LIM-kinase 1 effects on memory abilities and male courtship song in Drosophila depend on the neuronal type.

The signal pathway of actin remodeling, including LIM-kinase 1 (LIMK1) and its substrate cofilin, regulates multiple processes in neurons of vertebrates and invertebrates. Drosophila melanogaster is widely used as a model object for studying mechanisms of memory formation, storage, retrieval and forgetting. Previously, active forgetting in Drosophila was investigated in the standard Pavlovian olfactory conditioning paradigm. The role of specific dopaminergic neurons (DAN) and components of the actin remodeling pathway in different forms of forgetting was shown. In our research, we investigated the role of LIMK1 in Drosophila memory and forgetting in the conditioned courtship suppression paradigm (CCSP). In the Drosophila brain, LIMK1 and p-cofilin levels appeared to be low in specific neuropil structures, including the mushroom body (MB) lobes and the central complex. At the same time, LIMK1 was observed in cell bodies, such as DAN clusters regulating memory formation in CCSP. We applied GAL4 × UAS binary system to induce limk1 RNA interference in different types of neurons. The hybrid strain with limk1 interference in MB lobes and glia showed an increase in 3-h short-term memory (STM), without significant effects on long-term memory. limk1 interference in cholinergic neurons (CHN) impaired STM, while its interference in DAN and serotoninergic neurons (SRN) also dramatically impaired the flies' learning ability. By contrast, limk1 interference in fruitless neurons (FRN) resulted in increased 15-60 min STM, indicating a possible LIMK1 role in active forgetting. Males with limk1 interference in CHN and FRN also showed the opposite trends of courtship song parameters changes. Thus, LIMK1 effects on the Drosophila male memory and courtship song appeared to depend on the neuronal type or brain structure.

A possible mechanism of neural read-out from a molecular engram.

What is the physical basis of declarative memory? The predominant view holds that stored information is embedded in the structure of a neural net, that is, in the signs and weights of its synaptic connections. An alternative possibility is that storage and processing are separated, and that the engram is encoded chemically, most probably in the sequence of a nucleic acid. One deterrent to adoption of the latter hypothesis has been the difficulty of envisaging how neural actively could be converted to and from a molecular code. Our purpose here is limited to suggesting how a molecular sequence could be read out from nucleic acid to neural activity by means of nanopores.

[Learning and memory in Drosophila: physiologic and genetic bases].

Elucidation of molecular mechanisms of cognitive functions is one of the major achievements in neurobiology. At most, this is due to the studies on the simple nervous systems, such as the CNS in Drosophila melanogaster. Many of its functional characteristics are pretty similar to higher vertebrates. Among these are: 1) evolutionary conservation of genes and molecular systems involved in the regulation of learning acquisition and memory formation; 2) presence of highly specialized and differentiated sensory, associative and motor centers; 3) utilization of similar modes of informational coding and analysis; 4) availability of major learning forms including non-associative, as well as associative learning; 5) diversity of different memories, including short-term- and protein synthesis- dependent long-term memory; 6) presence of aminergic reinforcement systems in the brain; 7) feed-back loops of circadian clocks, current organism experience and individual organism characters affecting cognitive process per se. In this review the main attention is paid to the two mostly studied Drosophila learning forms, namely to olfactory Iearning and courtship suppression conditioning (CCS). A separate consideration is given to the impacts of kynurenins and metabolite of actin remodeling signal cascade.

[Expression of the Drosophila melanogaster limk1 gene 3'-UTRs mRNA in Yeast Saccharomyces cerevisiae].

The stability of mRNA and its translation efficacy in higher eukaryotes are influenced by the interaction of 3'-untranscribed regions (3'-UTRs) with microRNAs and RNA-binding proteins. Since Saccharomyces cerevisiae lack microRNAs, it is possible to evaluate the contribution of only 3'-UTRs' and RNA-binding proteins' interaction in post-transcriptional regulation. For this, the post-transcriptional regulation of Drosophila limk1 gene encoding for the key enzyme of actin remodeling was studied in yeast. Analysis of limkl mRNA 3'-UTRs revealed the potential sites of yeast transcriptional termination. Computer remodeling demonstrated the possibility of secondary structure formation in limkl mRNA 3'-UTRs. For an evaluation of the functional activity of Drosophila 3'-UTRs in yeast, the reporter gene PHO5 encoding for yeast acid phosphatase (AP) fused to different variants of Drosophila limk1 mRNA 3'-UTRs (513, 1075, 1554 bp) was used. Assessments of AP activity and RT-PCR demonstrated that Drosophila limkl gene 3'-UTRs were functionally active and recognized in yeast. Therefore, yeast might be used as an appropriate model system for studies of 3'-UTR's role in post-transcriptional regulation.

[Analysis of intermolecular interaction energy inputs in benzene-imidazole and imidazole-imidazole systems in parallel displaced and T-configuration].

Intermolecular interactions in several dimer aromatic systems were analyzed to determine how various energy contributions (electrostatic, exchange, repulsion, and polarization) change depending on the value of monomers separation. Different contributions to the intermolecular energy interactions between imidazole-imidazole and benzene-imidazole dimers are studied using the aug-cc-pVDZ basis set in the framework of ab initio Hartree-Fock and second-order Møller-Plesset perturbation theory methods. Special attention is paid to the exchange and dispersion energy binding contributions.

[The influence of an air ionizer on the air ionic composition].

The air ionic composition in a classroom was determined during the operation of a Neo Tec XJ-2100 ionizer (Germany). The amount of ions in the air was measured before and after the switch-on of the ionizer. It was shown to vary depending on the mode of operation of the device and differ from the recommended normal values. The necessity of checking up the work of air ionizers both in living quarters and at workplaces is discussed with the application of air ion counters making it possible to carry out monitoring of the air ionic composition and estimate its compliance with the sanitary and hygienic norms.

Molecular mechanisms of imidazole and benzene ring binding in proteins.

Aromatic bonds of amino acid radicals play an important role in arrangement of protein primary structure. Previously, the existence of a number of preferable conformations of aromatic dimers was shown theoretically and experimentally, the best known of which are parallel-displaced and perpendicular T conformations. To reveal principles that define preference of various conformations for His-His and Phe-His dimers, non-empirical quantum-chemical calculations of diimidazole and benzene-imidazole were carried out. Calculations were performed using the 6-31G** basis with account for electronic correlations in frames of MP2 and MP4 methods of perturbation theory. Comparative analysis of energetic and geometric parameters of the systems points to the preference of stacking contact or classical hydrogen bond in diimidazole. On the contrary, T conformation is maximally advantageous for benzene-imidazole.

[Stacking-interactions in the control-gear binding of kynurenic acid with NR2A- and GluR2-subunits of glutamate ionotropic receptors].

Kynurenine products in tryptophan metabolism are of crucial importance in modulation of neurodegenerative processes in the CNS. Kynurenic acid (KYNA): the endogenous antagonist of ionotropic glutamate receptors, displays specific affinity towards glycine site ofNMDA-receptor NR1 subunit. Mechanisms for the selective interaction of KYNA and its derivatives with other glutamate receptor subtypes are studied insufficiently. Ab initio quantum chemical calculations for KYNA-imidazole dimer, as a model for ligand interaction with His88 fragment of NR2A-subunit, along with KYNA-phenol dimer, as a model for ligand interaction with Tyr61 fragment of GluR2-subunit, were carried out in order to investigate stacking-interaction role of KYNA binding by NR2A subunit of NMDA-receptor and GluR2 subunit of AMPA-receptor. Stacking-interaction energy of KYNA-H88 for the assumed ligand orientation in the binding site is 3.0-5.0 kcal/mol and 102. kcal/mol for the optimized dimer KYNA-imidazole geometry. Stacking-interaction energy of KYNA-Tyr61 for the assumed ligand orientation in the binding site is 6.7-8.5 kcal/mol. The obtained values are comparable with the energies of hydrogen bonds. Thus, stacking-interaction should be taken into account while studing ligand glutamate receptor binding mechanisms. Stacking-interaction is evidently important for the initial ligand orientation inside the receptor binding site after which the delicate tuning of hydrogen bonding pattern is realized. On the other hand, the specific affinity of KYNA derivatives to the receptor subunits could be explained by ligand-aromatic receptor aminoacid stacking-interaction geometry difference.

[The diagnostic characteristics of late toxicosis in pregnant women with hypertension and chronic kidney diseases]. / Osobennosti diagnostiki pozdnego toksikoza u beremennykh s gipertonicheskoi bolezn'iu i khronicheskimi zabolevaniiami pochek.

A study was made of diagnostic significance (sensitivity and specificity) of early (precritical) signs of late gestosis (LG). A total of 179 females (187 pregnancies) with essential hypertension (EH) and chronic renal diseases (CRD) were examined. EH women are at high risk of LG when they have proteinuria above 0.3 g/s, of relative prognostic importance are severe hypertension and marked hyperuricemia. Severe hypertension, fetal growth inhibition, positive roll-over test may indicate LG in CRD. Primiparas with EH or CRD are especially at risk of LG. As all the above LG signs in its precritical stage are not specific and indicate only probability, they can be used primarily for screening of patients with high risk of LG onset. The diagnosis of LG in EH and CRD should be based on follow-up changes in the clinical and laboratory indices.

[The dynamic importance of proteinuria and arterial pressure for detecting late toxicosis in pregnant women with chronic kidney diseases and hypertension]. / Znachenie dinamiki proteinurii i arterial'nogo davleniia dlia vyiavleniia pozdnego toksikoza u beremennykh s khronicheskimi zabolevaniiami pochek i gipertonicheskoi bolezn'iu.

Time course of 187 pregnancies was followed up in 103 females with chronic renal diseases (CRD), 76 females with essential hypertension (EH) and 14 posteclampsia females. Three variants of arterial pressure (AP) and 5 types of proteinuria changes were recognized in CRD and EH patients. The pattern of these changes was compared to that in posteclampsia patients, the eclampsia being an absolute criterium of late toxicosis. It is shown that neither elevated AP and proteinuria nor their absolute values can serve reliable signs of late gestosis in CRD and EH patients. Only the trend in these parameters is significant. CRD and EH females with late gestosis exhibit rapidly growing proteinuria in line with the onset or exacerbation of EH. Retrospective analysis of the pregnancies has confirmed association of late gestosis in 15% of EH and 7% of chronic glomerulonephritis patients. These estimates are lower than commonly accepted. Early diagnosis of late gestosis in pregnant females with CRD and EH requires not only regular AP registration, but also dynamic, in some cases hourly, evaluation of proteinuria.

[Cellular composition and T-lymphocyte subpopulations in the bronchoalveolar lavage fluid in patients with fibrosing alveolitis and pulmonary granulomatosis]. / Kletochnyi sostav i subpopuliatsii T-limfotsitov v zhidkosti bronkhoal'veoliarnogo lavazha u bol'nykh fibroziruiushchim al'veolitom i granulematozom legkikh.

Cytological and immunological investigations of bronchoalveolar lavage fluid (BLF) have been performed in 87, 27, 32 and 94 patients with fibrosing alveolitis (FA), exogenous allergic alveolitis (EAA), histiocytosis and pulmonary sarcoidosis (PS), respectively. The diseases appeared to demonstrate significant differences in BLF cell composition and relations between T-lymphocyte theophyllin-resistent and theophyllin-sensitive subpopulations. The findings can be applied in differential diagnosis of disseminated processes in the lungs. The number of neutrophils and the subpopulations correlation in FA and EAA may serve criteria of the disease activity and adequacy of the treatment administered.

[Diagnostic bronchoalveolar lavage in assessing the efficacy of the treatment of idiopathic fibrosing alveolitis]. / Diagnosticheskii bronkhoal'veoliarnyi lavazh v otsenke éffektivnosti lecheniia idiopaticheskogo fibroziruiushchego al'veolita.

A study of the results of repeated diagnostic bronchoalveolar lavage in 27 patients with idiopathic fibrosing alveolitis (IFA) has shown that the investigation of cellular composition of the bronchoalveolar content (BAC) made it possible to specify IFA activity and its therapy-related change. Normalization or a decrease below 6% of the neutrophil content in BAC was typical of achieving low activity and remission of disease. A relatively high count of neutrophils in BAC (over 10%) during therapy was observed in preserved significant IFA activity resistant to drug therapy.

[Extra-intracranial anastomosis in the surgical treatment of arterial aneurysms of the brain]. / Ekstra-intrakranial'nyi anastomoz v khirurgii arterial'nykh anevrizm golovnogo mozga.

Appraisal of the results of surgical treatment of 7 patients with arterial aneurysms of the carotid channel convinced the authors of the useful applicability of extra-intracranial anastomosis in occlusion of the cerebral arteries. The anastomosis provides for adequate compensation of circulation in the brain in occlusion of not only the internal carotid artery but also the middle cerebral artery. Depending on the surgical situation, extra-intracranial anastomosis can be performed both as a planned procedure and as an emergency measure. Emergency establishment of the anastomosis is useful in all cases of complications of the operations terminating in occlusion of the internal carotid or middle cerebral artery.