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Chance and necessity do not explain the origin of life.

Where and how did the complex genetic instruction set programmed into DNA come into existence? The genetic set may have arisen elsewhere and was transported to the Earth. If not, it arose on the Earth, and became the genetic code in a previous lifeless, physical-chemical world. Even if RNA or DNA were inserted into a lifeless world, they would not contain any genetic instructions unless each nucleotide selection in the sequence was programmed for function. Even then, a predetermined communication system would have had to be in place for any message to be understood at the destination. Transcription and translation would not necessarily have been needed in an RNA world. Ribozymes could have accomplished some of the simpler functions of current protein enzymes. Templating of single RNA strands followed by retemplating back to a sense strand could have occurred. But this process does not explain the derivation of "sense" in any strand. "Sense" means algorithmic function achieved through sequences of certain decision-node switch-settings. These particular primary structures determine secondary and tertiary structures. Each sequence determines minimum-free-energy folding propensities, binding site specificity, and function. Minimal metabolism would be needed for cells to be capable of growth and division. All known metabolism is cybernetic--that is, it is programmatically and algorithmically organized and controlled.

Animals↗

Increase in high frequency EEG activity explains the poor performance of EEG spectral entropy monitor during S-ketamine anesthesia.

OBJECTIVE: To study the effects of S-ketamine on the EEG and to investigate whether spectral entropy of the EEG can be used to assess the depth of hypnosis during S-ketamine anesthesia. METHODS: The effects of sub-anesthetic (159 (21); mean (SD) ng/ml) and anesthetic (1,959 (442) ng/ml) serum concentrations of S-ketamine on state entropy (SE), response entropy (RE) and classical EEG spectral power variables (recorded using the Entropy Module, GE Healthcare, Helsinki, Finland) were studied in 8 healthy males. These EEG data were compared with EEG recordings from 6 matching subjects anesthetized with propofol. RESULTS: The entropy values decreased from the baseline SE 85 (3) and RE 96 (3) to SE 55 (18) and RE 72 (17) during S-ketamine anesthesia but both inter- and intra-individual variation of entropy indices was wide and their specificity to indicate unconsciousness was poor. Propofol induced more pronounced increase in delta power (P<0.02) than S-ketamine, whereas anesthetic S-ketamine induced more high frequency EEG activity in the gamma band (P<0.001). Relative power of 20-70 Hz EEG activity was associated with high SE (P=0.02) and RE (P=0.03) values during S-ketamine anesthesia. CONCLUSIONS: These differences in low and high frequency EEG power bands probably explain why entropy monitor, while adequate for propofol, is not suitable for assessing the depth of S-ketamine anesthesia. SIGNIFICANCE: The entropy monitor is not adequate for monitoring S-ketamine-induced hypnosis.

Adult↗

Explaining socioeconomic status effects in laryngeal cancer.

INTRODUCTION: People with lower socioeconomic status (SES) experience shorter survival times after a cancer diagnosis for many disease sites. We determined whether area-level SES was associated with the outcomes: cause-specific survival and local-regional failure in laryngeal cancer in Ontario, Canada. When we found an association we sought explanations that might be related to access to care including age, sex, rural residence, tumor stage, lymph node status, use of diagnostic imaging, treatment type, percentage of prescribed radiotherapy delivered, number of radiotherapy interruption days, treatment waiting time, and treating cancer center. MATERIALS AND METHODS: The study population consisted of 661 glottic and 495 supraglottic stage-stratified randomly-sampled patients identified using the Ontario Cancer Registry. Area-level SES quintiles were assigned using adjusted median household income from the Canadian Census. Other data were collected from patient charts. Explanations for SES effects were determined by measuring whether the effect moved toward the null value by at least 10% when an access indicator was added to a the model. RESULTS: Socioeconomic status was not related to either outcome for those with supraglottic cancer, but an association was present in glottic cancer. With the highest socioeconomic status quintile as the referent group, the relative risks for patients in the lowest socioeconomic quintile were 2.75 (95% CI 1.48, 5.12) for cause-specific survival and 1.90 (95% CI 1.24, 2.93) for local-regional failure. Disease stage as measured by T-category explained between 3% and 23% of these socioeconomic effects. None of the other access indicators met our 10% change criterion. CONCLUSION: We question why people in lower socioeconomic quintiles were not diagnosed earlier in the disease progression. Having ruled out several variables that may be related to access to care, additional biologic and social variables should be examined to further understand socioeconomic status effects.

Adult↗

Sex scripts and power: a framework to explain urban women's HIV sexual risk with male partners.

The risk of sexual transmission of HIV may be perceived to be real among young urban women; however, the risk of losing a male partner if one doesn't engage in unprotected sex may be perceived to be greater. Sex script theory, and Barrett's theory of power as knowing participation in change, are integrated into a framework to explain young adult urban women's sex scripted response of unprotected sex as a normative relationship-promoting behavior. It is proposed herein that by associating high-power sex scripts that involve health-promoting behaviors into the familiar sex scripts, new HIV risk-reducing behavior may be integrated into normative sex scripts because these are designed to fulfill familiar relationship needs.

Association Learning↗

The analysis of serum effects on structure, size and toxicity of DDAB-DOPE and DC-Chol-DOPE lipoplexes contributes to explain their different transfection efficiency.

The effect of serum on structural properties of dimethyl-dioctadecyl-ammonium bromide (DDAB)-1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) liposomes and DDAB-DOPE/DNA lipoplexes has been investigated by energy dispersive X-ray diffraction (EDXD) technique, at different cationic lipid/DNA weight ratios (rho). The role of serum on the size of lipoplexes has also been studied by dynamic light scattering. Lipoplex transfection efficiency (TE) as a function of rho, and lipoplex toxicity to C6 rat glioma cells have been evaluated in Dulbecco's Modified Eagle Medium (DMEM) with and without serum. A multi-parametric analysis concerning the role of size, structure and cytotoxicity on transfection efficiency contributes to explain the experimental observation that 3beta-[N-(N',N'-dimethylaminoethane)carbamoyl]-cholesterol (DC-Chol)-DOPE/DNA transfect C6 cells better than DDAB-DOPE/DNA lipoplexes.

Animals↗

A critical review of theories to explain violent relationship termination: implications for research and intervention.

The following review represents an update and extension to an influential article (see [Strube, M.J. (1988). The decision to leave an abusive relationship: Empirical evidence and theoretical issues. Psychological Bulletin, 104, 236-250.]), which evaluated empirical research and suggested potential theories to explain victimized women's decisions to terminate violent relationships. In contrast to the original review, this paper provides information on the importance of and means by which theory should be evaluated and critically determines which theoretical approach(es) might be most productive based on theoretical and atheoretical evidence. In addition, this paper discusses strengths and weaknesses of each approach, in light of certain criteria deemed to be important for the evaluation of theory (e.g., comprehensiveness, parsimony, etc.). Furthermore, this paper discusses current controversies regarding these issues, ramifications of differing theoretical approaches, and their potential impact on the field. Based on this analysis, it is determined that general approaches (e.g., reasoned action/planned behavior, investment model) may be better for understanding this complex and multifaceted decision. Suggestions for future theoretical and intervention research are discussed.

Couples Therapy↗

Can the survival difference between breast cancer patients in Denmark and Sweden 1989 and 1994 be explained by patho-anatomical variables?--a population-based study.

Analyses of data from cancer registries have shown a 10% unit difference in 5-year relative survival between Danish and Swedish patients with breast cancer. This study investigates the effect of age and patho-anatomic variables on this survival difference. Hospital records were collected for women over 40 years of age diagnosed in 1989 or 1994 in east Denmark and south Sweden; patho-anatomical variables and survival were compared between 2289 Danish and 1715 Swedish women. Tumours were smaller, node-negative axillae more frequent and well-differentiated tumours almost 10% more frequent in Sweden. A superior 5-year relative survival in Sweden was found in the 50- to 79-year age group. The adjusted hazard rate ratio between countries was 1.7 in 1989 and 1.3 in 1994. Conditional survival after surviving the first 5 years was similar for the two countries. Adjusting for patho-anatomical variables reduced but did not eliminate the higher risk of death among the Danish patients. Higher population death rates could explain some but not all of the residual elevated risk for Danish women.

Age of Onset↗

Bidirectional membrane transport: simulations of transport inhibition in uptake studies explain data obtained with flavonoids.

The purpose of the simulations was to obtain an estimate of concentration-dependent uptake curves when two counteracting transporters are present. On the basis of this experimental data obtained with a pair of ovarian carcinoma cell lines, one of which was not expressing the exsorptive transporter P-glycoprotein and one of which was an MDR1-transfected, P-glycoprotein expressing variant, the kinetics of cellular uptake of the radiolabel (3)H-talinolol were calculated and the inhibitory constants at P-gp were determined for different flavonoids. With respect to the inhibition of P-gp function, among others, naringenin and isoquercitrin were identified as inhibitors, yet estimation of the inhibitory constant was only possible for uptake values corrected for non-P-glycoprotein-mediated processes. It was assumed that an additional inside-directed transporting protein (Carrier B), which is inhibited by the presence of test compounds, uptake of radiolabel was simulated as a function of the concentration of test-compound, with exemplary parameters for the rate constant (k(B)) of the additional Carrier B and the inhibition constants (K(I)-values) for both transporting proteins. The obtained uncorrected experimental data, which showed either inhibition or enhancement of radiolabel uptake as a function of the inhibitor concentration, were appropriately explained by the respective model. The respective model included an exsorptive transporter as well as carrier-mediating facilitated diffusion. It is concluded that flavonoids, such as naringenin and isoquercitrin, inhibit an inside-directed process in addition to their inhibition of P-glycoprotein-mediated exsorption.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Reduction of intracellular calcium removal rate can explain changes in seizure dynamics: studies in neuronal network models.

Complex partial seizures originating from mesial temporal structures are characterized by relatively short durations of organized rhythmic activity (ORA) of 5-8 Hz, typically lasting less than 60s. Previous investigations into seizure dynamics have revealed that this ORA undergoes a monotonic decline prior to seizure evolution into intermittent bursting and subsequent seizure termination. Large neural network models of simplified single-compartment neurons were employed to address the hypothesis that changes in the free intracellular calcium ([Ca2+]i) removal rate during network bursting can result in the alterations of rhythmic seizure activity similar to that observed in recordings from humans. Both exponential and linear models of decreasing calcium removal rates resulted in changes in the predominant frequency of network bursting very similar in frequency and time course to those seen in human intracranial recordings. This supports the concept that changes in [Ca2+]i removal can explain this important network behavior, while not excluding alternative hypotheses. Identifying potential mechanisms underlying the dynamic changes seen in epileptogenic activity in large neural networks can provide important insights into seizure evolution and termination. Model neural network ensembles are attractive systems to address these questions that are difficult to investigate in biological preparations.

Calcium↗

Structural model of the OPA1 GTPase domain may explain the molecular consequences of a novel mutation in a family with autosomal dominant optic atrophy.

Autosomal dominant optic atrophy (ADOA) is the most frequent hereditary optic neuropathy. Three loci have been reported for ADOA: a major locus, harboring all identified mutations to date, maps to 3q28 (OPA1), a second locus is linked to 18q12.2-q12.3 (OPA4) and a third locus on 22q12.1-q13.1 (OPA5) has been reported recently. We describe a six-generation Iranian family in which optic atrophy runs as an autosomal dominant trait with an age of onset at 14-15years. We performed linkage analysis with markers mapping to 3q28 and 18q12.2-q12.3 and found linkage to 3q28. Subsequent sequencing of OPA1 identified a novel heterozygous missense mutation (c.1313A>G) replacing aspartic acid by glycine (p.D438G) in the GTPase domain of OPA1. Interestingly, another missense mutation at the same position (c.1313A>T, D438V) has been reported before in two unrelated German families, indicating a possible mutation hot spot. Further evidence supporting the importance of D438 is its conservation from human to acoelomata. OPA1 is believed to be the human orthologue of yeast MGM1, a dynamin-related protein required for the integrity of mitochondrial DNA. Homology modeling of the OPA1 GTPase domain revealed extensive structural similarity to the Dictyostelium dynamin A GTPase domain and showed that D438 may interact with residues of the G1 and the G4 motifs, which are crucial in coordinating GTP. Based on this analysis, we propose a mechanism which explains the gradual decline of vision in ADOA patients with OPA1 mutations at position 438.

Adolescent↗

Lifelong heterogeneity in fecundity is insufficient to explain late-life fecundity plateaus in Drosophila melanogaster.

Previous studies have demonstrated that fecundity, like mortality, plateaus at late ages in cohorts of Drosophila melanogaster. Although evolutionary theory can explain the decline and plateau in cohort fecundity at late ages, it is conceivable that lifelong heterogeneity in individual female fecundity is producing these plateaus. For example, consistently more fecund females may die at earlier ages, leaving only females that always laid a low number of eggs preponderant at later ages. We simulated fecundity within a cohort, assuming the two phenotypes described above, and tested these predictions by measuring age of death and age-specific fecundity for individual females from three large cohorts. We statistically tested whether there was enough lifelong heterogeneity in fecundity to produce a late-life plateau by testing whether early female fecundity could predict whether that female would live to lay eggs after the onset of the population fecundity plateau. Our results indicate that heterogeneity in fecundity is not lifelong and thus not likely to cause late-life fecundity plateaus. Because lifelong heterogeneity models for fecundity are based on the same underlying assumptions as heterogeneity models for late-life mortality rates, our test of this hypothesis is also an experimental test of lifelong heterogeneity models of late life generally.

Aging↗

A simple model to explain three-base periodicity in coding DNA.

A simple model is put forward to explain the long-known three-base periodicity in coding DNA. We propose the concept of same-phase triplet clustering, i.e. a condition wherein a triplet appears several times in one phase without interruption by the two other possible phases. For instance, in the sequence (i): NTT_GNN_NTT_GNN_NTT_GNN_NNN_NTT_GNN (where N is any nucleotide but combinations producing TTG are excluded) there would be clustering of same-phase TTG because this triplet appears uninterruptedly in phase 2. In contrast, in the sequence (ii): TTG_NTT_GNN_NNT_TGN_NNN_NTT_GNN there is no same-phase clustering because neighboring TTGs are all in different phases. Observe also that in sequence (i) TTG triplets are separated by 3, 3 and 6 nucleotides (3n distances), while in sequence (ii) they are separated by 1, 4 and 5 nucleotides (non-3n distances). In this work, we demonstrate that in coding DNA the 3n distances generated by (i)-type sequences proportionally outnumber the non-3n distances generated by (ii)-type sequences, this condition would be the basis of three-base periodicity. Randomized sequences had (i)- and (ii)-type sequences too but clustering was statistically different. To prove our model we generated (i)-type sequences in a randomized sequence by inducing clustering of same-phase triplets. In agreement with the model this sequence displayed three-base periodicity. Furthermore, two- and four-base periodicities could also be induced by artificially inducing clustering of duplets and tetraplets.

DNA↗

Asymmetric symbiont adaptation to Arctic conditions could explain why high Arctic plants are non-mycorrhizal.

Mycorrhizal symbiosis generally improves nutrient and water acquisition of the host plant. Furthermore, mycorrhizal fungi affect plant herbivory and pathogen resistance. The symbiotic condition of land plants is evolutionarily ancient and the functions performed by the fungal symbiont are thought to be pivotal to successful plant life. Although most land plants are mycorrhizal, the extreme high Arctic habitats are dominated by plant species and genera characteristically free of mycorrhiza. In this paper, previous attempts to explain the lack of mycorrhizas in high Arctic are reviewed as well as a new idea of asymmetric symbiont adaptation is proposed as potential explanation why high Arctic plants are non-mycorrhizal.

Adaptation, Biological↗

Variation in antimicrobial activity of lactoferricin-derived peptides explained by structure modelling.

Antimicrobial peptides bovine lactoferricin (LfcinB) and human lactoferricin (LfcinH) are produced from the respective lactoferrin, but are more active than their precursors. Despite sequence homology, the bovine peptide and its derivatives are more active than their human homologs. Such differences between not only the peptides and their precursor but also between the bovine and the human peptides could relate to structural differences. Upon sequence alignment of both peptides with their parental proteins, the structural differences observed between the bovine lactoferrin (BLf) and LfcinB were also found between the human lactoferrin (HLf) and the LfcinH. The helical structures in HLf are replaced by beta-strands separated by a strong turn in LfcinH suggesting an antiparallel beta-sheet structure similar to LfcinB. MIC assays with HLP-2 and BLP-2, 11-residue peptides derived from the active core of both Lfcins, against Escherichia coli, showed that the bovine derivative, BLP-2, is more active than its human homolog HLP-2. Both 3D models for HLP-2 and BLP-2 showed that the beta-strand is centred between the aromatic residues giving both side chains the same orientations. The displacement towards the N-terminus observed for the beta-strand in HLP-2, compared with its central location in BLP-2, could be less favourable to membrane interaction and therefore responsible for the decrease in activity. Such a model suggests for LfcinH a mechanism similar to the one observed for LfcinB, where the absence of long-range interaction, present in lactoferrin, destabilises the first alpha helix, as observed in solution and, upon interaction with the membrane, could result in the formation of a beta-strand, as observed in the presence of LPS. The location of the beta-strand in relation to the positive charges, seems to define the efficiency of the activity of the peptide and may explain the difference in activity obtained between HLP-2 and BLP-2.

Amino Acid Sequence↗

Models for explaining the homeopathic healing process: a historical and critical account of principles central to homeopathy.

The success of Homeopathy in curing many diseases has been a serious challenge to science. Nineteenth century explanations for the healing process of Homeopathy cannot withstand the scrutiny of modern science and need to be abandoned or modified. The surviving propositions are discussed. A biocybernetic model with multilevels of electromagnetic feedback loops offers a hope of explaining the healing process. This model, its explanation of the healing process and experimental support are elaborated.

Biophysical Phenomena↗

Explaining nurses' work behaviour from their perception of the environment and work values.

The present study examined how the relationship between nurses' perception of their environment and their work values could explain their job performance and whether they intended to quit their jobs. A survey (N=346) and a focus group (N=6) were used to collect data. The results revealed that nurses' job performance was maintained in an environment where they received few professional incentives due to their professionalism. In contrast, negative environmental characteristics directly impacted on nurses' intention to quit their jobs. The present study provides new insights into nurses' work behaviour.

Adult↗

Evaluating the Theory of Planned Behavior to explain intention to engage in premarital sex amongst Korean college students: a questionnaire survey.

BACKGROUND: To reduce risky adolescent sexual behavior, education programs must be tailored to specific cultures and stage of adolescence. OBJECTIVES: This study describes the self-reported sexual behavior of Korean college students and examines the efficiency of the Theory of Planned Behavior (TpB) in explaining intention of engaging in premarital sex in order to provide insights for a potential sex education program designed to reduce risky sexual behavior. DESIGN: A cross-sectional, correlational design using an exploratory survey method was used. PARTICIPANTS: Participants were recruited from a university in Korea with a flyer posted at the entrance of the student health service center, and self-referral in 2004. Male and female unmarried college students aged 18 to 25 were included. Foreign students and students with visible physical problems were excluded. Three hundred and twenty of 550 students returned the questionnaire packets. Final data analysis included 298 students after deleting incomplete data. METHODS: Participants completed six questionnaires: (1) Background and Sexual Behavior Questionnaire, including items related to perceived risk of sexual behavior, (2) Parent-Adolescent Communication Scale, and four scales related to TpB construct: (3) modified Premarital Sexual Attitude Scale, (4) Referent group Approval of Sex Behavior Scale, (5) Sexual Abstinence Efficacy Scale and (6) modified version of Doswell's Intention of Sexual Behavior Scale. RESULTS: Premarital sexual attitude, abstinence self-efficacy and referent group norms were significant predictors of intention of premarital sex for male students with a large effect, but only attitude and norms predicted intention of premarital sex for female students. CONCLUSION: The TpB may be an effective theory to guide the development of theory-driven sexual abstinence interventions to reduce risky sexual behavior for Korean males, while the Theory of Reasoned Action may be an effective theory for Korean females.

Adolescent↗