Highlights • Transcription, biosynthesis and secretion of OSM and IL-31. • OSM and IL-31 cytokine–receptor interaction. • OSM- and IL-31-mediated signal transduction. • Genetic models to evaluate the ...physiological function of OSM. • Animal models investigating IL-31 physiology and recent findings for IL-31 in human disease.
Quantum spin liquids have fascinated condensed matter physicists for decades because of their unusual properties such as spin fractionalization and long-range entanglement. Unlike conventional ...symmetry breaking, the topological order underlying quantum spin liquids is hard to detect experimentally. Even theoretical models are scarce for which the ground state is established to be a quantum spin liquid. The Kitaev honeycomb model and its generalizations to other tricoordinated lattices are chief counterexamples-they are exactly solvable, harbor a variety of quantum spin liquid phases, and are also relevant for certain transition metal compounds including the polymorphs of (Na,Li)
2
IrO
3
iridates and RuCl
3
. In this review, we give an overview of the rich physics of the Kitaev model, including two-dimensional and three-dimensional fractionalization as well as dynamic correlations and behavior at finite temperatures. We discuss the different materials and argue how the Kitaev model physics can be relevant even though most materials show magnetic ordering at low temperatures.
Motivated by the recent synthesis of Li beta -Li sub(2) IrO sub(3) -a spin-orbit entangled j = 1/2 Mott insulator with a three-dimensional lattice structure of the Ir super(4+) ions-we consider ...generalizations of the Kitaev model believed to capture some of the microscopic interactions between the iridium moments on various trivalent lattice structures in three spatial dimensions. Of particular interest is the so-called hyperoctagon lattice-the premedial lattice of the hyperkagome lattice, for which the ground state is a gapless quantum spin liquid where the gapless Majorana modes form an extended two-dimensional Majorana Fermi surface. We demonstrate that this Majorana Fermi surface is inherently protected by lattice symmetries and discuss possible instabilities. We thus provide the first example of an analytically tractable microscopic model of interacting SU(2) spin-1/2 degrees of freedom in three spatial dimensions that harbors a spin liquid with a two-dimensional spinon Fermi surface.
Weyl spin liquids Hermanns, M; O'Brien, K; Trebst, S
Physical review letters,
2015-Apr-17, Volume:
114, Issue:
15
Journal Article
Peer reviewed
The fractionalization of quantum numbers in interacting quantum many-body systems is a central motif in condensed-matter physics with prominent examples including the fractionalization of the ...electron in quantum Hall liquids or the emergence of magnetic monopoles in spin-ice materials. Here, we discuss the fractionalization of magnetic moments in three-dimensional Kitaev models into Majorana fermions (and a Z_{2} gauge field) and their emergent collective behavior. We analytically demonstrate that the Majorana fermions form a Weyl superconductor for the Kitaev model on the recently synthesized hyperhoneycomb structure of β-Li_{2}IrO_{3} when applying a magnetic field. We characterize the topologically protected bulk and surface features of this state, which we dub a Weyl spin liquid, including thermodynamic and transport signatures.
Peat humification or decomposition is a frequently used proxy to extract past time changes in hydrology and climate from peat bogs. During the past century several methods to determine changes in ...peat decomposition have been introduced. Most of these methods are operationally defined only and the chemical changes underlying the decomposition process are often poorly understood and lack validation. Owing to the chemically undefined nature of many humification analyses the comparison of results obtained by different methods is difficult. In this study we compared changes in peat decomposition proxies in cores of two peat bogs (Königsmoor, KK; Kleines Rotes Bruch, KRB) from the Harz Mountains (Germany) using C / N ratios, Fourier transform infrared spectra absorption (FTIR) intensities, Rock Eva® oxygen and hydrogen indices, δ13C and δ15N isotopic signatures and UV-absorption (UV-ABS) of NaOH peat extracts. In order to explain parallels and discrepancies between these methods, one of the cores was additionally analysed by pyrolysis gas chromatography mass spectrometry (pyrolysis-GC-MS). Pyrolysis-GC-MS data provide detailed information on a molecular level, which allows differentiation of both changes attributed to decomposition processes and changes in vegetation. Principal component analysis was used to identify and separate the effects of changes in vegetation pattern and decomposition processes because both may occur simultaneously upon changes in bog hydrology. Records of decomposition proxies show similar historical development at both sites, indicating external forcing such as climate as controlling the process. All decomposition proxies except UV-ABS and δ15N isotopes show similar patterns in their records and reflect to different extents signals of decomposition. The molecular composition of the KK core reveals that these changes are mainly attributed to decomposition processes and to a lesser extent to changes in vegetation. Changes in the molecular composition indicate that peat decomposition in the KK bog is mainly characterized by preferential decomposition of phenols and polysaccharides and relative enrichment of aliphatics during drier periods. Enrichment of lignin and other aromatics during decomposition was also observed but showed less variation than polysaccharides or aliphatics, and presumably reflects changes in vegetation associated with changes in hydrology of the bogs. Significant correlations with polysaccharide and aliphatic pyrolysis products were found for C / N ratios, FTIR-band intensities and for hydrogen index values, supporting that these decomposition indices provide reasonable information. Correlations of polysaccharide and aliphatic pyrolysis products with oxygen index values and δ13C was weaker, assumingly indicating carboxylation of the peat during drier periods and enrichment of isotopically lighter peat components during decomposition, respectively. FTIR, C / N ratio, pyrolysis-GC-MS analyses and Rock Eval hydrogen indices appear to reflect mass loss and related changes in the molecular peat composition during mineralization best. Pyrolysis-GC-MS allows disentangling the decomposition processes and vegetation changes. UV-ABS measurements of alkaline peat extracts show only weak correlation with other decomposition proxies and pyrolysis results as they mainly reflect the formation of humic acids through humification and to a lesser extent mass loss during mineralization.
The fractional quantum Hall effect, being one of the most studied phenomena in condensed matter physics during the past 30 years, has generated many ground-breaking new ideas and concepts. Very early ...on it was realized that the zoo of emerging states of matter would need to be understood in a systematic manner. The first attempts to do this, by Haldane and Halperin, set an agenda for further work which has continued to this day. Since that time the idea of hierarchies of quasiparticles condensing to form new states has been a pillar of our understanding of fractional quantum Hall physics. In the 30 years that have passed since then, a number of new directions of thought have advanced our understanding of fractional quantum Hall states and have extended it in new and unexpected ways. Among these directions is the extensive use of topological quantum field theories and conformal field theories, the application of the ideas of composite bosons and fermions, and the study of non-Abelian quantum Hall liquids. This article aims to present a comprehensive overview of this field, including the most recent developments.
Immune checkpoint inhibition and in particular anti-PD-1 immunotherapy have revolutionized the treatment of advanced melanoma. In this regard, higher tumoral PD-L1 protein (gene name: CD274) ...expression is associated with better clinical response and increased survival to anti-PD-1 therapy. Moreover, there is increasing evidence that tumor suppressor proteins are involved in immune regulation and are capable of modulating the expression of immune checkpoint proteins. Here, we determined the role of p53 protein (gene name: TP53) in the regulation of PD-L1 expression in melanoma.
We analyzed publicly available mRNA and protein expression data from the cancer genome/proteome atlas and performed immunohistochemistry on tumors with known TP53 status. Constitutive and IFN-ɣ-induced PD-L1 expression upon p53 knockdown in wildtype, TP53-mutated or JAK2-overexpressing melanoma cells or in cells, in which p53 was rendered transcriptionally inactive by CRISPR/Cas9, was determined by immunoblot or flow cytometry. Similarly, PD-L1 expression was investigated after overexpression of a transcriptionally-impaired p53 (L22Q, W23S) in TP53-wt or a TP53-knockout melanoma cell line. Immunoblot was applied to analyze the IFN-ɣ signaling pathway.
For TP53-mutated tumors, an increased CD274 mRNA expression and a higher frequency of PD-L1 positivity was observed. Interestingly, positive correlations of IFNG mRNA and PD-L1 protein in both TP53-wt and -mutated samples and of p53 and PD-L1 protein suggest a non-transcriptional mode of action of p53. Indeed, cell line experiments revealed a diminished IFN-ɣ-induced PD-L1 expression upon p53 knockdown in both wildtype and TP53-mutated melanoma cells, which was not the case when p53 wildtype protein was rendered transcriptionally inactive or by ectopic expression of p53
, a transcriptionally-impaired variant, in TP53-wt cells. Accordingly, expression of p53
in a TP53-knockout melanoma cell line boosted IFN-ɣ-induced PD-L1 expression. The impaired PD-L1-inducibility after p53 knockdown was associated with a reduced JAK2 expression in the cells and was almost abrogated by JAK2 overexpression.
While having only a small impact on basal PD-L1 expression, both wildtype and mutated p53 play an important positive role for IFN-ɣ-induced PD-L1 expression in melanoma cells by supporting JAK2 expression. Future studies should address, whether p53 expression levels might influence response to anti-PD-1 immunotherapy.
Thrombin generation may be a potential tool to improve risk stratification for cardiovascular diseases. This study aims to explore the relation between thrombin generation and cardiovascular risk ...factors, cardiovascular diseases, and total mortality. For this study, N=5000 subjects from the population-based Gutenberg Health Study were analysed in a highly standardized setting. Thrombin generation was assessed by the Calibrated Automated Thrombogram method at 1 and 5 pM tissue factors trigger in platelet poor plasma. Lag time, endogenous thrombin potential, and peak height were derived from the thrombin generation curve. Sex-specific multivariable linear regression analysis adjusted for age, cardiovascular risk factors, cardiovascular diseases and therapy, was used to assess clinical determinants of thrombin generation. Cox regression models adjusted for age, sex, cardiovascular risk factors and vitamin K antagonists investigated the association between thrombin generation parameters and total mortality. Lag time was positively associated with obesity and dyslipidaemia for both sexes (p<0.0001). Obesity was also positively associated with endogenous thrombin potential in both sexes (p<0.0001) and peak height in males (1 pM tissue factor, p=0.0048) and females (p<0.0001). Cox regression models showed an increased mortality in individuals with lag time (1 pM tissue factor, hazard ratio=1.46, 95% CI: 1.07; 2.00, p=0.018) and endogenous thrombin potential (5 pM tissue factor, hazard ratio = 1.50, 1.06; 2.13, p=0.023) above the 95th percentile of the reference group, independent of the cardiovascular risk profile. This large-scale study demonstrates traditional cardiovascular risk factors, particularly obesity, as relevant determinants of thrombin generation. Lag time and endogenous thrombin potential were found as potentially relevant predictors of increased total mortality, which deserves further investigation.
Abstract Interleukin (IL)-6-type cytokines are critically involved in health and disease. The duration and strength of IL-6-type cytokine-mediated signaling is tightly regulated to avoid overshooting ...activities. Here, molecular mechanisms of inter-familiar cytokine cross-talk are reviewed which regulate dynamics and strength of IL-6 signal transduction. Both plasticity and cytokine cross-talk are significantly involved in pro- and anti-inflammatory/regenerative properties of IL-6-type cytokines. Furthermore, we focus on IL-6-type cytokine/cytokine receptor plasticity and cross-talk exemplified by the recently identified composite cytokines IL-30/IL-6R and IL-35, the first inter-familiar IL-6/IL-12 family member. The complete understanding of the intra- and extracellular cytokine networks will aid to develop novel tailor-made therapeutic strategies with reduced side effects.
Highlights • FGF15/19 is a gut-derived hormone regulating enterohepatic bile acid homeostasis. • FGF15/19 controls energy metabolism in liver and extra-hepatic tissues. • Diverse mechanisms regulate ...intestinal FGF15/19 synthesis and release. • Several human diseases are associated with dysregulated FGF15/19 signaling. • Is FGF15/19 a potential therapeutic target?
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