Sample entropy analysis of cervical neoplasia gene-expression signatures

Background  

We introduce Approximate Entropy as a mathematical method of analysis for microarray data. Approximate entropy is applied here as a method to classify the complex gene expression patterns resultant of a clinical sample set. Since Entropy is a measure of disorder in a system, we believe that by choosing genes which display minimum entropy in normal controls and maximum entropy in the cancerous sample set we will be able to distinguish those genes which display the greatest variability in the cancerous set. Here we describe a method of utilizing Approximate Sample Entropy (ApSE) analysis to identify genes of interest with the highest probability of producing an accurate, predictive, classification model from our data set.     

Purification,characterization and thermodynamic analysis of cellulases produced from Thermomyces dupontii and its industrial applications

Cellulases involved in the hydrolysis of cellulose and plays a vital role in different industries like textile, detergent paper and Feed industry. Cellulases have been a prospective target for research by both the academic and industrial sectors because of the intricacy of the enzyme system and the enormous industrial potential. In the present work Thermomyces dupontii, which had previously been isolated and recorded as a promising cellulase producer were used. Both endoglucanases and betaglucosidases were purified to its homogeneity by ammonium sulfate followed by anion exchange and gel filtration chromatography. The recovery and purification fold for endoglucanases and betaglucosidases were 13.7, 10.7 % and 5.9, 2.7, respectively. The molecular weight of endoglucanases and betaglucosidases were estimated as 37 and 66 kDa on SDS-PAGE. Upon kinetic analysis the purified endoglucanases and betaglucosidases showed Km 0.63; 28.56 mg/ml and Vmax 82; 80 U/ml/min, respectively. Characterization revealed that enzyme was found to be acidophilic cellulase having optimal pH of 5.5 and 70 ?C. Furthermore, cellulases were accelerated in the presence of Ca²⁺ and EDTA. The cellulases had activation energy (Ea) of ?44.55; ?50.02 kJ/mol for carboxy-methyl-cellulose hydrolysis and Enthalpy (ΔH) 42.20; 47.70 kJ/mol and entropy ΔS ?5.1 and ?5.7 kJ/mol for EG and BGL, respectively. In addition to this the enzyme had a secondary structure of protein as represented by FTIR spectrum The current study suggested that purified cellulases can be used as a detergent additive to improve washing. Furthermore, it shows the biostoning ability when applied on jean fabric.     

Entropy principle for human development, growth and aging

Entropy productions within nude subjects in respiration calorimeters are calculated from the corresponding energetic data obtained by Du Bois et al. (1952, J. Nutr. 48, 257-293.). The entropy production for men is constant at environmental temperatures from 24-34 degrees C. The metabolic entropy production comprises 98.6% of the total entropy production. The entropy production for women shows a minimum at 30 degrees C (the middle of the neutral zone), a small rise in the cold zone and a trend toward a rise in the warm zone; the average entropy production for women is 8.7% smaller than that for men. The entropy production rises from 0-2 years of age, and decreases rapidly from 2-25 years of age and then gradually to 85 years of age. The entropy production does not seem to achieve a minimum or a level in the lives of men and women. Based on these results, a three-stage hypothesis of entropy production in human life is proposed.     

Thermodynamically stable aggregation-resistant antibody domains through directed evolution

Protein aggregates are usually formed by interactions between unfolded or partially unfolded species, and often occur when a protein is denatured by, for example, heat or low pH. In earlier work, we used a Darwinian selection strategy to create human antibody variable domains that resisted heat aggregation. The repertoires of domains were displayed on filamentous phage and denatured (at 80 °C in pH 7.4), and folded domains were selected by binding to a generic ligand after cooling. This process appeared to select for domains with denatured states that resisted aggregation, but the domains only had low free energies of folding (ΔG_N-D^o = 15-20 kJ/mol at 25 °C in pH 7.4). Here, using the same phage repertoire, we have extended the method to the selection of domains resistant to acid aggregation. In this case, however, the thermodynamic stabilities of selected domains were higher than those selected by thermal denaturation (under both neutral and acidic conditions; ΔG_N-D^o = 26-47 kJ/mol at 25 °C in pH 7.4, or ΔG_N-D^o = 27-34 kJ/mol in pH 3.2). Furthermore, we identified a key determinant (Arg28) that increased the aggregation resistance of the denatured states of the domains at low pH without compromising their thermodynamic stabilities. Thus, the selection process yielded domains that combined thermodynamic stability and aggregation-resistant unfolded states. We suggest that changes to these properties are controlled by the extent to which the folding equilibrium is displaced during the process of selection.     

Cell-based assay for the detection of chemically induced cellular stress by immortalized untransformed transgenic hepatocytes

Background  

Primary hepatocytes, one of the most widely used cell types for toxicological studies, have a very limited life span and must be freshly derived from mice or even humans. Attempts to use stable cell lines maintaining the enzymatic pattern of liver cells have been so far unsatisfactory. Stress proteins (heat shock proteins, HSPs) have been proposed as general markers of cellular injury and their use for environmental monitoring has been suggested. The aim of this work is to develop a bi-transgenic hepatocyte cell line in order to evaluate the ability of various organic and inorganic chemicals to induce the expression of the HSP70 driven reporter gene.     

Prevalence of Dyslipidemia in Urban and Rural India: The ICMR–INDIAB Study

Aim

To study the pattern and prevalence of dyslipidemia in a large representative sample of four selected regions in India.

Methods

Phase I of the Indian Council of Medical Research–India Diabetes (ICMR-INDIAB) study was conducted in a representative population of three states of India [Tamil Nadu, Maharashtra and Jharkhand] and one Union Territory [Chandigarh], and covered a population of 213 million people using stratified multistage sampling design to recruit individuals ≥20 years of age. All the study subjects (n = 16,607) underwent anthropometric measurements and oral glucose tolerance tests were done using capillary blood (except in self-reported diabetes). In addition, in every 5th subject (n = 2042), a fasting venous sample was collected and assayed for lipids. Dyslipidemia was diagnosed using National Cholesterol Education Programme (NCEP) guidelines.

Results

Of the subjects studied, 13.9% had hypercholesterolemia, 29.5% had hypertriglyceridemia, 72.3% had low HDL-C, 11.8% had high LDL-C levels and 79% had abnormalities in one of the lipid parameters. Regional disparity exists with the highest rates of hypercholesterolemia observed in Tamilnadu (18.3%), highest rates of hypertriglyceridemia in Chandigarh (38.6%), highest rates of low HDL-C in Jharkhand (76.8%) and highest rates of high LDL-C in Tamilnadu (15.8%). Except for low HDL-C and in the state of Maharashtra, in all other states, urban residents had the highest prevalence of lipid abnormalities compared to rural residents. Low HDL-C was the most common lipid abnormality (72.3%) in all the four regions studied; in 44.9% of subjects, it was present as an isolated abnormality. Common significant risk factors for dyslipidemia included obesity, diabetes, and dysglycemia.

Conclusion

The prevalence of dyslipidemia is very high in India, which calls for urgent lifestyle intervention strategies to prevent and manage this important cardiovascular risk factor.     

Dietary consumption of monosodium L‐glutamate induces adaptive response and reduction in the life span of Drosophila melanogaster

Adaptive response is the ability of an organism to better counterattack stress‐induced damage in response to a number of different cytotoxic agents. Monosodium L‐glutamate (MSG), the sodium salt of amino acid glutamate, is commonly used as a food additive. We investigated the effects of MSG on the life span and antioxidant response in Drosophila melanogaster (D. melanogaster). Both genders (1 to 3 days old) of flies were fed with diet containing MSG (0.1, 0.5, and 2.5‐g/kg diet) for 5 days to assess selected antioxidant and oxidative stress markers, while flies for longevity were fed for lifetime. Thereafter, the longevity assay, hydrogen peroxide (H₂O₂), and reactive oxygen and nitrogen species levels were determined. Also, catalase, glutathione S‐transferase and acetylcholinesterase activities, and total thiol content were evaluated in the flies. We found that MSG reduced the life span of the flies by up to 23% after continuous exposure. Also, MSG increased reactive oxygen and nitrogen species and H₂O₂ generations and total thiol content as well as the activities of catalase and glutathione S‐transferase in D. melanogaster (P < .05). In conclusion, consumption of MSG for 5 days by D. melanogaster induced adaptive response, but long‐term exposure reduced life span of flies. This study may therefore have public health significance in humans, and thus, moderate consumption of MSG is advocated by the authors.     

Entropy-Based Financial Asset Pricing

We investigate entropy as a financial risk measure. Entropy explains the equity premium of securities and portfolios in a simpler way and, at the same time, with higher explanatory power than the beta parameter of the capital asset pricing model. For asset pricing we define the continuous entropy as an alternative measure of risk. Our results show that entropy decreases in the function of the number of securities involved in a portfolio in a similar way to the standard deviation, and that efficient portfolios are situated on a hyperbola in the expected return – entropy system. For empirical investigation we use daily returns of 150 randomly selected securities for a period of 27 years. Our regression results show that entropy has a higher explanatory power for the expected return than the capital asset pricing model beta. Furthermore we show the time varying behavior of the beta along with entropy.     

Early Detection of Emerging Zoonotic Diseases with Animal Morbidity and Mortality Monitoring

EcoHealth - Diseases transmitted between animals and people have made up more than 50% of emerging infectious diseases in humans over the last 60&nbsp;years and have continued to arise in...     

Mitochondrial mutations and aging: random drift is insufficient to explain the accumulation of mitochondrial deletion mutants in short‐lived animals

Mitochondrial DNA deletions accumulate over the life course in post‐mitotic cells of many species and may contribute to aging. Often a single mutant expands clonally and finally replaces the wild‐type population of a whole cell. One proposal to explain the driving force behind this accumulation states that random drift alone, without any selection advantage, is sufficient to explain the clonal accumulation of a single mutant. Existing mathematical models show that such a process might indeed work for humans. However, to be a general explanation for the clonal accumulation of mtDNA mutants, it is important to know whether random drift could also explain the accumulation process in short‐lived species like rodents. To clarify this issue, we modelled this process mathematically and performed extensive computer simulations to study how different mutation rates affect accumulation time and the resulting degree of heteroplasmy. We show that random drift works for lifespans of around 100 years, but for short‐lived animals, the resulting degree of heteroplasmy is incompatible with experimental observations.     

Curing raisins with sulfur dioxide suppresses population growth of Indian meal moth,Plodia interpunctella (Hubner) (Lepidoptera: Pyralidae)

A sulfur dioxide treatment is often used to preserve the color and flavor of raisins. We used a life table approach to examine the effects of residual sulfites on Plodia interpunctella (Hubner) when larvae fed on raisins under controlled laboratory conditions. Raisins were fumigated with 66 g/m³ or 133 g/m³ SO₂ for either three or six hours, or received no SO₂ exposure (control). A two sex life table was constructed for insects in each treatment (n = 70 per treatment). Total immature mortality exceeded 90% in 66 g/m³ SO₂ treatments, and 80% in 133 g/m³ SO₂ treatments, compared to 28.6% in controls. Sulfur dioxide treatments significantly extended developmental time relative to controls, again more so in the 66 g/m³ SO₂ treatments than in the 133 g/m³ treatments, but did not affect the adult longevity of survivors. All SO₂ treatments reduced the fecundity of surviving female moths to a small fraction of controls, without significant differences among them. These effects combined to result in significantly diminished life table parameters in all treatments relative to controls, although generation times were increased more in the 66 g/m³ SO₂ treatments than in the 133 g/m³ treatments. These inverse dosage-dependent effects may reflect increased feeding avoidance of sulfite residues in the higher dose treatments that resulted in reduced consumption. We conclude that residual sulfur and sulfites deposited on fruit surfaces during SO₂ treatment provide substantial control of P. interpunctella, and should effectively suppress the proliferation of moths within bulk stores of dried raisins.     

Clustering of plant life strategies on meso-scale

The spatial pattern of life strategies gives us clues about what factors are important for structuring the vegetation and at which scale they work. In this study, we look at the spatial distribution of the CSR-strategies of Grime on a meso-scale (larger than 50 m × 50 m) in a temperate forest. To detect the spatial pattern of the different life forms, 79 plant species were surveyed according to a grid with 2431 cells of 50 m × 50 m. For each cell C, S and R-values were calculated and their spatial distribution was studied. The spatial patterns were then explained by available environmental factors. The different plant strategies clearly showed an aggregated pattern on a scale larger than 50 m × 50 m. This non-random and unequal distribution of the different life strategies could be explained by the factors that are under the control of the forest management, namely “distance to road” and “dominant (planted) tree species”. Patches with high C-values (C-biotopes) where found under pine, S-biotopes where found under mixed oak-beech and pure beech stands of 100 to 150 years old. R-biotopes were bound to the roads.     

Spatially resolved free-energy contributions of native fold and molten-globule-like Crambin

The folding stability of a protein is governed by the free-energy difference between its folded and unfolded states, which results from a delicate balance of much larger but almost compensating enthalpic and entropic contributions. The balance can therefore easily be shifted by an external disturbance, such as a mutation of a single amino acid or a change of temperature, in which case the protein unfolds. Effects such as cold denaturation, in which a protein unfolds because of cooling, provide evidence that proteins are strongly stabilized by the solvent entropy contribution to the free-energy balance. However, the molecular mechanisms behind this solvent-driven stability, their quantitative contribution in relation to other free-energy contributions, and how the involved solvent thermodynamics is affected by individual amino acids are largely unclear. Therefore, we addressed these questions using atomistic molecular dynamics simulations of the small protein Crambin in its native fold and a molten-globule-like conformation, which here served as a model for the unfolded state. The free-energy difference between these conformations was decomposed into enthalpic and entropic contributions from the protein and spatially resolved solvent contributions using the nonparametric method Per|Mut. From the spatial resolution, we quantified the local effects on the solvent free-energy difference at each amino acid and identified dependencies of the local enthalpy and entropy on the protein curvature. We identified a strong stabilization of the native fold by almost 500 kJ mol⁻¹ due to the solvent entropy, revealing it as an essential contribution to the total free-energy difference of (53 ± 84) kJ mol⁻¹. Remarkably, more than half of the solvent entropy contribution arose from induced water correlations.     

Long Cycle Life Rechargeable Moisture-Enabled Electricity Cell

Moisture-enabled electricity generation (MEG) is a prominent renewable energy harvesting technology in hydrovoltaic power generation, boasting the broadest energy harvesting spectrum. However, practical application faces limitations due to irreversible performance degradation caused by structural changes and moisture-generated carrier (MGC) losses in Moisture-enabled electricity (ME) materials, rendering them non-renewable. This study introduces a rechargeable moisture-enabled electricity cell (rMEC) based on dual ME functional layers and active metal electrodes. The rMEC demonstrates outstanding power generation performance, with a single cell providing an output voltage of 1.08 V and a power density of 5.83 µW cm⁻² through redox assistance. Moreover, it can be recharged when MGCs are lost, utilizing the reversibility of the redox reaction (moisture of H₂O₂ solution) for self-repair. Notebly, the rMEC maintains stable operation for over 2080 h and undergoes 100 charging/working cycles, marking the longest span life record in MEG research history. When exposed to industrial wastewater/gases with oxidation characteristics, the rMEC not only completes charging but also facilitates the reuse of toxic waste resources. The environmentally friendly rMEC, with its long cycle life, significantly overcomes the limitations of non-renewable ME materials, serving as a paradigm for promoting iterative upgrades in MEG technology.     

Physiology of aging among healthy,older bottlenose dolphins (<Emphasis Type="Italic">Tursiops truncatus</Emphasis>): comparisons with aging humans

Changes in hematological and serum chemistry values have been identified among older compared to younger humans. We hypothesized that healthy bottlenose dolphins (Tursiops truncatus) 30 years and older may demonstrate similar clinicopathological changes with increasing age. Retrospective hematological and serum chemistry data generated from routine, fasted blood samples collected over 10 to 20 years among six healthy dolphins that lived at least 40 years were analyzed to (1) assess linear trends in blood variable values with increasing age, (2) compare mean blood values by older age categories (30–35 years, 36–40 years, and >40 years), and (3) compare the prevalence of clinically high or low blood values by older age categories. Absolute lymphocytes, serum globulins, and mean platelet volume increased linearly with increasing old age. Mean white blood cells, neutrophils, serum globulins, erythrocyte sedimentation rates, serum cholesterol, and serum triglycerides; and the prevalence of neutrophilic leukocytosis, hyperglobulinemia, and hypercholesterolemia, were more likely to be higher as geriatric dolphins got older. A linear decrease in serum albumin with increasing age was present for five of six animals. Serum creatinine decreased among dolphins older than 40 years compared to when they were 30–40 years old. Our study demonstrates that older dolphins have changes in hematological and serum chemistry values similar to those found in older humans. As such, bottlenose dolphins may serve as a useful comparative model for aging in humans. Further studies are needed to assess whether these changes are associated with negative health outcomes and whether targeted therapeutics can help improve quality of life among aging dolphins.     

Calculation of Proteins’ Total Side-Chain Torsional Entropy and Its Influence on Protein-Ligand Interactions

Despite the high density within a typical protein fold, the ensemble of sterically permissible side-chain repackings is vast. Here, we examine the extent of this variability that survives energetic biases due to van der Waals interactions, hydrogen bonding, salt bridges, and solvation. Monte Carlo simulations of an atomistic model exhibit thermal fluctuations among a diverse set of side-chain arrangements, even with the peptide backbone fixed in its crystallographic conformation. We have quantified the torsional entropy of this native-state ensemble, relative to that of a noninteracting reference system, for 12 small proteins. The reduction in entropy per rotatable bond due to each kind of interaction is remarkably consistent across this set of molecules. To assess the biophysical importance of these fluctuations, we have estimated side-chain entropy contributions to the binding affinity of several peptide ligands with calmodulin. Calculations for our fixed-backbone model correlate very well with experimentally determined binding entropies over a range spanning more than 80 kJ/(mol·308 K).     

Interaction of aloe active compounds with calf thymus DNA

Natural anthraquinone compounds have emerged as potent anticancer chemotherapeutic agents because of their promising DNA‐binding properties. Aloe vera is among one of the very well‐known medicinal plants, and the anthraquinone derivatives like aloe emodin (ALM), aloins (ALN), and aloe emodin‐8‐glucoside (ALMG) are known to have immense biological activities. Here, we have used biophysical methods to elucidate the comparative DNA‐binding abilities of these three molecules. Steady‐state fluorescence study indicated complexation between calf thymus DNA (ctDNA) and both the molecules ALM and ALMG whereas ALN showed very weak interaction with DNA. Displacement assays with ctDNA‐bound intercalator (ethidium bromide) and a groove binder (Hoechst 33258) indicated preferential binding of both ALM and ALMG to minor groove of DNA. Isothermal titration calorimetric (ITC) data suggested spontaneous exothermic single binding mode of both the molecules: ALM and ALMG. Entropy is the most important factor which contributed to the standard molar Gibbs energy associated with relatively small favorable enthalpic contribution. The equilibrium constants of binding to ctDNA were (6.02 ± 0.10) × 10⁴ M^?1 and (4.90 ± 0.11) × 10⁴ M^?1 at 298.15 K, for ALM and ALMG, respectively. The enthalpy vs temperature plot yielded negative standard molar heat capacity value, and a strong negative correlation between enthalpy and entropy terms was observed which indicates the enthalpy entropy compensation behavior in both systems. All these thermodynamic phenomena indicate that hydrophobic force is the key factor which is involved in the binding process. Moreover, the enhancement of thermal stability of DNA helix by ALM and ALMG fully agreed to the complexation of these molecules with DNA.     

Assessing the utility of conserving evolutionary history

It is often claimed that conserving evolutionary history is more efficient than species‐based approaches for capturing the attributes of biodiversity that benefit people. This claim underpins academic analyses and recommendations about the distribution and prioritization of species and areas for conservation, but evolutionary history is rarely considered in practical conservation activities. One impediment to implementation is that arguments related to the human‐centric benefits of evolutionary history are often vague and the underlying mechanisms poorly explored. Herein we identify the arguments linking the prioritization of evolutionary history with benefits to people, and for each we explicate the purported mechanism, and evaluate its theoretical and empirical support. We find that, even after 25 years of academic research, the strength of evidence linking evolutionary history to human benefits is still fragile. Most – but not all – arguments rely on the assumption that evolutionary history is a useful surrogate for phenotypic diversity. This surrogacy relationship in turn underlies additional arguments, particularly that, by capturing more phenotypic diversity, evolutionary history will preserve greater ecosystem functioning, capture more of the natural variety that humans prefer, and allow the maintenance of future benefits to humans. A surrogate relationship between evolutionary history and phenotypic diversity appears reasonable given theoretical and empirical results, but the strength of this relationship varies greatly. To the extent that evolutionary history captures unmeasured phenotypic diversity, maximizing the representation of evolutionary history should capture variation in species characteristics that are otherwise unknown, supporting some of the existing arguments. However, there is great variation in the strength and availability of evidence for benefits associated with protecting phenotypic diversity. There are many studies finding positive biodiversity–ecosystem functioning relationships, but little work exists on the maintenance of future benefits or the degree to which humans prefer sets of species with high phenotypic diversity or evolutionary history. Although several arguments link the protection of evolutionary history directly with the reduction of extinction rates, and with the production of relatively greater future biodiversity via increased adaptation or diversification, there are few direct tests. Several of these putative benefits have mismatches between the relevant spatial scales for conservation actions and the spatial scales at which benefits to humans are realized. It will be important for future work to fill in some of these gaps through direct tests of the arguments we define here.     

Development of human antibody fragments using antibody phage display for the detection and diagnosis of Venezuelan equine encephalitis virus (VEEV)

Background  

Venezuelan equine encephalitis virus (VEEV) belongs to the Alphavirus group. Several species of this family are also pathogenic to humans and are recognized as potential agents of biological warfare and terrorism. The objective of this work was the generation of recombinant antibodies for the detection of VEEV after a potential bioterrorism assault or an natural outbreak of VEEV.