Identification of erythroferrone as an erythroid regulator of iron metabolism.

Recovery from blood loss requires a greatly enhanced supply of iron to support expanded erythropoiesis. After hemorrhage, suppression of the iron-regulatory hormone hepcidin allows increased iron absorption and mobilization from stores. We identified a new hormone, erythroferrone (ERFE), that mediates hepcidin suppression during stress erythropoiesis. ERFE is produced by erythroblasts in response to erythropoietin. ERFE-deficient mice fail to suppress hepcidin rapidly after hemorrhage and exhibit a delay in recovery from blood loss. ERFE expression is greatly increased in Hbb(th3/+) mice with thalassemia intermedia, where it contributes to the suppression of hepcidin and the systemic iron overload characteristic of this disease

The calcilytic agent NPS 2143 rectifies hypocalcemia in a mouse model with an activating calcium-sensing-receptor (CaSR) mutation:relevance to autosomal dominant hypocalcemia type 1 (ADH1)

Autosomal dominant hypocalcemia type 1 (ADH1) is caused by germline gain-of-function mutations of the calcium-sensing receptor (CaSR) and may lead to symptomatic hypocalcemia, inappropriately low serum parathyroid hormone (PTH) concentrations and hypercalciuria. Negative allosteric CaSR modulators, known as calcilytics, have been shown to normalise the gain-of-function associated with ADH-causing CaSR mutations in vitro and represent a potential targeted therapy for ADH1. However, the effectiveness of calcilytic drugs for the treatment of ADH1-associated hypocalcemia remains to be established. We have investigated NPS 2143, a calcilytic compound, for the treatment of ADH1 by in vitro and in vivo studies involving a mouse model, known as Nuf, which harbors a gain-of-function CaSR mutation, Leu723Gln. Wild-type (Leu723) and Nuf mutant (Gln723) CaSRs were expressed in HEK293 cells and the effect of NPS 2143 on their intracellular calcium responses determined by flow cytometry. NPS 2143 was also administered as a single intraperitoneal bolus to wild-type and Nuf mice and plasma concentrations of calcium and PTH, and urinary calcium excretion measured. In vitro administration of NPS 2143 decreased the intracellular calcium responses of HEK293 cells expressing the mutant Gln723 CaSR in a dose-dependent manner, thereby rectifying the gain-of-function associated with the Nuf mouse CaSR mutation. Intraperitoneal injection of NPS 2143 in Nuf mice led to significant increases in plasma calcium and PTH without elevating urinary calcium excretion. These studies of a mouse model with an activating CaSR mutation demonstrate NPS 2143 to normalize the gain-of-function causing ADH1, and improve the hypocalcemia associated with this disorder

Sleep has no critical role in implicit motor sequence learning in young and old adults

The influence of sleep on motor skill consolidation has been a research topic of increasing interest. In this study we distinguished general skill learning from sequence-specific learning in a probabilistic implicit sequence learning task (Alternating Serial Reaction Time) in young and old adults before and after a 12-hour offline interval which did or did not contain sleep (pm-am and am-pm groups respectively). The results showed that general skill learning, as assessed via overall RT, improved offline in both the young and older groups, with the young group improving more than the old. However, the improvement was not sleep-dependent, in that there was no difference between the am-pm and pm-am groups. We did not find sequence-specific offline improvement in either age group for either the am-pm or pm-am groups, suggesting that consolidation of this kind of implicit motor sequence learning may not be influenced by sleep

Advanced prevention against icing on high voltage power lines

Historical meteorological data indicates, that our weather is becoming more and more extreme. For the electrical utility operators (Distribution System Operators - DSOs and Transmission System Operators - TSOs), these changes arise in new operation challenges that need to be addressed. For example, frequent icing phenomenon affects all the components of the power line by a significant mechanical overload: it endangers the conductors, the insulators and the towers, as well. The result is often fatal and beside serious failures, it effects on operators’ decisions. These not only endanger the reliability of electrical grids by the loss of a power line for weeks or even months, but in general, the safety in the surroundings of the power line. As technology advances, we will be able to collected, analyses and predict very large databases in the field of meteorology and electrical engineering. The ability of processing mentioned data, combined with know-how results in the capacity to operate power lines at their thermal limits during different ambient parameters. This technology called Dynamic Line Rating (DLR) – is not only a great way to increase the transmission capacity of a given line, but can also be effectively used to prevent, or even solve icing-related issues. Higher currents result in higher Joule-heats, that consequently heat the conductors. If limits can be reached or approached, icing can be prevented. If prevention is not possible, detection and removal of ice layer is necessary. The proper handling of this icing issues, requires advanced algorithms (expert systems) and reliable measuring equipment. The combination and synchronization between algorithms, weather service and measuring equipment is the key of the successful operation. An EU H2020 financed project called FLEXITRANSTORE has just been launched to develop a cross-country co-operation, with objective to improve anti-icing and de-icing solutions. To establish and analyse different solutions, the project includes several universities, TSOs and DSOs. To solve mentioned icing issues Budapest University of Technology and Economics’ (BME) developed an advanced neural-network based algorithm which use OTLM system. It is planned to install and demonstrate the capabilities of this new technology on the DSOs grid (Electro Ljubljana - ELJ). Besides the introduction of DLR and icing, this paper also focuses on the preparation/organisation of co-operation between different companies and universities

Canine Saliva as a Possible Source of Antimicrobial Resistance Genes

While the One Health issues of intensive animal farming are commonly discussed, keeping companion animals is less associated with the interspecies headway of antimicrobial resistance. With the constant advance in veterinary standards, antibiotics are regularly applied in companion animal medicine. Due to the close coexistence of dogs and humans, dog bites and other casual encounters with dog saliva (e.g., licking the owner) are common. According to our metagenome study, based on 26 new generation sequencing canine saliva datasets from 2020 and 2021 reposited in NCBI SRA by The 10,000 Dog Genome Consortium and the Broad Institute within Darwin's Ark project, canine saliva is rich in bacteria with predictably transferable antimicrobial resistance genes (ARGs). In the genome of potentially pathogenic Bacteroides, Capnocytophaga, Corynebacterium, Fusobacterium, Pasteurella, Porphyromonas, Staphylococcus and Streptococcus species, which are some of the most relevant bacteria in dog bite infections, ARGs against aminoglycosides, carbapenems, cephalosporins, glycylcyclines, lincosamides, macrolides, oxazolidinone, penams, phenicols, pleuromutilins, streptogramins, sulfonamides and tetracyclines could be identified. Several ARGs, including ones against amoxicillin-clavulanate, the most commonly applied antimicrobial agent for dog bites, were predicted to be potentially transferable based on their association with mobile genetic elements (e.g., plasmids, prophages and integrated mobile genetic elements). According to our findings, canine saliva may be a source of transfer for ARG-rich bacteria that can either colonize the human body or transport ARGs to the host bacteriota, and thus can be considered as a risk in the spread of antimicrobial resistance.European Union's Horizon 2020 research and innovation program [874735]The research was supported by the European Union's Horizon 2020 research and innovation program under Grant Agreement No. 874735 (VEO)

Full characterization of vibrational coherence in a porphyrin chromophore by two-dimensional electronic spectroscopy

In this work we present experimental and calculated two-dimensional electronic spectra for a 5,15-bisalkynyl porphyrin chromophore. The lowest energy electronic Qy transition couples mainly to a single 380 cm–1 vibrational mode. The two-dimensional electronic spectra reveal diagonal and cross peaks which oscillate as a function of population time. We analyze both the amplitude and phase distribution of this main vibronic transition as a function of excitation and detection frequencies. Even though Feynman diagrams provide a good indication of where the amplitude of the oscillating components are located in the excitation-detection plane, other factors also affect this distribution. Specifically, the oscillation corresponding to each Feynman diagram is expected to have a phase that is a function of excitation and detection frequencies. Therefore, the overall phase of the experimentally observed oscillation will reflect this phase dependence. Another consequence is that the overall oscillation amplitude can show interference patterns resulting from overlapping contributions from neighboring Feynman diagrams. These observations are consistently reproduced through simulations based on third order perturbation theory coupled to a spectral density described by a Brownian oscillator model

Orbital Magnetism and Current Distribution of Two-Dimensional Electrons under Confining Potential

The spatial distribution of electric current under magnetic field and the resultant orbital magnetism have been studied for two-dimensional electrons under a harmonic confining potential V(\vecvar{r})=m \omega_0^2 r^2/2 in various regimes of temperature and magnetic field, and the microscopic conditions for the validity of Landau diamagnetism are clarified. Under a weak magnetic field (\omega_c\lsim\omega_0, \omega_c being a cyclotron frequency) and at low temperature (T\lsim\hbar\omega_0), where the orbital magnetic moment fluctuates as a function of the field, the currents are irregularly distributed paramagnetically or diamagnetically inside the bulk region. As the temperature is raised under such a weak field, however, the currents in the bulk region are immediately reduced and finally there only remains the diamagnetic current flowing along the edge. At the same time, the usual Landau diamagnetism results for the total magnetic moment. The origin of this dramatic temperature dependence is seen to be in the multiple reflection of electron waves by the boundary confining potential, which becomes important once the coherence length of electrons gets longer than the system length. Under a stronger field (\omega_c\gsim\omega_0), on the other hand, the currents in the bulk region cause de Haas-van Alphen effect at low temperature as T\lsim\hbar\omega_c. As the temperature gets higher (T\gsim\hbar\omega_c) under such a strong field, the bulk currents are reduced and the Landau diamagnetism by the edge current is recovered.Comment: 15 pages, 11 figure

Gravity-mode period spacings as seismic diagnostic for a sample of gamma Doradus stars from Kepler space photometry and high-resolution ground-based spectroscopy

Gamma Doradus stars (hereafter gamma Dor stars) are gravity-mode pulsators of spectral type A or F. Such modes probe the deep stellar interior, offering a detailed fingerprint of their structure. Four-year high-precision space-based Kepler photometry of gamma Dor stars has become available, allowing us to study these stars with unprecedented detail. We selected, analysed, and characterized a sample of 67 gamma Dor stars for which we have Kepler observations available. For all the targets in the sample we assembled high-resolution spectroscopy to confirm their F-type nature. We found fourteen binaries, among which four single-lined binaries, five double-lined binaries, two triple systems and three binaries with no detected radial velocity variations. We estimated the orbital parameters whenever possible. For the single stars and the single-lined binaries, fundamental parameter values were determined from spectroscopy. We searched for period spacing patterns in the photometric data and identified this diagnostic for 50 of the stars in the sample, 46 of which are single stars or single-lined binaries. We found a strong correlation between the spectroscopic vsini and the period spacing values, confirming the influence of rotation on gamma Dor-type pulsations as predicted by theory. We also found relations between the dominant g-mode frequency, the longest pulsation period detected in series of prograde modes, vsini, and log Teff.Comment: 61 pages, 61 figures, 6 tables, accepted for publication in ApJ

Two-Dimensional Spectroscopy of Extended Molecular Systems: Applications to Energy Transport and Relaxation in an α-Helix

A simulation study of the coupled dynamics of amide I and amide II vibrations in an α-helix dissolved in water shows that two-dimensional (2D) infrared spectroscopy may be used to disentangle the energy transport along the helix through each of these modes from the energy relaxation between them. Time scales for both types of processes are obtained. Using polarization-dependent 2D spectroscopy is an important ingredient in the method we propose. The method may also be applied to other two-band systems, both in the infrared (collective vibrations) and the visible (excitons) parts of the spectrum.