Association between Ultradian Rhythms of Body Temperature in Small Mammals and Earth's Crust Stress.

Association was assessed between the data harvested by a long-baseline laser interference deformograph and the dynamics of body temperature (BT) in hamsters deprived of natural daily light-darkness changes. The power spectral data revealed the positive correlation between simultaneous time series of hamster BT and the Earth's crust deformation (ECD). The superposed epoch analysis established an association between abrupt upstrokes of hamster BT and ECD increments. Thus, the direct relationships between BT dynamics (reflecting predominance of sympathetic part of autonomic nervous system) and ECD (according to long-baseline laser interference deformography) were established. The study observed synchronization of the free-running circadian rhythm of hamster BT with the tidal stress in Earth's lithosphere. Further studies are needed to find the physical factor underlying the revealed relationships.

Inside and outside of virus-like particles HBc and HBc/4M2e: A comprehensive study of the structure.

Hepatitis B virus core antigen (HBc) with the insertion of four external domains of the influenza A M2 protein (HBc/4M2e) form virus-like particles whose structure was studied using a combination of molecular modeling and cryo-electron microscopy (cryo-EM). It was also shown that self-assembling of the particles occurs inside bacterial cells, but despite the big inner volume of the core shell particle, purified HBc/4M2e contain an insignificant amount of bacterial proteins. It was shown that a fragment of the M2e corresponding to 4M2e insertion is prone to formation of amyloid-like fibrils. However, as the part of the immunodominant loop, M2e insertion does not show a tendency to intermolecular interaction. A full-atomic HBc-4M2e model with the resolution of about 3 Å (3.13 Å for particles of Т = 4 symmetry, 3.7 Å for particles of Т = 3 symmetry) was obtained by molecular modeling methods based on cryo-EM data.

[Interferon gamma in the treatment of patients with moderate COVID-19].

INTRODUCTION: Interferons are produced in response to the presence of pathogens in cells and are responsible for the proper formation of immune reaction. Preliminary data obtained in studies of properties of recombinant interferon gamma (IFN-γ) that involved patients with community-acquired pneumonia (including bacterial), acute respiratory viral infection (ARVI), influenza and new coronavirus infection have shown promising results.The purpose of the study was to assess the effect of subcutaneous administration of IFN-γ in patients with viral pneumonia on the changes of vital signs and the duration of hospital stay. MATERIAL AND METHODS: An open-label, randomized, low-interventional study included patients with moderate new coronavirus infection COVID-19 over 18 years of age of both sexes. IFN-γ 500,000 IU was administered s/c, daily, once a day, during 5 days. RESULTS: IFN-y in addition to complex therapy of the disease resulted in more favorable changes in the stabilization of vital signs, as well as in reduced length of fever and hospital stay by 2 days what allows suggesting a positive effect of this substance on the recovery processes in patients with moderate COVID-19. Special emphasis should be made to the fact that patients who received recombinant IFN- γ experienced no progression of respiratory failure and required no transfer to intensive care unit. DISCUSSION: This study confirms earlier obtained data on the positive effect of IFN-y on the rate of clinical stabilization and recovery of patients with community-acquired pneumonia and viral infections. Presented results are limited to a small number of patients; further study of drug properties in post-marketing studies is required. CONCLUSION: Progress in the treatment of patients with moderate COVID-19 by adding recombinant IFN-γ to the complex therapy may reasonably expand the range of existing treatment options for this infection.

Three-Dimensional Structure of Cytochrome c Nitrite Reductase As Determined by Cryo-Electron Microscopy.

The structure of cytochrome c nitrite reductase from the bacterium Thioalkalivibrio nitratireducens was determined by cryo-electron microscopy (cryo-EM) at a 2.56 Å resolution. Possible structural heterogeneity of the enzyme was assessed. The backbone and side-chain orientations in the cryo-EM-based model are, in general, similar to those in the high-resolution X-ray diffraction structure of this enzyme.

[Barotherapy in the military medicine].

Barotherapy in the military medicine. The authors present current data on place and role of hyperbaric oxygenation for military and extreme medicine. Main mechanisms of oxygen saturation and its <> to cells and tissues of the organisms is described in the given article. The authors proved advantages of the hyperbaric oxygenation over the normobaric and showed its high efficiency for the trauma and suppurative- septic lesion treatment, and for the combat therapeutic pathology. Main clinical and physiological effects of the hyperbaric oxygenation are showed. Modern indications and contra-indications for the use of the hyperbaric oxygenation as a therapeutic mean are proved.

Topology of mRNA chain in isolated eukaryotic double-row polyribosomes.

In the process of protein synthesis, the translating ribosomes of eukaryotic cells form polyribosomes that are found to be multiplex functional complexes possessing elements of ordered spatial organization. As revealed by a number of electron microscopy studies, the predominant visible configurations of the eukaryotic polyribosomes are circles (circular polyribosomes) and two-stranded formations (so-called double-row polyribosomes). The "long" (i.e. heavy loaded) polyribosomes are usually represented by double-row structures, which can be interpreted as either topologically circular ("collapsed rings"), or topologically linear (zigzags or helices). In the present work we have analyzed the mRNA path within the eukaryotic polyribosomes, isolated from a wheat germ cell-free translation system, by integrating two approaches: the visualization of mRNA ends in polyribosomes by marking them with gold nanoparticles (3'-end) and initiating 40S subunits (5'-end), as well as by the cryoelectron tomography. Examination of the location of the mRNA markers in polyribosomes and mutual orientation of ribosomes in them has shown that the double-row polyribosomes of the same sample can have both circular and linear arrangements of their mRNA.

A structural view of translation initiation in bacteria.

The assembly of the protein synthesis machinery occurs during translation initiation. In bacteria, this process involves the binding of messenger RNA(mRNA) start site and fMet-tRNA(fMet) to the ribosome, which results in the formation of the first codon-anticodon interaction and sets the reading frame for the decoding of the mRNA. This interaction takes place in the peptidyl site of the 30S ribosomal subunit and is controlled by the initiation factors IF1, IF2 and IF3 to form the 30S initiation complex. The binding of the 50S subunit and the ejection of the IFs mark the irreversible transition to the elongation phase. Visualization of these ligands on the ribosome has been achieved by cryo-electron microscopy and X-ray crystallography studies, which has helped to understand the mechanism of translation initiation at the molecular level. Conformational changes associated with different functional states provide a dynamic view of the initiation process and of its regulation.

Differential control of cortical activity by the basal forebrain in rats: a role for both cholinergic and inhibitory influences.

Using microdialysis and high-performance liquid chromatography, we measured acetylcholine (ACh) release simultaneously from two cortical sites in anesthetized rats. One site was always in the somatosensory cortex, and the other was in either the visual or the motor cortex. After baseline measurements were obtained, selected sites in the basal forebrain (BF) were stimulated to increase ACh release. Some BF sites provoked more release in one microdialysis probe than in the other, suggesting some degree of corticotropic organization of the cholinergic projections from the BF. BF sites optimal for release from the visual cortex were separated from optimal sites for release from the somatosensory cortex by greater distances than were the best sites for release from the somatosensory and the motor cortex. Stimulation of a single BF site often provoked similar release from the latter two cortical areas. Electrical stimulation of the BF also modified cortical neuronal activity. Activation of some BF sites provoked an intense discharge of many neurons in the vicinity of the cortical recording electrode, and the same stimulus site in the BF provoked release of large amounts of ACh in the cortex. Stimulation of other BF sites produced strong inhibition of ongoing cortical activity and no increase in cortical ACh release. When other sites were stimulated, they had no effect or they generated stereotyped bursting patterns in the cortex without any observable effect on ACh release. BF sites that generated inhibition of cortical neural activity were generally located near the sites that activated the cortex and provoked release of ACh. These data suggest an elaborate control of the sensory cortex by a mechanism involving both gamma-aminobutyric acid-containing and cholinergic neurons of the BF.

Correlating cytoarchitecture and function in cat primary somatosensory cortex: the challenge of individual differences.

Principles of organization for the primary somatosensory cortex are generalizations derived by examining data obtained in different individuals. The manner in which these data are combined influences the conclusions derived. We found the line representing the widest anteroposterior distance across the sigmoid gyrus to be a useful reference in the cat somatosensory cortex for combining and comparing electrophysiological and cytoarchitectonic data from different individuals when we constructed cytoarchitectonic and functional maps of the bank of the medial ansate sulcus; maps prepared from combined data sets had boundaries similar to those found among individuals. Nevertheless, we argue that, for reasons inherent to the nature of the cerebral hemispheres and cortical maps, such references will never allow combinations of data capable of defining a unique high resolution prototypical map of individual body parts; the somatotopic order of body representations is, as are certain other attributes of somatosensory cortex, idiosyncratic. The genetic, developmental and use-dependent reasons for this situation are discussed.

The effects of peripheral deafferentation on spontaneously bursting neurons in the somatosensory cortex of waking cats.

Single neurons (n = 356) were studied in the forelimb representation of awake, quietly resting cats. Thirty-five spontaneously bursting neurons in a sample of 206 cells recorded before forelimb deafferentation were compared to 39 spontaneously bursting neurons in a sample of 127 neurons studied 1-3 weeks after deafferentation. The probability of encountering bursting neurons increased significantly following deafferentation from 17% to 31% of the sample (P < 0.005). The same 5 classes of bursting cells were observed after deafferentation but there were significant changes in the duration of interspike intervals in some classes, in the probability of observing certain classes, and in the proportion of spikes found in bursts. The probability of encountering class III cells, a class thought to consist primarily of non-inactivating pyramidal burst neurons, nearly doubled and the average interspike interval length within the burst increased from 1.9 to 3.0 ms. The burst structure in the other classes did not change but they were found less frequently. These other classes may include inhibitory interneurons which receive less excitatory drive after deafferentation and therefore provide less inhibition to class III cells. The differential behavior of the different classes of bursting cells may be one reason why the overall level of spontaneous activity does not change after deafferentation and it suggests that there are homeostatic mechanisms in primary somatosensory cortex that maintain a certain level of neural activity.

Recognition of temporally structured activity in spontaneously discharging neurons in the somatosensory cortex in waking cats.

We describe a method to automate the detection and analysis of structured neuronal activity obtained in relatively non-restrictive experiments in awake animals. Several different, regularly occurring, discharge patterns consisting of groups of spikes were identified in extracellular recordings from the somatosensory cortex of awake cats. The introduction of an interspike interval threshold made it possible to segregate these bursts from single spikes. The threshold interval was obtained from the modal interval in high-resolution autocorrelograms (up to 0.1 ms/bin) of the spontaneous neural activity. Single spikes were those separated by intervals greater than the threshold, while those within the group were of less than threshold value. When intervals were arranged and averaged according to their order of occurrence within the burst, four distinctive burst patterns were observed. These four patterns occurred in both normal and deafferented cortex and we believe them to be characteristic of particular cell types, a feature that will be useful for studying such cells in intact cellular networks.

The bgl1 gene of Trichoderma reesei QM 9414 encodes an extracellular, cellulose-inducible beta-glucosidase involved in cellulase induction by sophorose.

We have investigated the effect of disruption of the bgl1-(beta-glucosidase l-encoding) gene of Trichoderma reesei on the formation of other beta-glucosidase activities and on the induction of cellulases. To this end the bgl1 locus was disrupted by insertion of the Aspergillus nidulans amdS (acetamidase-encoding) gene. The bgl1-disrupted strain did not produce the 75 kDa extracellular beta-glucosidase on cellulose or lactose, but still formed beta-glucosidase activity on glucose, cellobiose, xylan or beta-1,3-glucan, suggesting that the enzyme(s) exhibiting this beta-glucosidase activity is (are) not encoded by bgl1. The cellulase-inducer sophorose induced the bgl1-encoded beta-glucosidase, whereas the remaining beta-glucosidase activity was induced by methyl-beta-D-glucoside. The bgl1-gene product was mainly secreted into the medium, whereas the other beta-glucosidase activity was mainly associated with the cells. A bgl1-multicopy strain formed higher amounts of cellulases than the parent strain. Nonsaturating concentrations of sophorose efficiently induced cellobiohydrolase l formation in the bgl1-multicopy strain, but less efficiently in the bgl1-disrupted strain. The multicopy strain and the parent strain were comparably efficient at saturating sophorose concentrations. The beta-glucosidase inhibitor nojirimycin strongly inhibited induction in all strains. These data suggest that the bgl1-encoded beta-glucosidase is not identical to the plasma-membrane-bound, constitutive, methyl-beta-glucoside inducible beta-glucosidase, but represents an extracellular cellulose-induced enzyme. Both enzymes contribute to rapid induction of cellulases by modifying the inducer sophorose.

Significance of the interstimulus time interval in repeating combined presentations of L-glutamate and acetylcholine for change in the reactivity of cortical neurons.

A comparative study of the probability, directionally, and intensity of the changes in the baseline and L-glutamate (Gl)- and acetylcholine(ACh)-induced average frequency of the impulse activity (BIA, GlIA, and AChIA, respectively) of individual neurons of the sensorimotor cortex of unanesthetized rats in the course of repeated isolated and combined presentations of Gl and ACh showed that the process of reduction in reactivity to Gl is slowed in the population of cells which experienced the combined action of Gl and ACh with a 1.5 second postponement of applications of ACh in comparison with the situation of its isolated and combined presentation with a 3 second postponement of ACh. The AChIA decreases to a greater degree in the case of a 3 second postponement of ACh, and the probability of an increase in BIA is less than with the isolated application of ACh. It is concluded that the character of the dynamics of the reactivity of neurons is determine by the temporal relationships of local neurochemical stimuli.

Cytoarchitecture and responsiveness of the medial ansate region of the cat primary somatosensory cortex.

To understand its relationship to somatosensory areas in other species, we studied the rostral bank of the medial ansate sulcus in adult cats. Neurons in the shoulder and upper part of the sulcal wall responded to low-threshold cutaneous stimuli much like neurons on the crown of the gyrus, whereas neurons in some deeper portions of the sulcus required more intense but innocuous somatic stimuli. Because we found much of the body surface re-represented in this area, we suggest that, besides the representation in area 3b, there is another cutaneous representation of the hindlimb and trunk located on the gyral crown near the medial end of the medial ansate sulcus and of the forelimb and trunk within the medial ansate sulcus. Posterior to this second cutaneous representation, many parts of the body were also represented in regions activated by more intense stimuli and having a different cytoarchitecture, suggesting that they were part of another body representation. Area 3b and the shoulder of the gyrus were distinguished by relatively intense acetylcholinesterase staining of layers III and IV. In the wall of the sulcus, all layers except layer I were uniformly stained to a point where electrophysiological recordings showed the cortex to be unresponsive, whereupon the outer two-thirds of layer I became very pale. Neurons activated by afferents from knee joints were found only in a small area; we did not find a mediolateral band serving joint afferents as is reported in primates. These data suggest that cat somatosensory cortex differs in some ways from primates but that it contains multiple representations of the body, as do most other mammals.

The reactivity and interaction of neurons of the cerebral cortex of rats in the presence of the microiontophoretic action of acetylcholine in a model negative learning situation.

The activity of 46 pairs of neurons in the sensorimotor cortex of the brain of rats during multiple (up to 60) brief microiontophoretic applications of acetylcholine (ACh) was investigated by means of the method of multicellular recording, with subsequent division into separate impulse streams. It was demonstrated that neurons with high-amplitude spikes have a lower average frequency of discharges in comparison with low-amplitude [neurons]. It was established that cells located adjacent to one another exhibit responses in 63% of cases which are similar in their component makeup; the majority of these responses are inhibitory-excitatory and excitatory. Analysis of the dynamics of the structure of the cross-interval histograms plotted for pairs of cells on the basis of the data of their initial activity, as well as activity in the baseline, and upon termination of the action of ACh, attest to the relative invariability of the excitatory connections between the cells and a possibility of some increase in the efficiency of the inhibitory connections under the conditions of the manifestation of the dynamics of responses to ACh of habituation type by one of the cells.

Crystallization and preliminary X-ray investigation of phosphoribosylaminoimidazolesuccinocarboxamide synthase from the yeast Saccharomyces cerevisiae.

Crystals of phosphoribosylaminoimidazolesuccinocarboxamide synthase (EC 6.3.2.6) from the yeast Saccharomyces cerevisiae were grown by the vapor diffusion hanging-drop technique, using ammonium sulfate as the precipitant. The crystals had dimensions up to 1.2 mm. X-ray diffraction experiments indicated a space group of P2(1)2(1)2(1) and unit cell parameters of a = 62.3 A, b = 63.5 A and c = 80.9 A, with one molecule in the asymmetric unit. Native data have been collected to 2.5 A resolution.