Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Explainability”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 253 records · Page 14Linked to original sources
PubMed2005

Selection for high gamete encounter rates explains the evolution of anisogamy using plausible assumptions about size relationships of swimming speed and duration.

A previous general model describing physical constraints on gamete encounter rates was modified to incorporate assumptions that increased size causes decreased swimming speed and increased fertile period (or other proportional enhancement to gamete fertility). The analysis indicates that with moderately strong size dependence of fertile period and a range of speed dependencies, selection for high encounter rates pressures mating systems that develop any heritable difference in size between the gametes of different mating types to exaggerate the difference and evolve from isogamy to anisogamy. The smaller gamete has an optimal size, but the larger faces continuing selection for increased size. This continues to a size that is estimated to be sufficient to make pheromone production of sperm attractants practical. This mechanism then bridges the missing link between isogametes and oogamy in a previous analysis of the effectiveness of pheromones in explaining the success of male-female mating systems. The evolution and success of anisogamy and oogamy can be explained solely on the basis of physical effects on the encounter process.

Animals↗
PubMed2006

Why kin and group selection models may not be enough to explain human other-regarding behaviour.

Models of kin or group selection usually feature only one possible fitness transfer. The phenotypes are either to make this transfer or not to make it and for any given fitness transfer, Hamilton's rule predicts which of the two phenotypes will spread. In this article we allow for the possibility that different individuals or different generations face similar, but not necessarily identical possibilities for fitness transfers. In this setting, phenotypes are preference relations, which concisely specify behaviour for a range of possible fitness transfers (rather than being a specification for only one particular situation an animal or human can be in). For this more general set-up, we find that only preference relations that are linear in fitnesses can be explained using models of kin selection and that the same applies to a large class of group selection models. This provides a new implication of hierarchical selection models that could in principle falsify them, even if relatedness--or a parameter for assortativeness--is unknown. The empirical evidence for humans suggests that hierarchical selection models alone are not enough to explain their other-regarding or altruistic behaviour.

Altruism↗
PubMed2005

Are genes of human intelligence related to the metabolism of thyroid and steroids hormones? - endocrine changes may explain human evolution and higher intelligence.

We propose the hypothesis that genes of human intelligence are related with metabolism of thyroid and steroids hormones, which have a crucial role in brain development and function. First, there is evidence to support the idea that during hominid evolution small genetic differences were related with significant endocrine changes in thyroid and steroids hormones. Second, these neuroactive hormones are also related with unique features of human evolution such as body and brain size increase, penis and breast enlargement, pelvic sexual dimorphism, active sexuality, relative lack of hair and higher longevity. Besides underling many of the differences between humans and great apes, steroids hormones promote brain growth and development, are important in the myelination process, explain sexual dimorphisms in brain and intelligence and improve specific cognitive abilities in humans. Supporting our hypothesis, recent studies indicate differences in neuroactive hormones metabolism between humans and non-human primates. Furthermore, a link between X chromosome genes and sex steroids may explain why the frequency of genes affecting intelligence is so high on the X chromosome. This association suggests that, during hominid evolution, there was a positive feedback in both sexes on the same genes responsible for secondary sexual character development and intelligence. This interaction leads to acceleration of development of human brain and intelligence. Finally, we propose that neuroactive hormone therapy may provide significant improvement in some cognitive deficits in all stages of human life and in cases of neurodegenerative diseases. However, further investigation is needed, mainly in the enzymatic machinery, in order to understand the direct role of these hormones in intelligence.

Animals↗
PubMed2006

Time-estimation error following Weber-Fechner law may explain subadditive time-discounting.

Impulsivity in drug addicts have been associated with impatience in intertemporal choice, i.e., high degrees to which delayed rewards are discounted, indicating the importance of reducing the degree of discounting in drug addicts. Intertemporal choice (delay discounting) has been attracting attention in neuropsychopharmacology and behavioral neuroeconomics. Recently, behavioral economists have reported that impatience/impulsivity in intertemporal choice is increased if a delay period is presented as a sum of divided time-blocks, which is referred to as subadditive discounting (i.e., "total patience" over the delay period is larger than the "sum of patience" over divided delay periods). This finding implies that abstinent drug addicts may more readily relapse into addiction if an abstinence period is presented as a series of shorter abstinent periods, rather than a single block of a long abstinence period. Therefore, understanding of neuropsychological processing underlying subadditive discounting is important for establishing medical treatments of drug addiction, although to date, no study has addressed this question. In this study, we propose that time-estimation following Weber-Fechner law, formerly introduced for explaining hyperbolic discounting, may also explain subadditive discounting. Our present hypothesis also predicts that possibility of relapse into drug dependence can be decreased by helping abstinent patients to perceive time-duration of an abstinence/withdrawal period precisely.

Behavior, Addictive↗
PubMed2004

Negative symptoms of schizophrenia could explain discrepant data on the association between the 5-HT2A receptor gene and response to antipsychotics.

Pharmacogenetic studies assessing the role of 5-HT(2A) receptor gene in antipsychotic efficacy yielded conflicting data. Phenotypical heterogeneity of schizophrenia might explain such discrepancies. For example, negative symptoms are known to reflect severity of illness and to restrain therapeutic response. On this basis, we re-assessed the possible influence of the -1438A/G polymorphism of the 5-HT(2A) receptor gene on the clinical efficacy of atypical antipsychotics with focus on several relevant dimensions. One hundred and sixteen French schizophrenic subjects treated for at least 1 month by atypical antipsychotics were screened for treatment response according to the May and Dencker scale. Gender, age at onset, duration and severity of illness, intensity of negative and positive symptoms at discharge were investigated. The intensity of negative symptoms at discharge was the only variable explaining May and Dencker score (p < 0.001), and was significantly associated with the AA genotype of the -1438A/G polymorphism of the 5-HT(2A) receptor gene (p = 0.03). However, the A allele was not independently associated with refractoriness to atypical antipsychotics. Accordingly, the score reached in the Scale for the Assessment of Negative Symptoms (SANS) appeared as a confounding factor between therapeutic response and the -1438A/G polymorphism of the 5-HT(2A) receptor gene, at least in our sample. This data indicate that negative symptoms are worth being systematically assessed in pharmacogenetic studies aimed at analysing candidate genes in schizophrenia.

Adult↗
PubMed2005

Semantic relevance explains category effects in medial fusiform gyri.

We used functional Magnetic Resonance Imaging to explore the neural correlates of semantic relevance in 12 healthy participants performing a picture-naming task. In addition, we tested the hypothesis that category effects typically found in functional imaging can be partly explained in terms of different semantic relevance for animals and artefacts. We report that semantic relevance modulates neuronal responses in the medial fusiform gyrus bilaterally. As predicted, category effects in this region are strongly modulated by the semantic relevance of the items. Specifically, the effect of artefacts > animals is greatly reduced when the two categories are matched for semantic relevance. Thus, the present study demonstrates that neuronal responses during concept retrieval are modulated by the semantic relevance of the features. It also suggests that increased activation in the medial fusiform gyrus typically found for artefacts > animals can be explained by different semantic relevance for animal and artefact items.

Adult↗
PubMed2006

Neurocognitive performance and negative symptoms: are they equal in explaining disability in schizophrenia outpatients?

OBJECTIVE: The aim of this study is to assess if cognitive variables and symptom dimensions can predict disability in a sample of outpatients with schizophrenia. METHOD: A cross-sectional sample of 113 individuals with a diagnosis of schizophrenia (DSM-IV criteria) was selected from a computerized register of five Community Mental Health Centers. Patients were assessed by two trained psychologists, with a neuropsychological battery comprising measures for verbal memory, attention, operative memory and abstraction and flexibility functions. Symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS); a socio-demographic and clinical questionnaire, comprising the Disability Assessment Scale (DAS), was also completed. Test scores were standardized (t scores) to performance of healthy controls. To assess the relationship between clinical and sociodemographic factors and disability and cognitive functioning Pearson's correlation coefficients were computed. In order to establish the predictive capacity of the cognitive, clinical and symptom variables on disability linear regression models were fitted. RESULTS: Mean age of patients was 41.6 years and 68% were male. Higher ratings in the negative dimension were associated with more cognitive deficits. Association with the positive dimension was present but less strong. All disability areas, except for disability in occupational functioning, were partially explained by the negative dimension. Disability in family functioning was also partially explained by attention and number of admissions since onset. CONCLUSION: Negative symptoms are the major source of disability of our sample and are also associated to cognitive functioning. The present findings suggest that further investigation on the mediators between clinical and social outcomes may help to design specific treatments to reduce disability.

Adult↗
PubMed2004

Can climate change explain increases in DOC flux from upland peat catchments?

Long-term increases in DOC concentration in rivers draining areas of upland peat are a ubiquitous phenomenon in the UK. Several hypotheses have been proposed to explain these increases, but one compelling explanation is the observed long-term increase in temperature in UK uplands causing increases in peat decomposition rates, and increasing the depth of oxidation as evaporation increases depth to the water table. The study constructed an empirical model for water table depth and decomposition rate calibrated against observations from the Environmental Change Network monitoring site at Moor House in the North Pennines, UK. The study shows: (i) Depth of the water table has not changed significantly over a 30-year period, reflecting the fact that blanket peat is well buffered against climate change. (ii) Increases in temperature are responsible for a 12% increase in DOC production while an approximate 78% increase in DOC production has been observed. (iii) Overall DOC production is predicted to rise by 6% but observation suggests increases on the scale of 97%. (iv) The model inadequately represents changes in production and supply of DOC during periods of severe drought. The study shows that temperature change alone is insufficient to explain observed increases in DOC production. Alternative explanations for large increases in DOC production could include changes in land management, but an enzymic latch mechanism, i.e. derepression of anaerobic degradation, causing increased decomposition rates in response to severe drought is preferred.

Carbon↗
PubMed2006

Tumor necrosis factor antagonists: different kinetics and/or mechanisms of action may explain differences in the risk for developing granulomatous infection.

OBJECTIVE: Tumor necrosis factor (TNF) antagonists fall into 2 classes:etanercept (ETA) is a soluble TNF receptor, while infliximab (INF) and adalimumab (ADA) are monoclonal antibodies against TNF. All 3 drugs are effective in treating rheumatoid arthritis. However, these agents have been associated with an increased risk of granulomatous infections, such as tuberculosis and histoplasmosis. Several reports indicate that the incidence of granulomatous infections may potentially be higher in individuals treated with INF than ETA. METHODS: We conducted a comprehensive literature search (1966 to 2004) to review the role of TNF in normal and disease states, and the mechanisms of action of the TNF inhibitors. Specifically, we searched for possible mechanisms for the apparent increase in granulomatous infections associated with TNF inhibitors and for reasons that there may be differences between them. RESULTS: Infection may result from a number of differences between ETA and INF or ADA. First, binding avidities are different, with ETA binding in a 1:1 ratio and INF/ADA binding in 2 to 3:1 ratios. Second, the clearances of ADA, ETA, and INF are different, being about 13 times higher for ETA than INF or ADA, thus resulting in higher steady-state drug levels for ADA and INF. Also, the methods of administration are different, intravenously (for INF) versus subcutaneously (for ETA and ADA), which results in lower peak concentrations for ETA and ADA, potentially explaining some of the differences in effects on granuloma formation. Third, INF and ADA have somewhat different mechanisms of action from ETA: INF and ADA are associated with antibody-mediated cell lysis, while ETA is not; INF may induce apoptosis in some tissues (eg, gastrointestinal [GI] mucosa) while ETA does not--although this is controversial and may not be true at steady state in synovium, where both drugs seem to cause apoptosis; ETA binds lymphotoxin-alpha while INF does not (ETA may thus be more efficient at preventing granuloma formation by this mechanism than INF); finally, ADA and INF seem to inhibit IFN-gamma expression (probably indirectly), while ETA does not. CONCLUSIONS: There are significant differences between the 2 classes of TNF antagonists in terms of both their kinetics and mechanisms of action. These differences may help explain the apparent differences in the incidence of granuloma-dependent infections among them.

Antirheumatic Agents↗
PubMed2005

Is the urban excess in lung cancer in Scotland explained by patterns of smoking?

Numerous studies have shown that lung cancer rates are higher in urban than rural areas, controlling for differences in age and sex profiles. One explanation is that smoking rates are higher in urban areas, although it is not clear whether the variations in smoking behaviour fully account for the observed urban/rural gradient in lung cancer incidence. Indeed, some studies have demonstrated an excess of cases in urban areas, even controlling for smoking behaviour. However, previous studies have been hampered by the lack of small-area smoking estimates which are required if urban/rural variations are to be examined reliably. This paper considers whether there is an urban excess in lung cancer incidence in Scotland, a country with particularly high rates of the disease, for the period 1988-1991. First, we examine whether an urban excess exists in Scotland using Poisson probabilities and a cluster detection technique. Second, regression analysis was then used to test whether any urban excess in lung cancer incidence remained once smoking behaviour was controlled for, using smoking estimates calculated for small areas throughout Scotland. The results demonstrate that the rates of lung cancer were higher in urban areas and that all the significant clusters of cases of lung cancer were located in the large urban centres of Scotland. Smoking behaviour did account for much of this urban excess in lung cancer, although it did not explain the entire effect. These results suggest that there are urban effects that influence the incidence of lung cancer that are not explained entirely by smoking behaviour. Possible explanations include the variations in exposure to air pollution, occupational differences and the legacy of selective migration between urban and rural areas.

Adult↗
PubMed2005

The role of psychosocial factors in explaining socio-economic differences in mobility decline in a chronically ill population: results from the GLOBE study.

In chronically ill patients, mobility develops more unfavorably in persons with low socio-economic status (SES) than in their better-off counterparts. Using longitudinal data from the Dutch GLOBE study (a study of health and living conditions in Eindhoven and its surroundings), the present study examines whether psychosocial factors can explain socio-economic differences in mobility decline, independent of disease severity, co-morbidity, and health-related behavior in a chronically ill population. Data were from 1384 men and woman, aged 15-74 years, suffering from at least one of the four chronic diseases: asthma/COPD, heart disease, diabetes mellitus, and low back pain. Three indicators of SES were used: education, occupational class, and income. Change in physical mobility between 1991 and 1997 was measured with the Nottingham Health Profile (NHP). Psychosocial factors were measured extensively and included life events, long-term difficulties, coping styles, social support, and personality characteristics. Low occupational level and low income predicted an increased risk of mobility decline in comparison to people with a higher occupational level and income, even after controlling for sociodemographics, disease severity, co-morbidity, and health-related behavior. Additional adjustment for psychosocial factors hardly reduced the SES-related odds ratios of mobility decline. We conclude that psychosocial factors (and also health-related behaviors, disease severity and co-morbidity) cannot explain socio-economic differences in mobility decline in a chronically ill population. Our findings will not give us new tools for prevention and intervention strategies in order to reduce physical disability and particularly the SES differences therein.

Adolescent↗
PubMed1998

Hormone replacement therapy and body size: how much does lifestyle explain?

OBJECTIVE: Our purpose was to assess the association of hormone replacement therapy with body size. STUDY DESIGN: A total of 1658 randomly selected women aged 45 to 64 years in four regions (two provinces in eastern Finland, one southwestern province, and the capital area) were studied in a 1992 population survey. Linear regression analysis was used to assess the use of hormone replacement therapy as a determinant of body size, measured with the body mass index, the waist/hip ratio, and the body fat percentage and adjusted by sociodemographic (area and education) and lifestyle (diet, smoking, physical activity, and alcohol use) factors. The regression coefficients of hormone replacement therapy use obtained from the model when including sociodemographic and lifestyle variables (beta 1a[Hormone replacement therapy use] = -0.98) were compared with the coefficients obtained when these variables were excluded (beta 1b[Hormone replacement therapy use] = -1.36). The percentage of change (beta 1b-beta 1a/beta 1b%) in the regression coefficients denoted the variability explained by sociodemographic and lifestyle characteristics. RESULTS: Hormone replacement therapy users (28%, n = 463) had higher education, were more often from the capital area, had a significantly higher healthy diet factor score, and were leaner than nonusers. Use of hormone replacement therapy remained a significant determinant of body mass index, waist/hip ratio, and body fat percentage after adjusting for sociodemographic and lifestyle factors. Of the difference in body mass index between hormone replacement therapy users and non-users, 28% were explained by lifestyle and sociodemographic risk factors, respectively, 31% of the difference by use of the waist/hip ratio and 42% by use of the body fat percentage. CONCLUSIONS: The difference in body size between hormone replacement users and nonusers may not be the result of self-selection. The use of hormone replacement therapy was inversely associated with body size in menopause.

Body Composition↗
PubMed2000

Isoform-specific lidocaine block of sodium channels explained by differences in gating.

When depolarized from typical resting membrane potentials (V(rest) approximately -90 mV), cardiac sodium (Na) currents are more sensitive to local anesthetics than brain or skeletal muscle Na currents. When expressed in Xenopus oocytes, lidocaine block of hH1 (human cardiac) Na current greatly exceeded that of mu1 (rat skeletal muscle) at membrane potentials near V(rest), whereas hyperpolarization to -140 mV equalized block of the two isoforms. Because the isoform-specific tonic block roughly parallels the drug-free voltage dependence of channel availability, isoform differences in the voltage dependence of fast inactivation could underlie the differences in block. However, after a brief (50 ms) depolarizing pulse, recovery from lidocaine block is similar for the two isoforms despite marked kinetic differences in drug-free recovery, suggesting that differences in fast inactivation cannot entirely explain the isoform difference in lidocaine action. Given the strong coupling between fast inactivation and other gating processes linked to depolarization (activation, slow inactivation), we considered the possibility that isoform differences in lidocaine block are explained by differences in these other gating processes. In whole-cell recordings from HEK-293 cells, the voltage dependence of hH1 current activation was approximately 20 mV more negative than that of mu1. Because activation and closed-state inactivation are positively coupled, these differences in activation were sufficient to shift hH1 availability to more negative membrane potentials. A mutant channel with enhanced closed-state inactivation gating (mu1-R1441C) exhibited increased lidocaine sensitivity, emphasizing the importance of closed-state inactivation in lidocaine action. Moreover, when the depolarization was prolonged to 1 s, recovery from a "slow" inactivated state with intermediate kinetics (I(M)) was fourfold longer in hH1 than in mu1, and recovery from lidocaine block in hH1 was similarly delayed relative to mu1. We propose that gating processes coupled to fast inactivation (activation and slow inactivation) are the key determinants of isoform-specific local anesthetic action.

Animals↗
PubMed2002

Electrostatics explains the shift in VDAC gating with salt activity gradient.

We have analyzed voltage-dependent anion-selective channel (VDAC) gating on the assumption that the states occupied by the channel are determined mainly by their electrostatic energy. The voltage dependence of VDAC gating both in the presence and in the absence of a salt activity gradient was explained just by invoking electrostatic interactions. A model describing this energy in the main VDAC states has been developed. On the basis of the model, we have considered how external factors cause the redistribution of the channels among their conformational states. We propose that there is a difference in the electrostatic interaction between the voltage sensor and fixed charge within the channel when the former is located in the cis side of membrane as opposed to the trans. This could be the main cause of the shift in the probability curve. The theory describes satisfactorily the experimental data (Zizi et al., Biophys. J. 1998. 75:704-713) and explains some peculiarities of VDAC gating. The asymmetry of the probability curve was related to the apparent location of the VDAC voltage sensor in the open state. By analyzing published experimental data, we concluded that this apparent location is influenced by the diffusion potential. Also discussed is the possibility that VDAC gating at high voltage may be better described by assuming that the mobile charge consists of two parts that have to overcome different energetic barriers in the channel-closing process.

Biophysical Phenomena↗
PubMed1999

Differential dissociation kinetics explain the binding preference of insulin-like growth factor binding protein-6 for insulin-like growth factor-II over insulin-like growth factor-I.

Insulin-like growth factor binding protein-6 binds insulin-like growth factor-II with a marked preferential affinity over insulin-like growth factor-I. The kinetic basis of this binding preference was studied using surface plasmon resonance. Binding of insulin-like growth factor-I and insulin-like growth factor-II to immobilized insulin-like growth factor binding protein-6 fitted a two-site binding kinetic model. Insulin-like growth factor-I and insulin-like growth factor-II association rates were similar whereas the dissociation rate was approximately 60-fold lower for insulin-like growth factor-II, resulting in a higher equilibrium binding affinity for insulin-like growth factor-II. The equilibrium binding affinities of a series of insulin-like growth factor-II mutants were also explained by differential dissociation kinetics. O-glycosylation had a small effect on the association kinetics of insulin-like growth factor binding protein-6. The insulin-like growth factor binding properties of insulin-like growth factor binding protein-6 are explained by differential dissociation kinetics.

Binding, Competitive↗
PubMed2001

The -629C>A polymorphism in the CETP gene does not explain the association of TaqIB polymorphism with risk and age of myocardial infarction in Icelandic men.

The aim of this study was to examine whether the well-established effect of the common TaqIB polymorphism in intron 1 of the gene for cholesterol ester transfer protein (CETP) on high density lipoprotein cholesterol (HDL-C) concentration and increased risk of myocardial infarction (MI), could be explained by the recently identified -629C>A functional polymorphism in the promoter. Non-fatal MI cases (388 male) and a control group of 794 healthy men were recruited from the 30 year long prospective Reykjavik Study. In the healthy men the frequency of the TaqIB B2 allele was 0.47 (95% CI: 0.44-0.50) and there was a strong allelic association with the -629A allele (D=-0.21, P<0.0001), which had a frequency of 0.52 (95% CI: 0.49-0.56). B2B2 homozygotes displayed 15% higher HDL-C levels than subjects homozygous for the B1 allele (P<0.0001). Homozygotes for the -629A allele displayed 14% higher HDL-C concentrations than subjects homozygous for the -629C allele (P<0.0001). The frequencies of the alleles associated with lower HDL-C were significantly higher in cases compared with controls, 0.59 versus 0.53 (TaqIB B1) and 0.52 versus 0.48 (-629 C) respectively (P<0.05 for both). There was a significantly higher risk for MI in B1B1 homozygotes (OR=1.44, 95% CI: 1.10-1.87, P<0.01), compared to the other genotypes combined. This was not observed for the CC homozygotes (OR=1.16, 95% CI: 0.87-1.54). In addition, homozygotes for the TaqI B2 allele experienced a first MI 2 years later than men with other genotypes, 59 versus 61 years (P<0.05). This effect was not seen for the promoter polymorphism. These results strongly confirm the role of the CETP gene and the TaqIB variant as a risk factor for MI and suggest that another functional polymorphism is yet to be discovered in the CETP gene, that will explain the effect on MI associated with TaqIB observed in this study.

Aged↗
PubMed2003

Plasma fibrinogen explains much of the difference in risk of coronary heart disease between France and Northern Ireland. The PRIME study.

The incidence of coronary heart disease is higher in Northern Ireland than in France. These differences have not been adequately explained. We have investigated the associations of plasma fibrinogen concentration and factor VII activity with the incidence of coronary heart disease in a prospective cohort study involving 10600 men aged 50-59 living in four regions (Lille, Strasbourg, and Toulouse in France, Belfast in Northern Ireland). Baseline fibrinogen and factor VII were measured in 9489 men free of coronary heart disease at entry (7167 in France and 2322 in Northern Ireland). Over 5 years of follow-up, 161 participants developed myocardial infarction (MI) or coronary death (100 in France and 61 in Belfast) and 151 developed angina pectoris (94 in France and 57 in Belfast). The risk of future coronary events was 1.9 times higher in Belfast than in France (95% confidence interval: 1.5-2.4). Baseline mean levels of fibrinogen were significantly higher in Belfast than in France and they were higher in participants who experienced coronary events compared with those who did not in both countries. The age-adjusted relative risk of coronary heart disease associated with a rise of one standard deviation in fibrinogen level was 1.56 (95% confidence interval: 1.29-1.95, P<0.0001) in the whole cohort. This association remained significant after adjustment for other cardiovascular risk factors (relative risk:1.36; 95% confidence interval: 1.14-1.68; P<0.0001). There was no clear geographical variation in factor VII and no significant association between factor VII levels and the risk of coronary events was observed. Classic risk factors explained 25% of the excess risk of coronary heart disease in Belfast compared with France, while fibrinogen alone accounted for 30%. These findings add to the epidemiological evidence that elevated fibrinogen is a major risk factor for coronary heart disease.

Coronary Disease↗
PubMed2002

Models of skeletal muscle to explain the increase in passive stiffness in desmin knockout muscle.

Absence of desmin in skeletal muscle was found to induce an increase in passive stiffness. The present study aimed at developing rheological models of passive muscle to explain this stiffening. Models were elaborated by using experimental data depicting muscle viscoelastic behaviour. The experimental protocol included stepwise extension tests applied on control and desmin knockout soleus muscles from mice. Linear and non-linear models were composed of elastic and viscous elements. They were constructed with the aim at taking the presence or absence of desmin into account by simulating desmin as an elastic element. Furthermore, associated adaptation of connective tissues in absence of desmin was modelled as an additional elastic element. Differences in passive behaviour induced by absence of desmin were predicted by using a linear model and a non-linear one. The non-linear model was selected because: (1) it is able to predict experimental viscoelastic kinetics accounting for the increase in passive stiffness in muscles lacking desmin, (2) its design is consistent with morphological data, and (3) stiffness characteristics of its elements are in accordance with the literature. Finally, this modelling approach demonstrates that both absence of desmin and adaptation of connective tissue are required to explain the increase in passive stiffness in desmin knockout muscles.

Animals↗