Meaning, Medicine, and the "Placebo Effect"

Meaning, Medicine, and the "Placebo Effect" Daniel Moerman Cambridge: Cambridge University Press, 2002. xiii. 172 pp.     

"Extracts from "Clinical evidence": Menopausal symptoms

DefinitionMenopause begins one year after the last menstrual period. Symptoms often begin in the perimenopausal years.Incidence/prevalenceIn the United Kingdom the mean age for the menopause is 50 years 9 months. The median onset of the perimenopause is between 45.5 and 47.5 years. One Scottish survey (of 6096 women aged 45 to 54 years) found that 84% had experienced at least one of the classic menopausal symptoms, with 45% finding one or more symptoms a problem.¹

Interventions

• Beneficial:OestrogensTibolone

• Likely to be beneficial:ProgestogensClonidine

• Unknown effectiveness:Phyto-oestrogensTestosteroneAntidepressants

PrognosisMenopause is a physiological event. Its timing may be genetically determined. Although endocrine changes are permanent, menopausal symptoms such as hot flushes, which are experienced by about 70% of women, usually resolve with time.² However, some symptoms, such as genital atrophy, may remain the same or worsen.AimsTo reduce or prevent menopausal symptoms, and to improve quality of life with minimum adverse effects.OutcomesFrequency and severity of vasomotor, urogenital, and psychological symptoms; quality of life.MethodsClinical Evidence search and appraisal December 1999. We included only randomised controlled trials (RCTs) and systematic reviews that met Clinical Evidence quality criteria.BenefitsVasomotor symptoms: We found no systematic review. We found over 40 RCTs comparing oestrogen versus placebo and various preparations and/or routes against each other. Most found that oestrogen reduced vasomotor symptoms (data from one RCT in 875 women: odds ratio 0.53, 95% confidence interval 0.31 to 0.93).³ Two RCTs found that transdermal oestrogen at a low dose of 25 μg daily reduced severity of vasomotor symptoms compared with placebo.^4,5 Urogenital system: We found one systematic review (search date 1995) and three subsequent RCTs. The review pooled data from six RCTs.⁶ It found that oestrogen improved urogenital symptoms regardless of the route of administration (no figures available). One subsequent RCT (n=136) found that low dose transdermal oestrogen (25 μg daily) combined with norethisterone acetate significantly reduced vaginal dryness and dyspareunia compared with placebo over six months.⁴ Two other RCTs (n=192) found that local administration of oestrogen using a silicone oestradiol releasing vaginal ring over 24-36 weeks improved vaginal oestrogenisation and pH compared with placebo.^7,8 One of these trials also found a significant reduction in incidence of urinary tract infection in treated women (P=0.008).⁷ Psychological symptoms: We found one systematic review (search date 1995, 14 RCTs, 12 cohort studies), which found that oestrogen reduced depressed mood among menopausal women.⁹ Duration of treatment ranged from one month to two years. Data pooling for oestrogen versus placebo (10 studies) found that oestrogen reduced depressive symptoms (no figures available). We found no RCTs of oestrogen treatment in women with clinically proved depression. We found one systematic review (search date 1996, 10 controlled trials, 9 observational studies) of the effects of oestrogen on cognitive function in postmenopausal women and women with Alzheimer''s disease.¹⁰ Studies were too weak to allow reliable conclusions. An additional crossover RCT (n=62) found a beneficial effect of oestrogen on sleep quality compared with placebo over seven months.¹¹ Quality of life: We found no systematic review. We found four RCTs (639 women, 3 RCTs placebo controlled, 3 versus progestogen), which found significant improvement in quality of life in women treated with oestrogen compared with baseline or placebo.^12–15 The largest RCT (242 women) found that oestrogen improved quality of life (P=0.0003) and wellbeing (P=0.003) compared with placebo over 12 weeks.¹²HarmsMany RCTs have found that oestrogen causes weight gain and breast tenderness in the short term. Although many women report an increase in weight when starting oestrogen, we found no evidence from RCTs that oestrogen causes significant weight gain in the long term. The most important long term adverse effects are increased risk of venous thromboembolic disease, endometrial cancer, and breast cancer.^16–18 The relation between oestrogen (as hormone replacement therapy) and breast cancer was reviewed in a reanalysis of 51 studies of more than 160 000 women.¹⁹ The review found that the risk of breast cancer increased by 2.3% (1.1% to 3.6%) each year in women using hormone replacement therapy. Five or more years after hormone replacement therapy was stopped, there was no significant excess of breast cancer.¹⁹CommentMany studies used selected populations such as women attending hospital clinics, who may be different in their behaviour, personality, and symptom profile to women of the same age seen in primary care or those who do not seek medical advice. Option: ProgestogensSummary We found good evidence from RCTs that progestogens reduce vasomotor symptoms. We found no good quality evidence on other outcomes, including quality of life.BenefitsWe found no systematic review. Vasomotor symptoms: We found five RCTs (257 women, all trials less than a year long), which found that women taking progestogens experienced a significant reduction in vasomotor symptoms compared with placebo.^20–24 The single RCT comparing oestrogen alone with progestogen (150 mg of depot medroxyprogesterone for 25 days a month) found that over three months, 18% of women taking oestrogens and 33% taking progestogen reported no vasomotor symptoms.²¹ One RCT (n=102) found that transdermal progesterone cream 20 mg daily improved vasomotor symptoms compared with placebo (P<0.001) but had no beneficial effect on bone density.²⁵ Urogenital system: We found no RCTs evaluating the effects of progestogens alone on urinary incontinence, the lower genital tract, or sex life. Psychological symptoms: We found no RCTs. Quality of life: One RCT of cyclical progestogen plus oestrogen for six months found no evidence of an effect on quality of life.²⁶ We found no studies of progestogen alone on quality of life.HarmsWe found two RCTs that evaluated harms of progestogens. The first compared continuous progestogen (norgestrel) and placebo in 321 women who had undergone hysterectomy and were already taking conjugated oestrogen. It found no difference in symptoms (including weight gain and bloating).²⁷ The second RCT (875 women) compared various oestrogen-progestogen combinations over three years.³ It found that additional progestogen increased breast discomfort (odds ratio 1.92, 1.16 to 3.09). Neither trial found evidence of an effect on cardiovascular events.CommentProgestogen is seldom given alone, which makes it hard to isolate its effects. When it was given without oestrogen, doses of progestogens were high, the lowest dose being 20 mg medroxyprogesterone acetate per day. Option: TiboloneSummary RCTs found that tibolone significantly improved vasomotor symptoms, libido, and vaginal lubrication.BenefitsWe found no systematic review. Vasomotor symptoms: We found three RCTs, two of tibolone versus continuous combined oestrogen/progestogen treatment over 48 and 52 weeks (672 women with menopausal symptoms)^28,29 and one versus placebo over 16 weeks (82 women with menopausal symptoms).³⁰ The first RCT found a slightly greater reduction in hot flushes with the combined regimen than with tibolone over 48 weeks (P=0.01). The second trial found a significant reduction in vasomotor symptoms from baseline in both groups (67/72 women on HRT and 58/68 women on tibolone, P<0.001) but no significant difference between groups. The third trial found tibolone reduced vasomotor symptoms by 39% compared with placebo (P=0.001). Urogenital system: We found two RCTs. The first RCT found no significant difference between tibolone and combined hormonal treatment in terms of subjective reports of vaginal lubrication; both interventions improved lubrication compared with baseline.²⁸ The second RCT (437 women) found that tibolone improved sexual satisfaction compared with oestradiol plus norethisterone (P<0.05).³¹ We found no RCTs examining effects on urinary incontinence. Psychological symptoms: We found no RCTs. Quality of life: We found no RCTs. Bone density: We found nine RCTs, which found that tibolone increased bone density over periods from 6 to 36 months compared with baseline or placebo.³²HarmsWe found no evidence on adverse effects from RCTs. One non-randomised controlled trial found that the main unwanted effect of tibolone was breakthrough bleeding, which occurred in about 10% of users.³³ We found no good evidence of androgenic adverse effects such as hair growth and greasiness of the skin. Two RCTs of short term use found a 33% reduction in plasma high density lipoproteins with tibolone,^34,35 although the long term effects on cardiovascular disease are unknown.CommentNone. Option: Phyto-oestrogensSummary Limited evidence from small RCTs suggests that soy flour, which contains phyto-oestrogens, may relieve vasomotor menopausal symptoms.BenefitsWe found no systematic review. Vasomotor symptoms: We found three placebo controlled RCTs. Two evaluated soy supplements, which contain phyto-oestrogen, using double blind designs; the other, which was not blinded, evaluated isoflavone. The first RCT (58 postmenopausal women) compared soy flour versus wheat flour for 12 weeks and found that hot flushes were reduced significantly more in the group of women using soy flour (40% v 25% reduction).³⁶ The second RCT used a crossover design to evaluate six weeks'' administration of 34 mg soy protein daily. It found reduced severity but not frequency of vasomotor symptoms.³⁷ The third RCT (n=51) used a crossover design to compare isoflavone 40 mg daily with placebo. It found benefit from placebo compared with baseline, but not with isoflavone.³⁸ Urogenital system: We found no RCTs. Psychological symptoms: We found no RCTs. Beneficial effects of treatment on quality of life: We found no RCTs.HarmsWe found no evidence of significant adverse effects.CommentNone. Option: ClonidineSummary Two RCTs found that clonidine reduced vasomotor symptoms.BenefitsWe found no systematic review. Vasomotor symptoms: We found two RCTs.^39,40 One crossover RCT (66 women) found that clonidine reduced the mean number of flushing attacks in the 14 days after crossover compared with placebo (56.8 v 64.3, P<0.05).³⁰ The second RCT (30 women) found that more women taking clonidine reported reduced flushes at 8 weeks (12/15 v 5/14, P<0.04).⁴⁰ Psychological symptoms: We found no RCTs. Quality of life: We found no RCTs.HarmsThe two RCTs found no significant difference in the incidence of unwanted effects between placebo and active treatment groups.^39,40CommentNone. Option: TestosteroneSummary We found evidence from RCTs that testosterone improves sexual enjoyment and libido. We found no studies evaluating effects on other commonly experienced menopausal symptoms.BenefitsWe found no systematic review. Vasomotor symptoms: We found no RCTs evaluating testosterone alone in women with menopausal symptoms. We found one RCT (93 postmenopausal women) comparing oestrogen alone and oestrogen plus methyltestosterone. This concluded that addition of a small dose of methyltestosterone reduced the dose of oestrogen needed to control menopausal symptoms.⁴¹ Urogenital system: We found two RCTs, one in 40 women and one crossover study in 53 women. Both found benefit from exogenous testosterone on self reported sexual enjoyment, desire, and arousal.^42,43 Psychological symptoms: We found no RCTs. Beneficial effects of therapy on quality of life: We found no RCTs.HarmsWe found no evidence from RCTs or other controlled studies on the incidence of androgenic adverse effects with testosterone.CommentNone. Option: AntidepressantsSummary We found insufficient evidence on the effects of antidepressants on menopausal symptoms.BenefitsWe found no systematic review or RCTs that specifically addressed the effects of antidepressants on menopausal symptoms or quality of life in menopausal women.HarmsWe found no evidence on adverse effects in postmenopausal women. Antidepressants as a group can cause many central nervous system adverse effects, including sedation and agitation, as well as urinary and vision problems, liver dysfunction, and cardiac dysrhythmias.⁴⁴CommentNone.     

Further characterization of the glucocorticoid-induced antiphospholipase protein "renocortin"

The steroid-induced anti-phospholipase protein "Renocortin" has been further characterized by column chromatography and a monoclonal antibody. In medium devoid of foetal calf serum, renomedullary insterstitial cells in culture exposed to the anti-inflammatory steroid dexamethasone released 3 peptides of apparent MW: 15k, 30k, and 45k possessing similar biological properties to "renocortin", "lipomodulin" and "macrocortin". A monoclonal antibody directed against macrocortin also bound the 45k peptide released from the renomedullary cells. The 15k species was, like macrocortin, inactive in an "in vitro" enzymatic assay but recovered its full inhibitory activity after dephosphorylation by alkaline phosphatase treatment. We conclude that "macrocortin", "lipomodulin" and "renocortin" are similar if not identical proteins. We propose a scheme to account for "in vivo" secretion and regulation of these proteins.     

Children and Families "At Promise": Deconstructing the Discourse of Risk

Children and Families "At Promise": Deconstructing the Discourse of Risk. Beth Blue Swadener and Sally Lubeck, eds. Albany: State University of New York Press, 1995. 288 pp.     

Beyond "the State" and Failed Schemes

In this article, I propose five ways to move beyond the analytical scheme of James Scott's Seeing Like a State (1998). I question the spatial optic that posits an "up there," all-seeing state operating as a preformed repository of power, spread progressively outward to "nonstate" spaces beyond its reach. I highlight the role of parties beyond "the state" that attempt to govern—social reformers, scientists, and the so-called nongovernmental agencies, among others. I look beyond authoritarian high modernism to the more general problematic of "improvement" emerging from a governmental rationality focused on the welfare of populations. I explore the recourse to mētis (contextualized, local knowledge and practice) situated beyond the purview of planning. Finally, I reframe the question posed by Scott—why have certain schemes designed to improve the human condition failed?—to examine the question posed so provocatively by James Ferguson: What do these schemes do? What are their messy, contradictory, conjunctural effects?     

Chinchilla "big" and "little" gastrins

Gastrin heptadecapeptides (gastrins I and II which differ in the presence of sulfate on the tyrosine of the latter) have been purified and sequenced from several mammalian species including pig, dog, cat, sheep, cow, human and rat. A 34 amino acid precursor ("big" gastrin), generally accounting for only 5% of total gastrin immunoreactivity, has been purified and sequenced only from the pig, human, dog and goat. Recently we have demonstrated that guinea pig (GP) "little" gastrin is a hexadecapeptide due to a deletion of a glutamic acid in the region 6-9 from its NH2-terminus and that GP "big" gastrin is a 33 amino acid peptide. The chinchilla, like the GP, is a New World hystricomorph. This report describes the extraction and purification of "little" and "big" gastrins from 31 chinchilla antra. Chinchilla "little" gastrin is a hexadecapeptide with a sequence identical to that of the GP and its "big" gastrin is a 33 amino acid peptide with the following sequence: (See text)     

"Being Alive Well": Health and the Politics of Cree Well-Being.

"Being Alive Well": Health and the Politics of Cree Well-Being. Naomi Adelson. Toronto: University of Toronto Press, 2000. ix. 141 pp.     

“一枝好”育发液促进毛发生长及机制探讨

目的:考察利用新疆维吾尔族传统药物研制成的"一枝好"育发液促进毛发生长的效果,并探讨其可能的作用机制。方法:采用硫化钠溶液建立昆明小鼠化学性脱发实验模型,将30只昆明小鼠随机分为实验组、阳性对照组(章光101育发剂)、空白对照组,以毛发评分、毛长、毛重以及毛囊数为指标,考察小鼠新生毛发生长情况。对脱毛后21天的脱毛区皮肤毛长、毛重、毛囊数进行测量和统计分析。并利用MTT法初步探讨"一枝好"育发液对人脐静脉血管内皮细胞(HUVEC)增殖的影响。结果:实验组脱毛区体毛生长评分及毛长,与空白对照组差异显著,并且略高于阳性对照组。对小鼠毛重与毛囊数的统计结果显示,与空白对照组和阳性对照组相比,实验组均有显著性差异(P0.01,P0.001)。"一枝好"育发液能够促进人脐静脉血管内皮细胞(HUVEC)增殖。结论:利用新疆维吾尔族传统药物研制成的"一枝好"育发液,能够显著促进小鼠毛发生长,初步推断其作用机制与促进毛囊生长和促进血管内皮细胞增殖有关。     

Unraveling the "Model Minority" Stereotype: Listening to Asian American Youth.

Unraveling the "Model Minority" Stereotype: Listening to Asian American Youth. Stacey J. Lee. New York: Teachers College Press, 1996. 143 pp.     

About the "double" radioprotecting mechanism of some sulfur-containing substances

The hypothesis about the double-acting mechanism of some radioprotectors during the irradiation of the DNA solutions is expressed in literature: the water radicals interception and the formation up to the irradiation of the additional intermolecular bonds "protector-DNA" (stabilization of the double helix). The realization conditions of this hypothesis were obtained by the molecular mechanics methods and the free radical mechanism appearance of the intrastrand cross-links "protector-DNA" during the irradiation of the polymer is given.     

Opossum (Didelphis virginiana) "little" and "big" gastrins

1. "Little" gastrins from most mammalian species are 17 amino acid peptides and the precursor "big" gastrins are 34 amino acid peptides. 2. "Little" gastrins of the New World hystricomorphs, guinea-pig and chinchilla, are 16 amino acid peptides due to deletion of a glutamic acid in the region 6-9 from their NH2-terminus and the corresponding "big" gastrins are 33 amino acid peptides. 3. Antral gastrins from the opossum, a New World marsupial, have a glutamic acid deletion in the same region as the hystricomorph gastrins. 4. Opossum "big" gastrin is a 33 amino acid peptide with the following sequence: less than ELGPQDLPYLTADLSKKQGPWLEEEEAYGWMDF#.     

The Problem of the "Formative" Elements of Consciousness in the Activity Theory of the Mind

The problem of the structure and psychological mechanisms of consciousness has a rich history, to which M. M. Bakhtin, G. G. Shpet, L. S. Vygotsky, and, later, A. N. Leont'ev and S. L. Rubinshtein all made significant contributions. It is our purpose in the present article to discuss only one aspect of this problem: the structure of individual consciousness. Pursuing the line of research delineated by Vygotsky, Leont'ev (1977) posed some cardinal questions: Of what is consciousness composed? How does it arise? What are its components? He called the latter the "formative elements" of consciousness. According to Leont'ev, there are three such "forming" elements: the sensory fabric of perception (or of an image), meaning, and sense. The inclusion of the sensory fabric in the structure of consciousness along with ostensive meaning and sense was a definite step forward along the path toward the ontologization of conceptions of consciousness.¹ But I think that individual consciousness construed in this way is still insufficiently ontological. Leont'ev's three "formative elements" do not completely account for the connection between consciousness and being (see M. M. Bakhtin, for whom consciousness "participates" in being and is essential for life). One might even reproach Leont'ev for a certain inconsistency: activity, although it is the source of consciousness, is itself not one of its "formative elements." Of course, he could answer this reproach by saying that the "formative elements" are structural elements, constituents, not generative elements. However, it seems to me that the distinction between constitutive and generative is very, very relative in any analysis of living consciousness, which is continually in the process of being constructed.     

Orienting reflex: "targeting reaction" and "searchlight of attention"

The concept of orienting reflex based on the principle of vector coding of cognitive and executive processes is proposed. The orienting reflex to non-signal and signal stimuli is a set of orienting reactions: motor, autonomic, neuronal, and subjective emphasizing new and significant stimuli. Two basic mechanisms can be identified within the orienting reflex: a "targeting reaction" and a "searchlight of attention". In the visual system the first one consists in a foveation of a target stimulus. The foveation is performed with participation of premotor neurons excited by saccadic command neurons of the superior colliculi. The "searchlight of attention" is based on the resonance of gamma-oscillations in the reticular thalamus selectively enhancing responses of cortical neurons (involuntary attention). The novelty signal is generated in novelty neurons of the hippocampus, which are selectively tuned to a repeatedly presented standard stimulus. The selective tuning is caused by the depression of plastic synapses representing a "neuronal model" of the standard stimulus. A mismatch of the novel stimulus with the established neuronal model gives rise to a "novelty signal" enhancing the novel input. The novelty signal inhibits current conditioned reflexes (external inhibition) contributing to redirecting the behavior. By triggering the expression of early genes the novelty signal initiates the formation of the long-term memory connected with neoneurogenesis.     

Concept problem "the functional condition" in modern physiology

The concept "functional state" is discussing with attraction notion about fundamental components of live organism: substance, structure, production of energy and information, entropy. In the specified terms is giving working definition of functional condition. From such of positions the normal functional state, and its making--physiological state and psychological state, is considered.     

Cytogerontology at the beginning of the third millenium: from "correlative" to "gist" models

For the most part, research in the area of cytogerontology, i.e., investigation of the mechanisms of aging in the experiments on cultured cells, is carried out using the "Hayflick's model". More than forty years have passed since the appearance of that model, and during this period of time, very much data were obtained on its basis. These data contributed significantly to our knowledge of the behavior of both animal and human cultured cells. Specifically, we already know of the mechanisms underlying the aging in vitro. On the other hand, in my opinion, little has changed in our knowledge of the aging of the whole organism. In all likelihood, this can be explained by that the Hayflick's model is, like many others used in the experimental gerontology, correlative, i.e. based on a number of detected correlations. In the case of Hayflick's model, these are correlations between the mitotic potential of cells (cell population doubling potential) and some "gerontological" parameters and indices: species life-span, donor age, evidence of progeroid syndromes, etc., as well as various changes of normal (diploid) cells during long-term cultivation and during aging of the organism. It is, however, well known that very frequently a good correlation has nothing to do with the essence (gist) of the phenomenon. For example, we do know that the amount of gray hair correlates quite well with the age of an individual but is in no way related to the mechanisms of his/her aging and probability of death. In this case, the absence of cause-effect relationships is evident, which are, at the same time, indispensable for the development of gist models. These models, as distinct from the correlative ones, are based on a certain concept of aging. In the case of Hayflick's model, such a concept is absent: we cannot explain, using the "Hayflick's limit", why our organism ages. This conclusion was convincingly confirmed by the discovery of telomere mechanism which determines the aging of cells in vitro. That discovery initiated the appearance of theories attempting to explain the process of aging in vivo also on its basis. However, it has become clear that the mechanisms of aging of the entire organism, located, apparently, in its postmitotic cells, such as neurons or cardiomyocytes, cannot be explained in the framework of this approach. Hence, we believe that it is essential to develop "gist" models of aging using cultured cells. The mechanisms of cell aging in such models should be similar to the mechanisms of cell aging in the entire organism. Our "stationary phase aging" model could be one of such models, which is based on the assumption of the leading role of cell proliferation restriction in the processes of aging. We assume that the accumulation of "senile" damage is caused by the restriction of cell proliferation either due to the formation of differentiated cell populations during development (in vivo) or to the existence of saturation density phenomenon (in vitro). Cell proliferation changes themselves do not induce aging, they only lead to the accumulation of macromolecular defects, which, in turn, lead to the deterioration of tissues, organs, and, eventually, of the entire organism, increasing the probability of its death. Within the framework of our model, we define cell aging as the accumulation in a cell population of various types of damage identical to the damage arising in senescing multicellular organism. And, finally, it is essential to determine how the cell is dying and what the death of the cell is. These definitions will help to draw real parallels between the "genuine" aging of cells (i.e., increasing probability of their death with "age") and the aging of multicellular organisms.     

Proteolytic Digestion Patterns of "Soluble"and "Detergent-Soluble"Bovine Caudate Nucleus Acetylcholinesterases

Abstract: The structures of purified "soluble"and "detergent-soluble"bovine caudate nucleus acetylcholinesterases were compared by peptide mapping on polyacrylamide gels. The digestion products generated from the two acetylcholinesterases on proteolysis by a given protease ( Staphylococcus aureus V8 protease, α-chymotrypsin, or papain) are remarkably similar as judged from the electrophoretic band patterns. We conclude that the "soluble"and "detergent-soluble"acetylcholinesterases from bovine caudate nucleus share a common evolutionary origin.     

锌胁迫对“不知火”和“椪柑”的生理指标及锌分布的影响

采用砂基培养法,研究了0、0.05和0.5 mg·L^-1Zn²⁺（0.05 mg·L^-1为对照,0.5 mg·L^-1为锌过量,0 mg·L^-1为锌缺乏）处理下“不知火”和“椪柑”叶片的一些生理指标及不同部位锌含量的变化。结果表明：1）缺锌处理的“不知火”叶绿体色素含量和叶面积均显著低于其对照和锌过量处理;锌过量处理的“椪柑”叶绿体色素含量和叶面积均显著低于对照。2) 3个锌浓度处理间,“不知火”叶片POD、“椪柑”叶片CAT活性无显著性差异,“不知火”叶片CAT、SOD活性随着锌浓度的升高而升高,锌缺乏处理下“椪柑”叶片POD、CAT、SOD活性均显著地高于“不知火”,而锌过量时“不知火”叶片SOD活性显著高于“椪柑”;锌胁迫下“不知火”和“椪柑”叶片MDA含量均显著高于对照,锌过量时“椪柑”叶片MDA含量显著高于“不知火”。3）2品种柑橘不同部位的锌含量随着锌处理浓度的升高而升高,在相同浓度的锌处理下“椪柑”叶锌含量显著高于其他部位及“不知火”叶锌含量,“不知火”上部叶锌含量显著高于其下部叶。     

"Cap" on the tip of Salmonella flagella

Flagellar filaments isolated intact from a Salmonella short-flagella mutant are unable to serve as nuclei for flagellin polymerization in vitro, whereas the filaments reconstructed in vitro from the mutant flagellin are able to do so. The inability of intact flagella to nucleate flagellin polymerization appears to be common to wild-type bacteria and thus suggests that the tip of intact flagella are generally inactivated or capped in vivo. Careful observations of the tips of intact flagella and reconstructed flagellar filaments of a wild-type species have revealed marked difference between them: the intact flagella usually have blunt ends, whereas reconstructed filaments have concave, "fish-tail" ends. Moreover, a thin structure is often observed attaching to the very end of the intact flagella. We suspect that this "capping" structure is essential to the elongation mechanism of flagellar filaments.     

Equilibrium between the "genuine mutualists" and "symbiotic cheaters" in the bacterial population co-evolving with plants in a facultative symbiosis

The mathematical model for evolution of the plant-microbe facultative mutualistic interactions based on the partners’ symbiotic feedbacks is constructed. Using the example of rhizobia-legume symbiosis, we addressed these feedbacks in terms of the metabolic exchange resulting in the parallel improvements of the partners’ fitness (positive feedbacks). These improvements are correlated to the symbiotic efficiency dependent on the ratio of N₂-fixing bacterial strains (“genuine mutualists”) to the non- N₂-fixing strains (“symbiotic cheaters”) in the root nodules. The computer experiments demonstrated that an interplay between the frequency-dependent selection (FDS) and the Darwinian (frequency-independent) selection pressures implemented in the partners’ populations ensures an anchoring or even domination for the newly generated host-specific mutualists (which form N₂-fixing nodules only with one of two available plant genotypes) more successfully than for the non-host-specific mutualists (which form N₂-fixing nodules with both plant genotypes). The created model allows us to consider the mutualistic symbiosis as a finely balanced polymorphic system wherein the equilibrium in bacterial population may be shifted in favor of “genuine mutualists” due to the partner-stipulated selection for an improved symbiotic efficiency implemented in the plant population.     

Breathing patterns peculiarities as the index of the "animal hypnosis" state in the rabbit

Breathing patterns were recorded during "animal hypnosis" in seven Chinchilla rabbits. The state of "animal hypnosis" was evoked by the hand pressure on the thorax and the waist of a rabbit. Breathing pattern was recorded by means of an elastic coal-powder element that was set round the rabbit's thorax. Distortions of the breathing patterns in the active state and in the course of hypnosis development were marked by numbers 0, 1, 2. In all rabbits, modifications of the breathing patterns depended on the features of the animal state: quiet state, tension, and "animal hypnosis".