusoidal endothelial cells (LSECs) are responsible for the immunologic tolerance of liver which is a common site for visceral metastases, suggesting its potential role as an target for cancer immunotherapy. However, targeted modulation of LSECs is still not achieved thus far. Here, we report LSECs are specifically targeted and modulated by melittin nanoparticles (α-melittin-NPs). Intravital imaging shows that LSECs fluoresce within 20 s after intravenous injection of α-melittin-NPs. α-melittin-NPs trigger the activation of LSECs and lead to dramatic changes of cytokine/chemokine milieu in the liver, which switches the hepatic immunologic environment to the activated state. As a result, α-melittin-NPs resist the formation of metastatic lesions with high efficiency. More strikingly, the survival rate reaches 80% in the spontaneous liver metastatic tumor model. Our research provides support for the use of α-melittin-NPs to break LSEC-mediated immunologic tolerance, which opens an avenue to control liver metastasis through the immunomodulation of LSECs.
Publisher Correction: A general and flexible method for signal extraction from single-cell RNA-seq data
Authors: Risso Davide , Perraudeau Fanny , Gribkova Svetlana , Dudoit Sandrine , Vert Jean-Philippe
Published: February 2019

The original PDF version of this Article contained errors in two equations. In Eq. (1), all Γ symbols were inadvertently omitted. In the second equation in the subsection entitled ‘1. Dispersion optimization’ within the Methods section ‘ZINB-WaVE estimation procedure’, all Ψ symbols were inadvertently omitted. These errors have been corrected in the PDF version of the Article; the HTML version was correct from the time of publication.
pAKT pathway activation is associated with PIK3CA mutations and good prognosis in luminal breast cancer in contrast to p-mTOR pathway activation
Authors: Sonnenblick Amir , Venet David , Brohée Sylvain , Pondé Noam , Sotiriou Christos
Published: January 2019

Numerous studies have focused on the PI3K/AKT/mTOR pathway in estrogen receptor positive (ER) breast cancer (BC), as a linear signal transduction pathway and reported its association with worse clinical outcomes. We developed gene signatures that reflect the level of expression of phosphorylated-Serine473-AKT (pAKT) and phosphorylated-Serine2448-mTOR (p-mTOR) separately, capturing their corresponding level of pathway activation. Our analysis revealed that the pAKT pathway activation was associated with luminal A BC while the p-mTOR pathway activation was more associated with luminal B BC (Kruskal–Wallis test p < 10−10). pAKT pathway activation was significantly associated with better outcomes (multivariable HR, 0.79; 95%CI, 0.74–0.85; p = 2.5 × 10−10) and PIK3CA mutations (p = 0.0001) whereas p-mTOR pathway activation showed worse outcomes (multivariable HR,1.1; 95%CI, 1.1–1.2; p = 9.9 × 10−4) and associated with p53 mutations (p = 0.04). in conclusion, our data show that pAKT and p-mTOR pathway activation have differing impact on prognosis and suggest that they are not linearly connected in luminal breast cancers.
Express assessment of neurotoxicity of particles of planetary and interstellar dust
Authors: Borisova Tatiana
Published: February 2019

Establishment of high-quality, consistent on-board assessment of the neurotoxicity of planetary, and interstellar dust particles will be required to predict their potential threat to human health during long-term space missions. This Perspective article proposes an approach for the rapid assessment of potential neurotoxicity of micro-sized and nano-sized dust particles based on experimental results with other neurotoxic particles. Capacity of particles to affect membrane potential, integrity of nerve terminals, and consequently key synaptic transmission characteristics can be assessed using a planar lipid bilayer technique by monitoring artificial membrane conductivity in the presence of particles. Preliminary neurotoxicity data of nanoparticles, including lunar and Martian dust simulants, obtained using a planar lipid bilayer technique, is compared with that acquired using more-established methodological approaches. Under space flight conditions, neurotoxicity assessments of particulate matter could be rapidly and reproducibly performed using a planar lipid bilayer technique, which does not require biological material.
Multi-qubit Quantum Rabi Model and Multi-partite Entangled States in a Circuit QED System
Authors: Li Jialun , Wang Gangcheng , Xiao Ruoqi , Sun Chunfang , Wu Chunfeng , Xue Kang
Published: February 2019

Multi-qubit quantum Rabi model, which is a fundamental model describing light-matter interaction, plays an important role in various physical systems. In this paper, we propose a theoretical method to simulate multi-qubit quantum Rabi model in a circuit quantum electrodynamics system. By means of external transversal and longitudinal driving fields, an effective Hamiltonian describing the multi-qubit quantum Rabi model is derived. The effective frequency of the resonator and the effective splitting of the qubits depend on the external driving fields. By adjusting the frequencies and the amplitudes of the driving fields, the stronger coupling regimes could be reached. The numerical simulation shows that our proposal works well in a wide range of parameter space. Moreover, our scheme can be utilized to generate two-qubit gate, Schrödinger states, and multi-qubit GHZ states. The maximum displacement of the Schrödinger cat states can be enhanced by increasing the number of the qubits and the relative coupling strength. It should be mention that we can obtain high fidelity Schrödinger cat states and multi-qubit GHZ states even the system suffering dissipation. The presented proposal may open a way to study the stronger coupling regimes whose coupling strength is far away from ultrastrong coupling regimes.
The pleasantness of sensory dissonance is mediated by musical style and expertise
Authors: Popescu Tudor , Neuser Monja P. , Neuwirth Markus , Bravo Fernando , Mende Wolfgang , Boneh Oren , Moss Fabian C. , Rohrmeier Martin
Published: January 2019

Western musical styles use a large variety of chords and vertical sonorities. Based on objective acoustical properties, chords can be situated on a dissonant-consonant continuum. While this might to some extent converge with the unpleasant-pleasant continuum, subjective liking might diverge for various chord forms from music across different styles. Our study aimed to investigate how well appraisals of the roughness and pleasantness dimensions of isolated chords taken from real-world music are predicted by Parncutt’s established model of sensory dissonance. Furthermore, we related these subjective ratings to style of origin and acoustical features of the chords as well as musical sophistication of the raters. Ratings were obtained for chords deemed representative of the harmonic language of three different musical styles (classical, jazz and avant-garde music), plus randomly generated chords. Results indicate that pleasantness and roughness ratings were, on average, mirror opposites; however, their relative distribution differed greatly across styles, reflecting different underlying aesthetic ideals. Parncutt’s model only weakly predicted ratings for all but Classical chords, suggesting that listeners’ appraisal of the dissonance and pleasantness of chords bears not only on stimulus-side but also on listener-side factors. Indeed, we found that levels of musical sophistication negatively predicted listeners’ tendency to rate the consonance and pleasantness of any one chord as coupled measures, suggesting that musical education and expertise may serve to individuate how these musical dimensions are apprehended.
Serum GP73 - An Additional Biochemical Marker for Liver Inflammation in Chronic HBV Infected Patients with Normal or Slightly Raised ALT
Authors: Wei Meijuan , Xu Zhengju , Pan Xingnan , Zhang Xiaoman , Liu LiGuan , Yang Bishuang , Chen Yuxia
Published: February 2019

This study aimed to assess the feasibility of GP73 as a diagnostic marker for liver inflammation and fibrosis in chronic HBV patients with normal or slightly raised ALT (<2 ULN) and to develop models based on GP73 and other biochemical parameters to improve diagnostic accuracy. Serum GP73 levels were analyzed in 220 chronic HBV patients with normal or slightly raised ALT who underwent liver biopsy. The results showed that the area under the receiver operating characteristic (ROC) curve (AUC) was 0.806 for predicting significant liver inflammation (≥G2), while it was 0.742 for predicting significant fibrosis (≥S2). These results suggest that GP73 has higher diagnostic value for liver inflammation than liver fibrosis. Combining GP73, AST and ALB, as a diagnostic model for predicting significant liver inflammation, resulted in superior diagnostic performance over GP73 alone (AUC value increased from 0.806 to 0.854, z = 2.299, P = 0.021). By applying this diagnostic model, over 80% of chronic HBV patients with normal or slightly raised ALT will be correctly identified and hence avoid delay in diagnosis and treatment. In conclusion, GP73 would be an additional serum marker for predicting liver inflammation and fibrosis in chronic HBV patients with normal or slightly raised ALT.
Insights into the role of CuO in the CO2 photoreduction process
Authors: Nogueira André E. , Oliveira Jéssica A. , da Silva Gelson T. S. T. , Ribeiro Caue
Published: February 2019

The CO2 photoreduction process to produce light hydrocarbons is known to be influenced by the presence of CuO nanoparticles, but the actual role of this material, whether as a catalyst or a reactant, has not yet been revealed. In this work, we investigate the role of CuO nanoparticles produced by a solvothermal method as a catalyst in CO2-saturated water reaction media under UV light, considering the effects of different electrolytes (Na2C2O4, KBrO3, and NaOH) and temperatures on nanoparticle phase and activity. The electrolyte strongly influenced product selectivity (NaOH led to evolution of CH4, Na2C2O4 to CO, and KBrO3 to O2) and induced CuO phase change. A long-term analysis of these processes indicated that during the initial steps, CuO acted as a reactant, rather than as a catalyst, and was converted to CuCO3.Cu(OH)2, while the as-converted material acted as a catalyst in CO2 photoreduction, with conversion values comparable to those reported in the literature.
Proposed mechanism for the length dependence of the force developed in maximally activated muscles
Authors: Marcucci Lorenzo , Washio Takumi , Yanagida Toshio
Published: February 2019

The molecular bases of the Frank-Starling law of the heart and of its cellular counterpart, the length dependent activation (LDA), are largely unknown. However, the recent discovery of the thick filament activation, a second pathway beside the well-known calcium mediated thin filament activation, is promising for elucidating these mechanisms. The thick filament activation is mediated by the tension acting on it through the mechano-sensing (MS) mechanism and can be related to the LDA via the titin passive tension. Here, we propose a mechanism to explain the higher maximum tension at longer sarcomere lengths generated by a maximally activated muscle and test it in-silico with a single fiber and a ventricle model. The active tension distribution along the thick filament generates a reservoir of inactive motors at its free-end that can be activated by passive tension on a beat-to-beat timescale. The proposed mechanism is able to quantitatively account for the observed increment in tension at the fiber level, however, the ventricle model suggests that this component of the LDA is not crucial in physiological conditions.
Consistent Reanalysis of Genome-wide Imprinting Studies in Plants Using Generalized Linear Models Increases Concordance across Datasets
Authors: Wyder Stefan , Raissig Michael T. , Grossniklaus Ueli
Published: February 2019

Genomic imprinting leads to different expression levels of maternally and paternally derived alleles. Over the last years, major progress has been made in identifying novel imprinted candidate genes in plants, owing to affordable next-generation sequencing technologies. However, reports on sequencing the transcriptome of hybrid F1 seed tissues strongly disagree about how many and which genes are imprinted. This raises questions about the relative impact of biological, environmental, technical, and analytic differences or biases. Here, we adopt a statistical approach, frequently used in RNA-seq data analysis, which properly models count overdispersion and considers replicate information of reciprocal crosses. We show that our statistical pipeline outperforms other methods in identifying imprinted genes in simulated and real data. Accordingly, reanalysis of genome-wide imprinting studies inArabidopsisand maize shows that, at least forArabidopsis, an increased agreement across datasets could be observed. For maize, however, consistent reanalysis did not yield a larger overlap between the datasets. This suggests that the discrepancy across publications might be partially due to different analysis pipelines but that technical, biological, and environmental factors underlie much of the discrepancy between datasets. Finally, we show that the set of genes that can be characterized regarding allelic bias by all studies with minimal confidence is small (~8,000/27,416 genes forArabidopsisand ~12,000/39,469 for maize). In conclusion, we propose to use biologically replicated reciprocal crosses, high sequence coverage, and a generalized linear model approach to identify differentially expressed alleles in developing seeds.
Seawater temperature and buffering capacity modulate coral calcifying pH
Authors: Guo Weifu
Published: February 2019

Scleractinian corals promote the precipitation of their carbonate skeleton by elevating the pH and dissolved inorganic carbon (DIC) concentration of their calcifying fluid above that of seawater. The fact corals actively regulate their calcifying fluid chemistry implies the potential for acclimation to ocean acidification. However, the extent to which corals can adjust their regulation mechanism in the face of decreasing ocean pH has not been rigorously tested. Here I present a numerical model simulating pH and DIC up-regulation by corals, and use it to determine the relative importance of physiological regulation versus seawater conditions in controlling coral calcifying fluid chemistry. I show that external seawater temperature and buffering capacity exert the first-order control on the extent of pH elevation in the calcifying fluid and explain most of the observed inter- and intra-species variability. Conversely, physiological regulation, represented by the interplay between enzymatic proton pumping, carbon influx and the exchange of calcifying fluid with external seawater, contributes to some variability but remain relatively constant as seawater conditions change. The model quantitatively reproduces variations of calcifying fluid pH in natural Porites colonies, and predicts an average 0.16 unit decrease in Porites calcifying fluid pH, i.e., ~43% increase in H+ concentration, by the end of this century as a combined result of projected ocean warming and acidification, highlighting the susceptibility of coral calcification to future changes in ocean conditions. In addition, my findings support the development of coral-based seawater pH proxies, but suggest the influences of physicochemical and biological factors other than seawater pH must be considered.
Monolithically integrated white light LEDs on (11–22) semi-polar GaN templates
Authors: Poyiatzis N. , Athanasiou M. , Bai J. , Gong Y. , Wang T.
Published: February 2019

Carrier transport issues in a (11–22) semi-polar GaN based white light emitting diode (consisting of yellow and blue emissions) have been investigated by detailed simulations, demonstrating that the growth order of yellow and blue InGaN quantum wells plays a critically important role in achieving white emission. The growth order needs to be yellow InGaN quantum wells first and then a blue InGaN quantum well after the growth of n-type GaN. The fundamental reason is due to the poor hole concentration distribution across the whole InGaN quantum well region. In order to effectively capture holes in both the yellow InGaN quantum wells and the blue InGaN quantum well, a thin GaN spacer has been introduced prior to the blue InGaN quantum well. The detailed simulations of the band diagram and the hole concentration distribution across the yellow and the blue quantum wells have been conducted, showing that the thin GaN spacer can effectively balance the hole concentration between the yellow and the blue InGaN quantum wells, eventually determining their relative intensity between the yellow and the blue emissions. Based on this simulation, we have demonstrated a monolithically multi-colour LED grown on our high quality semi-polar (11–22) GaN templates.
Atomic structures of self-assembled epitaxially grown GdSi2 nanowires on Si(001) by STM
Authors: Song Sun Kyu , Kim Tae-Hwan , Yeom Han Woong
Published: February 2019

Self-assembled rare-earth (RE) silicide nanowires (NWs) on semiconductor surfaces are considered as good candidates for creating and investigating one-dimensional electron systems because of their exceptionally anisotropic growth behavior and metallic property. While detailed atomic structures are essential to understand electronic properties of these NWs, there have been only few successful observations of atomic structures with microscopy and reliable structure models are lacking. Here, we reinvestigate gadolinium silicide NWs with high resolution scanning tunneling microscopy (STM). We observe several different structures of Gd silicide NWs depending systematically on their widths, which consist of two distinct structural elements along the wires. The structure of a wide wire can be understood from that of a two dimensional silicide. Based on these STM observations, we propose new structure models of Gd silicide NWs.
Interactions within the microbiome alter microbial interactions with host chemical defences and affect disease in a marine holobiont
Authors: Longford Sharon R. , Campbell Alexandra H. , Nielsen Shaun , Case Rebecca J. , Kjelleberg Staffan , Steinberg Peter D.
Published: February 2019

Our understanding of diseases has been transformed by the realisation that people are holobionts, comprised of a host and its associated microbiome(s). Disease can also have devastating effects on populations of marine organisms, including dominant habitat formers such as seaweed holobionts. However, we know very little about how interactions between microorganisms within microbiomes - of humans or marine organisms – affect host health and there is no underpinning theoretical framework for exploring this. We applied ecological models of succession to bacterial communities to understand how interactions within a seaweed microbiome affect the host. We observed succession of surface microbiomes on the red seaweed Delisea pulchra in situ, following a disturbance, with communities ‘recovering’ to resemble undisturbed states after only 12 days. Further, if this recovery was perturbed, a bleaching disease previously described for this seaweed developed. Early successional strains of bacteria protected the host from colonisation by a pathogenic, later successional strain. Host chemical defences also prevented disease, such that within-microbiome interactions were most important when the host’s chemical defences were inhibited. This is the first experimental evidence that interactions within microbiomes have important implications for host health and disease in a dominant marine habitat-forming organism.
A PET Radiomics Model to Predict Refractory Mediastinal Hodgkin Lymphoma
Authors: Milgrom Sarah A. , Elhalawani Hesham , Lee Joonsang , Wang Qianghu , Mohamed Abdallah S. R. , Dabaja Bouthaina S. , Pinnix Chelsea C. , Gunther Jillian R. , Court Laurence , Rao Arvind , Fuller Clifton D. , Akhtari Mani , Aristophanous Michalis , Mawlawi Osama , Chuang Hubert H. , Sulman Erik P. , Lee Hun J. , Hagemeister Frederick B. , Oki Yasuhiro , Fanale Michelle , Smith Grace L.
Published: February 2019

First-order radiomic features, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), are associated with disease progression in early-stage classical Hodgkin lymphoma (HL). We hypothesized that a model incorporating first- and second-order radiomic features would more accurately predict outcome than MTV or TLG alone. We assessed whether radiomic features extracted from baseline PET scans predicted relapsed or refractory disease status in a cohort of 251 patients with stage I-II HL who were managed at a tertiary cancer center. Models were developed and tested using a machine-learning algorithm. Features extracted from mediastinal sites were highly predictive of primary refractory disease. A model incorporating 5 of the most predictive features had an area under the curve (AUC) of 95.2% and total error rate of 1.8%. By comparison, the AUC was 78% for both MTV and TLG and was 65% for maximum standardize uptake value (SUVmax). Furthermore, among the patients with refractory mediastinal disease, our model distinguished those who were successfully salvaged from those who ultimately died of HL. We conclude that our PET radiomic model may improve upfront stratification of early-stage HL patients with mediastinal disease and thus contribute to risk-adapted, individualized management.
Behavioral correlates of activity of optogenetically identified locus coeruleus noradrenergic neurons in rats performing T-maze tasks
Authors: Xiang Liyang , Harel Antoine , Gao HongYing , Pickering Anthony E. , Sara Susan J. , Wiener Sidney I.
Published: February 2019

The nucleusLocus Coeruleus (LC) is the major source of forebrain norepinephrine. LC is implicated in arousal, response to novelty, and cognitive functions, including decision-making and behavioral flexibility. One hypothesis is that LC activation promotes rapid shifts in cortical attentional networks following changes in environmental contingencies. Recent recordings further suggest LC is critical for mobilizing resources to deal with challenging situations. In the present study optogenetically identified LC neuronal activity was recorded in rats in a self-paced T-maze. Rats were trained on visual discrimination; then place-reward contingencies were instated. In the session where the animal shifted tasks the first time, the LC firing rate after visual cue onset increased significantly, even as the animal adhered to the previous rule. Firing rate also increased prior to crossing photodetectors that controlled stimulus onset and offset, and this was positively correlated with accelerations, consistent with a role in mobilizing effort. The results contribute to the growing evidence that the noradrenergic LC is essential for behavioral adaptation by promoting cognitive flexibility and mobilizing effort in face of changing environmental contingencies.
Detection of lost calamus challenges identity of isolated Archaeopteryx feather
Authors: Kaye Thomas G. , Pittman Michael , Mayr Gerald , Schwarz Daniela , Xu Xing
Published: February 2019

In 1862, a fossil feather from the Solnhofen quarries was described as the holotype of the iconic Archaeopteryx lithographica. The isolated feather’s identification has been problematic, and the fossil was considered either a primary, secondary or, most recently, a primary covert. The specimen is surrounded by the ‘mystery of the missing quill’. The calamus described in the original paper is unseen today, even under x-ray fluorescence and UV imaging, challenging its original existence. We answer this question using Laser-Stimulated Fluorescence (LSF) through the recovery of the geochemical halo from the original calamus matching the published description. Our study therefore shows that new techniques applied to well-studied iconic fossils can still provide valuable insights. The morphology of the complete feather excludes it as a primary, secondary or tail feather of Archaeopteryx. However, it could be a covert or a contour feather, especially since the latter are not well known in Archaeopteryx. The possibility remains that it stems from a different feathered dinosaur that lived in the Solnhofen Archipelago. The most recent analysis of the isolated feather considers it to be a primary covert. If this is the case, it lacks a distinct s-shaped centerline found in modern primary coverts that appears to be documented here for the first time.
Effects of a hypomagnetic field on DNA methylation during the differentiation of embryonic stem cells
Authors: Baek Soonbong , Choi Hwan , Park Hanseul , Cho Byunguk , Kim Siyoung , Kim Jongpil
Published: February 2019

It has been reported that hypomagnetic fields (HMFs) have a negative influence on mammalian physiological functions. We previously reported that HMFs were detrimental to cell fate changes during reprogramming into pluripotency. These studies led us to investigate whether HMFs affect cell fate determination during direct differentiation. Here, we found that an HMF environment attenuates differentiation capacity and is detrimental to cell fate changes during the in vitro differentiation of embryonic stem cells (ESCs). Moreover, HMF conditions cause abnormal DNA methylation through the dysregulation of DNA methyltransferase3b (Dnmt3b) expression, eventually resulting in incomplete DNA methylation during differentiation. Taken together, these results suggest that an appropriate electromagnetic field (EMF) environment may be essential for favorable epigenetic remodeling during cell fate determination via differentiation.
A step towards valid detection and quantification of lung cancer volume in experimental mice with contrast agent-based X-ray microtomography
Authors: Bidola Pidassa , Martins de Souza e Silva Juliana , Achterhold Klaus , Munkhbaatar Enkhtsetseg , Jost Philipp J. , Meinhardt Anna-Lena , Taphorn Kirsten , Zdora Marie-Christine , Pfeiffer Franz , Herzen Julia
Published: February 2019

Tumor volume is a parameter used to evaluate the performance of new therapies in lung cancer research. Conventional methods that are used to estimate tumor size in mouse models fail to provide fast and reliable volumetric data for tumors grown non-subcutaneously. Here, we evaluated the use of iodine-staining combined with micro-computed tomography (micro-CT) to estimate the tumor volume ofex vivotumor-burdened lungs. We obtained fast high spatial resolution three-dimensional information of the lungs, and we demonstrated that iodine-staining highlights tumors and unhealthy tissue. We processed iodine-stained lungs for histopathological analysis with routine hematoxylin and eosin (H&E) staining. We compared the traditional tumor burden estimation performed manually with H&E histological slices with a semi-automated method using micro-CT datasets. In mouse models that develop lung tumors with well precise boundaries, the method that we describe here enables to perform a quick estimation of tumorous tissue volume in micro-CT images. Our method overestimates the tumor burden in tumors surrounded by abnormal tissue, while traditional histopathological analysis underestimates tumor volume. We propose to embed micro-CT imaging to the traditional workflow of tumorous lung analyses in preclinical cancer research as a strategy to obtain a more accurate estimation of the total lung tumor burden.
Extracellular polysaccharide synthesis in a bloom-forming strain of Microcystis aeruginosa: implications for colonization and buoyancy
Authors: Chen Meng , Tian Li-Li , Ren Chong-Yang , Xu Chun-Yang , Wang Yi-Ying , Li Li
Published: February 2019

Microcystis, the dominant species among cyanobacterial blooms, normally forms colonies under natural conditions but exists as single cells or paired cells in axenic laboratory cultures after long-term cultivation. Here, a bloom-forming Microcystis aeruginosa strain CHAOHU 1326 was studied because it presents a colonial morphology and grows on the water surface during axenic laboratory culturing. We first examined the morphological features of strain CHAOHU 1326 and three other unicellular M. aeruginosa strains FACHB-925, FACHB-940, and FACHB-975 cultured under the same conditions by scanning and transmission electron microscopy. Then, we compared the extracellular polysaccharide (EPS)-producing ability of colonial strain CHAOHU 1326 to that of the three unicellular M. aeruginosa strains, and found that strain CHAOHU 1326 produced a higher amount of EPS than the other strains during growth. Moreover, based on genome sequencing, multiple gene clusters implicated in EPS biosynthesis and a cluster of 12 genes predicted to be involved in gas vesicle synthesis in strain CHAOHU 1326 were detected. These predicted genes were all functional and expressed in M. aeruginosa CHAOHU 1326 as determined by reverse transcription PCR. These findings provide a physiological and genetic basis to better understand colony formation and buoyancy control during M. aeruginosa blooming.