Parker Solar Probe Observations of Solar Wind Energetic Proton Beams Produced by Magnetic Reconnection in the Near-Sun Heliospheric Current Sheet.

We report observations of reconnection exhausts in the Heliospheric Current Sheet (HCS) during Parker Solar Probe Encounters 08 and 07, at 16 R s and 20 R s , respectively. Heliospheric current sheet (HCS) reconnection accelerated protons to almost twice the solar wind speed and increased the proton core energy by a factor of ∼3, due to the Alfvén speed being comparable to the solar wind flow speed at these near-Sun distances. Furthermore, protons were energized to super-thermal energies. During E08, energized protons were found to have leaked out of the exhaust along separatrix field lines, appearing as field-aligned energetic proton beams in a broad region outside the HCS. Concurrent dropouts of strahl electrons, indicating disconnection from the Sun, provide further evidence for the HCS being the source of the beams. Around the HCS in E07, there were also proton beams but without electron strahl dropouts, indicating that their origin was not the local HCS reconnection exhaust.

Prompt Response of the Dayside Magnetosphere to Discrete Structures Within the Sheath Region of a Coronal Mass Ejection.

A sequence of discrete solar wind structures within the sheath region of an interplanetary coronal mass ejection on November 6, 2015, caused a series of compressions and releases of the dayside magnetosphere. Each compression resulted in a brief adiabatic enhancement of ions (electrons) driving bursts of electromagnetic ion cyclotron (EMIC; whistler mode chorus) wave growth across the dayside magnetosphere. Fine-structured rising tones were observed in the EMIC wave bursts, resulting in nonlinear scattering of relativistic electrons in the outer radiation belt. Multipoint observations allow us to study the spatial structure and evolution of these sheath structures as they propagate Earthward from L1 as well as the spatio-temporal characteristics of the magnetospheric response. This event highlights the importance of fine-scale solar wind structure, in particular within complex sheath regions, in driving dayside phenomena within the inner magnetosphere.

[Small Noncoding 4.5SH and 4.5SI RNAs and Their Binding to Proteins].

The functions of small noncoding RNAs 4.5SH and 4.5SI found in murine-like rodents are unclear. These RNAs synthesized by RNA polymerase III are widely expressed in rodent organs and tissues. Using crosslinking assays, it was shown that approximately half of all 4.5SI and 4.5SH RNA molecules were bound to proteins provisionally called X and Y, respectively. An immunoprecipitation experiment showed that both these RNAs were associated with the La protein, which did not crosslink to them. The termini of 4.5SI RNA form a long duplex stem, which makes the molecule more stable than 4.5SH RNA. Modification of the 5'-end sequence destructing the stem of 4.5SI RNA altered its protein-binding properties; after the 3'-end sequence was changed to the complementary, both the stem structure and the RNA binding to protein X were restored. Presumably, this protein plays a role in increasing the half-life of 4.5SI RNA.

[4.5SI and 4.5SH RNAs: Expression in various rodent organs and abundance and distribution in the cell].

Studying the structure, functions, and cell physiology of small RNAs remains important. The 4.5SI and 4.5SH small RNAs, which were among the first to be discovered and sequenced, share several features, i.e., they are both approximately 100 nt in size, are synthesized by RNA polymerase III, and are found only in rodents of several related families. Genes coding for these RNAs are evolutionarily related to short interspersed elements (SINEs). However, the two RNAs differ in nucleotide sequence, half-life in the cell, and the organization of their genes in the genome. Although the 4.5SI and 4.5SH RNAs have been identified more than three decades ago, several aspects of their metabolism in the cell are still poorly understood. The 4.5SI and 4.5SH RNA levels were measured in various organs of three rodent species (mouse, rat, and hamster). Both of the RNAs were found to occur at high levels, which were much the same in different organs in the case of the 4.5SI RNA and varied among organs in the case of the 4.5SH RNA. Both 4.5SI and 4.5SH RNAs demonstrated a predominantly nuclear localization with a detectable presence in the cytoplasm. The copy number per cell for the RNAs was estimated at 0.4-2.4 × 10^(6). A quantitative study for the 4.5SI and 4.5SH RNAs was performed for the first time and resolved a number of contradictions in data from other studies.

[A rare case of metastatic tumor of heart from bladder cancer].

The article presents a case report of metastatic heart damage which developed in association with urothelial bladder carcinoma in a 79-year old female patient. Various masses may be found in the heart. In tumors, a secondary damage to the heart is observed much more frequently than a primary damage; however, metastasis of bladder carcinoma to the heart is extremely rare. Of interest is the fact of metastatic damage to all layers of the heart, including the endocardium, pericardium, and myocardium.

[Classification of EEG Patterns of Imagined Rhythmic Movements of the Fingers of One Hand].

The article presents the results of classification of EEG patterns registered during imagined rhytmic movements of the fingers of the right hand (little, thumb, index, middle fingers) in 8 healthy subjects. The subjects imagined finger movements in a given rhythm; no external stimuli were used. A two-level committee of classifiers was developed for decoding: the first level included support vector machines and artificial neural networks; the second level included artificial neural network used for generalizing. As the key parameters for classification, we used the area of zone under the envelope of EEG signal and the length of the envelope calculated in sliding time window for leads F3, C3 and Cz in system 10-20 were chosen as the key features for signals of sensorimotor and adjoining frontal area cortex contralateral to movements. The accuracy of classification of single trials for 4 movements averaged for all subjects for the pair of leads F3-C3 was 50 ± 7% [SD] (maximal - 58%); for the pair of leads C3-Cz, 46 ± 11% [SD] (maximal - 62%); theoretical guessing level is 25%.

Numerical simulation of stratospheric QBO impact on the planetary waves up to the thermosphere.

With the help of numerical simulation, a detailed analysis of the dynamical effect of the stratospheric quasi-biennial oscillation (QBO) of the equatorial zonal wind on the planetary waves (PWs) up to thermospheric heights is carried out for the first time. The 3-dimensional nonlinear mechanistic model of middle and upper atmosphere (MUAM) is used, which is capable of simulating the general atmospheric circulation from the surface up to 300-400 km altitude. The amplitudes of stationary and westward travelling PWs with periods from 4 to 10 days are calculated based on ensembles of model simulations for conditions corresponding to the easterly and westerly QBO phases. Fluxes of wave activity and refractive indices of the atmosphere are calculated to analyze the detailed behavior of the PWs. The important result to emerge is that the stratospheric QBO causes statistically significant changes in the amplitudes of individual wave components up to 25% in the mesosphere-lower thermosphere and 10% changes above 200 km. This change in wave structures should be especially noticeable in the atmosphere during periods of low solar activity, when the direct contribution of solar activity fluctuations is minimized. Propagating from the troposphere to the upper atmosphere, PWs contribute to the propagation of the QBO signal not only from the equatorial region to extratropical latitudes, but also from the stratosphere to the thermosphere. The need for a detailed analysis of large-scale wave disturbances in the upper atmosphere and their relationship with the underlying layers is due, in particular, to their significant impact on satellite navigation and communication systems, which is caused by amplitude and phase fluctuations of the radio signal.

Biochemical and technological properties of moose (Alces alces) recombinant chymosin.

Recombinant chymosins (rСhns) of the cow and the camel are currently considered as standard milk coagulants for cheese-making. The search for a new type of milk-clotting enzymes that may exist in nature and can surpass the existing "cheese-making" standards is an urgent biotechnological task. Within this study, we for the first time constructed an expression vector allowing production of a recombinant analog of moose chymosin in the expression system of Escherichia coli (strain SHuffle express). We built a model of the spatial structure of moose chymosin and compared the topography of positive and negative surface charges with the correspondent structures of cow and camel chymosins. We found that the distribution of charges on the surface of moose chymosin has common features with that of cow and camel chymosins. However, the moose enzyme carries a unique positively charged patch, which is likely to affect its interaction with the substrate. Biochemical and technological properties of the moose rChn were studied. Commercial rСhns of cow and camel were used as comparison enzymes. In some technological parameters, the moose rChn proved to be superior to the reference enzymes. Сompared with the cow and camel rСhns, the moose chymosin specific activity is less dependent on the changes in CaCl2 concentration in the range of 1-5 mM and pH in the range of 6-7, which is an attractive technological property. The total proteolytic activity of the moose rСhn occupies an intermediate position between the rСhns of cow and camel. The combination of biochemical and technological properties of the moose rСhn argues for further study of this enzyme.

A new function for CD38/ADP-ribosyl cyclase in nuclear Ca2+ homeostasis.

Nucleoplasmic calcium ions (Ca2+) influence nuclear functions as critical as gene transcription, apoptosis, DNA repair, topoisomerase activation and polymerase unfolding. Although both inositol trisphosphate receptors and ryanodine receptors, types of Ca2+ channel, are present in the nuclear membrane, their role in the homeostasis of nuclear Ca2+ remains unclear. Here we report the existence in the inner nuclear membrane of a functionally active CD38/ADP-ribosyl cyclase that has its catalytic site within the nucleoplasm. We propose that the enzyme catalyses the intranuclear cyclization of nicotinamide adenine dinucleotide to cyclic adenosine diphosphate ribose. The latter activates ryanodine receptors of the inner nuclear membrane to trigger nucleoplasmic Ca2+ release.

CD38/ADP-ribosyl cyclase: A new role in the regulation of osteoclastic bone resorption.

The multifunctional ADP-ribosyl cyclase, CD38, catalyzes the cyclization of NAD(+) to cyclic ADP-ribose (cADPr). The latter gates Ca(2+) release through microsomal membrane-resident ryanodine receptors (RyRs). We first cloned and sequenced full-length CD38 cDNA from a rabbit osteoclast cDNA library. The predicted amino acid sequence displayed 59, 59, and 50% similarity, respectively, to the mouse, rat, and human CD38. In situ RT-PCR revealed intense cytoplasmic staining of osteoclasts, confirming CD38 mRNA expression. Both confocal microscopy and Western blotting confirmed the plasma membrane localization of the CD38 protein. The ADP-ribosyl cyclase activity of osteoclastic CD38 was next demonstrated by its ability to cyclize the NAD(+) surrogate, NGD(+), to its fluorescent derivative cGDP-ribose. We then examined the effects of CD38 on osteoclast function. CD38 activation by an agonist antibody (A10) in the presence of substrate (NAD(+)) triggered a cytosolic Ca(2+) signal. Both ryanodine receptor modulators, ryanodine, and caffeine, markedly attenuated this cytosolic Ca(2+) change. Furthermore, the anti-CD38 agonist antibody expectedly inhibited bone resorption in the pit assay and elevated interleukin-6 (IL-6) secretion. IL-6, in turn, enhanced CD38 mRNA expression. Taken together, the results provide compelling evidence for a new role for CD38/ADP-ribosyl cyclase in the control of bone resorption, most likely exerted via cADPr.

Beneficial effects of testosterone administration on symptoms of the lower urinary tract in men with late-onset hypogonadism: a pilot study.

INTRODUCTION: Elderly men are bothered by lower urinary tract complaints designated as lower urinary tract symptoms (LUTS). In epidemiological studies LUTS appears strongly associated with erectile dysfunction, and also with metabolic syndrome. LUTS occurs at an age at which plasma testosterone levels decline, in some men to hypogonadal values. Objectives. This pilot study tested whether testosterone administration to elderly men complaining of LUTS and whose plasma testosterone levels are below normal, might alleviate LUTS. METHODS: Group 1 (n = 10) received treatment with testosterone gel (50 mg) daily for three months; group 2 (n = 20) received treatment with injections of testosterone undecanoate 1000 mg for 26 weeks. RESULTS: Upon these interventions, plasma testosterone increased to the normal range. Symptoms of LUTS, measured by the International Prostate Symptoms Score, improved significantly, and also scores of the Aging Males' Symptoms scale and international index of erectile function improved. There were no untoward effects on the prostate over this period of time of the study. CONCLUSION: Testosterone administration improved symptoms of LUTS in men with late-onset hypogonadism. The mechanism of action is as yet not understood, but it may be connected with or parallel with the effects of testosterone on penile tissues in hypogonadal men, such as on nitric oxide and phosphodiesterase.

[Oligomeric organization of recombinant human neurotrophins expressed in Escherichia coli cells].

Genes of human neurotrophins NGF, BDNF, NT-3 were cloned, and the corresponding proteins and their fragments were expressed in Escherichia coli BL-21 (DE3lambda) cells. Their intracellular localization was determined. The conditions for isolation and purification of the target recombinant proteins and for folding of BDNF and NT-3 precursors were selected. The recombinant proprecursors of human neurotrophines have been shown to possess complex oligomeric structure.

[The influence of vitamins A, E, C upon the respiration activity of the spleen lymphocytes ].

In the experiment on albino male mongrel rats some parameters of oxidative phosphorylation of spleen slices were studied after the animals were fed the antioxidant complex of vitamins E, A, and C. The stimulation of oxygen consumption rate and of tissue respiration of spleen was observed with endogenous substrates, and after exogenous substrates (succinate and glutamate) were added. After the ingestion of vegetable oil the uncoupling of oxidative phosphorylation was observed. The perspectives of alimentary and medicine immunocorrection by the influence upon the mitochondrial oxidation system of cell immune competence organ discussed.

[Trichinosis in the Kherson Region].

The paper describes the 2003-2004 outbreak oft richinosis in 2 districts of the Kherson Region. Pork was a source of infection. The disease occurred with the ingestion ofshashlik, raw meat, lard, or minced meat. The diagnosis of trichinosis was established 1-1.5 months after the onset of the disease. The patients received a course of therapy and were discharged in a satisfactory condition. The members of their families were prophylactically treated. Meats were bought at the markets and had negative veterinary sanitary tests. A package of antiepidemic and antiepizootic measures was implemented in the foci of trichinosis.

Revisiting the structure of low-Mach number, low-beta, quasi-perpendicular shocks.

A study of the structure of 145 low-Mach number (M ≤ 3), low-beta (ß ≤ 1), quasi-perpendicular interplanetary collisionless shock waves observed by the Wind spacecraft has provided strong evidence that these shocks have large-amplitude whistler precursors. The common occurrence and large amplitudes of the precursors raise doubts about the standard assumption that such shocks can be classified as laminar structures. This directly contradicts standard models. In 113 of the 145 shocks (~78%), we observe clear evidence of magnetosonic-whistler precursor fluctuations with frequencies ~0.1-7 Hz. We find no dependence on the upstream plasma beta, or any other shock parameter, for the presence or absence of precursors. The majority (~66%) of the precursors propagate at ≤45° with respect to the upstream average magnetic field and most (~87%) propagate ≥30° from the shock normal vector. Further, most (~79%) of the waves propagate at least 20° from the coplanarity plane. The peak-to-peak wave amplitudes (δB pk-pk) are large with a range of maximum values for the 113 precursors of ~0.4-13 nT with an average of ~2 nT. When we normalize the wave amplitudes to the upstream averaged magnetic field and the shock ramp amplitude, we find average values of ~40% and ~220%, respectively.

Alternative leader sequences in insulin-like growth factor I mRNAs modulate translational efficiency and encode multiple signal peptides.

Rat insulin-like growth factor I (IGF-I) mRNAs contain multiple 5'-untranslated regions due to the use of leader exons transcribed from several transcription initiation sites and to alternative splicing within leader exon 1. Synthetic RNAs with 5'-ends corresponding to the use of exon 1 transcription initiation sites were translated in vitro into prepro-IGF-I peptides initiated at a Met-48 codon in exon 1 or a Met-22 codon in exon 3, and RNAs with a 5'-end corresponding to the major exon 2 transcription start site were translated into a prepro-IGF-I peptide initiated at a Met-32 codon in exon 2. All forms of prepro-IGF-I were processed by canine pancreatic microsomes, suggesting that all these prepeptides function as signal peptides. The translational efficiency of IGF-I RNAs was inversely proportional to the length of the 5'-untranslated region. Mutation of the first of three upstream AUG codons in exon 1, which potentially initiates a 14-amino acid open reading frame, did not affect prepro-IGF-I translation. The other two AUG codons are immediately followed by stop codons. The absence of both upstream AUG codons in a completely spliced exon 1-derived RNA enhanced the in vitro and in vivo translatability of this RNA as compared with the full-length RNA. Mutation of the downstream initiation codon in particular increased translational efficiency in vitro and in intact cells, suggesting that an inefficient reinitiation event at the Met-48 codon contributes to the poorer translation of IGF-I mRNAs in which these upstream AUGUGA motifs occur. We conclude that IGF-I mRNAs potentially encode multiple forms of preproIGF and that specific differences in their 5'-untranslated regions provide a molecular basis for translational control of IGF-I biosynthesis.

The insulin-like growth factor I receptor-induced interaction of insulin receptor substrate-4 and Crk-II.

Stimulation of the insulin or insulin-like growth factor (IGF)-I receptor results in activation of several signaling pathways. Proteins of the insulin receptor substrate (IRS) family play important roles in mediating these signaling cascades. To date, four members of the IRS family of docking proteins have been characterized. Recently, we have reported that stimulation of the IGF-I receptor in 293 HEK cells regulates interaction of the newly discovered IRS-4 molecule with the Crk family of proteins. In the present study, we characterize the molecular basis of these interactions. C- and N termini truncation analysis of IRS-4 demonstrated that the region between amino acids 678 and 800 of the IRS-4 molecule is involved in this interaction. This region contains a cluster of four tyrosines (Y(700), Y(717), Y(743), and Y(779)). We hypothesize that one or more of these tyrosines are involved in the interaction between the SH2 domain of the Crk-II molecule when IRS-4 is phosphorylated upon IGF-I receptor activation. Additional mutational analyses confirmed this hypothesis. Interestingly, none of these four tyrosines was individually critical for the interaction between Crk-II and IRS-4, but when all four tyrosines were simultaneously mutated to phenylalanine, the IGF-I induced interaction between these molecules was abolished. Taken together, these results suggest a novel mechanism of Crk-II binding to tyrosine phosphorylated proteins.

Tyrosine residues in the C-terminal domain of the insulin-like growth factor-I receptor mediate mitogenic and tumorigenic signals.

We investigated cellular proliferation, the transforming activity, and activation of known signal transduction pathways in NIH-3T3 cells stably expressing insulin-like growth factor-I receptors (IGF-IRs) with amino acid substitutions in the carboxy(C)-terminal domain. The mutant receptors contained substitutions of both tyrosines 1250 and 1251 with phenylalanine and histidine (amino acids present in the analogous positions in the insulin receptor), as well as phenylalanine 1310 replaced by tyrosine (IsY clones) to resemble the placement of tyrosine residues in the C-terminal domain of the insulin receptor. As a control for the IsY clones, a second mutant receptor was expressed with a substitution of phenylalanine 1310 with tyrosine only (DBY clones). Clones expressing IGF-IRs with the IsY substitutions had a significantly slower rate of growth compared with cells expressing an equivalent number of wild-type IGF-IRs (NWT). In contrast, the DBY clones showed relatively normal growth rates. Cells with wild-type IGF-IR demonstrated a transformed phenotype in soft agar assays. The IsY clones lost the transforming ability of the wild type IGF-IR, whereas DBY clones formed colonies. IGF-I-stimulated autophosphorylation of the IGF-IR and tyrosine phosphorylation of IRS-1 and SHC, known substrates in the IGF-IR signal transduction pathway, were studied. Mutated IGF-IRs (IsY and DBY) did not alter the IGF-I-induced tyrosine phosphorylation of these proteins. Furthermore, the mutated IGF-IRs did not alter Grb2 association with phosphorylated IRS-1 and SHC. IGF-I stimulation of Crk-II phosphorylation, a novel substrate of the IGF-IR, was similar in cells expressing mutated and wild-type IGF-IRs. IGF-I-induced activation of phosphatidylinositol (PI) 3'-kinase was equivalent in cells expressing either mutant or wild-type IGF-IRs. These data suggest that the IGF-IR mediates, at least in part, cellular proliferation and increased transforming ability through its C-terminal domain. The exact postreceptor signaling pathway(s) involved have yet to be fully elucidated.

A growth hormone pseudogene in the salmon genome.

Representatives of the fish family Salmonidae were reported to possess two nonallelic growth hormone (GH)-encoding genes. In addition to those, we found a third GH-like sequence in a chum salmon genomic DNA library. A number of point mutations and large deletions abolished the possibility of expressing this sequence, showing that the chum salmon genomic DNA contains a GH pseudogene besides functional GH genes.

The carboxyl-terminal domain of insulin-like growth factor-I receptor interacts with the insulin receptor and activates its protein tyrosine kinase.

Receptors for insulin and insulin-like growth factor-I (IR and IGFIR) consisting of the alpha2beta2 structure are protein tyrosine kinases (PTKs). Carboxyl-terminal (CT) domains of their beta subunits are structurally diverse while the PTK domains share the highest homology. Interactions between CT and PTK domains of IR and IGFIR were studied by means of PTK activity, fluorescence energy transfer or surface plasmon resonance using BIAcore. We present evidence that IGFIR CT directly interacts with both IGFIR and IR. Although binding to both receptors, stimulation of PTK activity only occurs with IR but not IGFIR.