Effects of low frequency cyclic mechanical stretching on osteoclastogenesis

Bone cells are continuously exposed to mechanical deformations originating from movement. Mechanical stimulation at fundamental frequencies associated with most frequent normal locomotion (0.167–10 Hz) has been reported to suppress differentiation of osteoclasts. However, the effects of very low frequency (0.01 Hz) stimulation (which could be a frequency component of normal movement and also relevant to locomotion of movement-impaired individuals) on osteoclasts are poorly understood. We examined differentiation of osteoclasts from mouse bone marrow precursors and RAW 264.7 monocytes cultured on an extendable silicone surface that was dynamically stretched at 0.01 Hz. Three stimulation regimes were applied: (i) continuously during 4 days of differentiation, (ii) non-continuously, 8 h/day for 4 days, and (iii) post-differentiation, when stimulation was applied for 24 h after osteoclasts were noted. Low frequency mechanical stimulation did not inhibit osteoclastogenesis. Moreover, the expression of osteoclast marker genes was upregulated in mechanically stimulated cells compared to static control. Conditioned medium collected from osteoclast cultures stimulated non-continuously or post-differentiation induced differentiation of osteoclast precursors plated in standard tissue culture plates. Extracellular signal-regulated kinase (ERK) phosphorylation was increased in mechanically-stimulated cultures compared to static control. Thus, low frequency mechanical stimulation has qualitatively different effects on osteoclast formation compared to stimulation associated with the fundamental frequencies of normal movement.     

The evolutionary dynamics of grammar acquisition

Grammar is the computational system of language. It is a set of rules that specifies how to construct sentences out of words. Grammar is the basis of the unlimited expressibility of human language. Children acquire the grammar of their native language without formal education simply by hearing a number of sample sentences. Children could not solve this learning task if they did not have some pre-formed expectations. In other words, children have to evaluate the sample sentences and choose one grammar out of a limited set of candidate grammars. The restricted search space and the mechanism which allows to evaluate the sample sentences is called universal grammar. Universal grammar cannot be learned; it must be in place when the learning process starts. In this paper, we design a mathematical theory that places the problem of language acquisition into an evolutionary context. We formulate equations for the population dynamics of communication and grammar learning. We ask how accurate children have to learn the grammar of their parents' language for a population of individuals to evolve and maintain a coherent grammatical system. It turns out that there is a maximum error tolerance for which a predominant grammar is stable. We calculate the maximum size of the search space that is compatible with coherent communication in a population. Thus, we specify the conditions for the evolution of universal grammar.     

Mutation-selection networks of cancer initiation: tumor suppressor genes and chromosomal instability

In this paper, we derive analytic solutions of stochastic mutation-selection networks that describe early events of cancer formation. A main assumption is that cancer is initiated in tissue compartments, where only a relatively small number of cells are at risk of mutating into cells that escape from homeostatic regulation. In this case, the evolutionary dynamics can be approximated by a low-dimensional stochastic process with a linear Kolmogorov forward equation that can be solved analytically. Most of the time, the cell population is homogeneous with respect to relevant mutations. Occasionally, such homogeneous states are connected by 'stochastic tunnels'. We give a precise analysis of the existence of tunnels and calculate the rate of tunneling. Finally, we calculate the conditions for chromosomal instability (CIN) to precede inactivation of the first tumor suppressor gene. In this case, CIN is an early event and a driving force of cancer progression. The techniques developed in this paper can be used to study arbitrarily complex mutation-selection networks of the somatic evolution of cancer.     

Effect of aeration conditions on the biosynthesis of carminomycin by an actinomadura carminata culture]

The effect of the aeration rate on biosynthesis of carminomycin by Actinomadura carminata and biochemical changes in the fermentation broth on the use of 3 complex media of different composition was studied. The carminomycin-producing organism can grow and produce the antibiotic within the ranges of the aeration changes from 0.98 to 18.56 mgO2/1-min. A decrease in the maximum rate of oxygen dissolution up to 0.98 mgO2/1-min resulted in some decrease in the activity level. Intensive aeration, i.e. 18.56 mgO2/1-min induced suppression of the antibiotic production by 25 per cent.     

Physical criteria of pathological processes. I. Change in the functional hemispheric asymmetry at various stages of rheumatic diseases]

The functional interhemispheric asymmetry of brain in patients with systemic rheumatic diseases was estimated by measuring brain direct current potentials. It is shown that different types of functional interhemispheric asymmetry correspond to different stages of systemic rheumatic diseases. At early stages, the left hemisphere asymmetry dominates, at expressed stages, the right hemisphere asymmetry is prevalent, and the terminal stage is characterized by the loss of functional interhemispheric asymmetry.     

Biological Properties of Antisense Oligonucleotides Conjugated to Different High-Molecular Mass Poly(Ethylen Glycols)

Abstract

The effect of the different structures of high-molecular weight poly(ethylen glycol) chains on the biological properties of the conjugated antisense oligonucleotide has been investigated and compared.     

A review of sciarids of the genus <Emphasis Type="Italic">Leptosciarella</Emphasis> Tuomikoski 1960 (Diptera,Sciaridae) in the Altai fauna,with description of three new species

The taxonomy of the genus Leptosciarella Tuomikoski, 1960 in the Altai Area within Altai Territory and the Altai Republic was studied. Eleven species were recognized, including three new species which are described and illustrated here: Leptosciarella (L.) ulagana Komarova sp. n., L. (L.) angustistylus Komarova sp. n., L. (L.) senex Komarova sp. n. Additionally, L. (L.) fuscipalpa (Mohrig et Mamaev 1979) and L. (L.) truncata (Tuomikoski 1960) are recorded from Altai for the first time. A key to the Altai species is provided.     

Conformational changes in CLIP-170 regulate its binding to microtubules and dynactin localization

Cytoplasmic linker protein (CLIP)-170, CLIP-115, and the dynactin subunit p150(Glued) are structurally related proteins, which associate specifically with the ends of growing microtubules (MTs). Here, we show that down-regulation of CLIP-170 by RNA interference results in a strongly reduced accumulation of dynactin at the MT tips. The NH(2) terminus of p150(Glued) binds directly to the COOH terminus of CLIP-170 through its second metal-binding motif. p150(Glued) and LIS1, a dynein-associating protein, compete for the interaction with the CLIP-170 COOH terminus, suggesting that LIS1 can act to release dynactin from the MT tips. We also show that the NH(2)-terminal part of CLIP-170 itself associates with the CLIP-170 COOH terminus through its first metal-binding motif. By using scanning force microscopy and fluorescence resonance energy transfer-based experiments we provide evidence for an intramolecular interaction between the NH(2) and COOH termini of CLIP-170. This interaction interferes with the binding of the CLIP-170 to MTs. We propose that conformational changes in CLIP-170 are important for binding to dynactin, LIS1, and the MT tips.     

Pathologies Associated with the p53 Response

Although p53 is a major cancer preventive factor, under certain extreme stress conditions it may induce severe pathologies. Analyses of animal models indicate that p53 is largely responsible for the toxicity of ionizing radiation or DNA damaging drugs contributing to hematopoietic component of acute radiation syndrome and largely determining severe adverse effects of cancer treatment. p53-mediated damage is strictly tissue specific and occurs in tissues prone to p53-dependent apoptosis (e.g., hematopoietic system and hair follicles); on the contrary, p53 can serve as a survival factor in tissues that respond to p53 activation by cell cycle arrest (e.g., endothelium of small intestine). There are multiple experimental indications that p53 contributes to pathogenicity of acute ischemic diseases. Temporary reversible suppression of p53 by small molecules can be an effective and safe approach to reduce severity of p53-associated pathologies.     

Experimental model for studying the primary cilia in tissue culture cells.

In HeLa, PK, 3T3, PtK1 cells and rat embryo fibroblasts (REF), antibodies against acetylated tubulin stained centrioles, primary cilia, some cytoplasmic microtubules and microtubule bundles of the mid-body. The primary cilia were stained more intensively than cytoplasmic microtubules and could easily be distinguished. This makes it possible to detect the primary cilia in cultured cells and to estimate their number by light microscopy. The four cultures studied had 1/4 to 1/3 of interphase cells with detectable primary cilia, and only in HeLa cells the primary cilia were very rare. Comparison of electron microscopic and immunofluorescence data showed that the frequencies of occurrence of the primary cilia in four tissue cultures determined by these two methods were the same. Therefore, antibodies against acetylated tubulin can be used to study the primary cilia. In synchronized mitotic fibroblasts (3T3 and REF) the primary cilia appeared first 2 h after the cells had been plated on coverslips, which is 1 h after the cells had entered the interphase. Four hours after plating the number of ciliated cells reached the average level for nonsynchronous population. This model can be used for further studies of the expression of primary cilia.