bluuebunny/crossref_metadata_2025_split huggingface dataset:
CEMIP (KIAA1199) induces a fibrosis-like process in osteoarthritic chondrocytes
Authors: Deroyer Céline , Charlier Edith , Neuville Sophie , Malaise Olivier , Gillet Philippe , Kurth William , Chariot Alain , Malaise Michel , de Seny Dominique 
Published: February 2019

AbstractCEMIP (for “Cell migration-inducing protein” also called KIAA1199 and Hybid for “Hyaluronan-binding protein”) expression is increased in cancers and described as a regulator of cell survival, growth and invasion. In rheumatoid arthritis, CEMIP is referred to as an angiogenic marker and participates in hyaluronic acid degradation. In this study, CEMIP expression is investigated in healthy and osteoarthritis (OA) cartilage from human and mouse. Its role in OA physiopathology is deciphered, specifically in chondrocytes proliferation and dedifferentiation and in the extracellular matrix remodeling. To this end, CEMIP, αSMA and types I and III collagen expressions were assessed in human OA and non-OA cartilage. CEMIP expression was also investigated in a mouse OA model. CEMIP expression was studied in vitro using a chondrocyte dedifferentiation model. High-throughput RNA sequencing was performed on chondrocytes after CEMIP silencing. Results showed that CEMIP was overexpressed in human and murine OA cartilage and along chondrocytes dedifferentiation. Most of genes deregulated in CEMIP-depleted cells were involved in cartilage turnover (e.g., collagens), mesenchymal transition and fibrosis. CEMIP regulated β-catenin protein level. Moreover, CEMIP was essential for chondrocytes proliferation and promoted αSMA expression, a fibrosis marker, and TGFβ signaling towards the p-Smad2/3 (Alk5/PAI-1) pathway. Interestingly, CEMIP was induced by the pSmad1/5 (Alk1) pathway. αSMA and type III collagen expressions were overexpressed in human OA cartilage and along chondrocytes dedifferentiation. Finally, CEMIP was co-expressed in situ with αSMA in all OA cartilage layers. In conclusion, CEMIP was sharply overexpressed in human and mouse OA cartilage and along chondrocytes dedifferentiation. CEMIP-regulated transdifferentiation of chondrocytes into “chondro-myo-fibroblasts” expressing α-SMA and type III collagen, two fibrosis markers. Moreover, these “chondro-myo-fibroblasts” were found in OA cartilage but not in healthy cartilage.
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

AbstractArchaeogenetic 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

AbstractCertain 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

AbstractThe 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

AbstractVascularization 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

AbstractAlthough 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

AbstractMaxwell 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

AbstractEvanescently 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

AbstractPrenylation 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

AbstractMidbrain 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

AbstractCatalytic 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

AbstractCulture 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

AbstractAqueous 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

AbstractThe 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

AbstractLiver 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.
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

AbstractNumerous 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.