X-Ray Magnetic Circular Dichroism in Altermagnetic α-MnTe.

Altermagnetism is a recently identified magnetic symmetry class combining characteristics of conventional collinear ferromagnets and antiferromagnets, that were regarded as mutually exclusive, and enabling phenomena and functionalities unparalleled in either of the two traditional elementary magnetic classes. In this work we use symmetry, ab initio theory, and experiments to explore x-ray magnetic circular dichroism (XMCD) in the altermagnetic class. As a representative material for our XMCD study we choose α-MnTe with compensated antiparallel magnetic order in which an anomalous Hall effect has been already demonstrated. We predict and experimentally confirm a characteristic XMCD line shape for compensated moments lying in a plane perpendicular to the light propagation vector. Our results highlight the distinct phenomenology in altermagnets of this time-reversal symmetry breaking response, and its potential utility for element-specific spectroscopy and microscopy.

High-Fat Diet Induces Resistance to Ghrelin and LEAP2 Peptide Analogs in Mice.

Recent data suggest that the orexigenic peptide ghrelin and liver-expressed antimicrobial peptide 2 (LEAP2) have opposing effects on food intake regulation. Although circulating ghrelin is decreased in obesity, peripheral ghrelin administration does not induce food intake in obese mice. Limited information is available on ghrelin resistance in relation to LEAP2. In this study, the interplay between ghrelin and LEAP2 in obesity induced by a high-fat (HF) diet in mice was studied. First, the progression of obesity and intolerance to glucose together with plasma levels of active and total ghrelin, leptin, as well as liver LEAP2 mRNA expression at different time points of HF diet feeding was examined. In addition, the impact of switch from a HF diet to a standard diet on plasma ghrelin and LEAP2 production was studied. Second, sensitivity to the stable ghrelin analogue [Dpr3]Ghrelin or our novel LEAP2 analogue palm-LEAP2(1-14) during the progression of HF diet-induced obesity and after the switch for standard diet was investigated. Food intake was monitored after acute subcutaneous administration. HF diet feeding decreased both active and total plasma ghrelin and increased liver LEAP2 mRNA expression along with intolerance to glucose and the switch to a standard diet normalized liver LEAP2 mRNA expression and plasma level of active ghrelin, but not of total ghrelin. Additionally, our study demonstrates that a HF diet causes resistance to [Dpr3]Ghrelin, reversible by switch to St diet, followed by resistance to palm-LEAP2(1-14). Further studies are needed to determine the long-term effects of LEAP2 analogues on obesity-related ghrelin resistance.

Obesity, Cardiovascular and Neurodegenerative Diseases: Potential Common Mechanisms.

The worldwide increase in the incidence of obesity and cardiovascular and neurodegenerative diseases, e.g. Alzheimer's disease, is related to many factors, including an unhealthy lifestyle and aging populations. However, the interconnection between these diseases is not entirely clear, and it is unknown whether common mechanisms underlie these conditions. Moreover, there are currently no fully effective therapies for obesity and neurodegeneration. While there has been extensive research in preclinical models addressing these issues, the experimental findings have not been translated to the clinic. Another challenge relates to the time of onset of individual diseases, which may not be easily identified, since there are no specific indicators or biomarkers that define disease onset. Hence knowing when to commence preventive treatment is unclear. This is especially pertinent in neurodegenerative diseases, where the onset of the disease may be subtle and occur decades before the signs and symptoms manifest. In metabolic and cardiovascular disorders, the risk may occur in-utero, in line with the concept of fetal programming. This review provides a brief overview of the link between obesity, cardiovascular and neurodegenerative diseases and discusses potential common mechanisms including the role of the gut microbiome.

Kondo quasiparticle dynamics observed by resonant inelastic x-ray scattering.

Effective models focused on pertinent low-energy degrees of freedom have substantially contributed to our qualitative understanding of quantum materials. An iconic example, the Kondo model, was key to demonstrating that the rich phase diagrams of correlated metals originate from the interplay of localized and itinerant electrons. Modern electronic structure calculations suggest that to achieve quantitative material-specific models, accurate consideration of the crystal field and spin-orbit interactions is imperative. This poses the question of how local high-energy degrees of freedom become incorporated into a collective electronic state. Here, we use resonant inelastic x-ray scattering (RIXS) on CePd3 to clarify the fate of all relevant energy scales. We find that even spin-orbit excited states acquire pronounced momentum-dependence at low temperature-the telltale sign of hybridization with the underlying metallic state. Our results demonstrate how localized electronic degrees of freedom endow correlated metals with new properties, which is critical for a microscopic understanding of superconducting, electronic nematic, and topological states.

Pressure-Induced Excitations in the Out-of-Plane Optical Response of the Nodal-Line Semimetal ZrSiS.

The anisotropic optical response of the layered, nodal-line semimetal ZrSiS at ambient and high pressure is investigated by frequency-dependent reflectivity measurements for the polarization along and perpendicular to the layers. The highly anisotropic optical conductivity is in very good agreement with results from density-functional theory calculations and confirms the anisotropic character of ZrSiS. Whereas the in-plane optical conductivity shows only modest pressure-induced changes, we found strong effects on the out-of-plane optical conductivity spectrum of ZrSiS, with the appearance of two prominent excitations. These pronounced pressure-induced effects can neither be attributed to a structural phase transition according to our single-crystal x-ray diffraction measurements, nor can they be explained by electronic correlation and electron-hole pairing effects, as revealed by theoretical calculations. Our findings are discussed in the context of the recently proposed excitonic insulator phase in ZrSiS.

Cholecystokinin system is involved in the anorexigenic effect of peripherally applied palmitoylated prolactin-releasing peptide in fasted mice.

Prolactin-releasing peptide (PrRP) has been proposed to mediate the central satiating effects of cholecystokinin (CCK) through the vagal CCK1 receptor. PrRP acts as an endogenous ligand of G protein-coupled receptor 10 (GPR10), which is expressed at the highest levels in brain areas related to food intake regulation, e.g., the paraventricular hypothalamic nucleus (PVN) and nucleus of the solitary tract (NTS). The NTS and PVN are also significantly activated after peripheral CCK administration. The aim of this study was to determine whether the endogenous PrRP neuronal system in the brain is involved in the central anorexigenic effect of the peripherally administered CCK agonist JMV236 or the CCK1 antagonist devazepide and whether the CCK system is involved in the central anorexigenic effect of the peripherally applied lipidized PrRP analog palm-PrRP31 in fasted lean mice. The effect of devazepide and JMV236 on the anorexigenic effects of palm-PrRP31 as well as devazepide combined with JMV236 and palm-PrRP31 on food intake and Fos cell activation in the PVN and caudal NTS was examined. Our results suggest that the anorexigenic effect of JMV236 is accompanied by activation of PrRP neurons of the NTS in a CCK1 receptor-dependent manner. Moreover, while the anorexigenic effect of palm-PrRP31 was not affected by JMV236, it was partially attenuated by devazepide in fasted mice. The present findings indicate that the exogenously influenced CCK system may be involved in the central anorexigenic effect of peripherally applied palm-PrRP31, which possibly indicates some interaction between the CCK and PrRP neuronal systems.

Pathophysiology of NAFLD and NASH in Experimental Models: The Role of Food Intake Regulating Peptides.

Obesity, diabetes, insulin resistance, sedentary lifestyle, and Western diet are the key factors underlying non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases in developed countries. In many cases, NAFLD further progresses to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and to hepatocellular carcinoma. The hepatic lipotoxicity and non-liver factors, such as adipose tissue inflammation and gastrointestinal imbalances were linked to evolution of NAFLD. Nowadays, the degree of adipose tissue inflammation was shown to directly correlate with the severity of NAFLD. Consumption of higher caloric intake is increasingly emerging as a fuel of metabolic inflammation not only in obesity-related disorders but also NAFLD. However, multiple causes of NAFLD are the reason why the mechanisms of NAFLD progression to NASH are still not well understood. In this review, we explore the role of food intake regulating peptides in NAFLD and NASH mouse models. Leptin, an anorexigenic peptide, is involved in hepatic metabolism, and has an effect on NAFLD experimental models. Glucagon-like peptide-1 (GLP-1), another anorexigenic peptide, and GLP-1 receptor agonists (GLP-1R), represent potential therapeutic agents to prevent NAFLD progression to NASH. On the other hand, the deletion of ghrelin, an orexigenic peptide, prevents age-associated hepatic steatosis in mice. Because of the increasing incidence of NAFLD and NASH worldwide, the selection of appropriate animal models is important to clarify aspects of pathogenesis and progression in this field.

Collective Modes in Excitonic Magnets: Dynamical Mean-Field Study.

We present a dynamical mean-field study of dynamical susceptibilities in the two-band Hubbard model. Varying the model parameters we analyze the two-particle excitations in the normal as well as in the ordered phase, an excitonic condensate. The two-particle dynamical mean-field theory spectra in the ordered phase reveal the gapless Goldstone modes arising from spontaneous breaking of continuous symmetries. We also observe the gapped Higgs mode, characterized by vanishing of the gap at the phase boundary. Qualitative changes observed in the spin susceptibility can be used as an experimental probe to identify the excitonic condensation.

Theoretical investigation of excitonic magnetism in LaSrCoO4.

We use the LDA+U approach to search for possible ordered ground states of LaSrCoO4. We find a staggered arrangement of magnetic multipoles to be stable over a broad range of Co 3d interaction parameters. This ordered state can be described as a spin-density-wave-type condensate of [Formula: see text] excitons carrying spin S = 1. Further, we construct an effective strong-coupling model, calculate the exciton dispersion and investigate closing of the exciton gap, which marks the exciton condensation instability. Comparing the layered LaSrCoO4 with its pseudo cubic analog LaCoO3, we find that for the same interaction parameters the excitonic gap is smaller (possibly vanishing) in the layered cobaltite.

Potential neuroprotective and anti-apoptotic properties of a long-lasting stable analog of ghrelin: an in vitro study using SH-SY5Y cells.

Neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are increasing in prevalence. Currently, there are no effective and specific treatments for these disorders. Recently, positive effects of the orexigenic hormone ghrelin on memory and learning were demonstrated in mouse models of AD and PD. In this study, we tested the potential neuroprotective properties of a stable and long-lasting ghrelin analog, Dpr(3)ghrelin (Dpr(3)ghr), in SH-SY5Y neuroblastoma cells stressed with 1.2 mM methylglyoxal (MG), a toxic endogenous by-product of glycolysis, and we examined the impact of Dpr(3)ghr on apoptosis. Pre-treatment with both 10(-5) and 10(-7) M Dpr(3)ghr resulted in increased viability in SH-SY5Y cells (determined by MTT staining), as well as reduced cytotoxicity of MG in these cells (determined by LDH assay). Dpr(3)ghr increased viability by altering pro-apoptotic and viability markers: Bax was decreased, Bcl-2 was increased, and the Bax/Bcl-2 ratio was attenuated. The ghrelin receptor GHS-R1 and Dpr(3)ghr-induced activation of PBK/Akt were immuno-detected in SH-SY5Y cells to demonstrate the presence of GHS-R1 and GHS-R1 activation, respectively. We demonstrated that Dpr(3)ghr protected SH-SY5Y cells against MG-induced neurotoxicity and apoptosis. Our data suggest that stable ghrelin analogs may be candidates for the effective treatment of neurodegenerative disorders.

Nontoxic combretafuranone analogues with high in vitro antibacterial activity.

A library of thirty two 3,4-diphenylfuranones related to both combretastatin A-4 and antifungal 5-(acyloxymethyl)-3-(halophenyl)-2,5-dihydrofuran-2-ones was prepared. Cytotoxic effects on a panel of cancer and normal cell lines and antiinfective activity were evaluated, and the data were complemented with tests for the activation of caspase 3 and 7. High cytotoxicity was observed in some of the halogenated analogues, eg. 3-(3,4-dichlorophenyl)-4-(4-methylphenyl)-2,5-dihydrofuran-2-one with IC50 0.12-0.23 µM, but the compounds were also highly toxic against non-malignant control cells. More importantly, notable antibacterial activity indicating G+ selectivity has been found in the 3,4-diarylfuranone class of compounds for the first time. Hydroxymethylation of furanone C5 knocked out cytotoxic effects (up to 40 µM) while maintaining significant activity against Staphylococcus strains in some derivatives. MIC95 of the most promising compound, 3-(4-bromophenyl)-5,5-bis(hydroxymethyl)-4-(4-methylphenyl)-2,5-dihydrofuran-2-one against S. aureus strain ATCC 6538 was 0.98 µM (0.38 µg/mL) and 3.9 µM (1.52 µg/mL) after 24 and 48 h, respectively.

Control of antiferromagnetic spin axis orientation in bilayer Fe/CuMnAs films.

Using x-ray magnetic circular and linear dichroism techniques, we demonstrate a collinear exchange coupling between an epitaxial antiferromagnet, tetragonal CuMnAs, and an Fe surface layer. A small uncompensated Mn magnetic moment is observed which is antiparallel to the Fe magnetization. The staggered magnetization of the 5 nm thick CuMnAs layer is rotatable under small magnetic fields, due to the interlayer exchange coupling. This allows us to obtain the x-ray magnetic linear dichroism spectra for different crystalline orientations of CuMnAs in the (001) plane. This is a key parameter for enabling the understanding of domain structures in CuMnAs imaged using x-ray magnetic linear dichroism microscopy techniques.

The role of food intake regulating peptides in cardiovascular regulation.

Obesity is a risk factor that worsens cardiovascular events leading to higher morbidity and mortality. However, the exact mechanisms of relation between obesity and cardiovascular events are unclear. Nevertheless, it has been demonstrated that pharmacological therapy for obesity has great potential to improve some cardiovascular problems. Therefore, it is important to determine the common mechanisms regulating both food intake and blood pressure. Several hormones produced by peripheral tissues work together with neuropeptides involved in the regulation of both food intake and blood pressure. Anorexigenic (food intake lowering) hormones such as leptin, glucagon-like peptide-1 and cholecystokinin cooperate with α-melanocyte-stimulating hormone, cocaine- and amphetamine-regulated peptide as well as prolactin-releasing peptide. Curiously their collective actions result in increased sympathetic activity, especially in the kidney, which could be one of the factors responsible for the blood pressure increases seen in obesity. On the other hand, orexigenic (food intake enhancing) peptides, especially ghrelin released from the stomach and acting in the brain, cooperates with orexins, neuropeptide Y, melanin-concentrating hormone and galanin, which leads to decreased sympathetic activity and blood pressure. This paradox should be intensively studied in the future. Moreover, it is important to know that the hypothalamus together with the brainstem seem to be major structures in the regulation of food intake and blood pressure. Thus, the above mentioned regions might be essential brain components in the transmission of peripheral signals to the central effects. In this short review, we summarize the current information on cardiovascular effects of food intake regulating peptides.

Field-induced exciton condensation in LaCoO3.

Motivated by recent observation of magnetic field induced transition in LaCoO3 we study the effect of external field in systems close to instabilities towards spin-state ordering and exciton condensation. We show that, while in both cases the transition can be induced by an external field, temperature dependencies of the critical field have opposite slopes. Based on this result we argue that the experimental observations select the exciton condensation scenario. We show that such condensation is possible due to high mobility of the intermediate spin excitations. The estimated width of the corresponding dispersion is large enough to overrule the order of atomic multiplets and to make the intermediate spin excitation propagating with a specific wave vector the lowest excitation of the system.

Spontaneous Spin Textures in Multiorbital Mott Systems.

Spin textures in k-space arising from spin-orbit coupling in noncentrosymmetric crystals find numerous applications in spintronics. We present a mechanism that leads to the appearance of k-space spin texture due to spontaneous symmetry breaking driven by electronic correlations. Using dynamical mean-field theory we show that doping a spin-triplet excitonic insulator provides a means of creating new thermodynamic phases with unique properties. The numerical results are interpreted using analytic calculations within a generalized double-exchange framework.

The influence of erythrocyte maturity on ion transport and membrane lipid composition in the rat.

Significant relationships between ion transport and membrane lipid composition (cholesterol, total phospholipids and sphingomyelins) were found in erythrocytes of salt hypertensive Dahl rats. In these animals mean cellular hemoglobin content correlated negatively with Na(+)-K(+) pump activity and Na(+) leak but positively with Na(+)-K(+) cotransport activity. Immature erythrocytes exhibit lower mean cellular hemoglobin content (MCHC) than mature ones. The aim of the present study was to find a relationship between erythrocyte maturity, membrane lipid composition and ion transport activity in Wistar rats aged three months which were subjected to repeated hemorrhage (blood loss 2 ml/day for 6 days) to enrich circulating erythrocytes with immature forms. Immature and mature erythrocyte fractions in control and hemorrhaged rats were separated by repeated centrifugation. Hemorrhaged rats had increased number of reticulocytes but reduced hematocrit and MCHC compared to control rats. Immature erythrocytes of hemorrhaged rats differed from mature ones of control animals by elevated Na(+)-K(+) pump activity, reduced Na(+)-K(+) cotransport activity and increased Rb(+) leak. These ion transport changes in immature erythrocytes were accompanied by higher concentration of total phospholipids in their cell membranes. Membrane phospholipid content correlated positively with Na(+)-K(+) pump activity and cation leaks but negatively with Na(+)-K(+) cotransport activity. Moreover, they were also negatively related with MCHC which correlated negatively with Na(+)-K(+) pump activity and Rb(+) leak but positively with Na(+)-K(+) cotransport activity. Thus certain abnormalities of erythrocyte ion transport and membrane lipid composition detected in hypertensive animals might be caused by higher incidence of immature cells.

Electrical switching of an antiferromagnet.

Antiferromagnets are hard to control by external magnetic fields because of the alternating directions of magnetic moments on individual atoms and the resulting zero net magnetization. However, relativistic quantum mechanics allows for generating current-induced internal fields whose sign alternates with the periodicity of the antiferromagnetic lattice. Using these fields, which couple strongly to the antiferromagnetic order, we demonstrate room-temperature electrical switching between stable configurations in antiferromagnetic CuMnAs thin-film devices by applied current with magnitudes of order 10(6) ampere per square centimeter. Electrical writing is combined in our solid-state memory with electrical readout and the stored magnetic state is insensitive to and produces no external magnetic field perturbations, which illustrates the unique merits of antiferromagnets for spintronics.

Epigenetics and a new look on metabolic syndrome.

The incidence of metabolic syndrome increases in the developed countries, therefore biomedical research is focused on the understanding of its etiology. The study of exact mechanisms is very complicated because both genetic and environmental factors contribute to this complex disease. The ability of environmental factors to promote phenotype changes by epigenetic DNA modifications (i.e. DNA methylation, histone modifications) was demonstrated to play an important role in the development and predisposition to particular symptoms of metabolic syndrome. There is no doubt that the early life, such as the fetal and perinatal periods, is critical for metabolic syndrome development and therefore critical for prevention of this disease. Moreover, these changes are visible not only in individuals exposed to environmental factors but also in the subsequent progeny for multiple generations and this phenomenon is called transgenerational inheritance. The knowledge of molecular mechanisms, by which early minor environmental stimuli modify the expression of genetic information, might be the desired key for the understanding of mechanisms leading to the change of phenotype in adulthood. This review provides a short overview of metabolic syndrome epigenetics.

Novel lipidized analogs of prolactin-releasing peptide have prolonged half-lives and exert anti-obesity effects after peripheral administration.

OBJECTIVES: Obesity is a frequent metabolic disorder but an effective therapy is still scarce. Anorexigenic neuropeptides produced and acting in the brain have the potential to decrease food intake and ameliorate obesity but are ineffective after peripheral application. We have designed lipidized analogs of prolactin-releasing peptide (PrRP), which is involved in energy balance regulation as demonstrated by obesity phenotypes of both PrRP- and PrRP-receptor-knockout mice. RESULTS: Lipidized PrRP analogs showed binding affinity and signaling in PrRP receptor-expressing cells similar to natural PrRP. Moreover, these analogs showed high binding affinity also to anorexigenic neuropeptide FF-2 receptor. Peripheral administration of myristoylated and palmitoylated PrRP analogs to fasted mice induced strong and long-lasting anorexigenic effects and neuronal activation in the brain areas involved in food intake regulation. Two-week-long subcutaneous administration of palmitoylated PrRP31 and myristoylated PrRP20 lowered food intake, body weight and improved metabolic parameters, and attenuated lipogenesis in mice with diet-induced obesity. CONCLUSIONS: Our data suggest that the lipidization of PrRP enhances stability and mediates its effect in central nervous system. Strong anorexigenic and body-weight-reducing effects make lipidized PrRP an attractive candidate for anti-obesity treatment.