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PubMed1979

[Orientations and models in psychogerontology (author's transl)].

As Baltes and Willis (1977) state: theories, especially psychological theories are scarce in gerontology. When we look at the short history of psychogerontology, we can differ as the first period: the period of the biological model, which offered only a negative image of growing older. This deficit-model has been unmasked, especially by the growing consciousness of the difference between cross-sectional versus longitudinal research-data. Other models as the disengagement model have been stressed. The present development towards a life-span developmental model as the background for every period of the aging process appears as the only basis for a fruitful growth of the science of psychogerontology.

Aged↗
PubMed1975

Pancreatic neoplasms in an animal model: morphological, biological, and comparative studies.

After a short latency (15 weeks), a 100% incidence of pancreatic neoplasms was induced in Syrian golden hamsters, following the administration of 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN). Data extracted from reports of human pancreatic neoplasms were compared with findings relative to the induced neoplasms. The latter resembled human pancreatic tumors, in both biological and morphological aspects.

Adenocarcinoma↗
PubMed1978

Fluorine-19 nuclear magnetic resonance studies of lipid phase transitions in model and biological membranes.

Fluorinated fatty acids of the general formula CH3(CH2)13-mCF2(CH2)m-2COOH are informative spectroscopic probes of the gel to liquid-crystalline phase transitions in phospholipid dispersions and in biological membranes. We present theoretical considerations to suggest that the 19F nuclear magnetic resonance line shapes are very different for frozen and fluid lipid regions. Our studies confirm this expectation for mixed phospholipid multilamellar dispersions containing a trace of difluoromyristate. The method correctly measures the onset and completion temperatures of the transition in the well-studied dimyristoylphosphaditylcholine distearoylphosphatidylcholine system and also describes the motional behavior of the solid and fluid phases within the transition. Lipids extracted from Escherichia coli membranes show similar motional phenomena through the transition-temperature range according to 19F nuclear magnetic resonance studies of difluoromyristate biosynthetically incorporated into the K1060B5 strain, an unsaturated fatty acid auxotroph. Intact cells or membrane vesicles show substantially different behavior from extracted lipids, indicating that membrane proteins significantly perturb the phase transition. Evidence presented in this paper also shows that the 19F resonance from Escherichia coli phospholipids is sensitive to various intramembrane interactions. There is a general decrease in restriction of motion due to neutral lipids and an opposite effect due to the architecture of the native membrane. Neither effect is temperature sensitive. However, there are interactions in the intact membrane, affecting the 19F resonance, that are temperature dependent both due to the phase-transition process and due to processes occurring at high temperatures.

Cell Membrane↗
PubMedDate not supplied

[Phase transitions of model and biological membranes. II. Temperature-dependent structural reorganization of sarcoplasmic reticulum membranes].

Temperature-dependent structural transitions of sarcoplasmic reticulum membranes, Ca2+-activated ATPase from membranes and liposomes formed from total membrane lipids were studied by fluorescent probes such as 3-metoxybenzantron and dimetylaminochalkon. It was found that sarcoplasmic reticulum membranes undergo the structural transitions at 10, 17--18, 30, 41--43 and 49 degrees C; lipids at 14--15, 30 degrees C and ATPase at 47--49 degrees C. The data obtained here indicate that transitions at 10, 17--18 and 30 degrees C in sarcoplasmic reticulum membranes are associated with a melt of lipids, while the transitions at 41--43 and 49 degrees C apparently reflect changes in conformation of membrane proteins.

Adenosine Triphosphatases↗
PubMedDate not supplied

[Phase transition studies of model and biological membranes. I. Use of hydrophobic fluorescent probes for studying phase transitions in liposomes].

Phase transition induced by temperature changes in liposomes prepared from synthetic dimyristoyl-(DML), dipalmytoyl-(DPL) and distearyl-(DSL) lecithins and also from equimolar mixture of DML and DPL and mixtures of DPL and cholesterol were studied with fluorescent probes such as 3-metoxybenzantron (MBA) and dimetylaminocholkone (DMC). The significant changes of fluorescence intensity and maximum position of MBA and DMC were found in the regions of phase transitions at 23, 42, 54 and 31c in liposomes from DML, DPL, DSL and mixture of DML and DPL, respectively. Cholesterol incorporation into liposomes from DPL led to a decrease of transition temperature and cooperativity for these liposomes. At cholesterol concentration of 20 mol. percent or more the transition disappeared completely. It is concluded that MBA and DMC can be used for the investigation of biological membranes phase transitions.

Cholesterol↗
PubMed1978

[A model of biological structure adequate for a dynamic organicist concept of psychiatry].

A "dynamic organicist" conception of the psychiatry is credible only with a pattern of biological encephalic structure corresponding with the complexity and lability of the psychology and psychopathology features. The author reports the results of researches of his group by electron microscopy concerning the human cerebral cortex, permitting to elaborate adequate pattern. The encephalic structures are very complex, changeable, labile, therefor her variations can correspond with the "psychologics" variations.

Adolescent↗
PubMed2026

Dynamic metabolic modelling of ATP allocation during viral infection.

Viral pathogens, like SARS-CoV-2, hijack the host's macromolecular production machinery, imposing an energetic burden that is distributed across cellular metabolism. To explore the dynamic metabolic tension between the host's survival and viral replication, we developed a computational framework that uses genome-scale models to perform dynamic flux balance analysis of human cell metabolism during virus infections. Relative to previous models, our framework addresses the physiology of viral infections of non-proliferating host cells through two new features. First, by incorporating the lipid content of SARS-CoV-2 biomass, we discovered activation of previously overlooked pathways giving rise to new predictions of possible drug targets. Furthermore, we introduce a dynamic model that simulates the partitioning of resources between the virus and the host cell, capturing the extent to which the competition depletes the human cells from essential ATP. By incorporating viral dynamics into our COMETS framework for spatio-temporal modelling of metabolism, we provide a mechanistic, dynamic and generalizable starting point for bridging systems biology modelling with viral pathogenesis. This framework could be extended to broadly incorporate phage dynamics in microbial systems and ecosystems.

Humans↗
PubMed2026

Field strains of the unicellular alga Chlamydomonas reinhardtii exhibit multicellular characteristics that shape their interactions.

Chlamydomonas reinhardtii is a unicellular green alga long studied as a biological model system but rarely considered from the perspective of its own ecology, thus epitomizing the disconnection between reductionist biology in the laboratory and life in nature. Here, we present insights into its ecology, understood from field strains. We examined bacterial communities that coenriched with C. reinhardtii from the field, revealing specific associations. We then compared the biology of C. reinhardtii field strains to laboratory strains, illuminating strain-level heterogeneity and adaptations to life in the field vs. the laboratory. Field strains exhibited more robust photosynthesis, higher abundances of pherophorin proteins, a propensity for palmelloid formation, and high cell wall permeability. Finally, we phenotyped cocultures of C. reinhardtii with a coenriched bacterial partner, demonstrating how differences between field and laboratory strains manifest in biotic interactions. Although the organisms in question are classically understood as unicellular, our observations of field strains highlighted their participation in multicellular units, challenging the utility of unicellular frameworks in extending our knowledge of model organism biology in the laboratory towards understanding microbial ecology.

Chlamydomonas reinhardtii↗
PubMed2026

Prader-Willi syndrome as a neurogenetic model for psychosis and obsessive-compulsive disorder: A review of clinical, behavioral, and biological insights.

Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder classically defined by hyperphagia and obesity. However, its profound psychiatric phenotype offers a unique genetic framework for understanding major mental illnesses. This review positions PWS as a potentially informative biological model for psychosis and obsessive-compulsive disorder (OCD), bridging the gap between 15q11-q13 imprinting defects and neural circuit dysfunction. We synthesize evidence demonstrating that psychosis in PWS is not a uniform trait but is disproportionately linked to the maternal uniparental disomy (mUPD) subtype. This genotype-phenotype correlation suggests that overexpression of maternally imprinted genes and loss of paternal expression disrupt cortical excitatory-inhibitory balance, resembling the "schizophrenia-bipolar" genomic architecture. Furthermore, synthesized evidence characterizes the repetitive, ritualistic behaviors in PWS not merely as behavioral challenges, but as a developmentally arrested OCD-spectrum phenotype driven by distinct serotonergic-oxytocinergic imbalances and hypothalamic-limbic dysconnectivity. Mechanistic insights from preclinical models of MAGEL2, SNORD116, and NDN deficiency are integrated with clinical findings to highlight shared neurobiological substrates. Finally, we outline a roadmap for precision psychiatry in PWS, emphasizing the necessity of pharmacogenomics in antipsychotic management and the potential of targeted circuit-based therapeutics. By deconstructing the psychiatric comorbidities of PWS, we provide a framework for translating genomic architecture into mechanistic understanding and targeted treatment for complex neuropsychiatric disorders.

15q11-q13↗
PubMed1978

A linear models application of competing risks to multiple causes of death.

An analysis is performed to ascertain the joint incidence of two causes of death, acute myocardial infarct and stroke, for the deaths of residents of Massachusetts and North Carolina in 1969. To assay their association an explicit biological model of the nature of the relation is posited. It is shown that, under this model, Chiang's (1968) theory of competing risks may be extended to the case in which an individual's death may have multiple causes. Furthermore, techniques are developed which allow us to model the survival parameters derived under the model by categorical data procedures of the type introduced by Grizzle, Starmer and Koch (1969). The study shows that there is a greater incidence of the joint occurrence of stroke and myocardial infarct on death certificates in North Carolina than in Massachusetts, a pattern consistent with the generally higher stroke mortality in North Carolina. Furthermore, the incidence of the joint occurrence of the two diseases shows a clear age "gradient" increasing through the age range of the analysis. Males and females show somewhat different patterns of age variation in that state-by-age interaction terms are more prominent in the model fitted for females than for males.

Age Factors↗
PubMed1979

Lipophilicity and biological acitivity. Drug transport and drug distribution in model systems and in biological systems.

Different equilibrium and non-equilibrium models are used to simulate drug transport and drug distribution. The percentage of absorbed drug, the rate constants of drug absorption and the drug concentrations in the different compartments of the models can be described quantitatively by the bilinear model, e.g., log ci = a log P-b log (betaP + 1) + c. A nearly perfect fit is obtained for the simulated data from this model. Drug absorption and distribution in biological systems can be explained and described by the model-derived equations. Examples from the literature include buccal absorption, gastric and intestinal in situ and in vitro absorption, colonic absorption, renal clearance, and absorption through the skin and the blood-brain barrier; in all those cases the bilinear model gives an excellent fit of the experimental data. Combination of the pH-partition theory with the bilinear model leads to a simple quantitative model for the precise description of the relationships between lipophilicity, degree of ionization, and absorption, distribution and biological activity of drugs.

Absorption↗
PubMed1977

Mental development of preterm infants during the first year.

Developmental rates and standard scores are examined for 56 infants in 4 gestational age groups by repeated measurements on the mental scale of the Bayley Scales of Infant Development. Rates across the first year of life can be predicted largely by a biological model that assumes equality of development for infants of the same conceptual age. However, standard scores based on biological age are elevated during the early months for the most premature groups, indicating a transient advantage of increased extrauterine life. Scores from 3 to 12 months' biological age are slightly higher for the most premature groups but are consistent within groups, with no special acceleration of the premature.

Age Factors↗
PubMed1979

Longitudinal analysis of the dynamics and risk of coronary heart disease in the Framingham Study.

Statistical methods designed specifically for the analysis of chronic disease incidence and progression in longitudinal studies are presented. These method model the risk of acute phases of chronic disease separately from the temporal change in risk variables. This could be accomplished because, under a specific biological model of the disease mechanism, the problems of estimating the risk of an acute event and of predicting the change in risk variables are independent. Specifically, a quadratic equation relating risk variable values to chronic disease risk and a system of linear equations predicting future risk variable values from present values may beestimated separately. Taken together, they utilize the full information available in a longitudinal study on the temporal dimension of chronic disease progression. In addition, the model is found to possess a number of attractive statistical and theoretical properties. These methods are applied to longitudinal data from the Framingham Study on coronary heart disease (CHD) in males. A quadratic function relating the risk of a CHD event to selected risk variables (age, and the natural logarithms of serum cholesterol, uric acid, diastolic blood pressure and pulse pressure) was estimated from measurements made at four points equally spaced in time (two years) with a further morbidity follow-up at a fifth point. The risk function was found to predict CHD risk accurately. It showed that, apart from the linear effects of the risk variables, cohort effects, quadratic effects and interaction effects were important predictors of CHD risk. The linear regression equations used to predict future risk variable values showed that there was an intricate network of cross-temporal associations. Study of the two types of equations jointly show that putative risk variables could affect the risk of CHD incidence both directly, by being associated with higher levels of risk, and indirectly, by causing other risk variable values to change with time. The results led us to identify several different roles that risk variables might play in CHD incidence.

Coronary Disease↗
PubMed1977

In search of anti-Trypanosoma cruzi drugs: new leads from a mouse model.

Nine of 25 carefully selected compounds (from a stock of more than 200 000 chemical species amassed principally as a result of testing against other parasitic diseases) were found to have significant suppressive activity against the parasites in the blood of a Trypanosoma cruzi mouse model. Eight of these compounds evaluated in this model had suppressive activity equal to or greater than the reference compound, nifurtimox. For the first time, suppressive activity against T. cruzi is reported for a 7-aminoquinoline, a phosphonium salt, and TAC pamoate; The biological model is believed to be able to serve as a means of identifying other new "leads* in seeking drugs broadly effective against T=ruzi infections in man.

5-Amino-3-((5-nitro-2-furyl)vinyl)-1,2,4-oxadiazol↗