Migratory birds are able to choose the appropriate migratory direction under dim yellow narrowband light.

Currently, it is generally assumed that migratory birds are oriented in the appropriate migratory direction under UV, blue and green light (short-wavelength) and are unable to use their magnetic compass in total darkness and under yellow and red light (long-wavelength). However, it has also been suggested that the magnetic compass has two sensitivity peaks: in the short and long wavelengths, but with different intensities. In this project, we aimed to study the orientation of long-distance migrants, pied flycatchers (Ficedula hypoleuca), under different narrowband light conditions during autumn and spring migrations. The birds were tested in the natural magnetic field (NMF) and a changed magnetic field (CMF) rotated counterclockwise by 120° under dim green (autumn) and yellow (spring and autumn) light, which are on the 'threshold' between the short-wavelength and long-wavelength light. We showed that pied flycatchers (i) were completely disoriented under green light both in the NMF and CMF but (ii) showed the migratory direction in the NMF and the appropriate response to CMF under yellow light. Our data contradict the results of previous experiments under narrowband green and yellow light and raise doubts about the existence of only short-wavelength magnetoreception. The parameters of natural light change dramatically in spectral composition and intensity after local sunset, and the avian magnetic compass should be adapted to function properly under such constantly changing light conditions.

Genotype-Phenotype Correlations in 293 Russian Patients with Causal Fabry Disease Variants.

BACKGROUND: Fabry disease (FD) is a rare hereditary multisystem disease caused by variants of the GLA gene. Determination of GLA gene variants and identification of genotype-phenotype correlations allow us to explain the features of FD associated with predominant damage of one or another system, both in the classical and atypical forms of FD, as well as in cases with late manifestation and involvement of one of the systems. METHODS: The study included 293 Russian patients with pathogenic variants of the GLA gene, which were identified as a result of various selective screening programs. Screening was carried out for 48,428 high-risk patients using a two-step diagnostic algorithm, including the determination of the concentration of the biomarker lyso-Gb3 as a first-tier test. Screening of atypical FD among patients with HCM was carried out via high-throughput sequencing in another 2427 patients. RESULTS: 102 (0.20%) cases of FD were identified among unrelated patients as a result of the study of 50,855 patients. Molecular genetic testing allowed us to reveal the spectrum and frequencies of 104 different pathogenic variants of the GLA gene in 293 examined patients from 133 families. The spectrum and frequencies of clinical manifestations in patients with FD, including 20 pediatric patients, were described. Correlations between the concentration of the lyso-Gb3 biomarker and the type of pathogenic variants of the GLA gene have been established. Variants identified in patients with early stroke were described, and the association of certain variants with the development of stroke was established. CONCLUSIONS: The results of a large-scale selective FD screening, as well as clinical and molecular genetic features, in a cohort of 293 Russian patients with FD are described.

Unravelling the Collective Calcium Dynamics of Physiologically Aged Astrocytes under a Hypoxic State In Vitro.

Astrocytes serve many functions in the brain related to maintaining nerve tissue homeostasis and regulating neuronal function, including synaptic transmission. It is assumed that astrocytes are crucial players in determining the physiological or pathological outcome of the brain aging process and the development of neurodegenerative diseases. Therefore, studies on the peculiarities of astrocyte physiology and interastrocytic signaling during aging are of utmost importance. Calcium waves are one of the main mechanisms of signal transmission between astrocytes, and in the present study we investigated the features of calcium dynamics in primary cultures of murine cortical astrocytes in physiological aging and hypoxia modeling in vitro. Specifically, we focused on the assessment of calcium network dynamics and the restructuring of the functional network architecture in primary astrocytic cultures. Calcium imaging was performed on days 21 ("young" astrocyte group) and 150 ("old" astrocyte group) of cultures' development in vitro. While the number of active cells and frequency of calcium events were decreased, we observed a reduced degree of correlation in calcium dynamics between neighboring cells, which was accompanied by a reduced number of functionally connected cells with fewer and slower signaling events. At the same time, an increase in the mRNA expression of anti-apoptotic factor Bcl-2 and connexin 43 was observed in "old" astrocytic cultures, which can be considered as a compensatory response of cells with a decreased level of intercellular communication. A hypoxic episode aggravates the depression of the connectivity of calcium dynamics of "young" astrocytes rather than that of "old" ones.

Novel Algorithm of Network Calcium Dynamics Analysis for Studying the Role of Astrocytes in Neuronal Activity in Alzheimer's Disease Models.

Accumulated experimental data strongly suggest that astrocytes play an important role in the pathogenesis of neurodegeneration, including Alzheimer's disease (AD). The effect of astrocytes on the calcium activity of neuron-astroglia networks in AD modelling was the object of the present study. We have expanded and improved our approach's capabilities to analyze calcium activity. We have developed a novel algorithm to construct dynamic directed graphs of both astrocytic and neuronal networks. The proposed algorithm allows us not only to identify functional relationships between cells and determine the presence of network activity, but also to characterize the spread of the calcium signal from cell to cell. Our study showed that Alzheimer's astrocytes can change the functional pattern of the calcium activity of healthy nerve cells. When healthy nerve cells were cocultivated with astrocytes treated with Aß42, activation of calcium signaling was found. When healthy nerve cells were cocultivated with 5xFAD astrocytes, inhibition of calcium signaling was observed. In this regard, it seems relevant to further study astrocytic-neuronal interactions as an important factor in the regulation of the functional activity of brain cells during neurodegenerative processes. The approach to the analysis of streaming imaging data developed by the authors is a promising tool for studying the collective calcium dynamics of nerve cells.

Access to the sky near the horizon and stars does not play a crucial role in compass calibration of European songbird migrants.

Migratory birds use different global cues including celestial and magnetic information to determine and maintain their seasonally appropriate migratory direction. A hierarchy among different compass systems in songbird migrants is still a matter for discussion owing to highly variable and apparently contradictory results obtained in various experimental studies. How birds decide whether and how they should calibrate their compasses before departure remains unclear. A recent 'extended unified theory' suggested that access to both a view of the sky near the horizon and stars during the cue-conflict exposure might be crucial for the results of cue-conflict experiments. In this study, we performed cue-conflict experiments in three European songbird species with different migratory strategies (garden warbler, Sylvia borin; pied flycatcher, Ficedula hypoleuca; and European robin, Erithacus rubecula; juveniles and adults; spring and autumn migrations) using a uniform experimental protocol. We exposed birds to the natural celestial cues in a shifted (120 deg clockwise/counterclockwise) magnetic field from sunset to the end of the nautical twilight and tested them in orientation cages immediately after cue-conflict treatments. None of the species (apart from adult robins) showed any sign of calibration even if they had access to a view of the sky and local surroundings near the horizon and stars during cue-conflict treatments. Based on results of our experiments and data from previous contradictory studies, we suggest that no uniform theory can explain why birds calibrate or do not calibrate their compass systems. Each species (and possibly even different populations) may choose its calibration strategy differently.

Ontogeny of the star compass in birds: pied flycatchers (Ficedula hypoleuca) can establish the star compass in spring.

The star compass of birds, like the sun compass, is not innate. To possess either of them, birds have to observe the rotating sky and determine its centre of rotation (in the case of the star compass) or the sun's movement (for the sun compass). Young birds are believed to learn how to use the star compass before their first migration, even though the evidence of this is lacking. Here, we tested whether hand-raised Pied flycatchers (Ficedula hypoleuca) that had not established the star compass prior to their first autumn migration can gain it later in their ontogeny, in spring. We also attempted to examine whether the observation of diurnal celestial cues (the sun and polarized light) prior to autumn migration would affect the process of star compass learning in spring. When tested in the vertical magnetic field under the natural starry sky, the group of birds that observed the stars in spring as the first celestial cues were able to choose the migratory direction. In contrast, the birds that had never seen the stars were not able to use the nightly celestial cues in the vertical magnetic field. However, birds that had seen the daytime celestial cues till autumn and the stars at spring were disoriented, although this might be due to the small sample size. Our data suggest the possibility that the star compass may be learned in spring and emphasize the necessity for further research into the interaction of celestial compasses.

Drop Drying on the Sensor: One More Way for Comparative Analysis of Liquid Media.

It is known that the processes of self-organization of the components of drying a liquid drop on a solid substrate are well reproduced under the same external conditions and are determined only by the composition and dispersion of the liquid. If the drop dries on the surface of the sensor device, these processes can be recorded and used as a passport characteristic of the liquid. The first half of the article is devoted to the description of the principles of the method and the proof of the validity of our assumptions. The second half of the article is devoted to the development of a user-friendly version of the device, where the change in the real and imaginary parts of the electrical impedance of the resonator was used as an informative parameter. The measure of the closeness of the relative positions of the hodographs of the compared samples on the complex plane is used as a criterion for the similarity-/-difference of various liquids. The design of a new sensor device and the results of its tests for distinguishing between different brands of alcoholic beverages and reconstituted milk of different concentrations are presented.

No evidence for the use of magnetic declination for migratory navigation in two songbird species.

Determining the East-West position was a classical problem in human sea navigation until accurate clocks were manufactured and sailors were able to measure the difference between local time and a fixed reference to determine longitude. Experienced night-migratory songbirds can correct for East-West physical and virtual magnetic displacements to unknown locations. Migratory birds do not appear to possess a time-different clock sense; therefore, they must solve the longitude problem in a different way. We showed earlier that experienced adult (but not juvenile) Eurasian reed warblers (Acrocephalus scirpaceus) can use magnetic declination (the difference in direction between geographic and magnetic North) to solve this problem when they were virtually displaced from Rybachy on the eastern Baltic coast to Scotland. In this study, we aimed to test how general this effect was. Adult and juvenile European robins (Erithacus rubecula) and adult garden warblers (Sylvia borin) under the same experimental conditions did not respond to this virtual magnetic displacement, suggesting significant variation in how navigational maps are organised in different songbird migrants.

Magnetic compass of garden warblers is not affected by oscillating magnetic fields applied to their eyes.

The magnetic compass is an important element of the avian navigation system, which allows migratory birds to solve complex tasks of moving between distant breeding and wintering locations. The photochemical magnetoreception in the eye is believed to be the primary biophysical mechanism behind the magnetic sense of birds. It was shown previously that birds were disoriented in presence of weak oscillating magnetic fields (OMF) with frequencies in the megahertz range. The OMF effect was considered to be a fingerprint of the photochemical magnetoreception in the eye. In this work, we used miniaturized portable magnetic coils attached to the bird's head to specifically target the compass receptor. We performed behavioural experiments on orientation of long-distance migrants, garden warblers (Sylvia borin), in round arenas. The OMF with the amplitude of about 5 nT was applied locally to the birds' eyes. Surprisingly, the birds were not disoriented and showed the seasonally appropriate migratory direction. On the contrary, the same birds placed in a homogeneous 5 nT OMF generated by large stationary coils showed clear disorientation. On the basis of these findings, we suggest that the disruption of magnetic orientation of birds by oscillating magnetic fields is not related to photochemical magnetoreceptors in their eyes.

Magnetic map navigation in a migratory songbird requires trigeminal input.

Recently, virtual magnetic displacement experiments have shown that magnetic cues are indeed important for determining position in migratory birds; but which sensory system(s) do they use to detect the magnetic map cues? Here, we show that Eurasian reed warblers need trigeminal input to detect that they have been virtually magnetically displaced. Birds with bilaterally ablated ophthalmic branches of the trigeminal nerves were not able to re-orient towards their conspecific breeding grounds after a virtual magnetic displacement, exactly like they were not able to compensate for a real physical displacement. In contrast, sham-operated reed warblers re-oriented after the virtual displacement, like intact controls did in the past. Our results show that trigeminally mediated sensory information is necessary for the correct function of the reed warblers' magnetic positioning system.

Migratory Eurasian Reed Warblers Can Use Magnetic Declination to Solve the Longitude Problem.

The longitude problem (determining east-west position) is a classical problem in human sea navigation. Prior to the use of GPS satellites, extraordinarily accurate clocks measuring the difference between local time and a fixed reference (e.g., GMT) [1] were needed to determine longitude. Birds do not appear to possess a time-difference clock sense [2]. Nevertheless, experienced night-migratory songbirds can correct for east-west displacements to unknown locations [3-9]. Consequently, migratory birds must solve the longitude problem in a different way, but how they do so has remained a scientific mystery [10]. We suggest that experienced adult Eurasian reed warblers (Acrocephalus scirpaceus) can use magnetic declination to solve the longitude problem at least under some circumstances under clear skies. Experienced migrants tested during autumn migration in Rybachy, Russia, were exposed to an 8.5° change in declination while all other cues remained unchanged. This corresponds to a virtual magnetic displacement to Scotland if and only if magnetic declination is a part of their map. The adult migrants responded by changing their heading by 151° from WSW to ESE, consistent with compensation for the virtual magnetic displacement. Juvenile migrants that had not yet established a navigational map also oriented WSW at the capture site but became randomly oriented when the magnetic declination was shifted 8.5°. In combination with latitudinal cues, which birds are known to detect and use [10-12], magnetic declination could provide the mostly east-west component for a true bi-coordinate navigation system under clear skies for experienced migratory birds in some areas of the globe.

Very weak oscillating magnetic field disrupts the magnetic compass of songbird migrants.

Previously, it has been shown that long-distance migrants, garden warblers (Sylvia borin), were disoriented in the presence of narrow-band oscillating magnetic field (1.403 MHz OMF, 190 nT) during autumn migration. This agrees with the data of previous experiments with European robins (Erithacus rubecula). In this study, we report the results of experiments with garden warblers tested under a 1.403 MHz OMF with various amplitudes (∼0.4, 1, ∼2.4, 7 and 20 nT). We found that the ability of garden warblers to orient in round arenas using the magnetic compass could be disrupted by a very weak oscillating field, such as an approximate 2.4, 7 and 20 nT OMF, but not by an OMF with an approximate 0.4 nT amplitude. The results of the present study indicate that the sensitivity threshold of the magnetic compass to the OMF lies around 2-3 nT, while in experiments with European robins the birds were disoriented in a 15 nT OMF but could choose the appropriate migratory direction when a 5 nT OMF was added to the stationary magnetic field. The radical-pair model, one of the mainstream theories of avian magnetoreception, cannot explain the sensitivity to such a low-intensity OMF, and therefore, it needs further refinement.

Bacterial etiology of acute otitis media and characterization of pneumococcal serotypes and genotypes among children in Moscow, Russia.

BACKGROUND: We aimed to describe bacterial etiology of acute otitis media (AOM) and characterize resistance, serotypes and genotype profiles of AOM-causing pneumococci recovered in Moscow children. METHODS: Children with AOM and an available middle ear fluid specimen were prospectively enrolled in this study. Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae and Moraxella catarrhalis were considered as true otopathogens. All pneumococcal isolates were serotyped using the Quellung reaction; multidrug-resistant (MDR) pneumococci underwent multilocus sequence typing. RESULTS: In 172 of 541 enrolled AOM patients (32%) at least 1 otopathogen was recovered, with S. pneumoniae having the highest rate of 63% (109/172). When adjusted for antibiotic treatment before sampling, in untreated patients the rate of culture-positive AOM was 35% (124/352), S. pneumoniae had a prevalence of 69% (86/124), S. pyogenes 19% (24/124), H. influenzae 13% (16/124) and M. catarrhalis 9% (11/124). Among 107 examined pneumococci, 45% were penicillin-nonsusceptible, 34 and 30% were resistant to erythromycin and clindamycin, respectively; 30% had an MDR phenotype, but no amoxicillin-resistant isolates were found. Ten of 32 (31%) MDR pneumococci related to clonal complex 320, the remaining isolates belonged to 7 different clonal complex. Six leading serotypes were 19F (27%), 3 (12%), 6B (11%), 14 (11%), 19A (9%) and 23F (8%); overall polysaccharide conjugate vaccine13 coverage was 93%. CONCLUSIONS: S. pneumoniae, the leading bacterial AOM pathogen in Moscow children, is characterized by a substantial rate of antibiotic nonsusceptibility and clonality. A polysaccharide conjugate vaccine with expanded coverage seems to fit the current AOM pneumococcal serotype distribution in Russia better.

Magnetic orientation of garden warblers (Sylvia borin) under 1.4 MHz radiofrequency magnetic field.

We report on the experiments on orientation of a migratory songbird, the garden warbler (Sylvia borin), during the autumn migration period on the Courish Spit, Eastern Baltics. Birds in experimental cages, deprived of visual information, showed the seasonally appropriate direction of intended flight with respect to the magnetic meridian. Weak radiofrequency (RF) magnetic field (190 nT at 1.4 MHz) disrupted this orientation ability. These results may be considered as an independent replication of earlier experiments, performed by the group of R. and W. Wiltschko with European robins (Erithacus rubecula). Confirmed outstanding sensitivity of the birds' magnetic compass to RF fields in the lower megahertz range demands for a revision of one of the mainstream theories of magnetoreception, the radical-pair model of birds' magnetic compass.

Molecular characteristics of patients with glycosaminoglycan storage disorders in Russia.

BACKGROUND: The mucopolysaccharidoses (MPSs) are rare genetic disorders caused by mutations in lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). In this study, we analyzed a total of 48 patients including MPSI (n=6), MPSII (n=18), MPSIIIA (n=11), MPSIVA (n=3), and MPSVI (n=10). METHODS: In MPS patients, urinary GAGs were colorimetrically assayed. Enzyme activity was quantified by colorimetric and fluorimetric assays. To find mutations, all IDUA, IDS, SGSH, GALNS, and ARSB exons and intronic flanks were sequenced. New mutations were functionally assessed by reconstructing mutant alleles with site-directed mutagenesis followed with expression of wild-type and mutant genetic variants in CHO cells, measuring enzymatic activity, and Western blot analysis of protein expression of normal and mutated enzymes in cell lysates. RESULTS: A total of five novel mutations were found including p.Asn348Lys (IDUA) in MPSI, p.Tyr240Cys (GALNS) in MPSIVA, and three ARSB mutations (p.Gln110*, p.Asn262Lysfs*14, and pArg315*) in MPSVI patients. In case of mutations p.Asn348Lys, p.Asn262Lysfs*14, and p.Gln110*, no mutant protein was detected while activity of the mutant protein was <1% of that of the normal enzyme. For p.Tyr240Cys, a trace of mutant protein was observed with a remnant activity of 3.6% of the wild-type GALNS activity. For pArg315*, a truncated 30-kDa protein that had 7.9% of activity of the normal ARSB was detected. CONCLUSIONS: These data further enrich our knowledge of the genetic background of MPSs.