Genetic analysis of self-associating immunoglobulin G rheumatoid factors from two rheumatoid synovia implicates an antigen-driven response.

Although much has been learned about the molecular basis of immunoglobulin M (IgM) rheumatoid factors (RFs) in healthy individuals and in patients with mixed cryoglobulinemia and rheumatoid arthritis, little is known about the genetic origins of the potentially pathogenic IgG RFs in the inflamed rheumatoid synovia of patients. Recently, we generated from unmanipulated synovium B cells several hybridomas that secreted self-associating IgG RFs. To delineate the genetic origins of such potentially pathogenic RFs, we adapted the anchored polymerase chain reaction to rapidly clone and characterize the expressed Ig V genes for the L1 and the D1 IgG RFs. Then, we identified the germline counterparts of the expressed L1 IgG RF V genes. The results showed that the L1 heavy chain was encoded by a Vh gene that is expressed preferentially during early ontogenic development, and that is probably located within 240 kb upstream of the Jh locus. The overlap between this RF Vh gene and the restricted fetal antibody repertoire is reminiscent of the natural antibody-associated Vh genes, and suggests that at least part of the "potential pathogenic" IgG RFs in rheumatoid synovium may derive from the "physiological" natural antibody repertoire in a normal immune system. Indeed, the corresponding germline Vh gene for L1 encodes the heavy chain of an IgM RF found in a 19-wk-old fetal spleen. Furthermore, the comparisons of the expressed RF V genes and their germline counterparts reveal that the L1 heavy and light chain variable regions had, respectively, 16 and 7 somatic mutations, which resulted in eight and four amino acid changes. Strikingly, all eight mutations in the complementarity determining regions of the V gene-encoded regions were replacement changes, while only 6 of 11 mutations in the framework regions caused amino acid changes. Combined with L1's high binding affinity toward the Fc fragment, these results suggest strongly that the L1 IgG RF must have been driven by the Fc antigen

Boson Sampling Private-Key Quantum Cryptography

We introduce a quantum private-key encryption protocol based on multi-photon interference in linear optics networks. The scheme builds upon Boson Sampling, and we show that it is hard to break, even for a quantum computer. We present an information-theoretic proof of the security of our protocol against an eavesdropper with unlimited (quantum) computational power but time-limited quantum storage. This protocol is shown to be optimal in the sense that it asymptotically encrypts all the information that passes through the interferometer using an exponentially smaller private key. This is the first practical application of Boson Sampling in quantum communication. Our scheme requires only moderate photon numbers and is experimentally feasible with current technology

Quantum Rotor Engines

This chapter presents autonomous quantum engines that generate work in the form of directed motion for a rotor. We first formulate a prototypical clock-driven model in a time-dependent framework and demonstrate how it can be translated into an autonomous engine with the introduction of a planar rotor degree of freedom. The rotor plays both the roles of internal engine clock and of work repository. Using the example of a single-qubit piston engine, the thermodynamic performance is then reviewed. We evaluate the extractable work in terms of ergotropy, the kinetic energy associated to net directed rotation, as well as the intrinsic work based on the exerted torque under autonomous operation; and we compare them with the actual energy output to an external dissipative load. The chapter closes with a quantum-classical comparison of the engine's dynamics. For the single-qubit piston example, we propose two alternative representations of the qubit in an entirely classical framework: (i) a coin flip model and (ii) a classical magnet moment, showing subtle differences between the quantum and classical descriptions.Comment: Chapter of the upcoming book "Thermodynamics in the Quantum Regime - Recent Progress and Outlook

Multiphoton Interference in Quantum Fourier Transform Circuits and Applications to Quantum Metrology

© 2017 American Physical Society. Quantum Fourier transforms (QFTs) have gained increased attention with the rise of quantum walks, boson sampling, and quantum metrology. Here, we present and demonstrate a general technique that simplifies the construction of QFT interferometers using both path and polarization modes. On that basis, we first observe the generalized Hong-Ou-Mandel effect with up to four photons. Furthermore, we directly exploit number-path entanglement generated in these QFT interferometers and demonstrate optical phase supersensitivities deterministically

Dysbiosis of intestinal microbiota mediates tubulointerstitial injury in diabetic nephropathy via the disruption of cholesterol homeostasis

BACKGROUND: Our previous study demonstrated that the disruption of cholesterol homeostasis promotes tubulointerstitial injury in diabetic nephropathy (DN). This study aimed to further investigate the effects of gut microbiota dysbiosis on this process and explored its potential mechanism. METHODS: Diabetic rats treated with broad-spectrum oral antibiotics or faecal microbiota transplantation (FMT) from the healthy donor group and human kidney 2 (HK-2) cells stimulated with sodium acetate were used to observe the effects of gut microbiota on cholesterol homeostasis. The gut microbiota distribution was measured by 16S rDNA sequencing with faeces. Serum acetate level was examined by gas chromatographic analysis. Protein expression of G protein coupled receptor 43 (GPR43) and molecules involved in cholesterol homeostasis were assessed by immunohistochemical staining, immunofluorescence staining, and Western Blotting. RESULTS: Depletion of gut microbiota significantly attenuated albuminuria and tubulointerstitial injury. Interestingly, serum acetate levels were also markedly decreased in antibiotics-treated diabetic rats and positively correlated with the cholesterol contents in kidneys. An in vitro study demonstrated that acetate significantly increased cholesterol accumulation in HK-2 cells, which was caused by increased expression of proteins mainly modulating cholesterol synthesis and uptake. As expected, FMT effectively decreased serum acetate levels and alleviated tubulointerstitial injury in diabetic rats through overriding the disruption of cholesterol homeostasis. Furthermore, GPR43 siRNA treatment blocked acetate-mediated cholesterol homeostasis dysregulation in HK-2 cells through decreasing the expression of proteins governed cholesterol synthesis and uptake. CONCLUSIONS: Our studies for the first time demonstrated that the acetate produced from gut microbiota mediated the dysregulation of cholesterol homeostasis through the activation of GPR43, thereby contributing to the tubulointerstitial injury of DN, suggesting that gut microbiota reprogramming might be a new strategy for DN prevention and therapy

High-density information storage in an absolutely defined aperiodic sequence of monodisperse copolyester

Synthesis of a polymer composed of a large discrete number of chemically distinct monomers in an absolutely defined aperiodic sequence remains a challenge in polymer chemistry. The synthesis has largely been limited to oligomers having a limited number of repeating units due to the difficulties associated with the step-by-step addition of individual monomers to achieve high molecular weights. Here we report the copolymers of ??-hydroxy acids, poly(phenyllactic-co-lactic acid) (PcL) built via the cross-convergent method from four dyads of monomers as constituent units. Our proposed method allows scalable synthesis of sequence-defined PcL in a minimal number of coupling steps from reagents in stoichiometric amounts. Digital information can be stored in an aperiodic sequence of PcL, which can be fully retrieved as binary code by mass spectrometry sequencing. The information storage density (bit/Da) of PcL is 50% higher than DNA, and the storage capacity of PcL can also be increased by adjusting the molecular weight (~38???kDa)

SUCI02 inhibits the erbB-2 tyrosine kinase receptor signaling pathway and arrests the cell cycle in G 1 phase in breast cancer cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73321/1/j.1349-7006.2006.00143.x.pd

GPR43 deficiency protects against podocyte insulin resistance in diabetic nephropathy through the restoration of AMPKα activity

RATIONALE: Albuminuria is an early clinical feature in the progression of diabetic nephropathy (DN). Podocyte insulin resistance is a main cause of podocyte injury, playing crucial roles by contributing to albuminuria in early DN. G protein-coupled receptor 43 (GPR43) is a metabolite sensor modulating the cell signalling pathways to maintain metabolic homeostasis. However, the roles of GPR43 in podocyte insulin resistance and its potential mechanisms in the development of DN are unclear. METHODS: The experiments were conducted by using kidney tissues from biopsied DN patients, streptozotocin (STZ) induced diabetic mice with or without global GPR43 gene knockout, diabetic rats treated with broad-spectrum oral antibiotics or fecal microbiota transplantation, and cell culture model of podocytes. Renal pathological injuries were evaluated by periodic acid-schiff staining and transmission electron microscopy. The expression of GPR43 with other podocyte insulin resistance related molecules was checked by immunofluorescent staining, real-time PCR, and Western blotting. Serum acetate level was examined by gas chromatographic analysis. The distribution of gut microbiota was measured by 16S ribosomal DNA sequencing with faeces. RESULTS: Our results demonstrated that GPR43 expression was increased in kidney samples of DN patients, diabetic animal models, and high glucose-stimulated podocytes. Interestingly, deletion of GPR43 alleviated albuminuria and renal injury in diabetic mice. Pharmacological inhibition and knockdown of GPR43 expression in podocytes increased insulin-induced Akt phosphorylation through the restoration of adenosine 5'-monophosphate-activated protein kinase α (AMPKα) activity. This effect was associated with the suppression of AMPKα activity through post-transcriptional phosphorylation via the protein kinase C-phospholipase C (PKC-PLC) pathway. Antibiotic treatment-mediated gut microbiota depletion, and faecal microbiota transplantation from the healthy donor controls substantially improved podocyte insulin sensitivity and attenuated glomerular injury in diabetic rats accompanied by the downregulation of the GPR43 expression and a decrease in the level of serum acetate. CONCLUSION: These findings suggested that dysbiosis of gut microbiota-modulated GPR43 activation contributed to albuminuria in DN, which could be mediated by podocyte insulin resistance through the inhibition of AMPKα activity

Geospatial information infrastructures

Manual of Digital Earth / Editors: Huadong Guo, Michael F. Goodchild, Alessandro Annoni .- Springer, 2020 .- ISBN: 978-981-32-9915-3Geospatial information infrastructures (GIIs) provide the technological, semantic,organizationalandlegalstructurethatallowforthediscovery,sharing,and use of geospatial information (GI). In this chapter, we introduce the overall concept and surrounding notions such as geographic information systems (GIS) and spatial datainfrastructures(SDI).WeoutlinethehistoryofGIIsintermsoftheorganizational andtechnologicaldevelopmentsaswellasthecurrentstate-of-art,andreflectonsome of the central challenges and possible future trajectories. We focus on the tension betweenincreasedneedsforstandardizationandtheever-acceleratingtechnological changes. We conclude that GIIs evolved as a strong underpinning contribution to implementation of the Digital Earth vision. In the future, these infrastructures are challengedtobecomeflexibleandrobustenoughtoabsorbandembracetechnological transformationsandtheaccompanyingsocietalandorganizationalimplications.With this contribution, we present the reader a comprehensive overview of the field and a solid basis for reflections about future developments

Cytomolecular identification of individual wheat-wheat chromosome arm associations in wheat-rye hybrids

Chromosome pairing in the meiotic metaphase I of wheatrye hybrids has been characterized by sequential genomic and fluorescent in situ hybridization allowing not only the discrimination of wheat and rye chromosomes, but also the identification of the individual wheat and rye chromosome arms involved in the chromosome associations. The majority of associations (93.8%) were observed between the wheat chromosomes. The largest number of wheat-wheat chromosome associations (53%) was detected between the A and D genomes, while the frequency of B-D and A-B associations was significantly lower (32 and 8%, respectively). Among the A-D chromosome associations, pairing between the 3AL and 3DL arms was observed with the highest frequency, while the most frequent of all the chromosome associations (0.113/ cell) was found to be the 3DS-3BS. Differences in the pairing frequency of the individual chromosome arms of wheat-rye hybrids have been discussed in relation to the homoeologous relationships between the constituent genomes of hexaploid wheat